by
Timothy C. Wong;
Kayla M. Piehler;
Karolina M. Zareba;
Kathie Lin;
Ashley Phrampus;
Agam Patel;
James C. Moon;
Martin Ugander;
Uma Valeti;
Jonathan E. Holtz;
Bo Fu;
Chung-Chou H. Chang;
Michael Mathier;
Peter Kellman;
Javed Butler;
Mihai Gheorghiade;
Erik B. Schelbert
BACKGROUND: Hospitalization for heart failure (HHF) is among the most important problems confronting medicine. Late gadolinium enhancement (LGE) cardiovascular magnetic resonance (CMR) robustly identifies intrinsic myocardial damage. LGE may indicate inherent vulnerability to HHF, regardless of etiology, across the spectrum of heart failure stage or left ventricular ejection fraction (LVEF). METHODS AND RESULTS: We enrolled 1068 consecutive patients referred for CMR where 448 (42%) exhibited LGE. After a median of 1.4 years (Q1 to Q3: 0.9 to 2.0 years), 57 HHF events occurred, 15 deaths followed HHF, and 43 deaths occurred without antecedent HHF (58 total deaths). Using multivariable Cox regression adjusting for LVEF, heart failure stage, and other covariates, LGE was associated with first HHF after CMR (HR: 2.70, 95% CI: 1.32 to 5.50), death (HR: 2.13, 95% CI: 1.08 to 4.21), or either death or HHF (HR: 2.52, 95% CI: 1.49 to 4.25). Quantifying LGE extent yielded similar results; more LGE equated higher risks. LGE improved model discrimination (IDI: 0.016, 95% CI: 0.005 to 0.028, P=0.002) and reclassification of individuals at risk (continuous NRI: 0.40, 95% CI: 0.05 to 0.70, P=0.024). Adjustment for competing risks of death that shares common risk factors with HHF strengthened the LGE and HHF association (HR: 4.85, 95% CI: 1.40 to 16.9). CONCLUSIONS: The presence and extent of LGE is associated with vulnerability for HHF, including higher risks of HHF across the spectrum of heart failure stage and LVEF. Even when LVEF is severely decreased, those without LGE appear to fare reasonably well. LGE may enhance risk stratification for HHF and may enhance both clinical and research efforts to reduce HHF through targeted treatment.
by
Shashi Bhushan;
Kazuhisa Kondo;
David Polhemus;
Hiroyuki Otsuka;
Chad Nicholson;
Ya-Xiong Tao;
Hui Huang;
Vasiliki Georgiopoulou;
Toyoaki Murohara;
John Calvert;
Javed Butler;
David J. Lefer
Background-Tumor necrosis factor (TNF) levels are associated with risk for heart failure (HF). The soluble TNF type 1 (sTNF-R1) and type 2 (sTNF-R2) receptors are elevated in patients with manifest HF, but whether they are associated with risk for incident HF is unclear. Methods and Results-Using Cox proportional hazard models, we examined the association between baseline levels of sTNF-R1 and sTNF-R2 with incident HF risk among 1285 participants of the Health, Aging, and Body Composition Study (age, 74.0±2.9 years; 51.4% women; 41.1% black). At baseline, median (interquartile range) of TNF, sTNF-R1, and sTNF-R2 levels was 3.14 (2.42-4.06), 1.46 (1.25-1.76), and 3.43 (2.95-4.02) ng/mL, respectively. During a median follow-up of 11.4 (6.9-11.7) years, 233 (18.1%) participants developed HF. In models controlling for other HF risk factors, TNF (hazard ratio [HR], 1.28; 95% confidence interval [CI], 1.02-1.61 per log2 increase) and sTNF-R1 (HR, 1.68; 95% CI, 1.15-2.46 per log2 increase), but not sTNF-R2 (HR, 1.15; 95% CI, 0.80-1.63 per log2 increase), were associated with a higher risk for HF. These associations were consistent across whites and blacks (TNF, sTNF-R1, sTNF-R2; interaction P=0.531, 0.091, and 0.795, respectively) and in both sexes (TNF, sTNF-R1, sTNF-R2; interaction P=0.491, 0.672, and 0.999, respectively). TNF-R1 was associated with a higher risk for HF with preserved versus reduced ejection fraction (HR, 1.81; 95% CI, 1.03-3.18; P=0.038 for preserved versus HR, 0.90; 95% CI, 0.56-1.44; P=0.667 for reduced ejection fraction; interaction P=0.05). Conclusions-In older adults, elevated levels of sTNF-R1 are associated with increased risk for incident HF. However, addition of TNF-R1 to the previously validated Health ABC HF risk model did not demonstrate material improvement in net discrimination or reclassification.