Pacing for drug-refractory or drug-intolerant Hypertrophic cardiomyopathy

Hypertrophic cardiomyopathy (HCM) is a genetic disease with an autosomal-dominant inheritance, which can cause obstruction in the left ventricle outflow tract. This obstruction can lead to a variety of symptoms like dyspnoea, chest pain, syncope and palpitations. The prevalence of HCM in the general population, as determined from echocardiographic studies in the United States, Japan, and China, has ranged from 0.16 to 0.29 percent. Treatment options for HCM ranges from drugs to surgery with each having its own limitations. Active cardiac pacing was suggested as a treatment option in some trials. We conducted this review to assess the available evidence on the effects of active pacing in drug-refractory or drug-intolerant HCM patients. Five studies (reported in 10 papers) were found to be relevant. However, three of the five studies provided un-usable data. Thus data from only two studies (reported in seven papers) with 105 participants was included for this review. There was insufficient data to compare results on all-cause mortality, cost effectiveness, exercise capacity, Quality of life and Peak O2 consumption. There was no difference in exercise capacity when comparing active pacing versus placebo pacing. However left ventricular outflow tract obstruction decreased significantly in the active pacing group compared to placebo. New York Heart Association functional class increased in the active pacing group compared to the placebo group and this was also observed when comparing active pacing versus trancoronary ablation of septal hypertrophy. Interpretation of these data needs to be cautious because existing data is derived from small trials at high risk of bias, which concentrate on physiological measures. Their results are inconclusive. Further large and high quality trials with more appropriate outcomes are warranted.

Authors' conclusions: 

Trials published to date lack information on clinically relevant end-points. Existing data is derived from small trials at high risk of bias, which concentrate on physiological measures. Their results are inconclusive. Further large and high quality trials with more appropriate outcomes are warranted.

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Background: 

Hypertrophic cardiomyopathy (HCM) is a genetic disease with an autosomal-dominant inheritance for which negative inotropes are the most widely used initial therapies. Observational studies and small randomised trials have suggested symptomatic and functional benefits using pacing and several theories have been put forward to explain why. Pacing, although not the primary treatment for HCM, could be beneficial to patients with relative or absolute contraindications to surgery or alcohol ablation. Several randomised controlled trials comparing pacing to other therapeutic modalities have been conducted but no Cochrane-style systematic review has been done.

Objectives: 

To assess the effects of pacing in drug-refractory or drug-intolerant hypertrophic cardiomyopathy patients.

Search strategy: 

We searched the following on the 14/4/2010: CENTRAL (The Cochrane Library 2010, Issue 1), MEDLINE OVID (from 1950 onwards ), EMBASE OVID (from1980 onwards ), Web of Science with Conference Proceedings (from 1970 onwards). No language restrictions were applied.

Selection criteria: 

Randomised controlled trials of either parallel or crossover design that assess the beneficial and harmful effects of pacing for hypertrophic cardiomyopathy were included. When crossover studies were identified, we considered data only from the first phase.

Data collection and analysis: 

Data from included studies were extracted onto a pre-formed data extraction paper by two authors independently. Data was then entered into Review Manager 5.1 for analysis. Risk of bias was assessed using the guidance provided in the Cochrane Handbook. For dichotomous data, relative risk was calculated; and for continuous data, the mean differences were calculated. Where appropriate data were available, meta-analysis was performed. Where meta-analysis was not possible, a narrative synthesis was written. A QUROUM flow chart was provided to show the flow of papers.

Main results: 

Five studies (reported in 10 papers) were identified. However, three of the five studies provided un-usable data. Thus the data from only two studies (reported in seven papers) with 105 participants were included for this review. There was insufficient data to compare results on all-cause mortality, cost effectiveness, exercise capacity, Quality of life and Peak O2 consumption.

When comparing active pacing versus placebo pacing on exercise capacity, one study showed that exercise time decreased from (13.1 ± 4.4) minutes to (12.6 ± 4.3) minutes in the placebo group and increased from (12.1 ± 5.6) minutes to (12.9 ± 4.2) minutes in the treatment group (MD 0.30; 95% CI -1.54 to 2.14). Statistically significant data from the same study showed that left ventricular outflow tract obstruction decreased from (71 ± 32) mm Hg to (52 ± 34) mm Hg in the placebo group and from (70 ± 24) mm Hg to (33 ± 27) mm Hg in the active pacing group (MD -19.00; 95% CI -32.29 to -5.71). This study was also able to show that New York Heart Association (NYHA) functional class decreased from (2.5 ± 0.5) to (2.2 ± 0.6) in the inactive pacing group and decreased from (2.6 ± 0.5) to (1.7 ± 0.7) in the placebo group (MD -0.50; 95% CI -0.78 to -0.22).

When comparing active pacing versus trancoronary ablation of septal hypertrophy (TASH), data from one study showed that NYHA functional class decreased from (3.2 ± 0.7) to (1.5 ± 0.5) in the TASH group and decreased from (3.0 ± 0.1) to (1.9 ± 0.6) in the pacemaker group. This study also showed that LV wall thickness remained unchanged in the active pacing group compared to reduction from (22 ± 4) mm to (17 ± 3) mm in the TASH group (MD 0.60; 95% CI -5.65 to 6.85) and that LV outflow tract obstruction decreased from (80 ± 35.5) mm Hg in the TASH group to (49.3 ± 37.7) mm Hg in the pacemaker group.

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