DILATED CARDIOMYOPATHY

Dilated cardiomyopathy is a primary myocardial disease characterized by progressive dilation of the left ventricle (or both ventricles) and systolic dysfunction that is not attributable to pressure or volume overload, as seen in hypertensive or valvular heart disease. The dilated ventricle progressively loses its ability to contract effectively, leading to a decline in ejection fraction and a reduction in the volume of blood pumped into circulation.

This condition is distinguished from other cardiomyopathies by the predominance of eccentric ventricular remodeling, with an increase in the diameter of the ventricular chamber that is not accompanied by adequate compensatory hypertrophy. The final result is a reduction in contractile performance, with impaired cardiac output and progressive activation of neurohormonal compensatory mechanisms, which in the long term exacerbate myocardial damage.

Epidemiology

Dilated cardiomyopathy is the most common form of primary cardiomyopathy and represents one of the main causes of chronic heart failure.
The prevalence in the general population is estimated to be approximately 1 case per 250 individuals, with an annual incidence of about 7-10 cases per 100,000 inhabitants.

The disease can affect individuals of any age but is most frequently diagnosed between the ages of 20 and 50. It is more common in males, with a ratio of about 3:1 compared to females. This difference appears to be related to hormonal and genetic factors, as well as greater exposure to environmental risk factors.

In industrialized countries, dilated cardiomyopathy accounts for approximately 40% of non-ischemic heart failure cases and is the leading cause of heart transplantation in adults. The improvement of diagnostic techniques, particularly molecular genetics, has led to the recognition of an increasing number of familial forms, making screening of first-degree relatives in affected patients essential.

Pathophysiology

Dilated cardiomyopathy results from progressive ventricular remodeling that compromises the heart’s pumping function. Under normal conditions, an increase in ventricular volume during diastole allows for an adequate stroke volume through the Frank-Starling mechanism: the greater the myocardial fiber stretch in diastole, the stronger the contraction. However, in dilated cardiomyopathy, excessive chamber dilation surpasses the physiological limit of this mechanism, leading to a progressive loss of contractility.

The immediate consequence of this process is a reduction in ejection fraction, leading to decreased peripheral perfusion and a series of compensatory responses. The sympathetic nervous system and the renin-angiotensin-aldosterone system (RAAS) are activated in an attempt to increase contractility and fluid retention to maintain blood pressure and organ perfusion. However, when prolonged, these mechanisms contribute to worsening myocardial damage through a chronic overload effect and interstitial fibrosis.

A fundamental aspect of the pathophysiology of dilated cardiomyopathy is the progressive alteration of ventricular geometry. As ventricular diameter increases, mitral annular displacement occurs, preventing the proper coaptation of the valvular leaflets and leading to functional mitral regurgitation. This further worsens ventricular dilation and promotes a vicious cycle of worsening cardiac dysfunction.

Moreover, reduced ventricular contractility favors blood stasis, particularly at the left ventricular apex, creating an environment that predisposes to the formation of mural thrombi. These may fragment and cause systemic thromboembolic events, with severe consequences such as ischemic stroke or peripheral arterial embolism.

As the disease progresses, pressure overload is transmitted to the pulmonary circulation, causing an increase in atrial filling pressures and, in advanced cases, the development of secondary pulmonary hypertension. This condition gradually leads to right ventricular involvement, resulting in worsening biventricular function and further aggravation of the clinical picture.

Clinical Presentation

The medical history of a patient with dilated cardiomyopathy must be thorough and aimed at identifying both the specific symptoms of the disease and any predisposing factors. It is essential to investigate family history, as approximately 30-50% of cases have a genetic basis. The presence of relatives with heart failure, arrhythmias, sudden cardiac death, or heart transplant history should raise suspicion of a familial form.

It is also important to assess the presence of toxic factors or acquired causes, such as alcohol abuse, exposure to cardiotoxic substances (anthracyclines, cocaine), a history of suspected viral myocarditis, or systemic diseases that may secondarily affect the myocardium (hemochromatosis, amyloidosis, sarcoidosis, thyroid disorders).

The patient may report a progressive exercise intolerance, often underestimated in the early stages, followed by worsening symptoms associated with the degree of systolic dysfunction.
Initially, the patient may be asymptomatic, but as the disease progresses, the following symptoms appear:

• Fatigue and asthenia: due to reduced cardiac output and impaired peripheral blood flow.
• Exertional dyspnea: progressing to dyspnea at rest and orthopnea.
• Palpitations: often associated with atrial arrhythmias (atrial fibrillation) or ventricular arrhythmias.
• Atypical chest pain: not always related to epicardial ischemia.
• Dizziness or syncope: particularly in patients with complex ventricular arrhythmias.

On physical examination, patients with advanced dilated cardiomyopathy may present signs of cardiomegaly, functional valvular insufficiency, and hemodynamic alterations.

Palpation of the point of maximal impulse reveals a lateral and downward displacement, indicative of left ventricular enlargement. Cardiac auscultation may reveal a third heart sound (S3), suggestive of altered ventricular filling, and a holosystolic murmur at the apex, indicative of secondary mitral regurgitation. In patients with progression to right ventricular dysfunction, findings may include jugular vein distension, hepatomegaly due to venous congestion, and peripheral edema.

Diagnosis

The diagnosis of dilated cardiomyopathy requires a multimodal approach, based on instrumental tests aimed at confirming ventricular dilation and systolic dysfunction, while excluding other secondary cardiac diseases.

Diagnostic Tests

• Chest X-ray: useful for detecting cardiomegaly, pulmonary congestion, and an increase in cardiac shadow dimensions.
• Electrocardiogram (ECG): often shows nonspecific abnormalities, including left bundle branch block, atrial fibrillation, and repolarization abnormalities.
• Transthoracic echocardiography: the key diagnostic test, allowing assessment of reduced ejection fraction, left ventricular dilation, systolic dysfunction, and functional mitral regurgitation.
• Tissue Doppler and strain imaging: useful for detecting early myocardial contractility changes.
• Cardiac magnetic resonance imaging (CMR): a second-line test that helps differentiate primary dilated cardiomyopathy from secondary forms by assessing myocardial fibrosis using gadolinium.
• Endomyocardial biopsy: indicated in selected cases, such as suspected myocarditis or infiltrative diseases.
• Genetic testing: recommended in patients with suspected familial forms to identify mutations in genes such as TTN, LMNA, MYH7.

Diagnostic Process

The diagnosis of dilated cardiomyopathy is based on a combination of clinical criteria and instrumental investigations.
The echocardiographic finding of a dilated left ventricle with reduced ejection fraction (<40%) in the absence of secondary conditions (such as ischemic heart disease, valvular heart disease, or chronic hypertension) is sufficient for the diagnosis of dilated cardiomyopathy.

In patients with a positive family history, genetic testing is recommended to confirm a hereditary form.
Coronary angiography may be indicated in individuals with suspected underlying ischemic heart disease, while cardiac magnetic resonance imaging is useful for ruling out infiltrative or fibrotic diseases.

Treatment

The treatment of dilated cardiomyopathy focuses on strategies to reduce ventricular remodeling, improve systolic function, and prevent complications. Therapy includes pharmacological approaches, implantable devices, and, in advanced cases, heart transplantation.

The cornerstone of pharmacological treatment consists of drugs that modulate the renin-angiotensin-aldosterone system and the sympathetic nervous system, reducing hemodynamic overload and improving myocardial performance.

The most commonly used drugs include:

• ACE inhibitors and ARNI (sacubitril/valsartan): improve ventricular function, reduce pathological remodeling, and enhance survival.
• Beta-blockers (bisoprolol, carvedilol, metoprolol): reduce oxygen consumption, stabilize heart rhythm, and improve ejection fraction.
• Aldosterone antagonists (spironolactone, eplerenone): limit myocardial fibrosis and reduce mortality in patients with reduced ejection fraction.
• SGLT2 inhibitors (dapagliflozin, empagliflozin): have shown benefits independent of diabetes status, improving prognosis in heart failure patients.
• Loop diuretics (furosemide, torasemide): indicated only for managing congestion in patients with fluid retention.
• Ivabradine: used in patients with sinus rhythm and high heart rates despite beta-blockers.
• Anticoagulants: indicated in patients with atrial fibrillation or evidence of intracardiac thrombi.

In patients with severely reduced ejection fraction and high risk of sudden cardiac death, devices are indicated to prevent malignant arrhythmias and improve ventricular synchronization.

• Implantable cardioverter-defibrillator (ICD): recommended for patients with EF <35% to prevent sudden death from ventricular arrhythmias.
• Cardiac resynchronization therapy (CRT): useful in patients with left bundle branch block and ventricular dyssynchrony.

In patients with refractory heart failure who fail to respond to medical therapy and exhibit progressive ventricular dysfunction, heart transplantation remains the only definitive treatment. The decision is made on a case-by-case basis, considering strict selection criteria to ensure organ availability for those most in need.

Prognosis

The prognosis of dilated cardiomyopathy is variable and depends on the severity of ventricular dysfunction, response to therapy, and the presence of complications.
With optimized treatment, 5-year survival has significantly improved, reaching 50-70% in patients receiving advanced medical therapy.

In patients with aggressive genetic forms or rapid disease progression, the outcome is worse. Early identification and timely treatment are essential to improve quality of life and reduce mortality.

Complications

The complications of dilated cardiomyopathy mainly stem from the progression of ventricular dysfunction and structural myocardial changes. The most significant include:

Ventricular Arrhythmias and Sudden Cardiac Death

In patients with severe ventricular dysfunction, the risk of malignant ventricular arrhythmias, such as sustained ventricular tachycardia or ventricular fibrillation, is high. These arrhythmias can cause sudden cardiac death, particularly in patients with an EF <35%. For this reason, an ICD is recommended for high-risk individuals.

Thromboembolism

Ventricular dilation and reduced contractility promote blood stasis, predisposing to mural thrombus formation, most commonly at the apex of the left ventricle. These thrombi can embolize, leading to ischemic stroke or systemic embolism. Anticoagulant therapy is indicated in patients at high thrombotic risk.

Functional Mitral Regurgitation

Ventricular dilation leads to altered cardiac geometry, causing displacement of the mitral annulus and resulting in functional mitral regurgitation. This condition exacerbates ventricular dilation and worsens symptoms, contributing to heart failure progression.

Pulmonary Hypertension and Right Ventricular Dysfunction

The increased filling pressures of the left ventricle are transmitted to the left atrium and subsequently to the pulmonary circulation, leading to secondary pulmonary hypertension. In advanced cases, the pressure overload extends to the right ventricle, causing its progressive dysfunction with symptoms of systemic congestion (peripheral edema, ascites, congestive hepatomegaly).

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