Predictors of Major Adverse Cardiovascular Events in Patients With Moderate Aortic Stenosis: Implications for Aortic Valve Replacement.

BACKGROUND: Although the prognosis and management of severe aortic stenosis has been extensively studied, the risk stratification and outcomes of patients with moderate aortic stenosis remain elusive. METHODS: This study included 674 patients from the Cleveland Clinic Health System with moderate aortic stenosis (aortic valve area, 1-1.5 cm2; mean gradient, 20-40 mm Hg; and peak velocity <4 m/s) and an NT-proBNP (N-terminal pro-B-type natriuretic peptide) level within 3 months of index diagnosis. The primary outcome of major adverse cardiovascular events (defined as the composite outcome of progression to severe aortic stenosis requiring aortic valve replacement, heart failure hospitalization, or death) was extracted from the electronic medical record. RESULTS: The mean age was 75.3±12 years, and 57% were men. During a median follow-up of 316 days, the composite end point occurred in 305 patients. There were 132 (19.6%) deaths, 144 (21.4%) heart failure hospitalizations, and 114 (16.9%) patients underwent aortic valve replacement. Elevated NT-proBNP (1.41 [95% CI, 1.01-1.95]; P=0.048), diabetes (1.46 [95% CI, 1.08-1.96]; P=0.01), elevated averaged mitral valve E/e' ratio (hazard ratio, 1.57 [95% CI, 1.18-2.10]; P<0.01), and presence atrial fibrillation at the time of index echocardiogram (hazard ratio, 1.83 [95% CI, 1.15-2.91]; P=0.01) were each independently associated with an increased hazard for the composite outcome and when taken collectively, each of these factors incrementally increased risk. CONCLUSIONS: These results further elucidate the relatively poor short-medium term outcomes and risk stratification of patients with moderate aortic stenosis, supporting randomized trials assessing the efficacy of transcatheter aortic valve replacement in this population.

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.

Novel devices for managing heart failure.

PURPOSE OF REVIEW: Despite advances in heart failure (HF) therapies, the associated morbidity, mortality, hospitalization rates, and healthcare expenditures remain high. A significant proportion of patients with HF remain symptomatic despite receiving optimal medical therapy. Consequently, there exists a large unmet clinical need for novel therapies for treating acute and chronic HF. With the exponential growth of transcatheter interventions in structural heart disease, novel applications of minimally invasive, device-based therapies have been sought in an effort to bridge this treatment gap. The rationale, development, and current data underscoring these therapies will be summarized in this review. RECENT FINDINGS: Recent studies have demonstrated the safety and efficacy of devices that alter left ventricular geometry (i.e., ventriculoplasty), create anatomic shunts to decompress the left atrium, and modulate vena caval and renal blood flow. However pivotal large trials evaluating clinical outcomes are ongoing. SUMMARY: Innovative device-based therapies may expand our armamentarium against the growing heterogeneous and morbid HF syndrome.

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.

Treatment Gap in Primary Prevention Patients Presenting With Acute Coronary Syndrome.

Previous studies assessing healthcare provider compliance to the 2013 American College of Cardiology/American Heart Association (ACC/AHA) cholesterol guidelines indicate a significant underuse of statin therapy at appropriate intensity. However, data are limited in primary prevention patients. Our study aimed to evaluate the impact of the 2013 ACC/AHA guidelines through a retrospective analysis of primary prevention patients presenting with first time acute coronary syndrome (ACS). We retrospectively calculated the 10-year predicted Atherosclerotic Cardiovascular Disease (10yASCVD) risk in 1,265 patients ages 40 to 75 who presented with ACS and no previous ASCVD. In patients without known ambulatory systolic blood pressure, a multivariable linear regression model was used to predict outpatient systolic blood pressure. Outcomes analyzed in each 10yASCVD category included statin status and statin intensity (high/medium/low) with further categorization by type of ACS event and date of left heart catheterization. In both primary analysis and sensitivity analysis (patients with predicted systolic blood pressure), statistical significance was shown with respect to overall statin status, ST Elevation Myocardial Infarction, and date of left heart catheterization. In summary, retrospective calculation of 10yASCVD in patients with a first ACS event showed a significant number of ACS patients would have qualified for statin therapy per 2013 ACC/AHA guidelines before their event but had not been initiated on one.

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.

Polyarteritis nodosa.

The first description of polyarteritis nodosa (PAN) was in 1852 by Karl Rokitansky, a pathologist at the University of Vienna. The initial report describes a 23-year-old man who had a 5-day history of fever and diarrhea. Since then, the definition of PAN has evolved. The currently accepted definition of PAN comes from the 2012 Chapel Hill Conference, which classified PAN as a necrotizing arteritis not associated with antineutrophil cytoplasmic antibodies of medium or small arteries without glomerulonephritis or vasculitis in arterioles, capillaries, or venules.

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.