Left Ventricular Mass to QRS Voltage Ratio is Associated with Heart Failure Hospitalizations in Cardiac Amyloidosis
Author: Jeremy Slivnick, MD, Additional Authors**
Introduction: In cardiac amyloidosis (CA), myocardial deposition of misfolded amyloid protein leads to markedly increased left ventricular (LV) mass disproportionate to electrocardiographic (EKG) voltage. Compared with EKG voltage alone, the LV mass-voltage relationship appears to have superior diagnostic efficacy in CA as compared with EKG voltage alone. However, the prognostic significance of elevated LV mass-voltage ratio in CA is currently unclear. We sought to assess the relationship between indexed LV mass-voltage ratio using CMR with subsequent heart failure hospitalization (HHF) and mortality in CA.
Methods: Patients with confirmed CA based on expert consensus recommendations who underwent comprehensive cardiovascular magnetic resonance (CMR) and EKG exams were included. LV mass derived using CMR was indexed to body surface area. EKG voltage was assessed using Cornell criteria. HHF was defined as admission for HF with signs of congestion requiring intravenous diuretics. The optimal cutoff value for indexed LV mass-voltage ratio and outcomes of mortality and HF hospitalization was determined using receiver operating characteristic (ROC) curve analysis. Multivariable cox proportional hazards model, adjusting for age, LVEF, New York Heart Association (NYHA) functional class, ECV and BNP, was used to assess the association between LV mass-voltage ratio and the aforementioned outcomes. Further, given that those patients who die cannot experience HF re-hospitalization, competing risk survival analysis using the Fine and Gray proportional subdistribution hazards model as a sensitivity analysis was used to examine the association between LV-mass-voltage ratio and hospitalization.
Results: A total of 85 patients (mean 69±11 years, 22% female) were included, 42 with transthyretin and 43 with light chain CA. At a median of 3.4-year follow-up, 49% of patients experienced HHF and 60% had died. The median time between EKG and CMR was13 (2-35) days. The median indexed LV masses, Cornell voltages, and LV mass-voltage ratios were 200 (162-262), 11 (8-19), and8.8 (4.9-12.9) respectively. In unadjusted analysis, Cornell LV mass-voltage ratio was significantly associated with both HHF (HR 1.05 per 1 unit increase in mass-voltage; 95% CI:1.02-1.09, p =0.001) and mortality (HR 1.05 per 1 unit; 95% CI:1.02-1.07, p =0.001). After adjusting for age, BNP, NYHA class, ECV and LVEF, the Cornell LV mass-voltage ratio was independently associated with HHF (HR, 1.06 per 1 unit; 95% CI:1.03-1.09,p < 0.001) but not mortality (HR, 1.02 per 1 unit; 95% CI:0.99-1.05, p =0.17). Using ROC curve analysis, the optimal cutoff value for Cornell LV mass-voltage ratio to predict HHF was 6.7 gm/m2/mV. After adjusting for age, NYHA class, BNP, ECV, and LVEF, a Cornell LV mass-voltage ratio >6.7 gm/m2/mV was strongly associated with HHF (HR 2.25, 95% CI: 1.09-4.61; p=0.03) but not mortality.
Discussion: Indexed LV mass-voltage ratio as derived using CMR is an independent predictor of HHF in CA. While late gadolinium enhancement (LGE) and extracellular volume (ECV) are powerful prognostic markers in CA, both require the administration of gadolinium contrast. CMR-derived LV mass-voltage may be a complementary prognostic marker in CA, particularly in those who cannot receive gadolinium contrast.
**Additional Authors:
Jeremy Slivnick, MD, The Ohio State University Wexner Medical Center, Columbus, Ohio
Alexander Wallner, MD, The Ohio State University Wexner Medical Center, Columbus, Ohio
Ajay Vallakati, MD, The Ohio State University Wexner Medical Center, Columbus, Ohio
Vien Truong, MD, The Christ Hospital Network, Cincinnati, Ohio
Wojciech Mazur, MD, The Christ Hospital Network, Cincinnati, Ohio
Mohamed Elamin, MD, ProMedica Toledo Hospital, Toledo, Ohio
Matthew Tong, MD, The Ohio State University Wexner Medical Center, Columbus, Ohio
Subha Raman, MD, Indiana University School of Medicine, Indianapolis, Indiana
Karolina Zareba, MD, The Ohio State University Wexner Medical Center, Columbus, Ohio
