The present study included 82 patients with obstructive HCM, sinus rhythm, and disabling symptoms despite optimal medical therapy who were treated with SAVP in Hospital Universitario 12 de Octubre between 1991 and 2009. Each patient's treatment was discussed in a multidisciplinary clinical conference before the intervention, and the final decision considered comorbidities, alternative treatment availability, and patients’ wishes. Obstructive HCM was diagnosed using 2-dimensional echocardiographic visualization of unexplained ventricular hypertrophy > 15mm in any myocardial segment. All patients had severe LVOT obstruction (> 50mmHg) on continuous wave Doppler imaging. At the time of patient inclusion, disopyramide was not available in our center.

Informed consent was obtained from all patients before pacemaker implantation. Clinical and echocardiographic parameters were measured before and immediately after implantation and after a long follow-up (median, 8.5 years [range, 1-18] years). Final data collection was retrospective.

Functional class and angina were evaluated according to the classifications of the New York Heart Association (NYHA) and the Canadian Society of Cardiology, respectively. Information was also collected on history of syncope, presyncope, and heart failure. The echocardiographic variables measured were peak subaortic velocity, peak and mean LVOT gradients at rest and after Valsalva maneuvers, systolic anterior movement of the mitral valve (scored from 0 to 4),11 maximum wall thickness, maximum left atrial diameter in the apical 4-chamber plane, LV ejection fraction (LVEF; measured using the biplane Simpson method), and end-diastolic and end-systolic LV volumes and diameters. Mitral regurgitation was semiquantitatively evaluated based on visual estimation and information from pulsed, continuous, and color Doppler imaging. Regurgitation was classified into 5 grades (0, absent; I, trivial; II, mild; III, moderate, and IV, severe). Diastolic function was assessed using Doppler echocardiography. Also analyzed were the peak velocity of the E and A waves, E/A and E/E’ ratios, pressure half-time, mitral deceleration time of early filling, isovolumic relaxation time, and pulmonary systolic pressure. Calculation of the E/A ratio was omitted in patients with atrial fibrillation during follow-up.

A permanent dual-chamber pacemaker in DDD mode was implanted according to the standard method in all patients, with the ventricular lead placed in the right ventricular apex.3 The atrioventricular delay was determined using echocardiographic evaluation of acute changes in the LVOT and the transmitral filling pattern during pacing (Figure 1). We chose the atrioventricular delay achieving the highest LVOT gradient reduction without excessive shortening of the ventricular filling time, as indicated by the minimal deterioration in the qualitative morphology of the mitral filling pattern on echocardiography. Attempts were made to ensure a ventricular capture greater than 95%, associating this programming with increased treatment with the maximum doses of atrioventricular nodal blocking agents.

Figure 1.

Obstructive gradient of the left ventricular outflow tract (left panels) and transmitral Doppler flow imaging (right panels) in a patient with obstructive hypertrophic cardiomyopathy treated with sequential atrioventricular pacing and followed up for 18 years. A: baseline; B: 6-month follow-up; C: 12-month follow-up; D: final follow-up. Follow-up imaging revealed a permanent reduction in the obstructive gradient of the left ventricular outflow tract (left) and no progression in the baseline diastolic dysfunction (right, A).

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Data were collected in regularly scheduled (typically annually) clinical follow-up evaluations that included physical examination, assessment of functional class via clinical history, 12-lead electrocardiogram, and echocardiography. Pacemaker interrogation was performed annually in all patients and 24-Holter monitoring was performed every 1 to 3 years in asymptomatic patients and immediately after new symptom development to evaluate ventricular capture and potential pacemaker dysfunction or arrhythmia. Also recorded were deaths (both cardiac and noncardiac) occurring during follow-up and implant-related complications.

The normality of the quantitative variables was determined using the Kolmogorov-Smirnov test. Quantitative variables following a normal distribution are expressed as mean ± standard deviation; nonnormally distributed quantitative variables are expressed as median (range). Qualitative variables are expressed as percentages. For comparisons between 2 quantitative variables, the Student t test was used for independent variables if they followed a normal distribution; if not, the Wilcoxon test was used. Qualitative variables were compared using the chi-square test and McNemar's test. Differences were considered statistically significant at P < .05. All statistical analyses were performed using SPSS software (version 17.0, SPSS Inc.).

Despite the reported benefits of SAVP, its efficacy has been put in doubt by the possible placebo effect of pacemaker implantation.8,9 The reduced obstructive gradient and mitral regurgitation were maintained during the long follow-up, in conjunction with an improved functional class, indicating a direct relationship between the hemodynamic effect and the clinical benefit of the treatment. However, our study design does not allow exclusion of a potential placebo effect. Similar results were obtained in previous studies with long follow-up durations.3,6,15 The symptom reduction may also have been at least partly due to bradycardia improvement in the 12 patients with another pacemaker indication. However, the objective gradient reduction suggests that it was fundamental to symptom improvement.

The few randomized studies evaluating SAVP have shown moderate results. Nonetheless, the clinical benefit is clearer in older patients (> 65 years)8 and those with greater functional limitation.9 Notably, these studies included relatively young patients (mean age, 53 years) and with less severe symptoms (the Pacing in Cardiomyopathy study excluded patients in NYHA IV). The reduced pacing duration in these crossover studies (2-3 months) might be insufficient to permanently reduce the obstructive gradient, as has been indicated.3 Thus, the good results in our population could be explained by the significantly higher mean age of our cohort (66 years; 82% older than 65 years), the higher proportion of patients with disabling symptoms (predominantly NYHA III-IV or limiting angina), and the long pacing duration.

No significant differences were observed in gradient reduction or symptom reduction between patients with permanent atrial fibrillation and those in sinus rhythm during follow-up. The change induced in the ventricular activation pattern during right ventricular apex pacing delays septal contraction and induces premature activation of the papillary muscles and the subvalvular mitral apparatus, reducing the systolic anterior movement of the mitral valve.16,17 This mechanism could explain the benefit of the therapy in patients with atrial fibrillation.

In our series, there was no significant reduction in the systolic function or increase in the ventricular diameters at the end of follow-up. Diastolic function can also be decreased by SAVP, particularly when there is no previous diastolic dysfunction. In a retrospective study with a 12-month follow-up, patients with diastolic dysfunction (mainly elderly) seemed to benefit more from pacemaker implantation than patients with normal diastolic function.12 There was no significant worsening in diastolic function, probably due to the advanced age of the cohort and the presence of baseline diastolic dysfunction in most patients. On the other hand, no improvement was detected in the baseline diastolic function, as reported previously with a shorter follow-up.3

Cardiac pacing can reduce LV thickness.10 Left ventricular remodeling after prolonged pacing in patients with obstructive HCM could explain the late positive response to this therapy.5 No significant reductions were found in the maximum wall thickness, although a tendency for a decrease was seen.

In patients with obstructive HCM whose symptoms are refractory to medical treatment, surgical myectomy is the recommended intervention of choice. Because the results of septal ablation are similar to those of surgical myectomy, ablation is considered an alternative in patients who are not surgical candidates. The third option is considered to be SAVP, mainly in patients with another pacemaker implantation indication (recommendation IIa) or at high risk for septal reduction techniques or when these are unavailable (recommendation IIb).4,5

Notably, SAVP is the most studied invasive strategy in patients with obstructive HCM and has been evaluated in various controlled clinical studies. Although septal reduction techniques have been endorsed in some studies, they may not have been evaluated as exhaustively18 and their indications are based on expert consensus. Additionally, the superiority of surgical myectomy over SAVP has only been shown in highly specialized centers.19 Septal reduction techniques have a high success rate with low associated morbidity and mortality when performed in selected patients and in specialized centers.18 However, the morbidity and mortality associated with surgical myectomy is 15%,20 whereas that of septal ablation is 20% to 40%6,18,20,21 (particularly complete atrioventricular block), markedly higher than that associated with pacemaker implantation. Moreover, up to 20% of patients who undergo septal ablation require further surgery. Ventricular arrhythmias associated with the septal infarct scar have also been described after septal ablation.

Moreover, few centers have the experience and volume necessary to ensure the effectiveness and safety of these techniques, a required condition for their recommendation in clinical practice guidelines. Thus, their availability is limited, in contrast to the wide availability of centers implanting cardiac pacing devices. The economic impact of these techniques, due to the intervention, the hospital stay, and the management of potential complications, could be higher than that associated with pacemaker therapy.

Long-term SAVP causes prolonged symptomatic improvements without ventricular function deterioration and facilitates optimization of the medical treatment. For symptomatic patients despite pacing, beta-blocker and calcium antagonist doses can be increased without risk of extreme bradycardia; for therapy responders, the doses of these drugs can be reduced to avoid poorly tolerated adverse effects, such as hypotension.

Regarding the advantages of SAVP in the management of obstructive HCM, Galve et al,6 by applying a therapeutic strategy beginning with SAVP, indicated that only 18% of the patients required a more invasive procedure (septal ablation and/or surgical myectomy). In our series, only 6% of the patients who failed to improve with pacing required septal reduction techniques. Even under these circumstances, a pacemaker could be useful given the relatively common incidence of atrioventricular block associated with these techniques.

Although the initial study was prospectively planned and the baseline and postimplantation clinical and echocardiographic parameters were collected immediately after implantation, the final data collection was retrospective and could have been affected by the limitations inherent to this type of study.

Functional class was not objectively evaluated. Additionally, symptom evaluation was based on clinical interviews and, primarily, on a subjective NYHA classification. However, this classification is commonly used in clinical practice to guide changes in treatment strategies.

The symptom reduction may have been at least partly due to bradycardia improvement in the 12 patients with another pacemaker indication. However, the objective gradient reduction suggests that it was fundamental to symptom improvement. Similarly, it is possible that the increased doses of beta-blockers/calcium antagonists, which was only feasible after pacemaker implantation and was performed in some patients to ensure adequate ventricular capture, could have helped to improve the gradient and the symptoms.

The findings were not compared with those of a control group. Nonetheless, we believe that the results provide important information for future randomized studies.

To confirm these findings, further studies with larger sample sizes are required, as well as objective measurements of the functional class and longer follow-up periods.