The cause of cardiomegaly is not well understood and many cases of cardiomegaly are idiopathic (having no known cause). Prevention of cardiomegaly starts with detection. If a person has a family history of cardiomegaly, one should let one's doctor know so that treatments can be implemented to help prevent worsening of the condition. In addition, prevention includes avoiding certain lifestyle risk factors such as tobacco use and controlling one's high cholesterol, high blood pressure, and diabetes. Non-lifestyle risk factors include family history of cardiomegaly, coronary artery disease (CAD), congenital heart failure, Atherosclerotic disease, valvular heart disease, exposure to cardiac toxins, sleep disordered breathing (such as sleep apnea), sustained cardiac arrhythmias, abnormal electrocardiograms, and cardiomegaly on chest X-ray. Lifestyle factors which can help prevent cardiomegaly include eating a healthy diet, controlling blood pressure, exercise, medications, and not abusing alcohol and cocaine. Current research and the evidence of previous cases link the following (below) as possible causes of cardiomegaly.

The most common causes of Cardiomegaly are congenital (patients are born with the condition based on a genetic inheritance), high blood pressure which can enlarge the left ventricle causing the heart muscle to weaken over time, and coronary artery disease that creates blockages in the heart's blood supply, which can bring on a cardiac infarction (heart attack) leading to tissue death which causes other areas of the heart to work harder, increasing the heart size.

Other possible causes include:

- Heart Valve Disease

- Cardiomyopathy (disease to the heart muscle)

- Pulmonary Hypertension

- Pericardial Effusion (fluid around the heart)

- Thyroid Disorders

- Hemochromatosis (excessive iron in the blood)

- Other rare diseases like Amyloidosis

- Viral infection of the heart

- Pregnancy, with enlarged heart developing around the time of delivery (peripartum cardiomyopathy)

- Kidney disease requiring dialysis

- Alcohol or cocaine abuse

- HIV infection

- Diabetes

In 2015 heart failure affected about 40 million people globally. Overall around 2% of adults have heart failure and in those over the age of 65, this increases to 6–10%. Above 75 years old rates are greater than 10%.

Rates are predicted to increase. Increasing rates are mostly because of increasing life span, but also because of increased risk factors (hypertension, diabetes, dyslipidemia, and obesity) and improved survival rates from other types of cardiovascular disease (myocardial infarction, valvular disease, and arrhythmias). Heart failure is the leading cause of hospitalization in people older than 65.

A person's risk of developing heart failure is inversely related to their level of physical activity. Those who achieved at least 500 MET-minutes/week (the recommended minimum by U.S. guidelines) had lower heart failure risk than individuals who did not report exercising during their free time; the reduction in heart failure risk was even greater in those who engaged in higher levels of physical activity than the recommended minimum.

Hypertension or high blood pressure affects at least 4 billion people worldwide. Hypertensive heart disease is only one of several diseases attributable to high blood pressure. Other diseases caused by high blood pressure include ischemic heart disease, stroke, peripheral arterial disease, aneurysms and kidney disease. Hypertension increases the risk of heart failure by two or three-fold and probably accounts for about 25% of all cases of heart failure. In addition, hypertension precedes heart failure in 90% of cases, and the majority of heart failure in the elderly may be attributable to hypertension. Hypertensive heart disease was estimated to be responsible for 1.0 million deaths worldwide in 2004 (or approximately 1.7% of all deaths globally), and was ranked 13th in the leading global causes of death for all ages. A world map shows the estimated disability-adjusted life years per 100,000 inhabitants lost due to hypertensive heart disease in 2004.

There are more women than men with hypertension, and, although men develop hypertension earlier in life, hypertension in women is less well controlled. The consequences of high blood pressure in women are a major public health problem and hypertension is a more important contributory factor in heart attacks in women than men. Until recently women have been under-represented in clinical trials in hypertension and heart failure. Nevertheless, there is some evidence that the effectiveness of antihypertensive drugs differs between men and women and that treatment for heart failure may be less effective in women.

The risk factors for SCD are similar to those of coronary artery disease and include age, cigarette smoking, high blood pressure, high cholesterol, lack of physical exercise, obesity, diabetes, and family history. A prior episode of sudden cardiac arrest also increases the risk of future episodes.

Current cigarette smokers with coronary artery disease were found to have a two to threefold increase in the risk of sudden death between ages 30 and 59. Furthermore, it was found that former smokers risk was closer to that of those who had never smoked.

Marine-derived omega-3 polyunsaturated fatty acids (PUFAs) has been promoted for the prevention of sudden cardiac death due to its postulated ability to lower triglyceride levels, prevent arrhythmias, decrease platelet aggregation, and lower blood pressure. However, according to a recent systematic review, omega-3 PUFA supplementation are not being associated with a lower risk of sudden cardiac death.

It is estimated that the incidence of PPCM in the United States is between 1 in 1300 to 4000 live births. While it can affect women of all races, it is more prevalent in some countries; for example, estimates suggest that PPCM occurs at rates of one in 1000 live births in South African Bantus, and as high as one in 300 in Haiti.

Some studies assert that PPCM may be slightly more prevalent among older women who have had higher numbers of liveborn children and among women of older and younger extremes of childbearing age. However, a quarter to a third of PPCM patients are young women who have given birth for the first time.

While the use of tocolytic agents or the development of preeclampsia (toxemia of pregnancy) and pregnancy-induced hypertension (PIH) may contribute to the worsening of heart failure, they do not cause PPCM; the majority of women have developed PPCM who neither received tocolytics nor had preeclampsia nor PIH.

In short, PPCM can occur in any woman of any racial background, at any age during reproductive years, and in any pregnancy.

There are several potential challenges associated with routine screening for HCM in the United States. First, the U.S. athlete population of 15 million is almost twice as large as Italy's estimated athlete population. Second, these events are rare, with fewer than 100 deaths in the U.S. due to HCM in competitive athletes per year, or about 1 death per 220,000 athletes. Lastly, genetic testing would provide a definitive diagnosis; however, due to the numerous HCM-causing mutations, this method of screening is complex and is not cost-effective. Therefore, genetic testing in the United States is limited to individuals who exhibit clear symptoms of HCM, and their family members. This ensures that the test is not wasted on detecting other causes of ventricular hypertrophy (due to its low sensitivity), and that family members of the individual are educated on the potential risk of being carriers of the mutant gene(s).

Although the disease is more common in African-Americans than in Caucasians, it may occur in any patient population.

The true incidence of TIC is unclear. Some studies have noted the incidence of TIC in adults with irregular heart rhythms to range from 8% to 34%. Other studies of patients with atrial fibrillation and left ventricular dysfunction estimate that 25-50% of these study participants have some degree of TIC. TIC has been reported in all age groups.

The progression of HFpEF and its clinical course is poorly understood in comparison to HFrEF. Despite this, patients with HFrEF and HFpEF appear to have comparable outcomes in terms of hospitalization and mortality. Causes of death in patients vary substantially. However, among patients in more advanced heart failure (NYHA classes II-IV), cardiovascular death, including heart attacks and sudden cardiac death, was the predominant cause in population-based studies.

Although in many cases no cause is apparent, dilated cardiomyopathy is probably the result of damage to the myocardium produced by a variety of toxic, metabolic, or infectious agents. It may be due to fibrous change of the myocardium from a previous myocardial infarction. Or, it may be the late sequelae of acute viral myocarditis, such as with Coxsackie B virus and other enteroviruses possibly mediated through an immunologic mechanism.

Other causes include:

- Chagas disease, due to "Trypanosoma cruzi". This is the most common infectious cause of dilated cardiomyopathy in Latin America

- Pregnancy. Dilated cardiomyopathy occurs late in gestation or several weeks to months postpartum as a peripartum cardiomyopathy. It is reversible in half of cases.

- Alcohol abuse (alcoholic cardiomyopathy)

- Nonalcoholic toxic insults include administration of certain chemotherapeutic agents, in particular doxorubicin (Adriamycin), and cobalt.

- Thyroid disease

- Inflammatory diseases such as sarcoidosis and connective tissue diseases

- Tachycardia-induced cardiomyopathy

- Muscular dystrophy

- Tuberculosis - 1 to 2% of TB cases.

- Autoimmune mechanisms

Recent studies have shown that those subjects with an extremely high occurrence (several thousands a day) of premature ventricular contractions (extrasystole) can develop dilated cardiomyopathy. In these cases, if the extrasystole are reduced or removed (for example, via ablation therapy) the cardiomyopathy usually regresses.

Cardiomegaly is a condition affecting the cardiovascular system, specifically the heart. This condition is strongly associated with congestive heart failure. Within the heart, the working fibers of the myocardial tissue increase in size. As the heart works harder the actin and myosin filaments experience less overlap which increases the size of the myocardial fibers. If there is less overlap of the protein filaments actin and myosin within the sarcomeres of muscle fibers, they will not be able to effectively pull on one another. If the heart tissue (walls of left and right ventricle) gets too big and stretches too far, then those filaments cannot effectively pull on one another to shorten the muscle fibers, thus impacting the heart's sliding filament mechanism. If fibers cannot shorten properly, and the heart cannot contract properly, then blood cannot be effectively pumped to the lungs to be re-oxygenated and to the body to deliver oxygen to the working tissues of the body.

Kidney failure is very common in patients suffering from congestive heart failure. It was shown that kidney failure complicates one-third of all admissions for heart failure, which is the leading cause of hospitalization in the United States among adults over 65 years old. These complications led to longer hospital stay, higher mortality, and greater chance for readmission. Another study found that 39% of patients in NYHA class 4 and 31% of patients in NYHA class 3 had severely impaired kidney function. Similarly, kidney failure can have deleterious effects on cardiovascular function. It was estimated that about 44% of deaths in patients with end-stage kidney failure (ESKF) are due to cardiovascular disease.

Canadian genetic testing guidelines and recommendations for individuals diagnosed with HCM are as follows:

- The main purpose of genetic testing is for screening family members.

- According to the results, at-risk relatives may be encouraged to undergo extensive testing.

- Genetic testing is not meant for confirming a diagnosis.

- If the diagnosed individual has no relatives that are at risk, then genetic testing is not required.

- Genetic testing is not intended for risk assessment or treatment decisions.

- Evidence only supports clinical testing in predicting the progression and risk of developing complications of HCM.

For individuals "suspected" of having HCM:

- Genetic testing is not recommended for determining other causes of left ventricular hypertrophy (such as "athlete's heart", hypertension, and cardiac amyloidosis).

- HCM may be differentiated from other hypertrophy-causing conditions using clinical history and clinical testing.

Chronic stable heart failure may easily decompensate. This most commonly results from an intercurrent illness (such as pneumonia), myocardial infarction (a heart attack), abnormal heart rhythms (such as atrial fibrillation), uncontrolled high blood pressure, or the person's failure to maintain a fluid restriction, diet, or medication. Other well recognized precipitating factors include anemia and hyperthyroidism which place additional strain on the heart muscle. Excessive fluid or salt intake, and medication that causes fluid retention such as NSAIDs and thiazolidinediones, may also precipitate decompensation.

Acute myocardial infarction can precipitate acute decompensated heart failure and will necessitate emergent revascularization with thrombolytics, percutaneous coronary intervention, or coronary artery bypass graft.

Atrial fibrillation increases the risk of heart failure by 11 per 1000, kidney problems by 6 per 1000, death by 4 per 1000, stroke by 3 per 1000, and coronary heart disease by 1 per 1000. Women have a worse outcome overall than men. Evidence increasingly suggests that atrial fibrillation is independently associated with a higher risk of developing dementia.

Ultrafiltration can be used to remove fluids in people with ADHF associated with kidney failure. Studies have found that it decreases health care utilization at 90 days.

Clinical manifestations of HFpEF are similar to those observed in HFrEF and include shortness of breath including exercise induced dyspnea, paroxysmal nocturnal dyspnea and orthopnea, exercise intolerance, fatigue, elevated jugular venous pressure, and edema.

Patients with HFpEF poorly tolerate stress, particularly hemodynamic alterations of ventricular loading or increased diastolic pressures. Often there is a more dramatic elevation in systolic blood pressure in HFpEF than is typical of HFrEF.

The most recent studies indicate that with newer conventional heart failure treatment consisting of diuretics, ACE inhibitors and beta blockers, the survival rate is very high at 98% or better, and almost all PPCM patients improve with treatment. In the United States, over 50% of PPCM patients experience complete recovery of heart function (EF 55% or greater). Almost all recovered patients are eventually able to discontinue medications with no resulting relapse and have normal life expectancy.

It is a misconception that hope for recovery depends upon improvement or recovery within the first six to 12 months of diagnosis. Many women continue to improve or recover even years after diagnosis with continued medicinal treatment. Once fully recovered, if there is no subsequent pregnancy, the possibility of relapse or recurrence of heart failure is minimal.

Subsequent pregnancy should be avoided when left ventricular function has not recovered and the EF is lower than 55%. However, many women who have fully recovered from PPCM have gone on to have successful subsequent pregnancies. A significant study reports that the risk for recurrence of heart failure in recovered PPCM patients as a result of subsequent pregnancy is approximately 21% or better. The chance of relapse may be even smaller for those with normal contractile reserve as demonstrated by stress echocardiography. In any subsequent pregnancy, careful monitoring is necessary. Where relapse occurs, conventional treatment should be resumed, including hydralazine with nitrates plus beta-blockers during pregnancy, or ACE-inhibitors plus beta-blockers following pregnancy.

HIV is a major cause of cardiomyopathy – in particular dilated cardiomyopathy. Dilated cardiomyopathy can be due to pericardial effusion or infective endocarditis, especially in intravenous drug users which are common in the HIV population. However, the most researched causes of cardiomyopathy are myocardial inflammation and infection caused by HIV-1. Toxoplasma gondii is the most common opportunistic infectious agent associated with myocarditis in AIDS. Coinfection with viruses (usually, coxsackievirus B3 and cytomegalovirus) seems to have an important affect in myocarditis. HIV-1 infection produces additional virus and cytokines such as TNF-α. This induces cardiomyocyte apoptosis. TNF-α causes a negative inotropic effect by interfering with the intracellular calcium ion concentrations. The intensity of the stains for TNF-α and iNOS of the myocardium was greater in patients with HIV associated cardiomyopathy, myocardial viral infection and was inversely correlated with CD4 count with antiretroviral therapy having no effect. Cardiac autoimmunity affects the pathogenesis of HIV-related heart disease as HIV-infected patients with dilated cardiomyopathy are more likely to have cardiac-specific autoantibodies than HIV-infected patients with healthy hearts and HIV-negative controls. Many patients with HIV have nutritional deficiencies which have been linked to left ventricular dysfunction. HIV-infected patients with encephalopathy are more likely to die of congestive heart failure than are those without encephalopathy. HAART has reduced the incidence of myocarditis thus reducing the prevalence of HIV-associated cardiomyopathy. Intravenous immunoglobulins (IVIGs) can also help patients with HIV-associated myocarditis.

A family history of AF may increase the risk of AF. A study of more than 2,200 people found an increased risk factor for AF of 1.85 for those that had at least one parent with AF. Various genetic mutations may be responsible.

Four types of genetic disorder are associated with atrial fibrillation:

- Familial AF as a monogenic disease

- Familial AF presenting in the setting of another inherited cardiac disease (hypertrophic cardiomyopathy, dilated cardiomyopathy, familial amyloidosis)

- Inherited arrhythmic syndromes (congenital long QT syndrome, short QT syndrome, Brugada syndrome)

- Non-familial AF associated with genetic backgrounds (polymorphism in the ACE gene) that may predispose to atrial fibrillation

Alcoholic cardiomyopathy is a disease in which the chronic long-term abuse of alcohol (i.e., ethanol) leads to heart failure. Alcoholic cardiomyopathy is a type of dilated cardiomyopathy. Due to the direct toxic effects of alcohol on heart muscle, the heart is unable to pump blood efficiently, leading to heart failure. It can affect other parts of the body if the heart failure is severe. It is most common in males between the ages of 35-50.

The following risk factors have been associated with increased incidence of CRS.

- Older age

- Comorbid conditions (diabetes mellitus, uncontrolled hypertension, anemia)

- Drugs (anti-inflammatory agents, diuretics, ACE inhibitors, ARBs)

- History of heart failure or impaired left ventricular ejection fraction

- Prior myocardial infarction

- New York Heart Association (NYHA) functional class

- Elevated cardiac troponins

- Chronic kidney disease (reduced eGFR, elevated BUN, creatinine, or cystatin)