Dilated cardiomyopathy

I. Problem/Condition.

Dilated cardiomyopathy (DCM) is a condition of the failing heart where ventricles of the heart are dilated accompanied with decreased in ejection fraction.

Heart failure (HF) is a leading cause of death and disability in industrialized nations. Approximately 4.9 million Americans have been diagnosed with the disease and another 550,000 new cases are reported each year. HF is associated with high mortality and is responsible for 300,000 deaths annually in the United States. Despite all the treatment options, the one-year mortality is still 20% while 70% of women and 80% of men die within 8 years of the diagnosis.

DCM, the most common type of cardiomyopathy, is a combination of impaired contraction of myocardium (systolic dysfunction), and dilation of left or both ventricles of the heart. Etiologically DCM can be divided into two main categories: primary DCM including genetic, familial, mixed, and acquired; and secondary DCM that could be secondary to autoimmune infiltrative diseases (giant cell and infiltrative myocarditis, sarcoidosis, lupus, Wegener’s, SLE), drugs (antineoplastic drugs, psychiatric drugs, and chloroquine/anti-retroviral drugs), toxins (ethanol, cocaine/amphetamine), nutritional deficiencies (selenium, thiamine, zinc, copper), endocrine conditions (hypo/hyperthyroidism, Cushing’s syndrome, pheochromocytoma, acromegaly, and diabetes mellitus), infectious (HIV, Lyme disease, Chagas’ disease), and peripartum cardiomyopathy.

By definition, ischemic cardiomyopathy does come under DCM as it is associated with systemic dysfunction and ventricular dilation to maintain cardiac output. However, ischemic heart disease is usually categorized separately from DCM just because of the massive proportion, high prevalence, and distinct wall motion abnormalities. For all practical purposes, DCM is discussed as non-ischemic cardiomyopathy. Ischemic heart disease and resultant cardiomyopathy are discussed separately.

DCM is quite variable at presentation ranging from an asymptomatic condition to debilitated end-stage disease. The prevalence of DCM is variable involving any age, ethnicity, and population of the world. It has significant morbidity with immense social, economic, and disease burden. Its annual mortality is anywhere from 10-50%. The incidence of DCM in adults has been estimated to be 7 per 100,000 with a prevalence of 1 in 2,500 individuals. The prevalence of DCM in the pediatric population is estimated to be 0.57 per 100,000 per year. A higher frequency of DCM is seen in men than women, blacks than whites, and infants than children.

DCM is a progressive disease with shockingly high mortality rates. One-year mortality in untreated heart failure is 50% according to a consensus trial conducted in the 1980s. The mortality has improved since then, still leading to a 20% mortality rate in the Copernicus trial in the 1990s, and a 10% mortality rate in the 2000s. Approximately 25% of DCM patients with recent onset of heart failure (<6 months), have a relatively benign clinical course with spontaneous improvement in symptoms and partial, and in some cases complete recovery of LV function. For some etiologies of DCM, recovery of LV function and reverse LV remodelling occur when the inciting adverse event that precipitated heart failure is resolved or removed.

Prognosis

Though mortality of DCM remains high, prognosis of DCM essentially depends on etiology and presence of adverse variables. Hence identification of etiology and assessment of these adverse clinical variables is of utmost importance. For example, peripartum cardiomyopathy has excellent prognosis compared to amyloidosis related cardiomyopathy with bleak outcome. Genetic influences are likely to influence the overall prognosis.

The following clinical indicators are noted to have adverse association with outcomes: elderly patients, New York Heart Association (NYHA) class III and IV, S3 on cardiac exam, low exercise peak oxygen consumption (VO2), marked intraventricular conduction delay, ventricular arrhythmias, and increased brain natriuretic peptide (BNP), uric acid, and hyponatremia.

The following echocardiographic findings are related to poor outcomes: left ventricular ejection fraction (LVEF) less than 35%, marked LV dilation, low LV mass, more than moderate mitral regurgitation, diastolic dysfunction, and right ventricular (RV) dysfunction.

Right heart catheterization value with poor prognosis is elevated pulmonary capillary wedge pressure.

II. Diagnostic Approach

A. What is the differential diagnosis for this problem?

The main goal of the diagnostic testing is to differentiate different types of DCM given diagnosis of DCM is straightforward. The etiologies of DCM are discussed in detail in individual chapters elsewhere in this resource. However, a short introduction to them follows.

Ischemic heart disease

Ischemic heart disease typically leads to ischemic cardiomyopathy and accounts for 50-75% of all heart failure patients. Since ischemic cardiomyopathy causes specific and localized damage to myocardium with wall motion abnormalities, it is managed separately from other causes of DCM (otherwise also known as non-ischemic cardiomyopathy). Newer studies have also shown that ischemic heart disease still accounts for roughly 70% of the cases previously labeled as idiopathic cardiomyopathy. However, most patients with ischemic cardiomyopathy have a well established coronary artery disease. In a patient with no prior history of coronary artery disease but with risk factors presenting with new onset DCM, an alternative non-invasive yet promising way to differentiate between ischemic and non-ischemic DCM is by 2D ECHO with speckle tracking. In patients with non-ischemic DCM, left atrial systolic and late diastolic strain were significantly lower along with more severely impaired booster pump function.

Infectious cardiomyopathies

There are a variety of organisms identified as possible agents to induce myocarditis, the main mechanism to induce cardiomyopathy. To simplify the classification, the culprit organisms can be divided into viral and non-viral pathogens.

Viruses are the commonest cause for non-ischemic DCM. Commonly seen viruses are coxsackievirus, Cytomegalovirus (CMV), human herpes 6, Epstein-Barr virus (EBV), enteric cytopathic human orphan (ECHO) virus, hepatitis viruses, parvovirus B19 and human immunodeficiency virus (HIV). Both degree of viremia and adverse autoimmune response has been linked to pathogenesis of cardiomyopathy. HIV induced cardiomyopathy is increasingly recognized and is seen in co-existent viral infection with other cardiotropic viruses like Coxsackie, EBV, and CMV. HIV induced cardiomyopathy is shown to have poor outcome compared to other viral cardiomyopathies even when account for acquired immune deficiency syndrome (AIDS) related illness.

There are several non-viral infectious causes. A variety of parasitic and bacterial infections are shown to induce cardiomyopathy.

  • Chagas disease is caused by Trypanosoma cruzi and has a distinct cardiac component. It presents clinically as acute myocarditis with DCM associated with right bundle branch block (RBBB) and arrhythmias. Echocardiogram finding of LV apical aneurysm are pathognomonic of the disease.

  • Lyme Disease is associated with Lyme carditis and is usually a self-limiting disease with mild myocarditis. Ninety percent of patients with Lyme carditis develop cardiac conduction abnormality and 60% develop perimyocarditis. All patients with suspected Lyme carditis should undergo EKG evaluation to exclude atrioventricular conduction block which is mostly reversible. Echocardiogram may show pericardial effusion and LV dysfunction is usually transient.

  • Rheumatic fever leading to rheumatic heart disease may have DCM along with valvular heart disease. Rheumatic cardiomyopathy is associated with poor prognosis.

Stress-induced cardiomyopathy

Stress-induced cardiomyopathy is also known as Takotsubo cardiomyopathy, transient apical ballooning, and broken heart syndrome. It has been increasingly recognized more frequently now and many cases are identified in Japan after earthquake in 2005. Cardiomyopathy with LV dysfunction is precipitated by an intense psychological stress. Patient presents with suspicion for acute coronary syndrome with ST elevation. However cardiac catheterization fails to show any culprit lesion and most patients have non-obstructive coronary disease. Demographically it involves mostly women, middle age to elderly, and echocardiogram has characteristic apical ballooning with extent of wall motion dysfunction involving more than one major coronary vessel. The cardiac compromise is transient and patients recover relatively rapidly in 1-4 weeks. A repeat echocardiogram in 3-6 months should be able to demonstrate significant recovery. One of the prognostic factors which is associated with short-term morbidity and mortality is prolonged QT interval (QTc). Patients with prolonged QTc intervals are more likely to be intubated; require vasopressors; and develop shock, ventricular arrhythmias, and death than those with normal QTc interval.

Toxic cardiomyopathy

Many commonly used pharmacologic and non-pharmacologic agents can cause toxicity leading to cardiac toxicity.

  • Alcohol is the commonest cause for toxic cardiomyopathy. The LV dysfunction related to alcohol can be transient or permanent. Nonetheless, alcohol cessation has remarkable effect on myocardial recovery. The pathogenesis of alcohol toxicity is related to myocyte damage due to oxygen free radical production and protein synthesis defects.

  • Cocaine is particularly notorious for inducing cardiomyopathy and not merely by causing ischemic changes from intense vasoconstriction and atherosclerotic changes. Cocaine effects last longer but cessation does help and leads to significant recovery.

  • Methamphetamines and ecstasy are also increasingly recognized as a cause of cardiomyopathy. The exact mechanism of damage is not yet clearly known, but mitochondrial damage is responsible for focal contraction band necrosis in association with cellular degeneration and myocytolysis in the heart leading to cardiomyopathy.

  • Recently, synthetic cannabis has also been implicated to induce cardiomyopathy.

  • Trace elements toxicity: many trace elements are shown to be involved in DCM. Common toxins include cobalt, lead, mercury, and beryllium. Similarly, some elemental deficiency can also be involved like selenium deficiency.

Many drugs are shown to cause myocyte dysfunction and are involved in pathogenesis of DCM. Many other drugs are shown to worsen the already present myocyte dysfunction. Well-known pharmacologic agents causing DCM are anthracycline (for example, Adriamycin), trastuzumab, and cyclophosphamide. An echocardiogram is usually done prior to administration of these agents to evaluate LV functions.

Peripartum cardiomyopathy

Peripartum cardiomyopathy is associated with systolic dysfunction in late pregnancy or early post partum period (within 5 months). The pathogenesis is unclear, however, black ethnicity, advanced maternal age, multifetal pregnancy, prolonged use of beta-agonists, and hypertensive disorder-complicated pregnancy have been identified as contributing factors. Peripartum cardiomyopathy is a diagnosis of exclusion with absence of other etiologies in appropriate time frame. These patients have no known cardiac structural disease prior to pregnancy. The prognosis of this DCM is excellent with good recovery in 6 months, however level of recovery depends on the extent of dysfunction. A severe LV dysfunction may also take longer to recover. Termination of pregnancy is usually not required unless the severity of the dysfunction dictates otherwise. It has increased risk of LV dysfunction on the subsequent pregnancies.

It is important to note that the medications like angiotensin-converting enzyme inhibitors (ACEI) that form the main stay of DCM treatment are contraindicated in pregnancy or women who may get pregnant due to teratogenicity. Risk and benefits needs to be measured before prescribing ACEI to postpartum women and they need to be advised against lactation if taking them.

Tachycardia induced cardiomyopathy

Chronic tachycardia, or recurrent arrhythmia, is shown to induce cardiac dysfunction through a multitude of mechanisms. Atrial fibrillation is the most common cause of tachycardia-induced cardiomyopathy. Chronic/recurrent tachycardia is heart rate of more than 130 beats per minute of supraventricular (SVT) etiology (SVT like atrial fibrillation, atrial flutter, atrioventricular nodal re-entry tachycardia (AVNRT), preexcitation syndrome). Pathogenesis involves decreased contractility, low calcium sensitivity, calcium toxicity, and anomalous myocardial architecture. Degree of LV dysfunction appears to correlate with pulse rate. The prognosis is excellent once tachycardia is treated and significant recovery is seen in 3-6 months.

Nutritional deficiencies

Many trace elements are essential for the wellbeing of the microenvironment of cardiac myocyte. Well-established deficiencies associated with DCM are thiamine, selenium, and carnitine.

Hypoventilation syndrome

Obstructive sleep apnea, or obesity hypoventilation syndrome, leads to chronic hypoxia that along with sleep disturbances and many other systemic effects can cause DCM. Correction of sleep disturbance, weight loss and positive airway pressure can improve LV dysfunction. It is important to distinguish central sleep apnea from obstructive, as the former could be the result of DCM and not the etiology. Similarly, improving DCM may help with central sleep apnea.

Systemic disease associated with DCM

Many systemic illnesses can induce DCM.

  • Systemic lupus erythematosus (SLE): the cardiovascular system is involved in SLE just like any other system. Cardiac effects include valvular heart disease, pericarditis, myocarditis, atherosclerosis, and coronary artery vasculitis. SLE related myocardial dysfunction is usually resistant to treatments and may not always show clinical improvement.

  • Sarcoidosis: sarcoidosis is part of infiltrative cardiomyopathies with specific granulomatous inflammation. Cardiac involvement in sarcoidosis is associated with poor prognosis. Like most infiltrative diseases, the natural history is progressive with poor response to treatment. However, the spectrum of clinical involvement in sarcoidosis is variable. In addition to DCM, other cardiac manifestations of sarcoidosis include conduction abnormalities (heart block/sudden death), ventricular and supraventricular arrhythmia, pericardial involvement (pericardial effusion and pericarditis), valvular dysfunction due to papillary muscle involvement, and ventricular aneurysm. Myocardial dysfunction alone in sarcoidosis is sometimes reversible in early stages. Cardiac MRI, PET CT, and endomyocardial biopsy (EMB) are more specific tests to diagnose cardiac sarcoidosis.

Familial cardiomyopathy

There are many genetic abnormalities identified with DCM including sarcomere protein mutations, Z-band related (muscle LIM protein, TCAP), cytoskeletal genes (dystrophin, desmin, metavinculin, sarcoglycan complex, CRYAB and epicardin), nuclear membrane (lamin A/C, emerin), intercalated disc protein mutations, and mitochondrial cytopathy. The specific genes need to be tested if suspected and present in the family. Genetic testing is costly and should be limited to suspected cases.

B. Describe a diagnostic approach/method to the patient with this problem

Heart failure is a clinical diagnosis. Once DCM is suspected, the approach towards patient includes traditional involving comprehensive history and physical and essential laboratory and imaging testing followed by specialty related testing.

1. Historical information important in the diagnosis of this problem.

Adequate and comprehensive history form the basis for management of DCM like any other disease.

Symptoms

Patients may present with a spectrum of symptoms from asymptomatic LV dysfunction to end stage heart failure. Usual age at presentation for DCM is between 20 and 60 years. Patients may present with progressive dyspnea with exertion, impaired exercise capacity, orthopnea, paroxysmal nocturnal dyspnea, edema, weakness, lethargy, and loss of energy.

It is important to ask about the following comorbidities: hyperthyroidism or hypothyroidism, acromegaly, pulmonary or systemic embolization, eating disorders (bulimia, refeeding syndrome associated with hypocalcemia, and hypophosphatemia), anemia, bleeding disorder, alcoholism, sickle cell disease, thalassemia, HIV, and any illicit drug use.

It is pertinent to document current medication and the history of the following medications in the past as well: psychiatric medications like clozapine (notorious to cause myocarditis) and others like chlorpromazine, lithium, risperidone, haloperidol, and fluphenazine, and chemotherapy medications like doxorubicin (Adriamycin).

Functional class

Heart failure severity is depicted through NYHA functional class at presentation.

  • Class I: symptoms of heart failure at strenuous activity (activity that would limit functions of normal individual)

  • Class II: symptoms of heart failure at usual activity

  • Class III: symptoms of heart failure at minimal activity (symptoms at doing activities of daily life)

  • Class IV: symptoms of heart failure at rest

Stages of heart failure

Even though NYHA functional class is an excellent measure of grading symptoms of HF, it does not cover the significant portion of patients of heart failure who do not have symptoms yet but are in need of treatment. Hence the World Health Organization (WHO) came up with stages of heart failure.

  • Stage A: patients are risk of developing heart failure (no symptoms and no structural abnormality of heart with normal ejection fraction), such as patients with diabetes and hypertension or coronary artery disease

  • Stage B: asymptomatic left ventricular dysfunction (no symptoms with structural abnormality of heart like decreased ejection fraction)

  • Stage C: presence of symptoms (symptoms of HF as per NYHA class and anatomic defect associated with it)

  • Stage D: refractory heart failure (end stage heart failure) (symptoms are refractory to established treatment of heart failure and need advanced heart failure therapies)

2. Physical Examination maneuvers that are likely to be useful in diagnosing the cause of this problem.

During physical examination, the following evaluation needs to made for all suspected heart failure patients.

  • Vital signs: look for low pulse pressure. Presence of pulses alternans (during deflation of blood pressure (BP) cuff, Korotkoff sounds appear at lower pulse rate but it becomes equal to regular pulse rate at further deflation, indicating presence of high and low volume/pressure pulses).

  • Jugular venous pressure (JVP): JVP estimation is probably the single most important component of a heart failure examination. Presence or absence of jugular venous distention would dictate further heart failure therapies. JVP is usually 2-7cm at rest in normal individuals. More than 10cm of JVP indicates significant jugular venous distention (JVD). JVP of 5-10cm has significant overlap and needs further clinical correlation to assess volume status.

  • Cardiac auscultation: heart sounds, presence of murmur, and additional sounds. Look for presence of S3 or S4 gallop. Look for signs of mitral regurgitation.

  • Lungs: auscultate to hear pulmonary rales (pulmonary edema). Look for coexistent pulmonary disease, like chronic obstructive pulmonary disease (COPD), pneumonia, and asthma.

  • Abdomen: evaluate presence of cardiac ascites, liver margins, size and pulsation of liver. Look for spider angiomas (or the absence of them as are present more commonly with cirrhosis).

  • Extremities: Evaluate and quantify edema at legs (above the medial malleolus for follow-up consistencies) and at sacral bone.

3. Laboratory, radiographic and other tests that are likely to be useful in diagnosing the cause of this problem.

Diagnostic testing is needed to assess acuity, severity, and etiology of the disorder.

Electrocardiogram (EKG)

Look for:

  • Arrhythmias, tachycardia, premature ventricular contractions (PVCs), atrial fibrillation, non-sustained ventricular tachycardia;

  • Signs of ischemic heart disease (Q waves or acute ST or T wave changes);

  • Atrioventricular blocks (nonspecific conduction delay, left bundle branch block, left anterior fascicular block);

  • Left ventricular hypertrophy (LVH) indicative of long-standing hypertension, pseudo-infarct; and

  • Low voltage of QRS complex (infarction vs infiltrative diseases): low voltage in limb leads with LVH by precordial criteria or wide QRS complex is suggestive of non-ischemic DCM.

Chest x-ray (CXR)

Evaluate:

  • Interstitial pulmonary edema vs pulmonary vascular congestion

  • Any acute pulmonary infiltrates and masses, alveolar vs reticular changes

  • Size of the heart (cardiomegaly)

  • Pleural effusion

Laboratory testing

Laboratory tests are included in the initial workup of any heart failure or suspected cardiomyopathy to not only evaluate end organ damage but also suggest possible etiology.

Always do complete blood count (CBC), electrolytes, liver function test, and glucose.

Additional tests as indicated per clinical presentation include:

  • Thyroid stimulating hormone (TSH) and free thyroxine (FT4), iron studies, antinuclear antibody (ANA), and other autoimmune markers, viral serologies, and consider antimyosin antibody testing especially if viral myocarditis is suspected as a cause of DCM. Anti-myosin antibody can also be useful in differentiating viral myocarditis from ischemic cardiomyopathy.

  • Thiamine, carnitine, and selenium.

  • Genetic testing especially when familial cardiomyopathy is suggested.

  • B-type natriuretic peptide (BNP) or N-terminal pro b-type natriuretic peptide (NT pro-BNP).

Note, BNP has been studied in relation to heart failure and different cardiomyopathies for its possible role in prognosis and severity of the disease. It is important in the initial evaluation especially in the absence of other comorbidities where an elevated BNP or NT-pro BNP indicates increased fluid in atrium.

Echocardiography (ECHO)

ECHO is needed for the diagnosis of new onset heart failure and also for evaluation of any decompensation of chronic heart failure and any suspected heart failure syndromes. It can be helpful in the evaluation of:

  • LV, and RV size, ventricular functions

  • Possible identification of etiology

  • Infiltrative disease (sparkling pattern in myocyte is suggestive of amyloidosis)

  • Intra-cardiac mass/thrombus and shunts

  • Pericardial thickness to rule out constrictive pericarditis

  • Right and left atrial pressures

DCM is usually associated with biventricular dilation. Regional wall motion abnormalities usually indicate ischemic heart disease yet can be seen frequently in DCM (50-60% of patients).

Evaluation of ischemic heart disease

Atherosclerotic coronary disease could be a primary etiology leading to ischemic heart disease and ischemic cardiomyopathy or can be present concomitantly along with other cardiomyopathies. Stress testing should be part of initial workup of heart failure and may be done by nucleotide myocardial perfusion scan, positron emission tomography (PET) scan, or dobutamine echo.

Exercise testing in heart failure is usually avoided given exercise is poorly tolerated. However, progression of the disease to advance stages may be monitored with repeated exercise VO2 max (maximal oxygen uptake) evaluations. VO2 max is the best clinical prognostic indicator to predict need for advanced heart failure measures like mechanical circulatory support, continuous inotropic support or listing for cardiac transplant. An alternate to VO2 max is the 6-minute walk which can distinguish between class III and class IV heart failure; however, it correlates less well with class I and II when compared with VO2. It has been used with relatively less sensitivity and specificity, but with significant ease of testing. It is a well-tolerated and acceptable routine follow-up test.

Coronary angiography

The presence of ischemic heart disease is important prognostically even when it is not directly responsible for heart failure symptoms or LV dysfunction. The 2013 practice guideline from the American College of Cardiology (ACC)/American Heart Association (AHA) recommends: for patients with known CAD and angina, or with significant ischemia diagnosed by ECG, or noninvasive testing and impaired ventricular function; coronary angiography is indicated. Among those without a prior diagnosis, CAD should be considered as a potential etiology of impaired LV function and should be excluded wherever possible. Coronary angiography may be considered in these circumstances to detect and localize large-vessel coronary obstructions. In patients with whom CAD has been excluded as the cause of LV dysfunction, coronary angiography is generally not indicated unless a change in clinical status suggests interim development of ischemic disease. It is important to note that cardiac catheterization is a significant invasive procedure and has around 1% risk of serious complications such as embolization, infarction, arrhythmias, tamponade, stroke, or death.

Non-invasive coronary angiography can be obtained with cardiac computed tomography (CCT) and cardiac magnetic resonance (CMR). CCT is highly sensitive in identifying CAD using both 16-slice and 64-slice scanners with comparable sensitivities (86% vs. 90%) and specificities (96% vs. 97%). However, it is most useful in its high negative value. Hence, absence of coronary artery calcification on CCT indicates non-ischemic disease and invasive cardiac catheterization may not be needed in that case.

CMR is a useful non-invasive imaging tool in new onset heart failure evaluation as it is not only able to identify inflammation, fibrosis, myocardial perfusion, and viability, but can also isolate particular patterns of myocardial involvement to isolate cases of amyloidosis, hypertrophic cardiomyopathy (HCM), and arrhythmogenic right ventricular dysplasia (ARVD). CMR provides high anatomical resolution of all aspects of the heart and surrounding structures, leading to its recommended use in known or suspected congenital heart disease. Another ability of CMR is to assess strain pattern on myocardial walls which could be an early sign or etiology for LV dysfunction.

Despite significant superior functional evaluation of myocardial tissue by CMR, CCT is better able to depict coronary artery angiography or anatomic obstruction. The choice of test used depends on the need of a particular patient and the clinical suspicion of the provider.

Endomyocardial biopsy

EMB has become a major diagnostic tool in evaluation of new onset heart failure and suspected DCM. The procedure has been in use since 1962 with development of the first bioptome by Konno-Sakakibara. EMB has since then been modified with improved flexibility and small jaws leading to decline in procedural risks. EMB has been used primarily for the evaluation of allograft functions and rejection evaluation in transplanted patients. Its use is expanding especially after the joint AHA, ACC and European Society of Cardiology (ESC) 2007 statement regarding specific clinical conditions where EMB is recommended.

EMB should be performed in DCM evaluation for:

  • Unexplained new onset of DCM (symptoms started within 2 weeks)

  • Unexplained new onset of DCM (symptoms between 2 weeks to 3 months) with presence of ventricular arrhythmia or AV blocks (second or third degree)

EMB should be considered in the following conditions:

  • Unexplained new onset of DCM (symptoms over 3 months) with presence of ventricular arrhythmia or AV blocks (second or third degree) or failure to response to usual treatment

  • Unexplained heart failure of any duration with eosinophilia

  • Unexplained heart failure with history of anthracycline use

  • Heart failure with unexplained restrictive cardiomyopathy

  • Cardiac tumors

  • Unexplained heart failure in children

EMB can be done in following cases but should be avoided unless clinically necessary (weak recommendation):

  • Unexplained new onset of DCM (Symptoms between 2 weeks to 3 months) but no ventricular arrhythmia or AV blocks (second or third degree)

  • Unexplained DCM (symptoms over 3 months) with no ventricular arrhythmia or AV blocks (second or third degree)

  • Suspected HCM

  • Suspected ARVD

  • Unexplained arrhythmias

EMB should not be done in the following case:

  • Unexplained atrial fibrillation

Even with improved techniques, risk of life threatening complications of EMB is around 1%. These complications include pericardial tamponade, arrhythmias, heart block, pneumothorax, arterial puncture, hematoma, tricuspid valve damage, arteriovenous fistula, deep vein thrombosis, and death. The risk of myocardial perforation is 0.42% and the risk of death is 0.03%.

C. Criteria for Diagnosing Each Diagnosis in the Method Above.

DCM is diagnosed with the presence of the following on cardiac imaging:

  • Left ventricular end diastolic volume more than 112% of normal

  • Left ventricular ejection fraction is less than 45% of normal

Other conditions that are present along with this condition but may not be needed for diagnosis are:

  • LV spherical dilation

  • Normal or reduced wall thickness but poor wall thickening in systole

  • Dyssynchrony movement

  • Four chambers enlargement.

Once identified, different etiologies are subjected to different laboratory testing, CMR, and biopsy. The results of one or the other may suggest an etiology.

D. Over-utilized or “wasted” diagnostic tests associated with the evaluation of this problem.

Once heart failure is suspected, along with other testing, an echocardiogram is usually able to establish diagnosis of DCM. The workup to identify exact etiology does need extensive and further testing. If an obvious cause is present, it is more likely than not to be the etiology as well. However, many patients may have a multitude of causes and multifactorial etiology of their cardiomyopathy. Testing needs to be done using clinical acumen and should be decided on case-by-case basis.

However, there are many tests that need not be done if answers are not likely to change management. BNP or NT-pro-BNP has been extensively used and has been implicated in prognostic value as well. The use of BNP clinically needs to be evaluated and every patient may not need this on every encounter especially in the presence of other comorbidities. A renal failure patient is almost always expected to have higher BNP values. We know DCM is a state of high neurohormonal activation that is ill suited in the long and short term for patients. It is not needed to check renin and aldosterone levels.

If CMR is already done with good stress test showing no ischemic changes, a CCT to look for anatomy may not be needed. A low calcium score patient on CCT may not need a full angiogram. Use of EMB should be considered where needed and is probably underutilized. However, it is associated with high morbidity and complication risk needs to be discussed in detail with patients.

III. Management while the Diagnostic Process is Proceeding

A. Management of dilated cardiomyopathy

Treatment of DCM depends on accurate identification of etiology and severity of heart failure. 2013 AHA/ACC guidelines prompted early treatment of heart failure before the onset of symptoms hence utilizing WHO stages and starting appropriate therapy at the earliest opportunity.

Overall treatment of DCM can be divided into two main focus groups. One treating the etiology and the second treating systolic heart failure syndrome with generalized treatment options. Treatment of systolic heart failure has two main arms: acute heart failure including acute decompensated chronic heart failure and chronic heart failure. See Figure 1.

Figure 1.

Overview of treatment of DCM.

Treatment of acute heart failure

About half of the cost of HF management in the United States is through managing acute heart failure (AHF) and related hospitalizations. The focus of the acute heart failure treatment is to stabilize the patient and improve hemodynamics during the acute phase. Patients generally present in peripheral and/or pulmonary edema with worsening cardiac output and cardiogenic shock. The treatment is usually in hospitalized settings and includes following measures.

Preload reduction: treatment of edema required dieresis. Knowing the patient’s dry weight and weight at presentation usually help estimate excess of fluid on board. Physical examination with jugular venous pressure (JVP) estimation, peripheral edema and lung examination will help dictate the end point for diuresis. Diuresis can be achieved either through pharmacologic measures (usually through loop diuretics in combination with another class of diuretics) and mechanical measures including ultrafiltration or dialysis. In advanced cases or with cardiogenic shock patients, accurate fluid estimation is required to dictate further therapy, hence non-invasive measures like LiDCO or echocardiogram or invasive procedures like Swan-Ganz catheter placement are usually deployed as necessary.

Other than diuretics, many venodilators have also been used to improve preload, such as nitrates and opiates. The Acute Decompensated Heart Failure National Registry data did show increased mortality and intensive care unit (ICU) admissions with opiate use. European Society of Cardiology still supports its use for AHF treatment.

Afterload reduction: maladaptive renin-angiotensin-aldosterone system in DCM leads to increased afterload resulting in elevated systemic vascular resistance, increased ventricular wall stress, low stroke volume and dropping cardiac output. Vasodilators remain the main stay of therapy for years for systolic heart failure through blunting effects of neurohormonal activation.

Vasodilation can be achieved through a number of agents. Angiotensin-converting enzyme inhibitors (ACEI) are the most effect agents used for this purpose. ACEI will be discussed in detail with treatment of chronic systolic heart failure. It is important to note that with acute heart failure many patients present with cardiorenal syndrome with prerenal insufficiency making ACEI use dangerous. Other commonly used vasodilators in acute heart failure are nitrates, nitroprusside, nesiritide and milrinone for its addition vasodilatory effect. Unlike most other conditions, the goal of afterload reduction therapy is to use the highest dose of vasodilators that the patient can tolerate compared to lowest dose that is effective.

Inotropic augmentation: inotropes are used in the treatment of AHF especially with patients in cardiogenic shock. The three main groups of inotropes used in AHF are beta-adrenergic agonists, type III phosphodiesterase inhibitors (PDEIs) and calcium channel sensitizers. Dopamine is used frequently for its characteristics to improve renal blood flow and lower doses are used as it can cause vasoconstriction at higher dosing making treatment counterintuitive. Dobutamine is a specific beta-adrenergic agonist commonly used for cardiogenic shock therapy. Milrinone is a PDEI that causes inotropy and also vasodilation, making it ideal for systolic heart failure therapy.

Rhythm stabilization: optimal hemodynamics are obtained with sinus rhythm, however achieving sinus rhythm is not always possible. Tachycardia of any etiology is shown time and again to adversely affect myocardial systolic functions. A good rate control and use of antiarrhythmic drugs are recommended as necessary. Beta blockers have shown significant improvement in chronic heart failure. Usually beta blockers are not initiated in the initial phases of acute heart failure especially when hemodynamic compromise is present.

Reduce ischemic injury: presence of concomitant coronary ischemia should be minimized and if present should be treated promptly. Medications like aspirin, anticoagulants, nitrates and beta blockers all can be given as necessary.

Cao, S, Zhou, Q, Chen, JL, Hu, B. “The differences in left atrial function between ischemic and idiopathic dilated cardiomyopathy patients: A two-dimensional speckle tracking imaging study”. J Clin Ultrasound. 2016 Mar 16.

Pinto, YM, Elliott, PM, Arbustini, E, Adler, Y. “Proposal for a revised definition of dilated cardiomyopathy, hypokinetic non-dilated cardiomyopathy, and its implications for clinical practice: a position statement of the ESC working group on myocardial and pericardial diseases”. Eur Heart J. vol. 37. 2016 Jun 14. pp. 1850-8.

Scheffold, N, Herkommer, B, Kandolf, R, May, AE. “Lyme carditis–diagnosis, treatment and prognosis”. Dtsch Arztebl Int. vol. 112. 2015 Mar 20. pp. 202-8.

Imran, TF, Rahman, I, Dikdan, S, Shah, R. “QT Prolongation and Clinical Outcomes in Patients with Takotsubo Cardiomyopathy”. Pacing Clin Electrophysiol. vol. 39. 2016 Jun. pp. 607-11.

Varga, ZV, Ferdinandy, P, Liaudet, L, Pacher, P. “Drug-induced mitochondrial dysfunction and cardiotoxicity”. Am J Physiol Heart Circ Physiol. vol. 309. 2015 Nov. pp. H1453-67.

Bouabdallaoui, N, Mouquet, F, Lebreton, G, Demondion, P. “Current knowledge and recent development on management of peripartum cardiomyopathy”. Eur Heart J Acute Cardiovasc Care. 2015 Oct 16.

Gopinathannair, R, Etheridge, SP, Marchlinski, FE, Spinale, FG. “Arrhythmia-Induced Cardiomyopathies: Mechanisms, Recognition, and Management”. J Am Coll Cardiol. vol. 66. 2015 Oct 13. pp. 1714-28.

Ipek, E, Demirelli, S, Ermis, E, Inci, S. “Sarcoidosis and the heart: A review of the literature”. Intractable Rare Dis Res. vol. 4. 2015 Nov. pp. 170-80.

Givertz, MM, Mann, DL. “Epidemiology and Natural History of Recovery of Left Ventricular Function in Recent Onset Dilated Cardiomyopathies”. Curr Heart Fail Rep. vol. 10. 2013 Dec. pp. 321-30.

Caforio, AL, Goldman, JH, Haven, AJ, Baig, KM. “Circulating cardiac-specific autoantibodies as markers of autoimmunity in clinical and biopsy-proven myocarditis”. Eur Heart J. vol. 18. 1997 Feb. pp. 270-5.

Yancy, CW, Jessup, M, Bozkurt, B, Butler, J. “2013 ACCF/AHA guideline for the management of heart failure: a report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines”. J Am Coll Cardiol. vol. 62. 2013 Oct 15. pp. e147-239.