Cardiomyopathy (Nonischemic)

DCM · Alcoholic · PPCM · Takotsubo · HCM · Infiltrative · complete reference · all subtypes · Full Card

Nonischemic DCM — Full

Symptoms / Exam

• Progressive exertional dyspnea → orthopnea (needing 2–3 pillows to sleep) → PND (waking from sleep gasping) → dyspnea at rest; fatigue; bilateral ankle and leg edema worse by end of day; reduced exercise tolerance; palpitations (AF, VT)

• Exam: displaced PMI (lateral + inferior — LV dilation); S3 gallop at apex (↑LVEDP + rapid ventricular filling); S4 if diastolic dysfunction co-exists; functional MR murmur (holosystolic at apex from annular dilation); JVD; bilateral crackles; bilateral pitting edema

• Etiologies to systematically exclude: ischemic (coronary angiography), alcohol (quantity + duration), peripartum window (PPCM), thyroid disease (TSH), hemochromatosis (ferritin + transferrin saturation), sarcoidosis (FDG-PET), HIV, chemotherapy/radiation, viral myocarditis (recent viral illness), genetic (family hx SCD or CM — LMNA, TTN, SCN5A)

Neg

• Pt denies chest pain or pressure that came on suddenly during exertion or at rest, especially with radiation to the arm or jaw, in a pattern suggesting intermittent coronary supply-demand mismatch — argues against ischemic CM as the etiology (ischemic CM is the most common cause of reduced EF overall; coronary angiography or CT coronary angiography is mandatory before labeling any CM as nonischemic; missing ischemic CM means missing revascularization as treatment)

• Pt denies drinking more than a couple of drinks on special occasions over the past decade — argues against alcoholic CM as the etiology (>80 g/day for >5 years in men causes alcoholic CM; if underreporting suspected, check GGT + MCV + collateral history; labeling as nonischemic DCM without ruling out alcohol means missing the most reversible cause)

• Pt denies giving birth within the last 5 months or being in the final month of pregnancy — argues against PPCM (PPCM window: last month of pregnancy through 5 months postpartum; outside this window + no prior cardiac disease = seek other nonischemic etiology; PPCM has distinct management implications including bromocriptine [Parlodel] and future pregnancy counseling)

• Pt denies feeling fine and doing their usual activities until a sudden, severe emotional shock or acute physical illness triggered the onset of chest pain and shortness of breath within hours — argues against Takotsubo CM (Takotsubo requires an identifiable acute emotional or physical stressor + sudden onset + apical ballooning on echo/ventriculography + no obstructive CAD on cath; chronic progressive dyspnea without a trigger is nonischemic DCM, not Takotsubo)

RF

• Family history of CM or SCD before age 50 (LMNA/TTN/SCN5A mutations — autosomal dominant in many; cascade family screening mandatory); prior myocarditis; autoimmune disease; chemotherapy (anthracyclines — cumulative dose-dependent; trastuzumab [Herceptin] — reversible; cyclophosphamide [Cytoxan]); chest radiation; hemochromatosis; thyroid disease; HIV; heavy alcohol use; pregnancy (PPCM)

Data

• Echo TTE (EF [normal >55%; mildly reduced 41–55%; moderately reduced 30–40%; severely reduced <30%]; LV dilation [LVEDD >60 mm in men, >55 mm in women]; global hypokinesis [uniform — vs ischemic where wall motion anomaly is regional]; functional MR from annular dilation; LV thrombus [apical — anticoag if present]; diastolic function; LVOTO in HCM)

• Coronary angiography or CT coronary angiography (mandatory before labeling nonischemic; CT coronary angiography adequate if low-intermediate pre-test probability for CAD; invasive angiography if high probability or revascularization planned; ischemic CM = regional wall motion abnormality + obstructive CAD in culprit territory)

• Cardiac MRI (gold standard for CM etiology; LGE pattern: midmyocardial/subepicardial stripe = nonischemic DCM; subendocardial/transmural = ischemic; patchy RV-insertion points + lateral = sarcoidosis; diffuse subendocardial = amyloid; absence of LGE = better prognosis in DCM; LMNA: midmyocardial LGE + AV block on ECG; T1 mapping for inflammation; EF most accurate by MRI)

• Genetic testing (LMNA [lamin A/C — AV block + VT + SCD; early ICD]; TTN [titin — most common genetic DCM; ~20% of familial DCM]; SCN5A [Nav1.5 — AV block + Brugada]; MYBPC3/MYH7 [HCM]; cascade family screening for all first-degree relatives of identified mutation carriers)

• BNP or NT-proBNP (severity marker; treatment response; BNP >400 pg/mL = high risk; target ↓>30% with treatment)

• BMP (Cr/K+ — GDMT monitoring; hyperkalemia risk with Entresto + Aldactone; hyponatremia = poor prognosis)

• TSH, iron studies (ferritin + transferrin saturation), HIV serology, ANA + ANCA, viral serology (Coxsackievirus, parvovirus B19, CMV, HIV), endomyocardial biopsy (rapidly progressive CM + suspected giant cell myocarditis/eosinophilic/sarcoid — indicated when etiology unclear and management would change)

DDx

Ischemic CM (regional WMA + obstructive CAD on angiography — revascularization + GDMT; most common cause of reduced EF overall) · Alcoholic CM (EF recovers with abstinence; GGT + MCV elevated; thiamine before glucose) · PPCM (last month pregnancy→5 months postpartum; bromocriptine [Parlodel] + GDMT; no future pregnancy until EF recovered) · Takotsubo (acute emotional/physical trigger + apical ballooning + no CAD on cath; avoid inotropes if LVOTO) · HCM (thick walls + LVOTO + family hx SCD; BB + mavacamten [Camzyos]; myectomy if refractory) · Cardiac amyloid (thick walls + low ECG voltage + sparkling echo + 99mTc-PYP Grade 2–3; tafamidis [Vyndaqel]; avoid digoxin [Lanoxin]/ACEi/BB) · Cardiac sarcoidosis (AV block + VT + hilar adenopathy; FDG-PET diagnostic; prednisolone [Deltasone] + ICD)

Takotsubo — Full

Pathophysiology + Exam

• Catecholamine surge from acute emotional/physical stressor → transient apical myocardial stunning; apical and mid-ventricular ballooning with hyperdynamic basal segments; resolves fully in 4–8 weeks in most; STE in anterior leads on ECG mimics STEMI (but no obstructive CAD on cath); modest troponin elevation; LVOTO in 20% (basal hypercontractility narrows LVOT → dynamic gradient → hemodynamic compromise)

• Triggers: sudden emotional shock (death of loved one, relationship breakdown, argument — "broken heart syndrome"), acute medical illness (sepsis, surgery, stroke, hypoglycemia), physical stressors

• Predominantly postmenopausal women; recurrence rate 5–10%/year

Neg

• Pt denies any identifiable emotional shock, sudden bad news, acute hospitalization, or physical stress in the days before the chest pain started — argues against Takotsubo (Takotsubo requires an acute trigger; chest pain without a trigger + STE → treat as STEMI and take to cath; Takotsubo is always a diagnosis made at catheterization when no obstructive CAD is found)

• Pt denies the shortness of breath and fatigue having started gradually over weeks to months before the acute event — argues against a pre-existing CM being unmasked (Takotsubo is acute and fully reversible in most cases; chronic progressive symptoms before the acute event suggest underlying structural disease — seek alternative etiology)

• Pt denies feeling progressively worse despite being weeks out from the triggering event with an EF that has not recovered on repeat echo — argues against typical Takotsubo recovery (EF typically fully normalizes by 4–8 weeks; failure to recover EF at 3 months should prompt re-evaluation: cardiac MRI + endomyocardial biopsy to exclude myocarditis or alternative CM)

Plan

• Emergent coronary angiography (cannot distinguish from STEMI before cath; Takotsubo is a diagnosis of exclusion); if LVOTO gradient >25 mmHg on echo: avoid inotropes, vasodilators, diuretics; IV fluids + phenylephrine (Neo-Synephrine) 100–200 mcg IV bolus → 50–300 mcg/min infusion (↑SVR → ↓LVOTO gradient → ↑forward CO); IV BB: metoprolol tartrate (Lopressor) 5 mg IV over 5 min q5 min ×3 doses (↓HR → ↓LVOTO); if shock NOT from LVOTO: Impella CP (Abiomed) mechanical support

• ACEi/ARB or Entresto + BB ×3–6 months during recovery; repeat echo at 4–8 weeks; ICD deferred unless EF fails to recover at 3 months; anticoag if LV apical thrombus (warfarin [Coumadin] or rivaroxaban [Xarelto] ×3 months); anxiolytic/SSRI for recurrence prevention in emotionally-triggered Takotsubo (sertraline [Zoloft] 25–50 mg PO daily)

HCM — Full

Pathophysiology + Exam

• Sarcomere mutations (MYH7 [beta-myosin heavy chain] — most severe; MYBPC3 [myosin binding protein C] — most common; autosomal dominant; ↑myocyte disarray + fibrosis + diastolic dysfunction); asymmetric septal hypertrophy ≥15 mm; LVOTO in 70% (obstructive HCM — HOCM)

• Dynamic murmur: harsh crescendo-decrescendo at LLSB; increases with Valsalva straining, standing, nitrates (↓preload → ↑LVOTO); decreases with squatting, passive leg raise, phenylephrine (↑preload → ↓LVOTO) — dynamic maneuvers are the bedside diagnostic key; S4 gallop (stiff non-compliant LV); SAM of anterior mitral leaflet (systolic anterior motion → MR)

• SCD risk in young athletes — most common cardiac cause of sudden death in competitive athletes under 35; evaluate all young athletes with unexplained syncope or exertional symptoms

Neg

• Pt denies their chest discomfort and lightheadedness getting better when they squat down or sit down quickly after exertion, and worsening when they stand up abruptly after exercise — argues against obstructive HCM (HCM: ↑preload with squatting or passive leg raise relieves LVOTO gradient and symptoms; symptoms worsening with standing = ↓preload = ↑gradient = HCM; if symptoms unchanged with postural maneuvers, reconsider HCM)

• Pt denies a sibling or parent dying unexpectedly of a cardiac event before age 50 or being told they have a thick heart — argues against familial HCM as etiology (familial HCM: autosomal dominant; 50% of first-degree relatives carry the mutation; all first-degree relatives of HCM patients must undergo genetic testing + echo screening; the absence of family history does not exclude HCM — up to 40% are de novo mutations)

• Pt denies symptoms that started during childhood or adolescence or that have been present since their twenties — argues against HCM being missed for decades (HCM is often symptomatic from young adulthood; a 60-year-old presenting with new HF and thick walls is more likely amyloid than HCM; age at presentation + LGE pattern + 99mTc-PYP + ECG voltage are the distinguishing features)

Plan

• BB first-line for symptomatic HOCM: metoprolol succinate (Toprol-XL) 100–200 mg PO daily or atenolol (Tenormin) 50–100 mg PO daily (↓HR → ↑diastolic filling time → ↓LVOTO gradient + ↓SAM); verapamil (Calan SR) 120–480 mg PO daily (alternative if BB not tolerated; negative inotrope → ↓gradient; caution: avoid if severe LVOTO or HF)

• Disopyramide (Norpace) 100–300 mg PO BID + BB (refractory LVOTO gradient >50 mmHg on BB alone; potent negative inotrope + ↓SAM; QT prolongation — monitor; monitor with Holter; requires specialist)

• Mavacamten (Camzyos) 5 mg PO daily → titrate to 10 mg → 15 mg based on echo gradient at 8–12 weeks (EXPLORER-HCM 2020, NEJM: ↓LVOTO gradient; ↓symptoms NYHA class; FDA-approved 2022 for symptomatic obstructive HCM; cardiac myosin inhibitor — ↓force generation → ↓LVOTO; avoid if LVEF <55%; monitor EF q12 weeks; drug interaction with strong CYP2C19 inhibitors)

• Avoid vasodilators (nitrates, hydralazine [Apresoline], amlodipine [Norvasc]) — ↓preload → ↑LVOTO → worsening obstruction and syncope; avoid digoxin (Lanoxin) — positive inotrope → ↑LVOTO; avoid diuretics alone without BB (volume depletion → ↑LVOTO)

• Septal reduction therapy (refractory HOCM — NYHA III–IV despite maximized mavacamten + BB + disopyramide): surgical septal myectomy (gold standard; removes obstructing septal muscle; mortality <1% at expert centers; ↓gradient >90%; durable); alcohol septal ablation (catheter-based; inject absolute alcohol into septal perforator → controlled septal MI → ↓gradient; ↑AV block risk 10–20% requiring PM; preferred in elderly or high surgical risk)

• ICD (SCD prevention): Class I: prior cardiac arrest or sustained VT; Class IIa: ESC HCM SCD Risk Calculator >6%/5yr (inputs: age + max wall thickness + LA diameter + LVOTO gradient + family hx SCD + unexplained syncope + NSVT on Holter); Class IIb: 4–6%/5yr; LGE burden >15% of LV mass on MRI = additional risk marker regardless of score

• Competitive sport restriction: all patients with HCM should avoid competitive athletics; low-moderate intensity exercise (walking, swimming, cycling at low intensity) permitted; shared decision-making for recreational athletes

• AF management in HCM: anticoag mandatory (stroke risk very high in HCM+AF; DOAC or warfarin [Coumadin]); cardioversion if hemodynamic compromise; disopyramide (Norpace) or amiodarone (Pacerone) for rhythm control; BB for rate control; catheter ablation for refractory AF

• Genetic testing + cascade family screening: test for MYH7 + MYBPC3 + TNNT2 + TNNI3; if mutation found → screen all first-degree relatives; echo annually in gene-positive family members even if echo initially normal (may manifest later)

Cardiac Amyloidosis — Full

Neg

• Pt denies their heart failure symptoms responding well to standard diuretic doses without dizziness or lightheadedness on standing, and tolerating ACEi or ARB without significant drop in blood pressure — argues against cardiac amyloidosis (amyloid patients are exquisitely sensitive to preload reduction and GDMT; orthostatic hypotension + intolerance to ACEi/ARB in a patient with thick LV walls + HFpEF = amyloid until proven otherwise; GDMT that patients tolerate normally argues against amyloid)

• Pt denies noticing numbness or tingling in both hands for years before the heart failure, or needing carpal tunnel surgery — argues against ATTR-CM (ATTR amyloid: carpal tunnel syndrome is a sentinel feature that often precedes cardiac symptoms by 5–10 years in wild-type ATTR; bilateral carpal tunnel + HFpEF + thick walls in an elderly man = ATTR until proven otherwise)

• Pt denies bloody or frothy urine, foamy urine, or progressive kidney swelling suggesting protein loss — argues against AL amyloidosis with nephrotic syndrome as a concurrent feature (AL amyloid frequently involves kidneys with nephrotic-range proteinuria; the absence of renal involvement slightly favors ATTR over AL, but 99mTc-PYP scan and serum free light chains are required to distinguish definitively)

Plan

• 99mTc-PYP scan to confirm ATTR (Grade 2–3 uptake + H/CL ratio >1.5 = ATTR confirmed if AL excluded by serum/urine SPEP + free light chains); AL amyloid: serum free light chains + bone marrow biopsy + fat pad biopsy; cardiac MRI (T1 mapping + diffuse subendocardial LGE)

• Tafamidis (Vyndaqel) 61 mg PO daily (ATTR-ACT trial 2018, NEJM: ↓all-cause mortality 30%; ↓CV hospitalization 32%; approved for ATTR-CM wild-type and hereditary; start at diagnosis regardless of NYHA class; expensive — prior authorization required; start process early); eplontersen (Wainua) or patisiran (Onpattro) IV (hereditary ATTR — RNA interference → ↓TTR production; for concurrent polyneuropathy)

• AVOID: digoxin (Lanoxin) absolutely contraindicated — binds amyloid fibrils → toxicity at therapeutic levels; ACEi/ARB — profound hypotension (autonomic dysfunction from amyloid infiltration); BB — bradycardia + ↓CO in restrictive physiology; calcium channel blockers (diltiazem [Cardizem]/verapamil [Calan]) — negative inotropy → decompensation

• Diuretics (furosemil [Lasix] + spironolactone [Aldactone]) — use carefully; goal: dry weight without orthostasis; daily weights; compression stockings for orthostatic hypotension; fludrocortisone (Florinef) 0.1 mg PO daily (orthostatic hypotension)

• Anticoag for AF (extremely high stroke risk in amyloid + AF — start DOAC or warfarin [Coumadin] at first AF episode; amyloid patients are stroke-prone even with "paroxysmal" AF); ICD if sustained VT or complete AV block; genetic testing for TTR gene mutation (V30M most common hereditary; cascade family screening)

• AL amyloid: hematology-directed plasma cell therapy (bortezomib [Velcade]/cyclophosphamide [Cytoxan]/dexamethasone [Decadron] + daratumumab [Darzalex]; stem cell transplant if eligible and cardiac function sufficient); treat CM supportively while hematologic response monitored

Cardiac Sarcoidosis — Full

Neg

• Pt denies noticing visual changes (blurred vision, eye redness, floaters) or skin changes (raised red nodules on the shins or violaceous plaques on the face) alongside the heart rhythm problems — argues against systemic sarcoidosis with cardiac involvement (cardiac sarcoidosis often accompanies pulmonary + extracardiac sarcoidosis; uveitis + erythema nodosum/lupus pernio + hilar adenopathy on CXR + unexplained AV block = sarcoidosis until proven otherwise; the absence of extracardiac features does NOT exclude isolated cardiac sarcoidosis, however)

• Pt denies bilateral hilar lymphadenopathy on chest imaging or a prior diagnosis of sarcoidosis in the lungs or skin — argues against systemic sarcoidosis as the primary etiology (if hilar adenopathy absent + no prior sarcoidosis + AV block in a young patient, Lyme carditis and giant cell myocarditis enter the differential; FDG-PET is the test that establishes cardiac sarcoidosis regardless of extracardiac findings)

Plan

• FDG-PET (active myocardial inflammation — patchy uptake; distinguishes inflammation from scar; guides immunosuppression; baseline before starting steroids; repeat at 6 months to assess response)

• Prednisolone (Deltasone) 40–60 mg PO daily (initiate at diagnosis of active inflammation on FDG-PET; may reverse AV block if started in early inflammatory phase; taper over 6–12 months guided by repeat FDG-PET and CRP; do not taper if FDG-PET still active)

• Methotrexate (Rheumatrex) 10–25 mg PO weekly (steroid-sparing; add when prednisolone [Deltasone] tapering to avoid relapse; monitor LFTs + CBC monthly; folic acid 1 mg PO daily to ↓toxicity)

• ICD strongly preferred over PM for AV block in cardiac sarcoidosis (high SCD risk from VT even when presenting with bradycardia; implant ICD not isolated PM); amiodarone (Pacerone) 200 mg PO daily for VT suppression; VT ablation for recurrent VT despite antiarrhythmics; GDMT if EF reduced

• Pulmonology/rheumatology co-management; repeat FDG-PET at 6 months; ACE level and serum calcium quarterly (disease activity markers); annual echo + Holter

GDMT for All Reduced EF Cardiomyopathies

• ARNi (first-line, preferred over ACEi): sacubitril/valsartan (Entresto) 24/26 mg PO BID → target 97/103 mg PO BID (PARADIGM-HF 2014, NEJM: ↓CV death/HF hosp 20% vs enalapril [Vasotec]; ↓all-cause mortality 16%; washout ACEi ×36h before starting Entresto to avoid angioedema); if ACEi instead: lisinopril (Zestril) 2.5→40 mg PO daily or enalapril (Vasotec) 2.5→20 mg PO BID

• Beta-blocker (3 proven in HFrEF — no others): carvedilol (Coreg) 3.125 mg PO BID → 25 mg PO BID (COPERNICUS: ↓mortality 35%); metoprolol succinate (Toprol-XL) 12.5 mg PO daily → 200 mg PO daily (MERIT-HF: ↓mortality 34%); bisoprolol (Zebeta) 1.25 mg PO daily → 10 mg PO daily (CIBIS-II: ↓mortality 34%); start low and double every 2 weeks; do NOT start in acutely decompensated HF — must be euvolemic first

• MRA: spironolactone (Aldactone) 25→50 mg PO daily (RALES: ↓mortality 30%; K+ <5.0 + Cr <2.5 required); eplerenone (Inspra) 25→50 mg PO daily (EMPHASIS-HF: ↓mortality 24%; fewer gynecomastia side effects vs spironolactone [Aldactone]); monitor K+ weekly ×4 weeks then monthly; hold if K+ >5.5

• SGLT2i: dapagliflozin (Farxiga) 10 mg PO daily (DAPA-HF: ↓CV death/worsening HF 26%; works regardless of diabetes status); empagliflozin (Jardiance) 10 mg PO daily (EMPEROR-Reduced: ↓CV death/HF hosp 25%); avoid if eGFR <20; genital mycotic infections common

• Diuretics (symptom relief, not mortality benefit): furosemide (Lasix) 20–80 mg PO/IV daily → titrate to euvolemia; torsemide (Demadex) 10–40 mg PO daily (better oral bioavailability than furosemide [Lasix]; may be preferred in chronic HF); add metolazone (Zaroxolyn) 2.5–5 mg PO 30 min before furosemide (Lasix) for diuretic resistance (↓Na+ reabsorption at different nephron segment)

• ICD (primary prevention): EF ≤35% after ≥3 months optimized GDMT + NYHA II–III (MADIT-II 2002: ↓mortality 31%; SCD-HeFT 2005: ↓mortality 23%); exception: LMNA mutation CM — ICD regardless of EF (high SCD risk even at EF 45%); re-evaluate EF at 3–6 months on GDMT before ICD implant (may recover)

• CRT (cardiac resynchronization therapy): EF ≤35% + LBBB + QRS ≥150 ms + NYHA II–IV on GDMT (CARE-HF + COMPANION trials: ↓mortality + ↓HF hosp + ↑EF); CRT-D (defibrillator) preferred over CRT-P (pacemaker alone) if life expectancy >1 year; LBBB morphology required for maximum benefit; RBBB + QRS 120–149 ms = Class IIb only

• LV thrombus on echo: anticoag — warfarin (Coumadin) INR 2–3 ×3–6 months (traditional); rivaroxaban (Xarelto) 20 mg PO daily with meal is increasingly used (DOAC); repeat echo at 3 months (confirm resolution before stopping anticoag)

• Advanced HF therapies (refractory to max GDMT): IV inotropes: dobutamine (Dobutrex) 2–5 mcg/kg/min or milrinone (Primacor) 0.1–0.375 mcg/kg/min (bridge or palliative); LVAD (HeartMate 3 — FDA-approved; bridge to transplant or destination therapy); cardiac transplantation (EF <25% + max GDMT + VO2 max <12 mL/kg/min + no contraindications)

⚠ Red Flags

• Digoxin (Lanoxin) in cardiac amyloidosis → digoxin binds to amyloid fibrils → accumulates in myocardium → toxicity at normal serum levels (0.8–1.2 ng/mL); do NOT give digoxin (Lanoxin) to any patient with suspected or confirmed cardiac amyloidosis under any circumstances

• Inotropes (dobutamine [Dobutrex]) in Takotsubo with LVOTO → basal hypercontractility + inotrope → ↑LVOTO gradient → ↑dynamic obstruction → worsening cardiogenic shock; treat LVOTO-mediated shock with phenylephrine (Neo-Synephrine) + IV BB + volume, NOT inotropes

• ACEi/ARB/Entresto in cardiac amyloidosis → autonomic dysfunction from amyloid infiltration → absence of compensatory vasoconstriction → profound orthostatic hypotension; start at lowest dose possible if HF requires it; first dose in clinic with BP monitoring

• Starting BB before euvolemia in acute decompensated HF → negative inotropy + negative chronotropy in an already-failing, volume-overloaded ventricle → acute decompensation; never start or increase BB until the patient is euvolemic (dry weight, no rales, JVP normal)

• LMNA mutation CM without early ICD → LMNA patients have very high SCD risk from VT and complete AV block often occurring before EF reaches ≤35%; do not apply standard EF ≤35% ICD threshold to LMNA CM; ICD is indicated regardless of EF once diagnosis confirmed

• Missed PPCM future pregnancy counseling → PPCM recurs in 25–50% of subsequent pregnancies even after full EF recovery; maternal mortality is high in PPCM with recurrence; all PPCM patients must receive explicit counseling to defer pregnancy until EF fully recovers, and to discuss recurrence risk before conceiving again

Senior IM Resident Pearls

• Exclude ischemic CM before labeling nonischemic: ischemic CM is the most common cause of reduced EF; regional wall motion abnormality + obstructive CAD = ischemic CM (revascularization + GDMT); global hypokinesis + no obstructive CAD = nonischemic CM; coronary angiography or CT coronary angiography is the mandatory first step in every new CM workup

• ATTR-ACT trial (2018, NEJM) — tafamidis (Vyndaqel): tafamidis 80 mg (equivalent to Vyndaqel 61 mg) vs placebo in ATTR-CM → ↓all-cause mortality 30% (NNT ~6 over 30 months); ↓CV hospitalization 32%; approved for both wild-type and hereditary ATTR-CM; this is the only disease-modifying therapy for cardiac amyloidosis; start at diagnosis; the 99mTc-PYP scan is the key diagnostic test (Grade 2–3 uptake + negative AL markers = ATTR confirmed)

• Takotsubo LVOTO shock — completely opposite management to other cardiogenic shock: Takotsubo LVOTO: phenylephrine (Neo-Synephrine) + BB + volume (↑SVR + ↓HR → ↓gradient); regular cardiogenic shock: vasopressors + inotropes; giving inotropes (dobutamine [Dobutrex]) to Takotsubo LVOTO shock = ↑gradient = ↑shock = death; always check for LVOTO on bedside echo before initiating cardiogenic shock protocol in Takotsubo

• HCM dynamic murmur maneuvers — must know cold: murmur increases (↑LVOTO) with: Valsalva straining, standing, dehydration, nitrates, tachycardia; murmur decreases (↓LVOTO) with: squatting, passive leg raise, phenylephrine, bradycardia, handgrip; AS murmur is fixed and does not change significantly with preload maneuvers; this distinction is testable and clinically important when a patient presents with a systolic murmur at the LLSB

• EXPLORER-HCM (2020, NEJM) — mavacamten (Camzyos): mavacamten vs placebo in symptomatic obstructive HCM → ↓LVOTO gradient; ↑NYHA functional class; ↑exercise capacity; FDA-approved 2022; cardiac myosin inhibitor (first in class); titrate based on echo LVOTO gradient at 8–12 weeks; monitor EF q12 weeks (can ↓EF — hold if EF <50%); important CYP2C19 drug interactions (omeprazole [Prilosec] ↑mavacamten levels)

• LMNA cardiomyopathy — ICD before EF reaches 35%: LMNA (lamin A/C) mutation: DCM + AV block + VT + high SCD risk; SCD can occur when EF is still 40–50%; standard HFrEF ICD threshold (EF ≤35%) is too late; ICD is indicated once diagnosis confirmed regardless of EF; LMNA = AV block on ECG + midmyocardial LGE on cardiac MRI + DCM; genetic testing is confirmatory; all first-degree relatives must be screened

• Common mistake — not giving bromocriptine (Parlodel) in PPCM: bromocriptine (Parlodel) is Class IIa in PPCM (BROSC trial: ↑EF recovery rate; suppresses prolactin → ↓16-kDa prolactin fragment which directly damages cardiomyocytes); must add anticoag while on bromocriptine (thromboembolism risk); bromocriptine suppresses lactation — discuss with patient and OB; this therapy is frequently omitted; it is the most PPCM-specific intervention beyond standard GDMT