názov

The management of hypertrophic obstructive cardiomyopathy: the role of percutaneous transluminal septal myocardial ablation
Josef Veselka, Tomáš Honěk
Prague, Czech Republic

From Division of Cardiac Surgery, University Hospital, Motol, Prague, Czech Republic
Manuscript received May 22, 2000; accepted for publication August 7, 2000
Address for correspondence: MUDr. Josef Veselka, CSc., Oddělení srdeční chirurgie FN v Motole, V úvalu 84, Praha 5, 150 00, Česká republika

Veselka J, Honěk T. The management of hypertrophic obstructive cardiomyopathy: the role of percutaneous transluminal septal myocardial ablation. Cardiol 2000;9(6):335–340
Hypertrophic obstructive cardiomyopathy is a relatively common genetic malformation of the heart with significant clinical consequences. Conventional treatment to relieve the obstruction consists of medications such as beta-blockers and calcium channel blockers, DDD pacing or surgical myotomy – myectomy of the septum for patients with refractory symptoms. Recently, injection of ethanol into the septal branches of the left anterior descending artery to induce necrosis of the hypertrophied septum has been reported as an ameliorative procedure. This new concept is supported by observations that septal ablation reduces outflow pressure gradient, relieves symptoms and increases exercise tolerance. A randomized study to compare surgical myotomy and percutaneous transluminal septal myocardial ablation is needed.
Key words: Cardiomyopathy – Percutaneous transluminal septal myocardial ablation – Cardiac pacing – Echocardiography – Hypertrophy

Veselka J, Honěk T. Léčba hypertrofické obstrukční kardiomyopatie: role perkutánní transluminální septální ablace myokardu. Cardiol 2000;9(6):335–340
Hypertrofická obstrukční kardiomyopatie je relativně časté, geneticky podmíněné onemocnění srdce s řadou významných klinických konsekvencí. Tradiční léčba spočívá v podávání betablokátorů nebo blokátorů kalciových kanálů, DDD kardiostimulaci nebo chirurgické myotomii-myektomii u nemocných refrakterních k medikamentózní léčbě. V poslední době bylo referováno o alternativním způsobu léčby spočívajícím v injekci etanolu do septálních větví ramus interventrikularis anterior. Tato nová koncepce je podporována pozorováními ukazujícími, že perkutánní transluminální septální myokardiální ablace je spojena s poklesem tlakového gradientu ve výtokovém traktu levé komory, poklesem symptomatologie a zvýšením tolerance zátěže. Do budoucna je nezbytné provést randomizovanou studii srovnávající chirurgickou a katetrizační léčbu hypertrofické obstrukční kardiomyopatie.
Klíčová slova: kardiomyopatie – perkutánní transluminální septální ablace myokardu – kardiostimulace – echokardiografie – hypertrofie

Hypertrophic obstructive cardiomyopathy (HOCM) is a complex cardiac disease with unique pathophysiologic characteristics and a great diversity of morphologic, functional, and clinical features. HOCM is defined as primary myocardial hypertrophy, with a dynamic left ventricular outflow tract obstruction and a diastolic dysfunction of the left ventricle.

During the past few years, technological developments in non-surgical treatment have provided new therapeutic options for patients with this disease. The recent changes have also generated considerable questions about the optimal management of HOCM and the role of percutaneous transluminal septal myocardial hypertrophy (PTSMA) (1).

Recent observations suggest that the prevalence of hypertrophic cardiomyopathy (HCM) is higher (1 in 500) than previously thought (2). Twenty-five percent of patients with HCM have evidence of obstruction of the left ventricular outflow tract (LVOT). The condition therefore seems to be a common genetic malformation of the heart. However, up to now the clinical implications of various genetic abnormalities have not been determined. The clinical course varies markedly. Some patients remain asymptomatic throughout their whole life, some have severe symptomatology of heart failure or angina pectoris, and others die suddenly even in the absence of previous symptoms. The annual mortality rate varies in the different studies. In unselected populations it has been reported at about 1% (3). These observations suggest that a substantial proportion of patients with HCM has a more favourable course than previously believed.

With respect to the various clinical courses it seems to be impossible to define precise guidelines for management. As in many diseases, it is often necessary to individualize therapy.

Drug therapy of patients with HOCM

Drug therapy is used as the initial measure for controlling cardiac symptoms that have resulted in functional limitation. Beta-blockers and verapamil have traditionally been administered on an empirical basis, relying on the patient´s subjective perception of benefit. Drug selection is based on preferences of individual physicians (4). Most favour beta-blockers over verapamil as the initial treatment, although it is not of critical importance which drug is used first.

There is no evidence that beta-blockers or verapamil protect patients with HOCM from sudden death. Whether these drugs should be used prophylactically to delay disease progression and improve the prognosis in asymptomatic patients has been a subject of debate for many years. The effectiveness of prophylactic treatment has not been tested prospectively because the study populations are small and the traditional endpoints are infrequent (death, clinical deterioration). Accordingly, we reserve medical therapy just for symptomatic patients.

Surgery for relief of LVOT obstruction

The small subgroup of patients that have both a large outflow gradient and severe symptoms and that are unresponsive to medical treatment contains the best candidates for surgery. Until the early 1990s surgical myectomy (Morrow operation) represented the standard treatment for patients with HOCM and drug-refractory symptoms (5). Surgical reduction of the outflow gradient is achieved by removal of a small amount of muscle from the basal septum. Mitral valve replacement has been also used as an alternative therapy in selected patients.

Surgery substantially reduces the basal outflow gradient in more than 90 % of patients and provides large improvements in objective measures of symptoms and functional status. However, the procedure requires extracorporeal circulation and great surgical experience. A mortality rate less than 2 % is achieved only in heart centres with an extensive surgical experience and numerous performed procedures. The effect of surgery on survival is not known. Accordingly, surgery is not performed in asymptomatic or mildly symptomatic patients (6 – 8).

DDD pacing for relief of LVOT obstruction

The role of cardiac pacing in the reduction of the left ventricular outflow gradient in HOCM was first reported more than 30 years ago (9). At the same time it had been noticed anecdotally that patients who developed left bundle branch block after septal myectomy had a better functional outcome. Sporadic reports over the years have culminated in the interest of DDD pacing in the last decade.

In the early 1990s several observational studies reported that dual-chamber pacing with shortened A-V delay is associated with both substantial decrease of the outflow gradient and symptomatic improvement of patients unresponsive to drug treatment (10, 11). The mechanisms by which pacing might reduce outflow gradient are not understood. Recently, three more carefully controlled and randomized studies have found the effects of DDD pacing to be less favourable (12 – 14). These studies were randomized, double-blind and crossover. Subjective symptomatic improvement was reported with similar frequency by patients after three months pacing and after the same period without pacing. Objective measurements of exercise capacity (for example maximal oxygen consumption) with and without pacing did not differ significantly. These findings suggest that a placebo effect may play an important role in the symptomatic improvement reported by the paced patients. Currently, DDD pacing cannot be regarded as a primary treatment for patients with HOCM, although a modest reduction in outflow gradient is achieved in some of the paced patients. Probably a small subset of patients could profit from pacing. However, further randomized controlled trials should be undertaken to resolve the uncertainties surrounding the utility and efficacy of DDD pacing in patients with HOCM.

PTSMA for relief of LVOT obstruction

The idea of inducing a septal infarction by catheter techniques was suggested by the observation that myocardial function of selected areas of the left ventricle can be suppressed by balloon occlusion of the supplying artery during angioplasty. Outflow pressure gradient in HOCM decreased significantly when the first septal artery was temporarily occluded by an angioplasty balloon catheter (15, 16). This new concept was also supported by observations that outflow pressure gradient decreased after anterior myocardial infarction in hypertrophic obstructive cardiomyopathy patients (17, 18).

As the first, Sigwart (19) published his experience with “non-surgical myocardial reduction” of three patients with HOCM in 1995. Since that time several modifications of the original technique have been described. The majority of authors prefer echocardiography-guided anatomical approach for identifying the target septal branch (20 – 24). By this approach the target septal branch is detected using myocardial contrast echocardiography (MCE).

Estimation of the size of the septal vascular territory with MCE is accurate and safe. By using MCE it is possible to delineate the perfusion bed of the septal perforators and predict the infarct size that follows the ethanol injection. There is a significant correlation between MCE septal area and the reduction of ouflow gradient (24). In general, the greater the septum is infarcted the more significant decline is in the outflow gradient. However, because ethanol injection is directed mainly to the portion of the septum causing the obstruction, many patients have a small defect with a large reduction of outflow gradient (22). Additionally, it was found that MCE in 10 % of cases shows contrast within the myocardium away from the septal target area, indicating threatening misplacement of the myocardial necrosis. Accordingly, necrotization of myocardium distant from the septal target area as a source of potentially fatal complications can be avoided by this approach (25). The introduction of echocardiographic guidance of PTSMA has led to an improvement in hemodynamic results, despite a decrease of the infarcted septal area estimated by the maximal creatine kinase rise. The number of occluded arteries, the need for reinterventions and the risk of a complete heart block are decreased (22, 24).

PTSMA procedure

We usually recommend the following course of PTSMA procedure. All patients undergo coronary angiography. A temporary pacemaker is placed in the apex of the right ventricle in all patients except those who already have a permanent dual-chamber pacemaker in place. A multipurpose catheter is advanced through the aortic valve into the apex of the left ventricle, and the intraventricular gradient is measured by pull-back technique. A 7 or 8F guiding catheter is then engaged into the ostium of the left coronary artery. Initial angiography is performed to localize origin of the septal arteries (Figure 1). All patients are then sedated with diazepam. An over-the-wire balloon catheter is introduced over a coronary wire into the first septal perforator (Figure 2) and inflated. A contrast medium is injected through the central balloon lumen to delineate the area supplied by the septal branch and to ensure that balloon inflation prevents spillage into the left anterior descending artery (Figure 3). Contrast myocardial echocardiography by Levovist is done to delineate the area to be infarcted. Depending on the septal artery size and septal thickness, 2 to 5 ml of absolute ethanol is instilled through the lumen of the inflated balloon catheter and left in place for 5 minutes. After balloon deflation and removal, angiography is done to confirm the patency of the left anterior descending artery and occlusion of the target septal branch (Figure 4). Measurement of intraventricular gradient is performed by Multipurpose catheter and Doppler echocardiography. The gradient should decrease at least to one half. A temporary pacemaker is sutured in place. The patient is observed in ICU for at least 24 hours. If there is no high-degree atrioventricular block, the pacemaker lead is then removed (26).

PTSMA studies

Many observational studies have confirmed the positive effect of PTSMA on outflow gradient, symptoms, objective measurements of exercise capacity and left ventricular diastolic function.

Seggewiss et al. have performed 270 procedures up to now (22, 27). Selection criteria were as follows: symptomatology of NYHA class III or IV, symptoms in spite DDD pacing or myectomy, gradient more than 40 mmHg at rest or 100 mmHg at stress and achievable septal perforator by guidewire. They achieved encouraging acute hemodynamic results. Complete elimination of resting gradient was obtained in 26 % of cases. The average decrease of rest pressure gradient was from 72 mmHg to 20 mmHg and postextrasystolic gradient decreased from 149 mmHg to 62 mmHg. Permanent A-V block occurred in 10 % of cases and a permanent pacemaker has been implanted in 6 % of cases. Three patients died due to ventricular fibrillation, pulmonary embolism and pericardial tamponade related to the procedure. Gietzen et al. (28) performed 137 procedures in 119 patients. NYHA functional class improved from 3 to 1.6, exercise tolerance from 73 to 91 watts, peak oxygen consumption from 14.8 to 16.8 ml/kg/min and pulmonary artery mean pressure decreased from 43 to 35 mmHg. Recently, Ruzyllo et al. (21) have achieved a significant clinical improvement in 20 out of 25 patients. The clinical improvement was matched by an improvement in objective measures of exercise capacity with patients with significant left ventricular outflow gradient reduction. Exercise time increased from 571 to 703 s and peak oxygen consumption increased significantly from 14.6 to 20.5 ml/kg/min. Lakkis et al. (23) enrolled 33 symptomatic patients with a pressure gradient of more than 40 mmHg at rest or 60 mmHg after dobutamine stress echocardiography. All patients experienced symptomatic relief. NYHA class decreased from 3 to 0.9, exercise time increased from 286 to 421 s. Echocardiogram repeated within six weeks after the procedure showed 28 % reduction in septal thickness and 17 % reduction in the left ventricular mass.

After one year 50 % of patients showed further pressure gradient reduction and ongoing symptomatic improvement without increased the risk of cardiac complications. Remodelling after circumscribed septal infarction results in further reduction of outflow gradient in more than 50 % of patients. Furthermore, there is significant reduction of posterior wall thickness from 13.9 mm to 12.7 mm after 3 months and to 11.9 mm after 1 year (29). Positive changes in the left ventricular relaxation and compliance six months after PTSMA have been reported by Nagueh et al. (30).

It seems possible to combine PTSMA with both other methods of interventional cardiology and surgery procedures. Recently, there have been some reports about the combination of PTSMA with direct coronary stenting procedure and DDD pacing (31, 32).

Conclusion

At the present time, there is not a single therapy that should be applied to all patients with severely symptomatic HOCM unresponsive to medical management. There are benefits and disadvantages of both surgical myectomy and PTSMA. Septal myectomy requires specialized tertiary referral centers and is a more complex procedure than PTSMA. Furthermore, there is no cardio-thoracic surgical center in our country that would be able to perform this procedure routinely. On the other hand, there are no sufficient data concerning the long-term follow-up of patients after PTSMA.

Further investigation is required to be able to identify the best responders for DDD pacing, PTSMA and surgical myectomy and compare results among the available methods. Mainly, a randomized study comparing myectomy and PTSMA is badly needed.

Currently, a decision concerning the best therapy of patients with HOCM must be individualized to each patient depending on his wishes and expectations, way of life, age and hemodynamics. PTSMA may play a key role in this decision.

References

1. Spirito P, Maron BJ. Perspectives on the role of new treatment strategies in hypertrophic obstructive cardiomyopathy. J Am Coll Cardiol 1999;33:1071–1075.

2. Maron BJ, Gardin JM, Flack JM, Kurosaki TT, Bild TE. Prevalence of hypertrophic cardiomyopathy in general population of young adults: echocardiographic analysis of 4111 subjects in the CARDIA study. Circulation 1995;92:785–789.

3. Maron BJ, Casey SA, Poliac LC, Gohman TE, Almquist AK, Aeppli DM. Clinical course of hypertrophic cardiomyopathy in regional United States cohort. JAMA 1999;281:650–655.

4. Maron BJ. Hypertrophic cardiomyopathy. Lancet 1997;350:127–133.

5. Morrow AG, Reitz BA, Epstein SE, et al. Operative treatment in hypertrophic subaortic stenosis: techniques, and the results of pre and postoperative assessment in 83 patients. Circulation 1975;52:88–102.

6. McCully RB, Nishimura RA, Tajik AJ, et al. Extent of clinical improvement after surgical treatment of hypertrophic obstructive cardiomyopathy. Circulation 1996;94:467–471.

7. Heric B, Lytle BW, Miller DP, Rosenkranz ER, Lever HM, Cosgrove DM. Surgical management of hypertrophic obstructive cardiomyopathy: early and late results. J Thorac Cardiovasc Surg 1995;110:196–208.

8. Maron BJ, Nishimura RA, Danielason GK. Pitfalls in clinical recognition and a novel operative approach for hypertrophic cardiomyopathy with severe outflow obstruction due to anomalous papillary muscle. Circulation 1998;98:2505–2508.

9. Gilgenkrantz J, Cherrier F, Petitier H, Dodinot B, Houplon M, Legoux J. Cardiomyopathie obstructive du ventricle gauche avec block auriculo-ventriculaire complet. Considerations therapeutiques. Arch Mal Coeur 1968;61:439–453.

10. Jeanrenaud X, Goy JJ, Kappenberger L. Effects of dual-chamber pacing in hypertrophic obstructive cardiomyopathy. Lancet 1992;339:1318–1323.

11. Fanapazir L, Cannon RO, Tripodi D, Panza JA. Impact of dual-chamber pacing in patients with obstructive hypertrophic cardiomyopathy with symptoms refractory to verapamil and beta-adrenergic blocker therapy. Circulation 1992;85:2149–2161.

12. 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;99:2927–2933.

13. Linde C, Gadler F, Kappenberger L, et al. Placebo effect of pacemaker implantation in obstructive hypertrophic cardiomyopathy. Am J Cardiol 1999;83:903–907.

14. Nishimura RA, Trusty J, Hayes DL, et al. Dual-chamber pacing for hypertrophic cardiomyopathy: a randomised, double-blind, crossover trial. J Am Coll Cardiol 1997;435–441.

15. Sigwart U, Grbie M, Essinger A, Rivier JL. L ´effet aigu d´une occlusion coronarienne par ballonet de la dilatation transluminale. Schweiz Med Wochenschr 1982;45:1631A.

16. Gietzen F, Lenner C, Gerenkamp T, Kuhn H. Relief of obstruction in hypertrophic obstructive cardiomyopathy by transient occlusion of the first septal branch of the left anterior coronary artery. Eur Heart J 1994;15:125.

17. Come PC, Riley MF. Hypertrophic cardiomyopathy. Disappearence of auscultatory, carotid pulse, and echocardiographic manifestations of obstruction following myocardial infarction. Chest 1982;82:451–454.

18. Waller BF, Maron BJ, Epstein SE, Roberts WC. Transmural myocardial infarction in hypertrophic cardiomyopathy: A cause of conversion from left ventricular asymmetry and from normal-size to dilated left ventricular cavity. Chest 1981;79:461–465.

19. Sigwart U. Non-surgical myocardial reduction of hypertrophic obstructive cardiomyopathy. Lancet 1995;346:211–214.

20. Veselka J, Tesař D, Neužil P, et al. Perkutánní transluminální septální ablace myokardu a dvoudutinová stimulace jako alternativní terapie hypertrofické obstrukční kardiomyopatie. Cor Vasa 1999;41(Suppl.):63.

21. Ruzyllo W, Chojnowska L, Demkow M, et al. Left ventricular outflow tract gradient decrease with non-surgical myocardial reduction improves exercise capacity in patients with hypertrophic obstructive cardiomyopathy. Eur Heart J 2000;21:770–777.

22. Nagueh SF, Lakkis NM, He YX, et al. Role of myocardial contrast echocardiography during nonsurgical septal reduction therapy for hypertrophic obstructive cardiomyopathy. J Am Coll Cardiol 1998;32:225–229.

23. Lakkis NM, Nagueh SF, Kleinman NS, et al. Echocardiography-guided ethanol septal reduction for hypertrophic obstructive cardiomyopathy. Circulation 1998;98:1750–1755.

24. Seggewiss H. Percutaneous transluminal septal myocardial ablation: A new treatment for hypertrophic obstructive cardiomyopathy. Eur Heart J 2000;21:704–707.

25. Faber L, Seggewiss H, Ziemssen P, Gleichmann U. Percutaneous transluminal septal myocardial ablation in hypertrophic obstructive cardiomyopathy: intra-procedural myocardial contrast echocardiography as a routine procedure. J Am Coll Cardiol 1999;33(Suppl. A):501A.

26. Perkutánní transluminální septální ablace v léčbě hypertrofické obstrukční kardiomyopatie. Interna 2000;1:17–18.

27. Seggewiss H, Faber L, Gleichmann U. Percutaneous transluminal septal myocardial ablation for hypertrophic obstructive cardiomyopathy. Thorac Cardiovasc Surg 1999;47:94–100.

28. Gietzen FH, Leuner CJ, Hegselmann J, Strunk-Muller C, Kuhn HJ. Transcoronary ablation of septum hypertrophy by selective septal branch injection of ethanol: a 4-year experience in catheter interventional treatment for hypertrophic obstructive cardiomyopathy. Eur Heart J 1999;20(Suppl.):654.

29. Seggewiss H, Faber L, Ziemssen P, et al. Remodelling after percutaneous transluminal septal myocardial ablation in hypertrophic obstructive cardiomyopathy results in ongoing outflow tract gradient reduction. Eur Heart J 1999;20(Suppl.):17.

30. Nagueh SF, Lakkis NM, Middleton KJ, et al. Changes in left ventricular diastolic function 6 months after nonsurgical septal reduction therapy for hypertrophic obstructive cardiomyopathy. Circulation 1999;99:344–347.

31. Veselka J, Tesař D, Mates M, et al. Dvě nové metody v intervenční kardiologii: perkutánní transluminální septální ablace myokardu a stentování bez predilatace jako léčba hypertrofické obstrukční kardiomyopatie a významné koronární nemoci. Cardiol 1999;8:258–262.

32. Zvánovcová I, Veselka J, Tesař D, et al. Hypertrofická obstrukční kardiomyopatie: léčba perkutánní transluminální ablací myokardu a dvoudutinovou stimulací. Prakt Lék 1999;79:25–26.