Effect of four classes of antihypertensive drugs on cardiac repolarization heterogeneity: A double-blind rotational study

PLoS One. 2020 Mar 24;15(3):e0230655. doi: 10.1371/journal.pone.0230655. eCollection 2020.

Abstract

Background: T-wave area dispersion (TW-Ad) is a novel electrocardiographic (ECG) repolarization marker associated with sudden cardiac death. However, limited data is available on the clinical correlates of TW-Ad. In addition, there are no previous studies on cardiovascular drug effects on TW-Ad. In this study, we examined the relation between TW-Ad and left ventricular mass. We also studied the effects of four commonly used antihypertensive drugs on TW-Ad.

Methods: A total of 242 moderately hypertensive males (age, 51±6 years; office systolic/diastolic blood pressure during placebo, 153±14/100±8 mmHg), participating in the GENRES study, were included. Left ventricular mass index was determined by transthoracic echocardiography. Antihypertensive four-week monotherapies (a diuretic, a beta-blocker, a calcium channel blocker, and an angiotensin receptor antagonist) were administered in a randomized rotational fashion. Four-week placebo periods preceded all monotherapies. The average value of measurements (over 1700 ECGs in total) from all available placebo periods served as a reference to which measurements during each drug period were compared.

Results: Lower, i.e. risk-associated TW-Ad values correlated with a higher left ventricular mass index (r = -0.14, p = 0.03). Bisoprolol, a beta-blocker, elicited a positive change in TW-Ad (p = 1.9×10-5), but the three other drugs had no significant effect on TW-Ad.

Conclusions: Our results show that TW-Ad is correlated with left ventricular mass and can be modified favorably by the use of bisoprolol, although demonstration of any effects on clinical endpoints requires long-term prospective studies. Altogether, our results suggest that TW-Ad is an ECG repolarization measure of left ventricular arrhythmogenic substrate.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adrenergic beta-Antagonists / pharmacology
  • Adrenergic beta-Antagonists / therapeutic use
  • Angiotensin Receptor Antagonists / pharmacology
  • Angiotensin Receptor Antagonists / therapeutic use
  • Antihypertensive Agents / pharmacology
  • Antihypertensive Agents / therapeutic use*
  • Bisoprolol / pharmacology
  • Bisoprolol / therapeutic use
  • Blood Pressure
  • Calcium Channel Blockers / pharmacology
  • Calcium Channel Blockers / therapeutic use
  • Death, Sudden, Cardiac / prevention & control
  • Diuretics / pharmacology
  • Diuretics / therapeutic use
  • Double-Blind Method
  • Echocardiography
  • Heart Ventricles / anatomy & histology
  • Heart Ventricles / drug effects
  • Heart Ventricles / physiopathology*
  • Humans
  • Hypertension / drug therapy*
  • Hypertension / physiopathology
  • Male
  • Middle Aged
  • Ventricular Function / drug effects

Substances

  • Adrenergic beta-Antagonists
  • Angiotensin Receptor Antagonists
  • Antihypertensive Agents
  • Calcium Channel Blockers
  • Diuretics
  • Bisoprolol

Grants and funding

KKK: Sigrid Jusélius Foundation. Grant number 140318#3/3. https://sigridjuselius.fi/en/ KKK: Finnish Foundation for Cardiovascular Research. Grant number 190416KK. http://www.sydantutkimussaatio.fi/en/foundation The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.