1.6 Device Therapy, HFpEF & the Cardiomyopathies

1. Device Therapy: ICD and CRT Indications

Implantable Cardioverter-Defibrillator (ICD)

• Primary Prevention Criteria (MADIT-II, SCD-HeFT):
  • LVEF <= 35%, NYHA Functional Class II or III symptoms on >=3 months of optimal GDMT, with reasonable expectation of meaningful survival >1 year.
  • Timing for Ischemic Cardiomyopathy: Must be >40 days post-myocardial infarction and >90 days post-revascularization (CABG or PCI) to allow for potential myocardial recovery.
  • Non-Ischemic Dilated Cardiomyopathy: >=3 months of optimal GDMT with persistent LVEF <=35% and NYHA II-III.
• Secondary Prevention: Indicated for patients who have survived sustained VT, VF arrest, or hemodynamically unstable VT not attributable to a transient or reversible cause (e.g., acute ischemia, hypokalemia).

Cardiac Resynchronization Therapy (CRT / Biventricular Pacing)

• Class I Indication:
  • LVEF <= 35%
  • Normal Sinus Rhythm
  • Left Bundle Branch Block (LBBB) morphology
  • QRS duration >= 150 ms
  • Symptomatic NYHA Class II, III, or ambulatory Class IV heart failure on optimal GDMT.
• Class IIa Indications: LBBB with QRS 120-149 ms; or non-LBBB morphology with QRS >= 150 ms and LVEF <=35%.
• Physiology: Corrects ventricular dyssynchrony by pacing both the right ventricle and the left ventricular lateral wall via the coronary sinus, improving cardiac output, reversing LV remodeling, and reducing mortality.

2. Management of HFpEF (LVEF >= 50%)

HFpEF accounts for >50% of heart failure cases, primarily driven by aging, hypertension, obesity, diabetes, and arterial stiffness.

• SGLT2 Inhibitors (Empagliflozin, Dapagliflozin): Class 1 recommendation. Reduces CV death and HF hospitalizations in preserved EF (EMPEROR-Preserved, DELIVER trials).
• Mineralocorticoid Receptor Antagonists (Spironolactone): Class 2a recommendation to reduce hospitalizations, especially in patients with LVEF near 50% (TOPCAT trial Americas subgroup).
• ARNI (Sacubitril/Valsartan): Class 2b recommendation, with greatest benefit observed in patients with LVEF 45-57% and women (PARAGON-HF trial).
• Loop Diuretics: Essential for symptom control and decongestion.
• Blood Pressure & Comorbidity Control: Target SBP <130 mmHg; strict control of atrial fibrillation (rate and rhythm) and screening for obstructive sleep apnea.

3. Cardiomyopathies

Hypertrophic Cardiomyopathy (HCM)

• Genetics & Pathophysiology: Autosomal dominant mutation in cardiac sarcomere protein genes (most commonly MYBPC3 [myosin-binding protein C] and MYH7 [beta-myosin heavy chain]). Characterized by myocyte disarray, asymmetric septal hypertrophy, and dynamic left ventricular outflow tract (LVOT) obstruction in ~70% of patients due to systolic anterior motion (SAM) of the anterior mitral leaflet contacting the hypertrophied septum, producing concomitant eccentric mitral regurgitation.
• Physical Examination: Harsh crescendo-decrescendo systolic ejection murmur loudest at the lower left sternal border (LLSB), radiating to the base but NOT the carotids, with a brisk bifid carotid pulse (pulsus bisferiens).
  • Dynamic Murmur Maneuvers:
    • Increases Murmur: Maneuvers that decrease LV preload or afterload (Valsalva strain, sudden standing, nitroglycerin administration) decrease LV chamber size, bringing the anterior mitral leaflet closer to the septum and worsening dynamic LVOT obstruction.
    • Decreases Murmur: Maneuvers that increase LV preload or afterload (squatting, passive leg raise, sustained handgrip) increase LV cavity volume and widen the outflow tract, reducing obstruction and softening the murmur.
• Medical Management:
  • First-line: Non-vasodilating Beta-blockers (Metoprolol, Propranolol, Atenolol) or non-dihydropyridine Calcium Channel Blockers (Verapamil, Diltiazem) to prolong diastole, increase ventricular filling, and reduce LVOT gradient.
  • Second-line / Add-on: Disopyramide (Class IA antiarrhythmic with negative inotropic properties).
  • Targeted Cardiac Myosin Inhibitors: Mavacamten (Camzyos) selectively inhibits cardiac myosin ATPase, reducing excessive actin-myosin cross-bridging and abolishing LVOT obstruction in symptomatic obstructive HCM (EXPLORER-HCM trial).
  • Contraindicated Drugs: Pure vasodilators (dihydropyridine CCBs like amlodipine, nitrates, ACEi/ARBs) and excessive diuretics, which decrease LV volume and trigger hemodynamic collapse from severe LVOT obstruction.
• Invasive Septal Reduction: Surgical septal myectomy (Morrow procedure) or alcohol septal ablation for drug-refractory NYHA III-IV symptoms with resting or provoked LVOT gradient >= 50 mmHg.
• Sudden Cardiac Death (SCD) Risk & ICD Indications: Primary prevention ICD recommended if >=1 major risk factor: massive LV hypertrophy (wall thickness >= 30 mm), unexplained recent syncope, family history of premature SCD in a first-degree relative, LV apical aneurysm, LVEF < 50%, or extensive late gadolinium enhancement (LGE >=15% of LV mass) on cardiac MRI.

Dilated Cardiomyopathy (DCM)

• Characterized by LV dilation and systolic dysfunction (LVEF <50%) in the absence of abnormal loading conditions (severe HTN/valvular disease) or CAD.
• Etiologies: Genetic (TTN [titin] truncating mutations, lamin A/C LMNA associated with high-grade AV block and ventricular arrhythmias), viral myocarditis (Parvovirus B19, HHV-6, Coxsackie B), toxic (alcohol, cocaine, anthracyclines [doxorubicin: dose-dependent irreversible vs trastuzumab: non-dose-dependent reversible], checkpoint inhibitors), peripartum cardiomyopathy (last month of pregnancy to 5 months postpartum; avoid future pregnancies if EF remains <50%), tachycardia-induced cardiomyopathy (reversible with rate/rhythm control).

Restrictive Cardiomyopathies (RCM)

Characterized by non-dilated, rigid ventricles with severe diastolic dysfunction, biatrial enlargement, and normal or near-normal systolic function.

1. Cardiac Amyloidosis:
   • AL Amyloidosis: Clonal plasma cell dyscrasia producing monoclonal immunoglobulin light chains (lambda > kappa). Associated with macroglossia, periorbital purpura (raccoon eyes), nephrotic syndrome, and peripheral neuropathy. Screen with serum free light chains (kappa/lambda ratio) and serum/urine immunofixation electrophoresis (IFE). Confirm with tissue biopsy (fat pad, bone marrow, or endomyocardial biopsy showing apple-green birefringence under polarized light with Congo red stain) and mass spectrometry. Treatment: Chemotherapy (Daratumumab + CyBorD) and autologous stem cell transplant.
   • ATTR Amyloidosis (Transthyretin): Wild-type (senile, elderly men, associated with carpal tunnel syndrome, spinal stenosis, and bicep tendon rupture) or Variant/Hereditary (TTR gene mutation, e.g., Val122Ile in African Americans). Diagnostic pathway: Technetium-99m Pyrophosphate (99mTc-PYP) bone scintigraphy demonstrating Grade 2 or 3 cardiac uptake in the absence of monoclonal proteins in serum/urine confirms ATTR without requiring heart biopsy. Treatment: Tafamidis (Vyndaqel/Vyndamax), a TTR tetramer stabilizer that reduces all-cause mortality and cardiovascular hospitalizations (ATTR-ACT trial).
   • ECG-Echo Discordance: Classic board finding of low voltage QRS complexes on ECG despite prominent concentric ventricular wall thickening on echocardiogram.
2. Hemochromatosis: Autosomal recessive HFE gene mutation (C282Y); iron deposition in myocardium causing dilated or restrictive phenotype, bronze diabetes, arthropathy, cirrhosis. Screen with transferrin saturation (>45%) and ferritin (>1000 ng/mL); confirm with cardiac MRI (T2* relaxation time <20 ms indicating myocardial iron overload). Treatment: Therapeutic phlebotomy or iron chelation (deferasirox, deferoxamine).
3. Cardiac Sarcoidosis: Non-caseating granulomas in young-to-middle-aged adults. Frequently presents with high-grade AV block, ventricular tachycardia, or sudden cardiac death. Cardiac MRI reveals patchy non-ischemic mid-wall or epicardial LGE; 18F-FDG PET scan shows active myocardial inflammation. Treatment: High-dose systemic corticosteroids (Prednisone 0.5-1 mg/kg/day), steroid-sparing immunosuppressants (Methotrexate), and early ICD implantation.