Antiplatelet Agents and Survival: A Cohort Analysis From the Studies of Left Ventricular Dysfunction (SOLVD) Trial

Objectives. This study sought to evaluate the relation between antiplatelet agent (APA) use and survival and morbidity from cardiac disease in patients with left ventricular (LV) systolic dysfunction.Background. APAs play an important role in the prevention and treatment of coronary disease. Their effects in patients with LV systolic dysfunction are unknown.Methods. We reviewed data on APA use in 6,797 patients enrolled in the Studies of Left Ventricular Dysfunction (SOLVD) trial and analyzed the relation between their use and all-cause mortality as well as the combined end point of death or hospital admission for heart failure (HF). We used Cox regression to adjust for differences in baseline characteristics and to test for the interaction between APA use and selected patient variables in relation to outcome.Results. APA use (46.3% of patients) was associated with significantly reduced mortality from all causes (adjusted hazard ratio [HR] 0.82, 95% confidence interval [CI] 0.73 to 0.92, p = 0.0005) and reduced risk of death or hospital admission for HF (adjusted HR 0.81, 95% CI 0.74 to 0.89, p < 0.0001) but was not influenced by trial assignment, gender, LV ejection fraction, New York Heart Association class or etiology. A strong interaction was observed among APA use, randomization group and all-cause mortality. The association between APA use and survival was not observed in the enalapril group, nor was an enalapril benefit on survival detectable in patients receiving APAs at baseline. However, randomization to enalapril therapy significantly reduced the combined end point of death or hospital admission for HF in APA users.Conclusions. In patients with LV systolic dysfunction, use of APAs is associated with improved survival and reduced morbidity. This association is retained after adjustment for baseline characteristics. APA use is associated with retained but reduced benefit from enalapril.     

Studies of Left Ventricular Dysfunction (SOLVD)

Given the increasing incidence and dismal prognosis in congestive heart failure, it is not surprising that strenuous efforts have been made to limit the morbidity and mortality that result from this syndrome. The National Institutes of Health designed and implemented the Studies of Left Ventricular Dysfunction (SOLVD) to assess the effect of therapy with enalapril, an angiotensin-converting enzyme inhibitor, on all cause mortality in a population with left ventricular dysfunction (i.e., ejection fraction at or below 35%). Important secondary objectives included the effects of this therapy on cause-specific mortality, development of heart failure, and hospitalization for congestive heart failure. Patients within each of two arms of the trial were randomized on the basis of the administration (treatment arm) or lack (prevention arm) of concomitant therapy for congestive heart failure. The trial was double blind and placebo controlled. The mean follow-up period for the combined arms was 39.2 months, during which time there was a 16% risk reduction in all-cause mortality in the treatment arm of the trial (P equals 0.008) and an 8% risk reduction in the prevention arm (P equals NS). In the prevention arm, however, there was a 12% reduction risk for cardiovascular mortality (P equals 0.12) and a 37% reduction in risk of progression to heart failure (P is less than 0.001). Thus, the results of SOLVD indicate that therapy with an angiotensin-converting enzyme inhibitor has beneficial effects on morbidity and mortality that are apparent in a broad spectrum of patients with left ventricular dysfunction.     

Determinants of Left Ventricular Hypertrophy and Diastolic Dysfunction in an HIV Clinical Cohort

Objective

The aim of this work was to investigate determinants of structural myocardial abnormalities in persons living with human immunodeficiency virus (PLWH).

From Left Ventricular Dysfunction to Heart Failure in the Elderly Patient

The pathophysiology of the syndrome of congestive heart failure (CHF) is different in elderly patients compared to middle-aged subjects. When the syndrome of CHF predominantly results from left ventricular (LV) systolic dysfunction, peripheral mechanisms in elderly patients are less apt to compensate for the decline in LV performance due to deconditioning of the skeletal muscles, decreased vasodilatory response to exercise, and reduced capacity to excrete sodium. These all develop with age. LV diastolic dysfunction, i.e., LV filling impairment, appears to be a more frequent cause of CHF in elderly patients than in middle-aged subjects. Hypertrophy of the cardiac myocyte is associated with a prolongation of the calcium transient which, in turn, results from a decreased concentration of the enzyme responsible for reuptake of calcium in the sarcoplasmic reticulum. Cardiac myocyte hypertrophy results from a steady loss of myocytes and a progressive rise in arterial impedance which are both observed with aging. Notwithstanding subendocardial myocardial ischemia which is frequently associated with LV wall hypertrophy, prolongation of the calcium transient leads to impaired LV wall relaxation and the syndrome of LV diastolic dysfunction. The goals of therapy are also different in elderly patients compared to middle-aged patients. In elderly patients, one is less concerned about restoring a near normal exercise capacity, and aims at preventing acute episodes of decompensation which frequently accompany excessive sodium intake. Therefore, strict adherence to diet and careful titration of the dosages of medication to renal function are important considerations when treating CHF in elderly patients. In particular, cardiac glycosides, which should be avoided with CHF due to LV diastolic dysfunction, should be carefully titrated to creatinine clearance and body weight when treating elderly patients with LV systolic dysfunction in sinus rhythm. Similarly, the dosages of most angiotensin-converting enzyme inhibitors should be reduced in elderly patients.     

Periprocedural Anticoagulation Management of Patients receiving Warfarin in Qatar: A Prospective Cohort Study

Background: The use of anticoagulant bridging remains controversial. This study was conducted to evaluate our warfarin periprocedural management in Qatar and investigate the associated clinical outcomes with such management. Methods: A prospective cohort study was designed to describe the periprocedural clinical practice in warfarin patients in Qatar and to compare clinical safety and efficacy outcomes between anticoagulant bridging and nonbridging. Results: 103 patients were recruited. Bridging occurred in 82% of the participants. No thromboembolic events were observed, while 39.1% of patients experienced bleeding events during the study period. The incidence of overall bleeding and major bleeding were numerically higher for bridging group compared to nonbridging but did not reach statistical significance ([30.6% vs 22.2%, P = 0.478] and [12.9% vs 5.6%, P = 0.375], respectively). Conclusion: Warfarin interruption and bridging are overwhelmingly used in warfarin-treated patients in Qatar. While bridging was numerically associated with increased bleeding events, there is no statistical difference in reported clinical events between bridging and nonbridging strategies.     

左心辅助装置与右心衰

左心辅助装置 (L VAD)在临床中的成功应用 ,正受到越来越多人的肯定和接受 ,在术后严重低心排的病人 ,其抢救存活率可达 5 0 % [1] ,而在终末期心泵功能衰竭等待心脏移植的病人和急性心肌炎所致的心源性休克病人其存活率更高。但一个不容忽视的问题是在应用左心辅助的病人中 ,右心衰的发生率约占 2 0 %～ 30 % [2 ,3] ,是造成病人死亡的最重要原因之一。右心衰发生的原因和机制目前还没有完全清楚 ,在如何处理上也存在一定的争论。现多数学者认为 ,左心辅助后右心衰的发生原因和机制包括 [4] :右心室原已存在的病变引起右心功能损害 ;右心…     

Left Ventricular Dysfunction and Chemotherapeutic Agents

Purpose of Review

We aim to summarize the effect of cancer therapy-related cardiotoxicity on the development of left ventricular (LV) dysfunction.

Recent Findings

We discuss commonly used cancer therapeutics that have the potential for both acute and delayed cardiotoxicity. LV dysfunction from cancer therapies may be found by routine cardiac imaging prior to clinical manifestations of heart failure (HF) and we discuss the current multi-modality approaches for early detection of toxicity with the use of advanced echocardiographic parameters including strain techniques. Further, we discuss the role of biomarkers for detection of LV dysfunction from cancer therapies. Current approaches monitoring and treating LV dysfunction related to cancer therapy-related cardiotoxicity include addressing modifiable cardiovascular risk factors especially hypertension and early initiation of neurohormonal blockade (NHB) with disease-modifying beta-blockers and renin–angiotensin–aldosterone system (RAAS) inhibitors. Once LV dysfunction is identified, traditional ACC/AHA guideline-directed therapy is employed. Further, we highlight the use of advanced heart failure therapies including mechanical resynchronization devices, the use of durable ventricular assist devices, and cardiac transplantation as increasingly employed modalities for treatment of severe LV dysfunction and advanced heart failure in the cardio-oncology population.

Summary

This review seeks to highlight the importance of early detection, treatment, and prevention of LV dysfunction from cancer therapy-related cardiotoxicity.

     

Ventricular Arrhythmias and Left Ventricular Dysfunction in Familial Cardiomyopathy

ABSTRACT. In familial cardiomyopathy (CM), different forms of myocardial abnormalities including asymmetric and symmetric hypertrophy and dilated left ventricles are presented, mostly showing varying hereditary penetrance. This study presents a family with CM including three major clinical manifestations: severe ventricular arrhythmias, repolarization abnormalitites and left ventricular hypertrophy. This triad was strikingly consistent in the two generations examined. The familial pattern with an autosomal dominant inheritance did not show any linkage to the HLA region.     

孤立性心肌致密化不全患者左室收缩功能的相关因素分析

目的总结孤立性左室心肌致密化不全（ILVNC）患者的临床资料,并对其左室收缩功能的相关影响因素进行分析。方法连续入选自2006年1月至2010年9月经超声心动图确诊为ILVNC的患者共41例,总结其临床资料,并对可能影响该组患者左室射血分数（LVEF）的因素进行分析。结果 41例患者（男性35例）LVEF均值为31.41±11.21%;最常受累的心肌节段是心尖部（100%受累）,其次是心尖段外侧壁（92.7%受累）、心尖段下壁（82.9%受累）和心尖段前壁（70.7%受累）。相关性分析表明,LogNT-proBNP、左室舒张末内径（LVEDD）和室壁运动评分指数（WMSI）与LVEF均呈负相关,r分别为-0.441（P=0.007）、-0.357（P=0.022）以及-0.714（P=0.000）,具有显著的统计学意义;受累节段数目和NC/C比值则与LVEF无显著相关性;WMSI与受累节段数目呈正相关（r=0.362,P=0.020）,与NC/C比值无显著相关性（P=0.254）。结论 ILVNC患者LVEF左室整体收缩功能与NT-proBNP及LVEDD呈负相关,而与受累心肌节段数目、NC/C比值无明显关联。     

Using Deep-Learning Algorithms to Simultaneously Identify Right and Left Ventricular Dysfunction From the Electrocardiogram

ObjectivesThis study sought to develop DL models capable of comprehensively quantifying left and right ventricular dysfunction from ECG data in a large, diverse population.BackgroundRapid evaluation of left and right ventricular function using deep learning (DL) on electrocardiograms (ECGs) can assist diagnostic workflow. However, DL tools to estimate right ventricular (RV) function do not exist, whereas those to estimate left ventricular (LV) function are restricted to quantification of very low LV function only.MethodsA multicenter study was conducted with data from 5 New York City hospitals: 4 for internal testing and 1 serving as external validation. We created novel DL models to classify left ventricular ejection fraction (LVEF) into categories derived from the latest universal definition of heart failure, estimate LVEF through regression, and predict a composite outcome of either RV systolic dysfunction or RV dilation.ResultsWe obtained echocardiogram LVEF estimates for 147,636 patients paired to 715,890 ECGs. We used natural language processing (NLP) to extract RV size and systolic function information from 404,502 echocardiogram reports paired to 761,510 ECGs for 148,227 patients. For LVEF classification in internal testing, area under curve (AUC) at detection of LVEF ≤40%, 40% < LVEF ≤50%, and LVEF >50% was 0.94 (95% CI: 0.94-0.94), 0.82 (95% CI: 0.81-0.83), and 0.89 (95% CI: 0.89-0.89), respectively. For external validation, these results were 0.94 (95% CI: 0.94-0.95), 0.73 (95% CI: 0.72-0.74), and 0.87 (95% CI: 0.87-0.88). For regression, the mean absolute error was 5.84% (95% CI: 5.82%-5.85%) for internal testing and 6.14% (95% CI: 6.13%-6.16%) in external validation. For prediction of the composite RV outcome, AUC was 0.84 (95% CI: 0.84-0.84) in both internal testing and external validation.ConclusionsDL on ECG data can be used to create inexpensive screening, diagnostic, and predictive tools for both LV and RV dysfunction. Such tools may bridge the applicability of ECGs and echocardiography and enable prioritization of patients for further interventions for either sided failure progressing to biventricular disease.     

Cancer Therapy-Induced Left Ventricular Dysfunction: Interventions and Prognosis

BackgroundFor multiple chemotherapeutics, cardiotoxicity is dose limiting and can lead to substantial morbidity and mortality. Early cardiac intervention has the potential to positively affect clinical course.Methods and ResultsWe reviewed 247 consecutive patients referred to the Stanford cardiology clinic for cancer therapy-associated cardiac abnormalities from 2004 to 2012. A comprehensive review of records was performed, with documentation of baseline characteristics, cardiac imaging, medications, and clinical course. Seventy-nine patients who had left ventricular ejection fraction (LVEF) declines temporally associated with cancer therapy were included. The most common malignancies were breast (46%) and hematologic (35%); 71% of the patients were female, and overall mean age was 52 years. The primary cancer therapeutics associated with LVEF decline included anthracyclines, trastuzumab, and tyrosine kinase inhibitors. The mean LVEF was 60% before cancer therapy and 40% after cancer therapy. The most common cardiac interventions included beta-blockers (84%) and angiotensin-converting enzyme inhibitors/angiotensin receptor blockers (83%). Mean LVEF after cardiac intervention rose to 53%; 77% of patients had LVEF recovery to ≥50%, and 68% of these patients had recovery within 6 months of starting cardiac therapy; 76% of patients were able to continue their planned cancer therapy.ConclusionsWith appropriate cardiac intervention, the majority of patients with LVEF decline from cancer therapy can achieve LVEF recovery and complete their cancer therapy.     

Association of Left Ventricular Longitudinal and Circumferential Systolic Dysfunction With Diastolic Function in Hypertension: A Nonlinear Analysis Focused on the Interplay With Left Ventricular Geometry

BackgroundThe relationships of left ventricular (LV) longitudinal and circumferential systolic dysfunction with diastolic performance in hypertensive patients have never been compared.Methods and ResultsIn 532 asymptomatic hypertensive patients, circumferential function was assessed with the use of midwall fractional shortening (mFS) and stress-corrected mFS (SCmFS), whereas longitudinal function was assessed with the use of left atrioventricular plane displacement (AVPD) and systolic mitral annulus velocity (s′). Early diastolic annular velocity (e′) and the E/e′ ratio were measured. Global longitudinal and circumferential strain were determined in a subset of 210 patients. e′ was linearly related to all systolic indexes (AVPD: R = 0.40; s′: R = 0.39; mFS: R = 0.16; SCmFS: R = 0.17; all P < .0001), but the correlations were stronger with longitudinal indexes than with circumferential ones (P < .0001). E/e′ was nonlinearly related to AVPD (R = −0.49; P < .0001) and s′ (R = −0.34; P < .0001) and showed no relationship with mFS and SCmFS. Longitudinal indexes were superior to circumferential ones in predicting e′ <8 cm/s, E/e′ <8, and E/e′ ≥13. The effect of LV geometry on LV diastolic function was evident among patients with preserved systolic longitudinal function, but was blunted among patients with impaired longitudinal function. In multivariable analyses, only longitudinal indexes remained associated with e′ and E/e′. Analyses using strains provided similar results.ConclusionsIn asymptomatic hypertensive subjects, LV diastolic performance is independently associated with longitudinal systolic dysfunction, but not with circumferential systolic dysfunction. Subtle longitudinal systolic impairment plays a role in mediating the effect of LV geometry on diastolic performance. These findings may support the need of critically revising the concept of isolated diastolic dysfunction in these patients.     

中老年人左心室舒张功能减退及其相关危险因素——广州生物库心血管疾病亚队列研究

目的探讨广州市相对健康的中老年人左心室舒张功能减退及其相关危险因素。方法采用单纯随机方法收集390名年龄≥50岁,无脑卒中、心肌梗死、肺心病及恶性肿瘤等重大慢性疾病史的中老年人进行横断面研究,收集其个人资料及病史、体格检查并测定血清空腹血糖、血脂水平;采用彩色多普勒超声诊断仪,进行左心舒张功能指标测定,包括二尖瓣舒张早期血流峰值(E)和舒张晚期血流峰值(A)及E/A,E峰减速时间(DT)和等容舒张时间(IVRT)。结果①A峰随着年龄的增长而增高,E/A随着年龄的增长而减低(均P<0.05)。②调整了年龄和性别之后,随着腰围的增大,A峰和IVRT随之升高,而E/A则随之降低;同时也发现A峰随三酰甘油和空腹血糖水平升高而升高(均P<0.05)。③用三分位数分组,对310名未服用抗高血压药物者的血压水平,调整了年龄和性别,结果显示A峰随收缩压和脉压差升高而增高(P<0.05),而E/A则随收缩压和舒张压的升高而降低(P<0.05)。④理想血压组、正常血压高值组和高血压组的A峰水平呈逐步升高(P<0.05),而E/A则呈逐步下降的趋势(P<0.05)。结论血压升高是左心室舒张功能损伤的独立危险因素,即使血压在正常水平...     

Early Detection of Chemotherapy-Related Left Ventricular Dysfunction

Modern advances in cancer treatment have resulted in improved survival. As a result, effects of cancer therapy on other organ systems such as the heart are more likely to become clinically relevant. One such possibility is chemotherapy-related left ventricular dysfunction. Although in clinical practice cardiotoxicity is evaluated by symptoms and left ventricular ejection fraction, these occur relatively late in the disease process after the heart's compensatory mechanisms have been expended. Ideally, left ventricular dysfunction would be identified early so that cancer patients and their physicians can make informed decisions about their therapeutic options and institute careful surveillance and early initiation of cardioprotective medication where appropriate. This review discusses the role of echocardiography to detect subclinical left ventricular dysfunction in cancer patients exposed to chemotherapy with potential cardiotoxicity, particularly anthracyclines and trastuzumab.     

Slope of the Anterior Mitral Valve Leaflet: A New Measurement of Left Ventricular Unloading for Left Ventricular Assist Devices and Systolic Dysfunction

Left ventricular assist device (LVAD)-supported patients are evaluated routinely with use of transthoracic echocardiography. Values of left ventricular unloading in this unique patient population are needed to evaluate LVAD function and assist in patient follow-up.We introduce a new M-mode measurement, the slope of the anterior mitral valve leaflet (SLAM), and compare its efficacy with that of other standard echocardiographically evaluated values for left ventricular loading, including E/e′ and pulmonary artery systolic pressures. Average SLAM values were determined retrospectively for cohorts of random, non-LVAD patients with moderately to severely impaired left ventricular ejection fraction (LVEF) (<0.35, n=60). In addition, pre- and post-LVAD implantation echocardiographic images of 81 patients were reviewed.The average SLAM in patients with an LVEF <0.35 was 11.6 cm/s (95% confidence interval, 10.4–12.8); SLAM had a moderately strong correlation with E/e′ in these patients. Implantation of LVADs significantly increased the SLAM from 7.3 ± 2.44 to 14.7 ± 5.01 cm/s (n=42, P <0.0001). The LVAD-supported patients readmitted for exacerbation of congestive heart failure exhibited decreased SLAM from 12 ± 3.93 to 7.3 ± 3.5 cm/s (n=6, P=0.041). In addition, a cutpoint of 10 cm/s distinguished random patients with LVEF <0.35 from those in end-stage congestive heart failure (pre-LVAD) with an 88% sensitivity and a 55% specificity.Evaluating ventricular unloading in LVAD patients remains challenging. Our novel M-mode value correlates with echocardiographic values of left ventricular filling in patients with moderate-to-severe systolic function and dynamically improves with the ventricular unloading of an LVAD.     

Left Ventricular Diastolic Dysfunction in Peritoneal Dialysis: A Forgotten Risk Factor

Left ventricular diastolic dysfunction (LVDD) is common among patients undergoing peritoneal dialysis (PD). We examined the relationship between LVDD, major adverse cardiovascular events (MACE), and mortality in PD patients. A total of 149 patients undergoing PD with preserved left ventricular systolic function were included and followed for 3.5 years. LVDD was diagnosed (according to the European Society of Cardiology guidelines) by conventional and tissue Doppler echocardiography. Serum high-sensitivity C-reactive protein (hsCRP) was measured. The location and volume of adipose tissue were assessed by computed tomography (CT) at the level of the fourth lumbar vertebra. Subjects with LVDD had higher levels of hsCRP, and more visceral and peritoneal fat than controls. The relationship between adjusted visceral adipose tissue and LVDD became nonsignificant when hsCRP and baseline demographic data were introduced into the logistic regression model (odds ratio = 1.52, P = 0.07). Subsequent hierarchical multivariate Cox regression analysis showed that LVDD was one of the most powerful determinants of MACE and mortality after adjusting for all confounding factors (hazard ratio [HR]: 1.71, 95% confidence interval [CI]: 1.43–3.51, P = 0.02 and HR: 2.25, 95% CI: 1.45–2.91, P = 0.04, respectively). Systemic inflammation (hsCRP) was also significantly associated with MACE and mortality (HR: 2.03, P = 0.03 and HR: 2.16, P = 0.04, respectively). LVDD is associated with systemic inflammation and increased visceral fat in patients undergoing PD. LVDD is also a sensitive, independent indicator of future MACE and mortality in PD patients.     

Placebo Adherence and Its Association with Morbidity and Mortality in the Studies of Left Ventricular Dysfunction

BACKGROUND  

A provocative finding from several double-blind clinical trials has been the association between greater adherence to placebo study medication and better health outcomes. We used data from the Studies of Left Ventricular Dysfunction (SOLVD) Treatment Trial (SOLVD-TT) and the SOLVD Prevention Trial (SOLVD-PT) to examine whether such associations could be validated and to examine several sources of bias and potential confounding.