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Background Placement of an interatrial shunt device reduces pulmonary capillary wedge pressure during exercise in patients with heart failure and preserved or mildly reduced ejection fraction. We aimed to investigate whether an interatrial shunt can reduce heart failure events or improve health status in these patients.Methods In this randomised, international, blinded, sham-controlled trial performed at 89 health-care centres, we included patients (aged >= 40 years) with symptomatic heart failure, an ejection fraction of at least 40%, and pulmonary capillary wedge pressure during exercise of at least 25 mm Hg while exceeding right atrial pressure by at least 5 mm Hg. Patients were randomly assigned (1:1) to receive either a shunt device or sham procedure. Patients and outcome assessors were masked to randomisation. The primary endpoint was a hierarchical composite of cardiovascular death or non-fatal ischemic stroke at 12 months, rate of total heart failure events up to 24 months, and change in Kansas City Cardiomyopathy Questionnaire overall summary score at 12 months. Pre-specified subgroup analyses were conducted for the heart failure event endpoint. Analysis of the primary endpoint, all other efficacy endpoints, and safety endpoints was conducted in the modified intention-to-treat population, defined as all patients randomly allocated to receive treatment, excluding those found to be ineligible after randomisation and therefore not treated. This study is registered with ClinicalTrials.gov, NCT03088033.Findings Between May 25, 2017, and July 24, 2020, 1072 participants were enrolled, of whom 626 were randomly assigned to either the atrial shunt device (n=314) or sham procedure (n=312). There were no differences between groups in the primary composite endpoint (win ratio 1.0 [95% CI 0.8-1.2]; p=0.85) or in the individual components of the primary endpoint. The prespecified subgroups demonstrating a differential effect of atrial shunt device treatment on heart failure events were pulmonary artery systolic pressure at 20W of exercise (p(interaction)=0.002 [>70 mm Hg associated with worse outcomes]), right atrial volume index (p(interaction)=0.012 [>= 29.7 mL/m(2), worse outcomes]), and sex (p(interaction=)0.02 [men, worse outcomes]). There were no differences in the composite safety endpoint between the two groups (n=116 [38%] for shunt device vs n=97 [31%] for sham procedure; p=0.11).Interpretation Placement of an atrial shunt device did not reduce the total rate of heart failure events or improve health status in the overall population of patients with heart failure and ejection fraction of greater than or equal to 40%. Copyright (C) 2022 Elsevier Ltd. All rights reserved.

We reviewed the effects of hypertension and the means to prevent and treat it across the spectrum of a woman's lifespan and identified gaps in sex-specific mechanisms contributing to hypertension in women that need to be addressed.Hypertension continues to be an important public health problem for women across all life stages from adolescence through pregnancy, menopause, and older age. There remain racial, ethnic, and socioeconomic differences in hypertension rates not only overall but also between the sexes. Blood pressure cutoffs during pregnancy have not been updated to reflect the 2017 ACC/AHA changes due to a lack of data. Additionally, the mechanisms behind hypertension development in menopause, including sex hormones and genetic factors, are not well understood. In the setting of increasing inactivity and obesity, along with an aging population, hypertension rates are increasing in women. Screening and management of hypertension throughout a women's lifespan are necessary to reduce the burden of cardiovascular disease, and further research to understand sex-specific hypertension mechanisms is needed.

Hypertension is the most prevalent modifiable factor for the development of heart failure. However, the optimal blood pressure (BP) target for preventing heart failure remains uncertain. The SPRINT (Systolic BP Intervention Trial) was a large, randomized open-label trial (n=9361 participants) that showed the superiority of a systolic BP target of P =0.81). A separate analysis demonstrated that the reduction in ADHF events in the intensive treatment group in SPRINT was not due to the differential use of diuretics between the 2 treatment groups. Although intensive BP treatment resulted in a lower cardiovascular disease event rate, this was not significantly associated with changes in left ventricular mass, function, or fibrosis, as assessed in SPRINT HEART, an ancillary study to SPRINT. Intensive BP treatment, however, significantly attenuated increases in carotid-femoral pulse wave velocity. Overall, these data highlight the importance of preventing ADHF in high cardiovascular risk hypertensive patients by optimal BP reduction as tested in SPRINT.

BACKGROUND: Patients with heart failure (HF) with preserved ejection fraction (HFpEF) and obesity display a number of pathophysiologic features that may render them more or less vulnerable to negative effects of decongestion on renal function, including greater right ventricular remodeling, plasma volume expansion, and pericardial restraint. We aimed to contrast the renal response to decongestion in obese compared to non-obese HFpEF METHODS AND RESULTS: NIH heart failure network studies that enrolled patients with acute decompensated HFpEF (EF≥50%) were included [DOSE, CARRESS, ROSE and ATHENA]. Obese HFpEF was defined as a body mass index (BMI) ≥30 kg/m(2). Compared to non-obese HFpEF (n=118), patients with obese HFpEF (n=214) were an average of 9 years younger (71 vs 80 years,0.5mg/dl) (9 vs 0%, p=0.002). CONCLUSION: Despite being nearly a decade younger, obese HFpEF patients experience greater deterioration in renal function during decongestion compared to non-obese HFpEF. Further study to elucidate the complex relationships between volume distribution, cardiorenal hemodynamics and adiposity in HFpEF are needed.

We hypothesized that cannabis use is associated with cardiovascular disease (CVD) risk factors. This could explain the reported link between cannabis and cardiovascular events including stroke and myocardial infarction. This analysis included 7,159 participants (age 37.8 ± 12.4 years, 48.6% men, and 61.5% Caucasian) from the National Health and Nutrition Examination Survey years 2011 to 2018. Cannabis use was defined by self-report. Participants with a history of stroke or myocardial infarction were excluded. Composite CVD risk was assessed using the American College of Cardiology/American Heart Association 10-year atherosclerotic cardiovascular risk (ASCVD) score. Participants were classified based on their ASCVD risk levels as low (5.0%), borderline (5.0% to 7.4%), intermediate (7.5% to 19.9%), and high (≥20.0%). Multinomial logistic regression was used to examine the association between cannabis use and ASCVD risk category using low-risk ASCVD category as the reference level. About 63.9% (n = 4,573) of participants had ever used cannabis. Ever cannabis use was associated with 60% increased odds of high-risk ASCVD score (odds ratio [OR] 95% confidence interval [CI] 1.60 [1.04 to 2.45], p = 0.03). We also observed a dose-response relation between increased use of cannabis and a higher risk of ASCVD. Those reporting ≥2 uses per month had 79% increased odds of high-risk ASCVD score (OR [95% CI] 1.79 [1.10 to 2.92], p = 0.02) and those reporting ≥1 use per day had 87% increased odds of high-risk ASCVD score (OR [95% CI] 1.87 [1.16 to 3.01], p0.001]. In conclusion, cannabis use is associated with elevated CVD risk. Individuals using cannabis should be screened for CVD risk, and appropriate risk reduction strategies should be implemented.

Background: In the SPRINT (Systolic Blood Pressure Intervention Trial), intensive BP treatment reduced acute decompensated heart failure (ADHF) events. Here, we report the effect on HF with preserved ejection fraction (HFpEF) and HF with reduced EF (HFrEF) and their subsequent outcomes. Methods: Incident ADHF was defined as hospitalization or emergency department visit, confirmed, and formally adjudicated by a blinded events committee using standardized protocols. HFpEF was defined as EF ≥45%, and HFrEF was EF Results: Among the 133 participants with incident ADHF who had EF assessment, 69 (52%) had HFpEF and 64 (48%) had HFrEF ( P value: 0.73). During average 3.3 years follow-up in those who developed incident ADHF, rates of subsequent all-cause and HF hospital readmission and mortality were high, but there were no significant differences between those who developed HFpEF versus HFrEF. Randomization to the intensive arm had no effect on subsequent mortality or readmissions after the initial ADHF event, irrespective of EF subtype. During follow-up among participants who developed HFpEF, although relatively modest number of events limited statistical power, age was an independent predictor of all-cause mortality, and Black race independently predicted all-cause and HF hospital readmission. Conclusions: In SPRINT, intensive BP reduction decreased both acute decompensated HFpEF and HFrEF events. After initial incident ADHF, rates of subsequent hospital admission and mortality were high and were similar for those who developed HFpEF or HFrEF. Randomization to the intensive arm did not alter the risks for subsequent all-cause, or HF events in either HFpEF or HFrEF. Among those who developed HFpEF, age and Black race were independent predictors of clinical outcomes. Registration: URL: https://www.clinicaltrials.gov ; Unique identifier: NCT01206062.

This review aims to investigate the blood pressure (BP)-lowering effects of emerging drugs developed to treat diabetic kidney disease and heart failure (HF). We summarize the potential pathophysiological mechanisms responsible for mitigating hypertensive target organ damage and evaluating the available clinical data on these newer drugs.Nonsteroidal dihydropyridine-based mineralocorticoid receptor antagonists (MRAs), dual angiotensin II receptor-neprilysin inhibitors (valsartan with sacubitril), sodium-glucose cotransporter 2 inhibitors (SGLT2i), and soluble guanylate cyclase stimulators are new classes of chemical agents that have distinct mechanisms of action and have been shown to be effective for the treatment of cardiovascular (CV) disease (CVD), HF, and type 2 diabetes mellitus (T2D). These drugs can be used either alone or in combination with other antihypertensive and CV drugs. Among these, SGLT2i and valsartan with sacubitril offer new avenues to reduce CVD mortality. SGLT2i have a mild-to-moderate effect on BP lowering with a favorable effect on CV and renal hemodynamics and have been shown to produce a significant reduction in the incidence of major adverse CVD events (as monotherapy or add-on therapy) compared with controls (placebo or non-SGLT2i treatment). Most of the participants in these studies had hypertension (HTN) at baseline and were receiving antihypertensive therapy, including renin-angiotensin system blockers. The combination of valsartan with sacubitril also lowers BP in the short term and has demonstrated a striking reduction in CVD mortality and morbidity in HF patients with a reduced left ventricular ejection fraction. If widely adopted, these novel therapeutic agents hold significant promise for reducing the public health burden posed by HTN and CVD. Based on the results of several clinical trials and considering the high prevalence of HTN and T2D, these new classes of agents have emerged as powerful therapeutic tools in managing and lowering the BP of patients with diabetic kidney disease and HF.

Background: Obesity is common in heart failure with preserved ejection fraction (HFpEF), and a hypocaloric diet can improve functional capacity. Malnutrition, sarcopenia, and frailty are also frequently present, and calorie restriction could harm some patients. Resting metabolic rate (RMR) is an essential determinant of caloric needs; however, it is rarely measured in clinical practice. The accuracy of commonly used predictive equations in HFpEF is unknown. Methods: RMR was measured with indirect calorimetry in 43 patients with HFpEF undergoing right heart catheterization at the University of Michigan, and among 49 participants in the SECRET trial (Study of the Effects of Caloric Restriction and Exercise Training in Patients With Heart Failure and a Normal Ejection Fraction); SECRET patients also had dual-energy X-ray absorptiometry body composition measures. Measured RMR was compared with RMR estimated using the Harris Benedict, Mifflin-St Jeor, World Health Organization, and Academy for Nutrition and Dietetics equations. Results: All predictive equations overestimated RMR (by >10%, P P 2 =0.56). Conclusions: Commonly used predictive equations systematically overestimate measured RMR in patients with HFpEF. Direct measurement of RMR may be needed to effectively tailor dietary guidance in this population. Registration: URL: https://www.clinicaltrials.gov ; Unique Identifier: NCT00959660.

Better risk stratification strategies are needed to enhance clinical care and trial design in heart failure with preserved ejection fraction (HFpEF).The purpose of this study was to assess the value of a targeted plasma multi-marker approach to enhance our phenotypic characterization and risk prediction in HFpEF.In this study, the authors measured 49 plasma biomarkers from TOPCAT (Treatment of Preserved Cardiac Function Heart Failure With an Aldosterone Antagonist) trial participants (n = 379) using a Multiplex assay. The relationship between biomarkers and the risk of all-cause death or heart failure-related hospital admission (DHFA) was assessed. A tree-based pipeline optimizer platform was used to generate a multimarker predictive model for DHFA. We validated the model in an independent cohort of HFpEF patients enrolled in the PHFS (Penn Heart Failure Study) (n = 156).Two large, tightly related dominant biomarker clusters were found, which included biomarkers of fibrosis/tissue remodeling, inflammation, renal injury/dysfunction, and liver fibrosis. Other clusters were composed of neurohormonal regulators of mineral metabolism, intermediary metabolism, and biomarkers of myocardial injury. Multiple biomarkers predicted incident DHFA, including 2 biomarkers related to mineral metabolism/calcification (fibroblast growth factor-23 and OPG [osteoprotegerin]), 3 inflammatory biomarkers (tumor necrosis factor-alpha, sTNFRI [soluble tumor necrosis factor-receptor I], and interleukin-6), YKL-40 (related to liver injury and inflammation), 2 biomarkers related to intermediary metabolism and adipocyte biology (fatty acid binding protein-4 and growth differentiation factor-15), angiopoietin-2 (related to angiogenesis), matrix metalloproteinase-7 (related to extracellular matrix turnover), ST-2, and N-terminal pro-B-type natriuretic peptide. A machine-learning-derived model using a combination of biomarkers was strongly predictive of the risk of DHFA (standardized hazard ratio: 2.85; 95% confidence interval: 2.03 to 4.02; p 0.0001) and markedly improved the risk prediction when added to the MAGGIC (Meta-Analysis Global Group in Chronic Heart Failure Risk Score) risk score. In an independent cohort (PHFS), the model strongly predicted the risk of DHFA (standardized hazard ratio: 2.74; 95% confidence interval: 1.93 to 3.90; p 0.0001), which was also independent of the MAGGIC risk score.Various novel circulating biomarkers in key pathophysiological domains are predictive of outcomes in HFpEF, and a multimarker approach coupled with machine-learning represents a promising strategy for enhancing risk stratification in HFpEF.

The majority of older patients who develop heart failure (HF), particularly older women, have a preserved left ventricular ejection fraction (HFpEF). Patients with HFpEF have severe symptoms of exercise intolerance, poor quality‐of‐life, frequent hospitalizations, and increased mortality. The prevalence of HFpEF is increasing and its prognosis is worsening. However, despite its importance, our understanding of the pathophysiology of HFpEF is incomplete, and drug development has proved immensely challenging. Currently, there are no universally accepted therapies that alter the clinical course of HFpEF. Originally viewed as a disorder due solely to abnormalities in left ventricular (LV) diastolic function, our understanding has evolved such that HFpEF is now understood as a systemic syndrome, involving multiple organ systems, likely triggered by inflammation and with an important contribution of aging, lifestyle factors, genetic predisposition, and multiple‐comorbidities, features that are typical of a geriatric syndrome. HFpEF is usually progressive due to complex mechanisms of systemic and cardiac adaptation that vary over time, particularly with aging. In this review, we examine evolving data regarding HFpEF that may help explain past challenges and provide future directions to care patients with this highly prevalent, heterogeneous clinical syndrome.

PURPOSE: Approximately 5.7 million people in the US are affected by congestive heart failure. This study aimed to quantitatively evaluate cardiothoracic morphology and variability within a cohort of heart failure patients for the purpose of optimally engineering cardiac devices for a variety of heart failure patients. METHODS: Co-registered cardiac-gated and non-gated chest computed tomography (CT) scans were analyzed from 20 heart failure patients (12 males; 8 females) who were primarily older adults (79.5±8.8 years). Twelve cardiothoracic measurements were collected and compared to study sex and left ventricular (LV) ejection fraction (EF) type differences in cardiothoracic morphology. RESULTS: Four measures were significantly greater in males compared to females: LV long-axis length, LV end diastolic diameter (LVEDD) at 50% length of the LV long-axis, the minimal distance between the sternum and heart, and the angle between the LV long-axis and coronal plane. Four measures were significantly greater in patients with reduced EF compared to preserved LV: LV long-axis length, LVEDD at 50% length of the LV long-axis, left ventricular volume normalized by body surface area, and the angle between the mitral valve plane and LV long-axis. CONCLUSIONS: These cardiothoracic morphology measurements are important to consider in the design of cardiac devices for heart failure management (e.g. cardiac pacemakers, ventricular assist devices, and implantable defibrillators), since morphology differs by sex and ejection fraction.

Background The Wake‐Up T2MI Registry is a retrospective cohort study investigating patients with type 2 myocardial infarction (T2MI), acute myocardial injury, and chronic myocardial injury. We aim to explore risk stratification strategies and investigate clinical characteristics, management, and short‐ and long‐term outcomes in this high‐risk, understudied population. Methods From 1 January 2009 to 31 December 2010, 2846 patients were identified with T2MI or myocardial injury defined as elevated cardiac troponin I with at least one value above the 99th percentile upper reference limit and coefficient of variation of 10% (>40 ng/L) and meeting our inclusion criteria. Data of at least two serial troponin values will be collected from the electronic health records to differentiate between acute and chronic myocardial injury. The Fourth Universal Definition will be used to classify patients as having (a) T2MI, (b) acute myocardial injury, or (c) chronic myocardial injury during the index hospitalization. Long‐term mortality data will be collected through data linkage with the National Death Index and North Carolina State Vital Statistics. Results We have collected data for a total of 2205 patients as of November 2018. The mean age of the population was 65.6 ± 16.9 years, 48% were men, and 64% were white. Common comorbidities included hypertension (71%), hyperlipidemia (35%), and diabetes mellitus (30%). At presentation, 40% were on aspirin, 38% on β‐blockers, and 30% on statins. Conclusion Improved characterization and profiling of this cohort may further efforts to identify evidence‐based strategies to improve cardiovascular outcomes among patients with T2MI and myocardial injury.

Background Cannabis is the most commonly used illicit drug in the United States and has been associated with an increased risk of acute coronary syndrome (ACS) in multiple observational studies. Purpose The association of cannabis use with prevalent coronary artery disease (CAD) remains unclear. We hypothesized that cannabis use would also be associated with prevalent CAD among a nationally representative sample of patients. Methods This analysis included 12,543 participants (age 39.3±11.6 years, 48.8% male, 35.3% Caucasians) from the National Health and Nutrition Examination Survey years 2011–2018. Cannabis use was defined by self-report. Prevalent CAD was defined by physician diagnosis. Multivariable logistic regression was used to examine the association between cannabis use and prevalent CAD. The consistency of this association was tested among subgroups stratified by race, gender, tobacco smoking status, and comorbidities. Results In this analysis, 53.1% (n=6,650) of participants were ever-cannabis users and 1.1% (n=137) had prevalent CAD. After adjusting for covariates, ever-cannabis users had a 90% increased odds of prevalent CAD compared to never users (p=0.003). Those who had used cannabis at least once per month for at least one year had a 68% increased odds of prevalent CAD (p Conclusion Cannabis use is associated with prevalent CAD. This association remains consistent after adjusting for traditional cardiovascular disease risk factors. This is a novel finding that underscores the potential harmful effects of cannabis use on cardiovascular health and highlights the need for further controlled studies as the drug becomes more accepted by the general population. Funding Acknowledgement Type of funding sources: None.

Objectives This study assessed for treatment interactions by ejection fraction (EF) subgroup (≥45% [heart failure with preserved ejection fraction (HFpEF); vs Background The REHAB-HF trial showed that an early multidomain rehabilitation intervention improved physical function, frailty, quality-of-life, and depression in older patients hospitalized with acute decompensated heart failure (ADHF). Methods Three-month outcomes were: Short Physical Performance Battery (SPPB), 6-min walk distance (6MWD), and Kansas City Cardiomyopathy Questionnaire (KCCQ). Six-month end points included all-cause rehospitalization and death and a global rank of death, all-cause rehospitalization, and SPPB. Prespecified significance level for interaction was P ≤ 0.1. Results Among 349 total participants, 185 (53%) had HFpEF and 164 (47%) had HFrEF. Compared with HFrEF, HFpEF participants were more often women (61% vs 43%) and had significantly worse baseline physical function, frailty, quality of life, and depression. Although interaction P values for 3-month outcomes were not significant, effect sizes were larger for HFpEF vs HFrEF: SPPB +1.9 (95% CI: 1.1-2.6) vs +1.1 (95% CI: 0.3-1.9); 6MWD +40 meters (95% CI: 9 meters-72 meters) vs +27 (95% CI: −6 meters to 59 meters); KCCQ +9 (2-16) vs +6 (−2 to 14). All-cause rehospitalization rate was nominally lower with intervention in HFpEF but not HFrEF [effect size 0.83 (95% CI: 0.64-1.09) vs 0.99 (95% CI: 0.74-1.33); interaction P = 0.40]. There were significantly greater treatment benefits in HFpEF vs HFrEF for all-cause death [interaction P = 0.08; intervention rate ratio 0.63 (95% CI: 0.25-1.61) vs 2.21 (95% CI: 0.78-6.25)], and the global rank end point (interaction P = 0.098) with benefit seen in HFpEF [probability index 0.59 (95% CI: 0.50-0.68)] but not HFrEF. Conclusions Among older patients hospitalized with ADHF, compared with HFrEF those with HFpEF had significantly worse impairments at baseline and may derive greater benefit from the intervention. (A Trial of Rehabilitation Therapy in Older Acute Heart Failure Patients [REHAB-HF]; NCT02196038 )

Heart failure (HF) with preserved ejection fraction (HFpEF) is the most rapidly increasing form of HF, occurs primarily in older women, and is associated with high rates of morbidity, mortality, and health care expenditures. In the highest age decile (≥90 years old), nearly all patients with HFpEF. As our understanding of the disease has grown in the last few years, we now know that HFpEF is a systemic disorder influenced by aging processes. The involvement of this broad collection of abnormalities in HFpEF, the recognition of the high frequency and impact of noncardiac comorbidities, and systemic, multiorgan involvement, and its nearly exclusive existence in older persons, has led to the recognition of HFpEF as a true geriatric syndrome. Most of the conventional therapeutics used in other cardiac diseases have failed to improve HFpEF patient outcomes significantly. Several recent studies have evaluated exercise training (ET) as a therapeutic management strategy in patients with HFpEF. Although these studies were not designed to address clinical endpoints, such as HF hospitalizations and mortality, they have shown that ET is a safe and effective intervention to improve peak oxygen consumption, physical function, and quality of life in clinically stable HF patients. Recently, a progressive, multidomain physical rehabilitation study among older adults showed that it is feasible in older patients with acute decompensated HF who have high frailty and comorbidities and showed improvement in physical function. However, the lack of Centers for Medicare and Medicaid Services coverage can be a major barrier to formal cardiac rehabilitation in older HFpEF patients. Unfortunately, insistence upon demonstration of mortality improvement before approving reimbursement overlooks the valuable and demonstrated benefits of physical function and life quality.

In a subgroup of 337 participants (mean age 64±9 years; 45% women) from the SPRINT (Systolic Blood Pressure Intervention Trial), where participants were randomly assigned to intensive treatment (target systolic blood pressure P 2 [95% CI, 1.34–1.41] versus 1.48 mm Hg/mL per m 2 [95% CI, 1.44–1.51], P =0.002) compared with standard treatment. No significant between-group differences were observed for aortic distensibility and compliance. We conclude that intensive treatment significantly attenuated increases in carotid-femoral pulse wave velocity and aortic elastance index. Attenuation of increases in aortic stiffness may be one of the mechanisms contributing to the benefit of intensive blood pressure treatment observed in SPRINT. Registration: URL: https://www.clinicaltrials.gov ; Unique identifier: NCT01206062.

Multiple observational studies have demonstrated an association with cannabis use and acute myocardial infarction, especially among young adults. However, little is known about the connection with subclinical or electrocardiographic myocardial injury. We hypothesized that cannabis use would be associated with an increased risk of myocardial injury as defined by the cardiac infarction and/or injury score (CIIS). This analysis included 3,634 (age 48.0 ± 5.9 years, 47.1% male, 68.7% Caucasians) participants from the Third National Health and Examination Survey. Cannabis use was defined by self-report. Those with history of cardiovascular disease were excluded. Myocardial injury was defined as electrocardiographic CIIS ≥ 10. Multivariable logistic regression was used to examine the association between cannabis use and myocardial injury. The consistency of this association was tested among subgroups stratified by race, gender, tobacco smoking status, and comorbidities. About 26.0% (n = 900) of participants were ever-cannabis users and 15.5% (n = 538) had myocardial injury. In a model adjusted for potential confounders, ever-cannabis users had 43% increased odds of myocardial injury compared to never users (Odds ratio (95% confidence interval): 1.43 (1.14, 1.80); p = 0.002). This association was stronger among participants with a history of hypertension versus those without (Odds ratio (95% confidence interval): 1.83 (1.36, 2.47) vs 1.17 (0.83, 1.64), respectively; interaction p value 0.04). Cannabis use is associated with an increased risk of myocardial injury among those without cardiovascular disease with effect modification by co-existent hypertension. These novel findings underscore the harmful effects of cannabis use on cardiovascular health and also merit a personalized risk assessment when counseling patients with hypertension on its use.

This study tested the hypothesis that early left ventricular (LV) relaxation is impaired in older obese patients with heart failure with preserved ejection fraction (HFpEF), and related to decreased peak exercise oxygen uptake (peak V̇o(2)). LV strain and strain rate were measured by feature tracking of magnetic resonance cine images in 79 older obese patients with HFpEF (mean age: 66 yr; mean body mass index: 38 kg/m(2)) and 54 healthy control participants. LV diastolic strain rates were indexed to cardiac preload as estimated by echocardiography derived diastolic filling pressures (E/e′), and correlated to peak V̇o(2). LV circumferential early diastolic strain rate was impaired in HFpEF compared with controls (0.93 ± 0.05/s vs. 1.20 ± 0.07/s, P = 0.014); however, we observed no group differences in early LV radial or longitudinal diastolic strain rates. Isolating myocardial relaxation by indexing all three early LV diastolic strain rates (i.e. circumferential, radial, and longitudinal) to E/e′ amplified the group difference in early LV diastolic circumferential strain rate (0.08 ± 0.03 vs. 0.13 ± 0.05, P < 0.0001), and unmasked differences in early radial and longitudinal diastolic strain rate. Moreover, when indexing to E/e′, early LV diastolic strain rates from all three principal strains, were modestly related with peak V̇o(2) (R = 0.36, −0.27, and 0.35, respectively, all P < 0.01); this response, however, was almost entirely driven by E/e′ itself, (R = −0.52, P < 0.001). Taken together, we found that although LV relaxation is impaired in older obese patients with HFpEF, and modestly correlates with their severely reduced peak exercise V̇o(2), LV filling pressures appear to play a much more important role in determining exercise intolerance. NEW & NOTEWORTHY Using a multimodal imaging approach to uncouple tissue deformation from atrial pressure, we found that left ventricular (LV) relaxation is impaired in older obese patients with HFpEF, but only modestly correlates with their severely reduced peak V̇o(2). In contrast, the data show a much stronger relationship between elevated LV filling pressures and exercise intolerance, refocusing future therapeutic priorities.

Background Heavy alcohol consumption has a well‐established association with hypertension. However, doubt persists whether moderate alcohol consumption has a similar link. This relationship is not well‐studied in patients with diabetes mellitus. We aimed to describe the association of alcohol consumption with prevalent hypertension in participants in the ACCORD (Action to Control Cardiovascular Risk in Diabetes) trial. Methods and Results Alcohol consumption was categorized as none, light (1–7 drinks/week), moderate (8–14 drinks/week), and heavy (≥15 drinks/week). Blood pressure was categorized using American College of Cardiology/American Heart Association guidelines as normal, elevated blood pressure, stage 1 hypertension, and stage 2 hypertension. Multivariable logistic regression was used to explore the association between alcohol consumption and prevalent hypertension. A total of 10 200 eligible participants were analyzed. Light alcohol consumption was not associated with elevated blood pressure or any stage hypertension. Moderate alcohol consumption was associated with elevated blood pressure, stage 1, and stage 2 hypertension (odds ratio [OR], 1.79; 95% CI, 1.04–3.11, P =0.03; OR, 1.66; 95% CI, 1.05–2.60, P =0.03; and OR, 1.62; 95% CI, 1.03–2.54, P =0.03, respectively). Heavy alcohol consumption was associated with elevated blood pressure, stage 1, and stage 2 hypertension (OR, 1.91; 95% CI, 1.17–3.12, P =0.01; OR, 2.49; 95% CI, 1.03–6.17, P =0.03; and OR, 3.04; 95% CI, 1.28–7.22, P =0.01, respectively). Conclusions Despite prior research, our findings show moderate alcohol consumption is associated with hypertension in patients with type 2 diabetes mellitus and elevated cardiovascular risk. We also note a dose‐risk relationship with the amount of alcohol consumed and the degree of hypertension.

Active smoking is a widely accepted risk factor for cardiovascular disease and is recognized as a major public health problem. Passive smoking, also known as secondhand smoke exposure (SHSE), is thought to have similar cardiovascular consequences and the risk has been postulated to be equivalent to that of active smoking. A major component of this risk involves the connection with chronic hypertension. There are several population-based observational studies investigating the relationship between SHSE and chronic hypertension, all of which demonstrate a positive association. Given that SHSE appears to be a risk factor for chronic hypertension, SHSE should also be a risk factor for hypertensive end-organ disease. Many studies have sought to investigate this relationship, but this has yet to be fully elucidated. In this review, we focus on the current evidence regarding the association between SHSE and hypertension as well as exploration of the links between SHSE and hypertensive end-organ damage.

Hypertension heralds the diagnosis of heart failure (HF) with preserved ejection fraction (HFpEF) in 75–85% of cases and shares many of its adverse outcomes as well as its acute and chronic symptoms. This review provides important new data about the pathophysiology and mechanisms that connect hypertension and HFpEF as well as therapy used in both conditions. The traditional model of HFpEF pathophysiology emphasizes the role of hypertension causing increased afterload on the left ventricle (LV), leading to LV hypertrophy (LVH) and subsequent LV diastolic dysfunction. Recent work has provided valuable insights into the mechanisms underlying the transition from hypertension to HFpEF, showing that the pathophysiology extends beyond LVH and diastolic dysfunction. An evolving paradigm suggests that HFpEF is inflammatory in nature with multifactorial pathophysiology, affected by age-related changes and comorbidities. Hypertension shares many of the proinflammatory mechanisms of HFpEF. Furthermore, hypertension precedes HFpEF in the majority of cases. Because of its clinically heterogeneous nature, development of standardized therapies for HFpEF has been challenging. As there are standardized approaches to hypertension, we suggest that similar approaches be used for the treatment of HFpEF, including medical and non-medical therapies. With medical therapies, a treat-to-target blood pressure (BP) strategy could be employed, such as systolic BP

The choice of anticoagulant agents for newly implanted bioprosthetic valve varies significantly, particularly in the presence of postoperative atrial fibrillation with increasing use of nonvitamin K oral anticoagulation (NOACs) in recent years. We reported a challenging case with a coexisting bioprosthetic aortic valve thrombosis and significant anticoagulant-related bleeding. Clinical management strategy and brief literature review were presented.

Abnormal P-wave axis (PWA) has emerged as a novel marker of risk for both cardiovascular disease (CVD) and all-cause mortality (ACM) in the general population, though this relationship has not been adequately explored among those with type 2 diabetes (DM2). We aimed to explore the association between abnormal PWA and ACM among a large, well-phenotyped group of participants with DM2 from the Action to Control Cardiovascular Risk in Diabetes (ACCORD) trial. This analysis included 8899 ACCORD participants with available PWA data on baseline electrocardiogram. Cox proportional hazards models were used to examine the association between PWA and ACM in models adjusted for demographics, ACCORD trial treatment assignment, and potential confounders. PWA was modeled as either normal (0° -75°) or abnormal (0° or75°). Over 44,000 person-years of follow up, there were 609 deaths. Participants with abnormal PWA had increased risk of ACM (HR 1.61, 95% CI 1.25-2.08). After multivariable adjustment, the association remained significant (HR 1.33, 95% CI 1.03-1.72). This relationship was similar in subgroups stratified by age, race, sex, and history of CVD. Among ACCORD trial participants, abnormal PWA was associated with an increased risk of mortality. Abnormal PWA may have added value beyond traditional risk factors in prediction models.

Abnormal P-wave axis may reflect preclinical atrial dysfunction and has been associated with an increased risk of incident atrial fibrillation (AF) in the general population. Patients with diabetes mellitus (DM) have a higher prevalence of AF, but the association of abnormal P-wave axis and the risk of incident AF in those with diabetes has not been previously explored. For this analysis, we included 8,965 eligible participants from the Action to Control Cardiovascular Risk in Diabetes (ACCORD) trial. P-wave axis was automatically measured on study electrocardiogram and visually confirmed, with the normal range being between 0° and 75°. At baseline, 8% of the study population had an abnormal P-wave axis. During 43,856 person-years of follow-up, there were 145 cases of incident AF. Using multivariable-adjusted Cox proportional hazards models, participants with abnormal P-wave axis had an increased risk of incident AF (hazard ratio 2.65, 95% confidence interval 1.76 to 3.99, p < 0.0001). Findings were similar in prespecified subgroups, without evidence of effect modification. Both left- and right-axis deviation of the P-wave were associated with incident AF. Our results suggest that abnormal P-wave axis is associated with incident AF in those with DM and that this relation is conserved in prespecified subgroups. There may be utility in considering P-wave axis values from routine ECGs in these patients.

In older patients (70 ± 7 years) with chronic well-compensated heart failure with preserved ejection and controlled blood pressure, 6 months treatment with aliskiren (direct renin inhibitor) showed non-significant trends for modest improvements in peak exercise oxygen consumption (14.9 ± 0.2 mL kg-1 min-1 versus 14.4 ± 0.2 mL kg-1 min-1; P = .10, trend) and ventilatory anaerobic threshold (888 ± 19 mL/min versus 841 ± 18 mL/min; P = .08).

Heart failure (HF) with preserved ejection fraction (HFpEF) is the most common form of HF. Among elderly women, HFpEF comprises more than 80% of incident HF cases. Adverse outcomes – exercise intolerance, poor quality of life, frequent hospitalizations, and reduced survival – approach those of classic HF with reduced EF (HFrEF). However, despite its importance, our understanding of the pathophysiology of HFpEF is incomplete, and despite intensive efforts, optimal therapy remains uncertain, as most trials to date have been negative. This is in stark contrast to management of HFrEF, where dozens of positive trials have established a broad array of effective, guidelines based therapies that definitively improve a range of clinically meaningful outcomes. In addition to providing an overview of current management status, we examine evolving data that may help explain this paradox, overcome past challenges, provide a roadmap for future success, and that underpin a wave of new trials that will test novel approaches based on these insights.

The majority of older adults who develop heart failure (HF), particularly older women, have a preserved left ventricular ejection fraction (HFpEF). The prevalence of this syndrome is increasing, and the prognosis is not improving, unlike that of HF with reduced ejection fraction (HFrEF). Individuals with HFpEF have severe symptoms of effort intolerance, poor quality of life, frequent hospitalizations, and greater likelihood of death. Despite the importance of HFpEF, there are numerous major gaps in our understanding of its pathophysiology and management. Although it was originally viewed as a disorder due solely to abnormalities in left ventricular diastolic function, our understanding has evolved such that HFpEF is now understood as a systemic syndrome involving multiple organ systems, and it is likely that it is triggered by inflammation and other as-yet-unidentified circulating factors, with important contributions of aging and multiple comorbidities, features generally typical of other geriatric syndromes. We present an update on the pathophysiology, diagnosis, management, and future directions in this disorder in older persons.

Objectives To evaluate the effects of an aldosterone antagonist on exercise intolerance in older adults with heart failure and preserved ejection fraction (HFpEF). Design Randomized, placebo-controlled, double-blind trial. Setting Academic medical center, Winston-Salem, North Carolina. Participants Older adults (N = 80, aged 71 ± 1; 80% female) with stable compensated HFpEF and controlled blood pressure (BP). Measurements Participants were randomized into a 9-month treatment of spironolactone 25 mg/d vs placebo. Assessments were peak exercise oxygen consumption (VO2), 6-minute walk test, Minnesota Living with Heart Failure Questionnaire (MLHFQ), cardiac magnetic resonance imaging, Doppler echocardiography, and vascular ultrasound. Results Seventy-one participants completed the trial: 37 in the spironolactone group and 34 in the placebo group. Adherence according to pill count was excellent (spironolactone 95%, placebo 97%). Mean spironolactone dose was 24.3 ± 2.9 mg/d and was well tolerated. Spironolactone significantly reduced systolic and diastolic BP at rest and peak exercise. At 9-month follow-up, baseline-adjusted peak VO2, the primary outcome, was 13.5 ± 0.3 mL/kg per minute in the spironolactone group versus 13.9 ± 0.3 mL/kg per minute in the placebo group (adjusted mean difference −0.4 mL/kg per minute; 95% confidence interval = −1.1–0.4 mL/kg per minute; P = .38). The 95% confidence intervals of spironolactone's effect on peak VO2 (−8.2% to 3.2%) excluded a clinically significant beneficial effect. There were also no significant differences in 6-minute walk distance, arterial stiffness, left ventricular (LV) mass, LV mass/end-diastolic volume, or MLHFQ score. Conclusion In older adults with stable compensated HFpEF, 9 months of spironolactone 25 mg/d was well tolerated and reduced BP but did not improve exercise capacity, quality of life, LV mass, or arterial stiffness.

Heart failure (HF) with preserved ejection fraction (HFpEF) is the most common form of HF in patients older than 65 years. Among elderly women living in the community, HFpEF comprises nearly 90% of incident HF cases. The health and economic impact of HFpEF is at least as great as that of HF with reduced ejection fraction (HFrEF), with similar severity of acute hospitalization rates and substantial mortality. Despite the importance of HFpEF, our understanding of its pathophysiology is incomplete, and optimal treatment remains largely undefined. Unlike the management of HFrEF, there is a paucity of large evidence-based trials demonstrating morbidity and mortality benefit for the treatment of HFpEF. The agents tested in trials to date, which were based upon an incomplete understanding of the pathophysiology of HFpEF, have not been positive. There is an urgent need to understand HFpEF pathophysiology as well as focus on developing novel therapeutic targets.

This study sought to assess the prevalence of frailty, its associations with physical function, quality of life (QoL), cognition, and depression and to investigate more efficient methods of detection in older patients hospitalized with acute decompensated heart failure (ADHF).In contrast to the outpatient population with chronic HF, much less is known regarding frailty in older, hospitalized patients with ADHF.Older hospitalized patients (N = 202) with ADHF underwent assessment of frailty (using Fried criteria), short physical performance battery (SPPB), 6-min walk test (6-MWT) distance, quality of life (QoL using the Kansas City Cardiomyopathy Questionnaire), cognition (using the Montreal Cognition Assessment), and depression (using the Geriatric Depression Screen [GDS]). The associations of frailty with these patient-centered outcomes were assessed by using adjusted linear regression models. Novel strategies to identify frailty were examined.A total of 50% of older, hospitalized patients with ADHF were frail, 48% were pre-frail, and 2% were non-frail. Female sex, burden of comorbidity, and prior HF hospitalization were significantly associated with higher likelihood of frailty. Frailty (vs. pre-frail status) was associated with a significantly worse SPPB score (5 ± 2.2 vs. 7 ± 2.4, respectively), 6-MWT distance (143 ± 79 m vs. 221 ± 99 m, respectively), QoL (35 ± 19 vs. 46 ± 21, respectively), and more depression (GDS score: 5.5 ± 3.5 vs. 4.2 ± 3.3, respectively) but similar cognition. These associations were unchanged after adjustment for age, sex, race, total comorbidities, and body mass index. Slow gait speed plus low physical activity signaled frailty status as well (C-statistic = 0.85).Ninety-eight percent of older, hospitalized patients with ADHF are frail or pre-frail. Frailty (vs. pre-frail status) is associated with worse physical function, QoL, comorbidity, and depression. The simple 4-m walk test combined with self-reported physical activity may quickly and efficiently identify frailty in older patients with ADHF.

The purpose of this review is to answer the question whether left ventricular hypertrophy (LVH) could be considered a therapeutic target in patients with hypertension. To fulfill this purpose, we briefly outline different methods of measuring LVH, then discuss the current evidence and unresolved controversies regarding the relationships among LVH, blood pressure (BP), and cardiovascular disease (CVD) outcomes. The methods and criteria used for defining LVH in clinical studies lack consistency and are inherently different. Electrocardiogram (ECG) has been the most common method, but some studies used echocardiography, and recently, the cardiac magnetic resonance imaging was used by some studies as well. Regardless of the method, studies have shown that higher BP is a risk factor for LVH, regression of LVH is possible by successful BP lowering, and LVH is associated with CVD outcomes. Nevertheless, recent trials revealed that although intensive BP lowering (systolic BP target of

ObjectiveThe cross-sectional association between accelerometer-measured physical activity (PA), sedentary behaviour (SB) and cardiac structure and function is less well described. This study’s primary aim was to compare echocardiographic measures of cardiac structure and function with accelerometer measured PA and SB.MethodsParticipants included 1206 self-identified Hispanic/Latino men and women, age 45–74 years, from the Echocardiographic Study of Latinos. Standard echocardiographic measures included M-mode, two-dimensional, spectral, tissue Doppler and myocardial strain. Participants wore an Actical accelerometer at the hip for 1 week.ResultsThe mean±SE age for the cohort was 56±0.4 years, 57% were women. Average moderate to vigorous PA (MVPA) was 21±1.1 min/day, light PA was 217±4.2 min/day and SB was 737±8.1 min/day. Both higher levels of light PA and MVPA (min/day) were associated with lower left ventricular (LV) mass index (LVMI)/end-diastolic volume and a lower E/e′ ratio. Higher levels of MVPA (min/day) were associated with better right ventricular systolic function. Higher levels of SB were associated with increased LVMI. In a multivariable linear regression model adjusted for demographics and cardiovascular disease modifiable factors, every 10 additional min/day of light PA was associated with a 0.03 mL/m2 increase in left atrial volume index (LAVI) (p2 increase in LAVI (pConclusionsOur findings highlight the potential positive association between the MVPA and light PA on cardiac structure and function.

Previous trials definitively established that lowering systolic blood pressure (BP) to 140 mmHg prevented heart failure (HF) exacerbations, but the potential benefits and risks of further BP reduction remain unclear due to a paucity of trial-based data. A recent secondary analysis of the Systolic Blood Pressure Intervention Trial (SPRINT) found that in older, high-risk, non-diabetic participants with systolic hypertension, a BP treatment target

Older hospitalized acute decompensated heart failure (HF) patients have persistently poor outcomes and delayed recovery regardless of ejection fraction (EF). We hypothesized that impairments in physical function, frailty, cognition, mood, and quality of life (QoL) potentially contributing to poor clinical outcomes would be similarly severe in acute decompensated HF patients ≥60 years of age with preserved versus reduced EF (HFpEF and HFrEF).In 202 consecutive older (≥60 years) hospitalized acute decompensated HF patients in a multicenter trial, we prospectively performed at baseline: short physical performance battery, 6-minute walk distance, frailty assessment, Geriatric Depression Scale, Montreal Cognitive Assessment, and QoL assessments. Older acute decompensated HFpEF (EF ≥45%, n=96) and HFrEF (EF45%, n=106) patients had similar impairments in all physical function measures (short physical performance battery [5.9±0.3 versus 6.2±0.2]; 6-minute walk distance [184±10 versus 186±9 m]; and gait speed [0.60±0.02 versus 0.61±0.02 m/s]) and rates of frailty (55% versus 52%; P=0.70) and cognitive impairment (77% versus 81%; P=0.56) when adjusted for differences in sex, body mass index, and comorbidities. However, depression and QoL were consistently worse in HFpEF versus HFrEF. Depression was usually unrecognized clinically with 38% having Geriatric Depression Scale ≥5 and no documented history of depression.Patients ≥60 years hospitalized with acute decompensated HF patients have broad, marked impairments in physical function and high rates of frailty and impaired cognition: these impairments are similar in HFpEF versus HFrEF. Further, depression was common and QoL was reduced, and both were worse in HFpEF than HFrEF. Depression was usually unrecognized clinically. These findings suggest opportunities for novel interventions to improve these important patient-centered outcomes.URL: https://www.clinicaltrials.gov . Unique identifier: NCT02196038.

BACKGROUND: Recent studies indicate that excess total body adipose contributes to exercise intolerance in heart failure with preserved ejection fraction (HFpEF). However, the impact of the pattern of regional (abdominal, cardiac, intermuscular) adipose deposition on exercise intolerance in HFpEF is unknown. METHODS: We measured total body (dual-energy x-ray absorptiometry) and regional adipose (magnetic resonance imaging), peak oxygen uptake (peak VO(2)), 6-minute walk distance (6MWD), short physical performance battery (SPPB), and leg press power in 100 older obese HFpEF patients and 61 healthy controls (HC), and adjusted for age, gender, race, and body surface area. RESULTS: Peak VO(2) (15.7±0.4 vs. 23.0±0.6 ml/kg/min; p

Heart failure with preserved ejection fraction (HFpEF) is the most common form of heart failure (HF) in older adults. The primary chronic symptom in patients with HFpEF, even when well compensated, is severe exercise intolerance. Cardiac and peripheral functions contribute equally to exercise intolerance in HFpEF, though the latter has been the focus of fewer studies. Of note, multiple studies with exercise training have shown that exercise intolerance can improve significantly in the absence of improvements in exercise cardiac output, indicating a role of peripheral, non-cardiac adaptations. In addition, clinical drug trials performed to date in HFpEF, all of which have focused on influencing cardiovascular function, have not been positive on primary clinical outcomes and most have not improved exercise capacity. Mounting evidence indicates that sarcopenic obesity, characterized by the coexistence of excess fat mass and decreased muscle mass, could contribute to the pathophysiology of exercise intolerance in older HFpEF patients and may provide avenues for novel treatments.

The majority of elderly patients, particularly women, who have heart failure, have a preserved ejection fraction. Patients with this syndrome have severe symptoms of exercise intolerance, frequent hospitalizations, and increased mortality. Despite the importance of HFpEF, our understanding of its pathophysiology is incomplete, and optimal treatment remains largely undefined. Unlike the management of HFrEF, there is a paucity of large evidence-based trials demonstrating morbidity and mortality benefit for the treatment of HFpEF. There is an urgent need to understand HFpEF pathophysiology as well as focus on developing novel therapeutic targets. We present an update on information regarding pathophysiology, diagnosis, management, and future directions in this important and growing disorder.

Background— Acute decompensated heart failure (ADHF) was a frequent common outcome in SPRINT (Systolic Blood Pressure Intervention Trial). We examined whether there was differential reduction in ADHF events from intensive blood pressure [BP] treatment among the 6 key, prespecified subgroups in SPRINT: age ≥75 years, prior cardiovascular disease, chronic kidney disease, women, black race, and 3 levels of baseline systolic BP (≤132 versus >132 to Methods and Results— ADHF was defined as hospitalization for ADHF, confirmed and formally adjudicated by a blinded events committee using standardized protocols. At 3.29 years follow-up, there were 103 ADHF events (2.2%) among 4683 standard arm participants and 65 ADHF events (1.4%) among 4678 intensive arm participants (Cox proportional hazards ratio, 0.63; 95% confidence interval, 0.46–0.85; P value =0.003). In multivariable analyses, including treatment arm, baseline covariates that were significant predictors for ADHF included chronic kidney disease, cardiovascular disease, age≥75 years, body mass index, and higher systolic BP. The beneficial effect of the intervention on incident ADHF was consistent across all prespecified subgroups. Participants who had incident ADHF had markedly increased risk of subsequent cardiovascular events, including a 27-fold increase ( P Conclusions— Targeting a systolic BP Clinical Trial Registration— URL: http://www.clinicaltrials.gov . Unique identifier: NCT01206062

Cardiologists continue to struggle with the prognosis and significance of low-gradient, severe aortic stenosis (AS) with preserved ejection fraction (EF). Conflicting data makes more substantive decisions challenging. The study aim was to determine the prognosis and significance of severe AS by reviewing index cases from the authors' echocardiography laboratory.The study included 302 patients with AS and with aortic valve area (AVA) ≤1.0 cm2 who were identified from the echocardiography database between 2010 and 2011. AS was subdivided into four types based on AVA and mean pressure gradient (PG): (i) PG-matched, severe AS (AVA ≤1.0 cm2 and mean PG ≥40 mmHg; n = 143); (ii) low-PG, severe AS (AVA ≤1.0 cm2, mean PG40 mmHg, and reduced EF50%; n = 52); (iii) low-PG, severe AS (AVA ≤1.0 cm2, mean PG40 mmHg, preserved EF ≥50%; n = 107); and patients with moderate AS (mean PG25 mmHg and AVA ≥1.0 cm2; n = 104).Among patients medically managed, those with low-PG severe AS and a reduced EF had the worst outcome. Compared to low-PG severe AS with EF ≥50%, patients with a low-PG and severe AS with EF50%, and with matched-PG severe AS, had an increased risk of death (p0.001 and p = 0.052, respectively). For gradient-matched severe AS, those patients who were unoperated had a more than five-fold mortality risk compared to those who underwent surgery [Hazard Ratio (HR): 5; p0.001]. Similarly, among patients with low-PG severe AS with EF ≥50%, those medically managed had a threefold greater mortality risk compared to those who underwent surgery (HR: 3.3; p = 0.002).Patients with low-PG severe AS and a preserved EF have a worse survival than those with moderate AS, but survived better than those with gradient-matched severe AS.

Background Unexplained sudden death is common among patients with sickle cell diseases (SCD). QTc prolongation is a risk factor for fatal arrhythmias among adults. This study sought to identify the predictors for QTc prolongation and determine whether QTc prolongation is associated with increased mortality in patients with SCD. Methods We reviewed the electrocardiograms (EKG) and the transthoracic echocardiograms (TTE) of 140 consecutive adults (>18 years) with SCD from October 1996 to January of 2012. QTc prolongation was categorized into three gender-specific categories based on previous publications. Stepwise regression was performed to evaluate QTc interval and mortality as dependent variables. Hemolytic burden as reflected in laboratory evaluation, diastolic, and systolic TTE variables were included in this model. Results In a stepwise regression analysis, only increased tricuspid regurgitant jet velocity (TRV) (r = 0.483, P = 0.015) had a significant association with QTc interval. Among 49 (35%) patients, the QTc interval was persistently prolonged (PP) (>450 ms in men, >470 ms in women). Twenty-one patients (15%) died over 9 years of follow-up. PP QTc was associated with increased mortality (HR; 8.3 with 95% CI: 2.8–24.6, P

Although the clinical importance of left ventricular noncompaction cardiomyopathy (LVNC) is known, few data exist that describe the prognosis associated with intermediate levels of LV trabeculations that do not meet criteria for LVNC.Trabeculation/possible LVNC by CMR was retrospectively observed among 122 consecutive cases. We assessed the end-systolic noncompacted-to-compacted ratios (ESNCCR) along with deaths, embolic events, congestive heart failure (CHF) readmissions, ventricular arrhythmias, myocardial thickening (MT), and ejection fraction (EF). ESNCCRs were categorized as follows:1, 11.5, 1.52, ≥2. General linear models were used to compare combined events (death, CHF readmission, embolism, ventricular arrhythmia) between categories of ESNCCR. There were 3 models used: model 1: unadjusted; model 2: adjusted for age, race, gender, body surface area, LV ejection fraction, and trabeculated segments; model 3: model 2+adjustment for myocardial thickening.In model 1, those with an ESNCCR1 had a lower association with composite clinical events than those with a ratio between 1.52 and those≥2 (P0.002 and P0.001, respectively). In model 2, the lower association continued, (P=0.009 and P0.001, respectively), but in model 3, those with a ratio from 1.5-2 only had a trend towards a higher association with composite clinical events than those with a ratio1 (P=-0.09). Those with a ratio≥2 continued to have a higher association (P=-0.001).Patients with intermediate trabeculations not meeting criteria for LVNC had a higher association with composite clinical events, but it was mediated by decreased myocardial thickening in the associated compacted layer.

Previous case reports have described patients with left ventricular noncompaction cardiomyopathy (LVNC) with significant mitral regurgitation (MR). The study aim was to determine if LVNC is associated with MR, as assessed by cardiac magnetic resonance imaging (cMRI).LVNC, assessed with cMRI, was observed retrospectively among 122 consecutive cases, 31 of whom had an end-systolic noncompacted-to-compacted ratio (ESNCCR) ≥ 2. In addition, 40 normal subjects undergoing cMRI and 40 with moderate to severe MR were included as controls. Using cine images, the ESNCCR and left ventricular (LV) and right ventricular (RV) stroke volumes were measured. The mitral regurgitant fraction (MRF) was calculated by dividing the difference between the RV and LV stroke volumes by the LV stroke volume. The total papillary muscle (TPM) area was measured from the mid short-axis view. Adjusting for age, race, gender and body surface area, an analysis of covariance was conducted to determine whether MRF and TPM were associated with ESNCCR ≥ 2. Adjusted means were presented with 95% confidence intervals.After adjustment, the MRF in patients with ESNCCR ≥ 2 was higher than in controls, but did not differ from that in patients with significant MR (21 ± 6.5% versus 2.7 ± 12% versus 29.2 ± 11%, p = 0.039 and p = 0.3, respectively). Further, patients with ESNCCR ≥ 2 had a lower TPM than normal controls or those with moderate to severe MR (1.89 ± 0.28 cm2 versus 3.6 ± 0.26 cm2 versus 3.7 ± 0.24 cm2; p0.001 and p0.001, respectively).LVNC is associated with increased MR, as assessed using cMRI. LVNC is also associated with abnormalities in the papillary muscle anatomy, which may predispose to MR.

In 29 patients undergoing percutaneous coronary intervention (PCI), we obtained blood samples at baseline, 10 minutes after standard weight-based abciximab (n=15) or double-bolus eptifibatide (n=14) and 5 minutes after unfractionated heparin (UFH; 70 U/kg bolus). The median percent inhibition was significantly higher in the eptifibatide group compared with the abciximab group both before (96.5% [94-100] vs. 85% [77-89.5] [adenosine diphosphate; ADP]; 89.5% [84-95] vs. 59% [37.5-76.5] [thrombin receptor agonist peptide; TRAP], p

Objectives We sought to evaluate late clinical outcomes following elective percutaneous coronary interventions for saphenous vein graft with planned abciximab use in diabetics. Background Diabetes adversely affects long-term outcomes after percutaneous coronary intervention including percutaneous coronary intervention of saphenous vein grafts. Glycoprotein IIb/IIIa inhibitors reduce adverse outcomes of native vessel percutaneous coronary intervention in diabetics; however, their effects in diabetic patients undergoing percutaneous coronary interventions of saphenous vein grafts is not known. Methods We evaluated 509 elective percutaneous coronary interventions of saphenous vein grafts. Glycoprotein IIb/IIIa inhibitors were used in 99% of the percutaneous coronary interventions. Distal protection devices were not used. Clinical follow-up (mean 30±20 months) was available in 369/397 (93%). Results Overall, procedural success rate was 97% and was similar for diabetics and non-diabetics. Procedural major adverse cardiac events occurred in 4.8% diabetics, and 4.1% non-diabetics ( p =NS). Late outcomes were similar for diabetics and non-diabetics with major adverse cardiac event rates of 57.6%, and 54.9%, respectively, p =NS. Multivariate logistic regression identified graft age and the presence of thrombus as predictors of increased late major adverse cardiac events. Conclusions Following routine use of abciximab, late outcomes after percutaneous coronary interventions of saphenous vein grafts were similar for diabetics and non-diabetics suggesting that the historically observed adverse effect of diabetes on late outcomes after percutaneous coronary interventions of saphenous vein grafts may be attenuated by glycoprotein IIb/IIIa use. Selective use of glycoprotein IIb/IIIa inhibitor should be considered for diabetics undergoing percutaneous coronary interventions of saphenous vein grafts.

Elevation of white blood cells (WBCs) is associated with worse outcomes in patients with coronary artery disease (CAD), including patients undergoing percutaneous coronary intervention (PCI) of native coronary arteries, but this relation has not been studied in patients with saphenous vein graft disease undergoing PCI. A total of 530 patients who underwent PCI of saphenous vein grafts from May 1997 to July 2002 were followed for3 years. Major adverse coronary events (MACEs) were assessed as a composite of death, myocardial infarction, or revascularization during follow-up (mean 2.7 years). Patients with MACEs (n = 287) were younger and had more thrombotic and ostial lesions (p0.05) than those without MACEs (n = 243). The preprocedural WBC count was also significantly higher in the MACE group than in the non-MACE group (8.1 x 10(3)/mul, range 6.6 to 10.1, vs 7.0 x 10(3)/mul, range 5.6 to 8.2; p0.001). After adjusting for covariates, multiple logistic regression analysis revealed the preprocedural WBC count to be an independent predictor for MACEs (odds ratio 1.2; 95% confidence interval 1.1 to 1.3, p0.001). Patients in the highest quartile of the preprocedural WBC level had a significantly increased risk of MACEs (lowest vs highest quartile, 41.3% vs 72.4%; odds ratio 3.7; 95% confidence interval 2.2 to 6.3). Thus, an elevated preprocedural WBC count is associated with increased risk of MACEs in patients undergoing PCI for saphenous vein graft lesions.