Soundararajan, Deep Chandh2024-06-042024-06-04https://hdl.handle.net/1885/733713058Background: Sudden Cardiac Death (SCD) in patients with nonischemic cardiomyopathy (NICM) contributes to one-third of all-cause mortality. Left ventricular ejection fraction (LVEF) is the only objective risk-stratification tool suggested by guidelines. Large studies have exposed the inadequacies of LVEF. Better way to understand the risk of SCD in NICM is to analyse certain unexplored phenotypes. In addition, defining the substrate of NICM with invasive and noninvasive mapping tools can serve as better tools than only LVEF. Aims: 1. To explore certain phenotypes of NICM, namely heart failure mid-range ejection fraction (HFmrEF) and mixed cardiomyopathy 2. To gain further understanding on the endocardial electroanatomical mapping (EAM) variables and their role in risk stratification 3. To test cardiac MRI strain as a modality in addition to late gadolinium enhancement (LGE) for risk stratification Methods: 1. Systematic review and metanalysis was conducted to compare the long term outcomes of patients with HFmrEF, compared to heart failure reduced ejection fraction (HFrEF) and heart failure preserved ejection fraction (HFpEF). 2. Retrospective analysis of recipients of implantable cardoverter-defibrillator (ICD) was conducted to study a new phenotype of 'mixed' cardiomyopathy, wherein the patients with NICM and concomitant coronary artery disease were compared to ischemic cardiomyopathy (ICM) and NICM. 3. Prospective study was performed in NICM patients with invasive EAM variables and to correlate these variables with ventricular tachycardia (VT). A substudy in these prospectively analysed patients was conducted to study CMR-strain and its ability to predict ventricular arrhythmia substrates. Results: 1. The metanalysis from 18 large-scale studies including 126,239 patients revealed patients with HFmrEF had lower risk of all-cause death and cardiovascular deaths than those with HFrEF. Subgroup analysis showed that studies recruiting >50% of males had higher risk of deaths with HFrEF. When compared with HFpEF, patients with HFmrEF had comparable risk of all-cause death. 2. In 526 ICD recipients with a mean follow-up 8.7 years, there were 42.5% patients with ICM, 26.9% with NICM and 30.6% with 'mixed' cardiomyopathy. In our study, the cohort of mixed cardiomyopathy had elderly population with higher incidence of comorbidities. The prognosis, in terms of device shocks and all-cause mortality, in patients with mixed cardiomyopathy is similar to ischemic and worse than nonischemic cardiomyopathy. 3. The prospective analysis of high density endocardial EAM characteristics of the left ventricle in 43 patients of NICM revealed better correlation for unipolar EGM variables, with baseline LVEF, than bipolar EGM variables. Extent of unipolar low voltage zone (LVZ) and LVEF<35% had significant association with VT. ROC-curve analysis revealed cut-off of extent of >3 segments of unipolar LVZ and >33% area of unipolar LVZ to predict VT with good diagnostic accuracy. 4. 19 consecutive CMRs of patients with EAM were analysed by CMR-feature tracking strain. There was significant correlation between combined percentage circumferential and longitudinal (CS and LS) abnormality with percentage unipolar low voltage zone (LVZ). The concordance rates between CS and LS to localize segments with bipolar/unipolar LVZ was 79% and 95% compared to 63% with LGE. Myocardial strain picked up by CMR-feature tracking has good correlation with unipolar low voltage zones. Conclusion: Our studies give novel insights on the largely unexplored phenotypes of HFmrEF and mixed cardiomyopathy. The prospective analysis has defined novel cut-offs for extent of distribution of endocardial unipolar voltage abnormalities that can correlate with a ventricular arrythmia substrate in the myocardium. The substudy showed that CMR-strain is a novel CMR tool that can be used to predict the ventricular arrhythmia substrate.en-AU202410.25911/C958-T657