Transcatheter left ventriculoplasty.

Despite significant advances in pharmacological, electrophysiological and valve therapies for heart failure with reduced ejection fraction (HFrEF), the associated morbidity, mortality and healthcare costs remain high. With a constantly growing heart failure population, the existing treatment gap between current and advanced heart failure therapies (e.g., left ventricular [LV] assist devices, heart transplantation) reflects a large unmet need, calling for novel therapeutic approaches. Left ventricular remodelling and dilatation, with or without scar formation, is the hallmark of cardiomyopathy and is associated with poor prognosis. In the era of exciting advances in structural heart interventions, the advent of minimally invasive, device-based therapies directly targeting the LV geometry and promoting physical reverse remodelling has created a new frontier in the battle against heart failure. Interventional heart failure therapy is a rapidly emerging field, encompassing structural heart and minimally invasive hybrid procedures, with two left ventriculoplasty devices currently under investigation in pivotal clinical trials in the US. This review addresses the rationale for left ventriculoplasty, presents the prior surgical and percutaneous attempts in the field, provides an overview of the novel transcatheter left ventriculoplasty devices and their respective trials, and highlights potential challenges associated with establishing such device-based therapies in our armamentarium against heart failure.

Dual antiplatelet therapy after percutaneous coronary intervention: Personalize the duration.

The recommended duration of dual antiplatelet therapy (DAPT) after percutaneous coronary intervention with a drug-eluting stent has changed from 1 year for all to a more personalized approach based on the patient's risks of ischemia and bleeding. The trend is toward shorter treatment in view of lower rates of late and very late stent thrombosis with newer drug-eluting stents and the risk of bleeding with DAPT. But some patients at high risk of ischemic events and low risk of bleeding may benefit from longer treatment.

Transcatheter Aortic Valve Replacement Outcomes Based on the Presence of Chronic Total Occlusion.

AIMS: Chronic total occlusion (CTO) has been linked to worse survival. While controversial and limited to observational data, successful CTO percutaneous coronary intervention (PCI) has been associated with improved left ventricular (LV) function and mortality. However, the role of CTO PCI prior to transcatheter aortic valve replacement (TAVR) is not clear. We sought to explore the prognostic impact of a pre-TAVR CTO on post-TAVR outcomes. METHODS AND RESULTS: We retrospectively reviewed 783 consecutive TAVR cases performed at a single tertiary care medical center. Pre-TAVR angiograms were analyzed for the presence of a CTO. At the time of TAVR, 12.6% (n = 99) patients had a CTO. At one-year post-TAVR, there was no significant association between the presence of a CTO and death (14.2% vs 13.1%, p = 0.75), functional status, quality of life, or adverse events. There was also no difference in long-term survival (4.1 years vs 4.1 years, p = 0.55). LV ejection fraction was lower in the CTO group at baseline and one year (p < 0.01). CONCLUSIONS: The presence of a CTO did not have any prognostic impact on mortality, change in LV function, or improvement in functional status and angina scores following TAVR in our cohort of elderly, high-risk patients. CTO before TAVR was associated with decreased ejection fraction at baseline and at one year.

A New HOPE? Lessons from Heart Outcomes Prevention Evaluation-3.

Lifestyle modification is the cornerstone of preventing atherosclerotic cardiovascular disease. When this is not sufficient in reducing risk, statin therapy is first line. Heart Outcomes Prevention Evaluation (HOPE-3) was a randomized controlled trial of rosuvastatin versus placebo, which demonstrated a significant net benefit in a lower-risk population without known atherosclerotic cardiovascular disease. There were many novel characteristics about this trial that should not be overlooked. It contained a diverse population and was the first trial to base inclusion solely on easily ascertainable metabolic risk factors. It had high adherence in the statin arm, likely due to several factors, including a run-in phase, close follow-up, and low intolerance of moderate-dose rosuvastatin. Attempting to simulate these could increase adherence among clinic populations. Although HOPE-3 did not demonstrate a significant decrease in cardiovascular events among women, meta-analysis including prior randomized controlled trials still demonstrates significant benefit, supporting prior guidelines for statin therapy in this group. Finally, HOPE-3 provides data that potentially support the legacy effect of statins. Understanding these key points provides additional insight into the benefits of statin therapy.

Loss of the inducible Hsp70 delays the inflammatory response to skeletal muscle injury and severely impairs muscle regeneration.

Skeletal muscle regeneration following injury is a highly coordinated process that involves transient muscle inflammation, removal of necrotic cellular debris and subsequent replacement of damaged myofibers through secondary myogenesis. However, the molecular mechanisms which coordinate these events are only beginning to be defined. In the current study we demonstrate that Heat shock protein 70 (Hsp70) is increased following muscle injury, and is necessary for the normal sequence of events following severe injury induced by cardiotoxin, and physiological injury induced by modified muscle use. Indeed, Hsp70 ablated mice showed a significantly delayed inflammatory response to muscle injury induced by cardiotoxin, with nearly undetected levels of both neutrophil and macrophage markers 24 hours post-injury. At later time points, Hsp70 ablated mice showed sustained muscle inflammation and necrosis, calcium deposition and impaired fiber regeneration that persisted several weeks post-injury. Through rescue experiments reintroducing Hsp70 intracellular expression plasmids into muscles of Hsp70 ablated mice either prior to injury or post-injury, we confirm that Hsp70 optimally promotes muscle regeneration when expressed during both the inflammatory phase that predominates in the first four days following severe injury and the regenerative phase that predominates thereafter. Additional rescue experiments reintroducing Hsp70 protein into the extracellular microenvironment of injured muscles at the onset of injury provides further evidence that Hsp70 released from damaged muscle may drive the early inflammatory response to injury. Importantly, following induction of physiological injury through muscle reloading following a period of muscle disuse, reduced inflammation in 3-day reloaded muscles of Hsp70 ablated mice was associated with preservation of myofibers, and increased muscle force production at later time points compared to WT. Collectively our findings indicate that depending on the nature and severity of muscle injury, therapeutics which differentially target both intracellular and extracellular localized Hsp70 may optimally preserve muscle tissue and promote muscle functional recovery.