Tumor Necrosis Factor-α Predicts Response to Cardiac Resynchronization Therapy in Patients With Chronic Heart Failure

Abstract

Background: Pro-inflammatory cytokines contribute to the pathophysiology of heart failure (HF) and are up-regulated in affected patients. We investigated whether pro-inflammatory cytokines might predict the response to cardiac resynchronization therapy (CRT). Methods and Results:Plasma levels of tumor necrosis factor-α (TNF-α) and interleukin-6 were assessed in 91 patients before CRT. Response to CRT was defined as a decrease ≥15% in left ventricular end-systolic volume (LVESV) at 6 months. Baseline TNF-α did correlate with LVESV reduction (P=0.001) after CRT. The subject group was divided according to tertiles of TNF-α. From the lower to the upper tertile LVESV (-31±28%, -17±17%, -9±22%) and LV end-diastolic volume (-23±25%, -14±16%, -4±18%) were progressively less reduced after CRT (P<0.001). The proportion of responders to CRT was 70%, 42% and 33%, according to the lower, intermediate and upper tertile of TNF-α distribution (P=0.01). Serious cardiac events (cardiac death, HF hospitalization or urgent heart transplantation) occurred in 63% of patients in the upper tertile vs. 32% and 17% in the intermediate and lower tertiles, respectively, during a median follow-up of 47 months (P<0.001). Conclusions:Circulating TNF-α predicts the degree of LV reverse remodeling after CRT and may contribute to the early identification of those patients at higher risk of events after device implantation. (Circ J 2014; 78: 2232 -2239

Biochemical aspects of gender differences in response to cardiac resynchronization therapy

“…Дисбаланс в системе цитокинов может приве-сти к ремоделированию миокарда вследствие активации матриксных металлопротеиназ (MMPs), вызывающих деградацию коллагена и ремоделирование экстрацел-люлярного кардиального матрикса (ЭКМ) [19], а также к развитию фиброза миокарда [20,21]. Известно влияние СРТ на процессы воспаления [22][23][24][25], ремоделирования экстрацеллюлярного кардиального матрикса (ЭКМ) [26][27][28], фиброобразования [29,30]. Однако влияние этих процессов на гендерную специфику ремоделирова-ния миокарда на фоне СРТ не изучено.…”

“…Связь эффективности СРТ с активностью процес-са иммунного воспаления была отмечена рядом авто-ров [23][24][25]. В отличие от наших результатов Boriani G. с соавт.…”

Cellular and Molecular Aspects of Dyssynchrony and Resynchronization

“…CRT responders displayed lower baseline (pre-CRT) plasma levels of cardiotrophin-1, CT-1, which induces a hypertrophic response, and Tumor necrosis Factor alpha, TNF-α, which can trigger apoptosis, compared to non-reponders [101,102] . Using a small discovery cohort, and a validation cohort of 40 patients, circulating levels of miR-30d was a predictor of beneficial remodeling 6 months post-CRT [106].…”

“…CRT responders displayed lower baseline (pre-CRT) plasma levels of cardiotrophin-1, CT-1, which induces a hypertrophic response, and Tumor necrosis Factor alpha, TNF-α, which can trigger apoptosis, compared to non-reponders [101,102]. Endothelial progenitor cells (EPCs) are stem cells that can mature into endothelial cells that contribute to neoangiogenesis.…”

The Immunoregulatory Role of Cytokines in Congestive Heart Failure

“…This cytokine has both pro-and anti-inflammatory activities. However, elevated TNFα and IL-6 levels appears to portend severity of congestive heart failure and has been correlated with plaque instability, predicting a more severe index of an acute coronary syndrome with increased 6 and 12 month mortality, independent of cardiac Troponins [26][27][28][29][30][31][32].…”