De novo implantation vs. upgrade cardiac resynchronization therapy: a systematic review and meta-analysis

Patients with conventional pacemakers or implanted defibrillators are often considered for cardiac resynchronization therapy (CRT). Our aim was to summarize the available evidences regarding the clinical benefits of upgrade procedures. A systematic literature search was performed from studies published between 2006 and 2017 in order to compare the outcome of CRT upgrade vs. de novo implantations. Outcome data on all-cause mortality, heart failure events, New York Heart Association (NYHA) Class, QRS narrowing and echocardiographic parameters were analysed. A total of 16 reports were analysed comprising 489,568 CRT recipients, of whom 468,205 patients underwent de novo and 21,363 upgrade procedures. All-cause mortality was similar after CRT upgrade compared to de novo implantations (RR 1.19, 95% CI 0.88-1.60, p = 0.27). The risk of heart failure was also similar in both groups (RR 0.96, 95% CI 0.70-1.32, p = 0.81). There was no significant difference in clinical response after CRT upgrade compared to de novo implantations in terms of improvement in left ventricular ejection fraction (DeltaEF de novo - 6.85% vs. upgrade - 9.35%; p = 0.235), NYHA class (DeltaNYHA de novo - 0.74 vs. upgrade - 0.70; p = 0.737) and QRS narrowing (DeltaQRS de novo - 9.6 ms vs. upgrade - 29.5 ms; p = 0.485). Our systematic review and meta-analysis of currently available studies reports that CRT upgrade is associated with similar risk for all-cause mortality compared to de novo resynchronization therapy. Benefits on reverse remodelling and functional capacity improved similarly in both groups suggesting that CRT upgrade may be safely and effectively offered in routine practice. CLINICAL TRIAL REGISTRATION: Prospero Database-CRD42016043747

Effects of alirocumab on types of myocardial infarction: insights from the ODYSSEY OUTCOMES trial

Aims  The third Universal Definition of Myocardial Infarction (MI) Task Force classified MIs into five types: Type 1, spontaneous; Type 2, related to oxygen supply/demand imbalance; Type 3, fatal without ascertainment of cardiac biomarkers; Type 4, related to percutaneous coronary intervention; and Type 5, related to coronary artery bypass surgery. Low-density lipoprotein cholesterol (LDL-C) reduction with statins and proprotein convertase subtilisin–kexin Type 9 (PCSK9) inhibitors reduces risk of MI, but less is known about effects on types of MI. ODYSSEY OUTCOMES compared the PCSK9 inhibitor alirocumab with placebo in 18 924 patients with recent acute coronary syndrome (ACS) and elevated LDL-C (≥1.8 mmol/L) despite intensive statin therapy. In a pre-specified analysis, we assessed the effects of alirocumab on types of MI. Methods and results  Median follow-up was 2.8 years. Myocardial infarction types were prospectively adjudicated and classified. Of 1860 total MIs, 1223 (65.8%) were adjudicated as Type 1, 386 (20.8%) as Type 2, and 244 (13.1%) as Type 4. Few events were Type 3 (n = 2) or Type 5 (n = 5). Alirocumab reduced first MIs [hazard ratio (HR) 0.85, 95% confidence interval (CI) 0.77–0.95; P = 0.003], with reductions in both Type 1 (HR 0.87, 95% CI 0.77–0.99; P = 0.032) and Type 2 (0.77, 0.61–0.97; P = 0.025), but not Type 4 MI. Conclusion  After ACS, alirocumab added to intensive statin therapy favourably impacted on Type 1 and 2 MIs. The data indicate for the first time that a lipid-lowering therapy can attenuate the risk of Type 2 MI. Low-density lipoprotein cholesterol reduction below levels achievable with statins is an effective preventive strategy for both MI types.For complete list of authors see http://dx.doi.org/10.1093/eurheartj/ehz299</p

Kidney retransplantation following graft loss to polyoma virus-associated nephropathy : an effective treatment option in simultaneous pancreas and kidney transplant recipients

Polyomavirus-associated nephropathy (PVAN) has emerged as an important cause of graft loss following kidney transplantation. Experience with kidney retransplantation (reKT) in PVAN is very limited, especially in the setting of uninterrupted immunosuppression protecting the still functioning pancreatic graft after simultaneous pancreas/kidney transplantation (SPK). We present a review of five cases of reKT in four SPK recipients with Type 1 diabetes mellitus from a single centre (a second reKT was performed in one patient following first reKT failure due PVAN recurrence). Pre-emptive nephrectomy of the failed graft was performed in three of the cases and all kidney grafts for reKT were harvested from cadaveric donors. All patients are dialysis- and insulin-independent at 30 (9-55), median (range), months following last reKT with maintenance immunosuppression consisting of tacrolimus/sirolimus in three and cyclosporine A/mycophenolate mofetil in one patient. In conclusion, reKT represents an effective treatment option in SPK patients with kidney failure on account of PVAN. Use of interventions designed to reduce active viral replication, including pre-emptive nephrectomy of the failed graft, should be considered before reKT