cardiomyopathies

Cardiomyopathies

Moderator:Dr. Neeraj Pandit

Dr. HansrajDr. Nagina Aggarwal

Same symptoms, different disease….

• 28 year old man with history of dyspnea on exertion for 2 years and recent palpitations. Echo shows normal EF with septal thickening. Holter reveals frequent PVC’s.

• 55 year old female with recent viral illness. Progressive SOB, orthopnea and PND. CXR shows vascular congestion. Echo, 4 chamber dilatation and EF 15%.

• 43 year old female with Hodgkin's lymphoma treated with radiation and chemotherapy. Presents with worsening SOB, weight gain and fatigue. Echo reveals normal size ventricles with biatrial dilatation

Definition of cardiomyopathy

• Mid 1850s, chronic myocarditis was the only recognized cause of heart muscle disease

• In 1900, the designation of primary myocardial disease was introduced, and it was not until 1957 that the term “cardiomyopathy” was used for the first time

• WHO 1980: “ heart muscle disease of unknown cause”

• WHO 1995 : “ disease of the myocardium associated with cardiac dysfunction”

• “Cardiomyopathies are a heterogeneous group of diseases of the myocardium associated with mechanical and/or electrical dysfunction that usually (but not invariably) exhibit inappropriate ventricular hypertrophy or dilatation and are due to a variety of causes that frequently are genetic. Cardiomyopathies either are confined to the heart or are part of generalized systemic disorders, often leading to cardiovascular death or progressive heart failure–related disability.”

Maron BJ et al. Contemporary definitions and classification of the cardiomyopathies: an American Heart Association Scientific Statement. Circulation. 2006;113:1807–1816.

Common features and what it is not!

Often includes:• Heterogeneous group of

diseases of the myocardium

• Mechanical and/or electrical dysfunction

• Ventricular hypertrophy or dilatation

• Genetic basis to disease

Exclusion vs Inclusion• Heart disease caused by

cardiovascular disorders ( CAD, HTN and valvular abnormalities)

Classification & Types

Primary cardiomyopathy

• Cardiomyopathies are divided into 2 major groups based on predominant organ involvement

• Primary cardiomyopathies (genetic, nongenetic, acquired) are those solely or predominantly confined to heart muscle and are relatively few in number

Maron BJ et al. Contemporary definitions and classification of the cardiomyopathies: an American Heart Association Scientific Statement. Circulation. 2006;113:1807–1816.

Circulation 2006

HCM DCM Inflammatory

ARVC/D Restristive cardiomyopathy

Stress induced (“Tako-tsubo”)

LVNC Peripartum

Glycogen storage disease

Tachycardia induced

Conduction defects Infants of IDDM mothers

Mitochondriyal myopathies

Ion channel disorders

Primary cardiomyopathy

Genetic Mixed Acquired

Ion channel disorders

• LQTS• Brugada syndrome• SQTS• CVPT• Asian SUNDS

Inherited cardiomyopathy

Secondary cardiomyopathy

• Secondary cardiomyopathies show pathological myocardial involvement as part of a large number and variety of generalized systemic (multiorgan) disorders

Circulation. 2006;113:1807–1816

Individual cardiomyopathies

Dilated Cardiomyopathy (DCM)

Most common type

Ventricular chamber dilatation + systolic dysfunction

• DCM is a common and largely irreversible form of heart muscle disease

• Prevalence of 1:2500• Third most common cause of heart failure and the most

frequent cause of heart transplantation• DCM may manifest clinically at a wide range of ages

(most commonly in the third or fourth decade)• M>F

Main features:dilatation of both ventricles and atria

Mural thrombi are frequently present in LV

Scarring of the mitral and tricuspid leaflets and secondary dilatation of their Annuli

Reduced systolic function

Pathophysiology

Etiology

• Primary or idiopathic• Secondary

Electrolyte abnormalities

Endocrine abnormalities

Hypertension*

Infectious causes

Infiltrative diseases

Ischemia*

Neuromuscular diseases

Nutritional abnormalities

Rheumatologic diseases

Tachyarrhythmias

Toxins

Valvular heart disease*

X-ray chest

Echocardiography

Other investigations

• Coronary angiography & left ventriculography: Exclude epicardial coronary artery disease Increased left ventricular end diastolic pressure Increased pulmonary capillary wedge pressure 2009 AHA/ACC guidelines recommend CAG in

patients with clinical evidence of ischaemia Predictors: males > 35 years, with coronary risk

factors, a history of chest pain and/or regional wall motion abnormalities and/or perfusion defects at stress scintigraphy

Ital Heart J Suppl. 2002;3:412-8.

• Cardiac magnetic resonance imaging & multidetector CT scan: CMR emerging as a critical tool. Multidetector computed tomography (MDCT) is feasible, safe, and accurate for identification of idiopathic versus ischemic DCM, and may represent an alternative to coronary angiography (J Am Coll Cardiol 2007;49:2044–50)

• Radionuclide imaging: PET scan is an emerging noninvasive tool in differentiating idiopathic from ischaemic DCM

Chin Med J (Engl). 2000 ;113:392-5

• Endomyocardial biopsy: 1. New onset heart failure2. Before heart transplant3. Drug induced cardiomyopathy4. Cardiac amyloidosis

Management

• Pharmacologic and device therapy: Should follow the practice guidelines for treatment of

heart failure Prophylactic implantable cardiac defibrillator and

biventricular pacemakers is indicated in appropriate patients with ischaemic and non-ischaemic DCM

• Surgery: Patients with valvular heart disease, coronary artery

disease, pericardial disease, or congenital heart disease should have these conditions corrected surgically

Reverse remodelling surgery (SVR or Dor procedure)

Implantation of external restraint device or Cardiac support devices

Left ventricular assist device (LVAD) Heart transplantation

Emerging therapies

• Immunomodulatory agents• Stem cell therapy for cardiac regeneration• Gene therapy

Hypertrophic Cardiomyopathy

• HCM is characterized by a thickened but non-dilated left ventricle in the absence of other cardiac or systemic conditions (e.g., aortic valve stenosis, systemic hypertension, and some expressions of physiologic athlete's heart) capable of producing the magnitude of left ventricular (LV) hypertrophy evident.

Maron BJ. Hypertrophic cardiomyopathy: JAMA. 2002;287:1308 –1320

Hypertrophic Cardiomyopathy

Aetiology

• Unknown• Disorder of intracellular calcium metabolism• Neural crest disorder• Papillary muscle malpositioned and misoriented.• Genetic abnormality:

– Autosomal dominant.– Mutations in genes for cardiac sarcomeric proteins.– Polymorphism of ACE gene.– ß-myosin heavy chain gene on chromosome 14.

Variants of HCM

HCM vs Athletic heartHCM

• Can be asymmetric• Wall thickness: > 15

mm• LA: > 40

mm• LVEDD : < 45

mm• Diastolic function:

always abnormal

Athletic heart• Concentric &

regresses• < 15 mm• < 40 mm• > 45 mm• Normal

Hypertensive hypertrophic Cardiomyopathy

• Elderly women• Simulates HCM• Prognosis better than non-hypertensive HCM

Pathophysiology of HCM

• Dynamic LV outflow tract obstruction• Diastolic dysfunction• Myocardial ischemia• Mitral regurgitation• Arrhythmias

• Left ventricular outflow tract gradient• ↑ with decreased preload, decreased afterload, or

increased contractility.• Venturi effect: anterior mitral valve leaflets &

chordae sucked into outflow tract → ↑ obstruction, eccentric jet of MR in mid-late systole.

Effects of different maneuvers

Maneuvers that ↓ end-diastolic volume(↓ venous return & afterload, ↑ contractility) • Vasodilators• Inotropes• Dehydration • Valsalva• Amyl nitrite• Exercise → ↑ HCM murmur

Effects of different maneuvers

Maneuvers that ↑ end-diastolic volume(↑ arterial pressure, ↑ ventricular volume, ↓ myocardial contractility)• ß-blockers• Squatting• Isometric handgrip• Phenylephrine →↓ HCM murmur

Clinical features

Possible mechanism of SCD/Syncope

Arrhythmias:• Sustained V-Tachycardia and V-Fibrillation: most

likely mechanism of syncope/ sudden death.

• Dependant on atrial kick: CO ↓ by 40 % if A. Fib present.

Physical examination• Apex localized, sustained• Palpable S4• Prominent “a” wave• Rapid upstroke carotid pulse, “jerky” bifid (spike-

and-dome pulse)• Harsh systolic ejection murmur across entire

precordium → apex & heart base• MR: separate murmur: severity of MR related to

degree of outflow obstruction

ECG• Abnormal in >90% of probands with HCM and in

about 75% of asymptomatic relatives• Increased voltages consistent with LV hypertrophy• ST-T changes including marked T wave inversion • Left atrial enlargement• Deep and narrow Q waves• ↓ R waves in the lateral precordial leads

Echocardiography

2D-echo:• Asymmetric septal hypertrophy• Diffuse concentric or localized to apex/anterior wall• Systolic anterior motion of MV (SAM)

Doppler Echocardiocraphy:• Typical appearance: late-peaking signal “dagger-

shaped”• Simplified Bernoulli for peak systolic gradient • Obstructive or non-obstructive

Gradient on different manuevers

Predictors of poor outcome

Brockenbrough response

• ↑ LV systolic pressure• ↓ Ao systolic pressure• ↑ gradient between LV & Ao

Post PVC

Brockenbrough response

Management

• All first degree relatives: screening… echocardiography/genetic counseling• Avoid competitive athletics• Prophylactic antibiotics before medical & dental

procedures• Holter monitoring for 48 hours

Screening

• Screening includes history taking, physical examination, electrocardiography, echocardiography, CMR, and genetic testing

• Done on 12-18 month basis, begening at the age of 12 years

• If the studies does not show LV hypertrophy by the time of full growth (18 to 21 years), it is usually reasonable to conclude that an HCM causing mutation usually absent

Non-responders to Medical therapy

1- Surgery (Myotomy/Myectomy) +/- MVR 2- ICD 3- DDD pacemaker 4- NSRT (alcohol septal ablation)

SurgerySeptal myotomy/myectomy:• Patients < 40 years: mortality < 1 %• Patients > 65 years: mortality 10-15 %• Survival better than medically treated patients• Should be considered in: resting gradient > 50

mmHg, or refractory to medical Rx. • Young patients, particularly those with severe disease • Additional structural abnormalities affecting the

mitral valve or coronary arteries.

• Complication (rare): Aortic incompetence

Septal myectomy

ICD:• Previous sudden death• High risk of sudden death

DDD pacemaker:• Substantial ↓ gradient(~ 50 %)

Alcohol septal ablation

• Controlled myocardial infarction of the basal ventricular septum to ↓ gradient.

• First septal artery occluded with a balloon catheter and ETOH injected distally

NSRT (Non Surgical Septal Reduction Therapy)

The most appropriate candidates for NSRT should meet all of the following criteria :

- HCM with severe symptoms of heart failure (NYHA class III to IV) despite adequate tolerated drug therapy

- An LVOT gradient 50 mmHg at rest or after exercise or >30 mmHg at rest or 60 mmHg under stress

- Basal septal thickness 18 mm- NYHA class II heart failure with a resting LVOTgradient

>50 mmHg or >30 mmHg at rest and 100 mmHg with stress

- Elderly or comorbidities that may increase the risk of surgical correction.

Signs

• High JVP with diastolic collapse (Friedreich's sign).• JVP with rapid X and Y descents, but the most

prominent wave is the Y descent (atrium emptying into the “stiff” ventricle)

• Elevation of JVP with inspiration (Kussmaul's sign).• S4 in early disease (forceful atrial contraction against

a stiff ventricle).• S3 in advanced disease.• Murmurs due to mitral and tricuspid valve

regurgitation may be present.

Investigations

• CXR – Pulmonary venous congestion. The cardiac

silhouette can be normal (familial) or show cardiomegaly and/or atrial enlargement.

• ECG – usually has low-voltage and ST segment and T

wave abnormalities.

• Echocardiogram: symmetrical myocardial thickening and often a normal systolic ejection fraction, but impaired ventricular filling.

Apical four chamber view showing obliteration of left ventricular apex by an echogenic mass suggestive of left ventricular endomyocardial fibrosis

Atrium” outgrows “Ventricle”

• Cardiac catheterization and haemodynamic studies help distinction from constrictive pericarditis.

• Endomyocardial biopsy in contrast with other cardiomyopathies is often useful in this condition and may permit a specific diagnosis such as amyloidosis to be made.

Differential diagnosis

Clinical features of constrictive pericarditis vs restrictive cardiomyopathy

Clinical Features Constrictive Pericarditis Restrictive Cardiomyopathy

History Prior history of pericarditis or condition that causes pericardial disease

History of systemic disease (eg, amyloidosis, hemochromatosis)

General examination Peripheral stigmata of systemic disease

Systemic examination - Heart sounds

Pericardial knock, high-frequency sound

Presence of loud diastolic filling sound S3, Low-frequency sound

Murmurs No murmurs Murmurs of mitral and tricuspid insufficiency

Prior chest x-ray Pericardial calcification Normal results of prior chest x-ray

• Pericardial calcification on x-ray, which occurs in constrictive pericarditis, is absent.

• Right ventricular transvenous endomyocardial biopsy (by revealing myocardial infiltration or fibrosis in restrictive cardiomyopathy)

• CT scan or MRI (by demonstrating a thickened pericardium in constrictive pericarditis).

Treatment & Prognosis

• There is no specific treatment. Cardiac failure and embolic manifestations should be treated. Cardiac transplantation should be considered in some severe cases, especially the idiopathic variety.

• In primary amyloidosis, combination therapy with melphalan plus prednisolone with or without colchicine may improve survival.

• However, patients with cardiac amyloidosis have a worse prognosis than those with other forms of the disease, and the disease often recurs after transplantation.

• Liver transplantation may be effective in familial amyloidosis (due to production of mutant prealbumin) and may lead to reversal of the cardiac abnormalities.

Arrhythmogenic Right Ventricular Dysplasia/Cardiomyopathy

• First described in 1977 by Fontaine and coworkers, is a genetic form of cardiomyopathy characterized prototypically by fibrofatty infiltration of the right ventricle

• Accounts for 20% of cases of sudden cardiac death, and importantly, among young athletes dying suddenly, the prevalence of this condition is higher

Presenting Symptoms and Natural History

• Patients typically present between the teenage years and the forties

• Characterized by four phases: concealed phase, electrical system disturbance, right ventricular failure, frank biventricular congestive heart failure

• Presenting symptoms range from palpitations to syncope and sudden cardiac death

Pathology & Genetics

• ARVD/C exhibits fatty or fibrofatty replacement of the myocardium predominantly affecting the right ventricle. Rarely, the process extends to the left ventricle

• Several genes and gene loci encoding desmosomal proteins are associated with ARVD/C

Diagnosis

• “New task force criteria” present for diagnosis• History• ECG• 2D ECHO• CMR• Endomyocardial biopsy

Management

• Patients diagnosed with ARVD/C should receive an ICD

• Antiarrhythmic therapy: before ICD insertion & patients who have recurrent ICD firings

• Neurohormonal blockade with angiotensin-converting enzyme inhibitors and beta adrenoreceptor antagonists

• Heart transplantation: patients with overt biventricular failure

Other cardiomyopathies

Peripartum cardiomyopathy• Peripartum cardiomyopathy is a life-threatening

condition of unknown cause that occurs in previously healthy women during the peripartum period. It is characterized by left ventricular dysfunction and symptoms of heart failure that can arise in the last trimester of pregnancy or up to 5 months after delivery

• Highest among african-american• Third decade (27-33 years)• Parity: >50% patient in 1st or 2nd pregnancy• Associated with hypertension

• Recovery of LV function (LVEF >50%) at 6 months in 45% to 78% of patients

• Predictors of LV recovery: LV diastolic dimension (5.5 cm), LVEF >30% to 35%, lack of troponin elevation, lower level of plasma BNP, breast-feeding, absence of LV thrombus, diagnosis after the delivery

• The rate of recovery of LV function was significantly higher in lactating women

• Standard management of heart failure• Anticoagulation: from the time of the diagnosis until

LV function recovers (LVEF >35%) is advisable

JACC Vol. 58, No. 7, 2011

HIV cardiomyopathy

• HIV-Associated Cardiovascular Diseases• Dilated Cardiomyopathy• Lymphocytic Interstitial Myocarditis• Pericardial Effusion• Infective Endocarditis• Malignancy (myocardial Kaposi sarcoma and B-cell

immunoblastic lymphoma)• Vasculitis• Accelerated Atherosclerosis

• Prospective study conducted by Barbaro et al (952 asymptomatic patients/ 60 months follow up) found that the extent of immunodeficiency of the patients had a major role in the development of cardiomyopathy.

• It is strongly associated with CD4 count of less than 400/cumm

Therapy for Cardiomyopathy Associated with HIV

• Similar to therapy for non-ischemic cardiomyopathy• After medical therapy is begun, serial

echocardiographic studies should be performed at 4 months intervals.

Tako-subo cardiomyopathy

• Several relatively recent case reports and series have described a condition featuring symptoms and signs of acute myocardial infarction without demonstrable coronary artery stenosis or spasm in which the heart takes on the appearance of a Japanese octopus fishing pot called a takotsubo

• left ventricular dysfunction, which can be remarkably depressed, recovers within a few weeks

• Takotsubo cardiomyopathy occurs predominantly in postmenopausal women soon after exposure to sudden, unexpected emotional or physical stress

Mayo Clinic proposed diagnostic criteria

• Transient hypokinesis, akinesis, or dyskinesis in the left ventricular mid segments with or without apical involvement; regional wall motion abnormalities that extend beyond a single epicardial vascular distribution; and frequently, but not always, a stressful trigger;

• The absence of obstructive coronary disease or angiographic evidence of acute plaque rupture;

• New ECG abnormalities (ST-segment elevation and/or T-wave inversion) or modest elevation in cardiac troponin;

• The absence of pheochromocytoma and myocarditis.

Yoshihiro J. Akashi et al. Circulation 2011

Drugs causing cardiomyopathy

• Anthracyclines: Daunorubicin and doxorubicin• Cardiotoxicity may develop at any moment during or

after treatment with anthracyclines. Although anthracycline induced cardiotoxicity is usually characterized by heart failure, cardiac arrhythmias might be the first manifestation in some patients

• Early cardiac toxicity, which occurs during or soon after treatment with anthracyclines, is mainly dependent on the cumulative anthracycline dose

Other drugs

• Cyclophosphamide• 5-fluorouracil• Cytarabine• Herceptin• Paclitaxel• Mitoxantrone

Take home message• Cardiomyopathies are diseases of the heart muscle

and are classified based on their structural and functional phenotype

• Disorders are frequently genetic• Accurate differentiation is needed in order to guide

treatment and management

THANK YOU

cardiomyopathies

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