HCM

By Nick Jackson

Case

71 year old man who initially presented to his GP in the year 2000 with lethargy and SoB.

Could previously fit as a fiddle, then he found he was SoB on walking down the street.

He then had a number of tests ordered...

Routine bloods, TFTs, Stress sestamibi, sleep study, spirometry (none of which were very conclusive).

Past History

Rheumatic heart disease as a child (spent nine months in bed).

Partial gastrectomy for duodenal ulceration in 1986. Severe diarrhoea and weight loss since. Iron deficiency likely related to this but awaiting Inv with scopes.

Non-smoker, drinks 2 standard drinks a day. Father died suddenly at age 75.

Examination

AFeb. Pulse 80 (SR). BP 140/76.

Chest: Clear.

Heart sounds: Dual + PSM (lessens with squatting).

Mild peripheral oedema.

History

Admitted to hospital in 2004 with CP, turned out to have cholecystitis (had his gall bladder out soon after).

In 2008 he was admitted under cardiology with a possible infarct.

TTE

TTE

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TTE

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TTE

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TTE

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TTE

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TTE

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TTE

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TTE

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LV Gram

Normal coronary arteries.

Management

After a diagnosis of HCM with obstruction was made he was titrated up to a verapamil dose of 480mg daily.

A year later a TTE showed a resting LVOT gradient of 60mmHg.

Still substantially SoB, despite medication.

How do you manage this man?

HCM Recommendations

Defined as LVH (maximal wall thickness ≥15mm) without LV dilatation and without cardiac or systemic conditions that can explain the extent of hypertrophy.

It affects around 0.2% of the population in the US.

A resting or exercise outflow tract gradient is present in 70% of HCM patients and significant outflow tract obstruction at rest (present in 20-30%) is an independent predictor of mortality (adjusted RR of 1.6 for death). (6)

Prognosis is highly variable, many patients with this condition live a normal life expectancy. Consequences include SCD, dynamic outflow

HCM Recommendations

tract obstruction with associated MR, AF and thromboembolic complications.

Clinical screening with ECG and TTE is recommended for all first degree relatives of patients with HCM (class I).

(6)

HCM Recommendations

Genetic testing is not recommended unless the index patients has a defined pathogenic mutation (class III).

The usefulness of pharmacotherapy for HCM is unclear (class IIb). Septal reduction therapy should not be considered for asymptomatic patients regardless of their LVOT gradient (class III).

(6)

HCM Recommendations

Beta blockers to achieve a resting heart rate of 60-65 bpm is recommended for the treatment of angina or dyspnoea in patients with HCM or HOCM. Verapamil should be considered if Beta Blockers are not tolerated or contraindicated (class I).

Dihydropyridine CCBs, digitalis in the absence of AF and positive inotropes are all potentially harmful in patients with HCM (class III).

(6)

HCM Recommendations

Septal ablation should be considered only in patients with severe, drug refractory symptoms and a resting or provoked LVOT gradient of at least 50mmHg (class I). Alcohol septal ablation can be considered in those with serious co morbidity or a strong aversion to surgery (IIa).

(Around 5% of all HCM patients and 30% at tertiary referral centres require non-medical therapy). (6)

HCM Recommendations

ICD therapy is recommended in patients with prior cardiac arrest or sustained VT (class I), in patients with a history of SCD in a first degree relative, marked LVH or recent unexplained syncope (class IIa) or an abnormal blood pressure response to exercise (class IIa or IIb, depending on other risk modifiers such as marked LVOT obstruction). (6)

HCM Recommendations

HCM patients should not participate in intense competitive sports (eg. basketball, soccer, tennis), whether or not they have LVOT obstruction, prior septal reduction or an ICD (class III). (6)

Septal Myectomy

3-15 gms of septal muscle is removed by the surgeon via an approach through the aortic valve (aortotomy).

Text The region of septum to remove is that adjacent to the point of mitral septal contact (intraoperative TOE is needed). This septal myectomy can be extended and mitral subvalvular anomalies can also be repaired at the same time. (1)

Septal Myectomy

Perioperative mortality at expert centres is of the order of 0.8% (Toronto General and Cleveland clinic). With a concomitant surgical procedure (CABG, MVR) the 30 day mortality is around 3.4%.

Complications include VSD (around 2% in a Toronto General study). More common in patients with comparatively thin septums.

The hypertrophied myocardium is vulnerable to ischaemia which can lead to LV dysfunction at a later date.

(1)

Septal Myectomy

Traction on the aortic valve during surgery may lead to AR of varying severity. 4% in one series had significant AR.

A small AV annulus or a low MV septal contact point were present in all of these patients.

CHB requiring a PPM occurs in 5-10% of cases. The risk is lower in patients with a normal QRS at baseline (~1%). (1)

Outocmes

Surgical myectomy results in resolution of symptoms and LVOT gradient in almost all patients.

It may also reduce MR in patients without independent mitral valve disease., improve myocardial perfusion, reduce LVEDP and left atrial size and regress hypertrophy of other myocardial segments. Survival in a Mayo clinic series was 98, 96 and 83% at one, five and ten years post surgery (not different form patients with non-obstructive HCM or matched controls from the general population).

(1)

Outcomes

‘Outcome of patients with hypertrophic obstructive cardiomyopathy after percutaneous transluminal septal myocardial ablation and septal myectomy surgery’ JACC 2001.

Of 51 patients with HCM 25 were treated with PTSMA and 26 with myectomy in a non randomised fashion. The PTSMA group had a greater incidence of htn and of co-morbid illness. (2)

Gradients

(a) Alcoholic ablation (b) Surgical Myectomy.

(2)

Gradients

(a) Alcoholic ablation (b) Surgical Myectomy.

(2)

Gradients

(2)

NYHA class

(2)

Outcomes

‘Long term effects of surgical septal myectomy on survival in patients with obstructive hypertrophic cardiomyopathy’ JACC 2005 Total and HCM related mortality were compared in three subgroups of 1,337 consecutive HCM patients from 1983 to 2001. Surgical myectomy (289), LVOT obstruction without operation (228) and non-obstructive HCM (820). (3)

(3)

Survival

(3)

Survival

(3)

Survival

(3)

Outcomes

Independent predictors of overall mortality were concomitant CABG, pre-operative history of AF, pre operative left atrial diameter ≥46mm, age >50 and female gender in a Toronto General study that showed similar survival rates to the Mayo clinic series. A mitral valvuloplasty in patients with elongated leaflets can be performed at the same time as septotomy. MV replacement is generally only done if there is concurrent independent MV pathology.

(1)

Pacing

Early observational studies and small RCTs suggested that pacing may be beneficial by creating septal dys-synchrony. Subsequent larger RCTs (M-PATHY) demonstrated average LVOT gradient reductions of ~50% without good symptomatic improvement. The 2008 ACC guidelines accordingly recommend pacing in HCM primarily where there in sinus node disease or AV block.

(1)

Pacing

A subset of primarily older patients with localised mild to moderate septal hypertrophy may benefit, however. Best considered when there are contraindications to surgery and septal/MV anatomy is not suitable for alcohol ablation.

The RV pacing lead must be at the apex and must activate most of the LV myocardium before the native complex does.

Short AV delays will often lead to AV dys-synchrony with contraction of the atrium against a closed MV leading to pulmonary congestion, poor filling and decreased output.

(1)

M-PATHY (Circ ’99)

Prospective multicentre trial assessed pacing in 48 symptomatic HCM patients with ≥50mmHg LVOT gradient. Pts were randomised to 3 months each of DDD pacing or AAI-30 pacing (control) in a double blind cross-over study design. This was followed by an uncontrolled and unblinded 6 month pacing period. (4)

Patient Groups

(4)

LVOT Gradients

(4)

(4)

(4)

M-PATHY Subgroup

6 pts (12%) on retrospective analysis showed a beneficial response to pacing. NYHA class dropped ≥1, QoL score increase >10, ≥10% increase in treadmill exercise time and peak VO2.

Responders were 69+/- 4 vs 51+/- 16 tears of age. In five of these pts LVOT gradient dropped by 35-40mmHg, maximum wall thickness was moderate (17-23mm).

Several other parameters including PR interval were not significant;y different. (HCM is a heterogeneous disease). (4)

Alcohol septal ablation

Infarction and thinning of the proximal interventricular septum via infusing alcohol into the first septal perforator.

Proposed mechanism of benefit is improvement in LV relaxation and compliance via a reduction in regional asynchrony, resulting in an increased LV passive filling volume and reduced LA size and LV ejection force.

In the longer term septal scarring occurs, increasing LVOT diameter and leading to ‘therapeutic remodelling’. An increased LV size and decreased LV mass/hypertrophy and alteration of septal activation occurs leading to incoordinate contraction.

(1)

Alcohol septal ablation

A reduction in non-septal mass over time may suggest hypertrophy in HCM is in part afterload dependent and not entirely genetic. Or alcohol may damage other areas of the myocardium.

A meta-analysis of 42 observational studies (2959 patients, mean age 54) and a mean follow up of 13 months (Journal of interventional cardiology 2006): (1)

Baseline characteristics

(5)

Haemodynamics

(5)

TTE features

(5)

LVOT Gradients

(5)

NYHA/CCS Class

(5)

Complications

(5)

Alcohol septal ablation

Individual studies suggest alcohol ablation may be useful in patients with no resting gradient but a provocable gradient of ≥30 mmHg. Some patients who do not show initial benefit can respond late and develop a reduced gradient at three months.

Myocardial contrast echocardiography can accurately show the size of septal vascular territory and predict infarct size from alcohol ablation. In some series the use of MCE has been associated with greater success and less complications. (1)

Complications

CHB requirring a PPM occurs in 14-25% of patients. LBBB or first degree AV block prior to the procedure are significant predictors. As are injection by bolus, no use of MCE, injection of >1 septal artery and female sex. The benefits of alcohol septal ablation are not diminished in patients who experience CHB.

Other complications include ventricular arrhythmias, coronary dissection, pericardial effusion and rarely late myocardial infarction due to escape of ethanol from the target vessel.

(1)

Myectomy vs Alcohol ablation

In an observational study of 48 pts half underwent myectomy and half alcohol ablation. Baseline groups were reasonably matched apart from age (mean 62 vs 50 respectively).

Surgical myectomy consistently resulted in removal of the obstructing portion of the anterobasal septum, while in 25% of pts who underwent alcohol ablation there was sparing of the proximal basal septum at MRI and residual gradients at follow up. (1)

Clinical outcomes

In a meta-analysis of trials of 351 symptomatic HCM pts, baseline LVOT gradients were similar (81 and 77mmHg) and pts in the alcohol ablation group were older (mean 54 versus 45 years).

At a mean of two years: In hospital mortality was not significantly different (0.6 vs 1.6%). Improvement in NYHA class was also similar (mean reduction 1.3 vs 1.5).

Surgical technique was associated with less PPM insertion (3.3 vs 18.4%), an on average 6.6mmHg lower mean LVOT gradient and a lower rate of repeat procedure for recurrent obstruction (0.6 vs 5.5%).

(1)

Surgical myectomy advantages

Higher success in relieving resting and provoked obstruction (90-95% vs 80-90%).

Immediate relief of obstruction as opposed to a delay of up to 3 months. Lower CHB requiring PPM (3% vs 10-15% with newer techniques).

Better symptom resolution in pts less than 65 yo.

Proven long term efficacy (>20 years).

(1)

Surgical myectomy advantages

No risk of coronary dissection and minimal risk of myocardial damage away from the septum.

Ability to treat concomitant problems (MV disease, mid-ventricular obstruction, constricting muscle bridges or RVOT obstruction. Myectomy may reduce the risk of SCD and appropriate ICD discharges, while this evidence is lacking in alcohol ablation.

Survival benefit suggested with surgical ablation has not been demonstrated with alcohol ablation. (1)

Alcohol ablation advantages

Avoidance of sternotomy and cardiopulmonary bypass and their associated risks.

Shorter hospital stay and recovery time.

For older patients there is less risk of stroke with alcohol ablation than myectomy.

CAD requiring percutaneous intervention can be treated.

Less expense.

(1)

Management

? Stress TTE done.

Negative HCM genetic screen.

Had a dual chamber ICD inserted.

Relatively instantly became less SoB and LVOT gradient dropped to 30mmHg so alcohol septal ablation was not performed.

Now does 1km on the bike, leg presses 110 kgs, rowing machine etc...

References

1. McKenna WJ. Nonpharmacologic treatment of outflow obstruction in hypertrophic cardiomyopathy. UpToDate Online. June 2009.

2. Qin JX, Shiota T, Lever HM, et al. Outcome of patients with hypertrophic obstructive cardiomyopathy after percutaneous transluminal septal myocardial ablation and septal myectomy surgery. J Am Coll Cardiol 2001; 38:1994.

3. Ommen SR, Maron BJ, Olivotto I, et al. Long-term effects of surgical septal myectomy on survival in patients with obstructive hypertrophic cardiomyopathy. J Am Coll Cardiol 2005; 46:470.

4. Maron BJ, Nishimura RA, McKenna WJ, et al. Assessment of permanent dual-chamber pacing as a treatment for drug-refractory symptomatic patients with obstructive hypertrophic cardiomyopathy. A randomized, double-blind, crossover study (M-PATHY). Circulation 1999; 99:2927.

5. Alam M, Dokainish H, Lakkis N. Alcohol septal ablation for hypertrophic obstructive cardiomyopathy: a systematic review of published studies. J Interv Cardiol 2006; 19:319.

6. Bernard J. Gersh, Barry J. Maron, Robert O. Bonow, Joseph A. Dearani, Michael A. Fifer, Mark S. Link, Srihari S. Naidu, Rick A. Nishimura, Steve R. Ommen, Harry Rakowski, Christine E. Seidman, Jeffrey A. Towbin, James E. Udelson, and Clyde W. Yancy2011 ACCF/AHA Guideline for the Diagnosis and Treatment of Hypertrophic Cardiomyopathy: A Report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines Developed in Collaboration With the American Association for Thoracic Surgery, American Society of Echocardiography, American Society of Nuclear Cardiology, Heart Failure Society of America, Heart Rhythm Society, Society for Cardiovascular Angiography and Interventions, and Society of Thoracic SurgeonsJ. Am. Coll. Cardiol., December 13/20, 2011.