MANAGEMENT OF HCM

Dr Mohd Iqbal Dar

BROAD HEADINGS

• NATURAL HISTORY

• RISK STRATIFICATION & ROLE OF ICD

• PHARMACOLOGICAL RX , INCLUDING

AF TREATMENT , PREGNANCY ISSUES

• INVASIVE TREATMENT

ALCOHLIC SEPTAL ABLATION

Sx MYOMECTOMY

ROLE OF PACING

NATURAL HISTORY

• Clinical presentation

All phases of life effected –from birth to >90 yrs age.

• Overall HCM-related mortality rates of about 1%/yr ,

• Somewhat higher in children -2%/yr.

• Older literature.-Annual mortality rates of 4% to 6%

MANY PATIENTS DESERVE LARGE

MEASURE OF REASSURANCE …….

BUT SUBGROUPS AT HIGH RISK OF

PREMATURE DEATH & DISEASE

COMPLICATIONS DOES EXIST

• With history of Sudden & unexpected death in

family

• Progressive heart failure –LVOTO, ,Diastolic &

micro vascular dysfunction, LVEF<50%

• Atrial fibrillation, with risk for embolic stroke

DEFINITION - LVOTO

Probability of hypertrophic cardiomyopathy (HCM)–related death among 273 patients

with a left ventricular outflow gradient of at least 30 mm Hg under basal conditions and

828 patients without obstruction at entry. (Effect of Left Ventricular Outflow Tract

Obstruction on Clinical Outcome in Hypertrophic Cardiomyopathy N Engl J Med

2003;348:295-303).

Risk Stratification and Sudden

Death

Risk Stratification and Sudden

Death

ICD RECOMONDATIOS IN HCM

ACC Recommendations

Class I

1. The decision to place an ICD in patients with HCM

should include application of individual clinical

judgment, as well as a thorough discussion of

strength of evidence, benefits,& risks to allow

informed patient’s active participation in decision

making Level of Evidence: C)

2. ICD placement is recommended for patients with

HCM with prior documented cardiac arrest,

ventricular fibrillation, or hemodynamically significant

VT(Level of Evidence: B)

Selection of ICD Device

Type—RecommendationsClass IIa

1. In patients with HCM who meet indications for ICD , single-chamber devices are reasonable in younger patients without a need for atrial or ventricular pacing.

2. In patients with HCM who meet indications for ICD, dual-chamber ICDs are reasonable for patients with sinus bradycardia and/or paroxysma AF.

3. In patients with HCM who meet indications for ICD , dual-chamber ICDs are reasonable for patients with elevated resting outflow gradients greater than 50 mm Hg & significant heart failure symptoms who may benefit from RV pacing (most commonly, but not limited to, patients >65 years of age).

ICD IN HCM……2 INTERNATIONAL

MULTICENTRE REGISTRY…..

• Among patients who received a device for secondary

prevention , annualized rate of subsequent appropriate

ICD discharge was 10% per yr.

• Patients with primary prevention ICDs placed on basis

of 1 or more of conventional risk markers experienced

appropriate ICD therapy at a rate of 4% per yr.

• Number of risk markers present did not predict

subsequent device discharge

Maron BJ, Spirito P, Shen WK, et al. Implantable cardioverterdefibrillators and prevention of sudden cardiac

death in hypertrophic cardiomyopathy. JAMA. 2007;298:405–12.

Maron BJ, Shen WK, Link MS, et al. Efficacy of ICDfor the prevention of sudden death in patientswith hypertrophic

cardiomyopathy. N Engl J Med. 2000;342:365–73.

Risks of ICD implantation

Risks of ICD implantation may be thought of,

& communicated to patients, as 4 ‘‘I’s,’’

• Implantation risk,

• Infection,

• Inappropriate shock,

• Insurance risk & never using device (you

buy the policy but don’t die).

Asymptomatic Patients

• Large proportion are asymptomatic, & most will achieve a normal life expectancy.

• Educate patient

• Screening of 1st -degree relatives

• Avoiding strenuous activity .

• Risk stratification for SCD

Watchful waiting is often appropriate

SCREENING ….

Symptomatic Patients

Major goal is to alleviate exertional dyspnea,palpitations & chest discomfort, which mayreflect pathophysiologic mechanisms such asLVOT obstruction, reduced supply ofmyocardial O2 , MR and impaired LVdiastolic relaxation & compliance

Pharmacologic therapy of symptoms inobstructive HCM is successful in morethan two-thirds of patients

Pharmacologic therapy…

Beta blockers first choice(Class I)

• Negative inotropic effect

↓ejection accleration , ↓flow velocity in early systole

, ↓ early drag forces on mitral valve , ↓ mitral septal

contact ,↓SAM & gradient ,decreased adrenegic

induced tachycardia,increased diastolic filling period .

• If low dose ineffective then increases dose to maintain

resting HR <60-65 , generally max

recommended/tolerable doses can be used

Titration of beta blockers

Verapamil (class I)

• 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 therapyto look for high grade

AV block

Diltiazem• improves diastolic performance .

• Cautiously to be used in those with severe LVOTO,

increased PCWP, low BP

MANAGEMENT OF HCM

DISOPYRAMIDE (class II A)

• NOT USED AS A SOLO THERAPY

• ALWAYS AS AN ADD ON THERAPY TO BB AND VERAPAMIL

• INCREASED AV CONDUCTION, PROLONG QT INTERVAL, ANTICHOLINERGIC SIDE EFFECTS

ROLE OF DIURETICS

• USEFUL DRUGS WHEN WE KNOW

WHEN TO USE

• AVOIDED IN HOCM WITH PRESERVED

SYSTOLIC FUNCTION (class II B)

• CAN BE USED IN HOCM WITH

SYSTOLIC DYSFUNCTION (class II B),

NONOBSTRUCTIVE HCM (ONLY AS

ADD ON THERAPY-class II A)

MANAGEMENT OF ACUTE HYPOTENSION

IN HOCM• IV FLUIDS (class I)

• PHENYLEPHRINE (class I)-vasopressor

• Positive inotropes can cause harm (class III)

• MANAGEMENT OF HOCM WITH

“DEPRESSED SYSTOLIC FUNCTION” IS A

SEPERATE ENTITY

MANAGEMENT OF HCM WITH LV SYSTOLIC

DYSFUNCTION

• ACEi/ARBs, Diuretics-STANDARD HF TREATMENT

(class I)

• DISCONTINUE VERAPAMIL, DILTIAZEM,

DISOPYRAMIDE (class III)

• CAD, VALVULAR HEART DISEASE, METABOLIC

DISORDERS TO BE RULED OUT

• ICDs TO BE CONSIDERED (class IIB)

• ANTICOAGULATION IN PRESENCE OF AF/LV APICAL

ANEURYSMS

• HEART TRANSPLANTATION FOR REFRACTORY NYHA

CLASS III/IV SYMPTOMS

ACC Recommendations…

Class III(HARM)

• Nifedipine or other dihydropyridine CCB in patients with LVOT obstruction.

• Verapamil -obstructive HCM in setting of systemic hypotension or severe dyspnea at rest.

• Digitalis in the absence of AF.

• Disopyramide alone without beta blockers or verapamil in patients with HCM with AF .

• Dopamine, dobutamine, norepinephrine, & other intravenous positive inotropic drugs in acute hypotension in patients with obstructive HCM

Pharmacotherapy in Non

Obstructive HCM

• Limited options

• Verapramil, beta blockers may be used ,

not that helpful as in Obstructive cases

• Disopyramide not recommended

• Diuretics if HF +

INVASIVE THERAPIES

Alcohol Septal Ablation (ASA)

Alcohol Septal Ablation (ASA)• A 68-year-old lady, unresponsive to DDD pacemaker & optimal medical

therapy for HOCM, agreed to become first patient for ASA for Dr

Sigwart 1994 who initially noticed that significant reduction in LVOT

gradient when angioplasty balloon was inflated in 1st septal artery,

• This was further supported by disappearance of typical auscultatory

findings, & echo manifestations of obstruction of HOCM following MI

• However it took a decade for ethical clearance for this revolutionary

idea of instilling alcohol & producing a controlled infarction.

Patient selection ….• Clinical: NYHA III or IV DOE , AOE or occasionally

other exertional symptoms (such as syncope or near

syncope) that interfere with everyday activity or quality of

life despite optimal medical therapy.

• Hemodynamic: Dynamic LVOT gradient at rest or with

physiologic provocation 50 mm Hg associated with

septal hypertrophy & SAM of mitral valve.

• Anatomic: Targeted anterior septal thickness sufficient

to perform the procedure safely and effectively in the

judgment of individual operator.,Avoided if septal

thickness <18 mm

ASA…..Experienced operators

• Individual operator with a cumulative case

volume of at least 20 procedures

• Individual operator who is working in a

dedicated HCM program with a cumulative

total of at least 50 procedures

Alcohol Septal Ablation (ASA)…Technique

• Contrast angiography of septal perforator through

balloon central lumen with simultaneous echo Guidance

confirms delivery to only target myocardium.

• A short (∼10mm) OTW balloon is advanced into septal

artery, balloon material should not disintegrate on

exposure, should be at least equal or slightly bigger than

septal artery (2- 2.5 mm)

• About 1 -3mL of alcohol is infused in controlled fashion.

• It is important that balloon be inflated & that a contrast

injection also show that there is no extravasation of dye

into distal LAD.

• Contrast enhancement of other regions (papillary

muscles, free wall) indicates collateral circulation from

septal perforator artery, & alcohol should not be infused .

LVOTO gradient shows a triphasic response

following ASA.

• Stage 1: Stunning phase: There is immediate decrease in gradient following ASA. stunning of septum.

• Stage 2: Edema phase: There might be some increase in LVOTO due to peri-infarction edema. This is reason for recurrence of gradient during discharge time. Lasts for 5–10 days after procedure .

• Stage 3: Scar phase:LVOTO gradually decreases, as scar forms over weeks -months & septum becomes thinner gradually. This stage lasts for 3–12 months after ASA. Thus, accurate success of ASA can only be determined after 3 months.

Alcohol septal ablation :

Advantages

Greater patient satisfaction :

• Absence of a surgical incision & GA

• Less overall discomfort

• Much shorter recovery time.

Selective advantage in older patients.

Complications

• Temporary CHB 50% occurs during

procedure.

• Persistent CHB prompting permanent

pacemaker occurs in 10% - 20%

Complications

• 5% of patients have sustained VT during

hospitalization.

• In-hospital mortality rate is up to 2%.(0-

4%)

• Because of potential for creating a VSD ,

septal ablation should not be performed if

target septal thickness is < 18 mm.

• LAD dissection, remote infarction,

ventricular fibrillation, stroke, pericardial

effusion, are relatively uncommon

complications

FABERS SCORING SYSTEM TO PREDICT

PPI NEED

• Upto 8, Low risk, discharge from monitoring;

• 8–12, intermediate risk,prolonged monitoring;

• >12, high risk, prepare for early pacemaker implantation.

PREDICTORS OF CHB AFTER

ASA…CHANG etal

ACC……..Class II a

• When surgery is contraindicated or risk is

considered unacceptable because of

serious comorbidities or advanced

age,ASA, when performed in experienced

centers, can be beneficial in eligible adult

patients with HCM with LVOT obstruction

& severe drug-refractory symptoms

(usually NYHA functional classes III or IV).

(Level of Evidence: B)

ACC……..Class II b

• ASA, when performed in experienced centers, may be considered as an alternative to surgical myectomy for eligible adult patients with HCM with severe drug-refractory symptoms & LVOT obstruction when, after a balanced and thorough discussion, the patient expresses a preference for septal ablation. (Level of Evidence: B)

• Effectiveness of ASA is uncertain in patients with HCM with marked (i.e., >30 mm) septal hypertrophy, and therefore the procedure is generally discouraged in such patients. (Level of Evidence: C)

Class III : HARM

• Adult patients with HCM who are asymptomatic with normal exercise tolerance or whose symptoms are controlled or minimized on optimal medical therapy. (Level of evidence: C)

• Septal reduction therapy should not be done unless performed as part of a program dedicated to the longitudinal and multidisciplinary care of patients with HCM. (Level of Evidence: C)

• Mitral valve replacement for relief of LVOT obstruction should not be performed in patients with HCM in whom septalreduction therapy is an option. (Level of Evidence: C)

• Alcohol septal ablation should not be done in patients with HCM with concomitant disease that independently warrants surgical correction , in whom surgical myectomy can be performed as part of the operation. (Level of Evidence: C)

Clinical outcome of ASA……

• In a pooled analysis of 42 published studies between 1996 and 2005, Alam et al. have analyzed the outcome of ASA in 2959 patients. After a mean follow-up of 12.7 months,

• LVOTO gradients Resting from 65.3 to 15.8 mmHg

• Provocable from 125.4 to 31.5 mmHg,

• Basal septal diameter decreased from 20.9 to 13.9 mm.

• Mean NYHA functional class from 2.9 to 1.2.

• Mean exercise capacity ↑34%

• Peak oxygen consumption ↑ 33%,

• Procedural success rate was 89%.

• 6.6% of patients required multiple ablations

• 1.9% went on to septal myectomy.

• Mean 30-day mortality was 1.5%.

• Late all-cause mortality was 0.5%.

Surgical Therapy

Surgical Therapy

• Transaortic septal myectomy is currently considered most appropriate treatment for majority of patients with obstructive HCM & severe symptoms unresponsive to medical therapy .

• Traditional myectomy (Morrow procedure) with about a 3-cm long resection(Tips of MV)

• Extended myectomy (a resection of about 7 cm)( upto apex) are currently used.

• RPRrepair- (R) resection of septum, (P) plicationof anterior leaflet of mitral valve, & (R) release of abnormal papillary muscle attachments.

Mechanism…• LVOT gradient reduction with myectomy

results from basal septal thinning with resultant enlargement of LVOT area (and redirection of forward flow with loss of the drag & Venturi effects on mitral valve)& consequently abolition of SAM &mitral-septal contact.

• MR is also usually eliminated without need for additional MV surgery.

• With myectomy, LA size,risk for AF is reduced, & LV pressures & wall stress are normalized.

Complications

• Complications following myectomy are rare when performed in experienced centers.

• The risk of CHB is approximately 2% with myectomy (higher with preexisting RBBB), but in myectomy patients who have had previous ASA, risk is much higher (50% to 85%)

• Iatrogenic VSD occurs in 1% of patients

• Aortic valve or mitral valve injury - 1%

• Operative mortality - < 1%

ACC …… Class II a

• Surgical septal myectomy, when

performed in experienced centers, can be

beneficial and is the first consideration for

majority of eligible patients with HCM with

severe drug-refractory symptoms and

LVOT obstruction. (Level of Evidence: B)

ROLE OF MYOMECTOMY

• Surgery is clearly indicated for the relief of

symptoms in medically refractory obstructive

HCM.

• However, till date, there is no evidence to

suggest that septal myectomy improves survival

in patients who achieve relief of gradient and

symptoms through pharmacologic therapy or

those who have only mild symptoms.

DDD Pacing• Implantation of a dual-chamber pacemaker with short

AV delay was proposed as alternative treatment for patients with severe symptomatic HOCM.

Mechanism ??

• Paradoxical septal movement widening LVOT

• Dyssynchrony—RV pacing, Short AV delay, decreased LV ejection acceleration &decreases early forces on mitral valve

• However, 3 randomized crossover trials showed that although symptomatic improvement was reported by majority of patients following continuous DDD pacing, a similar frequency of improvement was reported by patients during AAI mode (control mode without pacing).Suggesting a placebo effect

DDD Pacing

• There are no data that dual-chamber pacing either reduces the risk of SCD in patients with HCM, alters the underlying progression of disease, or is of benefit to patients with non obstructive HCM.

• A trial of dual chamber pacing may be considered for symptomatic patients with obstruction in whom an ICD has already been implanted for high-risk status. (Class IIa )

ACC …. Recommendations .

Class IIb:

• Permanent pacing may be considered in medically refractory symptomatic patients with obstructive HCM who are suboptimal candidates for septal reduction therapy.

Class III:

• Asymptomatic, medically controlled & as first line therapy for those eligible for septalreduction .

ACC…. AF GUIDELINESCLASS I :

• Anticoagulation , INR 2-3 …

• Rate control with Beta blockers, Non DiHydropyridine CCBs

Class IIa :

• Disopyramide( with rate controlling drugs), Amidarone ----

Antiarrythmics..

• RFA ---Refractory, unable to take medicines

• Maze procedure—during myomectomy or in selected patients

Class IIb

• Sotalol, Dofetilide, Dronaderone

ACC…..Pregnancy/Delivery—

RecommendationsClass I

In women with HCM who are asymptomatic or whose

symptoms are controlled with beta-blocking drugs, the

drugs should be continued during pregnancy, but

increased surveillance for fetal bradycardia or other

complications is warranted.

For patients (mother or father) with HCM, genetic

counseling is indicated before planned conception.

ACC…..Pregnancy/Delivery—

Recommendations

• In women with HCM & resting or provocable LVOT

obstruction greater than or equal to 50 mm Hg and/or

cardiac symptoms not controlled by medical therapy

alone, pregnancy is associated with increased risk, and

these patients should be referred to a high-risk

obstetrician. (Level of Evidence: C)

• The diagnosis of HCM among asymptomatic women is

not considered a contraindication for pregnancy, but

patients should be carefully evaluated in regarding to

the risk of pregnancy.

ACC…..Pregnancy/Delivery—

Recommendations

Class IIa

• For women with HCM whose symptoms are controlled (mild to moderate), pregnancy is reasonable but expert maternal/fetal medical specialist care including cardiovascular and prenatal monitoring, is advised. (Level of Evidence: C)

Class III

• Harm For women with advanced heart failure symptoms and HCM, pregnancy is associated with excess morbidity/ mortality. (Level of Evidence: C)

HCM & ATHELETES

Recommendation to Avoid Competition

• HCM is most common structural heart disease found at autopsy in those young atheletes who have SCD in playing field.

It is recommended

• Patients with HCM should avoid competition & extremes of exertion.

• To avoid activities where syncope would have disastrous effect such as scuba diving or surfing.

• Patients not lift more than 40 lb.

ACC …. Guidelines

Class III

Patients with HCM should not participate in

intense competitive sports regardless of age,

sex, race, presence or absence of LVOT

obstruction, prior septal reduction therapy,

or implantation of a cardioverter-defibrillator

for high-risk status

CONCLUSION

• There is a need for basic understanding of mechanisms that transform a genotype-positive individual into a patient with HCM.

• If these were understood, means to prevent or modify pathologic hypertrophy might be found

• More medications are needed for this condition for both palliation of symptoms & preventing disease progression. In particular, to prevent fibrosis and improve chamber compliance.

• For obstruction, long-term study of benefits &risks of alcohol ablation must be compiled &compared to myectomy.

• Current paradigms for sudden death risk stratification lack predictive accuracy

THANK YOU