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Percutaneous radiofrequency ablation of the left bundle branch: An alternative modality of treatment for patients with hypertrophic obstructive cardiomyopathy
Medical Hypotheses I Medical Hyporhesrs (1994) 43. 141-144 0 Longman Group Ltd 1994
Percutaneous Radiofrequency Ablation of the Left Bundle Branch: An Alternative Modality of Treatment for Patients with Hypertrophic Obstructive Cardiomyopathy 6. DALVI Department of Cardiology, King Edward VII Memorial Hospital, Pare/, Bombay 400 012, India (Correspondence to Depattment of Cardiology Children’s Hospital, 300 Longwood Avenue, Boston, MA 02115, USA)
Abstract - Hypertrophic obstructive cardiomyopathy (HOCM), which is characterized by asymmetric septal and ventricular obstructive hypertrophy, is currently palliated with a number of pharmacological, electrical and surgical interventions. Although none of the methods have been successful in reducing the incidence of sudden death, most of the patients have shown significant symptomatic improvement. Currently, pacemaker implantation and surgical procedures have been offered only to those patients who do not respond to a medical line of treatment. Since obstructive pressure gradients correlate fairly well with the clinical condition of a patient, the principal aim of surgical or pacemaker therapy has been to reduce the left ventricular pressure gradient. Surgical procedure achieves this objective by septal myotomy and myectomy whereas pacemakers attain it by altering the sequence of electrical stimulation of the ventricles. A right ventricular pacing, which behaves like a left bundle branch block, is known to alter the pattern of interventricular septal contraction and hence delay the onset of mitral leaflet-septal contact. The latter has been implicated in the pathogenesis of subvalvar dynamic left ventricular outflow tract obstruction, which is the hallmark of this condition. Currently, radiofrequency ablation of the left bundle branch has been successfully carried out for patients with resistant macrore-entry ventricular tachycardia, I, therefore, propose that radiofrequency ablation of the left bundle branch be used as a palliative procedure of choice for patients with HOCM who are resistant to a medical line of treatment. This would result in left bundle branch block which in turn would cause an altered pattern of septal contraction resulting in the reduction or elimination of left ventricular outflow tract obstruction. Such a procedure theoretically appears more physiological, safer and cost-effective than surgery or dual chamber pacing which are being currently offered to patients who are resistant to drug therapy. Date received 18 November 1993 Date accepted 7 February 1994
141
142
MEDICAL HYPOTHESES
Introduction The World Health Organization defines hypertrophic cardiomyopathy as an idiopathic heart muscle disorder characterized by unexplained left ventricular hypertrophy (1). Hypertrophic obstructive cardiomyopathy (HOCM) is morphologically characterized by septal and ventricular hypertrophy of varying extent and location; fibrosis and myofibrillar disarray; narrowing of small intramural coronary arteries; hypercontractile left ventricle, which overempties itself; impaired relaxation and compliance; and systolic pressure gradients in the left ventricular cavity (2). Many patients have mild disease which may go unnoticed or may be accidentally detected. However, the less fortunate could have sudden cardiac death as their first and only manifestation. Symptoms, when they occur, are in the form of chest pain, dyspnea, syncope and palpitations and are due to &hernia, high left atria1 pressure and repetitive arrhythmias (3). Sudden death, is usually arrhythmogenic. In children, however, it is more likely to be due to impaired hemodynamic function than to arrhythmia (2). The diagnosis is based on clinical findings characterized by palpable left ventricular fourth heart sound, apical pansystolic murmur due to associated mitral regurgitation and ejection systolic murmur in the third and fourth left intercostal space due to left ventricular outflow tract obstruction. Since the nature of obstruction is ‘dynamic’, the murmur changes in length and intensity with various manoeuvres which alter the left ventricular filling, afterload and contractility (4). In addition, thorough echocardiographic and sometimes angiographic imaging with appropriate hemodynamic data is required for establishing the diagnosis and for prognosticating a given case. Current status of various therapeutic in HOCM
modalities
It is important to realize that the current strategies in the management of HOCM are essentially targeted towards symptomatic relief since there is no definitive curative therapy available. At the time of initial presentation, approximately 25% of the patients are asymptomatic, 55% are in NYHA class II or III and less than 5% are in class IV (5). In patients who do not exhibit significant left ventricular systolic impairment or severe mitral regurgitation, beta blockers are the drug of first choice. They are known to slow the heart rate, prolong ventricular filling, decrease ventricular systolic performance and decrease the outflow tract gradients. Propranolol, which is the agent of choice, was suggested
to improve left ventricular relaxation and end diastolic pressure volume relationships in patients with HOCM (6,7). However, the subsequent studies reveal that beta blockers usually have no consistent effect on the left ventricular function (8,9) though individual patients may clearly show benefit. Calcium channel blockers have been extensively studied in HOCM. Verapamil has been used most extensively and has been found to improve the symptomatic status and exercise tolerance during shortand long-term therapy (10-13). The possible mechanisms responsible for these beneficial effects of verapamil include negative inotropic effect, negative chronotropic effect and changes in the left ventricular relaxation and diastolic filling (14). It is also known to reduce the left ventricular outflow tract gradients (15). Besides the beta blockers and calcium channel blockers, other agents used for the relief of symptoms are disopyramide and amiodarone. Disopyramide helps in the relief of symptoms due to its negative inotropic action on the heart. This leads to improvement in the left ventricular filling during diastole and probably reduces the left ventricular outflow tract gradients (16,17). Amiodarone is occasionally found to be very effective for the control of refractory chest pain in patients with HOCM (18). It is also found to be useful in improving the exercise tolerance of these patients (19). Although the exact mechanism of action is ill understood, it may be related to a reduced heart rate, effect on peripheral circulation and improvement of left ventricular diastolic function (20). In addition to improving the symptoms, it can also control supraventricular and ventricular arrhythmias in this group of patients (21). Patients who are resistant to medical treatment are offered either surgical or pacemaker therapy. The major prerequisites for offering the surgical treatment are a left ventricular outflow tract gradient of = >50 mmHg, moderate to severe symptomatic limitation of physical activity (NYHA class III-IV) despite medical therapy and young patients below 20 years of age with a family history of HOCM and sudden death or syncope, life-threatening tachyarrhythmias or requiring resuscitation (22). Although the operative risk for myotomy-myectomy has been reported to be as low as 0% (23), the generally accepted risk is about 5-8% (24). Follow-up studies indicate a 70-88% survival rate with a significant improvement in symptoms (23,25). The mechanism by which surgery reduces the left ventricular outflow tract obstruction appears to be an increase in the left ventricular outflow tract cross sectional area (26,27). This increase in the area reduces the velocities of the ejected blood in the
PERCUTANEOUS RADIOFREQUENCY ABLATION OF THE LEFI- BUNDLE BRANCH
left ventricular outflow such that the venturi forces responsible for the development of systolic anterior motion of the mitral valve do not develop (28,29). Hemodynamic evidence (30,31) of a reduction of subaortic gradient by right ventricular pacing led to occasional attempts to treat HOCM with a pacemaker (3 1,32) with significant improvement in functional capacity in some patients. Recently, in a long-term follow-up study, dual chamber pacing has been shown to reduce peak subaortic pressure gradients without concomitantly reducing aortic blood pressure or cardiac output with symptomatic improvement (33). It is now a well accepted fact that the subaortic pressure gradient is due to dynamic obstruction of the left ventricular outflow tract by the mitral leaflet, which is brought against the hypertrophied septum during systole (34). Moreover, the severity of obstruction and hence the pressure gradient, correlates strongly with the time of onset or duration of mitral leaflet-septal contact during systole (35). Right ventricular apical stimulation results in an altered pattern of septal contraction which could delay the onset and duration of mitral leaflet-septal contact. Such an alteration of septal motion on 2D echo and left ventricular angiography has been documented (33).
Hypothesis Right ventricular apical pacing is electrophysiologitally akin to left bundle branch block. Abnormality of the septal motion has been reported in patients with left bundle branch block (36). I therefore propose that causation of left bundle branch block could result in diminution or elimination of left ventricular outflow tract gradients comparable to dual chamber pacing. Moreover, it will be far too physiological in terms of rate responsiveness and atrio-ventricular synchrony as compared to the dual chamber pacemaker. Since it is now possible to map and ablate the left bundle branch percutaneously by radiofrequency technique, as has been occasionally used for the treatment of macro reentry ventricular tachycardia, it would not be difficult to do it technically in patients with HOCM.
How to prove this hypothesis It would be worth studying the hemodynamic variables such as the left ventricular systolic gradient, cardiac output, systemic blood pressure before and after induction of left bundle branch block in an animal model with HOCM. In addition to these, septal motion could be studied on 2D echo and left ventricular angiograms to see abnormalities of contractility as a result of left bundle branch block. One can also compare the gradients in patients of HOCM with left
143
bundle branch block and those without it to look for any significant difference in magnitude of gradients as a group, especially if these groups are comparable with respect to age, left ventricular mass, loading conditions and contractility. Since it may be difficult to find such comparative groups, it would be worth studying patients with HOCM prospectively from the point of development of left bundle branch block in the course of their disease. If left bundle branch block were to develop in patients under surveillance, comparison of various hemodynamic variables before and after development of the block could prove or disprove this hypothesis. If such patients have reduction in their gradients without significant change in the left ventricular function, the current hypothesis will be validated.
Conclusion After proving the efficacy of induced left bundle branch block in animal experiments, one can proceed to offer this modality as yet another palliation for patients with failure of medical therapy. If the results in human studies are encouraging then it could also be offered to patients who cannot tolerate drugs or have poor compliance. On the face of it, this therapy appears to be much more physiological from the point of rate-responsiveness and atrioventricular sequential contractions as compared to pacemaker therapy and will probably have less morbidity and mortality as compared to surgery. Moreover, it could also prove to be more cost-effective as compared to any of the available modalities of treatment.
References I. 2.
3. 4.
5.
6.
I.
8.
Maron BJ, Epstein SE. Hypettrophic cardiomyopathy: a discussion of nomenclature. Am J Cardiol 1979; 43: 1242-1244. Goodwin JF. Cardiomyopathies and specific heart muscle disease. Definition, terminology, classifications and new and old approaches. Postgrad Med J 1992; 68 (suppl I): S3-S6. Bokhari AM, McKenna WJ. Management of hypertrophic cardiomyopathy. Indian Heart J 1992; 44: 195-202. Colan SD, Spevak PJ. Pamess IA, Nadas AS. Cardiomyopathies. Nadas’ Pediatric Cardiology, 4th edn. Philadelphia: Hartley and Belfus, 1991: 341. McKenna WJ, Borggrefe M, England D, Deanfield J, Oakley CM, Goodwin JF. The natural history of left ventricular hypettrophy in hypertrophic cardiomyopathy: an electrocardiographic study. Circulation 1982; 66: 1233-1240. Swonton RH, Brooksby IAB, Jenkins BS, Webb-Peploe MM. Hemodynamic studies of beta blockade in IHSS. Eur J Cardiol 1977;5: 327-341. Spieser KW, Krayenbuehl HP. Reappraisal of the effect of acute beta blockade on left ventricular filling dynamics in hypertrophic cardiomyopathy. Eur Heart J 1981; 2: 21-29. Hess OM, Grimm J. Krayenbuehl HP Diastolic function in hypertrophic cardiomyopathy: effects of propranolol and verapamil on diastolic stiffness. Eur Heart J 1983; 4 (suppl F);
144 F47-F56. 9. Frank MJ, Abdulla AM, Canedo MI, Saylors RE. Long-term medical management of hypertrophic cardiomyopathy. Am J Cardiol 1978; 42: 993-1101. 10. Rosing DR. Kent M, Maron BJ, Epstein SE. Verapamil therapy: a new approach to pharmacological treatment of hypertrophic cardiomyopathy. Circulation 1979; 60: 1208-1213. Il. Rosing DR. Condit JR, Maron BJ et al. Verapamil therapy: a new approach to pharmacological treatment of hypertrophic cardiomyopathy III. Effects of long-term administration in hypertrophic cardiomyopathy. Am J Cardiol 198 I ; 48: 545-553. 12. Bonow RO. Dilsizian V, Rosing DR. Maron BJ, Bacharach SL, Green MV. Verapamil induced improvement in left ventricular filling and increased exercise tolerance in patients with hypertrophic cardiomyopathy: short- and long-term effects. Circulation 1985; 72: 853-864. 13. Bonow RO, Ostrow HG, Rosing DR et al. Effects of verapamil on left ventricular systolic and diastolic functions in patients with hypertrophic cardiomyopathy: pressure-volume analysis with non-imaging scintillating probe. Circulation 1983; 68: 1062-1073. 14. Hess OM, Murakami T, Krayenbuehl HP. Does verapamil improve left ventricular relaxation in patients with myocardial hypertrophy Circulation 1986; 74: 530-543. 15. Hanrath P, Mathey DG, Kremer P, Sonntag F, Bleifeld W. Effect of verapamil on left ventricular isovolumetric relaxation time and regional left ventricular filling in hypertrophic cardiomvooathv. Am J Cardiol 1980: 45: 1258-1264. 16. Pollick ‘C, Detsky A, Ogilvie RI, Wilansky S. Disopyramide and propranolol in hypertrophic cardiomyopathy: double blind randomized trial (abstr). Circulation 1985; 72 (suppl III) III155. and 17. Pollick C. Muscular subaortic stenosis: hemodynamic clinical improvement after disopyramide. N Engl J Med 1982; 307:997-999. 18. Leon MB, Rosing DR, Maron BJ, Bonow RO, Lesko LJ, Epstein SE. Amiodarone in patients with hypertrophic cardiomyopathy and refractory cardiac symptoms: an alternative to current medical therapy (abstr). Circulation 1984; 70 (suppl II) II-1 8. 19. Sugrue DD, Dickie S, Myers MJ, Lavender JP, McKenna WJ. Effect of amiodarone on left ventricular ejection and filling in hypertrophic cardiomyopathy as assessed by radionuclide angiography. Am J Cardiol 1984; 54: 1054-1058. 20. Paulus WJ. Nellens P, Heyndrick GR, Andries E. The influence of chronic amiodarone therapy on left ventricular relaxation: rest and exercise hemodynamics in patients with hypertrophic cardiomyopathy. Circulation 1986; 74: 544-554. 21. McKena WJ, Harris L, Perez G, Krikler DM, Oakley C, Goodwin JF. Arrhythmias in hypertrophic cardiomyopathy Il. Comparison of amiodarone and verapamil in treatment. Br Heart J 1981; 46: 173-178. 22. Schulte HD, Bircks WH, Locsse B, Godehardt EAJ, Schwart-
MEDlCAL HYPOTHESES
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36.
zkopff B. Prognosis of patients with hypertrophic obstructive cardiomyopathy after transaortic myectomy. Late results up to 25 years. J Thorac Cardiovasc Surg 1993; 106: 709-717. Seiler C, Hess OM. Schoenbeck M et al. Long-term follow-up of medical versus surgical therapy for hypertrophic cardiomyopathy: A retrospective study. J Am Co11 Cardiol 1991; 17: 634-642. Maron BJ, Bonow RO, Canon RO, Leon MB, Epstein SE. Hypertrophic cardiomyopathy: interrelations of clinical manifestations, pathophysiology and therapy (second part). N Engl J Med 1987; 316: 844-852. Beahrs MM, Tajik AJ, Seward JB, Giuliani ER, McGoon D C. HCM: 10-21 year follow-up after partial myectomy. Am J Cardiol 1983; 51: 1160-1166. Spirit0 P, Maron BJ, Rosing DR. Morphologic determinants of hemodynamic states following myotomy-myectomy in patients with hypertrophic cardiomyopathy: M mode 2D echocardiographic assessment. Circulation 1984; 70: 984-995. Schapira JN, Stemple DR. Martin RP, Rakowski H, Stinson EB, Popp RL. Single and 2D echocardiographic visualization of the effects of septal myectomy in IHS. Circulation 1978; 58: 850-860. Henry WL. Clark CE, Griffith JM, Epstein SE. Mechanism of left ventricular outflow tract obstruction in patients with IHSS. Am J Cardiol 1975; 35: 337-344. Spirit0 P, Maron BJ. Significance of left ventricular outflow tract cross sectional area in hypertrophic cardiomyopathy: a 2D echocardiographic assessment. Circulation 1983; 67: 1100-1108. Hassenstein P, Walter HH. Therapeutische Beherrschung einer bedrohlichen Situation bei der idiopatischen hypertrophischen Subaortenstenose. Verth Dtsch Ges Kreislaufforsch 1967; 33: 242-246. Hassenstein P, Starch HH, Schmitz W. Results of electrical pacing in patients with hypertrophic obstructive cardiomyopathy. Thoraxchirurgie 1975; 23: 496-498. McDonald K, McWilliams E, O’Keffe B, Maurer B. Functional assessment of patients treated with permanent dual chamber pacing as a primary treatment for hypertrophic cardiomyopathy. Eur Heart J 1988; 9: 893-898. Jeanrenaud X, Goy J, Kappenberger L. Effects of dual chamber pacing in hypettrophic obstruction cardiomyopathy. Lancet 1992; 339: 1318-1323. Wigle E D, Sasson Z. Henderson MA et al. Hypertrophic cardiomyopathy. The importance of the site and the extent of hypertrophy. A review. Prog Cardiovasc Dis 1985; 28: 1-83. Pollick C, Rakowski H, Wigle ED. Muscular subaortic stenosis: the quantitative relationship between systolic anterior motion and the pressure gradient. Circulation 1984; 69: 43-49. Games JAC, Damato AN, Akhtar M et al. Ventricular septal motion and left ventricular dimensions during abnormal ventricular activation. Am J Cardiol 1977: 39: 641-650.
Percutaneous Radiofrequency Ablation of the Left Bundle Branch: An Alternative Modality of Treatment for Patients with Hypertrophic Obstructive Cardiomyopathy 6. DALVI Department of Cardiology, King Edward VII Memorial Hospital, Pare/, Bombay 400 012, India (Correspondence to Depattment of Cardiology Children’s Hospital, 300 Longwood Avenue, Boston, MA 02115, USA)
Abstract - Hypertrophic obstructive cardiomyopathy (HOCM), which is characterized by asymmetric septal and ventricular obstructive hypertrophy, is currently palliated with a number of pharmacological, electrical and surgical interventions. Although none of the methods have been successful in reducing the incidence of sudden death, most of the patients have shown significant symptomatic improvement. Currently, pacemaker implantation and surgical procedures have been offered only to those patients who do not respond to a medical line of treatment. Since obstructive pressure gradients correlate fairly well with the clinical condition of a patient, the principal aim of surgical or pacemaker therapy has been to reduce the left ventricular pressure gradient. Surgical procedure achieves this objective by septal myotomy and myectomy whereas pacemakers attain it by altering the sequence of electrical stimulation of the ventricles. A right ventricular pacing, which behaves like a left bundle branch block, is known to alter the pattern of interventricular septal contraction and hence delay the onset of mitral leaflet-septal contact. The latter has been implicated in the pathogenesis of subvalvar dynamic left ventricular outflow tract obstruction, which is the hallmark of this condition. Currently, radiofrequency ablation of the left bundle branch has been successfully carried out for patients with resistant macrore-entry ventricular tachycardia, I, therefore, propose that radiofrequency ablation of the left bundle branch be used as a palliative procedure of choice for patients with HOCM who are resistant to a medical line of treatment. This would result in left bundle branch block which in turn would cause an altered pattern of septal contraction resulting in the reduction or elimination of left ventricular outflow tract obstruction. Such a procedure theoretically appears more physiological, safer and cost-effective than surgery or dual chamber pacing which are being currently offered to patients who are resistant to drug therapy. Date received 18 November 1993 Date accepted 7 February 1994
141
142
MEDICAL HYPOTHESES
Introduction The World Health Organization defines hypertrophic cardiomyopathy as an idiopathic heart muscle disorder characterized by unexplained left ventricular hypertrophy (1). Hypertrophic obstructive cardiomyopathy (HOCM) is morphologically characterized by septal and ventricular hypertrophy of varying extent and location; fibrosis and myofibrillar disarray; narrowing of small intramural coronary arteries; hypercontractile left ventricle, which overempties itself; impaired relaxation and compliance; and systolic pressure gradients in the left ventricular cavity (2). Many patients have mild disease which may go unnoticed or may be accidentally detected. However, the less fortunate could have sudden cardiac death as their first and only manifestation. Symptoms, when they occur, are in the form of chest pain, dyspnea, syncope and palpitations and are due to &hernia, high left atria1 pressure and repetitive arrhythmias (3). Sudden death, is usually arrhythmogenic. In children, however, it is more likely to be due to impaired hemodynamic function than to arrhythmia (2). The diagnosis is based on clinical findings characterized by palpable left ventricular fourth heart sound, apical pansystolic murmur due to associated mitral regurgitation and ejection systolic murmur in the third and fourth left intercostal space due to left ventricular outflow tract obstruction. Since the nature of obstruction is ‘dynamic’, the murmur changes in length and intensity with various manoeuvres which alter the left ventricular filling, afterload and contractility (4). In addition, thorough echocardiographic and sometimes angiographic imaging with appropriate hemodynamic data is required for establishing the diagnosis and for prognosticating a given case. Current status of various therapeutic in HOCM
modalities
It is important to realize that the current strategies in the management of HOCM are essentially targeted towards symptomatic relief since there is no definitive curative therapy available. At the time of initial presentation, approximately 25% of the patients are asymptomatic, 55% are in NYHA class II or III and less than 5% are in class IV (5). In patients who do not exhibit significant left ventricular systolic impairment or severe mitral regurgitation, beta blockers are the drug of first choice. They are known to slow the heart rate, prolong ventricular filling, decrease ventricular systolic performance and decrease the outflow tract gradients. Propranolol, which is the agent of choice, was suggested
to improve left ventricular relaxation and end diastolic pressure volume relationships in patients with HOCM (6,7). However, the subsequent studies reveal that beta blockers usually have no consistent effect on the left ventricular function (8,9) though individual patients may clearly show benefit. Calcium channel blockers have been extensively studied in HOCM. Verapamil has been used most extensively and has been found to improve the symptomatic status and exercise tolerance during shortand long-term therapy (10-13). The possible mechanisms responsible for these beneficial effects of verapamil include negative inotropic effect, negative chronotropic effect and changes in the left ventricular relaxation and diastolic filling (14). It is also known to reduce the left ventricular outflow tract gradients (15). Besides the beta blockers and calcium channel blockers, other agents used for the relief of symptoms are disopyramide and amiodarone. Disopyramide helps in the relief of symptoms due to its negative inotropic action on the heart. This leads to improvement in the left ventricular filling during diastole and probably reduces the left ventricular outflow tract gradients (16,17). Amiodarone is occasionally found to be very effective for the control of refractory chest pain in patients with HOCM (18). It is also found to be useful in improving the exercise tolerance of these patients (19). Although the exact mechanism of action is ill understood, it may be related to a reduced heart rate, effect on peripheral circulation and improvement of left ventricular diastolic function (20). In addition to improving the symptoms, it can also control supraventricular and ventricular arrhythmias in this group of patients (21). Patients who are resistant to medical treatment are offered either surgical or pacemaker therapy. The major prerequisites for offering the surgical treatment are a left ventricular outflow tract gradient of = >50 mmHg, moderate to severe symptomatic limitation of physical activity (NYHA class III-IV) despite medical therapy and young patients below 20 years of age with a family history of HOCM and sudden death or syncope, life-threatening tachyarrhythmias or requiring resuscitation (22). Although the operative risk for myotomy-myectomy has been reported to be as low as 0% (23), the generally accepted risk is about 5-8% (24). Follow-up studies indicate a 70-88% survival rate with a significant improvement in symptoms (23,25). The mechanism by which surgery reduces the left ventricular outflow tract obstruction appears to be an increase in the left ventricular outflow tract cross sectional area (26,27). This increase in the area reduces the velocities of the ejected blood in the
PERCUTANEOUS RADIOFREQUENCY ABLATION OF THE LEFI- BUNDLE BRANCH
left ventricular outflow such that the venturi forces responsible for the development of systolic anterior motion of the mitral valve do not develop (28,29). Hemodynamic evidence (30,31) of a reduction of subaortic gradient by right ventricular pacing led to occasional attempts to treat HOCM with a pacemaker (3 1,32) with significant improvement in functional capacity in some patients. Recently, in a long-term follow-up study, dual chamber pacing has been shown to reduce peak subaortic pressure gradients without concomitantly reducing aortic blood pressure or cardiac output with symptomatic improvement (33). It is now a well accepted fact that the subaortic pressure gradient is due to dynamic obstruction of the left ventricular outflow tract by the mitral leaflet, which is brought against the hypertrophied septum during systole (34). Moreover, the severity of obstruction and hence the pressure gradient, correlates strongly with the time of onset or duration of mitral leaflet-septal contact during systole (35). Right ventricular apical stimulation results in an altered pattern of septal contraction which could delay the onset and duration of mitral leaflet-septal contact. Such an alteration of septal motion on 2D echo and left ventricular angiography has been documented (33).
Hypothesis Right ventricular apical pacing is electrophysiologitally akin to left bundle branch block. Abnormality of the septal motion has been reported in patients with left bundle branch block (36). I therefore propose that causation of left bundle branch block could result in diminution or elimination of left ventricular outflow tract gradients comparable to dual chamber pacing. Moreover, it will be far too physiological in terms of rate responsiveness and atrio-ventricular synchrony as compared to the dual chamber pacemaker. Since it is now possible to map and ablate the left bundle branch percutaneously by radiofrequency technique, as has been occasionally used for the treatment of macro reentry ventricular tachycardia, it would not be difficult to do it technically in patients with HOCM.
How to prove this hypothesis It would be worth studying the hemodynamic variables such as the left ventricular systolic gradient, cardiac output, systemic blood pressure before and after induction of left bundle branch block in an animal model with HOCM. In addition to these, septal motion could be studied on 2D echo and left ventricular angiograms to see abnormalities of contractility as a result of left bundle branch block. One can also compare the gradients in patients of HOCM with left
143
bundle branch block and those without it to look for any significant difference in magnitude of gradients as a group, especially if these groups are comparable with respect to age, left ventricular mass, loading conditions and contractility. Since it may be difficult to find such comparative groups, it would be worth studying patients with HOCM prospectively from the point of development of left bundle branch block in the course of their disease. If left bundle branch block were to develop in patients under surveillance, comparison of various hemodynamic variables before and after development of the block could prove or disprove this hypothesis. If such patients have reduction in their gradients without significant change in the left ventricular function, the current hypothesis will be validated.
Conclusion After proving the efficacy of induced left bundle branch block in animal experiments, one can proceed to offer this modality as yet another palliation for patients with failure of medical therapy. If the results in human studies are encouraging then it could also be offered to patients who cannot tolerate drugs or have poor compliance. On the face of it, this therapy appears to be much more physiological from the point of rate-responsiveness and atrioventricular sequential contractions as compared to pacemaker therapy and will probably have less morbidity and mortality as compared to surgery. Moreover, it could also prove to be more cost-effective as compared to any of the available modalities of treatment.
References I. 2.
3. 4.
5.
6.
I.
8.
Maron BJ, Epstein SE. Hypettrophic cardiomyopathy: a discussion of nomenclature. Am J Cardiol 1979; 43: 1242-1244. Goodwin JF. Cardiomyopathies and specific heart muscle disease. Definition, terminology, classifications and new and old approaches. Postgrad Med J 1992; 68 (suppl I): S3-S6. Bokhari AM, McKenna WJ. Management of hypertrophic cardiomyopathy. Indian Heart J 1992; 44: 195-202. Colan SD, Spevak PJ. Pamess IA, Nadas AS. Cardiomyopathies. Nadas’ Pediatric Cardiology, 4th edn. Philadelphia: Hartley and Belfus, 1991: 341. McKenna WJ, Borggrefe M, England D, Deanfield J, Oakley CM, Goodwin JF. The natural history of left ventricular hypettrophy in hypertrophic cardiomyopathy: an electrocardiographic study. Circulation 1982; 66: 1233-1240. Swonton RH, Brooksby IAB, Jenkins BS, Webb-Peploe MM. Hemodynamic studies of beta blockade in IHSS. Eur J Cardiol 1977;5: 327-341. Spieser KW, Krayenbuehl HP. Reappraisal of the effect of acute beta blockade on left ventricular filling dynamics in hypertrophic cardiomyopathy. Eur Heart J 1981; 2: 21-29. Hess OM, Grimm J. Krayenbuehl HP Diastolic function in hypertrophic cardiomyopathy: effects of propranolol and verapamil on diastolic stiffness. Eur Heart J 1983; 4 (suppl F);
144 F47-F56. 9. Frank MJ, Abdulla AM, Canedo MI, Saylors RE. Long-term medical management of hypertrophic cardiomyopathy. Am J Cardiol 1978; 42: 993-1101. 10. Rosing DR. Kent M, Maron BJ, Epstein SE. Verapamil therapy: a new approach to pharmacological treatment of hypertrophic cardiomyopathy. Circulation 1979; 60: 1208-1213. Il. Rosing DR. Condit JR, Maron BJ et al. Verapamil therapy: a new approach to pharmacological treatment of hypertrophic cardiomyopathy III. Effects of long-term administration in hypertrophic cardiomyopathy. Am J Cardiol 198 I ; 48: 545-553. 12. Bonow RO. Dilsizian V, Rosing DR. Maron BJ, Bacharach SL, Green MV. Verapamil induced improvement in left ventricular filling and increased exercise tolerance in patients with hypertrophic cardiomyopathy: short- and long-term effects. Circulation 1985; 72: 853-864. 13. Bonow RO, Ostrow HG, Rosing DR et al. Effects of verapamil on left ventricular systolic and diastolic functions in patients with hypertrophic cardiomyopathy: pressure-volume analysis with non-imaging scintillating probe. Circulation 1983; 68: 1062-1073. 14. Hess OM, Murakami T, Krayenbuehl HP. Does verapamil improve left ventricular relaxation in patients with myocardial hypertrophy Circulation 1986; 74: 530-543. 15. Hanrath P, Mathey DG, Kremer P, Sonntag F, Bleifeld W. Effect of verapamil on left ventricular isovolumetric relaxation time and regional left ventricular filling in hypertrophic cardiomvooathv. Am J Cardiol 1980: 45: 1258-1264. 16. Pollick ‘C, Detsky A, Ogilvie RI, Wilansky S. Disopyramide and propranolol in hypertrophic cardiomyopathy: double blind randomized trial (abstr). Circulation 1985; 72 (suppl III) III155. and 17. Pollick C. Muscular subaortic stenosis: hemodynamic clinical improvement after disopyramide. N Engl J Med 1982; 307:997-999. 18. Leon MB, Rosing DR, Maron BJ, Bonow RO, Lesko LJ, Epstein SE. Amiodarone in patients with hypertrophic cardiomyopathy and refractory cardiac symptoms: an alternative to current medical therapy (abstr). Circulation 1984; 70 (suppl II) II-1 8. 19. Sugrue DD, Dickie S, Myers MJ, Lavender JP, McKenna WJ. Effect of amiodarone on left ventricular ejection and filling in hypertrophic cardiomyopathy as assessed by radionuclide angiography. Am J Cardiol 1984; 54: 1054-1058. 20. Paulus WJ. Nellens P, Heyndrick GR, Andries E. The influence of chronic amiodarone therapy on left ventricular relaxation: rest and exercise hemodynamics in patients with hypertrophic cardiomyopathy. Circulation 1986; 74: 544-554. 21. McKena WJ, Harris L, Perez G, Krikler DM, Oakley C, Goodwin JF. Arrhythmias in hypertrophic cardiomyopathy Il. Comparison of amiodarone and verapamil in treatment. Br Heart J 1981; 46: 173-178. 22. Schulte HD, Bircks WH, Locsse B, Godehardt EAJ, Schwart-
MEDlCAL HYPOTHESES
23
24
25
26.
27.
28.
29.
30.
31.
32.
33.
34.
35.
36.
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