Changes and Prognostic Impact of Apoptotic and Inflammatory Cytokines in Patients Treated with Cardiac Resynchronization Therapy

Abstract

Objectives: In patients with heart failure, increased apoptosis, inflammation and activation of the transforming growth factor (TGF)-β cytokine system have been documented. The aim of the present study was to establish (i) whether cytokine concentrations decrease in patients who respond to cardiac resynchronization therapy (CRT), and (ii) whether pre-implant values have any prognostic value. Methods: Eighty-one CRT candidates were prospectively studied. The success of CRT was assessed based on clinical and echocardiographic improvement 6 months after implantation. Mortality was assessed 2 years after implantation. Blood samples were drawn before and 6 months after implantation. Serum concentrations of Fas, TNF-related apoptosis-inducing ligand, tumor necrosis factor (TNF)-α, TNF-receptor 1, TGF-β1 and interleukin (IL)-6 were measured using ELISA. Results: At 6 months, 46 (56.8%) patients were classified as responders and 35 (43.2%) as nonresponders. Neither group differed with respect to baseline characteristics. In responders, the concentrations of IL-6, TNF-α and TGF-β1 decreased significantly. In nonresponders, the concentration of TGF-β1 even increased significantly. In multivariate analysis, the concentration of TGF-β1 was a significant predictor of death during follow-up. Conclusions: The response to CRT implantation was associated with a decrease of TGF-β1, IL-6 and TNF-α. Higher pre-implant concentrations of TGF-1β were independently associated with a poor prognosis in CRT patients.

Biomarkers of apoptosis, inflammation, and cardiac extracellular matrix remodelling in the prognosis of heart failure

“…In patients with end-stage HF undergoing cardiac transplant, TGF-b1 bioactivity measured in cardiac tissue was substantially higher in diseased heart tissue compared to tissue samples of healthy donor hearts. In human cardiac resynchronisation therapy (CRT) recipients, the concentration of TGF-b1 decreases in CRT responders, compared to non-responders [53]. It was shown in a small study with 18 patients that the concentration of osteopontin, a matrix glycoprotein required for fibroblast activation in response to TGF-b1 stimulation, decreased in CRT responders while remaining unchanged in non-responders [54].…”

“…However, while BNP is a sensitive marker of short-term cardiac function and overload, indexes from the TGF-b family (as markers of extracellular matrix turnover) might provide additional and better information regarding LV remodelling and long-term prognosis. Not surprisingly, higher pre-implantation values, in CRT recipients, were independently associated with a poor prognosis in CRT patients [53]. Extracellular matrix gene expression was also studied in patients with advanced DCMP being treated with an LV assist device.…”

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.…”

“…С гиперпро-дукцией ИЛ-6 ассоциируется развитие диастолической дисфункции ЛЖ [39]. В исследованиях снижение уровня ИЛ-6, ФНО-α было описано только у респондеров [24,31]. Бóльший процент пациентов с благоприятным отве-том на СРТ во II группе закономерно сопровождается бóльшим снижением уровня цитокинов.…”