Cardiomyopathy & Myocarditis

Hye Young Lee

Sanggye Paik Hospital

Clinical Classification

1. Dilated: LV and/or RV enlargement, impaired systolic function

2. Hypertrophic: Disproportionate left ventricular hypertrophy,

with or without an intraventricular systolic pressure gradient

3. Restrictive: Endomyocardial scarring or myocardial infiltration

resulting in restriction to LV and/or RV filling

Dilated Restrictive Hypertrophic

Cause

Myocarditis

Metabolic/endocrine

Genetic

Infiltrative/storage diseases

Endomyocardial

Genetic

Genetic

Ejection fraction (normal

>55%)

Usually <30% when symptoms

severe25–50% >60%

LV diastolic dimension

(normal <55 mm)≥60 mm <60 mm (may be decreased) Often decreased

LV wall thickness Normal or decreased Normal or increased Markedly increased

Atrial sizeIncreased, may also be primarily

affectedIncreased; may be massive

Increased; related to elevated

filling pressures

Valvular regurgitation

Related to annular dilation; mitral

appears earlier during

decompensation; TR with RV

dysfunction

Related to endocardial

involvement;

frequent MR & TR, rarely severe

Related to valve-septum

interaction; mitral regurgitation

Common first Symptom Exertional intolerance

Exertional intolerance, fluid

retention early, may have

dominant right-sided symptoms

Exertional intolerance; may have

chest pain

Congestive SymptomLeft before right, except right

prominent in young adultsRight often dominates

Left-sided congestion at rest

may develop late

Arrhythmias

Ventricular tachyarrhythmia;

conduction block in Chagas’

disease, and some families. Atrial

fibrillation.

Ventricular uncommon except in

sarcoidosis, conduction block in

sarcoidosis and amyloidosis.

Atrial fibrillation.

Ventricular tachyarrhythmias;

atrial fibrillation

Presentation with Symptomatic Cardiomyopathy

• The early symptoms often relate to exertional intolerance with breathlessness or fatigue, usually from inadequate cardiac reserve during exercise

Genetic Etiologies of Cardiomyopathy

• HCMP: Well-recognized

• DCMP: Heritability is present in at least 30% of DCMP without other clear etiology.

• Careful family history should elicit not only known cardiomyopathy and heart failure, but also family members

– who have had sudden death

– who have had atrial fibrillation or pacemaker implantation by middle age

– who have muscular dystrophy

확장성 심근병증Dilated Cardiomyopathy

Major Causes of Dilated Cardiomyopathy

Inflammatory Myocarditis (Myocarditis + LV dysfunction)

Infective; viral parasitic, bacterial, fungal

Noninfective; sarcoidosis, eosinophillic myocarditis

Toxic

Alcohol

Catecholamines (amphetamines, cocaine)

Chemotherapeutic agents (anthracyclines, trastuzumab)

Metabolic

Nutritional deficiencies (thiamine, selenium, carnitine)

Electrolyte deficiencies (calcium, phosphate, magnesium)

Endocrinopathy (thyroid disease, pheochromocytoma,

diabetes)

Obesity

Familial

Skeletal and cardiac myopathy

Dystrophin-related dystrophy (Duchenne’s, Becker’s)

Mitochondrial myopathies (e.g., Kearns-Sayre syndrome)

Arrhythmogenic ventricular dysplasia

Hemochromatosis

Susceptibility to immune-mediated myocarditis

Familial

Skeletal and cardiac myopathy

Dystrophin-related dystrophy (Duchenne’s, Becker’s)

Mitochondrial myopathies (e.g., Kearns-Sayre

syndrome)

Arrhythmogenic ventricular dysplasia

Hemochromatosis

Susceptibility to immune-mediated myocarditis

Overlap with Nondilated Cardiomyopathy

“Minimally dilated cardiomyopathy”

Hemochromatosis

Amyloidosis

Hypertrophic cardiomyopathy (“burned-out”)

"Idiopathic"

Miscellaneous (Shared Elements of Above

Etiologies)

Arrhythmogenic right ventricular dysplasia

Left ventricular noncompaction

Peripartum cardiomyopathy

Tachycardia-related cardiomyopathy

Late after idiopathic LBBB

DCMP - Diagnosis

• Symptom & Sign– Heart failure

• DOE, orthopnea, edema• Narrow pulse pressure, JVP• 3rd & 4th heart sound, pansystolic murmur (MR or TR)

– Arrhythmia: palpitation, syncope– Systemic embolism d/t LV thrombus

• Laboratory exam– CXR, ECG– Echocardiography– Cardiac catheterization– Brain natriuretic peptide (BNP)

Chest PA

CardioThoracic Ratio

A

C

B

CT ratio = (B+C) /A

Echocardiography

DCMP

Chamber enlargement

Valvular regurgitation d/t annulus dilatation

Apical thrombus

Normal Echocardiography

심 근 염Myocarditis

Myocarditis - Overview

• Cardiac inflammation– Infectious causes

• Viral: 5% of all viral infection (Coxsackie B, influenza B)

• Trypanosoma cruzi

– Non-infectious causes

• Hypersensitivity (drugs, radiation, chemicals, etc)

• Sarcoidosis, giant cell myocarditis

• Most often self-limited and without sequelae

• Severe involvement may recur

• Occasionally progresses to a chronic form and to dilated cardiomyopathy

Infective Myocarditis

• Viral infection and replication can cause myocardial injury and lysis.

• Host response to infection

– Nonspecific innate immune response

• Toll-like receptors: recognize DAMP (Damage-associated molecular pattern)

– Cytokine release

– Activation and expansion of specific T- and B-cell populations

• Successful recovery from viral infection

– Immune response to limit viral infection

– Downregulation to prevent overreaction and autoimmune injury

• Secondary acquired immune response.

– Chronic viral myocarditis DCMP

Progression from infection through immune responses to DCMP

European Heart J 2011;32:2616–2625

Myocarditis – Diagnosis

• Hx of a preceding viral syndrome (fever, myalgia)

• Chest pain/discomfort, heart failure

• ECG

– Nonspecific ST-T abnormalities, Arrhythmia

– Myopericarditis: diffuse concave ST elevation

• Elevation of cardiac enzymes

• Echocardiography

• Cardiac MRI: mid-wall Gd enhancement

• Isolation of virus / specific antibody titers

• Endomyocardial biopsy

– Dallas criteria: Extensive lymphocyte infiltration with adjacent myocyte necrosis

– 전형적인 심근염 증상이 있는 환자의 10~20%에서만 양성

– Immunohistochemistry criteria

Myocarditis – Treatment

• Conservative care– Standard care for heart failure

– During acute infection, therapy with antiinflammatory or immunosuppressive medications is avoided,

– Exercise may be deleterious in patients with viral myocarditis, and strenuous activity should be proscribed until the ECG has returned to normal

• 심폐체외순환(ECMO, PCPS)

– In fulminant case

• Endomyocardial biopsy guided Tx (with immunohistology)

– Antiviral Therapy

– Immunosuppressive therapy

Toxic cardiomyopathy; Alcoholic cardiomyopathy

• Alcohol 및 acetaldehyde의 직접적인 심독성, 영양결핍(thiamin), 주류첨가제에 의한 독성

• 잦은 폭음 vs. 5~10년간 매일 알코올 ~120 ml 섭취

• 3~6개월 이상 알콜 섭취를 중지하면 이 질환의 경과를회복시키거나 진행되는 것을 방지

• 음주를 계속할 경우 심근손상과 섬유화가 진행되면서 심각한 심부전이 초래되어 예후가 나쁘다. (3년 생존율< 25 %)

• 심방세동이 동반되어 나타나는 경우가 많다. (Holiday heart syndrome)

Toxic cardiomyopathy; chemotherapyAnthracycline / Trastuzumab

Type I(Myocardial damage)

Type II(Myocardial dysfunction)

Typical agentAnthracyclin

(Doxorubicin)Trastuzumab(Herceptin)

MechanismFree radical formation,

oxidative stress/damageBlocked ErbB2 signaling

Cardiac tissueUltrastructural abnormalities

(e.g.. vacuoles, necrosis)

No ultrastructural abnormalities

Clinical course/response to therapy

Underlying damage permanent and

irreversible; may stabilize

Typically reversible; high likelihood of recovery in

2-4 mo

Dose effects Cumulative, dose related Not dose related

Metabolic cause of CMP

• Endocrine disorders; hyperthyroidism, hypothyroidism

pheochromocytoma

• Obesity

• Diabetes

• Nutritional deficiencies : Beri-Beri heart disease due to thiamin deficiency, carnitine metabolism abnormality

• Hemochromatosis : HFE gene mutation, iron overload due to hemolytic anemia

Familial DCMP

• ~30% of all DCMP

• Mutations in TTN, encoding the giant sarcomericprotein titin, are the most common cause

• The most recognizable familial cardiomyopathy syndromes with extracardiac manifestations are the muscular dystrophies.

• A prominent family history of sudden death or ventricular tachycardia before clinical cardiomyopathy suggests genetic defects in the desmosomal proteins. (ARVD)

• Left ventricular noncompaction

Arrhythmogenic Right Ventricular Dysplasia (ARVD)

ECG; Post-excitation epsilon wave (arrows) in right precordial leads.

VT with left bundle branch block morphology

Cardiac MRI ; Fibrofatty tissue replacement of RV free wall

- Autosomal dominant- VT, SCD in young age- Treatment

amiodaronecatheter ablationICD cardiac transplantation

Noncompaction CMP

• Multiple trabeculation in the left ventricle distal to the papillary muscle – sponge like apperance

• TAZ (tafazzin) gene mutation

• Three cardinal clinical feature

; ventricular arrhythmia, embolic event, heart failure

Peripartum cardiomyopathy• 원인을 설명할 수 없는 심장 확장과 심부전이 임신말기나

출산 후 6개월 내에 나타난다.

• Risk factors– Increased maternal age (>30)

– Increased parity, twin pregnancy

– Malnutrition

– Use of tocolytic therapy for premature labor

– Preeclampsia

• 증상, 진찰소견, 치료는 DCMP와 유사

• 심장의 크기가 정상으로 회복되는지의 여부가 중요– 확장성 심비대 및 EF 감소가 남아있으면 다음 임신은 피하도록 한다

– Mortality rate: 10~20% (d/t arrhythmia, embolism)

Stress-induced Cardiomyopahty

• Apical ballooning syndrome, Takotsubo cardiomyopathy

• Occur typically in women after sudden intense emotional stress

• Sx & Sign

– pulmonary edema, hypotension, and chest pain with ECG changes mimicking an acute infarction

– Ventricle; global ventricular dilatation with basal contraction

• Pathophysiology

– intense sympathetic activation with heterogeneity of myocardial autonomic innervation

– diffuse microvascular spasm

– direct catecholamine toxicity.

Takotsubo cardiomyopathy

DCMP - Treatment• Standard Tx of HF

– Bed rest, salt restriction, alcohol abstinence– ACEI / ARB, diuretics– Beta blocker– Aldosterone antagonist (spironolactone)– ARNI (Angiotensin receptor Neprilysin inhibition)

• Antiarrhythmic drug

• Anticoagulation

• Immunosuppressive Tx

– 조직검사로 심근의 염증소견이 확인된 경우

– 장기적효과는 미지수

• Resynchronization Tx

• ICD for symptomatic ventricular arrhythmia

• Cardiac transplantation

Cardiac Resynchronization Tx (CRT)

Therapeutic algorithm for a

patient with symptomatic heart

failure with reduced ejection

fraction

Hypertrophic Cardiomyopathy (HCMP)비후성 심근병증

HCMP - Overview• Characterized by LVH without obvious cause such as

hypertension or aortic stenosis.

• 1 in 500 of the general population

• Leading cause of death in young

• Two features1) Heterogenous LV hypertrophy

• Asymmetric LV hypertrophy (ASH)

• stiffness of the hypertrophied muscle diastolic dysfunction

• ~10% : concentric involvement of the ventricle

2) Dynamic LV outflow tract pressure gradient• Systolic anterior motion(SAM) of MV

• IHSS(idiopathic hypertrophic subaortic stenosis) / HOCM(hypertrophic obstructive cardiomyopathy)

HCMP - Genetic considerations

• About ½ of patients, autosomal dominant inheritance

• Mutation; 14번 염색체의 β-myosin heavy chain (14번염색체, 40%, m/C), Troponin T(1번 염색체), α-Tropomyosin (15번 염색체), myosin binding protein C(11번 염색체), essential light chain, Troponin I

• 심초음파 검사상 비후성 심근병증환자의 1차 친족의 1/3에서 심근비후 소견을 보임.

Genetics in HCM

J Am Coll Cardiol 2014;64:83–99

HCMP – Clinical features

• Exertional dyspnea : most common symptom

• fatigue, chest pain, syncope, palpitation

• In some, sudden cardiac arrest may be initial presentation

• LV outflow obstruction 의 존재 및 압력차의 정도가 증상의심한 정도와 일치하지 않는다

• 진찰 소견– 수축기 심잡음(ejection midsystolic murmur)

– 이중의 심첨 박동(double apical impulse), 제 4 심음

HCMP - Hemodynamics

• LV Diastolic dysfunction

LVEDP LAP LA enlargement

• 좌심실의 수축기능은 정상 또는 증가

• Mechanisms of the dynamic LVOT PG

① LV contractility: 운동, isoproterenol, digitalis

② LV volume (preload): Valsalva maneuver, sudden standing, nitrate.

③ Aortic impedence & pressure

– phenylephrine, squatting, sustained handgrip, beta-blocker에 의한 전부하 증가 또는 수축력 감소는 압력차와 심잡음을 감소시킨다.

• 심근 허혈(myocardial ischemia)

① 심근 비후로 인한 심근 산소요구량의 증가

② 심실의 확장기 이완부전으로 intramural coronary flow가 감소

HCMP – Lab. evaluation

• ECG– LVH with strain

– ST-T abnormality, tachyarrhythmia

– Giant T wave apical HCMP

• CXR

• Echocardiogram – mainstay of the Dx– Asymmetric LVH (>1.3:1)

– “ground-glass” appearance of myocardium

– SAM of the MV

• Radionuclide scintigraphy : myocardial perfusion defect

• Cardiac catheterization

Apical HCMP

HCMP - Treatment• 내과적 치료

– 베타 차단제– 칼슘길항제(verapamil, diltiazem)– Disopyramide– Amiodarone: asymptomatic patients with nonsustained VT– Septal ablation– 금기: nifedipine, digitalis, diuretics, nitrates, beta-agonists– Implantable cardioverter defibrillator (ICD) for selected patients

• 외과적 치료– 내과적 치료에 반응하지 않는 경우– 비후된 중격에 대한 근절개/근절제 수술법

• 기타– Vigorous, competitive activity 금기: ventricular arrhythmia 유발– Dehydration 예방

HCMP - Prognosis• Atrial fibrillation : 환자의 2/3에서 증상의 악화를 유발

• Infective endocarditis : 10% 미만에서 발생

• 5~10 %에서 좌심실 확장 및 수축기능 부전으로 진행

• m/c cause of deatn : SCD from ventricular arrhythmia

– 증상의 정도나 좌심실유출로의 압력차는 급사와 상관관계가 불분명

• 급사의 위험 인자

① history of cardiac arrest or spontaneous sustained VT

② syncope

③ family history of sudden cardiac arrest

④ spontaneous nonsustained VT (3 beat at rate >120)

⑤ LV thickness >30mm

⑥ abnormal blood pressure response to exercise

ICD advised for patients

- with prior arrest or sustained VT regardless of other risk factor

- with two or more risk factors

Restrictive Cardiomyopathy (RCMP)

RCMP - Pathophysiology

• Abnormal diastolic function

– Ventricular walls are excessively rigid and impede ventricular filling

– Myocardial fibrosis, hypertrophy, or infiltration due to a variety of causes (Amyloidosis, hemochromatosis, endomyocardial fibrosis, Fabry’s disease, eosinophilia, scleroderma, irradiation)

• Normal or slightly reduced systolic function

Causes of Restrictive Cardiomyopathies

Infiltrative (Between Myocytes)

Amyloidosis

Primary (light chain amyloid)

Familial (abnormal transthyretin)

Senile (normal transthyretin or atrial peptides)

Inherited metabolic defects

Storage (Within Myocytes)

Hemochromatosis (iron)

Inherited metabolic defects

Fabry’s disease

Glycogen storage disease (II, III)

Fibrotic

Radiation

Scleroderma

Endomyocardial

Possibly related fibrotic diseases

Tropical endomyocardial fibrosis

Hypereosinophilic syndrome (Loffler’s endocarditis)

Carcinoid syndrome

Radiation

Drugs: e.g., serotonin, ergotamine

Overlap with Other Cardiomyopathies

Hypertrophic cardiomyopathy/”pseudohypertrophic”

“Minimally dilated” cardiomyopathy

Early-stage dilated cardiomyopathy

Partial recovery from dilated cardiomyopathy

Sarcoidosis

Idiopathic

RCMP – Clinical features

• 운동시 호흡곤란 / 운동능력 감소,

• 피로감, 부종, 복수, 간비대(압통동반), 복수

• 경정맥압의 상승 (prominent x,y descent)

• Kussmaul's sign(sometimes): inspiratory elevation of JVP

• S3(early diastolic gallop), S4

• Amyloidosis : major cause

Cardiac Amyloidosis• Major cause of restrictive cardiomyopathy

• Classification

– Primary amyloidosis (immunoglobulin light chains)

– Familial amyloidosis (genetic abnormalities of transthyretin)

– Senile amyloidosis

• Diagnosis

– 조직 생검: 복부지방, 직장점막, 간, 신장

– 심내막 생검: Congo-red stain

– 심초음파

– MRI

• Treatment– Conservative: Diuretics, anticoagulation,…

– Chemotherapy

– Transplantation: Heart, BM, Liver

RCMP - Dx & Tx

• ECG & CXR

• Echocardiography

• Cardiac cath

• Endomyocardial biopsy

• Treatment

– Specific treatment of underlying cause

– Usually disappointing

– Anticoagulation