NYHA Functional Classification and Outcomes After Transcatheter Mitral Valve Repair in Heart Failure: The COAPT Trial

ObjectivesThe aim of this study was to evaluate the outcomes of MitraClip implantation versus guideline-directed medical therapy (GDMT) in patients with secondary mitral regurgitation (SMR) according to baseline functional status as assessed by the widely used New York Heart Association (NYHA) functional classification.BackgroundPatients with heart failure (HF) and impaired functional status at baseline have poor prognosis. Whether the effects of transcatheter repair of secondary SMR in patients with HF are influenced by baseline functional status is unknown.MethodsIn the COAPT (Cardiovascular Outcomes Assessment of the MitraClip Percutaneous Therapy for Heart Failure Patients with Functional Mitral Regurgitation) trial, patients with HF with moderate to severe or severe SMR who remained symptomatic despite maximally tolerated GDMT were randomized to MitraClip implantation versus GDMT alone. Outcomes were evaluated according to baseline functional status as assessed using the NYHA functional classification. The primary endpoint of interest was the rate of death or HF-related hospitalization (HFH) at 2 years in time-to-first-event analyses.ResultsAmong 613 randomized patients, 240 were in NYHA functional class II (39.2%), 322 were in NYHA functional class III (52.5%), and 51 were in ambulatory NYHA functional class IV (8.3%). Rates of death or HFH were progressively higher with increasing NYHA functional class. Compared with GDMT alone, MitraClip implantation resulted in lower 2-year rates of death or HFH consistently in patients in NYHA functional class II (39.7% vs. 63.7%; hazard ratio [HR]: 0.54; 95% confidence interval [CI]: 0.37 to 0.77), NYHA functional class III (46.6% vs. 65.5%; HR: 0.60; 95% CI: 0.45 to 0.82), and NYHA functional class IV (66.7% vs. 85.2%; HR: 0.55; 95% CI: 0.28 to 1.10; p_interaction = 0.86). Greater improvements in quality of life at 2 years were observed in patients treated with the MitraClip compared with GDMT irrespective of baseline functional status.ConclusionsThe NYHA functional classification provides prognostic utility in patients with HF and moderate to severe or severe SMR. In the COAPT trial, the benefits of MitraClip implantation were consistent in patients with better or worse functional status as assessed by NYHA functional class. (Cardiovascular Outcomes Assessment of the MitraClip Percutaneous Therapy for Heart Failure Patients With Functional Mitral Regurgitation [The COAPT Trial] [COAPT]; NCT01626079)     

Prevention of type 1 diabetes: today and tomorrow

The aim of therapeutic interventions for type 1 diabetes is to suppress pathogenic autoreactivity and to preserve/restore beta-cell mass and function to physiologically sufficient levels to maintain good metabolic control. During the natural history of type 1 diabetes, several strategies have been applied at various stages in the form of primary, secondary or tertiary prevention approaches. Clinical trials using antigen-specific (e.g. DiaPep277, human glutamic acid decarboxylase 65 (GAD65)) or non-specific immune therapies (e.g. anti-CD3 monoclonal antibodies) have shown some benefit in the modulation of the autoimmune process and prevention of the insulin secretion loss in the short term after diagnosis of diabetes. A single long-term effective therapy has not been identified yet, and it is likely that in most cases a rationally designed combinatorial approach using immunotherapeutic methods coupled with islet regeneration or replacement will prove to be most effective.     

Systematic Coronary Risk Evaluation (SCORE): JACC Focus Seminar 4/8

Clinical estimation of the combined effect of several risk factors is unreliable and this resulted in the development of a number of risk estimation systems to guide clinical practice. Here, after defining general principles of risk estimation, the authors describe the evolution of the European Society of Cardiology’s (ESC) Systematic COronary Risk Evaluation (SCORE) risk estimation system and some learnings from the data. They move on to describe the establishment of the ESC’s Cardiovascular Risk Collaboration and outline its proposed research directions. First among these is the evolution of SCORE 2, which provides updated, calibrated risk estimates for total cardiovascular events for low, moderate, high, and very high-risk regions of Europe. The authors conclude by considering that the future of risk estimation may be to express risk as years of exposure to a cardiovascular risk factor profile rather than risk over a fixed time period, such as 10 years, and how advances in genetics may permit individualized lifetime risk estimation from childhood on.     

Management of Intracerebral Hemorrhage: JACC Focus Seminar

Intracerebral hemorrhage (ICH) accounts for a disproportionate amount of stroke-related morbidity and mortality. Although chronic hypertension and cerebral amyloid angiopathy are the underlying cerebral vasculopathies accounting for the majority of ICH, there are a broad range of potential causes, and effective management requires accurate identification and treatment of the underlying mechanism of hemorrhage. Magnetic resonance imaging and vascular imaging techniques play a critical role in identifying disease mechanisms. Modern treatment of ICH focuses on rapid stabilization, often requiring urgent treatment of mass effect, aggressive blood pressure reduction and correction of contributing coagulopathies to achieve hemostasis. We discuss management of patients with ICH who continue to require long-term anticoagulation, the interaction of ICH with neurodegenerative diseases, and our approach to prognostication after ICH. We close this review with a discussion of novel medical and surgical approaches to ICH treatment that are being tested in clinical trials.     

Determinism and stochasticity during maturation of the zebrafish antibody repertoire

It is thought that the adaptive immune system of immature organisms follows a more deterministic program of antibody creation than is found in adults. We used high-throughput sequencing to characterize the diversifying antibody repertoire in zebrafish over five developmental time points. We found that the immune system begins in a highly stereotyped state with preferential use of a small number of V (variable) D (diverse) J (joining) gene segment combinations, but that this stereotypy decreases dramatically as the zebrafish mature, with many of the top VDJ combinations observed in 2-wk-old zebrafish virtually disappearing by 1 mo. However, we discovered that, in the primary repertoire, there are strong correlations in VDJ use that increase with zebrafish maturity, suggesting that VDJ recombination involves a level of deterministic programming that is unexpected. This stereotypy is masked by the complex diversification processes of antibody maturation; the variation and lack of correlation in full repertoires between individuals appears to be derived from randomness in clonal expansion during the affinity maturation process. These data provide a window into the mechanisms of VDJ recombination and diversity creation and allow us to better understand how the adaptive immune system achieves diversity.     

主动脉瓣及二尖瓣双瓣膜替换手术（附28例报告）

本文叙述了主动脉瓣及二尖瓣双瓣膜替换术。２８例病人均为风湿性心脏病。其中２例合并先天性心脏畸型。全组病例均置入人工机械瓣膜，其中８例同时行三尖瓣成形术。术后早期死亡１例，晚期死亡３例。本文对广义的心肌保护，主动脉瓣病变的判定，二尖瓣全周连续缝合，保留二尖瓣装置，三尖瓣的处理，主动脉瓣替换的一些方法，自体输血以及晚期死亡原因及预防等问题做了讨论。     

《血吸虫病防治知识与行为题库》预试验

目的检验《血吸虫病防治知识与行为题库》（《题库》）编写的科学性、严谨性、可行性、适用性和可理解性,并征求进一步修改和完善的意见与建议。方法随机选择江西和四川两省93名血防专业人员、血吸虫病疫区121名学生和107名成年村民为预试验对象。采用“专题小组讨论”法对《题库》进行预试验。结果认为《题库》具有科学性、严谨性、可行性、适用性和可理解性的预试验对象分别占72.04%、92.47%、68.82%、81.14%和70.13%,同时对某些题项提出修改完善意见。结论《题库》经修改完善后可用于疫区现场血吸虫病健康教育效果调查与评价。     

CAD Severity on Cardiac CTA Identifies Patients With Most Benefit of Treating LDL-Cholesterol to ACC/AHA and ESC/EAS Targets

ObjectivesThis study aimed to assess if information on CAD severity from coronary computed tomography angiography (CTA) can identify patients that benefit most from treating low-density lipoprotein-cholesterol (LDL-C) to American Heart Association/American College of Cardiology (ACC/AHA) and European Society of Cardiology (ESC) guidelines targets.BackgroundCurrent treatment guidelines for secondary prevention of atherosclerotic cardiovascular disease (ASCVD) disregard severity of coronary artery disease (CAD) for treatment choices. It is unclear whether severity of CAD should be considered in treatment recommendations.MethodsAmong 20,241 symptomatic patients undergoing diagnostic CTA from the Western Denmark Heart Registry, we assessed the number needed to treat (NNT) in 6 years to prevent 1 ASCVD event as well as the proportion of all events that could be prevented by treating LDL-C to targets. We assumed a 22% relative reduction of ASCVD events per 1 mmol/l reduction in LDL-C.ResultsIn multivariable analysis with no CAD as the reference, the subdistribution hazard ratio for ASCVD events was 4.0 (95% confidence interval [CI]: 3.3 to 4.9) for 1-vessel disease, 4.6 (3.5 to 6.0) for 2-vessel disease, and 5.6 (4.0 to 8.0) for 3-vessel disease. Consequently, the NNT to prevent 1 ASCVD event in 6 years by treating LDL-C to targets varied greatly from 233 (ESC) and 110 (ACC/AHA) for patients with no CAD to 8-9 for patients with 3-vessel disease (both ACC/AHA and ESC). The estimated percentage of ASCVD events that could be prevented by achieving guideline targets was 30% to 36% for patients with obstructive disease. However, <20% of patients achieved targets.ConclusionsAn individualized approach based on CAD severity can identify symptomatic patients that are likely to derive most and least benefit from treating LDL-C to ACC/AHA and ESC treatment targets.