Cardiac dyssynchrony and response to cardiac resynchronisation therapy in heart failure: can genetic predisposition play a role?

N Lahrouchi,C.R Bezzina

doi:10.1007/s12471-015-0766-6

Abstract

Cardiac resynchronisation therapy (CRT) is an accepted treatment for heart failure patients with depressed left ventricular (LV) function and dyssynchrony. However, despite better clinical outcome and improved cardiac function after CRT in the majority of eligible heart failure patients, a large proportion of implanted patients do not seem to benefit clinically from this therapy. In this review we consider whether genetic factors may play a role in modulating response to CRT and summarise the few genetic studies that have investigated the role of genetic variation in candidate genes.

Highlights

Patients with heart failure and decreased function often develop dyssynchronous contraction of the ventricles because of electric activation delay
Artificial electrical stimulation to restore synchronous ventricular activation, referred to as cardiac resynchronisation therapy (CRT), which was developed in the 1990s is an established treatment for heart failure patients with a left ventricular ejection fraction (LVEF) ≤ 35 % and a broad QRS complex
Further support for the possible role of genetic factors stems from clear evidence of heritability of clinically measurable phenotypes that are underpinned by biological processes that likely play a role in mediating dyssynchrony or Cardiac resynchronisation therapy (CRT) response

Summary

Introduction

Patients with heart failure and decreased function often develop dyssynchronous contraction of the ventricles because of electric activation delay. This further decreases systolic function and chamber efficiency and contributes to morbidity and mortality [1]. Artificial electrical stimulation to restore synchronous ventricular activation, referred to as cardiac resynchronisation therapy (CRT), which was developed in the 1990s is an established treatment for heart failure patients with a left ventricular ejection fraction (LVEF) ≤ 35 % and a broad QRS complex

Do genetic factors play a role?

What is the likely genetic architecture of response to CRT?

Candidate gene studies

Findings

Pathways involved in dyssynchrony and response to CRT