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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.

Introduction: Abnormal P-wave axis (PWA) has emerged as a novel marker of risk for both cardiovascular disease and all-cause mortality in the general population, though this relationship has not been adequately explored among those with type 2 diabetes. Hypothesis: We hypothesized that abnormal PWA is associated with all-cause mortality in a large, well-phenotyped group of participants with type 2 diabetes from the Action to Control Cardiovascular Risk in Diabetes (ACCORD) trial. Methods: This analysis included 8,899 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 (75°). We evaluated the predictive value of PWA by comparing area under the receiver operating characteristic curves in models with and without PWA. Results: Over 44,000 person-years, there were 609 deaths. Participants with abnormal PWA had increased risk of all-cause mortality (HR 1.61, 95% CI 1.25 – 2.08). After multivariable adjustment, the association remained significant (HR 1.32, 95% CI 1.02 – 1.71; see TABLE). Inclusion of abnormal PWA in prediction models afforded a small increase in area under the receiver operating characteristic curves (AUC 0.653 vs. 0.643, p-value for difference of 0.002). Conclusions: In conclusion, 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.

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. However, its pathophysiology is poorly understood; thus, the therapeutic options for patients with HFpEF remain limited. A cardinal feature of HFpEF is exercise intolerance, measured objectively as peak exercise oxygen uptake (peak VO2), that results in decreased quality of life. Several recent studies have evaluated exercise training as a therapeutic management strategy in patients with HFpEF. Although these studies were not designed to address clinical end points, such as HF hospitalizations and mortality, they have shown that exercise training is a safe and effective intervention to improve peak VO2 and quality of life in clinically stable HF patients. Of note, studies with exercise training have shown that exercise intolerance can improve in patents with HFpEF through mechanism independent of LV systolic or diastolic function. In this chapter, we will discuss the systemic nature of HFpEF and its role in development and worsening of exercise intolerance, results from completed exercise training trials in HFpEF, mechanisms of benefit, and future directions.

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.

In observational studies, left ventricular mass (LVM) and structure are strong predictors of mortality and cardiovascular events. However, the effect of hypertension treatment on LVM reduction and its relation to subsequent outcomes is unclear, particularly at lower blood pressure (BP) targets. In an ancillary study of SPRINT (Systolic Blood Pressure Intervention Trial), where participants were randomly assigned to intensive BP control (target systolic BP target P =0.368), ejection fraction, or native T1 ( P =0.79), but there was a larger decrease in LVM/end-diastolic volume ratio (−0.04±0.01 versus −0.01±0.01; P =0.002) a measure of concentric LV remodeling. There were fewer cardiovascular events in the intensive control group, but no significant association between the reduced events and change in LVM or any other cardiac magnetic resonance imaging measure. In SPRINT-HEART, contrary to our hypothesis, there were no significant between-group differences in LVM, function, or myocardial T1 at 18-month follow-up. These results suggests that mediators other than these LV measures contribute to the improved cardiovascular outcomes with intensive BP control.

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

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

Recent studies show diabetes mellitus (DM) is an independent risk factor for atrial fibrillation (AF). The P-wave axis (PWA) can be found on electrocardiograms (ECGs); a normal value is between 0 and 75 degrees. New evidence supports an association between abnormal PWA (PWA) and incidence of AF. The

Recent studies continue to highlight the significance and prognosis of silent myocardial infarctions, but few studies identify the burden and significance of myocardial ischemia without symptoms. Patients with positive electrocardiography (ECG) and/or positive echocardiography stress test were

Persistent left superior vena cava (PLSVC) is a rare congenital malformation which results in a right-to-left intracardiac shunt when the left superior vena cava persists and drains into the left atrium. Acute stroke is an unusual presenting symptom. We present a case of PLSVC diagnosed after

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

We appreciate the thoughtful comments by Drs. Goldsmith and Simegn. We agree that a clearer understanding of various heart failure with preserved ejection (HFpEF) phenotypes, such as the 5 phenotypes proposed by Shah et al. [(1)][1] can facilitate advances in understanding and treating this

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.

Introduction: Physical activity (PA) is associated with cardiovascular health benefits including prevention of age related cardiac remodeling, systolic and diastolic dysfunction, and adaptive pro-hypertrophic effect. In this study we aim to measure the associations between PA and LV structure and function in a diverse Hispanic/Latino population. Methods: Participants included 1,818 self-identified Hispanic/Latino men and women, age 45-74 from the Echocardiographic Study of Latinos (ECHO-SOL). Standard echo measures included M-mode, two-dimensional (2-D), spectral, tissue Doppler and color flow. Participants wore an Actical hip accelerometer for 1 week. Multivariable regression models were completed to relate PA to echocardiographic parameters. Results: The mean ± SE age for the cohort was 56 ±0.4, 57% were female, the prevalence of diabetes was 28%, hypertension 50%, hypercholesterolemia 49%, and coronary heart disease 7%. Average moderate to vigorous PA (MVPA) was 20.9 ± 1.1 min/day and sedentary time ±SE was 736.5 ± 8.1 min/day. In multivariable models adjusted for age, gender, diabetes, hypertension, hypercholesterolemia, coronary heart disease, alcohol and cigarette use we found the following: left atrium volume index (LAVI) decrease by quartiles of MVPA (p-value Conclusion: MVPA was significantly associated with lower LAVI. There was also a significant association with sedentary behavior. Our findings illustrate the complex relationship between PA, sedentary time and cardiac structure and function.

This is a case of a 48-year-old man who presented with a pulmonary embolism and was found to have left ventricular non-compaction cardiomyopathy. Initial echocardiograms demonstrated prominent apical trabeculations with reduced biventricular function. These findings were further confirmed and characterized by cardiac magnetic resonance imaging. He met all major criteria used to identify left ventricular non-compaction cardiomyopathy. He underwent medical management for heart failure and during follow-up was noted to have significant improvement in left ventricular systolic function and symptoms. While most management attention is focused on rhythm disturbances or embolic risk, particular attention should also be exercised to ensure that heart failure medical therapy is optimized. While many with left ventricular non-compaction cardiomyopathy have irreversible dysfunction, this case highlights that there may be some who will respond well to aggressive medical therapy. The diagnosis and medical management of left ventricular non-compaction cardiomyopathy are reviewed in light of our patient and his clinical course.

Heart failure (HF) with preserved ejection fraction (HFpEF) is the most common form of HF. Approximately 90% of new HF cases in older women are HFpEF.1 Adverse outcomes – exercise intolerance, poor quality of life, frequent hospitalizations, and reduced survival – approach those of HF with reduced EF (HFrEF). In contrast to HFrEF, the prevalence of HFpEF is increasing and its prognosis is worsening.2 Despite the strong public health importance of HFpEF, its pathogenesis is poorly understood. Our lack of understanding of HFpEF and its treatment is punctuated by the fact that 6 large, well-designed, randomized, clinical trials and several smaller ones were all neutral on their primary outcomes. The combination of high prevalence and lack of evidence-based treatments makes HFpEF a high-priority topic for research in cardiovascular disease. Article see p 550 A glaring absence among HFpEF studies has been a systematic autopsy-based study. Such studies have become more difficult as autopsy rates have declined with the availability of advanced multimodality imaging and deep-tissue biopsy techniques. Despite the increasing array of modern research techniques, postmortem methods continue to be uniquely valuable because of the ability to perform comprehensive, in-depth, detailed examinations of tissues and organs in humans. In this issue of Circulation , Mohammed and colleagues3 at the Mayo Clinic fill this critical gap with the first autopsy series of HFpEF. From a tissue registry patiently accumulated over a period of 19 years, their multidisciplinary team methodically collected and comprehensively analyzed specimens, medical records, electrocardiograms, and echocardiograms from 255 individuals, including patients with premortem diagnosis of HFpEF (n=124) and HFrEF (n=27), and from age-matched case controls who died of noncardiovascular causes (n=104). Characteristics of the HFpEF patients were relatively similar to community-based reports, including advanced age and a high prevalence of common comorbidities, including hypertension, diabetes …

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

Heart failure with preserved ejection fraction (HFpEF) is the most common form of HF in the population.1 Among elderly women living in the community, HFpEF comprises nearly 90% of incident HF cases.2 Furthermore, HFpEF is increasing out of proportion to HF with reduced EF (HFrEF), and its prognosis is worsening while that of HFrEF is improving.3 The health and economic impact of HFpEF is at least as great as that of HFrEF, with similar severity of chronic exercise intolerance,4 acute hospitalization rates3,5 and substantial mortality.3

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.

Background: Decision of intervention for low gradient severe aortic stenosis (AS) with normal left ventricular ejection fraction (LVEF) is clinically challenging. The study was to determine the impact of stroke volume index (SVi) on prognosis in patients (pts) with AS. Methods: We examined 410 pts with moderate or severe AS and normal EF (≥50%). Pts were divided into four groups based on aortic valve area (AVA), mean pressure gradient (MPG) and SVi: Group I: low flow low gradient severe AS (AVA≤1.0cm 2 , MPG2 , n=75); Group II: normal flow low gradient severe AS (AVA≤1.0cm 2 , MPG2 , n=97); Group III: severe AS with matched gradient-AVA (AVA≤1.0cm 2 and MPG≥40mmHg, n=88); Group IV: moderate AS (AVA>1.0cm 2 and MPG>20mmHg, Results: Group I had higher prevalence of atrial fibrillation, more pronounced LV hypertrophy, lower SVi, smaller AVA, higher valvuloarterial impedance (Zva) (Table) and lower 3-year cumulative survival compared to Group II and Group IV (61% vs. 75% and 80%, p=0.004). Group II had a 3-year cumulative survival similar to moderate AS (75% vs. 80%, p>0.05). In pts with medical management, Group I and Group III had lower 3-year cumulative survival in comparison with Group II and Group IV (48% and 56% vs. 73% and 76%, p=0.001). Multivariate analysis showed SVi was a strong predictor of mortality in low gradient severe AS (HR 0.95, CI: 0.91-0.99, P=0.02). However, in gradient-AVA matched severe AS and moderate AS, SVi was not associated with mortality (p>0.05). Conclusions: Without AS intervention, low flow low gradient severe AS with normal EF carries poor prognosis similar to high gradient AS, but normal flow low gradient AS does not, suggesting that SVi may be used to identify the pts benefiting most from AS intervention in pts with low gradient AS.

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.

Most measures of LV noncompaction cardiomyopathy (LVNC) are acquired from 2-D assessments. This study describes the changes in trabeculated volume during the cardiac cycle and its relationship to events related to LVNC. We retrospectively identified 122 cases of cardiac magnetic resonance with

Heart failure (HF) with preserved ejection fraction (HFpEF) is the most common form of HF in older adults, and is increasing in prevalence as the population ages. Furthermore, HFpEF is increasing out of proportion to HF with reduced EF (HFrEF), and its prognosis is worsening while that of HFrEF is improving. Despite the importance of HFpEF, our understanding of its pathophysiology is incomplete, and optimal treatment remains largely undefined. A cardinal feature of HFpEF is reduced exercise tolerance, which correlates with symptoms as well as reduced quality of life. The traditional concepts of exercise limitations have focused on central dysfunction related to poor cardiac pump function. However, the mechanisms are not exclusive to the heart and lungs, and the understanding of the pathophysiology of this disease has evolved. Substantial attention has focused on defining the central versus peripheral mechanisms underlying the reduced functional capacity and exercise tolerance among patients with HF. In fact, physical training can improve exercise tolerance via peripheral adaptive mechanisms even in the absence of favorable central hemodynamic function. In addition, the drug trials performed to date in HFpEF that have focused on influencing cardiovascular function have not improved exercise capacity. This suggests that peripheral limitations may play a significant role in HF limiting exercise tolerance, a hallmark feature of HFpEF.

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.