Diastolic dysfunction in aortic stenosis results primarily from left ventricular hypertrophy and myocardial fibrosis due to chronically elevated left ventricular systolic pressure. Currently, diastolic dysfunction does not have an explicit clinical role in management of patients with aortic stenosis. Studies have shown that improvement in diastolic dysfunction follows left ventricular remodelling after aortic valve replacement and that it occurs gradually or incompletely. Retrospective studies suggest that advanced grades of diastolic dysfunction at baseline are associated with increased mortality and adverse events even after aortic valve replacement. Recent studies have also associated myocardial fibrosis, a hallmark of diastolic dysfunction, with worse outcomes. In addition, these results were independent of the degree of aortic stenosis or valve replacement. Indirect evidence of the role of diastolic dysfunction in aortic stenosis also comes from paradoxical low-flow, low-gradient aortic stenosis, where disproportionate left ventricular hypertrophy leads to underfilling of the left ventricle, low-flow state and is associated with worse prognosis. Lastly, a limited number of studies suggest that worse diastolic dysfunction at baseline is detrimental in patients who develop aortic regurgitation after transcatheteraortic valve replacement, due to superimposition of volume overload on a stiff left ventricle. Current major limitations in our understanding of the prognostic role of diastolic dysfunction are the lack of universally accepted classification schemes, its dependence on dynamic loading conditions and the lack of larger prospective studies.

High-intensity statins are recommended for patients with peripheral artery disease (PAD). Critical limb ischemia (CLI) is the most advanced presentation of PAD. The benefit of statins in the CLI population is unclear based on the existent studies. Our objective was to perform a systematic review and meta-analysis regarding the efficacy of statin therapy in patients with CLI. PRISMA guidelines were followed. PubMed, EMBASE, and Cochrane CENTRAL databases were reviewed up to April 30, 2019. The primary outcomes included amputation rates and all-cause mortality. Secondary outcomes included primary patency rates, amputation-free survival and major adverse cardiac or cerebrovascular events (MACCE). Risk of bias was assessed with the Robins-I tool for observational studies. A random-effects model meta-analysis was performed. Heterogeneity was assessed with I². Funnel plots and Egger’s test were used to assess publication bias. Nineteen studies including 26,985 patients with CLI were included in this systematic review. Among patients with known data on statin status, 12,292 (49.6%) were on statins versus 12,513 (50.4%) not on statins. Patients treated with statins were 25% less likely to undergo amputation (HR 0.75; 95% CI: 0.59–0.95; I² = 79%) and 38% less likely to have a fatal event (HR 0.62; 95% CI: 0.52–0.75; I² = 41.2%). Statin therapy was also associated with increased overall patency rates and lower incidence of MACCE. There was substantial heterogeneity in the analysis for amputation and amputation-free survival (I² > 70%). In conclusion, statins are associated with decreased risk for amputation, mortality, and MACCE, as well as increased overall patency rates among patients with CLI. Future studies should assess whether other lipid-lowering medications in addition to high-intensity statins can further improve outcomes among patients with CLI. (PROSPERO registration number: CRD42019134160)

Background: The relative benefit of higher statin dosing in patients with peripheral artery disease has not been reported previously. We compared the effectiveness of low‐ or moderate‐intensity ( LMI ) versus high‐intensity ( HI ) statin dose on clinical outcomes in patients with peripheral artery disease. Methods and Results: We reviewed patients with symptomatic peripheral artery disease who underwent peripheral angiography and/or endovascular intervention from 2006 to 2013 who were not taking other lipid‐lowering medications. HI statin use was defined as atorvastatin 40–80 mg or rosuvastatin 20–40 mg. Baseline demographics, procedural data, and outcomes were retrospectively analyzed. Among 909 patients, 629 (69%) were prescribed statins, and 124 (13.6%) were treated with HI statin therapy. Mean low‐density lipoprotein level was similar in patients on LMI versus HI (80±30 versus 87±44 mg/dL, P =0.14). Demographics including age (68±12 versus 67±10 years, P =0.25), smoking history (76% versus 80%, P =0.42), diabetes mellitus (54% versus 48%, P =0.17), and hypertension (88% versus 89%, P =0.78) were similar between groups ( LMI versus HI ). There was a higher prevalence of coronary artery disease (56% versus 75%, P =0.0001) among patients on HI statin (versus LMI ). After propensity weighting, HI statin therapy was associated with improved survival (hazard ratio for mortality: 0.52; 95% confidence interval, 0.33–0.81; P =0.004) and decreased major adverse cardiovascular events (hazard ratio: 0.58; 95% confidence interval 0.37–0.92, P =0.02). Conclusions: In patients with peripheral artery disease who were referred for peripheral angiography or endovascular intervention, HI statin therapy was associated with improved survival and fewer major adverse cardiovascular events compared with LMI statin therapy.

Background: The optimal treatment for advanced heart failure (HF) patients with regards to mortality remains unknown. Heart transplantation (HTx) and left ventricular assist devices (LVAD) used either as a bridge to transplant (BTT) or destination therapy (DT) have been compared in a number of studies, without definite conclusions with regards to mortality benefit. We sought to systematically review the pertinent literature and perform a meta-analysis of all the available studies presenting head-to-head comparisons between HTx and LVAD BTT or LVAD DT for late (>6 months) all-cause mortality. Methods: We performed a systematic search of Medline and Cochrane Central databases in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. We conducted a meta-analysis of late mortality comparing HTx vs. BTT LVAD and HTx vs. DT LVAD using a random effects model. Results: Eight studies were included in our meta-analysis, reporting data on 7,957 patients in total. Although the available studies are of high quality [8 stars in Newcastle-Ottawa Scale (NOS) on average], there is paucity of mortality data. Specifically, seven studies compared HTx with BTT and five studies compared HTx with DT for 1-year mortality. Our pooled estimates showed that there was no difference in late mortality among these strategies. Conclusions: Our meta-analysis highlights the small number and the heterogeneity of available studies referring to the optimal invasive management of advanced HF, and shows that there are no differences between HTx and LVAD for these patients with regards to late mortality.

Although drug-eluting stents (DES) have significantly reduced the incidence and prevalence of coronary in-stent restenosis (ISR), ISR still occurs in approximately 10% of patients in real-world practice. Areas covered: The development of newer generations of DES, drug-coated balloons (DCB) and increased use of intracoronary imaging have improved our treatment options for and pathophysiologic understanding of ISR. These technological advancements have also largely supplanted older modalities for treatment of ISR, such as brachytherapy, bare metal stents, conventional and cutting balloon angioplasty, and atherectomy devices. This article reviews the presentation, pathophysiology, and treatment of coronary artery ISR, with a focus on recent clinical data and emerging therapies for this difficult to treat clinical problem. Expert commentary: DCB and second-generation DES are the most effective treatment options for ISR. Most trials support a slight superiority of second-generation DES, while DCB have the advantage of not adding another metal layer. The role of bioresorbable vascular scaffolds will be determined in the near future.