Renal Artery Stenosis

Background

Specialists have known for a long time that renal artery stenosis (RAS) is the major cause of renovascular hypertension and that it may account for 1-10% of the 50 million people in the United States who have hypertension.

Apart from its role in the pathogenesis of hypertension, renal artery stenosis is also being increasingly recognized as an important cause of chronic renal insufficiency and end-stage renal disease. In older individuals, atherosclerosis (ATH) is by far the most common etiology of renal artery stenosis.[1, 2] As the renal artery lumen progressively narrows, renal blood flow decreases and eventually compromises renal function and structure.

With the increase in the elderly population and the possible increase in the prevalence of renal artery stenosis and ischemic nephropathy, clinicians dealing with renovascular disease (RVD) need noninvasive diagnostic tools and effective therapeutic measures to resolve the problem successfully. This article explores the natural history of this disorder, the value of a variety of invasive and noninvasive diagnostic procedures, and the consequence of allowing the artery to remain obstructed versus reversing renal artery occlusion.

NextPathophysiology

In patients with ATH, the initiator of endothelial injury is not clear; however, dyslipidemia, hypertension, cigarette smoking, diabetes mellitus, viral infection, immune injury, and increased homocysteine levels may contribute to endothelial injury. In the atherosclerotic lesion site, endothelium permeability to plasma macromolecules (eg, low-density lipoprotein [LDL]) increases, turnover of endothelial cells and smooth muscle cells increases, and intimal macrophages increase. When atherogenic lipoproteins exceed certain critical levels, the mechanical forces may enhance lipoprotein insudation in these regions, leading to early atheromatous lesions.

Renal blood flow is 3- to 5-fold greater than the perfusion to other organs because it drives glomerular capillary filtration. Both glomerular capillary hydrostatic pressure and renal blood flow are important determinants of the glomerular filtration rate (GFR).[3]

In patients with renal artery stenosis, the chronic ischemia produced by the obstruction of renal blood flow produces adaptive changes in the kidney that are more pronounced in the tubular tissue. These changes include atrophy with decreased tubular cell size, patchy inflammation and fibrosis, tubulosclerosis, atrophy of the glomerular capillary tuft, thickening and duplication of the Bowman capsule, and intrarenal arterial medial thickening. In patients with renal artery stenosis, the GFR is dependent on angiotensin II and other modulators that maintain the autoregulation system between the afferent and efferent arteries and can fail to maintain the GFR when renal perfusion pressure drops below 70-85 mm Hg. Significant functional impairment of autoregulation, leading to a decrease in the GFR, is not likely to be observed until arterial luminal narrowing exceeds 50%.

The degree of renal artery stenosis that would justify any attempt at either surgical intervention or radiologic intervention is not known. One study suggested that a ratio of pressure, measured distal to renal artery stenosis, less than 90% relative to aortic pressure, was found to be associated with significant renin release from the affected kidney, renin being measured in the ipsilateral renal vein. This might be useful as a functional measurement of significant renovascular stenosis leading to hypertension and, thus, a marker of those individuals more likely to benefit from angioplasty and stenting.[4, 5]

PreviousNextEpidemiologyFrequencyUnited States

Studies suggest that ischemic nephropathy may be responsible for 5-22% of advanced renal disease in all patients older than 50 years.

Mortality/Morbidity

The consequences of renal artery stenosis are hypertension, which may be particularly difficult to control or may require multiple antihypertensive agents (with increased adverse effects), and progressive loss of renal function (ischemic nephropathy).

In addition, the discovery of atherosclerotic RVD frequently occurs in the setting of generalized vascular disease (ie, cerebral, cardiac, peripheral), with the co-morbidity associated with disease in those vascular beds. Thus, any therapeutic intervention for renal artery stenosis should logically take into account the underlying prognosis associated with these co-morbidities.

Race

RVD is less common in African American patients. The incidence rate in 2 studies of patients with severe hypertension was 27-45% in white persons compared to 8-19% in African American persons.[6]

Sex

While the incidence of atherosclerotic RVD is independent of sex, Crowley et al showed that female sex (as well as older age, elevated serum creatinine level, coronary artery disease, peripheral vascular disease, hypertension, and cerebrovascular disease) is an independent predictor of RVD progression.[7]

Age

In 1964, Holley et al reported data from 295 consecutive autopsies performed in their institution during a 10-month period.[8] The mean age at death was 61 years. The prevalence rate of renal artery stenosis was 27% of 256 cases identified as having history of hypertension, while 56% showed significant stenosis (>50% luminal narrowing), and, among normotensive patients, 17% had severe renal artery stenosis (>80% luminal narrowing). Among those older than 70 years, 62% had severe renal artery stenosis.

Another similar autopsy study reported similar results, with 5% of patients older than 64 years showing severe stenosis; this figure increased to 18% for patients aged 65-74 years and 42% for patients older than 75 years.

PreviousProceed to Clinical Presentation , Renal Artery Stenosis

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Heart Transplantation

Background

Heart transplantation is the procedure by which the failing heart is replaced with another heart from a suitable donor.[1] It is generally reserved for patients with end-stage congestive heart failure (CHF) who are estimated to have less than 1 year to live without the transplant and who are not candidates for or have not been helped by conventional medical therapy. In addition, most candidates are excluded from other surgical options because of the poor condition of the heart.

Candidacy determination and evaluation are key components of the process, as are postoperative follow-up care and immunosuppression management. Proper execution of these steps can culminate in an extremely satisfying outcome for both the physician and patient.[2]

Candidates for cardiac transplantation generally present with New York Heart Association (NYHA) class III (moderate) symptoms or class IV (severe) symptoms.[3] Evaluation demonstrates ejection fractions of less than 25%. Attempts are made to stabilize the cardiac condition while the evaluation process is undertaken.

Interim therapy can include oral agents as well as inotropic support. Mechanical support with the intra-aortic balloon pump (IABP) or implantable assist devices may be appropriate in some patients as a bridge to transplantation.[4, 5, 6] However, mechanical support does not improve waiting list survival in adult patients with congenital heart disease.[7]

The annual frequency of heart transplantation is about 1% of the general population with heart failure, both candidates and noncandidates. Improved medical management of CHF has decreased the candidate population; however, organ availability remains an issue.[8, 9] Further information on organ availability and waiting lists is available from the United Network for Organ Sharing.

For patient education resources, see the Heart Center, as well as Heart and Lung Transplant and Congestive Heart Failure.

NextDisease Processes Necessitating Heart Transplantation

The disease processes that necessitate cardiac transplantation can be divided into the following categories:

Dilated cardiomyopathy (54%) - This often has an unclear originIschemic cardiomyopathy (45%) - This percentage is rising because of the increase in coronary artery disease (CAD) in younger age groupsCongenital heart disease and other diseases not amenable to surgical correction (1%)

The pathophysiology of cardiomyopathy that may necessitate cardiac replacement depends on the primary disease process. Chronic ischemic conditions precipitate myocardial cell damage, with progressive enlargement of the myocyte followed by cell death and scarring. The condition can be treated with angioplasty or bypass; however, the small-vessel disease is progressive and thus causes progressive loss of myocardial tissue. This eventually results in significant functional loss and progressive cardiac dilatation.

The pathologic process involved in the functional deterioration of a dilated cardiomyopathy is still unclear. Mechanical dilatation and disruption of energy stores appear to play roles.

The pathophysiology of the transplanted heart is unique. The denervation of the organ makes it dependent on its intrinsic rate. As a result of the lack of neuronal input, some left ventricular hypertrophy results. The right-side function is directly dependent on the ischemic time before reimplantation and the adequacy of preservation. The right ventricle is easily damaged and may initially function as a passive conduit until recovery occurs.

The rejection process that can occur in the allograft has 2 primary forms, cellular and humoral. Cellular rejection is the classic form of rejection and is characterized by perivascular infiltration of lymphocytes with subsequent myocyte damage and necrosis if left untreated.

Humoral rejection is much more difficult to characterize and diagnose. It is thought to be a generalized antibody response initiated by several unknown factors. The antibody deposition into the myocardium results in global cardiac dysfunction. This diagnosis is generally made on the basis of clinical suspicion and exclusion; endomyocardial biopsy is of little value in this context.

CAD is a late pathologic process common to all cardiac allografts, characterized by myointimal hyperplasia of small and medium-sized vessels. The lesions are diffuse and may appear any time from 3 months to several years after implantation. The inciting causes are unclear, though cytomegalovirus (CMV) infection and chronic rejection have been implicated. The mechanism of the process is thought to depend on growth-factor production in the allograft initiated by circulating lymphocytes. Currently, there is no treatment other than retransplantation.

PreviousNextFuture and Controversies

The future of cardiac transplantation will be determined by the outcomes of several issues. One is the ongoing shortage of donor organs, which has fueled a search for alternative therapies for the failing heart. Such therapies include artificial assist devices, dual-chamber pacing, new drug interventions, and genetic therapy.[10] These efforts have proven to be successful in reducing the need for transplantation. Research in the area of xenografts continues.[11, 12]

Another issue is the prevention of allograft vascular disease, which remains a paramount challenge. The pathology of allograft vascular disease is clearly multifactorial in origin, making the research and therapy equally complex. Resolution of this issue will prolong graft survival and lives.

A third issue is the question of recipient selection and listing status, which continues to pose medical and ethical dilemmas. If the donor situation were not an issue, then the listing of potential recipients would not be troublesome.

The final issue is financial. In this era of cost containment in health care, the escalating costs of heart transplantation raises the questions of who should pay for the therapy and whether the procedure should be available on demand.

PreviousNextIndications

The general indications for cardiac transplantation include deteriorating cardiac function and a prognosis of less than 1 year to live. Specific indications include the following:

Dilated cardiomyopathyIschemic cardiomyopathyCongenital heart disease for which no conventional therapy exists or for which conventional therapy has failedEjection fraction less than 20%Intractable angina or malignant cardiac arrhythmias for which conventional therapy has been exhaustedPulmonary vascular resistance of less than 2 Wood unitsAge younger than 65 yearsAbility to comply with medical follow-up carePreviousNextContraindications

Contraindications for heart transplantation include the following:

Age greater than 65 years - This is a relative contraindication; patients who are older than 65 years are evaluated on an individual basis Fixed pulmonary vascular resistance of greater than 4 Wood unitsActive systemic infectionActive systemic disease such as collagen-vascular disease or sickle cell diseaseActive malignancy - Patients with malignancies who have demonstrated a 3- to 5-year disease-free interval may be considered, depending on the tumor type and the evaluating program An ongoing history of substance abuse (eg, alcohol, drugs, or tobacco)Psychosocial instabilityInability to comply with medical follow-up care[13] PreviousNextOutcomes

The 1-year survival rate after cardiac transplantation is as high as 81.8%, with a 5-year survival rate of 69.8%. A significant number of recipients survive more than 10 years after the procedure. After transplantation, adult patients with congenital heart disease have high 30-day mortality but better late survival.[7] The functional status of the recipient after the procedure is generally excellent, depending on the his or her level of motivation.

In patients with severe biventricular failure who received pneumatic biventricular assist devices as a bridge to transplant, the 1-year actuarial survival rate was 89%, compared with 92% in patients without a ventricular assist device.[14]

Hypertension, diabetes mellitus, and obesity are associated with exponential increases in postoperative mortality rates. Heart transplant recipients with all three of these metabolic risk factors were found to have a 63% increased mortality compared to patients without any of the risk factors.[15]

Arnaoutakis et al found that high-risk patients had better 1-year survival rates at high-volume centers (ie, centers that perform more than 15 procedures per year) than at lower volume centers (79% vs 64%, respectively). These differences dissipated among lower-risk patients. Based on these findings, the authors recommended that all high-risk heart transplantation procedures be performed at higher-volume centers.[16]

PreviousProceed to Periprocedural Care , Heart Transplantation

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Cardiac Syndrome X

Background

Cardiac syndrome X (CSX) is typical anginalike chest pain with evidence of myocardial ischemia in the absence of flow-limiting stenosis on coronary angiography. Cannon et al termed this entity, characterized by a decrease in coronary flow reserve without epicardial artery stenosis, microvascular angina.[1] Cardiac syndrome X is a heterogeneous entity, both clinically and pathophysiologically, involving various pathogenic mechanisms.

NextPathophysiology

Many mechanisms have been proposed to result in cardiac syndrome X, including the following:

Endothelial dysfunction (microvascular angina)Myocardial ischemiaInsulin resistanceAbnormal autonomic controlAltered cardiac sensitivityEstrogen deficiencyEndothelial dysfunction

Endothelial dysfunction in cardiac syndrome X appears to be multifactorial and linked to risk factors such as smoking, obesity, hypercholesterolemia, and inflammation.[2] Elevated plasma C-reactive protein levels, a marker of inflammation, have been shown to correlate with disease activity and endothelial dysfunction.[3]

Endothelial dysfunction, with reduced bioavailability of endogenous nitric oxide and increased plasma levels of endothelin-1 (ET-1), may explain, at least in part, the abnormal coronary microvasculature in cardiac syndrome X.[4, 5, 6]

Insulin resistance

Several studies support the presence of hyperinsulinemia in many patients with cardiac syndrome X.[7, 8, 9] Additionally, metformin has been shown to improve vascular function and decrease myocardial ischemia in nondiabetic women with chest pain and angiographically normal coronary arteries.[10]

Abnormal autonomic control

Abnormalities of the autonomic nervous system characterized by adrenergic hyperactivity and baroreceptor dysfunction have been demonstrated by several investigators.[11, 12, 13, 14] In patients with cardiac syndrome X, Camici et al showed improvement of coronary flow reserve by α-adrenergic blockade with doxazosin.[15]

Altered cardiac sensitivity

Multiple studies have suggested that abnormalities in pain perception are the principal abnormality in patients with chest pain and normal findings on coronary angiography. Altered central neural handling of afferent signals may contribute to the abnormal pain perception in these patients.[16]

Estrogen deficiency

Cardiac syndrome X frequently occurs in perimenopausal or postmenopausal women, supporting a pathogenic role for estrogen deficiency.[17] In postmenopausal women with cardiac syndrome X, estrogen replacement therapy improves coronary endothelial function, decreases anginal frequency, and improves exercise-induced angina.[18, 19, 20]

PreviousNextEpidemiology

Approximately 20%-30% of patients undergoing coronary angiography for evaluation of anginalike chest pain may have nonobstructive coronary artery disease.[21, 22]

Cardiac syndrome X is more common in women than in men.[23]

Cardiac syndrome X frequently occurs in perimenopausal and postmenopausal women.

PreviousNextPrognosis

Patients with angina and normal coronary arteries at angiography, fulfilling the diagnostic criteria of cardiac syndrome X, have an excellent prognosis.[24, 25, 26, 27, 28] However, an increased coronary atherosclerotic burden at 10-year follow-up was specifically observed in a group of women with cardiac syndrome X who also displayed coronary endothelial dysfunction.[29] The Women’s Ischemic Syndrome Evaluation study, the largest and most thoroughly investigated cohort of middle-aged women with cardiac syndrome X, showed that these patients often have atherosclerosis on intravascular coronary ultrasound and face a 2.5% annual rate adverse cardiac events.[30]

PreviousProceed to Clinical Presentation , Cardiac Syndrome X

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Eisenmenger Syndrome

Background

Eisenmenger syndrome refers to any untreated congenital cardiac defect with intracardiac communication that leads to pulmonary hypertension, reversal of flow, and cyanosis.[1, 2, 3] The previous left-to-right shunt is converted into a right-to-left shunt secondary to elevated pulmonary artery pressures and associated pulmonary vascular disease. (See Etiology, Treatment, and Medication.)

Lesions in Eisenmenger syndrome, such as large septal defects, are characterized by high pulmonary pressure and/or a high pulmonary flow state. Development of the syndrome represents a point at which pulmonary hypertension is irreversible and is an indication that the cardiac lesion is likely inoperable (see the image below). (See Etiology, Workup, and Treatment.)

This radiograph reveals an enlarged right heart and pulmonary artery dilatation in a 24-year-old woman with an unrestricted patent ductus arteriosus (PDA) and Eisenmenger syndrome.

Eisenmenger syndrome was initially described in 1897, when Victor Eisenmenger reported on a patient with symptoms of dyspnea and cyanosis from infancy who subsequently developed heart failure and succumbed to massive hemoptysis.[4] An autopsy revealed a large ventricular septal defect (VSD) and an overriding aorta. This was the first description of a link between a large congenital cardiac shunt defect and the development of pulmonary hypertension. (See Presentation and Workup.)

Advances in the medical treatment of patients with severe pulmonary hypertension may improve survival in patients with Eisenmenger syndrome and may potentially reverse the process in selected patients to a point at which they again become candidates for surgical repair. (See Treatment and Medication.)[5]

Pulmonary hypertension

Pulmonary hypertension is defined as a mean pulmonary artery pressure of more than 25 mm Hg at rest or more than 30 mm Hg during exercise. The World Health Organization (WHO) has published a classification system of various etiologies of pulmonary hypertension; the most recent updates were in 2003 and 2008.[6, 7] Eisenmenger syndrome is considered part of the group 1 causes of pulmonary hypertension, according to the Venice classification.

Intracardiac communication

An intracardiac communication allows high pulmonary artery pressures to develop and produces right-to-left intracardiac blood flow. Originally described in association with a large VSD, Eisenmenger syndrome can also manifest with a patent ductus arteriosus (PDA) or, less frequently, with other congenital cardiac anomalies. (See the images below.)

This transesophageal image is from the midesophagus of a patient with Eisenmenger syndrome secondary to an unrestricted patent ductus arteriosus (PDA). It shows a severely dilated pulmonary artery. PA = pulmonary artery, Asc Ao = ascending aorta. This computed tomography (CT) chest scan shows a large, unrestricted patent ductus arteriosus (PDA) in a 24-year-old woman with Eisenmenger syndrome.

Examples of congenital heart disease subtypes that may cause pulmonary vascular disease and proceed to Eisenmenger syndrome include the following:

Increased pulmonary arterial flow -Atrial septal defect (ASD), systemic arteriovenous fistulae, total anomalous pulmonary venous returnIncreased pulmonary arterial pressure and flow - Large VSD, large PDA, truncus arteriosus, single ventricle with unobstructed pulmonary blood flowElevated pulmonary venous pressure - Mitral stenosis, cor triatriatum, obstructed pulmonary venous returnNextEpidemiology

Eisenmenger syndrome usually develops before puberty but may develop in adolescence and early adulthood.

Patients in underdeveloped countries are more likely to present late with uncorrected congenital cardiac lesions and a markedly elevated pulmonary vascular resistance (PVR). They are more likely to be inoperable secondary to Eisenmenger physiology.

PreviousNextEtiology

Eisenmenger syndrome occurs in patients with large, congenital cardiac or surgically created extracardiac left-to-right shunts. These shunts initially cause increased pulmonary blood flow.

If left unchecked, increased pulmonary blood flow and/or elevated pulmonary arterial pressure can result in remodeling of the pulmonary microvasculature, with subsequent obstruction to pulmonary blood flow. This is commonly referred to as pulmonary vascular obstructive disease (PVOD).

According to Ohms law, flow (Q) is inversely related to resistance (R) and is directly proportional to pressure (P), as represented by the equation Q = P/R. Any increase in flow, as is observed in patients with intracardiac defects and initial left-to-right shunts, results in increased pulmonary artery pressures. Additionally, any increase in resistance, as occurs in PVOD, results in a decrease in effective flow at the same pressure.

The progression to Eisenmenger physiology is represented by a spectrum of morphologic changes in the capillary bed that progress from reversible lesions to irreversible ones. Endothelial dysfunction and smooth muscle proliferation result from the changes in flow and pressure, increasing the PVR.[8]

The cellular and molecular mechanisms remain fully uncharacterized, representing pathways of inflammation, cell proliferation, vasoconstriction, and fibrosis.[9] The mechanism of pulmonary hypertension in congenital heart disease may share characteristics with other mechanisms of pulmonary hypertension, but the pathways remain complex.

In 1958, Heath and Edwards proposed a histologic classification to describe the changes in Eisenmenger syndrome.[10] Stages I and II represent disease that is most likely reversible. Stage III disease may still be reversible, but in progressing to stages IV-VI, the disease is thought to become irreversible. Pulmonary biopsies are rarely performed today for this condition.

Natural history

Failure to reduce pulmonary pressures in the first 2 years of life may result in the failure of the normal regression of the intimal smooth muscle. This is followed by the progressive changes described by Heath and Edwards.[10] The condition then advances to irreversible pulmonary hypertension, defined as unresponsiveness to inhalation of 100% oxygen or nitric oxide. This point usually correlates to a PVR of more than 12 Woods units.

Clinically, patients gradually develop the following complications of advanced pulmonary vascular disease:

Dyspnea upon exertionSyncopeChest painStrokeBrain abscessCyanosisCongestive heart failureDysrhythmiaHyperviscosity complicationsPulmonary hemorrhage/hemoptysisEndocarditis

The timeframe for this process depends on the anatomic nature of the lesion and whether conditions, such as trisomy 21 (Down syndrome), that are known to accelerate the development of PVOD are present.[11] Without intervention, reversal of flow may happen in early childhood or around puberty, and progression of symptoms may lead to death by the second or third decade of life.[12, 13] Interestingly, adult patients with Eisenmenger syndrome may have a better prognosis compared with those with other causes of pulmonary hypertension.[14]

Causes

Causes of Eisenmenger syndrome include the following:

Large, uncorrected cardiac shunt or palliative, surgically created systemic-to-pulmonary shunt for congenital heart diseaseLarge, nonrestrictive VSDNonrestrictive PDAAtrioventricular septal defect, including a large ostium primum ASD without a ventricular componentAortopulmonary windowPalliative, surgically created systemic-to-pulmonary anastomosis for treatment of congenital heart diseasePreviousNextPrognosis

Eisenmenger syndrome is uniformly fatal; however, some patients survive into the sixth decade of life. The usual life expectancy of a patient with Eisenmenger syndrome is 20-50 years if the syndrome is diagnosed promptly and treated with vigilance. The onset of pulmonary hemorrhage is usually the hallmark of a rapid progression of the disease.[15]

The complications of chronic cyanotic heart disease affect multiple organ systems, including the hematologic, skeletal, renal, and neurologic systems, causing significant morbidity and mortality.

The quality of life is poor in patients with Eisenmenger syndrome because exercise tolerance is extremely limited (due to limited oxygen uptake resulting from an inability to increase pulmonary blood flow) and complications are profound. Poor prognosis is predicted by syncope, elevated-right sided pressures, and hypoxemia.

A study by Salehian et al reported that left ventricular dysfunction (defined as left ventricular ejection fraction [LVEF] [16] A simple echocardiographic score relying on right ventricular and right atrial characteristics was found to predict adverse outcomes in patients with Eisenmenger syndrome that is not associated with complex congenital heart disease.[17]

Uncorrected congenital heart disease with development of Eisenmenger complex portends an insidious progression to near complete physical disability.

PreviousNextOccurrence

The frequency of pulmonary hypertension and the subsequent development of reversed shunting vary depending on the specific heart defect and operative intervention. Such variations include the following:

Large, nonrestrictive VSD or PDA - Approximately 50% of infants with one of these defects develop pulmonary hypertension by early childhood VSD or PDA and transposition of the great arteries - Forty percent of patients develop pulmonary hypertension within the first year of life Large secundum ASD - The natural history of a large secundum ASD differs in that the 10% of cases that progress to pulmonary hypertension do so more slowly and usually not until after the third decade of life Persistent truncus arteriosus and unrestricted pulmonary blood flow - All patients develop severe pulmonary hypertension by the second year of life Common atrioventricular canal - Almost all patients develop severe pulmonary hypertension by the second year of lifeSurgically created systemic-to-pulmonary shunt - The frequency of pulmonary hypertension varies depending on size and anatomyBlalock-Taussig anastomosis (subclavian artery to pulmonary artery) - Ten percent of patients develop pulmonary hypertensionWaterston (ascending aorta to pulmonary artery) or Potts (descending aorta to pulmonary artery) shunt - Thirty percent of patients develop pulmonary hypertension. PreviousNextMorbidity

Complications in Eisenmenger syndrome include the following:

Hematologic complications - These include hyperviscosity syndromes related to secondary erythrocytosis and bleeding diathesesNervous system complications – These include brain abscess, transient cerebral ischemia, thrombotic stroke, and intracerebral hemorrhage Hyperbilirubinemia - Increases the risk of gallstonesHyperuricemia - Can cause nephrolithiasis and secondary goutHypertrophic osteoarthropathy - Causes bone pain and tendernessVision loss - Reports document transient vision loss related to peripheral retinal microvascular abnormalitiesCongestive heart failureDysrhythmiaPulmonary infarction and hemorrhageInfective endocarditisSyncope - The systemic vascular bed is prone to vasodilation and subsequent systemic arterial hypotension, which can cause syncope Sudden deathPreviousNextMortality

Patients with Eisenmenger syndrome usually do not survive beyond the second or third decade. Long-term survival depends on the patient’s age at the onset of pulmonary hypertension and the coexistence of additional adverse features, such as Down syndrome. Survival predominantly depends on right ventricular function. The mortality rate in pregnant patients with Eisenmenger syndrome is reported to be approximately 50%, although it may be higher.

The most frequent terminal event in this syndrome is a combination of hypoxemia and arrhythmia in the setting of rapid increases in pulmonary vascular resistance or decreases in systemic vascular resistance (SVR). Death also commonly results from congestive heart failure, massive hemoptysis, or thromboembolism.[12]

PreviousNextPatient Education

The following points should be considered in patient education:

Inform patients that diet and weight control are essentialEducate patients to avoid smokingProvide an exercise prescriptionAdvise abstinence from or only moderate intake of alcoholEducate patients about contraception options and pregnancy risk (the mortality rate in pregnant patients with Eisenmenger syndrome is approximately 50%)[18] Contraception by means of tubal ligation (with subacute bacterial endocarditis [SBE] prophylaxis) may be recommendedOral or implantable contraceptives may promote pulmonary infarction through activation of the coagulation cascadeEducate patients about the signs and symptoms of polycythemia and hyperviscosityInform patients about the importance of dental hygiene

Additional resources for patients with pulmonary hypertension can be found at the Pulmonary Hypertension Association Web site.

PreviousProceed to Clinical Presentation , Eisenmenger Syndrome

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Cor Triatriatum

Background

First reported in 1868,[1] cor triatriatum, that is, a heart with 3 atria (triatrial heart), is a congenital anomaly in which the left atrium (cor triatriatum sinistrum) or right atrium (cor triatriatum dextrum) is divided into 2 compartments by a fold of tissue, a membrane, or a fibromuscular band.[2, 3, 4, 5, 6, 7] Classically, the proximal (upper or superior) portion of the corresponding atrium receives venous blood, whereas the distal (lower or inferior) portion is in contact with the atrioventricular valve and contains the atrial appendage and the true atrial septum that bears the fossa ovalis. The membrane that separates the atrium into 2 parts varies significantly in size and shape. It may appear similar to a diaphragm or be funnel-shaped, bandlike, entirely intact (imperforate) or contain 1 or more openings (fenestrations) ranging from small, restrictive-type to large and widely open. See the images below.

Cor triatriatum. Echocardiogram showing the proximal chamber (PC) and distal chamber (DC) of the left atrium; the right atrium (RA), left ventricle (LV), and right ventricle (RV) also are shown. Image courtesy of Guido Giordano, MD, Cardiovascular Department, Azienda Ospedaliera Cannizzaro, Catania, Italy. Cor triatriatum. Image courtesy of Guido Giordano, MD, Cardiovascular Department, Azienda Ospedaliera Cannizzaro, Catania, Italy. Cor triatriatum. Image courtesy of Guido Giordano, MD, Cardiovascular Department, Azienda Ospedaliera Cannizzaro, Catania, Italy.

In the pediatric population, this anomaly may be associated with major congenital cardiac lesions such as tetralogy of Fallot, double outlet right ventricle, coarctation of the aorta, partial anomalous pulmonary venous connection, persistent left superior vena cava with unroofed coronary sinus, ventricular septal defect, atrioventricular septal (endocardial cushion) defect, and common atrioventricular canal.[8, 9, 10] Rarely, asplenia or polysplenia has been reported in these patients. Although frequently an isolated finding,[11, 12, 13, 14, 15, 16, 17, 18] cor triatriatum in the adult has been reported in association with ostium secundum atrial septal defect, dilated coronary sinus due to persistent left superior vena cava, and bicuspid aortic valve.[19]

Cor triatriatum dextrum is extremely rare and results from the complete persistence of the right sinus valve of the embryonic heart. The membrane divides the right atrium into a proximal (upper) and a distal (lower) chamber. The upper chamber receives the venous blood from both vena cavae and the lower chamber is in contact with the tricuspid valve and the right atrial appendage.

NextPathophysiologyCor triatriatum sinistrum

The most popular theory holds that cor triatriatum sinister occurs when the common pulmonary vein fails to incorporate the pulmonary circulation into the left atrium and the common pulmonary venous ostium remains narrow (malincorporation theory). The result is a septum-like structure that divides the left atrium into 2 compartments. However, this theory fails to explain the presence of fossa ovalis and atrial muscle fibers within the walls of the proximal chamber where only a venous wall is supposed to be present.[20, 21, 22, 23, 24, 25, 26, 27, 28]

In addition, several cases have been reported in which 1 or 2 pulmonary veins drain into the proximal (accessory) chamber and the others drain directly into the true left atrium. Others believe that the membrane dividing the left atrium is an abnormal growth of the septum primum (malseptation theory) or that the right horn of the embryonic sinus venosus entraps the common pulmonary vein and thereby prevents its incorporation into the left atrium (entrapment theory). The significance of a prominent or persistent left superior vena cava in the pathogenesis of cor triatriatum is unclear.

Cor triatriatum dextrum

During embryogenesis, the right horn of the sinus venosus gradually incorporates into the right atrium to form the smooth posterior portion of the right atrium, whereas the original embryologic right atrium forms the trabeculated anterior portion. The right horn of the sinus venosus and the embryologic right atrium are then connected through the sinoatrial orifice, which has on either side the 2 valvular folds called the right and left venous valves. During this incorporation, the right valve of the right horn of the sinus venosus divides the right atrium in 2. This right valve forms a sheet that serves to direct the oxygenated venous return from the inferior vena cava across the foramen ovale to the left side of the heart during fetal life (Chiari network).[29, 30, 31, 32, 33, 34, 35, 36]

Normally, this network regresses and leaves behind the crista terminalis superiorly and the eustachian valve of the inferior vena cava and the thebesian valve of the coronary sinus inferiorly. Complete persistence of the right sinus valve of embryonic life results in separation of the smooth and trabeculated portions of the right atrium and constitutes cor triatriatum dextrum. If this membrane is extensively fenestrated and weblike in appearance, then it is referred to as the Chiari network.

PreviousNextEpidemiologyFrequencyUnited StatesThe incidence of cor triatriatum has been variously reported as 0.1-0.4%.An incidence of 0.4% has been reported at autopsy of patients with congenital cardiac disease.An incidence of 0.2% was reported among patients undergoing transesophageal echocardiography.In high-volume echocardiographic laboratories, the incidence of cor triatriatum is less than 1 in 10,000. However, this is expected to rise with the increasing use of cardiac diagnostic studies.[37] Cor triatriatum dextrum is extremely rare.Cor triatriatum sinistrum can be misdiagnosed as other common cardiac or pulmonary conditions such as bronchial asthma or mitral stenosis. Mortality/MorbidityThe morbidity and mortality of cor triatriatum sinistrum is high in those who are symptomatic in infancy. This is due to the severely restrictive opening in the accessory membrane and the association with major cyanotic or acyanotic congenital heart lesions. Mortality may exceed 75% in untreated symptomatic infants. Significant sequelae is unusual with cor triatriatum dextrum as it is not commonly associated with life-threatening symptoms or major congenital cardiac defects. Sex

No clear difference has been noted in incidence or clinical presentation among men or women.

AgeIn symptomatic infants, cor triatriatum sinistrum is often associated with other major congenital cardiovascular defects.In the adult, cor triatriatum sinistrum can be as follows: Asymptomatic (found incidentally on cardiac imaging)An isolated finding with a large non-restrictive communication between the superior and inferior left atrial chambersAssociated with minor congenital defects such as patent foramen ovale, atrial septal defect, or persistent left superior vena cava Cor triatriatum dextrum can be diagnosed at any age, especially if incidentally discovered. Other congenital cardiac defects, such as atrial septal defect, may be present and demand evaluation. Cor triatriatum can also be misdiagnosed as other common cardiac conditions such as constrictive pericarditis. The cross-sectional area of the fenestration within the accessory membrane likely remains unchanged with aging. Late presentation of symptomatic disease is, thus, related to the additive effects of other cardiac conditions, such as mitral regurgitation or atrial fibrillation.[38] PreviousProceed to Clinical Presentation , Cor Triatriatum

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Holt-Oram Syndrome

Background

Holt-Oram syndrome, also called heart-hand syndrome, is an inherited disorder characterized by abnormalities of the upper limbs and heart. Holt and Oram first described this condition in 1960 in a 4-generation family with atrial septal defects and thumb abnormalities.[1]

NextPathophysiology

The syndrome is inherited as an autosomal dominant trait that is completely penetrant. The disease is due to mutations in the transcription factor TBX5, which is important in the development of both the heart and upper limbs. The pathophysiologic sequelae are a direct result of malformations of the heart and upper limbs. No contributory environmental factors are known.[2]

Upper limb involvement

Although the clinical manifestations are variable, upper limb abnormalities are always present. Abnormalities may be unilateral or bilateral and asymmetric and may involve the radial, carpal, and thenar bones. Aplasia, hypoplasia, fusion, or anomalous development of these bones produces a spectrum of phenotypes, including triphalangeal or absent thumbs. Occasionally, upper limb malformation can be sufficiently severe to produce phocomelia (a malformation in which the hands are attached close to the body); this has been termed pseudothalidomide syndrome. The most prevalent findings in persons with Holt-Oram syndrome are malformations or fusions of the carpal bones. Carpal bone abnormalities are the only findings present in every affected individual, although these anomalies may be evident only radiographically in some patients.

Cardiac involvement

Approximately 75% of patients have some cardiac abnormality. In most patients, the abnormality is either an atrial septal defect (ASD) or a ventricular septal defect (VSD), which varies in number, size, and location. ASDs are usually of the secundum variety, while VSDs tend to occur in the muscular trabeculated septum. Cardiac anomalies also may include cardiac conduction defects such as progressive atrioventricular block and atrial fibrillation.[3, 4] These anomalies are frequently present even in the absence of septal defects.

PreviousNextEpidemiologyFrequencyUnited States

Holt-Oram syndrome is the most common form of heart-hand syndrome, with prevalence estimated at 0.95 cases per 100,000 total births. Approximately 85% of cases are attributed to new mutations.

Mortality/Morbidity

Structural lesions are present at birth. Prognosis depends on the severity of the cardiac lesions.

Significant intracardiac shunts can be associated with sudden death or the development of pulmonary hypertension and Eisenmenger syndrome. The first clinical manifestation of the disease may be heart failure, cardiac arrhythmias (including heart block), or infective endocarditis. Considerable physical and psychologic morbidity may be associated with limb abnormalities, particularly in severe cases.Sex

Holt-Oram syndrome has no sexual predilection.

AgeA congenital disease, Holt-Oram syndrome is present at birth. Subtle limb involvement may not become clinically apparent until later in life when the cardiac symptoms of the disease manifest or when an individual has a child with a more severe presentation of the syndrome. Cardiac conduction disease is progressive with aging.Middle-aged individuals often present with significant atrioventricular block or atrial fibrillation.PreviousProceed to Clinical Presentation , Holt-Oram Syndrome

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Lutembacher Syndrome

Background

Lutembacher syndrome is defined as a combination of mitral stenosis and a left-to-right shunt at the atrial level. Typically, the left-to-right shunt is an atrial septal defect (ASD) of the ostium secundum variety. Both these defects, ASD and mitral stenosis, can be either congenital or acquired.

The definition of Lutembacher syndrome has undergone many changes. The earliest description in medical literature is found in a letter written by anatomist Johann Friedrich Meckel to Albrecht von Haller in 1750.[1] In 1916, Lutembacher described his first case of this syndrome, involving a 61-year-old woman, and he attributed the mitral valvular lesion to congenital mitral stenosis. Because the mitral stenosis was, in fact, rheumatic in etiology, the syndrome was defined eventually as a combination of congenital ASD and acquired, almost always rheumatic, mitral stenosis.

In the current era of mitral valvuloplasty for acquired mitral stenosis, however, residual iatrogenic ASD secondary to transseptal puncture is more common than congenital ASD, as is the combination of ASD and mitral stenosis. Although this syndrome is generally defined as mitral stenosis in combination with ASD, some have argued to define the syndrome as a combination of ASD and any mitral valve lesion, ie, mitral stenosis, mitral insufficiency, or mixed lesion. Currently, any combination of ASD, congenital or iatrogenic, and mitral stenosis, congenital or acquired, is referred as Lutembacher syndrome.

NextPathophysiology

Mitral stenosis can be either congenital, as initially described, or acquired in origin, most commonly due to rheumatic mitral valve disease. Isolated mitral stenosis is now known to be a rare congenital disorder, and most cases of mitral stenosis initially thought to be congenital were, in fact, caused by rheumatic mitral valve disease.

Similarly, understanding of the etiology of ASD as associated with Lutembacher syndrome has evolved over time. Initially, high left atrial pressure due to mitral stenosis was thought to stretch open the patent foramen ovale (PFO), causing left-to-right shunt and providing another outlet for the left atrium. Now ASD in this syndrome, like mitral stenosis, is recognized as being either congenital or acquired, as already described.

Acquired ASD is almost always iatrogenic, either intentional or as a complication of a percutaneous interventional procedure. The incidence of left-to-right atrial shunt following mitral valvuloplasty is estimated at 11-12%. Although most of these ASDs are small and hemodynamically insignificant, some can be large enough to have hemodynamic consequences, especially in patients who develop restenosis of the mitral valve.

The hemodynamic effects of this syndrome are a result of the interplay between the relative effects of ASD and mitral stenosis. In its initial description, the ASD was typically large in Lutembacher syndrome, thus providing another route for blood flow. Iatrogenic ASDs tend to be smaller but still may be hemodynamically significant. The direction of blood flow is determined largely by the compliance of left and right ventricles. Normally, the right ventricle is more compliant than the left ventricle.

As a result, in the presence of mitral stenosis, blood flows to the right atrium through the ASD instead of going backward into the pulmonary veins, thus avoiding pulmonary congestion. This happens at the cost of progressive dilatation and, ultimately, failure of the right ventricle and reduced blood flow to the left ventricle. Development of Eisenmenger syndrome or irreversible pulmonary vascular disease is very uncommon in the presence of large ASD and high left atrial pressure because of mitral stenosis.

The term reverse Lutembacher syndrome is sometimes used to describe those rare cases in which a predominant right-to-left shunt develops owing to development of severe tricuspid stenosis.

PreviousNextEpidemiologyFrequencyUnited States

The true incidence of the syndrome is not clearly known. Although mitral stenosis is encountered in 4% of patients with an ASD, congenital mitral stenosis itself is very rare, accounting for only 0.6% of congenital heart disease cases at autopsy. The incidence of ASD in patients with mitral stenosis is 0.6-0.7%. In one US study, the combination was found in 5 of 25,000 autopsies. The syndrome was diagnosed more frequently in the past for the following reasons:

Without echocardiography, the combination of mid diastolic murmur, actually due to increased blood flow across the tricuspid valve, and systolic murmur of ASD led to a mistaken diagnosis of Lutembacher syndrome. The prevalence of both rheumatic heart disease and mitral stenosis was higher in western developed countries before the antibiotic era. With the decline in the frequency of rheumatic fever, the prevalence of mitral stenosis has decreased and so has diagnosis of the syndrome. A history of rheumatic fever is frequently absent. Even though ASD may be underdiagnosed in the United States, the combination of ASD and mitral stenosis may not be evident on physical examination and for that reason is best confirmed by echocardiography. International

Although the exact prevalence of Lutembacher syndrome is not known, it is probably higher in areas where rheumatic heart disease is still common.

Mortality/Morbidity

No definite data are available. Mortality and morbidity rates are related to the relative severity of the individual lesions.

Race

No data are available regarding racial distribution of the condition.

Sex

Lutembacher syndrome is more common in females than males. Part of the reason is the higher incidence of both congenital ASD and rheumatic mitral stenosis in females.

Age

This syndrome can present at any age. Cases have been diagnosed in the seventh decade of life. Lutembacher's original case was a 61-year-old woman who had been pregnant 7 times. In the current era of balloon mitral valvuloplasty and development of ASD, the age of presentation may change.

PreviousProceed to Clinical Presentation , Lutembacher Syndrome

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Tetralogy of Fallot

Practice Essentials

Tetralogy of Fallot, which is one of the most common congenital heart disorders, comprises right ventricular (RV) outflow tract obstruction (RVOTO) (infundibular stenosis), ventricular septal defect (VSD), aorta dextroposition, and RV hypertrophy. The mortality rate in untreated patients reaches 50% by age 6 years, but in the present era of cardiac surgery, children with simple forms of tetralogy of Fallot enjoy good long-term survival with an excellent quality of life.

Essential update: Fluconazole linked to increased risk of tetralogy of Fallot

In an analysis of the incidence of 15 specific birth defects among 976,300 live births recorded in the Medical Birth Registry in Denmark between January 1, 1996, and March 31, 2011, researchers found a 3-fold increased risk for tetralogy of Fallot among infants whose mothers took fluconazole in the first trimester. The absolute risk for tetralogy of Fallot was small, with an estimated 6.5 excess cases per 10,000 infants exposed to fluconazole. The study showed no association between the antifungal and 14 other birth defects previously linked to it.[1, 2]

Signs and symptoms

The clinical features of tetralogy of Fallot are directly related to the severity of the anatomic defects. Infants often display the following:

Difficulty with feedingFailure to thriveEpisodes of bluish pale skin during crying or feeding (ie, "Tet" spells)Exertional dyspnea, usually worsening with age

Physical findings include the following:

Most infants are smaller than expected for ageCyanosis of the lips and nail bed is usually pronounced at birthAfter age 3-6 months, the fingers and toes show clubbingA systolic thrill is usually present anteriorly along the left sternal borderA harsh systolic ejection murmur (SEM) is heard over the pulmonic area and left sternal borderDuring cyanotic episodes, murmurs may disappearIn individuals with aortopulmonary collaterals, continuous murmurs may be auscultated

The following may also be noted:

RV predominance on palpationA bulging left hemithoraxAortic ejection clickSquatting position (compensatory mechanism)Scoliosis (common)Retinal engorgementHemoptysis

See Clinical Presentation for more detail.

Diagnosis

Hemoglobin and hematocrit values are usually elevated in proportion to the degree of cyanosis. Patients with significant cyanosis have the following, in association with a tendency to bleed:

Decreased clotting factorsLow platelet countDiminished coagulation factorsDiminished total fibrinogenProlonged prothrombin and coagulation times

Arterial blood gas (ABG) results are as follows:

Oxygen saturation variespH and partial pressure of carbon dioxide (pCO2) are normal unless the patient is in extremis

Imaging studies include the following:

EchocardiographyChest radiographsMagnetic resonance imaging (MRI)

Echocardiography has the following attributes:

Color-flow Doppler echocardiography accurately diagnoses ductus arteriosus, muscular VSD, or atrial septal defectThe coronary anatomy can be revealed with some degree of accuracyValvar alterations can be detected with easeIn many institutions, echocardiography is the only diagnostic study used before surgery

Chest radiographs have the following attributes:

Often normal initiallyDiminished vascularity in the lungs and diminished prominence of the pulmonary arteries gradually become apparentThe classic boot-shaped heart (coeur en sabot) is the hallmark of the disorder

MRI has the following attributes:

Provides good delineation of the aorta, RVOT, VSDs, RV hypertrophy, and the pulmonary artery and its branches[3] Can also be used to measure intracardiac pressures, gradients, and blood flows

Cardiac catheterization is extremely useful in any of the following instances:

The anatomy cannot be completely defined by echocardiographyDisease in the pulmonary arteries is a concernPulmonary vascular hypertension is possible

Cardiac catheterization findings include the following:

Assessment of the pulmonary annulus size and pulmonary arteriesAssessment of the severity of RVOTOLocation of the position and size of the VSDRuling out possible coronary artery anomalies

See Workup for more detail.

Management

Acute treatment for hypercyanosis is as follows:

Place the baby on the mother's shoulder with the infant's knees tucked up underneath; this provides a calming effect, reduces systemic venous return, and increases systemic vascular resistance (SVR) Oxygen is of limited value, as the primary abnormality is reduced pulmonary blood flowMorphine sulfate, 0.1-0.2 mg/kg intramuscularly (IM) or subcutaneously (SC), may reduce the ventilatory drive and decrease systemic venous return Phenylephrine, 0.02 mg/kg IV, is used to increase SVRDexmedetomidine infusion has been used, but requires caution and careful titration[4] General anesthesia is a last resort

Most infants with tetralogy of Fallot require some type of surgical procedure. Surgery is preferably done at or about 12 months of age. Primary correction is the ideal operation and is usually performed under cardiopulmonary bypass. Palliative procedures (eg, placement of the modified Blalock-Taussig shunt) may be necessary in patients with contraindications to primary repair, which include the following:

The presence of an anomalous coronary arteryVery low birth weightSmall pulmonary arteriesMultiple VSDsMultiple coexisting intracardiac malformations

See Treatment and Medication for more detail.

Image libraryAnatomic findings in tetralogy of Fallot. NextBackground

Tetralogy of Fallot (TOF) is one of the most common congenital heart disorders (CHDs). This condition is classified as a cyanotic heart disorder, because tetralogy of Fallot results in an inadequate flow of blood to the lungs for oxygenation (right-to-left shunt) (see the following image). Patients with tetralogy of Fallot initially present with cyanosis shortly after birth, thereby attracting early medical attention.

Anatomic findings in tetralogy of Fallot. Typical features

The 4 features typical of tetralogy of Fallot include right ventricular (RV) outflow tract obstruction (RVOTO) (infundibular stenosis), ventricular septal defect (VSD), aorta dextroposition, and right ventricular hypertrophy. Occasionally, a few children also have an atrial septal defect (ASD), which makes up the pentad of Fallot. The basic pathology of tetralogy is due to the underdevelopment of the right ventricular infundibulum, which results in an anterior-leftward malalignment of the infundibular septum. This malalignment determines the degree of RVOTO.

The clinical features of tetralogy of Fallot are generally typical, and a preliminary clinical diagnosis can almost always be made. Because most infants with this disorder require surgery, it is fortunate that the availability of cardiopulmonary bypass (CPB), cardioplegia, and surgical techniques is now well established. Most surgical series report excellent clinical results with low morbidity and mortality rates.

See also Tetralogy of Fallot With Pulmonary Stenosis, Tetralogy of Fallot With Pulmonary Atresia, and Tetralogy of Fallot With Absent Pulmonary Valve.

Historical information

Louis Arthur Fallot, after whom the name tetralogy of Fallot is derived, was not the first person to recognize the condition. Stensen first described it in 1672; however, it was Fallot who first accurately described the clinical and complete pathologic features of the defects.

Although the disorder was clinically diagnosed much earlier, no treatment was available until the 1940s. Cardiologist Helen Taussig recognized that cyanosis progressed and inevitably led to death in infants with tetralogy of Fallot. She postulated that the cyanosis was due to inadequate pulmonary blood flow. Her collaboration with Alfred Blalock led to the first type of palliation for these infants. In 1944, Blalock operated on an infant with tetralogy of Fallot and created the first Blalock-Taussig shunt between the subclavian artery and the pulmonary artery (see the image below).

This image shows completed blocking with a Taussig shunt

The pioneering Blalock-Taussig shunt surgical technique opened a new era in neonatal cardiac surgery. Development of the Potts shunt (from the descending aorta to the left pulmonary artery), the Glenn shunt (from the superior vena cava to the right pulmonary artery), and the Waterston shunt (from the ascending aorta to the right pulmonary artery) followed.

Scott performed the first open correction in 1954. Less than half a year later, Lillehei performed the first successful open repair for tetralogy of Fallot using controlled cross-circulation, with another patient serving as oxygenator and blood reservoir. The following year, with the advent of cardiopulmonary bypass by Gibbons, another historic era of cardiac surgery was established. Since then, numerous advances in surgical technique and myocardial preservation have evolved in the treatment of tetralogy of Fallot.

PreviousNextAnatomy

Patients with tetralogy of Fallot (TOF) can present with a broad range of anatomic deformities. Fallot initially described 4 major defects consisting of[5] : (1) pulmonary artery stenosis, (2) ventricular septal defect (VSD), (3) deviation of the aortic origin to the right, and (4) right ventricular hypertrophy (RV).

In the present day, however, the most important features of tetralogy of Fallot are recognized as (1) the right ventricular (RV) outflow tract obstruction (RVOTO), which is nearly always infundibular and/or valvular, and (2) an unrestricted VSD associated with malalignment of the conal septum (see the following image).

Anatomic findings in tetralogy of Fallot. Right ventricle outflow tract obstruction

Clinically, most patients with tetralogy of Fallot have an increased resistance to right ventricle emptying because of the pulmonary outflow tract obstruction. The anterior displacement and rotation of the infundibular septum causes RV obstruction of variable degree and location. The obstruction may be adjacent to the pulmonary valve, causing additional obstruction.

Pulmonary arteries

The pulmonary arteries can vary in size and distribution, and they may be atretic or hypoplastic. Rarely, the left pulmonary artery is absent. In some individuals, a varying degree of stenosis of the peripheral pulmonary arteries occurs, which further restricts pulmonary blood flow.

Pulmonary atresia results in no communication between the RV and the main pulmonary artery; in this case, pulmonary blood flow is maintained by either the ductus arteriosus or collateral circulation from the bronchial vessels. With minimal RVOTO, pulmonary vascular disease may develop secondary to excessive pulmonary blood flow from the large left-to-right shunt or large aortopulmonary collaterals.

In up to 75% of children with tetralogy of Fallot, some degree of pulmonary valve stenosis may occur. Stenosis is usually due to leaflet tethering rather than commissural fusion. The pulmonary annulus is narrowed in virtually every case.

Aorta

True dextroposition and abnormal rotation of the aortic root result in aortic overriding (ie, an aorta that, to varying degrees, originates from the RV). In some cases, more than 50% of the aorta may thus originate from the RV. A right aortic arch may occur, which may lead to an abnormal origin of the arch vessels.

Associated anomalies

Associated defects are also common. The coexistence of an atrial septal defect (ASD) occurs often enough to prompt its inclusion in a so-called pentalogy of Fallot. Other possible defects include patent ductus arteriosus (PDA), atrioventricular septal defects (AVSD), muscular VSD, anomalous pulmonary venous return, anomalous coronary arteries, absent pulmonary valve, aorticopulmonary window, and aortic incompetence.

The coronary anatomy may also be abnormal. Among these abnormalities is the origin of the left anterior descending (LAD) coronary artery from the proximal right coronary artery (PRCA), which crosses the RV outflow at variable distances from the pulmonary valve annulus. The anomalous LAD coronary artery is observed in 9% of cases of tetralogy of Fallot, and this abnormality makes placement of a patch across the pulmonary annulus risky, possibly requiring an external conduit. During the VSD repair, the anomalous LAD coronary artery is prone to injury. Occasionally, all coronary arteries arise from a single left main coronary ostium.

PreviousNextEtiology and Pathophysiology

The cause(s) of most congenital heart diseases (CHDs) are unknown, although genetic studies suggest a multifactorial etiology. A study from Portugal reported that methylene tetrahydrofolate reductase (MTHFR) gene polymorphism can be considered a susceptibility gene for tetralogy of Fallot.[6, 7]

Prenatal factors associated with a higher incidence of tetralogy of Fallot (TOF) include maternal rubella (or other viral illnesses) during pregnancy, poor prenatal nutrition, maternal alcohol use, maternal age older than 40 years, maternal phenylketonuria (PKU) birth defects, and diabetes. Children with Down syndrome also have a higher incidence of tetralogy of Fallot, as do infants with fetal hydantoin syndrome or fetal carbamazepine syndrome.

As one of the conotruncal malformations, tetralogy of Fallot can be associated with a spectrum of lesions known as CATCH 22 (cardiac defects, abnormal facies, thymic hypoplasia, cleft palate, hypocalcemia). Cytogenetic analysis may demonstrate deletions of a segment of chromosome band 22q11 (DiGeorge critical region). Ablation of cells of the neural crest has been shown to reproduce conotruncal malformations.

These abnormalities are associated with the DiGeorge syndrome and branchial arch abnormalities.

The hemodynamics of tetralogy of Fallot depend on the degree of right ventricular (RV) outflow tract obstruction (RVOTO). The ventricular septal defect (VSD) is usually nonrestrictive, and the RV and left ventricular (LV) pressures are equalized. If the obstruction is severe, the intracardiac shunt is from right to left, and pulmonary blood flow may be markedly diminished. In this instance, blood flow may depend on the patent ductus arteriosus (PDA) or bronchial collaterals.

PreviousNextEpidemiology

Tetralogy of Fallot (TOF) represents approximately 10% of cases of congenital heart disease (CHD), occurs in 3-6 infants for every 10,000 births, and is the most common cause of cyanotic CHD. This disorder accounts for one third of all CHD in patients younger than 15 years.

In most cases, tetralogy of Fallot is sporadic and nonfamilial. The incidence in siblings of affected parents is 1-5%, and it occurs more commonly in males than in females. The disorder is associated with extracardiac anomalies such as cleft lip and palate, hypospadias, and skeletal and craniofacial abnormalities. Genetic studies indicate that in some patients with tetralogy of Fallot, there may be 22q11.2 deletion and other submicroscopic copy number alterations.[8]

Tetralogy of Fallot is also observed in other mammals, including horses and rats.

PreviousNextPrognosis

Early surgery is not indicated for all infants with tetralogy of Fallot (TOF), although, without surgery, the natural progression of the disorder indicates a poor prognosis. The progression of the disorder depends on the severity of right ventricular (RV) outflow tract obstruction (RVOTO).

In the present era of cardiac surgery, children with simple forms of tetralogy of Fallot enjoy good long-term survival with an excellent quality of life. Late outcome data suggest that most survivors are in New York Heart Association (NYHA) classification I, although maximal exercise capability is reduced in some.

Sudden death from ventricular arrhythmias has been reported in 1-5% of patients at a later stage in life, and the cause remains unknown. It has been suspected that ventricular dysfunction may be the cause. One study found left ventricular longitudinal dysfunction to be associated with a greater risk of developing life-threatening arrhythmias.[9] Continued cardiac monitoring into adult life is necessary. For some time, it has been suspected that certain children may have inherited a predispostion to developing long QT syndrome. A 2012 study by Chiu confirmed this suspicion.[10]

If left untreated, patients with tetralogy of Fallot face additional risks that include paradoxical emboli leading to stroke, pulmonary embolus, and subacute bacterial endocarditis. It is well known that children with congenital heart disease are prone to stroke. In most of these children the causes of stroke have been related to thromboemboli, prolonged hypotension/anoxix and polycythemia. What is often forgotten is that residual shunts or a patent foramen ovale are also known causes of strokes. The investigation of strokes in these children usually begins with a CT scan of the brain followed by an ECHO.[11]

Without surgery, mortality rates gradually increase, ranging from 30% at age 2 years to 50% by age 6 years. The mortality rate is highest in the first year and then remains constant until the second decade. No more than 20% of patients can be expected to reach the age of 10 years, and fewer than 5-10% of patients are alive by the end of their second decade.

Most individuals who survive to age 30 years develop congestive heart failure (CHF), although individuals whose shunts produce minimal hemodynamic compromise have been noted, albeit rarely, and these individuals achieve a normal life span. However, cases of survival of patients into their 80s have been reported. Due to advanced surgical techniques, a 40% reduction in deaths associated with tetralogy of Fallot was noted from 1979 to 2005.[12]

As might be expected, individuals with tetralogy of Fallot and pulmonary atresia have the worst prognoses, and only 50% survive to age 1 year and 8% to age 10 years.

PreviousProceed to Clinical Presentation , Tetralogy of Fallot

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Sinus of Valsalva Aneurysm

Background

John Thurnam first described sinus of Valsalva aneurysm (SVA) in 1840. Hope further described it in 1939. SVA is usually referred to as a rare congenital anomaly. A congenital SVA is usually clinically silent but may vary from a mild, asymptomatic dilatation detected in routine 2-dimensional echocardiography to symptomatic presentations related to the compression of adjacent structures or intracardiac shunting caused by rupture of the SVA into the right side of the heart.[1] Approximately 65-85% of SVAs originate from the right sinus of Valsalva, while SVAs originating from noncoronary (10-30%) and left sinuses ([2]

NextPathophysiology

Congenital SVA is caused by a dilation, usually of a single sinus of Valsalva, from a separation between the aortic media and the annulus fibrosus. A deficiency of normal elastic tissue and abnormal development of the bulbus cordis have been associated with the development of SVA.[3] Other disease processes that involve the aortic root (eg, atherosclerotic aneurysms, syphilis, endocarditis, cystic medial necrosis, chest trauma) may also produce SVA, although this usually involves multiple sinuses. Rupture of the dilated sinus may lead to intracardiac shunting when a communication is established with the right atrium (Gerbode defect [10%]) or directly into the right ventricle (60-90%). Cardiac tamponade may occur if the rupture involves the pericardial space.[1]

PreviousNextEpidemiologyFrequencyUnited States

SVA was present in 0.09% of cadavers in a large autopsy series and ranged to 0.14-0.23% in a Western surgical series.[4] Two-dimensional echocardiography is likely to determine a higher incidence of SVA, although researchers note the incremental value of 3-dimensional echocardiography.[5]

International

SVA is more prevalent in Asian surgical series (0.46-3.5%) and correlates with more supracristal ventricular septal defects (~60%).[6]

Mortality/Morbidity

The true natural history of SVA is unclear. Clinical complications from SVA are often the initial presentation of SVA (see Complications).

Associated structural defects in congenital SVAs included supracristal or perimembranous ventricular septal defect (30-60%), bicuspid aortic valve (15-20%) and aortic regurgitation (44-50%). Approximately 10% of patients with Marfan syndrome have some form of SVA. Less commonly observed anomalies include pulmonary stenosis, coarctation, and atrial septal defects. Rupture of SVA (with progressive heart failure and left-to-right shunting or endocarditis) is the main cause of death and rarely occurs before age 20 years in congenital SVA. Race

Race differences in SVA are unclear, although a higher frequency was observed in the Asian surgical series.

Sex

Male-to-female ratio is 4:1, including frequencies of both ruptured and unruptured SVA.

AgeUnruptured SVA is usually asymptomatic and is often detected serendipitously by routine 2-dimensional echocardiography, even in patients older than 60 years. Most ruptured SVAs occur from puberty to age 30 years and are often diagnosed or presented clinically at this age.A retrospective review of an institutional database identified 86 patients who underwent SVA repair from 1956-2003 found the median age to be 45 years (range 5-80 y).[7] PreviousProceed to Clinical Presentation , Sinus of Valsalva Aneurysm

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Acute Coronary Syndrome

Practice Essentials

Acute coronary syndrome (ACS) refers to a spectrum of clinical presentations ranging from those for ST-segment elevation myocardial infarction (STEMI) to presentations found in non–ST-segment elevation myocardial infarction (NSTEMI) or in unstable angina. It is almost always associated with rupture of an atherosclerotic plaque and partial or complete thrombosis of the infarct-related artery.

Essential update: Discharge safe in suspected ACS if troponin and copeptin are negative

Patients with suspected ACS who test negative for troponin and copeptin can be safely discharged from the hospital without further testing, according to a recent study, the Biomarkers in Cardiology 8 (BiC-8) trial. Copeptin, a marker of severe hemodynamic stress, can be detected immediately in acute myocardial infarction.[1]

The study involved 902 patients at low to intermediate risk of ACS; half of the patients were treated with standard care, and the other 451 patients underwent a copeptin assay. In the latter group, patients with a positive copeptin test, defined as a level of 10 pmol/L or greater, were treated with standard ACS care, while patients with a copeptin level below 10 pmol/L were discharged into ambulant care, including an outpatient visit within 72 hours.

In the 451 patients tested for troponin and treated with standard care, the 30-day rate of major adverse cardiovascular events was 5.5%, compared with 5.46% in the 451 patients tested for troponin and copeptin, a statistically insignificant difference.

Signs and symptoms

Atherosclerosis is the primary cause of ACS, with most cases occurring from the disruption of a previously nonsevere lesion. Complaints reported by patients with ACS include the following:

PalpitationsPain, which is usually described as pressure, squeezing, or a burning sensation across the precordium and may radiate to the neck, shoulder, jaw, back, upper abdomen, or either arm Exertional dyspnea that resolves with pain or restDiaphoresis from sympathetic dischargeNausea from vagal stimulationDecreased exercise tolerance

Physical findings can range from normal to any of the following:

Hypotension: Indicates ventricular dysfunction due to myocardial ischemia, myocardial infarction (MI), or acute valvular dysfunctionHypertension: May precipitate angina or reflect elevated catecholamine levels due to anxiety or to exogenous sympathomimetic stimulation DiaphoresisPulmonary edema and other signs of left heart failureExtracardiac vascular diseaseJugular venous distentionCool, clammy skin and diaphoresis in patients with cardiogenic shockA third heart sound (S3) and, frequently, a fourth heart sound (S4)A systolic murmur related to dynamic obstruction of the left ventricular outflow tractRales on pulmonary examination (suggestive of left ventricular dysfunction or mitral regurgitation)

Potential complications include the following:

Ischemia: Pulmonary edemaMyocardial infarction: Rupture of the papillary muscle, left ventricular free wall, and ventricular septum

See Clinical Presentation for more detail.

Diagnosis

Guidelines for the management of non-ST-segment elevation ACS were released in 2011 by the European Society of Cardiology (ESC).[2] The guidelines include the use of the CRUSADE risk score (Can Rapid risk stratification of Unstable angina patients Suppress ADverse outcomes with Early implementation of the ACC/AHA guidelines).

In the emergency setting, electrocardiography (ECG) is the most important diagnostic test for angina. ECG changes that may be seen during anginal episodes include the following:

Transient ST-segment elevationsDynamic T-wave changes: Inversions, normalizations, or hyperacute changesST depressions: These may be junctional, downsloping, or horizontal

Laboratory studies that may be helpful include the following:

Creatine kinase isoenzyme MB (CK-MB) levelsCardiac troponin levelsMyoglobin levelsComplete blood countBasic metabolic panel

Diagnostic imaging modalities that may be useful include the following:

Chest radiographyEchocardiographyMyocardial perfusion imagingCardiac angiographyComputed tomography, including CT coronary angiography and CT coronary artery calcium scoring

See Workup for more detail.

Management

Initial therapy focuses on the following:

Stabilizing the patient’s conditionRelieving ischemic painProviding antithrombotic therapy

Pharmacologic anti-ischemic therapy includes the following:

Nitrates (for symptomatic relief)Beta blockers (eg, metoprolol): These are indicated in all patients unless contraindicated

Pharmacologic antithrombotic therapy includes the following:

AspirinClopidogrelPrasugrelTicagrelorGlycoprotein IIb/IIIa receptor antagonists (abciximab, eptifibatide, tirofiban)

Pharmacologic anticoagulant therapy includes the following:

Unfractionated heparin (UFH)Low-molecular-weight heparin (LMWH; dalteparin, nadroparin, enoxaparin)Factor Xa inhibitors (rivaroxaban, fondaparinux)

Additional therapeutic measures that may be indicated include the following:

ThrombolysisPercutaneous coronary intervention (preferred treatment for ST-elevation MI)

Current guidelines for patients with moderate- or high-risk ACS include the following:

Early invasive approachConcomitant antithrombotic therapy, including aspirin and clopidogrel, as well as UFH or LMWH

See Treatment and Medication for more detail.

Image libraryA 62-year-old woman with a history of chronic stable angina and a "valve problem" presents with new chest pain. She is symptomatic on arrival, complaining of shortness of breath and precordial chest tightness. Her initial vital signs are blood pressure = 140/90 mm Hg and heart rate = 98. Her electrocardiogram (ECG) is as shown. She is given nitroglycerin sublingually, and her pressure decreases to 80/palpation. Right ventricular ischemia should be considered in this patient. NextBackground

Acute coronary syndrome (ACS) refers to a spectrum of clinical presentations ranging from those for ST-segment elevation myocardial infarction (STEMI) to presentations found in non–ST-segment elevation myocardial infarction (NSTEMI) or in unstable angina. In terms of pathology, ACS is almost always associated with rupture of an atherosclerotic plaque and partial or complete thrombosis of the infarct-related artery. (See Etiology.)

In some instances, however, stable coronary artery disease (CAD) may result in ACS in the absence of plaque rupture and thrombosis, when physiologic stress (eg, trauma, blood loss, anemia, infection, tachyarrhythmia) increases demands on the heart. The diagnosis of acute myocardial infarction in this setting requires a finding of the typical rise and fall of biochemical markers of myocardial necrosis in addition to at least 1 of the following[3] (See Workup.):

Ischemic symptomsDevelopment of pathologic Q wavesIschemic ST-segment changes on electrocardiogram (ECG) or in the setting of a coronary intervention

The terms transmural and nontransmural (subendocardial) myocardial infarction are no longer used because ECG findings in patients with this condition are not closely correlated with pathologic changes in the myocardium. Therefore, a transmural infarct may occur in the absence of Q waves on ECGs, and many Q-wave myocardial infarctions may be subendocardial, as noted on pathologic examination. Because elevation of the ST segment during ACS is correlated with coronary occlusion and because it affects the choice of therapy (urgent reperfusion therapy), ACS-related myocardial infarction should be designated STEMI or NSTEMI. (See Workup.)

Attention to the underlying mechanisms of ischemia is important when managing ACS. A simple predictor of demand is rate-pressure product, which can be lowered by beta blockers (eg, metoprolol or atenolol) and pain/stress relievers (eg, morphine), while supply may be improved by oxygen, adequate hematocrit, blood thinners (eg, heparin, IIb/IIIa agents such as abciximab, eptifibatide, tirofiban, or thrombolytics), and/or vasodilators (eg, nitrates, amlodipine). (See Medications.)

In 2010, the American Heart Association (AHA) published new guideline recommendations for the diagnosis and treatment of ACS.[4]

PreviousNextEtiology

Acute coronary syndrome (ACS) is caused primarily by atherosclerosis. Most cases of ACS occur from disruption of a previously nonsevere lesion (an atherosclerotic lesion that was previously hemodynamically insignificant yet vulnerable to rupture). The vulnerable plaque is typified by a large lipid pool, numerous inflammatory cells, and a thin, fibrous cap.

Elevated demand can produce ACS in the presence of a high-grade fixed coronary obstruction, due to increased myocardial oxygen and nutrition requirements, such as those resulting from exertion, emotional stress, or physiologic stress (eg, from dehydration, blood loss, hypotension, infection, thyrotoxicosis, or surgery).

ACS without elevation in demand requires a new impairment in supply, typically due to thrombosis and/or plaque hemorrhage.

The major trigger for coronary thrombosis is considered to be plaque rupture caused by the dissolution of the fibrous cap, the dissolution itself being the result of the release of metalloproteinases (collagenases) from activated inflammatory cells. This event is followed by platelet activation and aggregation, activation of the coagulation pathway, and vasoconstriction. This process culminates in coronary intraluminal thrombosis and variable degrees of vascular occlusion. Distal embolization may occur. The severity and duration of coronary arterial obstruction, the volume of myocardium affected, the level of demand on the heart, and the ability of the rest of the heart to compensate are major determinants of a patient's clinical presentation and outcome. (Anemia and hypoxemia can precipitate myocardial ischemia in the absence of severe reduction in coronary artery blood flow.)

A syndrome consisting of chest pain, ischemic ST-segment and T-wave changes, elevated levels of biomarkers of myocyte injury, and transient left ventricular apical ballooning (takotsubo syndrome) has been shown to occur in the absence of clinical CAD, after emotional or physical stress. The etiology of this syndrome is not well understood but is thought to relate to a surge of catechol stress hormones and/or high sensitivity to those hormones.

PreviousNextPrognosis

Six-month mortality rates in the Global Registry of Acute Coronary Events (GRACE) were 13% for patients with NSTEMI ACS and 8% for those with unstable angina.

An elevated level of troponin (a type of regulatory protein found in skeletal and cardiac muscle) permits risk stratification of patients with ACS and identifies patients at high risk for adverse cardiac events (ie, myocardial infarction, death) up to 6 months after the index event.[5, 6] (See Workup.)

The PROVE IT-TIMI trial found that after ACS, a J-shaped or U-shaped curve association is observed between BP and the risk of future cardiovascular events.[7]

LeLeiko et al determined that serum choline and free F(2)-isoprostane are also predictors of cardiac events in ACS. The authors evaluated the prognostic value of vascular inflammation and oxidative stress biomarkers in patients with ACS to determine their role in predicting 30-day clinical outcomes. Serum F(2)-isoprostane had an optimal cutoff level of 124.5 pg/mL, and serum choline had a cutoff level of 30.5 µmol/L. Choline and F(2)-isoprostane had a positive predictive value of 44% and 57% and a negative predictive value of 89% and 90%, respectively.[8]

Testosterone deficiency is common in patients with coronary disease and has a significant negative impact on mortality. Further study is needed to assess the effect of treatment on survival.[9]

A study by Sanchis et al suggests renal dysfunction, dementia, peripheral artery disease, previous heart failure, and previous myocardial infarction are the comorbid conditions that predict mortality in NSTEMI ACS.[10] In patients with comorbid conditions, the highest risk period was in the first weeks after NSTEMI ACS. In-hospital management of patients with comorbid conditions merits further investigation.

Patients with end-stage renal disease often develop ACS, and little is known about the natural history of ACS in patients receiving dialysis. Gurm et al examined the presentation, management, and outcomes of patients with ACS who received dialysis before presentation for an ACS. These patients were enrolled in the Global Registry of Acute Coronary Events (GRACE) at 123 hospitals in 14 countries from 1999-2007.

NSTEMI ACS was the most common in patients receiving dialysis, occurring in 50% of patients (290 of 579) versus 33% (17,955 of 54,610) of those not receiving dialysis The in-hospital mortality rates were higher among patients receiving dialysis (12% vs 4.8%; p [11]

In a study that assessed the impact of prehospital time on STEMI outcome, Chughatai et al suggest that “total time to treatment” should be used as a core measure instead of “door-to-balloon time.”[12] This is because on-scene time was the biggest fraction of "pre-hospital time.” The study compared groups with total time to treatment of more than 120 minutes compared with 120 minutes or less and found mortalities were 4 compared with 0 and transfers to a tertiary care facility were 3 compared with 1, respectively.

PreviousNextPatient Education

Patient education of risk factors is important, but more attention is needed regarding delays in door-to-balloon time, and one major barrier to improving this delay is patient education regarding his or her symptoms. Lack of recognition of symptoms may cause tremendous delays in seeking medical attention.

Educate patients about the dangers of cigarette smoking, a major risk factor for coronary artery disease (CAD). The risk of recurrent coronary events decreases 50% at 1 year after smoking cessation. Provide all patients who smoke with guidance, education, and support to avoid smoking. Smoking-cessation classes should be offered to help patients avoid smoking after a myocardial infarction. Bupropion increases the likelihood of successful smoking cessation.

Diet plays an important role in the development of CAD. Therefore, prior to hospital discharge, a patient who has had a myocardial infarction should be evaluated by a dietitian. Patients should be informed about the benefits of a low-cholesterol, low-salt diet. In addition, educate patients about AHA dietary guidelines regarding a low-fat, low-cholesterol diet.

A cardiac rehabilitation program after discharge may reinforce education and enhance compliance.

The following mnemonic may useful in educating patients with CAD regarding treatments and lifestyle changes necessitated by their condition:

A = Aspirin and antianginalsB = Beta blockers and blood pressure (BP)C = Cholesterol and cigarettesD = Diet and diabetesE = Exercise and education

For patients being discharged home, emphasize the following:

Timely follow-up with primary care providerCompliance with discharge medications, specifically aspirin and other medications used to control symptomsNeed to return to the ED for any change in frequency or severity of symptomsPreviousProceed to Clinical Presentation , Acute Coronary Syndrome

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Endocardial Cushion Defects

Background

Endocardial cushion defects, more commonly known as atrioventricular (AV) canal or septal defects, include a range of defects characterized by involvement of the atrial septum, the ventricular septum, and one or both of the AV valves.

These defects can be classified by several methods. A distinction generally is made between partial and complete defects. A complete AV septal defect indicates the presence of both atrial and ventricular septal defects with a common AV valve (see image below). A partial defect indicates atrial septal involvement with separate mitral and tricuspid valve orifices.

Anatomy of the endocardial cushion defect (ie, complete form); note the common atrioventricular valve straddling the atrial septal and ventricular septal defects.

AV canal defects arise from abnormal development of the endocardial cushions. In these patients, the superior and inferior cushions do not close completely. An interatrial communication is left at the lower portion of the atrial septum. This is called an ostium primum defect. The failure of the endocardial cushions to fuse results in an abnormally low position of the AV valves and an abnormally high position of the aortic valve. A portion of the AV valves originates from the endocardial cushions, and their improper fusion results in anterior and posterior components to the mitral valve leaflet.[1]

NextPathophysiology

Predominant left-to-right shunting of blood through the heart occurs in these patients. In patients with partial defects, this occurs through the ostium primum atrial septal defect. When a complete endocardial cushion defect is present, a large ventricular septal defect as well as valvular insufficiency may develop, resulting in volume overload of both the left and right ventricles associated with heart failure in early life. In patients with long-standing pulmonary overload, pulmonary vascular disease may develop and congestive heart failure (CHF) symptoms may improve. This improvement is a poor prognostic indicator because it heralds the development of right-to-left shunting and irreversible pulmonary hypertension (ie, Eisenmenger syndrome).[2]

PreviousNextEpidemiologyFrequencyUnited States

The frequency rate is about 3% of children with congenital heart disease. Sixty to seventy percent of these defects are of the complete form. More than half of those affected with the complete form have Down syndrome.

International

The frequency rate is about 3% of children who have congenital heart disease.

Mortality/Morbidity

Patients with only ostium primum atrial septal defect and minimal insufficiency of the left AV valve (ie, mitral valve) do well without treatment during infancy, childhood, and adolescence. During adulthood, these patients develop symptoms of CHF and atrial arrhythmia.

Patients with septal defects and mitral valve insufficiency develop CHF early in life, with high rates of morbidity and mortality if the valvular insufficiency is pronounced. Patients with a complete defect develop CHF in infancy, with frequent respiratory infections and poor weight gain.

Race

No racial predilection is apparent.

Sex

Girls are affected slightly more frequently than boys.

Age

Endocardial cushion defect is a congenital defect present at birth. The severity of the symptom complex and presentation is dependent directly upon the severity of the defect and the presence of mitral insufficiency.

PreviousProceed to Clinical Presentation , Endocardial Cushion Defects

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Complications of Myocardial Infarction

Overview of MI Complications

Myocardial infarction (MI) due to coronary artery disease is a leading cause of death in the United States, where more than 1 million people have acute myocardial infarctions (AMIs) each year.[1]

The advent of coronary care units and early reperfusion therapy (lytic or percutaneous coronary intervention) has substantially decreased in-hospital mortality rates and has improved the outcome in survivors of the acute phase of MI.

Complications of MI include arrhythmic, mechanical, and inflammatory (early pericarditis and post-MI syndrome) sequelae, as well as left ventricular mural thrombus (LVMT). In addition to these broad categories, right ventricular (RV) infarction and cardiogenic shock are other possible complications of acute MI. (See the image below.)

Modified 2-dimensional (top) echocardiogram and color flow Doppler image (bottom). Apical 4-chamber views show a breach in the interventricular septum and free communication between ventricles through a large apical septum ventricular septal defect in a patient who recently had an anterior myocardial infarction.

For other discussions on myocardial infarction, see the overview topics Myocardial Infarction and Right Ventricular Infarction, as well as the articles Imaging of Acute Myocardial Infarcts and Use of Cardiac Markers in the Emergency Department.

NextArrhythmic Complications of MI

About 90% of patients who have an acute myocardial infarction (AMI) develop some form of cardiac arrhythmia during or immediately after the event. In 25% of patients, such rhythm abnormalities manifest within the first 24 hours. In this group of patients, the risk of serious arrhythmias, such as ventricular fibrillation, is greatest in the first hour and declines thereafter. The incidence of arrhythmia is higher with an ST-elevation myocardial infarction (STEMI) and lower with a non–ST-elevation myocardial infarction (NSTEMI).[2]

The clinician must be aware of these arrhythmias, in addition to reperfusion strategies, and must treat those that require intervention to avoid exacerbation of ischemia and subsequent hemodynamic compromise. Most peri-infarct arrhythmias are benign and self-limited. However, those that result in hypotension, increase myocardial oxygen requirements, and/or predispose the patient to develop additional malignant ventricular arrhythmias should be aggressively monitored and treated.

Pathophysiology of arrhythmic complications

AMI is characterized by generalized autonomic dysfunction that results in enhanced automaticity of the myocardium and conduction system. Electrolyte imbalances (eg, hypokalemia and hypomagnesemia) and hypoxia further contribute to the development of cardiac arrhythmia. The damaged myocardium acts as substrate for re-entrant circuits, due to changes in tissue refractoriness.

Enhanced efferent sympathetic activity, increased concentrations of circulating catecholamines, and local release of catecholamines from nerve endings in the heart muscle itself have been proposed to play roles in the development of peri-infarction arrhythmias. Furthermore, transmural infarction can interrupt afferent and efferent limbs of the sympathetic nervous system that innervates myocardium distal to the area of infarction. The net result of this autonomic imbalance is the promotion of arrhythmias.

Classification of peri-infarction arrhythmias

Peri-infarction arrhythmias can be broadly classified into the following categories:

Supraventricular tachyarrhythmias, including sinus tachycardia, premature atrial contractions, paroxysmal supraventricular tachycardia, atrial flutter, and atrial fibrillationAccelerated junctional rhythmsBradyarrhythmias, including sinus bradycardia and junctional bradycardiaAtrioventricular (AV) blocks, including first-degree AV block, second-degree AV block, and third-degree AV blockIntraventricular blocks, including left anterior fascicular block, right bundle branch block (RBBB), and left bundle branch block (LBBB)Ventricular arrhythmias, including premature ventricular contractions (PVCs), accelerated idioventricular rhythm, ventricular tachycardia, and ventricular fibrillationReperfusion arrhythmiasPreviousNextArrhythmic Complications: Supraventricular Tachyarrhythmias

Sinus tachycardia is associated with enhanced sympathetic activity and can result in transient hypertension or hypotension. The elevated heart rate increases myocardial oxygen demand, and a decreased length of diastole compromises coronary flow, worsening myocardial ischemia.

Causes of persistent sinus tachycardia include the following:

Pain AnxietyHeart failureHypovolemiaHypoxiaAnemiaPericarditisPulmonary embolism

In the setting of an AMI, sinus tachycardia must be identified, and appropriate treatment strategies must be devised. Treatment strategies include adequate pain medication, diuresis to manage heart failure, oxygenation, volume repletion for hypovolemia, administration of anti-inflammatory agents to treat pericarditis, and use of beta-blockers and/or nitroglycerin to relieve ischemia.

Premature atrial contractions

Premature atrial contractions often occur before the development of paroxysmal supraventricular tachycardia, atrial flutter, or atrial fibrillation. The usual cause of these extra impulses is atrial distention due to increased left ventricular (LV) diastolic pressure or inflammation associated with pericarditis.

No specific therapy is indicated. However, attention should be given to identifying the underlying disease process, particularly occult heart failure.

Paroxysmal supraventricular tachycardia

The incidence of a paroxysmal supraventricular tachycardia in the setting of an AMI is less than 10%. In the absence of definitive data in the patient with AMI, the consensus is that adenosine can be used when hypotension is not present. In patients without clinically significant LV failure, intravenous diltiazem or a beta-blocker can be used instead. In patients who develop severe heart failure or hypotension, synchronized electrical cardioversion is required.

Atrial flutter

Atrial flutter occurs in less than 5% of patients with AMI. Atrial flutter is usually transient and results from sympathetic overstimulation of the atria.

Treatment strategies for persistent atrial flutter are similar to those for atrial fibrillation, except that ventricular-rate control with drugs is less easily accomplished with atrial flutter than with atrial fibrillation. Therefore, synchronized electrical cardioversion (beginning with 50 J, or the biphasic equivalent) may be needed relatively promptly because of a decrease coronary blood flow and/or hemodynamic compromise. For patients whose atrial flutter is refractory to medical therapy, overdrive atrial pacing may be considered.

Atrial fibrillation

The rate of atrial fibrillation is 10-15% among patients who have AMIs. The onset of atrial fibrillation in the first hours of AMI is usually caused by LV failure, ischemic injury to the atria, or RV infarction. Pericarditis and all conditions leading to elevated left atrial pressure can also lead to atrial fibrillation in association with an AMI. The presence of atrial fibrillation during an AMI is associated with an increased risk of mortality and stroke, particularly in patients who have anterior-wall MIs.

Immediate electrical cardioversion is indicated for the patient in unstable condition, such as one with new or worsening ischemic pain and/or hypotension. Synchronized electrical cardioversion to treat atrial fibrillation begins with 200 J (or the biphasic equivalent). Conscious sedation (preferred) or general anesthesia is advisable prior to cardioversion.

For patients in stable condition, controlling the ventricular response is the immediate objective. If the atrial fibrillation does not respond to cardioversion, IV amiodarone[3] or IV digoxin (in patients with LV dysfunction or heart failure) can be used to achieve ventricular rate control.

For patients who do not develop hypotension, a beta-blocker can be used. For example, metoprolol may be given in 5-mg intravenous boluses every 5-10 min, with a maximum dose of 15 mg. Intravenous diltiazem is an alternative for slowing the ventricular rate, but it should be used with caution in patients with moderate-to-severe heart failure. In patients with new-onset sustained tachycardia (absent before MI), conversion to sinus rhythm should be considered as an option.

Atrial fibrillation and atrial flutter confer an increased risk of thromboembolism (see Deep Venous Thrombosis and Pulmonary Embolism). Therefore, anticoagulation with either unfractionated heparin or low molecular weight heparin (LMWH) should be started if contraindications are absent. It is unclear whether anticoagulation is needed in cases of transient atrial fibrillation and how long after the onset of atrial fibrillation should the anticoagulation be started.

PreviousNextArrhythmic Complications: Accelerated Junctional Rhythm

An accelerated junctional rhythm results from increased automaticity of the junctional tissue that leads to a heart rate of 70-130 bpm. This type of dysrhythmia is most common in patients who develop inferior myocardial infarctions. Treatment is directed at correcting the underlying ischemia.

PreviousNextArrhythmic Complications: BradyarrhythmiasSinus bradycardia

Sinus bradycardia is a common arrhythmia in patients with inferior or posterior acute myocardial infarctions (AMIs). The highest incidence, 40%, is observed in the first 1-2 hours after AMI.

The likely mechanism leading to bradycardia and hypotension is stimulation of cardiac vagal afferent receptors that result in efferent cholinergic stimulation of the heart. In the early phases of an AMI, resultant sinus bradycardia may actually be protective, reducing myocardial oxygen demand. Clinically significant bradycardia that decreases cardiac output and hypotension may result in ventricular arrhythmias and should, therefore, be treated aggressively. Isolated sinus bradycardia is not associated with an increase in the acute mortality risk, and therapy is typically unnecessary when the patient has no adverse signs or symptoms.

When emergency therapy is indicated (eg, in a patient with a sinus rate of

When atropine is ineffective and the patient is symptomatic or hypotensive, transcutaneous or transvenous pacing is indicated (see our main article on External Pacemakers). Denervate, transplanted hearts do not respond to atropine and, therefore, require cardiac pacing.

If these interventions fail, additional pharmacologic intervention may be useful. Examples are dopamine 5-20 mcg/kg/min given intravenously, epinephrine 2-10 mcg/min, and/or dobutamine.

Junctional bradycardia

Junctional bradycardia is a protective AV junctional escape rhythm at a rate of 35-60 bpm in patients who have an inferior MI. This arrhythmia is not usually associated with hemodynamic compromise, and treatment is typically not required.

PreviousNextArrhythmic Complications: AV and Intraventricular BlocksFirst-degree AV block

First-degree AV block is characterized by prolongation of the PR interval to longer than 0.20 seconds. This type of block occurs in approximately 15% of patients who have an acute myocardial infarction (AMI), most commonly an inferior infarction. Almost all patients who develop first-degree AV block have conduction disturbances above the His bundle. In these patients, the progression to complete heart block or ventricular asystole is rare. No specific therapy is indicated unless associated hemodynamic compromise is present.

Calcium channel blockers and beta-blockers may cause or exacerbate a first-degree AV block, but they should be stopped only if hemodynamic impairment or a higher-degree block occurs. For a first-degree AV block associated with sinus bradycardia and hypotension, atropine should be administered. Continued cardiac monitoring is advisable in view of possible progression to higher degrees of block.

Second-degree AV block

Mobitz type I, or Wenckebach, AV block occurs in approximately 10% of patients who have an AMI and accounts for 90% of all patients who have an AMI and a second-degree AV block. A second-degree AV block is associated with a narrow QRS complex and is most commonly associated with an inferior MI. It does not affect the patient's overall prognosis.

A Mobitz type I block does not necessarily require treatment. If the heart rate is inadequate for perfusion, immediate treatment with atropine 0.5-1 mg administered intravenously is indicated. Transcutaneous or temporary transvenous pacing is rarely required.

A Mobitz type II AV block accounts for 10% of all second-degree AV blocks (overall rate of

Mobitz type II AV blocks are associated with a poor prognosis, as the mortality rate associated with their progression to a complete heart block is approximately 80%. Therefore, this type of second-degree AV block should be immediately treated with transcutaneous pacing or atropine. Atropine helps in about 50% of cases, but it occasionally worsens the block with an increased heart rate. A temporary transvenous pacemaker, and possibly a permanent demand pacemaker, must ultimately be placed.

Third-degree AV block

A third-degree AV block (ie, a complete heart block), occurs in 5-15% of patients who have an AMI and may occur with anterior or inferior infarctions. In patients with inferior infarctions, this type of block usually develops gradually, progressing from first-degree or a type I second-degree block. In most patients, the level of the block is supranodal or intranodal, and the escape rhythm is usually stable with a narrow QRS and rates exceeding 40 bpm. In 30% of patients, the block is below the His bundle, where it results in an escape rhythm with a rate slower than 40 bpm and a wide QRS complex.

Complete heart block in patients with an inferior MI usually responds to atropine. In most patients, it resolves within a few days without the need for a temporary or permanent pacemaker. The mortality rate for patients with inferior MI who develop complete heart block is approximately 15% unless a coexisting RV infarction is present, in which case the mortality rate is higher.

Immediate treatment with atropine is indicated for patients with third-degree AV blocks. As with therapy for a Mobitz type II block, this treatment may not help and may sometimes worsen the block. Temporary transcutaneous or transvenous pacing is indicated for symptomatic patients whose condition is unresponsive to atropine. Permanent pacing should be considered in patients with persistent symptomatic bradycardia that remains unresolved with lysis or percutaneous coronary intervention.

In patients with an anterior MI, an intraventricular block or a Mobitz type II AV block usually precedes a third-degree AV block. The third-degree block occurs suddenly and is associated with a high mortality rate. The Cardiac Arrhythmias and Risk Stratification After Myocardial Infarction (CARISMA) trial monitored patients with acute myocardial infarction and reduced left ventricular ejection fraction and found that high-degree atrioventricular block was the most powerful predictor of cardiac death.[4] Patients with these blocks typically have unstable escape rhythms with wide QRS complexes and at rates of less than 40 bpm.

Immediate treatment with atropine and/or transcutaneous pacing is indicated. This is followed by temporary transvenous pacing. Patients with an anterior MI who develop a third-degree AV block and who survive to hospitalization often receive a permanent pacemaker.

Intraventricular blocks

Conduction from the His bundle is transmitted through 3 fascicles: the anterior division of the left bundle, the posterior division of the left bundle, and the right bundle. An abnormality of electrical conduction in 1 or more of these fascicles is noted in about 15% of patients with AMI. Isolated left anterior fascicular block (LAFB) occurs in 3-5% of patients with AMI; progression to complete AV block is uncommon. Isolated left posterior fascicular block occurs in only 1-2% of patients who have an AMI. The blood supply of the posterior fascicle is larger than that of the anterior fascicle; therefore, a block here is associated with a relatively large infarct and high mortality rate.

The right bundle branch receives its dominant blood supply from the left anterior descending (LAD) artery. Therefore, a new RBBB, which is seen in approximately 2% of patients with AMI, suggests a large infarct territory. However, progression to complete heart block is uncommon. In patients who develop an anterior MI and a new RBBB, the substantial risk for death is mostly from cardiogenic shock, which is presumably due to the large size of the myocardial infarct.

The combination of RBBB with an LAFB is known as bifascicular block and commonly occurs with occlusion of the proximal LAD coronary artery. The risk of developing complete AV block is heightened, but complete block is still uncommon. Mortality is mostly related to the amount of muscle loss. Bifascicular block in the presence of first-degree AV block is called a trifascicular block. In 40% of patients, a trifascicular block progresses to a complete heart block.

PreviousNextArrhythmic Complications: Ventricular ArrhythmiasPremature ventricular contractions

In the past, frequent premature ventricular contractions (PVCs) were considered to represent warning arrhythmias and indicators of impending malignant ventricular arrhythmias. However, presumed warning arrhythmias are frequently observed in patients who have an acute myocardial infarction (AMI) and who never develop ventricular fibrillation. On the converse, primary ventricular fibrillation often occurs without antecedent premature ventricular ectopy.

For these reasons, prophylactic suppression of PVCs with antiarrhythmic drugs, such as lidocaine, is no longer recommended. Prophylaxis has been associated with an increased risk of fatal bradycardia or asystole because of the suppression of escape pacemakers.

Given this evidence, most clinicians pursue a conservative course when PVCs are observed in a patient with an AMI, and they do not routinely administer prophylactic antiarrhythmics. Instead, attention should be directed toward correcting any electrolytic or metabolic abnormalities, plus identifying and treating recurrent ischemia.

Accelerated idioventricular rhythm

An accelerated idioventricular rhythm is seen in as many as 20% of patients who have an AMI. This pattern is defined as a ventricular rhythm characterized by a wide QRS complex with a regular escape rate faster than the atrial rate, but less than 100 bpm. AV dissociation is frequent. Slow, nonconducted P waves are seen; these are unrelated to the fast, wide QRS rhythm.

Most episodes are short and terminate spontaneously. They occur with equal frequency in anterior and inferior infarctions. The mechanism might involve (1) the sinoatrial node or the AV node, which may sustain structural damage and depress nodal automaticity, and/or (2) an abnormal ectopic focus in the ventricle that takes over as the dominant pacemaker.

The presence of accelerated idioventricular rhythm does not affect the patient's prognosis; no definitive evidence has shown that an untreated occurrence increases the incidence of ventricular fibrillation or death. This rhythm occurs somewhat more frequently in patients who develop early reperfusion than in others; however, it is neither sensitive nor specific as a marker of reperfusion.

Temporary pacing is not indicated unless the rhythm is sustained and results in hypotension or ischemic symptoms. An accelerated idioventricular rhythm represents an appropriate escape rhythm. Suppression of this escape rhythm with an antiarrhythmic drug can result in clinically significant bradycardia or asystole. Therefore, an accelerated idioventricular rhythm should be left untreated.

Nonsustained ventricular tachycardia

Nonsustained ventricular tachycardia is defined as 3 or more consecutive ventricular ectopic beats at a rate of greater than 100 bpm and lasting less than 30 seconds. In patients who experience multiple runs of nonsustained ventricular tachycardia, the risk for sudden hemodynamic collapse may be substantial.

Nonetheless, nonsustained ventricular tachycardia in the immediate peri-infarction period does not appear to be associated with an increased mortality risk, and no evidence suggests that antiarrhythmic treatment offers a morbidity or mortality benefit. However, nonsustained ventricular tachycardia occurring more than 48 hours after infarction in patients with LV systolic dysfunction (LV ejection fraction

Multiple episodes of nonsustained ventricular tachycardia require intensified monitoring and attention to electrolyte imbalances. Serum potassium levels should be maintained above 4.5 mEq/L, and serum magnesium levels should be kept above 2.0 mEq/L. Ongoing ischemia should aggressively be sought and corrected if found.

Sustained ventricular tachycardia

Sustained ventricular tachycardia is defined as 3 or more consecutive ventricular ectopic beats at a rate greater than 100 bpm and lasting longer than 30 seconds or causing hemodynamic compromise that requires intervention. Monomorphic ventricular tachycardia is most likely to be caused by a myocardial scar, whereas polymorphic ventricular tachycardia may be most responsive to measures directed against ischemia. Sustained polymorphic ventricular tachycardia after an AMI is associated with a hospital mortality rate of 20%.

Emergency treatment of sustained ventricular tachycardia is mandatory because of its hemodynamic effects and because it frequently deteriorates into ventricular fibrillation. Rapid polymorphic ventricular tachycardia (rate >150 bpm) associated with hemodynamic instability should be treated with immediate direct-current unsynchronized cardioversion of 200 J (or biphasic energy equivalent). Monomorphic ventricular tachycardia should be treated with a synchronized discharge of 100 J (or biphasic energy equivalent).

If sustained ventricular tachycardia is well tolerated, antiarrhythmic therapy with amiodarone (drug of choice) or procainamide may be attempted before electrical cardioversion. Precipitating causes, such as electrolyte abnormalities, acid-base disturbances, hypoxia, or medication, should be sought and corrected. For persistent or recurrent ventricular tachycardia, overdrive pacing may be effective in electrically converting the patient's rhythm to a sinus rhythm.

Ventricular fibrillation

The incidence of primary ventricular fibrillation is greatest in the first hour after the onset of infarct (4.5%) and declines rapidly thereafter. Approximately 60% of episodes occur within 4 hours, and 80% occur within 12 hours.

Secondary or late ventricular fibrillation occurring more than 48 hours after an MI is usually associated with pump failure and cardiogenic shock. Factors associated with an increased risk of secondary ventricular fibrillation are a large infarct, an intraventricular conduction delay, and an anteroseptal AMI. Secondary ventricular fibrillation in conjunction with cardiogenic shock is associated with an in-hospital mortality rate of 40-60%.

Treatment for ventricular fibrillation is unsynchronized electrical countershock with at least 200-300 J (or biphasic energy equivalent) administered as rapidly as possible. Each minute after the onset of uncorrected ventricular fibrillation is associated a 10% decrease in the likelihood of survival. Restoration of synchronous cardiac electrical activity without the return of effective contraction (ie, electromechanical dissociation, or pulseless electrical activity) is generally due to extensive myocardial ischemia and/or necrosis or cardiac rupture.

Antiarrhythmics, such as intravenous amiodarone and lidocaine, facilitate successful electrical defibrillation and help prevent recurrent or refractory episodes. After ventricular fibrillation is successfully converted, antiarrhythmic therapy is generally continued as a constant intravenous infusion for 12-24 hours.

Prophylactic lidocaine reduces the incidence of ventricular fibrillation, but it is not used because it seems to be associated with an excessive mortality risk owing to bradycardic and asystolic events[5] . On the other hand, early use of beta-blockers in patients with AMI reduces the incidence of ventricular fibrillation as well as death[6] .

PreviousNextArrhythmic Complications: Reperfusion Arrhythmias

In the past, the sudden onset of rhythm disturbances after thrombolytic therapy in patients with AMI was believed to be a marker of successful coronary reperfusion. However, a high incidence of identical rhythm disturbances is observed in patients with AMI in whom coronary reperfusion is unsuccessful. Therefore, these so-called reperfusion arrhythmias are neither sensitive nor specific for reperfusion and should be treated as discussed under Accelerated Idioventricular Rhythm in the Arrhythmic Complications: Ventricular Arrhythmias section above.

PreviousNextMechanical Complications of MI

The 3 major mechanical complications of AMI are ventricular free wall rupture (VFWR), ventricular septal rupture (VSR), and papillary muscle rupture with severe mitral regurgitation (MR). Each of these complications can result in cardiogenic shock. Clinical issues related to these mechanical problems are discussed below. (See also Myocardial Rupture.)

Overview of ventricular free wall rupture

VFWR is the most serious complication of AMI. VFWR is usually associated with large transmural infarctions and antecedent infarct expansion. It is the most common cause of death, second only to LV failure, and it accounts for 15-30% of the deaths associated with AMI. Incontrovertibly the most catastrophic of mechanical complications, VFWR leads to acute hemopericardium and death from cardiac tamponade.

The overall incidence of VFWR ranges from 0.8-6.2%. The incidence of this complication has declined over the years with better 24 hour systolic blood pressure control; increased use of reperfusion therapy, beta blockers, and ACE inhibitors; and decreased use of heparin[7] .

Data from the National Registry of Myocardial Infarction (NRMI) showed an elevated incidence of in-hospital mortality among patients who received thrombolytic therapy (12.1%) than among patients who did not (6.1%).[8] In the Thrombolysis in Myocardial Infarction Phase II (TIMI II) trial, 16% of patients died from cardiac rupture within 18 hours of therapy.[9] Patients who underwent percutaneous transluminal coronary angioplasty (PTCA) had an incidence of free wall rupture lower than that of patients receiving thrombolytic therapy.

Risk factors for VFWR include advanced age greater than 70 years, female sex, no previous MIs, Q waves on ECG, hypertension during the initial phase of STEMI, corticosteroid or NSAID use, and fibrinolytic therapy more than 14 hours after STEMI onset. Patients with a history of angina pectoris, previous AMI, multivessel coronary disease, and chronic heart failure are less likely than others to develop VFWR of the LV because they develop collaterals and ischemic preconditioning.[8, 10, 11]

Clinical presentation of VFWR

VFWRs are dramatic; they present acutely or occasionally subacutely as pseudoaneurysms; and they most often involve the anterior or lateral wall of the LV. Most VFWRs occur within the first week after AMI.

Becker et al classified the following 3 types of VFWRs[12] :

Type I - an abrupt slitlike tear that is frequently associated with anterior infarcts and that occurs early (within 24 h)Type II - an erosion of infarcted myocardium at the border between the infarcted and viable myocardiumType III - an early aneurysm formation correlated with older and severely expanded infarcts

Type III usually occurs later than type I or type II ruptures. Thrombolytic therapy accelerates the occurrence of cardiac rupture in Becker type I and type II VFWRs. In severely expanded infarctions (type III), thrombolytic therapy decreases the incidence of cardiac rupture.

A pseudoaneurysm is formed when adjacent pericardium and hematoma seals off a myocardial rupture or perforation. The wall of a pseudoaneurysm is most often visualized as an aneurysmal outpouching that communicates with the LV cavity by means of a narrow neck. This wall is composed of pericardium and organized thrombus and/or hematoma. It is devoid of myocardial elements, whereas a true aneurysm has all the elements of the original myocardial wall and a relatively wide base. The pseudoaneurysm may vary in size and is at high risk of rupturing.

Clinical presentations of VFWR vary depending on the acuity, location, and size of the rupture. Patients with acute VFWR present with severe chest pain, abrupt electromechanical dissociation or asystole, hemodynamic collapse, and possibly death. In about one third of the patients, the course is subacute, and they present with symptoms such as syncope, hypotension, shock, arrhythmia, and prolonged and recurrent chest pain.

Diagnosis of VFWR

Early diagnosis of VFWRs and intervention are critical to patient survival. A high index of suspicion is required when patients with AMI present with severe chest pain, shock or arrhythmias, and abrupt development of electromechanical dissociation. ECG signs of impending VFWR have limited specificity but include sinus tachycardia, intraventricular conduction defect, and persistent or recurrent ST-segment elevation.

Echocardiography is the diagnostic tool of choice. The key diagnostic finding is a moderate-to-large pericardial effusion with clinical and echocardiographic signs of impending pericardial tamponade. In patients with cardiac tamponade and electromechanical dissociation, moderate-to-severe pericardial effusion increases the mortality risk. Those patients without initial cardiac tamponade, while at a lower rate of mortality, should still be followed, as late rupture may still occur.[13] The absence of pericardial effusion on echocardiography has high negative predictive value. If the ability to obtain transthoracic echocardiograms is limited in patients receiving mechanical ventilation, transesophageal echocardiography can assist in confirming VFWR.

MRI provides superior image quality and permits identification of the site and anatomy of a ventricular pseudoaneurysm (ie, ruptured LV restrained by the pericardium with enclosed clot). However, MRI is of limited use in the acute setting because of the time involved and nonportability of imaging units.

Treatment of VFWR

The most important prevention strategy is early reperfusion therapy, with percutaneous coronary intervention (PCI) being the preferred modality. Fibrinolytic therapy is associated with overall decreased risk of VFWR; however, its use more than 14 hours after STEMI onset can increase the risk of early rupture.[14, 15]

The standard treatment for VFWR is emergency surgical repair after hemodynamic stability is achieved. Patients may first need intravenous fluids, inotropic agents, and emergency pericardiocentesis.

Pifarré and associates recommended the deployment of an intra-aortic balloon pump to decrease systolic afterload and improve diastolic myocardial perfusion.[16]

Several surgical techniques have been applied, including infarctectomy, adhering with biologic glue patches made of polyethylene terephthalate polyester fiber (Dacron; DuPont, Wilmington, DE) or polytetrafluoroethylene fluoropolymer resin (Teflon; DuPont); and use of pledgeted sutures without infarctectomy.

The mortality rate is significantly high and largely depends on the patient's preoperative hemodynamic status. Early diagnosis, rapid institution of the measures described above to achieve hemodynamic stability, and prompt surgical repair can improve survival rates. A follow-up to the Acorn randomized trial demonstrated long-term improvement in left ventricular structure and function after mitral valve surgery for as long as 5 years. These data provide evidence supporting mitral valve repair in combination with the Acorn CorCap device for patients with nonischemic heart failure with severe left ventricular dysfunction who have been medically optimized yet remain symptomatic with significant mitral regurgitation.[17]

Overview of ventricular septal rupture

VSR is an infrequent but life-threatening complication of AMI. Despite optimal medical and surgical treatment, patients with VSR have a high in-hospital mortality rate. During the prethrombolytic era, VSRs occurred in 1-3% of individuals with MIs. The incidence declined with thrombolytic therapy (to 0.2-0.34%) because of improvements in reperfusion and myocardial salvage. The bimodal distribution of VSR is characterized by a high incidence in the first 24 hours, with another peak on days 3-5 and rarely more than 2 weeks after AMI.

In patients receiving thrombolytics, the median time from the onset of symptoms of AMI to septal rupture was 1 day in the Global Utilization of Streptokinase and TPA [tissue plasminogen activator] for Occluded Coronary Arteries (GUSTO-I) trial[18] and 16 hours in the Should We Emergently Revascularize Occluded Coronaries for Cardiogenic Shock? (SHOCK) trial.[19]

Risk factors for septal rupture include advanced age (>65 y), female sex, single-vessel disease, extensive MI, and poor septal collateral circulation.[20, 21] Before the advent of thrombolytics, hypertension and absence of a history of angina were risk factors for VSR. Extensive infarct size and RV involvement are other known risk factors for septal rupture.

In patients with AMI without reperfusion, coagulation necrosis develops within 3-5 days after infarction. Neutrophils migrate to the necrotic zone and undergo apoptosis, release lytic enzymes, and hasten the disintegration of necrotic myocardium. Some patients have infarcts with large intramural hematomas, which dissect into the tissue and result in early septal rupture. The size of the septal rupture ranges from a few millimeters to several centimeters.

VSR is categorized as simple or complex depending on its length, course, and location. In simple septal rupture, the perforation is at the same level on both sides of the septum, and a direct through-and-through communication is present across the septum. A complex septal rupture is characterized by extensive hemorrhage with irregular, serpiginous tracts in the necrotic tissue.

Septal ruptures are most common in patients with large anterior MIs due to occlusion of the LAD artery causing extensive septal infarcts. These infarcts are associated with ST-segment elevations and Q waves in inferior leads (II, III, aVF) and these ECG changes are therefore more commonly seen in septal ruptures.[22] These ruptures are generally apical and simple.

Septal ruptures in patients with inferior MI occur relatively infrequently. These ruptures involve the basal inferoposterior septum and are often complex.

Clinical presentation of VSR

Symptoms of VSR complicating AMI include chest pain, shortness of breath, hypotension, biventricular failure, and shock within hours to days. Patients often present with a new, loud, and harsh holosystolic murmur. This murmur is loudest along the lower left sternal border and is associated with a palpable parasternal systolic thrill. RV and LV S3 gallops are common.

In patients with cardiogenic shock complicating septal rupture, the murmur and thrill may be difficult to identify. In contrast, patients with acute MR often have a soft systolic murmur at the apex without a thrill.

Diagnosis of VSR

Echocardiography with color flow Doppler imaging is the diagnostic tool of choice for identifying a VSR. (See the image below.) Its sensitivity and specificity have been reported to be as high as 100%. In addition, it can be used for the following:

Define the site and size of septal ruptureAssess the LV and RV functionEstimate the RV systolic pressureQuantify the left-to-right shunt

Cardiac catheterization is usually required to confirm the diagnosis, quantitate the degree of left-to-right shunt, differentiate VSR from other conditions (eg, mitral regurgitation), plus visualize the coronary arteries.

Modified 2-dimensional (top) echocardiogram and color flow Doppler image (bottom). Apical 4-chamber views show a breach in the interventricular septum and free communication between ventricles through a large apical septum ventricular septal defect in a patient who recently had an anterior myocardial infarction.

In patients with VSR, right-heart catheterization shows a step-up in oxygen saturation from the right atrium to the RV; in contrast, no step-up in oxygen saturation occurs among patients with MR. The presence of large V waves in the pulmonary capillary wedge tracing supports the diagnosis of severe acute MR.

Left ventriculography can also be used to identify the site of ventricular rupture (see Cardiac Catheterization [Left Heart]). However, this study is usually unnecessary after a good-quality echocardiographic and Doppler examination is conducted.

Treatment of VSR

The key to management of VSR is prompt diagnosis and an aggressive approach to hemodynamic stabilization, angiography, and surgery. The optimal approach includes hemodynamic stabilization with the administration of oxygen and mechanical support with use of an intra-aortic balloon pump, as well as the administration of vasodilators (to reduce afterload and thus LV pressure and the left-to-right shunt), diuretics, and inotropic agents.

Cardiac catheterization is needed to define the coronary anatomy; this is followed by urgent surgical repair.

Medical therapy is intended only for temporary stabilization before surgery, as most patients' conditions deteriorate rapidly and they die in the absence of surgical intervention. In the GUSTO-I trial, the 30-day mortality rate was lower in patients with VSR who underwent surgical repair than in patients treated medically (47% vs 94%), as was the 1-year mortality rate (53% vs 97%).[18] Lemery et al reported a 30-day survival rate of 24% in patients treated medically compared with 47% in those treated surgically.[23]

Current guidelines of the American College of Cardiology/American Heart Association for the treatment of patients with septal rupture complicating AMI highlight urgent surgical intervention, regardless of their clinical status. Surgical management of septal rupture includes the following elements:

Prompt establishment of hypothermic cardiopulmonary bypassAn approach to the septal rupture through the infarct area and the excision of all necrotic, friable margins of the septum and ventricular walls to avoid postoperative hemorrhage, residual septal defect, or both Reconstruction of the septum and ventricular walls by using prosthetic material and preservation of the geometric configuration of the ventricles and heart function

Percutaneous closure of septal rupture is a relatively new approach, one used in select patients as an alternative to surgical repair or for the acute stabilization of critically ill patients. However, percutaneous closure is currently unavailable in many institutions, and no long-term outcome data are available.

Several studies failed to show a relationship between perioperative mortality and concomitant coronary revascularization (coronary artery bypass grafting). Patients with cardiogenic shock due to septal rupture have the poorest outcome. In the SHOCK trial, the in-hospital mortality rate was higher in patients with cardiogenic shock due to septal rupture (87.3%) than in patients with cardiogenic shock from all other causes (59.2% with pure LV failure and 55.1% with acute MR).[19, 24]

In patients who survive surgical repair, the rate of recurrent or residual septal defect is reported to be about 28%, and the associated mortality rate is high.

Repeat surgical intervention is indicated in patients who have clinical heart failure or a pulmonary-systemic fraction greater than 2.

Overview of acute mitral regurgitation

MR is a common complication of AMI that results from local and global LV remodeling and that is an independent predictor of heart failure and death. MR typically occurs 7-10 days after an AMI, though this onset may vary according to the mechanism of MR. Papillary muscle rupture resulting in MR occurs within 1-14 days (median, 1 d).

Mild-to-moderate MR is often clinically silent and detected on Doppler echocardiography performed during the early phase of AMI. In such cases, MR rarely causes hemodynamic compromise.

Speckle tracking and 3-dimensional echocardiography proved to be important imaging tools in assessing reverse LV remodeling after degenerative mitral valve regurgitation surgery. Subtle regional preoperative changes in diastolic function of the septal and lateral wall could be preoperatively identified, aiding in optimizing the referral timing and recognizing potential culprits as indicators of disease recurrence after mitral repair.[25]

Severe acute MR that results from the rupture of papillary muscles or chordae tendineae results in abrupt hemodynamic deterioration with cardiogenic shock. Rapid diagnosis, hemodynamic stabilization, and prompt surgical intervention are needed because acute severe MR is associated with a high mortality rate.

The reported incidence of MR may vary because of several factors, including the diagnostic methods used, the presence or absence of heart failure, the degree of MR reported, the type of therapy rendered, and the time from infarct onset to testing.

During the GUSTO-I trial, the incidence of MR in patients receiving thrombolytic therapy was 1.73%.[18] The SHOCK trial, which included MI patients presenting with cardiogenic shock, noted a 39.1% incidence of moderate to severe MR.[26] Kinn et al reported that reperfusion with angioplasty resulted in an 82% decrease in the rate of acute MR, as compared with thrombolytic therapy (0.31% vs 1.73%).[27]

Risk factors for MR are advanced age, female sex, large infarct, previous AMI, recurrent ischemia, multivessel coronary artery disease, and heart failure.

Several mechanisms can cause MR after AMI. Rupture of the papillary muscle is the most commonly reported mechanism.

Such rupture occurs in 1% of patients with AMI and frequently involves the posteromedial papillary muscle rather than the anterolateral papillary muscle, as the former has a single blood supply versus the dual supply for the latter. Papillary muscle rupture may lead to flailing or prolapse of the leaflets, resulting in severe MR. Papillary muscle dysfunction due to scarring or recurrent ischemia may also lead to MR in the subacute and chronic phases after MI; this condition can resolve spontaneously.

Large posterior infarctions produce acute MR due to asymmetric annular dilation and altered function and geometry of the papillary muscle.

Clinical presentation of MR

Patients with functional mild or moderate MR are often asymptomatic. The severity of symptoms varies depending on ventricular function. Clinical features of acute severe MR include shortness of breath, fatigue, a new apical holosystolic murmur, flash pulmonary edema, and shock.

The new systolic murmur may be only early-to-mid systolic, not holosystolic. It may be soft or even absent because of the abrupt rise in left atrial pressure, which lessens the pressure gradient between the left atrium and the LV, as compared with chronic MR. The murmur is best heard at the apex rather than the lower left sternal border, and it is uncommonly associated with a thrill. S3 and S4 gallops are expected.

Diagnosis of MR

The clinician cannot rely on a new holosystolic murmur to diagnose MR or assess its severity because of the variable hemodynamic status. In a patient with AMI who presents with a new apical systolic murmur, acute pulmonary edema, and cardiogenic shock, a high index of clinical suspicion for severe MR is the key to diagnosis.

Chest radiography may show evidence of pulmonary edema in the acute setting without clinically significant cardiac enlargement.

Echocardiography with color flow Doppler imaging is the standard diagnostic tool for detecting MR. Transthoracic echocardiography is the preferred initial screening tool, but transesophageal echocardiography is invaluable in defining the severity and exact mechanism of acute MR, especially when suspicion for papillary muscle rupture is high. Cardiac catheterization should be performed in all patients to determine the extent and severity of coronary artery disease.

Treatment of MR

Determination of hemodynamic stability, elucidation of the exact mechanism of acute MR, and expedient therapy are all necessary for a favorable outcome. Medical management includes afterload reduction with the use of diuretics, sodium nitroprusside, and nitrates in patients who are not hypotensive.

In patients who have hemodynamic compromise, intra-aortic balloon counterpulsation should be deployed rapidly. This intervention usually substantially reduces afterload and regurgitant volume, improving cardiac output in preparation for surgical repair. Without surgical repair, medical therapy alone in patients with papillary muscle rupture results in inadequate hemodynamic improvement and a poor short-term prognosis.

Emergency surgical intervention is the treatment of choice for papillary muscle rupture. Surgical approaches may include mitral valve repair or replacement. In the absence of papillary muscle necrosis, mitral valve repair improves the survival rate more than mitral valve replacement does. This difference is because the subvalvular apparatus is usually preserved. Mitral valve repair also eliminates complications related to malfunction of the prosthesis.

In patients with extensive necrosis of papillary muscle and/or ventricular free wall, mitral valve replacement is the preferred modality. Coronary artery bypass grafting (CABG) performed at the time of surgery was shown in one study to improve short- and long-term survival.[28]

The only situation in which emergency surgery can safely be avoided is in the case of intermittent MR due to recurrent ischemia. In these patients, successful myocardial revascularization may be effective. This procedure is accomplished by means of either angioplasty or coronary artery bypass grafting.

PreviousNextLeft Ventricular AneurysmOverview of LVA

Left ventricular aneurysm (LVA) is defined as a localized area of myocardium with abnormal outward bulging and deformation during both systole and diastole. The rate of LVAs after AMI is approximately 3-15%. Risk factors for LVA after AMI include female sex, total occlusion of the LAD artery, single-vessel disease, and absence of previous angina.

More than 80% of LVAs affect the anterolateral wall; these are usually associated with total occlusion of the LAD. The posterior and inferior walls are less commonly affected. LVAs generally range from 1-8 cm. Histologically, LVAs are composed of fibrous scar that is notably thinned. This scar is clearly delineated from the adjacent ventricular muscle on microscopic examination.

A history of MI and third or fourth heart sounds are common findings from the patient's history and physical examination.

Diagnosis of LVA

The chest radiograph may reveal an enlarged cardiac silhouette.

Electrocardiography is characterized by ST elevation that persists several weeks after AMI and that appears in the same leads as those showing the acute infarct. Echocardiography is 93% sensitive and 94% specific for detection of LVA (see the image below), but cardiac catheterization remains the standard for establishing the diagnosis.

Parasternal long-axis view of the left ventricle demonstrates a large inferobasal aneurysm. Note the wide neck and base of the aneurysm. Treatment of LVA

Patients with small or clinically insignificant aneurysms can be treated conservatively with close follow-up. Medical therapy generally consists of the use of angiotensin-converting enzyme (ACE) inhibitors, which reduce afterload, infarct extension, and LV remodeling. Anticoagulation is required when patients have severe LV dysfunction and/or thrombus in the LV or aneurysm.

Surgical resection of the LVA is indicated if severe heart failure, ventricular tachyarrhythmias refractory to medical treatment, or recurrent thromboembolism is present.

PreviousNextMiscellaneous ComplicationsLeft ventricular mural thrombus

LVMT is a well-known complication of AMI and frequently develops after anterior infarcts of the LV wall. The incidence of LVMT as a complication of AMI ranges from 20-40% and may reach 60% in patients with large anterior-wall AMIs who are not treated with anticoagulant therapy. LVMT is associated with a high risk of systemic embolization. Anticoagulant therapy may substantially decrease the rate of embolic events by 33% compared with no anticoagulation.

Factors contributing to LVMT formation include LV regional-wall akinesia or dyskinesia with blood stasis, injury to and inflammation of the endocardial tissue that provides a thrombogenic surface, and a hypercoagulable state. The most common clinical presentation of patients with LVMT complicating an MI is stroke. Most episodes occur within the first 10 days after AMI. Physical findings depend on the site of embolism.

Transthoracic echocardiography remains the imaging modality of choice and is 92% sensitive and 88% specific for detecting LVMT (see the image below). Management of LVMT includes heparin treatment followed by oral warfarin therapy for 3-6 months. In patients with LVAs, lifelong anticoagulation may be appropriate if a mural clot persists.

Apical 2-chamber view depicts a large left ventricular apical thrombus with mobile extensions. Pericarditis

The incidence of early pericarditis after MI is approximately 10%, and this complication usually develops within 24-96. Pericarditis is caused by inflammation of pericardial tissue overlying infarcted myocardium. The clinical presentation may include severe chest pain, usually pleuritic, and pericardial friction rub.

The key ECG change is diffuse ST-segment elevation in all or nearly all of leads. Echocardiography may reveal a small pericardial effusion. The mainstay of therapy usually includes aspirin and nonsteroidal anti-inflammatory drugs (NSAIDs). Colchicine may be beneficial in patients with recurrent pericarditis.

Post-MI syndrome (Dressler syndrome)

Before the era of reperfusion, the incidence of post-MI syndrome ranged from 1-5% after AMI, but this rate has dramatically declined with the advent of thrombolysis and coronary angioplasty.

Although the exact mechanism has yet to be elucidated, post-MI syndrome is considered to be an autoimmune process. Clinical features include fever, chest pain, and other signs and symptoms of pericarditis occurring 2-3 weeks after AMI. Management involves hospitalization and observation for any evidence of cardiac tamponade. Treatment comprises rest, use of NSAIDs, and/or steroids in patients with recurrent post-MI syndrome with disabling symptoms.

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