The Effect of Metoprolol in Patients With Hypertrophic Obstructive Cardiomyopathy - TEMPO

Dec 14, 2021
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Author/Summarized by Author:
Anthony A. Bavry, MD, MPH, FACC
Summary Reviewer:
Deepak L. Bhatt, MD, MPH, MBA, FACC
Trial Sponsor:
Novo Nordic Foundation
Date Published:
12/13/2021
Original Posted Date:
12/14/2021
References

Contribution To Literature:

The TEMPO trial showed that metoprolol succinate reduced LVOT obstruction, provided symptom relief, and improved quality of life.

Description:

The goal of the trial was to evaluate metoprolol succinate compared with placebo among patients with hypertrophic obstructive cardiomyopathy (HOCM).

Study Design

  • Randomization
  • Parallel
  • Placebo
  • Crossover

Patients with HOCM were randomized to metoprolol succinate (n = 29) versus placebo (n = 29) for 2 weeks, after which time they crossed over to the opposite treatment for 2 weeks.

  • Total number of enrollees: 29
  • Duration of follow-up: 6 weeks
  • Mean patient age: 60 years
  • Percentage female: 38%

Inclusion criteria:

  • Patients ≥18 years of age with HOCM
  • Wall thickness ≥15 mm in ≥1 left ventricular segments
  • Peak left ventricular outflow tract (LVOT) gradient ≥30 mm Hg at rest and/or ≥50 mm Hg with Valsalva or post-exercise
  • New York Heart Association (NYHA) functional class II or higher

Exclusion criteria:

  • Permanent atrial fibrillation
  • Bradycardia
  • Hypotension
  • Bifascicular block or contraindication to beta-blocker therapy

Principal Findings:

  • LVOT gradient at rest: 25 mm Hg with metoprolol succinate vs. 72 mm Hg with placebo (p = 0.007)
  • LVOT gradient at peak exercise: 28 mm Hg with metoprolol succinate vs. 62 mm Hg with placebo (p < 0.001)
  • LVOT gradient post-exercise: 45 mm Hg with metoprolol succinate vs. 115 mm Hg with placebo (p < 0.0001)
  • LVOT gradient during Valsalva: 94 mm Hg with metoprolol succinate vs. 119 mm Hg with placebo (p = 0.08)

Secondary outcomes:

  • Global longitudinal strain (the more negative the number the better): -15.9% with metoprolol succinate vs. -14.5% with placebo (p < 0.001)
  • New York Heart Association class III or higher: 14% with metoprolol succinate vs. 38% with placebo (p < 0.01)
  • Kansas City Cardiomyopathy Questionnaire Overall Summary Score (the larger the number the better): 76.2 with metoprolol succinate vs. 73.8 with placebo (p = 0.039)
  • Heart rate at peak exercise: 107 bpm with metoprolol succinate vs. 138 with placebo (p < 0.001)
  • Exercise duration: 13 minutes with metoprolol succinate vs. 13 with placebo (p = 0.70)

Interpretation:

Among symptomatic patients with HOCM, the use of metoprolol succinate was beneficial. Metoprolol succinate versus placebo was associated with lower LVOT gradients, and improved symptoms and quality of life. Metoprolol succinate did not improve exercise capacity. There were no serious adverse events from metoprolol succinate. Beta-blockers have long been considered first-line treatment for HOCM; however, few studies have examined this practice.

References:

Dybro AM, Rasmussen TB, Nielsen RR, Andersen MJ, Jensen MK, Poulsen SH. Randomized Trial of Metoprolol in Patients With Obstructive Hypertrophic Cardiomyopathy. J Am Coll Cardiol 2021;78:2505-17.

Editorial Comment: Masri A. A New Dawn in HCM: Rise of the RCTs. J Am Coll Cardiol 2021;78:2533-6.

Clinical Topics: Diabetes and Cardiometabolic Disease, Heart Failure and Cardiomyopathies, Prevention, Acute Heart Failure, Exercise

Keywords: Adrenergic beta-Antagonists, Cardiomyopathy, Hypertrophic, Exercise, Exercise Tolerance, Heart Failure, Heart Rate, Metoprolol, Quality of Life, Sinus of Valsalva, Ventricular Outflow Obstruction


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