LV dysfunction and dilated cardiomyopathy: Etiologies and evaluation

1

What is the definition and incidence of heart failure?

• Heart failure (HF) is a clinical syndrome resulting from progressive myocardial dysfunction that compromises ventricular filling and cardiac output. HF patients may be broadly categorized as having HF with preserved ejection fraction (HFpEF) defined as left ventricular ejection fraction (LVEF) >50% to 55%, or patients who have HF with reduced ventricular ejection fraction (HFrEF) defined as LVEF <40%. HF phenotypes have been further stratified to include HF with mid-range ejection fraction (HFmEF) (LVEF 41%–49%), which has overlapping disease features and intermediate prognostic implications to that of HFpEF and HFrEF. HFmEF patients may include de novo HF and HF patients with previously reduced LV function that have recovered (HFm-recEF). These HF definitions represent a continuum of disease on the basis of LVEF. Categorical distinction is important as there are established therapeutic interventions from large clinical trials for patients with LVEF <40%; however, there are no specific therapies of proven benefit for patients with HFpEF.

• The lifetime risk of developing HF is approximately 20%, and the incidence increases with age. Overall survival has improved for HF; however, absolute mortality remains high at 50% within 5 years of diagnosis.

2

What is the major pathophysiology of HFrEF?

• Despite different etiologies for HFrEF, the compensatory mechanisms, pathophysiology, and maladaptive responses to LV dysfunction are similar. A primary insult to the myocardium (myocardial infarction, myocarditis, genetic mutation, toxins, etc.) leads to depression in LV systolic function and decreased systemic blood flow. The initial neurohormonal response activates the sympathetic nervous system and the renin-angiotensin-aldosterone system (RAAS) to maintain systemic perfusion through vasoconstriction and sodium and fluid retention. However, prolonged activation of the RAAS pathway is deleterious and leads to adverse cardiac remodeling, increased cardiac fibrosis, and inexorable disease progression. Evidenced-based pharmacologic therapies in HF powerfully target these pathways to stabilize disease and promote reverse remodeling ( Fig. 22.1 ).

  

3

What is dilated cardiomyopathy?

• Dilated cardiomyopathy (DCM) is a unifying term describing myocardial dysfunction with progressive LV wall thinning and dilation and reduced LVEF in the absence of abnormal loading conditions (i.e., hypertension or valvular disease). DCM is the most common form of cardiomyopathy; it represents a shared phenotype for a myriad of cardiac disorders that lead to myocardial damage and chamber dilation.

4

What are the common causes of DCM?

• Causes of DCM include genetic causes, toxins, infection, inflammatory disorders and collagen vascular diseases, nutritional disorders, pregnancy (also termed peripartum cardiomyopathy [PPCM]), endocrine disorders, tachycardia-induced cardiomyopathy, and stress-induced cardiomyopathy. Table 22.1 summarizes the various forms of DCM and management considerations.

  Table 22.1

  Dilated Cardiomyopathy: Different Etiologies and Management

  CAUSE	EXAMPLES	RISK FACTORS AND SELECTIVE TESTING a	MANAGEMENT
  Infectious	Viral: Adenovirus Parvovirus Enterovirus Influenza HIV COVID-19 Bacterial: Staphylococcus Streptococcus Borrelia burgdorferi Fungal Protozoal: Chagas disease	Troponin ESR/CRP HIV testing Trypanosoma cruzi serology Cardiac MRI Endomyocardial biopsy in certain cases	Immunosuppression for giant cell myocarditis Supportive care with lymphocytic myocarditis Consideration of early temporary mechanical support
  Genetic	Titin Lamin A/C B-Myosin heavy chain Myosin binding protein C Troponin T Troponin I Desmoplakin	Obtain a three-generation family history. Higher suspicion if >2 first-degree relatives with HF and/or family member <35 years of age with SCD	Genetic testing for first-degree relatives when proband is positive for disease-causing mutation
  Toxins	Alcohol Cocaine Amphetamines	Urine drug screen PeTH testing In cocaine use, consider coronary angiogram due to accelerated CAD risk	Abstinence may partially or completely reverse cardiomyopathy
  Arrhythmia	Tachycardia-mediated cardiomyopathy: Atrial fibrillation Atrial flutter PVC-mediated (>10% of heartbeats)	Holter or event monitoring	Arrhythmia control with pharmacotherapy or ablation
  Pregnancy	Peripartum cardiomyopathy	Pregnancy history (preeclampsia, maternal age, multiparty)	Beta-blockers, diuretics, hydralazine/isosorbide dinitrate, and digoxin used with caution during pregnancy (avoid ACEI) Limited evidence for routine use of bromocriptine
  Chemotherapy	Anthracyclines HER2 inhibitors Checkpoint inhibitors	Echo longitudinal strain imaging If concomitant radiation, assess risks for valvular and coronary disease	Reduce or discontinue offending agent, with cardio-oncology input Optimize cardioprotective drug therapy (i.e. beta-blockade and ACEI) Optimize vascular disease prevention (i.e., statin)
  Stress mediated	Takotsubo’s Sepsis	Coronary angiogram to r/o CAD; diagnosis of exclusion	Typically has self-limited course with recovery of LVEF Beta-blockers and ACEI may help prevent recurrence
  Endocrine/nutritional causes	Hyperthyroidism Hypothyroidism Cushing’s disease Pheochromocytoma Selenium deficiency Thiamine deficiency Acromegaly	TSH Vitamin testing Plasma/urine metanephrines Cortisol level	Repletion of depleted hormone/nutrient
  Collagen vascular disease/inflammatory disorders	Lupus Scleroderma Rheumatoid	ESR/CRP ANA/SCL-70 Assess for PVD	Immunosuppression Consideration of PH therapies in patients who develop associated PVD Screening for early CAD in select patients
  Iron overload	Hemochromatosis	Iron panel Ferritin level Cardiac MRI Biopsy	Iron chelation and phlebotomy

  ACEI, Angiotensin-converting enzyme inhibitor; ANA, antinuclear antibody; CAD, coronary artery disease; COVID-19 , coronavirus disease-2019; CRP, C-reactive protein; ESR, erythrocyte sedimentation rate; HER2, human epidermal growth factor receptor; HF , heart failure; HIV, human immunodeficiency virus; LVEF, left ventricular ejection fraction; MRI, magnetic resonance imaging; PeTH, phosphatidylethanol; PH, pulmonary hypertension; PVC, premature ventricular contraction; PVD , pulmonary vascular disease; SCD, sudden cardiac death; SCL-70 , topoisomerase 1; TSH , thyroid-stimulating hormone.

  a Selective workup in addition to the standard clinical evaluation including chest x-ray, electrocardiogram, echocardiogram, and laboratory data.

5

How does DCM present?

• Typical presenting symptoms of DCM include exertional dyspnea, fatigue, reduced exercise tolerance, weakness, orthopnea, paroxysmal nocturnal dyspnea, weight gain, early satiety, nausea, bendopnea, and lower extremity edema. Physical examination is notable for elevated jugular vein pressure (JVP), extra heart sounds (S3, S4), pulmonary congestion, and lower extremity edema. Physical exam signs that are most specific and associated with poor prognosis include elevated JVP and an S3 heart sound. With disease progression and development of right-sided dysfunction, patients can develop ascites, hepatomegaly, cardiac cirrhosis, and worse cardiorenal syndrome. In advanced HF, cardiac cachexia may develop, which manifests as muscle loss, temporal wasting, and higher degrees of frailty.

6

What diagnostic testing is part of the initial evaluation for patients with newly diagnosed DCM?

• A thorough history and physical examination should be performed on all patients with incident HF as this often provides clues for etiology. DCM may be genetic and/or acquired; a careful family history and review of risk factors and toxic exposures must be obtained. The recommended initial diagnostic testing includes a complete blood count, comprehensive metabolic panel, fasting lipid profile, urinalysis, thyroid-stimulating hormone (TSH), natriuretic peptide levels (B-type natriuretic peptide [BNP] or N-terminal pro B-type natriuretic peptide [NT-proBNP]), cardiac enzymes, chest radiograph, electrocardiogram (ECG), and echocardiography.

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