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Purpose of ReviewThiazolidinediones (TZDs) are the only pharmacologic agents that specifically treat insulin resistance. The beneficial effects of TZDs on the cardiovascular risk factors associated with insulin resistance have been well documented. TZD use has been limited because of concern about safety issues and side effects.Recent FindingsRecent studies indicate that cardiovascular toxicity with rosiglitazone and increase in bladder cancer with pioglitazone are no longer significant issues. There are new data which show that pioglitazone treatment reduces myocardial infarctions and ischemic strokes. New data concerning TZD-mediated edema, congestive heart failure, and bone fractures improves the clinician’s ability to select patients that will have minimal significant side effects.SummaryThiazolidinediones are now generic and less costly than pharmaceutical company–promoted therapies. Better understanding of the side effects coupled with clear benefits on the components of the insulin resistance syndrome should promote TZD use in treating patients with type 2 diabetes.

Background To determine whether glucagon-like peptide 1 receptor agonists (GLP-1RAs) have cardiovascular and renal protective effects in patients with advanced diabetic kidney disease (DKD) with an estimated glomerular filtration rate (eGFR) < 30 mL/min per 1.73 m 2 . Methods In this cohort study, patients with type 2 diabetes mellitus and eGFR < 30 mL/min per 1.73 m 2 with a first prescription for GLP-1RAs or dipeptidyl peptidase 4 inhibitors (DPP-4is) from 2012 to 2021 (n = 125,392) were enrolled. A Cox proportional hazard model was used to assess the cardiorenal protective effects between the GLP-1RA and DDP-4i groups. Results A total of 8922 participants [mean (SD) age 68.4 (11.5) years; 4516 (50.6%) males; GLP-1RAs, n = 759; DPP-4is, n = 8163] were eligible for this study. During a mean follow-up of 2.1 years, 78 (13%) and 204 (13.8%) patients developed composite cardiovascular events in the GLP-1RA and DPP-4i groups, respectively [hazard ratio (HR) 0.88, 95% confidence interval CI 0.68–1.13]. Composite kidney events were reported in 134 (38.2%) and 393 (44.2%) patients in the GLP-1RA and DPP-4i groups, respectively (subdistribution HR 0.72, 95% CI 0.56–0.93). Conclusions GLP-1RAs had a neutral effect on the composite cardiovascular outcomes but reduced composite kidney events in the patients with advanced DKD compared with DPP-4is.

The impact of coronavirus disease, 2019 (COVID-19), has been profound. Though COVID-19 primarily affects the respiratory system, it has also been associated with a wide range of cardiovascular (CV) manifestations portending extremely poor prognosis. The principal hypothesis for CV involvement is through direct myocardial infection and systemic inflammation. We conducted a systematic review of the current literature to provide a foundation for understanding the CV manifestations and outcomes of COVID-19. PubMed and EMBASE databases were electronically searched from the inception of the databases through 27 April 2020. A second literature review was conducted to include major trials and guidelines that were published after the initial search but before submission. The inclusion criteria for studies to be eligible were case reports, case series, and observation studies reporting CV outcomes among patients with COVID-19 infection. This review of the current COVID-19 disease and CV outcomes literature revealed a myriad of CV manifestations with potential avenues for treatment and prevention. Future studies are required to understand on a more mechanistic level the effect of COVID-19 on the myocardium and thus provide avenues to improve mortality and morbidity.

BackgroundCoronary computed tomography angiography (CCTA) enables improved diagnosis of subclinical, coronary artery disease (CAD). This retrospective cohort study investigated the association between different treatment modalities guided by CCTA and the prevention of major adverse cardiovascular events (MACEs) in patients with stable CAD.MethodsFrom 2005 to 2013, a total of 9338 patients, including both asymptomatic individuals with risk factors and symptomatic patients with suspected CAD, who underwent CCTA were analyzed. The patients were categorized into one of three groups based on results of CCTA: obstructive CAD (≥ 50% stenosis in at least one vessel), non-obstructive CAD (1–49% stenosis in at least one vessel), and no observed CAD (0% stenosis). They were subsequently followed up to assess the treatment they received and the occurrence of MACEs (cardiovascular death, non-fatal myocardial infarction, non-fatal stroke, or late revascularization).ResultsDuring an average follow-up period of 9.9 ± 2.4 years, patients with obstructive CAD had the highest incidence of MACEs (19.8%), followed by those with non-obstructive CAD and no coronary artery stenosis (10.3 and 5.5%, respectively). After adjusting for confounding variables, it was found that patients treated with statins alone were the least likely to develop MACEs in all three groups, compared to those receiving no treatment, with hazard ratios (95% CI) of 0.43 (0.32, 0.58), 0.47 (0.34, 0.64), and 0.46 (0.31, 0.69), respectively. In patients with obstructive CAD, treatment with a combination of statin and aspirin, or early revascularization was associated with a lower likelihood of experiencing MACEs compared to no treatment with hazard ratios of 0.43 (0.33, 0.58) and 0.64 (0.43, 0.97), respectively.ConclusionCCTA offers useful guidance for the treatment of patients with stable CAD and shows potential for prevention of CV events. However, the full validation of a given strategy utilizing CCTA will require a prospective longitudinal study, utilizing a randomized clinical trial design.

Background: Left atrial volume indexed to body surface area (LAVi) is the recommended method for LA size quantification. Assessing LAVi in Indian patients undergoing coronary interventions for acute coronary syndrome (STEMI, NSTEMI, and UA) is clinically relevant. Methods and Results: Amongst 190 patients (66.4 yrs, 68.4% males), 29.5%, 40.5%, and 30% respectively had STEMI, NSTEMI and UA. Mean LAVi was 32.29 ± 12.06 ml/m2 and 111 (58.4%) had LAVi ≥32 while 79 (41.6%) had LAVi <32. Patients were divided into 2 groups (group 1 LAVi >32 and group 2 LAVi <32). Group 1 patients had higher prevalence of TVD [n = 49 vs n = 5, p = <0.001] and higher mean Syntax score (24.47 vs 14.64, p = <0.001). Despite similar LVEF, those with higher LAVi had had higher incidence of mild MR (50.4 vs 27.8, P = 0.0002) and moderate/severe MR was present only in Group 1 patients (27.9% and 5.4%). Grade I, II, and III diastolic dysfunction was present in 71.2, 17.1, and 9.9% patients in Group 1 vs 45.6%, 0%, and 0% in group 2. Diastolic parameters like septal E/e' and lateral E/e'ratio were also higher in Group 1. Major adverse cardiovascular events (MACE) at 30 days was significantly higher in group 1 (20.7 vs 6.3%, P = 0.006). On multivariate analysis, triple vessel disease and LAVi were the only predictors of MACE while LVEF was not. ROC curve analysis for LAVi demonstrated that a cut-off 33.35 ml/m2, predicted 30 day MACE with Area under curve (AUC) 0.775 (95% CI 0.700-0.850); sensitivity and specificity of 86.7% and 61.4%. Inter-quartile analysis of LAVi (<26.3, 26.3-33.35, 33.36-36.3, and >36.3 ml/m2) demonstrated that 30 day MACE increased across quartiles (4.16%, 4.25%, 22.44%, and 28.26%, respectively, P < 0.001). Conclusion: Amongst patients with ACS undergoing revascularization, those with higher LAVi had more severe CAD, diastolic dysfunction and higher 30 day MACE. LAVi provides superior prognostic information as compared to conventional LV systolic and diastolic parameters in patients with ACS and should be incorporated in routine echocardiographic analysis. More studies with larger numbers and longer follow up are required to further elucidate on this.

Background: TAVR is a safe alternative to surgical aortic valve replacement (SAVR); however, sex-related differences are still debated. This research aimed to examine gender differences in a real-world transcatheter aortic valve replacement (TAVR) cohort. Methods: All-comer aortic stenosis (AS) patients undergoing TAVR with a Medtronic valve across 19 Italian sites were prospectively included in the Italian Clinical Service Project (NCT01007474) between 2007 and 2019. The primary endpoint was 1-year mortality. We also investigated 3-year mortality, and ischemic and hemorrhagic endpoints, and we performed a propensity score matching to assemble patients with similar baseline characteristics. Results: Out of 3821 patients, 2149 (56.2%) women were enrolled. Compared with men, women were older (83 ± 6 vs. 81 ± 6 years, p < 0.001), more likely to present severe renal impairment (GFR ≤ 30 mL/min, 26.3% vs. 16.3%, p < 0.001) but had less previous cardiovascular events (all p < 0.001), with a higher mean Society of Thoracic Surgeons (STS) score (7.8% ± 7.1% vs. 7.2 ± 7.5, p < 0.001) and a greater mean aortic gradient (52.4 ± 15.3 vs. 47.3 ± 12.8 mmHg, p < 0.001). Transfemoral TAVR was performed more frequently in women (87.2% vs. 82.1%, p < 0.001), with a higher rate of major vascular complications and life-threatening bleeding (3.9% vs. 2.4%, p = 0.012 and 2.5% vs. 1.4%, p = 0.024). One-year mortality differed between female and male (11.5% vs. 15.0%, p = 0.002), and this difference persisted after adjustment for significant confounding variables (Adj.HR1yr 1.47, 95%IC 1.18–1.82, p < 0.001). Three-year mortality was also significantly lower in women compared with men (19.8% vs. 24.9%, p < 0.001) even after adjustment for age, STS score, eGFR, diabetes and severe COPD (Adj.HR3yr 1.42, 95%IC 1.21–1.68, p < 0.001). These results were confirmed in 689 pairs after propensity score matching. Conclusion: Despite higher rates of peri-procedural complications, women presented better survival than men. This better adaptive response to TAVR may be driven by sex-specific factors.

Background and Objectives: Dual antiplatelet therapy (DAPT) with aspirin and a P2Y12 inhibitor is standard care for acute coronary syndrome (ACS). Although ticagrelor showed superiority over clopidogrel in pivotal trials, patients with advanced chronic kidney disease (CKD) or on dialysis were underrepresented and results in Asian populations have been inconsistent. Materials and Methods: We conducted a retrospective cohort study using the Taiwan Society of Cardiology Acute Coronary Syndrome-Diabetes Mellitus (TSOC ACS-DM) registry between 1 October 2013, and 30 September 2016. Eligible patients had type 2 diabetes mellitus and ACS with stage III–V CKD or were on dialysis at index hospitalization and were discharged on aspirin plus either ticagrelor or clopidogrel. The primary endpoint was a composite of cardiovascular (CV) death, CV-related readmission, and repeated revascularization. Cumulative incidence functions were compared using expectation maximization (EM) weighting and propensity score adjustment. Results: After exclusions, 451 patients were analyzed (ticagrelor n = 116; clopidogrel n = 335). Ticagrelor associated with higher myocardial infarction (HR 1.59, 95% CI 1.12–2.28, p = 0.010), CV-related readmission (HR 1.72, 95% CI 1.12–2.65, p = 0.014), repeated revascularization (HR 2.24, 95% CI 1.36–3.68, p = 0.002), and the composite endpoint (HR 1.63, 95% CI 1.06–2.48, p = 0.024) at 2 years. Conclusions: Among real-world Taiwanese patients with type 2 diabetes mellitus, ACS, and CKD, ticagrelor use was linked to increased risks of cardiovascular events compared to clopidogrel. However, these relationships might be affected by potential confounding factors. Randomized controlled trials are necessary to establish the best antiplatelet strategy for this high-risk group.

Background Multiple modifiable risk factors for late complications in patients with diabetic kidney disease (DKD), including hyperglycemia, hypertension and dyslipidemia, increase the risk of a poor outcome. DKD is associated with a very high cardiovascular risk, which requires simultaneous treatment of these risk factors by implementing an intensified multifactorial treatment approach. However, the efficacy of a multifactorial intervention on major fatal/non-fatal cardiovascular events (MACEs) in DKD patients has been poorly investigated. Methods Nephropathy in Diabetes type 2 (NID-2) study is a multicentre, cluster-randomized, open-label clinical trial enrolling 395 DKD patients with albuminuria, diabetic retinopathy (DR) and negative history of CV events in 14 Italian diabetology clinics. Centres were randomly assigned to either Standard-of-Care (SoC) (n = 188) or multifactorial intensive therapy (MT, n = 207) of main cardiovascular risk factors (blood pressure < 130/80 mmHg, glycated haemoglobin < 7%, LDL, HDL and total cholesterol < 100 mg/dL, > 40/50 mg/dL for men/women and < 175 mg/dL, respectively). Primary endpoint was MACEs occurrence by end of follow-up phase. Secondary endpoints included single components of primary endpoint and all-cause death. Results At the end of intervention period (median 3.84 and 3.40 years in MT and SoC group, respectively), targets achievement was significantly higher in MT. During 13.0 years (IQR 12.4–13.3) of follow-up, 262 MACEs were recorded (116 in MT vs. 146 in SoC). The adjusted Cox shared-frailty model demonstrated 53% lower risk of MACEs in MT arm (adjusted HR 0.47, 95%CI 0.30–0.74, P  =  0.001 ). Similarly, all-cause death risk was 47% lower (adjusted HR 0.53, 95%CI 0.29–0.93, P  =  0.027 ). Conclusion MT induces a remarkable benefit on the risk of MACEs and mortality in high-risk DKD patients. Clinical Trial Registration ClinicalTrials.gov number, NCT00535925. https://clinicaltrials.gov/ct2/show/NCT00535925

Purpose of Review Cardiovascular diseases (CVDs) are a leading cause of morbidity and mortality globally with an accelerated increase in CVD‑related death in Africa and other low‑middle‑income countries. This review is aimed at highlighting the burden of coronary artery disease CAD, its peculiarities as well as challenges of management in sub-Saharan Africa. Recent Findings Recent data revealed a shift from high incidence of CVDs associated with poverty and malnutrition (such as rheumatic heart disease) initially, which are now falling, to rising incidence of other non-communicable CVDs (such as hypertension, coronary artery disease (CAD), and heart failure). Africa disproportionately bears the brunt of CVD burden and has one of the highest risks of dying from non-communicable diseases (NCDs) worldwide, which is projected to supersede communicable diseases in the future. Previous studies have shown that CAD was rare among Africans. Those studies conducted in Africa in the 1940s–1960s reported that Black Africans were almost immune to developing CAD and were even thought to have specific genetic make-up protecting them from CAD. However, the continent is now experiencing a steady rise in the prevalence of CAD associated with severe disease burden, compared to other regions of the world. The changes seen have been attributed to the current epidemiological transition with increase in CVD risk factors that are poorly controlled, lack of awareness as well as the poor health facilities to tackle the menace of the disease. The Global Burden of Disease (GBD) estimates have also shown that over the past three decades the highest contribution to CVD burden in Africa is attributed to atherosclerotic diseases, with 71.4, 37.7, and 154% increases in the burden of ischemic heart disease, stroke, and peripheral artery disease respectively. Summary There is a steady increase of CAD prevalence in Africa as a result of increase in CV risk factors. Hypertension, obesity, diabetes, dyslipidemia, and cigarette smoking are the rapidly rising risk factors for CAD on the continent. Africa also faces challenges in diagnosis and management of CAD. There is need for increased public and health personnel awareness on prevention and control of commonly identifiable risk factors, provision of prehospital emergency services, and provision of modern therapeutic facilities for treatment of CAD including reperfusion therapy. These are priority areas where efforts could be intensified in the future with potential to improve the current rate of progress of the disease on the continent.