Ramipril and left ventricular diastolic function in stable patients with pulmonary regurgitation after repair of tetralogy of Fallot

Int J Cardiol. 2018 Dec 1:272:64-69. doi: 10.1016/j.ijcard.2018.07.132. Epub 2018 Aug 1.

Abstract

Background: Measures of left ventricular (LV) systolic and diastolic function are known predictors of mortality after repair of tetralogy of Fallot. We aimed to characterise LV reverse remodelling achievable with ramipril therapy.

Methods and results: A blinded post-hoc analysis of baseline and 6-month follow-up echocardiograms from the APPROPRIATE (ISRCTN: 97515585) randomised double-blinded placebo-controlled trial of ramipril therapy was performed in 64 patients: 32 in ramipril and 32 in placebo group. Tissue Doppler systolic and diastolic myocardial velocities, mitral inflow velocities and time intervals were measured. Left atrial area and left atrial emptying fraction were calculated. There was significant increase in long axis shortening mean (standard deviation); MAPSE [1.9 (4.2) mm vs -0.2 (3.7) mm; p = 0.030], peak lateral systolic velocity; S' lateral [1.0 (2.0) cm/s vs -0.3 (2.2) cm/s; p = 0.025], peak lateral early diastolic velocity; E' lateral [0.57 (2.4) cm/s vs -3.3 (3.9) cm/s; p < 0.001], transmitral to lateral mitral annular early diastolic velocity ratio; E/E' lateral [-0.7 (1.9) vs 1.5 (1.9); p < 0.001] over the study period in the ramipril compared to the placebo group. Significantly higher measurements were observed in the ramipril arm of the subgroup of patients with right ventricular restrictive physiology in terms of peak late diastolic velocity; A [5.9 (13.5) cm/s vs -5.8 (12.5) cm/s; p = 0.041] and early to late diastolic transmitral velocity ratio; E/A [-0.18 (0.42) vs 0.23 (0.48); p = 0.037].

Conclusion: Six months' ramipril treatment appears to limit progression of both diastolic and systolic LV function in adults late after tetralogy of Fallot repair. With increased appreciation that even subtle LV disease predicts tetralogy of Fallot outcomes, further clinical trials of drug therapies are justified.

Keywords: ACE inhibitor; Pulmonary regurgitation; Tetralogy of Fallot.

Publication types

  • Randomized Controlled Trial

MeSH terms

  • Adult
  • Angiotensin-Converting Enzyme Inhibitors / pharmacology
  • Angiotensin-Converting Enzyme Inhibitors / therapeutic use*
  • Double-Blind Method
  • Female
  • Follow-Up Studies
  • Humans
  • Male
  • Postoperative Complications / diagnostic imaging
  • Postoperative Complications / drug therapy*
  • Postoperative Complications / epidemiology
  • Prospective Studies
  • Pulmonary Valve Insufficiency / diagnostic imaging
  • Pulmonary Valve Insufficiency / drug therapy*
  • Pulmonary Valve Insufficiency / epidemiology
  • Ramipril / pharmacology
  • Ramipril / therapeutic use*
  • Single-Blind Method
  • Tetralogy of Fallot / diagnostic imaging
  • Tetralogy of Fallot / drug therapy*
  • Tetralogy of Fallot / surgery
  • Ventricular Dysfunction, Left / diagnostic imaging
  • Ventricular Dysfunction, Left / epidemiology
  • Ventricular Dysfunction, Left / prevention & control
  • Ventricular Function, Left / drug effects*
  • Ventricular Function, Left / physiology
  • Young Adult

Substances

  • Angiotensin-Converting Enzyme Inhibitors
  • Ramipril