Alexandros Briasoulis

The influence of anti-hyperglycemic drug therapy on cardiovascular and heart failure outcomes in patients with type 2 diabetes mellitus

Patients with type 2 diabetes mellitus (DM) are at a substantially increased risk of heart failure (HF) and HF mortality. Despite the lack of evidence that tight glycemic control reduces the incidence of cardiovascular (CV) events, a growing body of evidence suggests that the choice of glucose-lowering agents may influence outcomes including HF. Thiazolidinediones are associated with a significant risk of HF. For metformin, sulphonylureas and insulin, little data is available to indicate the impact on HF. The glucagon-like peptide-1 (GLP-1) agonists, liraglutide and semaglutide, have been shown to reduce major CV events, but did not affect rates of hospitalization for HF. Clinical trials have demonstrated diverse effects of Dipeptidyl peptidase-4 (DPP-4) inhibitors on HF; saxagliptin showed an increased risk of HF admissions, alogliptin was associated with higher rates of new HF admissions, while sitagliptin had a neutral effect. The sodium-glucose cotransporter 2 (SGLT2) inhibitors, empagliflozin and canagliflozin, have been recently shown to reduce the incidence of HF and cardiovascular mortality in patients with and without a history of HF. This review will summarize key findings of the impact of glucose-lowering agents on CV safety and HF-associated outcomes, present available data on the underlying mechanisms for the benefits of the SGLT2 inhibitors on HF, and discuss strategies to improve outcomes in patients with DM and high CV risk.

Induction immunosuppressive therapy in cardiac transplantation: a systematic review and meta-analysis

Approximately 50% of heart transplant programs currently employ a strategy of induction therapy (IT) with either interleukin-2 receptor antagonists (IL2RA) or polyclonal anti-thymocyte antibodies (ATG) during the early postoperative period. However, the overall utility of such therapy is uncertain and data comparing induction protocols are limited. The authors searched PubMed, the Cochrane Central Register of Controlled Trials, and ClinicalTrials.gov through January 2018 for randomized controlled trials (RCTs) or observational controlled studies of IT vs no IT and IL2RA vs ATG. Inverse variance fixed effects models with odds ratio (OR) as the effect measure were used for primary analyses. Main outcomes include moderate and severe rejection, all-cause mortality, infection, and cancer. The authors’ search retrieved 2449 studies, of which 11 met criteria for inclusion (8 RCTs and 3 observational case-control studies). Quality of evidence for RCTs was moderate to high. Overall, patients receiving IT had similar risk of moderate-to-severe rejection, all-cause death, infection, and cancer with patients who did not receive IT. The use of IL2RA was associated with significantly higher risk of moderate-to-severe rejection than ATG (OR 3.4; 95% CI 1.4 to 8.1), but similar risk of death, infections, and cancer. The use of IT was not associated with any benefits or harms compared with no IT. Moderate-to-severe rejection may be reduced by ATG compared with IL2RA.

Angiogenesis in peripheral arterial disease

HIGHLIGHTSThe goal of angiogenesis in PAD is formation of collateral circulation.It may be particularly useful for patients no deemed candidates for revascularization.Angiogenic growth factors dont improve ulcer healing and amputation rates.Intra‐arterial or intra‐muscular injection of stem cells did not improve outcomes. &NA; Peripheral arterial disease (PAD) refers to narrowing of the peripheral arteries and atherosclerosis is the most important cause. In patients with PAD, revascularization is the preferred therapeutic strategy; nonetheless several patients are not deemed candidates for it due to advanced disease or several comorbidities. The main target of therapeutic angiogenesis is to promote development of new arterial vessels and improve perfusion of ischemic tissue. Angiogenic growth factors such as vascular endothelial growth factor (VEGF), fibroblast growth factor (FGF), hepatocyte growth factor (HGF), administered intramuscularly or intra‐arterially, have been shown to promote angiogenesis and development of collateral vasculature in preclinical studies. However, clinical studies failed to confirm their efficacy in ulcer healing and prevention of amputation, among patients with claudication or critical limb ischemia (CLI). Autologous progenitor cell therapy with bone marrow or adipose‐derived progenitor cells administered intra‐arterially or intra‐muscularly, was shown to improve claudication symptoms and ankle–brachial index in small studies. However, subsequent randomized controlled studies did not demonstrate any beneficial effects of stem cell therapy on amputation rates and survival. Although, therapeutic angiogenesis remains an area of interest in PAD with several ongoing studies of investigational therapies, so far the use of these strategies in clinical practice has not been successful.

Trends in Utilization, Mortality, Major Complications, and Cost After Left Ventricular Assist Device Implantation in the United States (2009 to 2014)

The utilization of contemporary continuous-flow left ventricular assist device (CF-LVADs) has increased, accounting for >90% of implants from 2009 to 2014. The present study aimed to identify the annual national estimates in utilization, in-hospital mortality, and major complications with CF-LVAD using data from the National Inpatient Sample, the largest all-payer inpatient data set in the United States, and the US Census Bureau, for the years 2009 to 2014. Participants included all adult patients who received CF-LVADs from 2009 to 2014. End points included in-hospital mortality, in-hospital complications, length of stay, cost, and disposition at the time of discharge. A total of 3,572 (weightedu2009=u200917,552) patients with left ventricular assist device (LVAD) implants were analyzed. LVAD implants increased significantly, with average annual change (%) of +12.6% (pu2009<0.001). Rates of in-hospital mortality decreased by average annual rate of -5.3% (pu2009=u20090.02). The rates of major complications including ischemic stroke, major bleeding, and cardiac tamponade did not change significantly over the study period. However, we found a significant decrease in postoperative infections (pu2009=u20090.001) and respiratory complications (pu2009=u20090.03). Although the length of stay and disposition patterns did not change over time, we found a significant decrease in cost of hospitalization (pu2009=u20090.001). In conclusion, from 2009 to 2014, utilization of LVADs increased with concomitant decrease in in-hospital mortality rates, without significant changes in major complications.

Hemodynamic Assessment of Patients With and Without Heart Failure Symptoms Supported by a Continuous-Flow Left Ventricular Assist Device

Objective: To investigate differences in invasive hemodynamic parameters and outcomes in patients with and without heart failure (HF) symptoms after left ventricular assist device (LVAD) implantation. Patients and Methods: We performed a single‐center retrospective analysis of 51 symptomatic patients and 50 patients with resolved HF symptoms who underwent right‐sided heart catheterization (RHC) after LVAD implantation from March 1, 2007, through June 30, 2016. Patient characteristics and outcomes including all‐cause mortality and right ventricular (RV) failure were compared between groups. Results: Fifty‐one patients had development of HF symptoms after LVAD implantation and underwent RHC a mean ± SD of 243.7±288 days postoperatively. Fifty asymptomatic LVAD recipients underwent routine RHC 278.6±205 days after implantation. Compared with patients who had resolved HF symptoms, symptomatic patients were older, more likely to be male, and more likely to have ischemic cardiomyopathy. Symptomatic patients had higher right atrial pressure (P<.001), mean pulmonary arterial pressure (P<.001), and pulmonary capillary wedge pressure (P<.001). Improvements in right atrial pressure, mean pulmonary arterial pressure, and pulmonary capillary wedge pressure before and after LVAD implantation were less remarkable in symptomatic patients. The frequency of RV dysfunction was significantly higher among symptomatic patients than patients with resolved HF symptoms (P=.001). Symptomatic patients displayed significantly higher risk of all‐cause mortality (hazard ratio, 3.0; 95% CI, 1.3‐6.5; P=.007) and RV failure (hazard ratio, 6.2; 95% CI, 1.3‐29.7; P=.02) independent of other predictors of outcome. Conclusion: Patients with recurrent HF symptoms after LVAD implantation display more profound hemodynamic derangements, greater burden of RV failure, and increased rates of all‐cause mortality compared with LVAD recipients with resolved HF symptoms.

Safety and Efficacy of Novel Oral Anticoagulants Versus Warfarin in Medicare Beneficiaries With Atrial Fibrillation and Valvular Heart Disease

Background We examined a large community‐based sample of patients with atrial fibrillation (AF) and valvular heart disease (VHD) (excluding prosthetic valves) with a goal to compare outcomes among patients with AF, with and without VHD, taking warfarin, dabigatran, and rivaroxaban. Methods and Results We identified Medicare beneficiaries enrolled in Medicare Part D benefit plan from 2011 to 2013 with newly diagnosed AF (18 137 patients with VHD [dabigatran, 1979; rivaroxaban, 2027; warfarin, 14 131] and 85 596 patients without VHD [dabigatran, 13 522; rivaroxaban, 14 257; warfarin, 57 817]). Primary outcomes of all‐cause mortality, ischemic strokes, major bleeding, and myocardial infarction were compared across the 3 anticoagulants using 3‐way propensity‐matched samples. After propensity matching, a total of 5871 patients with VHD and 40 221 patients without VHD and AF were studied. Both dabigatran and rivaroxaban were associated with significantly lower risk of death in patients with VHD with AF (dabigatran versus warfarin: hazard ratio, 0.71; 95% confidence interval, 0.52–0.98; P=0.038; rivaroxaban versus warfarin: hazard ratio, 0.68; 95% confidence interval, 0.49–0.95; P=0.022). Nongastrointestinal bleeding was significantly reduced with dabigatran and rivaroxaban versus warfarin in those with VHD (dabigatran versus warfarin: hazard ratio, 0.17; 95% confidence interval, 0.06–0.49; P=0.001; rivaroxaban versus warfarin: hazard ratio, 0.37; 95% confidence interval, 0.17–0.84; P=0.017). Ischemic stroke and gastrointestinal bleeding rates did not differ between rivaroxaban, dabigatran, and warfarin in patients with VHD. The effects of the 3 anticoagulants on outcomes were comparable in patients with and without VHD and with AF. Conclusions In this cohort of Medicare beneficiaries with VHD (excluding patients with prosthetic valves) and new‐onset AF between 2011 and 2013, novel oral non–vitamin K anticoagulants were safe and effective options for prevention of systemic thromboembolism.

Comparison of Health Related Quality of Life in Transcatheter Versus Surgical Aortic Valve Replacement: A Meta-Analysis

BACKGROUNDnData on the effects of transcatheter aortic valve replacement (TAVR) compared to surgical aortic valve replacement (SAVR) on health-related quality of life (HRQOL) outcomes are limited. To assess the comparative HRQOL outcomes between TAVR and SAVR, we performed a systematic review and meta-analysis.nnnMETHODSnPubMed and EMBASE databases were searched for articles that compared the HRQOL scores, Kansas City Cardiomyopathy Questionnaire (KCCQ), Medical Outcomes Study Short-Form Health Survey 12 or 36 (SF-12/36), or the EuroQoL 5 Dimension score (EQ-5D) at 30days and 1year between TAVR and SAVR. Mean difference (MD) and 95% confidence interval (CI) was calculated with inverse variance statistical method and random-effects model.nnnRESULTSnA total of four studies with 4,125 patients (1268 transfemoral [TF]-TAVR, 1261 Non-TF TAVR [transsubclavian, transapical or transaortic], and 1,596 SAVR) were included in the studies. KCCQ overall summary scores and its subscales, SF-12/36, and EQ-5D were significantly higher in TF-TAVR compared to SAVR but were similar in non-TF TAVR vs. SAVR at 30 days. At 1-year follow-up, TF-TAVR and non-TF TAVR conferred similar HRQOL scores in KCCQ overall summary and subscales scores, SF-12/36, and EQ-5D compared to SAVR.nnnCONCLUSIONSnTransfermoral-TAVR achieved better HRQOL at 30days but similar HRQOL at 1year compared to SAVR. Non-TF TAVR resulted in similar improvements in HRQOL at both 30days and 1year compared with SAVR.

SGLT2 Inhibitors and Mechanisms of Hypertension

Purpose of ReviewWe sought to review currently available data on the safety and efficacy of sodium-glucose cotransporter 2 (SGLT2) inhibitors in type 2 diabetes mellitus patients with hypertension.Recent FindingsInhibition of SGLT2 in the renal proximal tubule results in increased urinary glucose excretion and modest improvements of hemoglobin A1C. Treatment with any of the three currently FDA-approved SGLT2 inhibitors (canagliflozin, dapagliflozin, empagliflozin) results in sustained systolic and diastolic blood pressure reduction, in part via minimal natriuresis and possible reductions in sympathetic tone. Recent randomized clinical trials in high cardiovascular risk patients with type 2 diabetes suggest that the unique effects of SGLT2 inhibitors on blood pressure and body weight may translate into reduced cardiovascular events and slowed kidney disease progression. However, concerns about volume depletion and acute kidney injury have been raised.SummarySGLT2 inhibitors are viable second-line glucose-lowering agents for people with type 2 diabetes with high cardiovascular risk.

Ticagrelor Versus Clopidogrel as Part of Dual or Triple Antithrombotic Therapy: a Systematic Review and Meta-Analysis

PurposeClopidogrel is the standard P2Y12 receptor inhibitor used in patients requiring both antiplatelet therapy and oral anticoagulation (OAC). We investigated the safety and efficacy of ticagrelor as an alternative to clopidogrel in patients on OAC.MethodsA systematic electronic literature search was performed in MEDLINE, EMBASE, and the Cochrane Library for randomised controlled studies that examined the relative safety and efficacy of clopidogrel versus ticagrelor among patients requiring therapy with antiplatelet agents plus OAC.ResultsThree randomised controlled trials were identified with a total of 5659 patients. The risk of clinically significant bleeding was significantly increased among patients on dual or triple antithrombotic therapy who received ticagrelor compared with patients on clopidogrel (OR 1.52, 95% CI 1.12 to 2.06, and OR 1.7, 95% CI 1.24 to 2.33, respectively). Among those on triple therapy, ticagrelor was associated with a significantly higher risk of major adverse cardiovascular events (MACE) compared to clopidogrel (OR 1.88, 95% CI 1.26 to 2.80). Patients who received dual therapy exhibited similar risk of MACE and stroke with ticagrelor versus clopidogrel (OR 1.14, 95% CI 0.83 to 1.56, and OR 0.42, 95% CI 0.10 to 1.74, respectively).ConclusionThe use of ticagrelor as part of dual or triple antithrombotic therapy is associated with significantly higher rates of clinically relevant haemorrhagic complications compared with clopidogrel. Among triple therapy-treated patients, the use of ticagrelor might increase thromboembolic and ischaemic cardiac events.

Regional Variation in Mortality, Major Complications, and Cost After Left Ventricular Assist Device Implantation in the United States (2009 to 2014)

The objective of this analysis was to provide evidence on regional differences in outcomes, cost and disposition among patients who undergo continuous-flow LVAD implantation. Using data from the National Inpatient Sample and US Census Bureau, annual national estimates in utilization, in-hospital mortality, major complications, cost, length of stay (LOS), and disposition were estimated for years 2009 to 2014. Main outcomes and complications were identified using patient safety indicators and International Classification of Diseases-Ninth Revision, Clinical Modification codes. We analyzed a total of 3,572 (weighted = 17,552) patients with LVAD implants among the 4 Census regions of the United States. The patient population in the Southern region was younger with higher percentage of African-Americans. Overall, the comorbidity burden was higher in the Midwest. The risk-adjusted rate of in-hospital mortality did not differ significantly among the geographical regions (p = 0.8). With the exception of cardiac tamponade rates which were higher in the Northeast and West, all other post-operative complications did not differ between regions. LOS was higher in the Northeast (median 32 days) and lower in the South (median 27 days). The cost analysis suggested higher median cost in the West (median