Summary
Background
The very long-term effects of dual chamber pacing as a primary treatment for hypertrophic obstructive cardiomyopathy (HOCM) are poorly known and controversial.
Aims
To examine the intermediate- and long-term clinical and haemodynamic effects of permanent dual chamber pacing in patients presenting with HOCM.
Methods
Between 1991 and 2007, 51 patients (mean age 59 ± 14 years) presenting with HOCM and New York Heart Association (NYHA) functional class ≥ II despite optimal medical therapy underwent implantation of DDD pacemakers with or without a defibrillator and were followed for 11.5 years (range 0.4–21.8 years).
Results
During follow-up, no patient underwent myectomy or septal alcohol ablation. NYHA functional class and other disease manifestations decreased significantly over 1–2 years of follow-up and remained stable thereafter. The left intraventricular (LV) gradient decreased by a mean of 78% over 1–2 years, reaching 89% at end of follow-up, along with disappearance of systolic anterior motion of the mitral valve. Mean LV ejection fraction decreased from a mean of 64 ± 8% before pacing to 56 ± 9% at end of follow-up ( P = 0.05), while LV end-diastolic diameter did not change significantly. The 5- and 10-year actuarial survival rates were 90% and 65%, respectively. Among 22 deaths, 10 were due to cardiovascular and 12 to non-cardiovascular causes; two patients underwent cardiac transplantation after 8 and 13 years of DDD pacing, respectively.
Conclusions
In this sample of patients with HOCM, DDD pacing alleviated symptoms and improved haemodynamic function over the very long term. The merits of this treatment should be revisited in a controlled trial.
Résumé
Contexte
L’efficacité de la stimulation cardiaque double-chambre comme traitement primaire de la cardiomyopathie hypertrophique obstructive (CMHO) reste controversée. Les effets à très long terme ne sont pas connus.
Objectifs
Décrire les effets cliniques et hémodynamiques à moyen et à long terme observés après traitement électrique.
Méthodes
Cinquante-quatre patients (59 ± 14 ans) ayant une CMHO et demeurant symptomatiques (dyspnée NYHA > 2) sous traitement médical optimisé, ont bénéficié de l’implantation d’un stimulateur double-chambre DDD avec ou sans fonction de défibrillation entre 1991 et 2007. Le suivi moyen est de 11,5 ans (extrêmes : 0,4–21,8).
Résultats
Aucun patient n’a eu de myectomie ou d’ablation septale secondaire. Le stade NYHA diminue au cours du suivi (93 % en stade 1–2 en fin de suivi vs 43 % avant l’implantation, p < 0,0001). Angor et lipothymies/syncopes diminuent significativement. Le gradient intraventriculaire gauche initialement de 79 ± 36 mmHg diminue à 20 ± 24 à trois mois, 11 ± 15 entre un et deux ans et 8 ± 21 en fin de suivi ( p < 0,0001). Le SAM présent initialement chez 52 patients n’est retrouvé que sept fois après implantation ( p < 0,0001). La fraction d’éjection tend à diminuer en fin de suivi (56 ± 9 % vs 64 ± 8 % ; p < 0,05) alors que le diamètre télédiastolique VG reste sable. Le taux de survie actuariel est de 90 % à cinq ans et de 65 % à dix ans. Parmi les 22 décès, dix sont de cause cardiovasculaire et 12 de cause non cardiovasculaire.
Conclusions
Le traitement par stimulation DDD semble être bénéfique à très long terme sur les symptômes et les paramètres hémodynamiques. Il altère peu ou pas la fonction systolique VG. Ces résultats incitent à réévaluer cette modalité de traitement dans de nouveaux essais contrôlés.
Background
Right ventricular (RV) apical pacing with preservation of atrioventricular (AV) synchrony lowers the left intraventricular gradient and increases cardiac output in patients with obstructive hypertrophic cardiomyopathy (HOCM) . A delay in septal contraction and long-term ventricular remodelling have been suggested as putative mechanisms . The implantation of a DDD pacemaker has therefore been proposed in selected patients with HOCM who remain symptomatic despite optimal medical management . In contrast with other non-pharmacologic treatments of obstruction, i.e. surgical or alcohol septal reduction, DDD pacing has been evaluated in several small short randomized studies, which showed no significant short-term clinical benefit compared with a placebo effect . While its long-term effect is poorly known, a few observational studies have suggested a sustained benefit after 4–5 years of pacing . This study was performed to evaluate the clinical and haemodynamic effects of this treatment over the very long term in patients whose symptoms were insufficiently alleviated by medical management alone.
Methods
Inclusion criteria
We included in this study all patients who, between June 1991 and January 2007, underwent implantation of permanent DDD pacemakers, with or without an implantable cardioverter defibrillator (ICD), for the treatment of HOCM that remained symptomatic despite optimal medical management. During the study period, short AV delay DDD pacing was the preferred option for treating obstruction at our institution; eight other patients had surgical myectomy and five had transcatheter septal ablation as the primary approach. Inclusions were stopped from 2007 to have a minimum follow-up time of 5 years. The diagnosis of HOCM was based on the World Health Organization criteria, i.e. diastolic interventricular septal thickness ≥ 15 mm (≥ 13 mm in familial HOCM) measured by transthoracic echocardiography. Intra left ventricular (LV) dynamic obstruction was defined as ≥ 30 mmHg resting or provoked peak subaortic gradient. All patients were in New York Heart Association (NYHA) functional class ≥ II and had undergone unsuccessful treatment attempts with one or more pharmaceutical known to be effective in the treatment of HOCM, including beta-adrenergic blockers, verapamil/diltiazem or disopyramide, or were intolerant of these medications. Patients with NYHA functional class II had to report at least one other symptom, syncope/presyncope or chest pain to be included. No patient had a primary indication for permanent cardiac pacing .
Pacemaker implantation
All patients underwent implantation of a DDD pacemaker, with or without ICD , and with the ventricular lead implanted at the very apex of the right ventricle. Before hospital discharge, the AV delay was systematically programmed at an ‘optimal’ value, i.e. the longest interval associated with complete ventricular capture, at rest and during exercise. Radiofrequency modification of the AV junction was performed in patients whose short spontaneous PR interval precluded the complete capture of the ventricles ( Fig. 1 ) or in patients with histories of poorly tolerated recurrent atrial fibrillation refractory to antiarrhythmic drug therapy. In patients whose P wave duration was ≥ 120 ms, a third lead was placed in the coronary sinus and connected to a biatrial DDD pacemaker to resynchronize the atria . Pharmacological treatment was continued in all patients.
Patient follow-up
After device implantation, follow-up data were collected at 3 months, between 1 and 2 years, in the year preceding the patient’s death or in 2011 in all survivors. The sources of information included pacemaker implantation records and the cardiologists’ and primary physicians’ progress notes. In patients whose medical information was missing, vital status was ascertained by consulting the public records. At each visit at the implanting centre, the patient’s functional status was estimated, based on NYHA classification and other reported symptoms, ongoing treatment and possible interim adverse events were recorded and the patients underwent a physical examination, a 12-lead electrocardiogram recording with interrogation and verification of the pacing system’s proper function and transthoracic echocardiography with the AV interval programmed to obtain the smallest left intraventricular gradient.
Statistical analyses
Continuous variables are expressed as means ± standard deviations and categorical variables as counts and percentages. Continuous variables were compared using repeated measures analysis of variance and categorical variables were compared using McNemar’s Chi-square test. Survival analyses were performed using the Kaplan-Meier method and compared using the log-rank test. A P value < 0.05 was considered significant.
Results
Patient population
This retrospective observational study included 51 DDD pacemaker recipients who were followed at Rennes University Medical Centre. The main baseline characteristics of the sample are shown in Table 1 . Before undergoing device implantation, 41% of patients had a history of syncope or presyncope, more than 20% complained of angina pectoris and more than 60% were in NYHA functional class > II. All but one patient, who tolerated neither drug regimen, were treated with drugs recommended for the treatment of symptomatic HOCM. Beta-blockers were prescribed to two-thirds of patients, alone or in combination with amiodarone ( n = 7), a calcium channel blocker (verapamil; n = 3) or disopyramide ( n = 1). Verapamil alone was prescribed to 20% of patients. A single patient had undergone myectomy 12 years before pacemaker implantation.
| Characteristic | |
|---|---|
| Men | 24 (47) |
| Age (years) | 59 ± 14 (24–83) |
| NYHA functional class | |
| II | 20 (39) |
| III | 28 (54) |
| IV | 3 (6) |
| Syncope or presyncope | 21 (41) |
| Angina pectoris | 10 (21) |
| History of myectomy | 1 (2) |
| Echocardiographic measurements | |
| Left ventricular ejection fraction (%) | 63.5 ± 7.5 (44–81) |
| Diastolic interventricular septal thickness (mm) | 18 ± 4 (13–26) |
| Peak left ventricular outflow tract gradient at rest (mmHg) | 79 ± 36 (0–155) |
| Mitral systolic anterior motion | 49 (96) |
| Mitral regurgitation grade | |
| 0 | 2 (4) |
| 1 | 21 (41) |
| 2 | 23 (45) |
| 3 | 5 (10) |
| Drug therapy | |
| None | 1 (2) |
| Beta-adrenergic blocker | 36 (71) |
| Calcium antagonist | 14 (27) |
| Amiodarone | 9 (18) |
| Disopyramide | 1 (2) |
| Type of device implanted | |
| Dual chamber pacemaker | 47 (92) |
| Dual chamber implantable cardioverter defibrillator | 4 (8) |
The maximum diastolic interventricular septal thickness ranged between 13 and 26 mm. Systolic anterior motion of the mitral valve was present in 49/51 patients. In five patients without severe LV outflow tract (LVOT) obstruction under basal conditions, the administration of nitroglycerine increased the LVOT gradient from a mean of 22 ± 9 mmHg to 65 ± 23 mmHg. While nearly all patients presented with some degree of mitral insufficiency, it was > 2 in only five patients.
Procedural data
Dual chamber ICDs were implanted in four patients for secondary prevention indications. Interruption or modulation of the AV junction was performed before hospital discharge in four patients, to optimize AV synchrony for very short PR intervals during sinus rhythm ( n = 2) and for recurrent atrial fibrillation with a rapid ventricular rate ( n = 2). Biatrial DDD pacemakers were implanted to resynchronize the atria in 21 patients (41%). In all cases, biatrial pacing was activated at the time of implantation.
Clinical outcomes
Over a median of 11.5 years (range 0.4–21.8 years), 22 patients died and two patients underwent cardiac transplantation after 8 and 13 years of DDD pacing, respectively ( Fig. 2 ). Among 10 patients who died of cardiovascular causes, four died suddenly, none had an ICD implanted, three died of end-stage heart failure, two died of stroke and one died in the wake of implantation of a ventricular assist device as a bridge to transplantation, after 5 years of pacing. The 12 remaining patients died of non-cardiovascular causes, 8 years on average after the implantation of the DDD pacing system. No patient underwent a supplemental procedure during follow-up, such as surgical myectomy or alcohol septal ablation with a view to alleviate residual LVOT obstruction. The actuarial survival of the sample is shown in Fig. 2 .
