Ischemic Cardiomyopathy

Etiology

CAD most commonly causes ischemic cardiomyopathy. Lack of adequate blood supply is not able to meet the myocardial metabolic demands that lead to cell death, fibrosis, left ventricular enlargement and dilation.

Risk factors for ischemic cardiomyopathy can be classified as modifiable and non-modifiable.

• Modifiable: Diabetes mellitus, hypertension, tobacco abuse, hyperlipidemia, obesity, and sedentary lifestyle
• Non-modifiable: Age, gender, and family predisposition

Epidemiology

CAD is the leading cause of death in adults in the United States. The 2016 Heart Disease and Stroke Statistics update of the American Heart Association (AHA) reported that there are about 15.5 million adults in the United States who have CAD, and the overall death rate from CAD was 102.6 per 100,000. There is one myocardial infarction every 42 seconds. Age is an independent risk factor for CAD. In the United States, the lifetime risk of developing CAD with at least two major risk factors is 37.5% for men and 18.3% for women.[1][2][1]

Pathophysiology

Worsening CAD is a precursor of ischemic cardiomyopathy. CAD starts as vascular endothelial cell dysfunction which leads to macrophage and LDL accumulation. This results in foam cell formation and fatty streaks. There is a migration of smooth muscle cells on the coronary vessel. Once there is proliferation with extracellular matrix deposition, it forms fibrous plaque which has a potential for rupture and thrombosis. In ischemic cardiomyopathy, there is a significant impairment of the left ventricular systolic function, with a left ventricular ejection fraction (LVEF) less than 40%. Previous myocardial infarctions with consequent ventricular remodeling lead to an irreversible loss of myocardial tissue. There is no recovery of contractile function in these patients, even with coronary revascularization since the infarcted tissue is no longer viable.

History and Physical

On the history, there will be evidence of longstanding coronary arterial disease (CAD) and possibly previous myocardial infarctions. It is also important to consider the patient's family and social history. Delineating risk factors (as mentioned above) for CAD from a complete history is essential. Signs and symptoms may vary between patients and their degree of physiological compensation. Some patient may be asymptomatic or present with mild anginal chest pain and dyspnea on exertion whereas some patients may present with overt heart failure symptoms which include dyspnea, orthopnea, poor exercise tolerance, and increased fatigability. Physical evaluation can reveal bibasilar crackles, S3 gallop (found when the left ventricle is dilated), displaced PMI, carotid bruits, JVD, hepato-jugular reflex and bilateral lower extremity edema.

Evaluation

After getting a detailed history and physical examination, there are several diagnostic modalities which can help with the diagnosis of ischemic cardiomyopathy.

Chest x-ray: Simple and readily available test. It may show cardiomegaly and other findings of heart failure if a patient has progressed to that stage. Some x-ray findings in heart failure patients include pulmonary congestion, Kerley B lines, pleural effusion, and blunting of costophrenic angle.

ECG: Assesses electrical activity of the heart. Useful in looking at the heart rate, rhythm, past/current ischemic episode, chamber enlargement and information about heart's electrical conductivity.

Transthoracic echocardiography (TTE):  This ultrasound-based imaging modality is useful in looking at cardiac anatomy and valvular function. It will assess for ventricular systolic/diastolic function, cardiac wall motion, pericardial pathology, and valvular function. All this information is useful in diagnosing ischemic cardiomyopathy.

Cardiac stress test: There are different stress tests available depending on the patient's health, functional status, baseline heart rhythm and exercise tolerance. The goal of these stress tests is to assess for cardiac ischemia. Some stress test modality can also provide information about myocardial viability.

Coronary angiography: Allows for direct visualization of the coronary arteries, level of obstruction and the blood flow to the myocardium. They also use it for percutaneous coronary intervention (PCI) with balloon angioplasty and coronary stents to allow for better blood flow across occluded coronary artery.

CTCA: It uses computed tomography (CT) to take angiograms of the coronary arteries. Aids with the diagnosis of CAD in patients with low-intermediate risk.[3]

Brain natriuretic peptide (BNP) test: BNP is synthesized in the ventricles, and it is secreted when the myocardial muscle has a high wall tension. Important biomarker for heart failure patients.

Cardiac magnetic resonance imaging: Differentiate ischemic from non-ischemic cardiomyopathies using Late gadolinium imaging. Late Gadolinium Enhancement (LGE) reflects irreversible damage to the myocardium and fibrosis. When LGE is absent in a dysfunctional segment of the myocardium, it implies the potential for recovery with time (stunning) or by medical treatment or revascularization.[4]

Nuclear medicine: 99mTechnetium sestamibi myocardial perfusion imaging is a diagnostic tool for assessing myocardial viability. Patients with hibernating myocardium have better outcomes after revascularization.[5]

Treatment / Management

Ischemic cardiomyopathy is managed primarily with an optimal goal-directed medical therapy (GDMA). However, for appropriate patient population cardiac intervention for revascularization is a common treatment option. Foremost, the patient will benefit from lifestyle modification which includes smoking cessation, exercise, and diet changes. Below are the medical interventions that can be done to optimize patients with ICM.

Revascularization: Patients with ischemic cardiomyopathy may benefit from revascularization. There was a 7% absolute reduction in overall mortality over a 10-year time between patients who had CABG versus GDMA[6]. Revascularization followed by GDMA is recommended for these patients; however, it is important to assess their procedural candidacy. The primary goal is to reperfuse viable ischemic areas of the myocardium. However, a general test for myocardial viability is not recommended.(A1)

Aspirin: It is shown to have major reductions in cardiovascular morbidity and mortality for patients with coronary heart disease. Historically, low dose aspirin (75 to 100 mg) once daily used; however, new data suggest that patients may need a higher dose (300 to 325 mg) if they weigh over 70 kg[7].

Beta-adrenergic antagonist (beta-blockers): Atenolol, esmolol, labetalol, metoprolol, and propranolol. This group antagonizes the effects of epinephrine on beta receptors on the heart. B1 receptors are present in the heart, and when antagonized they decrease heart rate and heart muscle contractility that leads to decreasing oxygen consumption by the heart. B1 selective blockers decrease mortality in patients with heart failure, but should not be initiated when the patient is having acutely decompensated heart failure.

High Potency Statin: Atorvastatin 40 to 80 mg or rosuvastatin 20 to 40 mg orally once daily. Mechanism of action is via HMG-CoA reductase inhibition. These medications inhibit the conversion of HMG-CoA to mevalonate, which is a cholesterol precursor. Statins decrease mortality in patients with coronary artery disease (CAD).

Angiotensin-converting enzyme (ACE) inhibitors: Enalapril, lisinopril, captopril, and ramipril. This group of antihypertensive medications decreases mortality in patients with heart failure. The inhibition of the ACE leads to a decrease of angiotensin II which, when inhibited, decreases glomerular filtration rate by preventing constriction of efferent arterioles. This class of medication has cardio and renal protective effects when it comes to remodeling. An undesired added effect is the prevention of inactivation of bradykinin, which is a potent vasodilator that produces a cough and possibly angioedema in patients with C1 esterase inhibitor deficiency.

Angiotensin II receptor blockers (ARB): Valsartan, losartan, candesartan. This group has the same effect as the ACEI by selectively blocking angiotensin II from binding in its AT1 receptor. This group does not affect bradykinin and therefore is the medication of choice, replacing ACE inhibitors, when a patient complains of a cough or presents with angioedema after being started on ACEI.

Hydralazine and nitrate: This group of medication can be used in patients who are unable to tolerate ACEI or an ARB.

Angiotensin receptor neprilysin inhibitor (ARNI): Recent clinical trial, PARADIGM-HF, showed a reduction in cardiovascular and all-cause mortality along with a reduction in heart failure hospitalization while on valsartan/sacubitril compared to enalapril[8].                       (A1)

Spironolactone: Shown to reduce morbidity and mortality in patients with heart failure (NYHA class III and IV) with LVEF 35% or less. It is a potassium-sparing diuretic that works as an antagonist to the aldosterone receptor at the nephron’s cortical collecting tubule.

Digoxin does not decrease mortality but is helpful in decreasing symptoms and hospitalizations in patients with congestive heart failure (CHF). Digoxin works by inhibiting the effects of the enzyme sodium/potassium ATPase in the heart muscle, stopping the sodium/calcium exchange, leaving more calcium inside the cell which increases contractility.

Inhibitors of the cardiac late sodium current (INA): Ranolazine is a drug with anti-ischemic and anti-arrhythmic therapeutic effects. The mechanism of action of this drug is the inhibition of the myocardium late sodium current, calcium antagonisms, and effects on the B1, B2 receptors. In chronic ischemic cardiomyopathy, it has been shown that it decreases premature ventricular complexes, ventricular tachycardia, and symptomatic improvement. [9][10][11][12](B3)

ICD placement: Select patients with ischemic cardiomyopathy qualify for ICD to prevent sudden cardiac death (SCD). Patients with ischemic cardiomyopathy (evaluated at least 40 days post-MI or 3 months after revascularization), LVEF of 35% or less, and associated heart failure (HF) with New York Heart Association (NYHA) functional class II or III status, there is a class IA recommendation for ICD placement. Additionally, if a patient with ICM has LVEF of 30% or less and NYHA class I, ICD therapy is indicated for primary prevention of SCD.

Biventricular pacing: If a patient has ischemic cardiomyopathy and LVEF 35% or less, then they may be a candidate for cardiac resynchronization therapy (CRT) if their heart failure symptoms are not controlled despite revascularization and GDMA.

Ultimately, a heart transplant is the only option when the disease progresses, and no alleviation is achieved with intervention mentioned above.

Differential Diagnosis

Ischemic cardiomyopathy results into dilated ventricles which manifests as decreased left ventricular ejection fraction on echocardiogram and symptoms of heart failure in decompensated patients. However, there are many other medical conditions which can mimic these findings. Patients with a high adrenergic state either via physical/mental stress or ingestion of sympathomimetic drugs can present with abnormal cardiac wall motion abnormality and reduced LVEF. This condition is commonly referred to as Takotsubo cardiomyopathy. One can differentiate stress-mediated cardiomyopathy by looking at the demographics of the patient population and cardiac catheterization when indicated. Other differential diagnosis includes thyrotoxicosis, beriberi caused by thiamine deficiency, cardiac tamponade, heavy metal toxicity, late-stage hypertrophic cardiomyopathy, myocarditis, and restrictive cardiomyopathy.

Prognosis

Ischemic cardiomyopathy's prognosis depends on disease state and chronicity. A big component in determining prognosis is myocardial viability. Larger myocardial viability is associated with better outcomes in patients who undergo revascularization as there is a possibility of muscle recovery. Patients with non-viable myocardial injury are recommended pharmaceutical management as outlined above. With proper treatment and lifestyle modifications, the clinical course of IC can be stabilized significantly.

Complications

There is a wide spectrum of complications from ischemic cardiomyopathy. The most common complication is the development of clinical congestive heart failure which is often the most common form of presentation for ICM; as the cardiac chambers dilate, innate conduction system of the heart changes leading to abnormal heart rhythms which could be life-threatening.