Cardiomyopathies

Șef lucrări Dr. Sascau Radu

IBCV Iasi
 Definition
European Society of Cardiology (ESC):

Diseases with abnormal myocardial structure

or function in the absence of ischemic insult
or loading conditions capable of causing such
disorder (CAD, hypertension, valvular disease,
congenital heart disease).
 Classification
Cardiomyopathies

HCM DCM ARVC RCM Unclassified

Familial/Genetic Non-familial/Non.genetic

Unidentified Disease Idiopathic Disease

gene defect sub-type sub-type
Left ventricular non-compaction
 Pathophysiology
Mutation Exogenous insult

Contraction and relaxation disorder

Ineffective energy utilization
Altered Ca ions handling

Activation of compensatory
neurohumoral mechanisms
Apoptosis
Fibrosis
Hypertrophy

Heart failure Arrhythmia, sudden death Thromboembolic complication

Hypertrophic cardiomyopathy

Increased left ventricular

thickness and/or mass in the
absence of loading conditions
capable of causing such extent of
hypertrophy (hypertension,
valvular disease, congenital
heart disease).
 Sudden cardiac death in HCM
• Most common cause of death
in young people.

Incidence of Sudden Death

20
18

(per 1,000 person/yr)

• The magnitude of left 16
14
ventricular hypertrophy is 12
10
directly correlated to the risk of 8
SCD. 6
4
2
0
• Young patients with extreme < 15 16-19 20-24 25-29 > 30

hypertrophy and few or no

Maximum Left-Ventricular-Wall Thickness (mm)
symptoms are at substantial
long-term risk of SCD.
 Etiology
Familial in ~ 55% of cases with autosomal dominant transmission
Mutations in one of 4 genes encoding proteins of cardiac sarcomere
account for majority of familial cases

-MHC
cardiac troponin T
myosin binding protein C
-tropomyosin

-the rest are spontaneous

mutations.
Hypertrophy - variable in both severity and location:
-asymmetric septal hypertrophy
-symmetric (non-obstructive)
-apical hypertrophy
Pathophysiology
 HCM with outflow obstruction
Dynamic LVOT obstruction (may not be present at rest)

SAM (systolic anterior motion of mitral valve)

LVOT Obstruction  LVOT gradient  wall stress

 MVO2  ischemia/angina

 LVOT gradient:  HR, preload (LVEDV), afterload (BP).

 LVOT gradient:  BP (Afterload),  LVEDV(preload)

Symptoms of dyspnea and angina more related to diastolic dysfunction than to outflow tract obstruction
Syncope: LVOT obstruction (failure to increase CO during exercise or after vasodilatory stress) or arrhythmia.
Presence of obstruction – increased risk of death
 Dynamic LVOT obstruction – DDx
• Hypercontractile states

• Anomalous papillary muscle insertion

• Anteroapical infarction with hyperkinetic basal

segments

• Elderly women with LVH/sigmoid septum and

hyperdynamic ventricular function

• After mitral valve repair

 Diastolic dysfunction

• Impaired relaxation
• Decreased compliance
• Hypertrophy
• Disorganised cellular architecture
• Replacement scarring
• Interstitial fibrosis
• Accounts for symptoms of exertional dyspnea
• Increased filling pressures  increased pulmonary
venous pressure
 Myocardial ischemia

Often occurs without atherosclerotic coronary artery disease

Postulated mechanisms
• Abnormally small and partially obliterated intramural coronary
arteries as a result of hypertrophy
• Inadequate number of capillaries for the degree of LV mass and
increased myocardial oxygen consumption-supply demand
mismatch
• Increased filling pressures resulting in subendocardial ischemia
Mitral valve apparatus
 Mitral valve apparatus
• Twice the normal size due to elongation of both leaflets or segmental enlargement of only
anterior leaflet or mid portion of posteror leaflet

• Congenital and anomalous anterolateral papillary muscle insertion into the anterior leaflet
without interposition of chordae tendineae and produce muscular midcavity outflow
obstruction >>SAM>>LVOTO

• Variations in leaflet length (posterior/anterior leaflet length mismatch) – restrict the ability of
the posterior leaflet to follow the anterior leaflet and to coapt effectively resulting in MR

• Severity of MR directly proportional to LV outflow obstruction

• Results in symptoms of dyspnea, orthopnea

 Arrhythmias

Adabag AS1 J Am Coll Cardiol. 2005 Mar 1;45(5):697-704- total 178 patients.
 Clinical presentation
• Majority are asymptomatic
• Dyspnea on exertion (90%), orthopnea, PND
• Palpitations (PAC, PVC, sinus pauses, AF, A flutter, SVT and VT)
• Congestive heart failure (increased filling pressures and myocardial
ischemia)
• Sudden cardiac death (<1%)
• Angina (70-80%)
• Syncope (20%), Presyncope (50%)
• Outflow obstruction worsens with increased contractility during exertional activities
resulting in decrease in cardiac output
• Secondary to arrhythmias
 Physical exam
• Jugular venous pulse: prominent a- wave
• Double carotid arterial pulse: declines in mid systole as gradient develop
• Double apical impulse:
• Forceful left atrial contraction against non-compliant ventricle
• Triple apical impulse:
• Late systolic bulge near isometric contraction
• S1: normal
• S2: normal or paradoxical split
• S3 gallop: decompensated Lt. ventricle
• S4: atrial systole against hypertrophic ventricle

22
 Physical Exam

Crescendo/Descrescendo systolic ejection murmur

HOCM vs. Valvular AS Intensity of murmur
HOCM AS
Valsalva (preload,  afterload)  
Squatting ( preload,  afterload)  
Standing (preload,  afterload)  

Holosystolic apical blowing murmur of mitral regurgitation

 ECG
Abnormal - >90% of pts & >75% of asymptomatic relatives
• Increased voltages consistent with LV hypertrophy
• ST-T changes - marked T wave inversion in the lateral precordial leads
• Left atrial enlargement
• Deep and narrow Q waves lateral precardial leads
• Diminished R waves in the lateral precordial leads.

Normal ECG - 5% of pts

• Less severe phenotype and favorable course
• Not predictive of future sudden death
 ECHOCARDIOGRAPHY
A COMPREHENSIVE ECHO EVALUATION REPORT
 LV hypertrophy (>15 mm)

• Diffuse hypertrophy of the ventricular septum and anterolateral free

wall (70% to 75%)

• Basal septal hypertrophy (10% to 15%)

• Concentric hypertrophy (5%)

• Apical hypertrophy (<5%)

• Hypertrophy of the lateral wall (1% to 2%).

“THE DAGGER”
 LVEF
• Usually normal or increased

• Can have small LV end-diastolic volumes and therefore reduced stroke

volumes despite having normal Efs

• Overt LV systolic dysfunction, termed the ‘‘dilated or progressive

phase of HCM,’’ ‘‘end-stage HCM,’’ or ‘‘burnt-out HCM,’’ is usually
defined as an LV EF < 50% and occurs in a minority (2%–5%) of
patients

• Prognosis is worse in the presence of LV systolic dysfunction

LV DIASTOLIC DYSFUNCTION
TOE
 CARDIAC MRI
• Useful when echocardiography is questionable, particularly with apical hypertrophy

• Cines loops typically show obstruction and velocity mapping is useful in the assessment
of peak velocities

• SAM of the mitral valve is clearly seen on cardiac MRI

• Improvement in obstruction after septal ablation or myomectomy can be demonstrated, as

can the location and size of the associated infarction, which are useful for planning repeat
procedures

• Cardiac MRI tagging identifies abnormal patterns of strain, shear, and torsion in cases of
HCM, demonstrating significant dysfunction in hypertrophic areas of the ventricle
 CARDIAC MRI
• Gadolinium contrast cardiac MRI - differentiating HCM
from other causes of cardiac hypertrophy and other
types of cardiomyopathy such as, amyloidosis, athletic
heart, and Fabry’s disease
• Late gadolinium enhancement occurring in HCM
represents myocardial fibrosis
• The greater the degree of late gadolinium enhancement, the
more likely that the particular HCM patient has 2 or more risk
factors for sudden death
• More likely the patient has or will develop progression of
ventricular dilation toward heart failure, thereby indicating a
poorer prognosis
• Most patients with HCM have no gadolinium
enhancement
• Common benign pattern is 2 stripes running along the junction
of the right ventricle insertion into the left ventricle
 CARDIAC CATHETERIZATION
• Diagnostic cardiac catheterization is useful to determine the degree
of LVOT obstruction, cardiac hemodynamics, the diastolic
characteristics of the left ventricle, LV anatomy and coronary
anatomy
• Reserved for situations when invasive modalities of therapy, such as
a pacemaker or surgery, are being considered
• Therapeutic cardiac catheterization interventions, include
transcatheter septal alcohol ablation
• The arterial pressure tracing found on cardiac catheterization may
demonstrate a "spike and dome" configuration
CARDIAC CATHETERIZATION
CARDIAC CT
Treatment
 Medical Treatment
Beta blockers Long-acting preparations - propranolol,
atenolol, metoprolol or nadolol
• Slowing heart rate
• Reducing force of LV contraction
• Augmenting ventricular filling and relaxation
• Decreasing myocardial oxygen consumption
• Blunt LV outflow gradient triggered by physiologic exercise.
• Target resting heart rate - 60 beats/min
 Verapamil
• Add on therapy to beta blockers if high doses of beta blockers are not
tolerated
• First choice when beta blockers are contraindicated
• Maximal doses of 280 mg/day
• AVOID in NYHA class IV dyspnoea and hypotension
• When used as add-on therapyto look for high grade AV block
• Diltiazem – when verapamil cannot be used
 Disopyramide
• Negative inotropic effect decreases the gradient and improve symptoms.
• Concomitant beta blockade may be important to prevent rapid
atrioventricular node conduction
• Between 300 and 600 mg/day
• The corrected QT interval must be monitored
• Anticholinergic side effects in older patients
 DRUGS THAN CAN HARM
• Nifedipine, Nitrates, Diuretics -potent vasodilator and hence
avoided
• Digoxin, dobutamine, noradrenaline, dopamine-positive inotropes
• MANAGEMENT OF ACUTE HYPOTENSION IN HOCM
• i.v fluids
• phenylephrine
• Iv beta blockers
• MANAGEMENT OF HCM WITH LV SYSTOLIC DYSFUNCTION
• ACEI/ARBS, diuretics-standard HF treatment
• Discontinue verapamil, diltiazem, disopyramide
 Management of atrial fibrillation
• A/c AF+ hemodynamically unstable= electrical cardioversion
• A/C AF + angina /pulmonary edema = BB/A–iv
• Hemodynamically stable= 3W OAC >>DC
• Rate control with oral BB/ CCB
• rhythm control with amiodarone
• Flecainide and propafenone, should be avoided as they may prolong QRS duration and the
QT intervaL
• AV nodal ablation F/B DDD/VVIR/CRT IN drug refractory
• Radiofrequency ablation
 HCM: Surgical Treatment
For severe symptoms with large outflow gradient (>50mmHg)
Does not prevent Sudden Cardiac Death

Myomyectomy
removal of small portion of upper IV septum
+/- mitral valve replacement
5 year symptomatic benefit in ~ 70% of patients

Dual Camber (DDD pacemaker) pacing

decreases LVOT gradient (by~25%)
randomized trials have shown little longterm benefit
possible favorable morphologic changes

ETOH septal ablation

ICD to prevent sudden death

 Conclusion
Septal alcohol ablation does seem to show promise in treatment
of HOCM owing to similar mortality rates as well as functional
status compared with myectomy;however, the caveat is increased
conduction abnormalities and a higher post-intervention LVOTG.
The choice of treatment strategy should be made after a
thorough discussion of the procedures with the individual
patient.
(J Am Coll Cardiol 2010;55:823–34)
NATURAL HISTORY
 Prognosis
Sudden Death 2-4%/year in adults
4-6% in children/adolescents

ICD for: survivors of SCD with Vfib

episodes of Sustained VT
pts with family hx of SCD in young family members
High risk mutation (TnT, Arg403Gln)

Predictors of adverse prognosis:

early age of diagnosis
familial form with SCD in 1st degree relative
history of syncope
ischemia
presence of ventricular arrhythmias on Holter (EPS)
 Restrictive Cardiomyopathy
Characterized by:
• impaired ventricular filling due to an abnormally stiff (rigid) ventricle
• normal systolic function (early on in disease)
• intraventricular pressure rises precipitously with small increases in volume

restriction

Pressure
normal

Volume

Causes : infiltration of myocardium by abnormal substance fibrosis or scarring of endocardium

Amyloid infiltrative CM
 Amyloidosis
Primary Amyloidosis
immunoglobulin light chains -- multiple myeloma

Secondary Amyloidosis
deposition of protein other than immunoglobulin
senile
familial
chronic inflammatory process

Restriction caused by replacement of normal myocardial contractile

elements by infiltrative interstitial deposits
Amyloidosis
 ECG in
amyloidosis

- low voltage on
the ECG despite
LVH on echo

- AV block
 Sarcoidosis

Restriction
Conduction System Disease
Ventricular Arrhythmias (Sudden Cardiac Death)
 Endomyocardial Fibrosis
Endemic in parts of Africa, India, South and Central America, Asia
15-25% of cardiac deaths in equatorial Africa
hypereosinophilic syndrome (Loffler’s endocarditis)

• Thickening of basal inferior

wall
• endocardial deposition of
thrombus
• apical obliteration
• mitral regurgitation
• 80-90% die within 1-2 years
 Pathophysiology of Restriction

Elevated systemic and pulmonary venous pressures

right and left sided congestion
reduced ventricular cavity size with SV and CO
 Clinical Findings

Right > Left heart failure

Dyspnea
Orthopnea/PND
Peripheral edema
Ascites/Hepatomegaly
Fatigue/ exercise tolerance

Clinically mimics constrictive Pericarditis

 Diagnostic Studies
2D-Echo/Doppler-
mitral in-flow velocity
rapid early diastolic filling

Catheterization –
diastolic pressure equilibration
restrictive vs constrictive
hemodynamics

Endomyocardial biopsy-
definite Dx of restrictive pathology
 Cardiac Catheterization

Prominent y descent “dip and plateau”

rapid atrial emptying rapid ventricular filling
then abrupt cessation of blood flow due to non-compliant myocardium
Constriction vs. Restrictive CM
 Treatment
Treat underlying cause!
r/o constriction which is treatable (restriction poor prognosis)
amyloid (melphalan/prednisone/colchicine)
Endomyocardial Fibrosis (steroids, cytotoxic drugs, MVR)
Hemochromatosis (chelation, phlebotomy)
Sarcoidosis (steroids)
Diuretics
For congestive symptoms, but  LV/RV filling   CO
Digoxin (avoid in amyloidosis)
Antiarrhythmics for afib
amiodarone
Pacemaker for conduction system disease
Anticoagulation for thrombus (esp in atrial appendages)