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Multipolar pacing by cardiac resynchronization therapy with a defibrillators treatment in type 2 diabetes mellitus failing heart patients: impact on responders rate, and clinical outcomes.

ABSTRACT: BACKGROUND:Type 2 diabetes mellitus (T2DM) is a multi factorial disease, affecting clinical outcomes in failing heart patients treated by cardiac resynchronization therapy with a defibrillator (CRT-d). METHODS:One hundred and ninety-five T2DM patients received a CRT-d treatment. Randomly the study population received a CRT-d via multipolar left ventricle (LV) lead pacing (n 99, multipolar group), vs a CRT-d via bipolar LV pacing (n 96, bipolar group). These patients were followed by clinical, and instrumental assessment, and telemetric device control at follow up. In this study we evaluated, in a population of failing heart T2DM patients, cardiac deaths, all cause deaths, arrhythmic events, CRT-d responders rate, hospitalizations for HF worsening, phrenic nerve stimulation (PNS), and LV catheter dislodgment events (and re-intervention for LV catheter re-positioning), comparing multipolar CRT-d vs bipolar CRT-d group of patients at follow up. RESULTS:At follow up there was a statistical significant difference about atrial arrhythmic events [7 (7%) vs 16 (16.7%), p value 0.019], hospitalizations for HF worsening [15 (15.2% vs 24 (25%), p value 0.046], LV catheter dislodgments [1 (1%) vs 9 (9.4%), p value 0018], PNS [5 (5%) vs 18 (18.7%), p value 0.007], and LV re-positioning [1 (1%) vs 9 (9.4%), p value 0.018], comparing multipolar CRT-d vs bipolar CRT-d group of patients. Multipolar pacing was an independent predictor of all these events. CONCLUSIONS:CRT-d pacing via multipolar LV lead vs bipolar LV lead may reduce arrhythmic burden, hospitalization rate, PNS, LV catheters dislodgments, and re-interventions in T2DM failing heart patients. Clinical trial number NCT03095196.

SUBMITTER: Sardu C

PROVIDER: S-EPMC5466779 | biostudies-literature | 2017 Jun

REPOSITORIES: biostudies-literature

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Multipolar pacing by cardiac resynchronization therapy with a defibrillators treatment in type 2 diabetes mellitus failing heart patients: impact on responders rate, and clinical outcomes.

Sardu Celestino C Barbieri Michelangela M Santamaria Matteo M Giordano Valerio V Sacra Cosimo C Paolisso Pasquale P Spirito Alessandro A Marfella Raffaele R Paolisso Giuseppe G Rizzo Maria Rosaria MR

Cardiovascular diabetology 20170609 1

<h4>Background</h4>Type 2 diabetes mellitus (T2DM) is a multi factorial disease, affecting clinical outcomes in failing heart patients treated by cardiac resynchronization therapy with a defibrillator (CRT-d).<h4>Methods</h4>One hundred and ninety-five T2DM patients received a CRT-d treatment. Randomly the study population received a CRT-d via multipolar left ventricle (LV) lead pacing (n 99, multipolar group), vs a CRT-d via bipolar LV pacing (n 96, bipolar group). These patients were followed ...[more]

PMID: 28599667

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Project description:OBJECTIVES:To evaluate clinical outcomes in patients with diabetes, treated by cardiac resynchronization therapy with a defibrillator (CRT-d), and glucagon-like peptide 1 receptor agonists (GLP-1 RA) in addition to conventional hypoglycemic therapy vs. CRTd patients under conventional hypoglycemic drugs. BACKGROUND:Patients with diabetes treated by CRTd experienced an amelioration of functional New York Association Heart class, reduction of hospital admissions, and mortality, in a percentage about 60%. However, about 40% of CRTd patients with diabetes experience a worse prognosis. MATERIALS AND METHODS:We investigated the 12-months prognosis of CRTd patients with diabetes, previously treated with hypoglycemic drugs therapy (n 271) vs. a matched cohort of CRTd patients with diabetes treated with GLP-1 RA in addition to conventional hypoglycemic therapy (n 288). RESULTS:At follow up CRTd patients with diabetes treated by GLP-1 RA therapy vs. CRTd patients with diabetes that did not receive GLP-1 RA therapy, experienced a significant reduction of NYHA class (p value?<?0.05), associated to higher values of 6 min walking test (p value?<?0.05), and higher rate of CRTd responders (p value?<?0.05). GLP-1 RA patients vs. controls at follow up end experienced lower AF events (p value?<?0.05), lower VT events (p value?<?0.05), lower rate of hospitalization for heart failure worsening (p value?<?0.05), and higher rate of CRTd responders (p value?<?0.05). To date, GLP-1 RA therapy may predict a reduction of AF events (HR 0.603, CI [0.411-0.884]), VT events (HR 0.964, CI [0.963-0.992]), and hospitalization for heart failure worsening (HR 0.119, CI [0.028-0.508]), and a higher CRT responders rate (HR 3.707, CI [1.226-14.570]). CONCLUSIONS:GLP-1 RA drugs in addition to conventional hypoglycemic therapy may significantly reduce systemic inflammation and circulating BNP levels in CRTd patients with diabetes, leading to a significant improvement of LVEF and of the 6 min walking test, and to a reduction of the arrhythmic burden. Consequently, GLP-1 RA drugs in addition to conventional hypoglycemic therapy may reduce hospital admissions for heart failure worsening, by increasing CRTd responders rate. Trial registration NCT03282136. Registered 9 December 2017 "retrospectively registered".

Project description:RationaleCardiac resynchronization therapy (CRT) is the only heart failure (HF) therapy documented to improve left ventricular function and reduce mortality. The underlying mechanisms are incompletely understood. Although β-adrenergic signaling has been studied extensively, the effect of CRT on cholinergic signaling is unexplored.ObjectiveWe hypothesized that remodeling of cholinergic signaling plays an important role in the aberrant calcium signaling and depressed contractile and β-adrenergic responsiveness in dyssynchronous HF that are restored by CRT.Methods and resultsCanine tachypaced dyssynchronous HF and CRT models were generated to interrogate responses specific to dyssynchronous versus resynchronized ventricular contraction during hemodynamic decompensation. Echocardiographic, electrocardiographic, and invasive hemodynamic data were collected from normal controls, dyssynchronous HF and CRT models. Left ventricular tissue was used for biochemical analyses and functional measurements (calcium transient, sarcomere shortening) from isolated myocytes (n=42-104 myocytes per model; 6-9 hearts per model). Human left ventricular myocardium was obtained for biochemical analyses from explanted failing (n=18) and nonfailing (n=7) hearts. The M2 subtype of muscarinic acetylcholine receptors was upregulated in human and canine HF compared with nonfailing controls. CRT attenuated the increased M2 subtype of muscarinic acetylcholine receptor expression and Gαi coupling and enhanced M3 subtype of muscarinic acetylcholine receptor expression in association with enhanced calcium cycling, sarcomere shortening, and β-adrenergic responsiveness. Despite model-dependent remodeling, cholinergic stimulation completely abolished isoproterenol-induced triggered activity in both dyssynchronous HF and CRT myocytes.ConclusionsRemodeling of cholinergic signaling is a critical pathological component of human and canine HF. Differential remodeling of cholinergic signaling represents a novel mechanism for enhancing sympathovagal balance with CRT and may identify new targets for treatment of systolic HF.

Dataset Information

Multipolar pacing by cardiac resynchronization therapy with a defibrillators treatment in type 2 diabetes mellitus failing heart patients: impact on responders rate, and clinical outcomes.

Publications

Multipolar pacing by cardiac resynchronization therapy with a defibrillators treatment in type 2 diabetes mellitus failing heart patients: impact on responders rate, and clinical outcomes.

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