Continuing Education Activity

Cardiomegaly is an umbrella designation for a variety of conditions leading to enlargement of the heart which usually remains undiagnosed until the symptoms ensue. It has become increasingly prevalent and carries a high mortality. This activity reviews the etiology, epidemiology, pathophysiology, signs and symptoms, evaluation and management of cardiomegaly and highlights the role of the interprofessional team in improving outcomes for patients with this condition.

Objectives:

• Review the risk factors for developing cardiomegaly.
• Describe the typical presentation of a patient with cardiomegaly.
• Summarize the treatment considerations in a patient with cardiomegaly.
• Explain the importance of improving care coordination amongst the interprofessional team to enhance the delivery of care for patients affected by cardiomegaly.

Introduction

Cardiomegaly means enlargement of the heart. The definition is when the transverse diameter of the cardiac silhouette is greater than or equal to 50% of the transverse diameter of the chest (increased cardiothoracic ratio) on a posterior-anterior projection of a chest radiograph or a computed tomography. It should not be confused with an enlargement of the cardiomediastinal outline. Cardiomegaly is usually a manifestation of another pathologic process and presents with several forms of primary or acquired cardiomyopathies. It may involve enlargement of the right, left, or both ventricles or the atria. 

Etiology

There are several etiologies have been attributed to the development of cardiomegaly that result in either dilated or hypertrophic cardiomyopathy listed below.[1][2][3]

• Coronary artery disease including myocardial infarction and ischemia (most common cause)
• Hypertensive heart disease
• Valvular heart diseases including stenosis or regurgitation of the aortic, mitral, pulmonary or tricuspid valves and sub-acute bacterial endocarditis
• Congenital heart disorders including atrial septal defect, ventricular septal defect, patent ductus arteriosus, tetralogy of Fallot, Ebstein anomaly, and coarctation of the aorta
• Pulmonary diseases such as primary pulmonary hypertension, COPD, obstructive sleep apnea, and pulmonary embolism leading to cor-pulmonale
• Infectious myocarditis secondary to viral infection (most commonly), HIV, Chaga disease
• Infiltrative/deposition disease such as amyloidosis, sarcoidosis, hypothyroidism, acromegaly, and hemochromatosis
• Toxin-induced cardiomyopathy including alcohol, cocaine, chemotherapeutic agents such as doxorubicin, cyclophosphamide, trastuzumab, and radiation
• Autoimmune cardiomyopathy including eosinophilic myocarditis, idiopathic giant cell myocarditis, and collagen vascular disease
• Arrhythmia including atrial fibrillation and flutter leading to tachycardia-induced cardiomyopathy, arrhythmogenic right ventricular cardiomyopathy (ARVC) with the fibro-fatty replacement of RV
• Systemic disease leading to high output state including anemia, hyperthyroidism, vitamin B1 deficiency (“Beriberi”), AV fistula
• Physiologic conditions including stress cardiomyopathy, exercise-induced cardiomegaly or “athletic” heart, and pregnancy
• Familial cardiomyopathy, hypertrophic obstructive cardiomyopathy (HOCM)
• Idiopathic cardiomyopathy

Epidemiology

Enlargement of the heart both in the form of dilatation or hypertrophy leads to a spectrum of clinical heart failure syndrome, with a prevalence of nearly 5.8 million people in the United States. Heart failure with preserved Ejection Fraction (HFpEF) represents more than half of these cases. The incidence of heart failure increases with age, male gender, and African American race. About half of the people diagnosed with heart failure die within 5 years of diagnosis.[4]

Pathophysiology

The development of cardiac remodeling and hypertrophy is complex with genetic and non-genetic components.  The most critical pathophysiological changes leading to cardiomegaly include dilated hypertrophy, fibrosis, and contractile malfunction. Contractile dysfunction and abnormal myocardial remodeling can lead to hypertrophic cardiomyopathy or dilated cardiomyopathy. Mechanical stretching, circulating neurohormones and oxidative stress are significant stimuli for the signal transduction of inflammatory cytokines and MAP kinase in cardiomyocytes. Signal transduction leads to changes in structural proteins and proteins that regulate excitation-contraction. Dilated cardiomyopathy mutations result in a reduced force of the sarcomere contraction and a reduction in sarcomere content. Hypertrophic cardiomyopathy mutations result in a molecular phenotype of hyperdynamic contractility, poor relaxation, and increased energy consumption.[5][6]

History and Physical

Many patients with cardiomegaly are asymptomatic, and the presence of symptoms alone is neither sensitive nor specific to diagnosis. The diagnosis of cardiomegaly has its basis on imaging, and history is only helpful to determine the cause of heart failure symptoms which results in systemic congestion and impaired organ perfusion.[7]

A detailed history should elicit the presence or absence of:

• Shortness of breath on exertion or rest, orthopnea, and paroxysmal nocturnal dyspnea
• Peripheral edema and abdominal distension
• Fatigue and poor exercise tolerance
• Palpitations lightheadedness and/or syncope
• Angina
• Anorexia, nausea and early satiety
• Family history of cardiomyopathy

It is worth mentioning that cardiac function is adequate during rest may become inadequate with exertion. Hence it is not at all uncommon for patients to be asymptomatic at rest and experience symptoms on exertion only. The New York Heart Association classifies the severity of disease based on symptoms where class I disease is asymptomatic with ordinary physical activity and class IV denotes symptoms with rest. 

Perhaps the most specific sign of cardiomegaly is a displaced point of maximal impulse (PMI). The precordial examination will reveal a displaced PMI usually below the 5th intercostal space and lateral to the midclavicular line and palpable across 2 intercostal spaces. Sustained PMI is a sign of severe left ventricular hypertrophy. A sustained and prolonged left parasternal heave is indicative of right ventricular hypertrophy. Another physical finding observed in cardiomegaly is the holosystolic murmur of mitral and/or tricuspid regurgitation resulting from dilatation of the mitral annulus and displacement of papillary muscles with abnormal myocardial remodeling. Other exam findings may be seen depending on the presence of decompensated heart failure. In such cases, a detailed physical exam may reveal the following abnormalities: 

• Sinus tachycardia resulting from increased sympathetic drive
• Diminished pulse pressure reflecting reduced stroke volume
• Varying degrees of respiratory distress based on the severity of the disease
• Cool, cyanotic extremities secondary to peripheral vasoconstriction
• Jugular venous distension and/or positive abdominojugular reflex indicating elevated right-sided filling pressures
• Ascites, hepatomegaly and peripheral edema resulting from increased pressure in the hepatic veins and systemic veins
• Pulmonary crackles resulting from elevated left-sided filling pressure and transudation of fluid into alveoli
• S3 gallop in early diastole resulting from volume overload and systolic dysfunction; S4 gallop in late diastole resulting from diastolic dysfunction

Evaluation

Diagnosis of cardiomegaly is primarily through imaging techniques that provide an assessment of the size and function of the heart. Diagnostic testing includes one of the following:

• A chest X-ray with an enlarged cardiac silhouette and a cardiothoracic ratio of more than 50% is suggestive of cardiomegaly. Further delineation of specific chamber enlargement is also possible. RV enlargement produces an upward deviation of the left apical margin while LV enlargement leads to a leftward displacement of the left heart border. RA enlargement leads to increased convexity of the right heart border. LA enlargement and its extension to the right leads to “double density” sign. Also, cephalization of the pulmonary vessels, Kerley B-lines, pulmonary edema, and pleural effusions present in heart failure
• A transthoracic echocardiogram can be used to assess LV, RV and atrial size and systolic/diastolic function. It can also provide an assessment of valve structure and function and wall motion changes which suggest ischemia
• Cardiac MRI is an emerging diagnostic modality for the accurate evaluation of LV and RV mass, size, and function. It also can characterize ischemic and non-ischemic causes such as myocarditis 
• Electrocardiogram (ECG) can reveal non-specific changes including LV/RV hypertrophy, low voltage QRS in case of fibrosis/dilated cardiomyopathy, conduction abnormality, arrhythmia, PVC’s,  ST-T wave changes and Q waves suggestive of prior MI.
• Serum levels of brain natriuretic peptide (pro-BNP), troponin I and T, renal function, and liver function tests are useful in the setting of heart failure
• Stress test and/or coronary angiogram to evaluate for coronary artery disease
• Often the etiology of cardiomegaly is unclear despite standard work up. In such cases, additional testing may be pursued to determine the underlying etiology

Treatment / Management

Treatment of mild cardiomegaly centers upon the treatment of the underlying condition. In moderate to severe cardiomegaly associated with heart failure, standard HF treatment guidelines also apply. 

• Patients at risk of cardiomyopathy benefit from risk factor modification such as smoking cessation, limiting alcohol intake, weight loss, exercise, and consuming a healthy diet. Recommendations include treating any underlying risk factors such as hypertension, dyslipidemia, and diabetes. Other underlying conditions, including obstructive sleep apnea, arrhythmias, anemia, and thyroid disorders also require treatment.
• Patients with early onset cardiomyopathy who are asymptomatic are managed with risk factor modification and the addition of ACE inhibitor or ARB (if intolerant to ACE) and beta blocker if there is a history of MI or reduced ejection fraction (EF).
• Patients with cardiomyopathy and symptoms of heart failure are managed with diuretics and salt restriction in addition to the above therapies. All such patients should receive ACE inhibitor or ARB (if intolerant to ACE) and beta blocker if they have reduced EF. An ARNI (ARB plus neprilysin inhibitor) is occasionally used instead of ACE/ARB to reduce hospitalization in heart failure and mortality. For patients with moderate to severe symptoms and reduced EF, the addition of aldosterone antagonists further reduces mortality. A hydralazine/nitrate combination when added to ACE inhibitor, beta blocker, and diuretics improve outcomes in Black patients. Digoxin is added in some patients to reduce the rate of hospitalization with heart failure; however, it does not impact outcomes. An ICD (implantable cardioverter defibrillator) is placed in patients with EF 35% or less to reduce mortality from sudden cardiac death. CRT (cardiac resynchronization) is performed with or without ICD in patients with EF 35% or less and moderate to severe symptoms with evidence of left bundle branch block
• Patients with refractory heart failure should receive optimal medical management. Also, eligible patients can be considered for cardiac transplantation and bridge therapy such as ventricle assist device [8] 

Of special consideration, no pharmacologic agent has shown benefit in HFpEF, and the mainstay of treatment is controlling underlying conditions such as hypertension, heart rate in patients with atrial fibrillation, ischemia with medication and/or coronary intervention, and diuretics for fluid overload. Patients with HOCM (hypertrophic obstructive cardiomyopathy) who are asymptomatic can be safely monitored. Patients who have symptoms of HF and left ventricular outflow tract obstruction, they may get benefit from negative inotropes such as beta blocker, calcium channel blocker or dipyridamole. Vasodilators and diuretics should be avoided in such patients. 

Differential Diagnosis

Differentials of cardiomegaly include disorders that can result in an enlarged cardiomediastinal silhouette on a frontal (or posteroanterior) chest X-ray. These include: 

• Pericardial effusion
• Anterior mediastinal mass
• Prominent epicardial fat pad
• Mediastinal widening secondary to pulmonary/aortic pathology

Prognosis

Despite the advent of new therapies, mortality remains high in patients with symptomatic HF. Roughly, 1-year mortality is 30% while 5-year mortality is 50%. The severity of symptoms, advanced age, and HF hospitalization are significant predictors of mortality in HF.[9]

Complications

• Decompensated heart failure
• Sudden cardiac death and malignant ventricular arrhythmias
• Thromboembolism secondary to mural thrombi

Pearls and Other Issues

Cardiac transplantation is an emerging treatment for patients with refractory end-stage heart failure. Patients undergo cardiopulmonary assessment and prognostication using specific scoring systems to determine their candidacy for transplant. Patients with systemic illness, life expectancy under 2 years, active substance and alcohol abuse, and non-compliance with medical therapy are considered poor candidates for cardiac transplantation. Patients should have a robust psychosocial support system to qualify. Ultimately, a risk-benefit assessment is necessary before the patient is a candidate for the transplant list. Patients who are not candidates for a cardiac transplant can qualify for a durable ventricular assist device.[10]

Enhancing Healthcare Team Outcomes

Heart failure readmissions account for a majority of national healthcare expenditures. Support programs are operating nationwide to minimize the number of CHF related hospitalizations and thereby reduce the economic strain. These programs utilize a collaborative approach with many integrated disciplines and providers. Some of the inpatient strategies include guideline-based care, discharge support by nurses, patient education, medication reconciliation by the pharmacist, and early post-discharge follow up. A board-certified cardiology pharmacist can assist the clinicians in selecting medications for blood pressure control, as well as other factors where medication can provide ancillary benefit. Promising outpatient strategies include an interprofessional HF clinics and disease management programs that make in-person contact with patients and providing individualized education.[11]

Cardiomegaly and HF require an interprofessional team approach that includes physicians and specialists, specialty-trained nurses, and pharmacists and therapists, all working collaboratively to bring about optimal therapeutic choices leading to the best possible patient outcomes. [Level V]