CARDIOLOGY
CARDIOMYOPATHIES
Diseases with mechanical and/or electrical dysfunction of the myocardium
DILATED CARDIOMYOPATHY (DCMP)
Definition and epidemiology (Circ 2006;113:1807)
• Ventricular dilatation and ↓ contractility ± ↓ wall thickness
• Incidence: 5–8/100,000/yr; prevalence: 1/2500. Most common reason for heart transplant.
Etiologies (NEJM 2000;342:1077; Circ Res 2012;111:131)
• Ischemia/infarct: systolic dysfxn & dilation due to poor remodeling post-MI
• Valvular disease: systolic dysfxn due to chronic volume overload in MR & AI
• Familial (~25%): mutations in cytoskeletal, nuclear and filament proteins (NEJM 1992;362:77)
• Idiopathic (~25%): ? undiagnosed infectious, alcoholic or genetic cause
• Infectious myocarditis (10–15%, autoimmune response; Lancet 2012;379:738)
Viruses (parvoB19 & HHV6 > coxsackie, adeno, echo, CMV, HCV): from subacute (dilated LV, mild–mod dysfxn) to fulminant (nondil., thick, edematous LV, sev dysfxn)
Bacterial, fungal, rickettsial, TB, Lyme (mild myocarditis, often with AVB)
HIV: ~8% of asx HIV 
; due to HIV, other virus or antiretrovirals; HIV also associated w/ premature CAD (Circ 2008;118:e36; Heart 2009;95:1193)
Chagas: apical aneurysm ± thrombus, RBBB, megaesophagus/colon (NEJM 1993;329:639)
• Toxic: alcohol (5%) typ. 7–8 drinks/d × >5 y, but variable; cocaine; XRT (usu RCMP);
anthracyclines (risk ↑ >550 mg/m2, may manifest late), cyclophosphamide, trastuzumab
• Infiltrative (5%): often mix of DCMP + RCMP (qv) with thickened wall
amyloidosis, sarcoidosis, hemochromatosis, tumor
• Autoimmune: collagen vasc. dis. (3%): PM, SLE, scleroderma, PAN, RA, Wegener’s;
peripartum (last month → 5 mo postpartum; JACC 2011;58:659): ~1:3000 preg. ↑ risk w/ multiparity, ↑ age, Afr Am; stnd HF Rx except if preg then select drugs based on safety; ? bromocriptine to ↓ prolactin; ~½ normalize EF; even if nl EF ~30% recur w/ next preg
Idiopathic giant cell myocarditis (GCM): avg age 42 y, fulminant, VT (NEJM 1997;336:1860)
Eosinophilic (variable peripheral eos): hypersensitivity (mild HF) or acute necrotizing eosinophilic myocarditis (ANEM; STE, effusion, severe HF)
• Stress-induced (Takotsubo = apical ballooning): mimics MI (pain, ± STE & ↑ Tn; deep TWI & ↑ QT); mid/apex dyskinesis; ? Rx w/ bB, ACEI; usu. improves over wks (JAMA 2011;306:277)
• Tachycardia: likelihood ∝ rate/duration; often resolves w/ rate cntl (Circ 2005;112:1092)
• Arrhythmogenic right ventricular cardiomyopathy (ARVC): fibrofatty replacement of RV → dilation (dx w/ MRI); ECG: ± RBBB, TWI V1–V3, e wave; risk VT (Lancet 2009;373:1289)
• Metab/other: hypothyroid., acromegaly, pheo, OSA, thiamine, selenium or carnitine defic
Clinical manifestations
• Heart failure: both congestive & poor forward flow sx; signs of L- & R-sided HF
diffuse, laterally displaced PMI, S3, ± MR or TR (annular dilat., displaced pap. muscle)
• Embolic events (~10%), supraventricular/ventricular arrhythmias, & palpitations
• Chest pain can be seen w/ some etiologies (eg, myocarditis)
Diagnostic studies and workup
• CXR: moderate to marked cardiomegaly, ± pulmonary edema & pleural effusions
• ECG: may see PRWP, Q waves or BBB; low-voltage; AF (20%); may be normal
• Echocardiogram: LV dilatation, ↓ EF, regional or global LV HK ± RV HK, ± mural thrombi
• Cardiac MRI: up to 76% Se, 96% Sp for myocarditis or infiltrative dis. ( JACC 2005;45:1815); extent of midwall fibrosis correlated w/ mortality in NICMP ( JAMA 2013;309:896)
• Laboratory evaluation: TFTs, iron studies, HIV, SPEP, ANA; others per clinical suspicion; viral serologies not recommended ( JACC 2012;59:779)
• Family hx (20–35% w/ familial dis.), genetic counseling ± genetic testing ( JAMA 2009;302:2471)
• Stress test: useful to r/o ischemia (low false 
rate), high false rate, even w/ imaging
• Coronary angiography to r/o CAD if risk factors, h/o angina, Qw MI on ECG, equivocal ETT; consider CT angiography (JACC 2007;49:2044)
• ? Endomyocardial biopsy (JACC 2007;50:1914): yield 10% (of these, 75% myocarditis, 25% systemic disease); 40% false rate (patchy dis.) & false (necrosis → inflammation)no proven Rx for myocarditis; ∴ biopsy if: acute & hemodyn compromise (r/o GCM, ANEM); arrhythmia or RCMP features (r/o infiltrative); or suspect toxic, allergic, tumor
Treatment (see “Heart Failure” for standard HF Rx)
• Implantation of devices may be tempered by possibility of reversibility of CMP
• Immunosuppression: for giant cell myocarditis (prednisone + AZA), collagen vascular disease, peripartum (? IVIg), & eosinophilic; no proven benefit for viral myocarditis
• Prognosis differs by etiology (NEJM 2000;342:1077): postpartum (best), ischemic/GCM (worst)
HYPERTROPHIC CARDIOMYOPATHY (HCMP)
Definition and epidemiology
• LV (usually ≥15 mm) and/or RV hypertrophy disproportionate to hemodynamic load
• Prevalence: 1/500; 50% sporadic, 50% familial, most asymptomatic
• Ddx: LVH 2° to HTN, AS, elite athletes (wall usually <13 mm & symmetric and nl/↑ rates of tissue Doppler diastolic relaxation; Circ 2011;123:2723), Fabry dis. (↑ Cr, skin findings)
Pathology
• Autosomal dominant mutations in cardiac sarcomere genes (eg, b-myosin heavy chain)
• Myocardial fiber disarray with hypertrophy, which creates arrhythmogenic substrate
• Morphologic hypertrophy variants: asymmetric septal; concentric; midcavity; apical
Pathophysiology
• Subaortic outflow obstruction: narrowed tract 2° hypertrophied septum + systolic anterior motion (SAM) of ant. MV leaflet (may be fixed, variable or nonexistent) and papillary muscle displacement. Gradient (∇) worse w/ ↑ contractility (digoxin, b- agonists, exercise, PVCs), ↓ preload or ↓ afterload.
• Mitral regurgitation: due to SAM (mid-to-late, post.-directed regurg. jet) and/or abnl
mitral leaflets and papillary muscles (pansystolic, ant.-directed regurg. jet)
• Diastolic dysfunction: ↑ chamber stiffness + impaired relaxation
• Ischemia: small vessel dis., perforating artery compression (bridging), ↓ coronary perfusion
• Syncope: Δs in load-dependent CO, arrhythmias
Clinical manifestations (70% are asymptomatic at dx)
• Dyspnea (90%): due to ↑ LVEDP, MR, and diastolic dysfunction
• Angina (25%) even w/o epicardial CAD; microvasc. dysfxn (NEJM 2003;349:1027)
• Arrhythmias (AF in 20–25%; VT/VF) → palpitations, syncope, sudden cardiac death
Physical exam
• Sustained PMI, S2 paradoxically split if severe outflow obstruction, S4 (occ. palpable)
• Systolic murmur: crescendo-decrescendo; LLSB; ↑ w/ Valsalva & standing (↓ preload)
• ± mid-to-late or holosystolic murmur of MR at apex
• Bifid carotid pulse (brisk rise, decline, then 2nd rise); JVP w/ prominent a wave
• Contrast to AS, which has murmur that ↓ w/ Valsalva and ↓ carotid pulses
Diagnostic studies
• CXR: cardiomegaly (LV and LA)
• ECG: LVH, anterolateral and inferior pseudo-Qw, ± apical giant TWI (apical variant)
• Echo: no absolute cutoffs for degree of LVH but septum/post. wall ≥1.3 suggestive,
as is septum >15 mm; other findings include dynamic outflow obstruction, SAM, MR
• MRI: hypertrophy + patchy delayed enhancement (useful for dx & prog) ( JACC CV Imag 2012;2:370)
• Cardiac cath: subaortic pressure ∇; Brockenbrough sign = ↓ pulse pressure post-PVC (in contrast to AS, in which pulse pressure ↑ post-PVC)
• ? Genotyping for family screening, but pathogenic mutation ID’d in <½ (Circ 2011;124:2761)
Treatment (Circ 2011;124:e783 & 2012;125:1432; Lancet 2013;381:242)
• Heart failure
inotropes/chronotropes: b-blockers, CCB (verapamil), disopyramide
Careful use of diuretics, as may further ↓ preload. Vasodilators only if systolic dysfxn. Avoid digoxin.
If sx refractory to drug Rx + obstructive physiology (∇ >50 mmHg):
(a) Surgical myectomy: long-term ↓ symptoms in 90% (Circ 2005;112:482)
(b) Alcohol septal ablation (Circ CV Interv 2011;4;256; JACC 2011;58:2322): gradient ↓ by ~80%, only 5–20% remain w/ NYHA III–IV sx; 14% require repeat ablation or myectomy. Good alternative for older Pts, multiple comorbidities. Complic: transient (& occ. delayed) 3° AVB w/ 10–20% req. PPM; VT due to scar formation.
No clear benefit of dual-chamber pacing ( JACC 1997;29:435; Circ 1999;99:2927)
If refractory to drug therapy and there is nonobstructive pathophysiology: transplant
• Acute HF: can be precip. by dehydration or tachycardia; Rx w/ fluids, bB, phenylephrine
• AF: rate control with bB, maintain SR with disopyramide, amiodarone
• SCD: ICD ( JACC 2003;42:1687). Risk factors: h/o VT/VF, FHx SCD, unexplained syncope, NSVT, ↓ SBP or rel HoTN (↑ SBP <20 mmHg) w/ exercise, LV wall ≥30 mm, extensive MRI delayed enhancement. EPS not useful. Risk 4%/y if high-risk (JAMA 2007;298:405).
• Counsel to avoid dehydration, extreme exertion
• Endocarditis prophylaxis not recommended (Circ 2007;16:1736)
• First-degree relatives: periodic screening w/ echo, ECG (as timing of HCMP onset variable). Genetic testing if known mutation.
RESTRICTIVE CARDIOMYOPATHY (RCMP)
Definition (Circ 2006;113:1807)
• Impaired ventricular filling with ↓ complicance in nonhypertrophied, nondilated ventricles; normal or ↓ diastolic volumes, normal or near-normal EF; must r/o pericardial disease
Etiology ( JACC 2010;55:1769)
• Myocardial processes
Autoimmune (scleroderma, polymyositis-dermatomyositis)
Infiltrative diseases (see primary entries for extracardiac manifestations, Dx, Rx)
Amyloidosis (CIrc 2011;124:1079): age at presentation ~60 y; 
:
= 3:2 AL (MM, light-chain, MGUS, WM); familial (transthyretin, TTR); AA/senile (TTR, ANP) ECG: ↓ QRS amplitude (50%), pseudoinfarction pattern (Qw), AVB (10–20%), hemiblock (20%), BBB (5–20%)
Echo: biventricular wall thickening (yet w/ low voltage on ECG), granular sparkling texture (30%), biatrial enlargement (40%), thickened atrial septum, valve thickening (65%), diastolic dysfxn, small effusions
Normal voltage & normal septal thickness has NPV ~90%
MRI: distinct late gadolinium enhancement pattern ( JACC 2008;51:1022)
Sarcoidosis: age at present. ~30 y; more common in blacks, N. Europeans, women
5% of those w/ sarcoid have overt cardiac involvement; cardiac w/o systemic in 10%
ECG: AVB (75%), RBBB (20–60%), VT; PET: ↑ FDG uptake in affected area
Echo: regional WMA (particularly basal septum) with thinning or mild hypertrophy
Nuclear imaging: gallium uptake in areas of sestaMIBI perfusion defects; cardiac MR
Hemochromatosis: in middle-aged men (esp. N. European); 15% p/w cardiac sx
Storage diseases: Gaucher’s, Fabry, Hurler’s, glycogen storage diseases
Diabetes mellitus
• Endomyocardial processes
Chronic eosinophilic: Löffler’s endocarditis (temperate climates; ↑ eos; mural thrombi that embolize); endomyocardial fibrosis (tropical climates; var. eos; mural thrombi)
Toxins: radiation (also p/w constrictive pericarditis, valvular dis, ostial CAD), anthracyclines
Serotonin: carcinoid, serotonin agonists, ergot alkaloids
Metastatic cancer
Pathology & pathophysiology
• Path: normal or ↑ wall thickness ± infiltration or abnormal deposition
• ↓ myocardial compliance → nl EDV but ↑ EDP → ↑ systemic & pulm. venous pressures
• ↓ ventricular cavity size → ↓ SV and ↓ CO
Clinical manifestations (Circ 2000;101:2490)
• Right-sided > left-sided heart failure with peripheral edema > pulmonary edema
• Diuretic “refractoriness”
• Thromboembolic events
• Poorly tolerated tachyarrhythmias; VT → syncope/sudden cardiac death
Physical exam
• ↑ JVP, ± Kussmaul’s sign ( JVP ↑ w/ inspiration, classically seen in constrictive pericarditis)
• Cardiac: ± S3 and S4, ± murmurs of MR and TR
• Congestive hepatomegaly, ± ascites and jaundice, peripheral edema
Diagnostic studies
• CXR: normal ventricular chamber size, enlarged atria, ± pulmonary congestion
• ECG: low voltage, pseudoinfarction pattern (Qw), ± arrhythmias
• Echo: symmetric wall thickening, biatrial enlarge., ± mural thrombi, ± cavity oblit. w/ diast dysfxn: ↑ early diast (E) and ↓ late atrial (A) filling, ↑ E/A ratio, ↓ decel. time
• Cardiac MRI/PET: may reveal inflammation or evidence of infiltration (but nonspecific)
• Cardiac catheterization
Atria: M’s or W’s (prominent x and y descents)
Ventricles: dip & plateau (rapid ↓ pressure at onset of diastole, rapid ↑ to early plateau)
Concordance of LV and RV pressure peaks during respiratory cycle (vs. discordance in constrictive pericarditis; Circ 1996;93:2007)
• Endomyocardial biopsy if suspect infiltrative process
• Restrictive cardiomyopathy vs. constrictive pericarditis: see “Pericardial Disease”
Treatment (in addition to Rx’ing underlying disease)
• Gentle diuresis. May not tolerate CCB or other vasodilators.
• Control HR (but can ↓ CO); maintain SR (helps filling). Digoxin ↑ arrhythmias in amyloid.
• Anticoagulation (particularly with AF or low CO)
• Transplantation for refractory cases