Cardiometabolic Syndrome and Increased Risk of Heart Failure.

Approximately 50 % of patients with heart failure have diastolic heart failure (HFPEF) with the major predisposing risk factors age, inactivity, obesity, insulin resistance (IR), type-2 diabetes, and hypertension. The prognosis of HFPEF is comparable to that of systolic heart failure, but without any specific or effective treatment. This review presents a biomathematically corrected diagnostic approach for quantification of diastolic dysfunction (DD) via the age dependency of diastolic function. Pathophysiological mechanisms for DD in the cardiometabolic syndrome (CMS) are mainly based on downstream effects of IR including insufficient myocardial energy supply. The second section discusses therapeutic strategies for the control and therapy of CMS, IR, and the associated DD/HFPEF with a focus on dietary therapy that is independent of weight loss but improves all manifestations of the CMS and reduces cardiovascular risk.

Hospital utilization in adults with single ventricle congenital heart disease and cardiac arrhythmias.

OBJECTIVES: The study sought to identify the impact of cardiac arrhythmias on hospitalizations in adults with single ventricle (SV) congenital heart disease (CHD). BACKGROUND: Surgical advances have dramatically improved survival in patients with CHD. Cardiac arrhythmias and sudden cardiac death are common in adults with CHD. METHODS AND RESULTS: Data from 43 pediatric hospitals in the 2004 to 2011 Pediatric Health Information System database were used to identify patients ≥18 years of age admitted with International Classification of Diseases-9th Revision codes for a diagnosis of either hypoplastic left heart syndrome (HLHS), tricuspid atresia (TA) or common ventricle (CV), and a cardiac arrhythmia. Primary and secondary diagnoses, length of stay (LOS), hospital charges, and interventional procedures were determined. Multilevel models were used to evaluate differences in demographics, diagnoses, and clinical outcomes among the 3 subgroups (HLHS, TA, and CV). Interactions of charges with arrhythmia and admission year were examined using ANOVA. There were 642 admissions in 424 patients with SV CHD and an arrhythmia diagnosis. A single arrhythmia diagnosis was present in 454 admissions (71%). Total hospital charges were $80.7 million with mean charge per admission of $127,296 ± 243,094. The mean charge per hospital day was $16,653 ± 17,516 and increased across the study period (P < 0.01). Arrhythmia distributions were impacted by SV anatomic subtype (P < 0.001). Hospital resource utilization was significantly different among arrhythmia groups (P < 0.001). CONCLUSIONS: In adults with SV CHD, arrhythmias are affected by SV anatomic subtype and impact adversely upon hospital resource utilization.

Longitudinal strain in Friedreich Ataxia: a potential marker for early left ventricular dysfunction.

BACKGROUND: Friedreich's ataxia (FRDA) is a neurodegenerative disorder resulting from deficiency of frataxin, characterized by cardiac hypertrophy associated with heart failure and sudden cardiac death. However, the relationship between remodeling and novel measures of cardiac function such as strain, and the time-dependent changes in these measures are poorly defined. METHODS AND RESULTS: We compared echocardiographic parameters of cardiac size, hypertrophy, and function in 50 FRDA patients with 50 normal controls and quantified the following measures of cardiac remodeling and function: left ventricular (LV) volumes, mass, relative wall thickness (RWT), ejection fraction (EF), and myocardial strain. Linear regression analysis was used to identify significant differences in echocardiographic parameters in FRDA compared with normal subjects. In analyses adjusted for age, sex, and body surface area, significant differences were observed between parameters of remodeling (LV mass, RWT, and volumes) and function in FRDA patients compared with controls. In particular, longitudinal strain was significantly decreased in FRDA patients compared with controls (-12.4% vs. -16.0%, P < 0.001), despite similar and normal left ventricular ejection fraction (LVEF). Over 3 years of follow-up, there was no change in strain, LV size, LV mass, or LVEF among FRDA patients. CONCLUSION: Longitudinal strain is reduced in FRDA despite normal LVEF, indicative of subclinical cardiac dysfunction. Given late declines in LVEF in FRDA, longitudinal strain may provide an earlier index of myocardial dysfunction in FRDA.

Long-term impact of cardiac resynchronization therapy in mild heart failure: 5-year results from the REsynchronization reVErses Remodeling in Systolic left vEntricular dysfunction (REVERSE) study.

BACKGROUND: The benefit of cardiac resynchronization therapy (CRT) among patients with mild heart failure (HF), reduced left ventricular (LV) function and wide QRS is well established. We studied the long-term stability of CRT. METHODS: REVERSE was a randomized, double-blind study on CRT in NYHA Class I and II HF patients with QRS ≥120 ms and left ventricular ejection fraction (LVEF) ≤40%. After the randomized phase, all were programmed to CRT ON and prospectively followed through 5 years for functional capacity, echocardiography, HF hospitalizations, mortality, and adverse events. We report the results of the 419 patients initially assigned to CRT ON. FINDINGS: The mean follow-up time was 54.8 ± 13.0 months. After 2 years, the functional and LV remodelling improvements were maximal. The 6-min hall walk increased by 18.8 ± 102.3 m and the Minnesota and Kansas City scores improved by 8.2 ± 17.8 and 8.2 ± 17.2 units, respectively. The mean decrease in left ventricular end-systolic volume index and left ventricular end-diastolic volume index was 23.5 ± 34.1 mL/m(2) (P < 0.0001) and 25.4 ± 37.0 mL/m2 (P < 0.0001) and the mean increase in LVEF 6.0 ± 10.8% (P < 0.0001) with sustained improvement thereafter. The annualized and 5-year mortality was 2.9 and 13.5% and the annualized and 5-year rate of death or first HF hospitalization 6.4, and 28.1%. The 5-year LV lead-related complication rate was 12.5%. CONCLUSION: In patients with mild HF, CRT produced reverse LV remodelling accompanied by very low mortality and need for heart failure hospitalization. These effects were sustained over 5 years. Cardiac resynchronization therapy in addition to optimal medical therapy produces long-standing clinical benefits in mild heart failure. CLINICAL TRIAL REGISTRATION: Clinicaltrials.gov identifier NCT00271154.

Effect of QRS duration and morphology on cardiac resynchronization therapy outcomes in mild heart failure: results from the Resynchronization Reverses Remodeling in Systolic Left Ventricular Dysfunction (REVERSE) study.

BACKGROUND: Cardiac resynchronization therapy (CRT) decreases mortality, improves functional status, and induces reverse left ventricular remodeling in selected populations with heart failure. We aimed to assess the impact of baseline QRS duration and morphology and the change in QRS duration with pacing on CRT outcomes in mild heart failure. METHODS AND RESULTS: Resynchronization Reverses Remodeling in Systolic Left Ventricular Dysfunction (REVERSE) was a multicenter randomized trial of CRT among 610 patients with mild heart failure. Baseline and CRT-paced QRS durations and baseline QRS morphology were evaluated by blinded core laboratories. The mean baseline QRS duration was 151±23 milliseconds, and 60.5% of subjects had left bundle-branch block (LBBB). Patients with LBBB experienced a 25.3-mL/m(2) mean reduction in left ventricular end-systolic volume index (P<0.0001), whereas non-LBBB patients had smaller decreases (6.7 mL/m(2); P=0.18). Baseline QRS duration was also a strong predictor of change in left ventricular end-systolic volume index with monotonic increases as QRS duration prolonged. Similarly, the clinical composite score improved with CRT for LBBB subjects (odds ratio, 0.530; P=0.0034) but not for non-LBBB subjects (odds ratio, 0.724; P=0.21). The association between clinical composite score and QRS duration was highly significant (odds ratio, 0.831 for each 10-millisecond increase in QRS duration; P<0.0001), with improved response at longer QRS durations. The change in QRS duration with CRT pacing was not an independent predictor of any outcomes after correction for baseline variables. CONCLUSION: REVERSE demonstrated that LBBB and QRS prolongation are markers of reverse remodeling and clinical benefit with CRT in mild heart failure. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifier: NCT00271154.

Randomized controlled trial comparing simultaneous versus optimized sequential interventricular stimulation during cardiac resynchronization therapy.

BACKGROUND: Cardiac resynchronization therapy (CRT) reduces morbidity and mortality and improves symptoms in patients with systolic heart failure (HF) and ventricular dyssynchrony. This randomized, double-blind, controlled study evaluated whether optimizing the interventricular stimulating interval (V-V) to sequentially activate the ventricles is clinically better than simultaneous V-V stimulation during CRT. METHODS: Patients with New York Heart Association (NYHA) III or IV HF, meeting both CRT and implantable cardioverter-defibrillator indications, randomly received either simultaneous CRT or CRT with optimized V-V settings for 6 months. Patients also underwent echocardiography-guided atrioventricular delay optimization to maximize left ventricular filling. The V-V optimization involved minimizing the left ventricular septal to posterior wall motion delay during CRT. The primary objective was to demonstrate noninferiority using a clinical composite end point that included mortality, HF hospitalization, NYHA functional class, and patient global assessment. Secondary end points included changes in NYHA classification, 6-minute hall walk distance, quality of life, peak VO(2), and event-free survival. RESULTS: The composite score improved in 75 (64.7%) of 116 simultaneous patients and in 92 (75.4%) of 122 optimized patients (P < .001, for noninferiority). A prespecified test of superiority showed that more optimized patients improved (P = .03). New York Heart Association functional class improved in 58.0% of simultaneous patients versus 75.0% of optimized patients (P = .01). No significant differences in exercise capacity, quality of life, peak VO(2), or HF-related event rate between the 2 groups were observed. CONCLUSIONS: These findings demonstrate modest clinical benefit with optimized sequential V-V stimulation during CRT in patients with NYHA class III and IV HF. Optimizing V-V timing may provide an additional tool for increasing the proportion of patients who respond to CRT.

Left ventricular remodeling in human heart failure: quantitative echocardiographic assessment of 1,794 patients.

BACKGROUND: The left ventricle (LV) undergoes significant architectural remodeling in heart failure (HF). However, the fundamental associations between cardiac function and LV size and performance have not been thoroughly characterized in this population. We sought to define the adaptive remodeling that occurs in chronic human HF through the detailed analyses of a large quantitative echocardiography database. METHODS: Baseline echocardiograms were performed in 1,794 patients with HF across a broad range of ejection fraction (EF), from less than 10% to greater than 70%. Core lab measurements of LV volumes and length were made, from which EF, mass, sphericity indices, stroke volume (SV), and stroke work were derived. Spearman correlation coefficients and linear regression methods were used to determine the relationships between remodeling parameters. RESULTS: The median EF was 28.6% (IQR 21.9-37.0). Across a multitude of parameters of cardiac structure and function, indexed end-systolic volumes (ESVs) explained the greatest proportion of the variance in EF (R =-0.87, P < 0.0001). Systolic sphericity index and LV mass were also strongly correlated with EF (R =-0.62 and -0.63, P < 0.0001), reflective of the alterations in LV shape and size that occur as EF declines. SV was rigorously maintained across a broad spectrum of EF, until the EF fell below 20%, at which point SV decreased significantly (P < 0.0001). CONCLUSIONS: In chronic HF, the LV undergoes extensive structural adaptive remodeling in order to maintain SV across a broad range of EF. However, when the EF falls below 20%, further modulation of SV is no longer possible through alterations in ventricular architecture.

Conjoined hearts in thoracopagus twins.

This study aimed to identify the anatomic and pathologic structural cardiac abnormalities in conjoined twins and to focus on those that have prevented the successful separation of conjoined hearts. A retrospective review was undertaken to examine consecutive cases of thoracopagus conjoined twins with conjoined hearts evaluated at The Children's Hospital of Philadelphia from 1 January 1980 through 6 October 2008. The records included autopsy and surgical findings as well as clinical reports. The study group included nine sets of conjoined twins with a mean gestational age at birth of 33.8 ± 5.5 weeks. Three twin pairs were stillborn. Five twin pairs died afterward. One pair died of cardiopulmonary failure. The median age at death was 22 days (range, 0-345 days). Major congenital heart disease was present in 94.4% (17/18) of the hearts, and 72.2% (13/18) of the hearts had single-ventricle physiology. Total anomalous pulmonary venous return occurred in 39% (7/18) of the cases. The clinical outcome for thoracopagus twins with conjoined hearts remains poor because of inability to separate conjoined and single ventricles. Surgical nonintervention and palliative care should be strongly considered for these patients.

Assessment of ventricular remodeling in heart failure clinical trials.

Adverse remodeling involves a complicated process of structural and functional changes in the left ventricle (LV). LV remodeling is progressive and, if left unchecked, culminates in heart failure that portends a poor prognosis. Clinical trials in heart failure have employed various techniques to assess ventricular remodeling while focusing on therapeutic-specific strategies to halt or reverse remodeling. These strategies include (1) those designed to reduce wall stress by limiting LV dilatation and reducing LV loading conditions (nitrates and epicardial restraint), (2) those designed to block neurohormonal activation, including angiotensin converting enzyme inhibitors, angiotensin receptor blockers, ß-adrenergic receptor blockers, and aldosterone receptor blockers, (3) ionotropic agents/cardiac glycosides, and (4) cardiac resynchronization therapy. Strategies in development include mechanical assist devices and myocardial regeneration. To date, trials have demonstrated a linkage between indices of remodeling and clinical outcomes measures. Indices of remodeling have facilitated identification of targets for novel pharmaceutical agents and new device therapies.

Tricuspid annular plane systolic excursion and response to cardiac resynchronization therapy: results from the REVERSE trial.

BACKGROUND: The aims of this study were to evaluate tricuspid annular plane systolic excursion (TAPSE) as a predictor of left ventricular (LV) reverse remodeling and clinical benefit of cardiac synchronization therapy (CRT) and to evaluate the effect of CRT on TAPSE in patients with mildly symptomatic systolic heart failure as a substudy of the REsyncronization reVErses Remodeling in Systolic left vEntricular dysfunction (REVERSE) trial. METHODS AND RESULTS: Patients (n = 450) were randomized in a 2:1 fashion to CRT ON or CRT OFF and followed for 12 months. End points were reverse LV remodeling defined as a reduction in LV end-systolic volume of ≥20 mL/m(2) by echocardiography and a clinical composite score, defined as freedom from clinical deterioration. TAPSE was an independent predictor of reverse remodeling, OR = 1.08 (95% CI 1.03-1.14) per mm increase and a favorable clinical composite score, OR = 1.08 (95% CI 1.02-1.14). No significant interactions were observed between TAPSE and CRT ON. CRT ON was not associated with a significant effect on TAPSE compared to CRT OFF, -0.8 ± 4.7 vs. 0.3 ± 5 mm, P = .06. CONCLUSION: TAPSE is an independent predictor of clinical response and improved reverse remodeling in patients with mildly symptomatic heart failure. The effect of CRT is not modified by TAPSE in the present population. CRT is not associated with a clinically significant effect on TAPSE.

The utility of prescreening transesophageal echocardiograms: a prospective study.

BACKGROUND: Recent emphasis on the judicious use of imaging prompted the publication of the 2007 ACC/ASE Appropriateness Use Criteria (AUC) for Echocardiography. However, the intersection of the AUC with the safety and clinical use of transesophageal echocardiography (TEE) is not well established. METHODS: We reviewed 490 consecutive orders for TEEs for appropriateness, significant findings, and reasons for cancellation. RESULTS: We found that 79% (389/490) of ordered studies were performed and 21% (101/490) were not. The number of TEEs cancelled for safety reasons (n = 29) was similar to that cancelled for inappropriateness (n = 36). Only 2% (6/389) of those performed were inappropriate vs. 16% of those that were cancelled. New or unsuspected findings were obtained in half of all performed TEEs; the majority of which were ordered to detect cardiac source of embolism (CSE). CONCLUSIONS: The AUC should specifically consider the utility of clinician-based prescreening of TEEs to encourage appropriate use and safety. Furthermore, given the incremental value of TEE over transthoracic echocardiography in detection of CSE, in some cases, TEE may be considered an appropriate initial test for this indication.

Impact of diabetes on postinfarction heart failure and left ventricular remodeling.

Diabetes mellitus, the metabolic syndrome, and the underlying insulin resistance are increasingly associated with diastolic dysfunction and reduced stress tolerance. The poor prognosis associated with heart failure in patients with diabetes after myocardial infarction is likely attributable to many factors, important among which is the metabolic impact from insulin resistance and hyperglycemia on the regulation of microvascular perfusion and energy generation in the cardiac myocyte. This review summarizes epidemiologic, pathophysiologic, diagnostic, and therapeutic data related to diabetes and heart failure in acute myocardial infarction and discusses novel perceptions and strategies that hold promise for the future and deserve further investigation.

Mesenchymal cell transplantation and myocardial remodeling after myocardial infarction.

BACKGROUND: Targeted delivery of mesenchymal precursor cells (MPCs) can modify left ventricular (LV) cellular and extracellular remodeling after myocardial infarction (MI). However, whether and to what degree LV remodeling may be affected by MPC injection post-MI, and whether these effects are concentration-dependent, remain unknown. METHODS AND RESULTS: Allogeneic MPCs were expanded from sheep bone marrow, and direct intramyocardial injection was performed within the borderzone region 1 hour after MI induction (coronary ligation) in sheep at the following concentrations: 25x10(6) (25 M, n=7), 75x10(6) (75 M, n=7), 225x10(6) (225 M, n=10), 450x10(6) (450 M, n=8), and MPC free media only (MI Only, n=14). LV end diastolic volume increased in all groups but was attenuated in the 25 and 75 M groups. Collagen content within the borderzone region was increased in the MI Only, 225, and 450 M groups, whereas plasma ICTP, an index of collagen degradation, was highest in the 25 M group. Within the borderzone region matrix metalloproteinases (MMPs) and MMP tissue inhibitors (TIMPs) also changed in a MPC concentration-dependent manner. For example, borderzone levels of MMP-9 were highest in the 25 M group when compared to the MI Only and other MPC treatment group values. CONCLUSIONS: MPC injection altered collagen dynamics, MMP, and TIMP levels in a concentration-dependent manner, and thereby influenced indices of post-MI LV remodeling. However, the greatest effects with respect to post-MI remodeling were identified at lower MPC concentrations, thus suggesting a therapeutic threshold exists for this particular cell therapy.

Cardiac resynchronization induces major structural and functional reverse remodeling in patients with New York Heart Association class I/II heart failure.

BACKGROUND: Cardiac resynchronization therapy (CRT) improves LV structure, function, and clinical outcomes in New York Heart Association class III/IV heart failure with prolonged QRS. It is not known whether patients with New York Heart Association class I/II systolic heart failure exhibit left ventricular (LV) reverse remodeling with CRT or whether reverse remodeling is modified by the cause of heart failure. METHODS AND RESULTS: Six hundred ten patients with New York Heart Association class I/II heart failure, QRS duration > or =120 ms, LV end-diastolic dimension > or =55 mm, and LV ejection fraction < or =40% were randomized to active therapy (CRT on; n=419) or control (CRT off; n=191) for 12 months. Doppler echocardiograms were recorded at baseline, before hospital discharge, and at 6 and 12 months. When CRT was turned on initially, immediate changes occurred in LV volumes and ejection fraction; however, these changes did not correlate with the long-term changes (12 months) in LV end-systolic (r=0.11, P=0.31) or end-diastolic (r=0.10, P=0.38) volume indexes or LV ejection fraction (r=0.07, P=0.72). LV end-diastolic and end-systolic volume indexes decreased in patients with CRT turned on (both P<0.001 compared with CRT off), whereas LV ejection fraction in CRT-on patients increased (P<0.0001 compared with CRT off) from baseline through 12 months. LV mass, mitral regurgitation, and LV diastolic function did not change in either group by 12 months; however, there was a 3-fold greater reduction in LV end-diastolic and end-systolic volume indexes and a 3-fold greater increase in LV ejection fraction in patients with nonischemic causes of heart failure. CONCLUSIONS: CRT in patients with New York Heart Association I/II resulted in major structural and functional reverse remodeling at 1 year, with the greatest changes occurring in patients with a nonischemic cause of heart failure. CRT may interrupt the natural disease progression in these patients. Clinical Trial Registration- Clinicaltrials.gov Identifier: NCT00271154.

Time-varying myocardial stress and systolic pressure-stress relationship: role in myocardial-arterial coupling in hypertension.

BACKGROUND: Myocardial afterload depends on left ventricular (LV) cavity size, pressure, and wall thickness, all of which change markedly throughout ejection. We assessed the relationship between instantaneous ejection-phase pressure and myocardial stress and the effect of arterial wave reflections on myocardial stress in hypertensive and normotensive adults. METHODS AND RESULTS: We studied 42 untreated hypertensive, 42 treated hypertensive, and 42 normotensive adults with normal LV ejection fraction. Time-resolved central pressure, flow, and LV geometry were measured with carotid tonometry, Doppler, and speckle-tracking echocardiography for computation of arterial load and time-varying circumferential and longitudinal myocardial stress. In all 3 groups, peak myocardial stress typically occurred in early systole (within the first 100 milliseconds of ejection), followed by a marked midsystolic shift in the pressure-stress relationship, which favored lower late systolic stress values (P<0.001) relative to pressure. The mean magnitude of this midsystolic shift was quantitatively important in all 3 groups (circumferential stress, 144 to 148 kdynes/cm(2)) and was independently predicted by a higher LV ejection fraction and ratio of LV end-diastolic cavity to wall volume. Time of peak myocardial stress independently correlated with time of the first systolic but not with time of the second systolic central pressure peak. CONCLUSIONS: Peak myocardial stress occurs in early systole, before important contributions of reflected waves to central pressure. In the presence of normal LV ejection fraction, a midsystolic shift in the pressure-stress relationship protects cardiomyocytes against excessive late systolic stress (despite pressure augmentation associated with wave reflections), a coupling mechanism that may be altered in various disease states.

Arterial pulsatile hemodynamic load induced by isometric exercise strongly predicts left ventricular mass in hypertension.

Although resting hemodynamic load has been extensively investigated as a determinant of left ventricular (LV) hypertrophy, little is known about the relationship between provoked hemodynamic load and the risk of LV hypertrophy. We studied central pressure-flow relations among 40 hypertensive and 19 normotensive adults using carotid applanation tonometry and Doppler echocardiography at rest and during a 40% maximal voluntary forearm contraction (handgrip) maneuver. Carotid-femoral pulse wave velocity (CF-PWV) was measured at rest. Hypertensive subjects demonstrated various abnormalities in resting and induced pulsatile load. Isometric exercise significantly increased systemic vascular resistance, aortic characteristic impedance (Zc), induced earlier wave reflections, increased augmentation index, and decreased total arterial compliance (TAC; all P < or = 0.01). In hypertensive subjects, CF-PWV was the strongest resting predictor of LV mass index (LVMI) and remained an independent predictor after adjustment for age, gender, systemic vascular resistance, reflection magnitude, aortic Zc, and TAC (beta = 2.52 m/s; P < 0.0001). Age, sex, CF-PWV, and resting hemodynamic indexes explained 48% of the interindividual variability in LVMI. In stepwise regression, TAC (beta = -17.85; P < 0.0001) during handgrip, Zc during handgrip (beta = -150; P < 0.0001), and the change in the timing of wave reflections during handgrip (beta = -0.63; P = 0.03) were independent predictors of LVMI. A model that included indexes of provoked hemodynamic load explained 68% of the interindividual variability in LVMI. Hemodynamic load provoked by isometric exercise strongly predicts LVMI in hypertension. The magnitude of this association is far greater than for resting hemodynamic load, suggesting that provoked testing captures important arterial properties that are not apparent at rest and is advantageous to assess dynamic arterial load in hypertension.

Familial occurrence of peripartum cardiomyopathy presages a genetic rather than an environmental cause.

Peripartum cardiomyopathy (PPCM) is an uncommon form of left ventricular dysfunction associated with pregnancy and triggered by a number of obstetric factors including pre-eclampsia, plural gestations and multiparity. PPCM is the most frequent cause of pregnancy-related maternal death. Although the clinical outcome of PPCM has been determined, its patho-etiology has not been elucidated. Two recent studies have demonstrated for the first time in a small proportion of patients, convincing evidence of a genetic predisposition for PPCM, activated by modifier genes responding to biochemical and hemodynamic signals during mid to late pregnancy.

Transition from chronic compensated to acute decompensated heart failure: pathophysiological insights obtained from continuous monitoring of intracardiac pressures.

BACKGROUND: Approximately half of all patients with chronic heart failure (HF) have a decreased ejection fraction (EF) (systolic HF [SHF]); the other half have HF with a normal EF (diastolic HF [DHF]). However, the underlying pathophysiological differences between DHF and SHF patients are incompletely defined. The purpose of this study was to use echocardiographic and implantable hemodynamic monitor data to examine the pathophysiology of chronic compensated and acute decompensated HF in SHF versus DHF patients. METHODS AND RESULTS: Patients were divided into 2 subgroups: 204 had EF <50% (SHF) and 70 had EF >or=50% (DHF). DHF patients had EF of 58+/-8%, end-diastolic dimension of 50+/-10 mm, estimated resting pulmonary artery diastolic pressure (ePAD) of 16+/-9 mm Hg, and diastolic distensibility index (ratio of ePAD to end-diastolic volume) of 0.11+/-0.06 mm Hg/mL. In contrast, SHF patients had EF of 24+/-10%, end-diastolic dimension of 68+/-11 mm, ePAD of 18+/-7 mm Hg, and diastolic distensibility index of 0.06+/-0.04 mm Hg/mL (P<0.05 versus DHF for all variables except ePAD). In SHF and DHF patients who developed acute decompensated HF, these events were associated with a significant increase in ePAD, from 17+/-7 to 22+/-7 mm Hg (P<0.05) in DHF and from 21+/-9 to 24+/-8 mm Hg (P<0.05) in SHF. As a group, patients who did not have acute decompensated HF events had no significant changes in ePAD. CONCLUSIONS: Significant structural and functional differences were found between patients with SHF and those with DHF; however, elevated diastolic pressures play a pivotal role in the underlying pathophysiology of chronic compensated and acute decompensated HF in both SHF and DHF.

Results of the Predictors of Response to CRT (PROSPECT) trial.

BACKGROUND: Data from single-center studies suggest that echocardiographic parameters of mechanical dyssynchrony may improve patient selection for cardiac resynchronization therapy (CRT). In a prospective, multicenter setting, the Predictors of Response to CRT (PROSPECT) study tested the performance of these parameters to predict CRT response. METHODS AND RESULTS: Fifty-three centers in Europe, Hong Kong, and the United States enrolled 498 patients with standard CRT indications (New York Heart Association class III or IV heart failure, left ventricular ejection fraction < or = 35%, QRS > or = 130 ms, stable medical regimen). Twelve echocardiographic parameters of dyssynchrony, based on both conventional and tissue Doppler-based methods, were evaluated after site training in acquisition methods and blinded core laboratory analysis. Indicators of positive CRT response were improved clinical composite score and > or = 15% reduction in left ventricular end-systolic volume at 6 months. Clinical composite score was improved in 69% of 426 patients, whereas left ventricular end-systolic volume decreased > or = 15% in 56% of 286 patients with paired data. The ability of the 12 echocardiographic parameters to predict clinical composite score response varied widely, with sensitivity ranging from 6% to 74% and specificity ranging from 35% to 91%; for predicting left ventricular end-systolic volume response, sensitivity ranged from 9% to 77% and specificity from 31% to 93%. For all the parameters, the area under the receiver-operating characteristics curve for positive clinical or volume response to CRT was < or = 0.62. There was large variability in the analysis of the dyssynchrony parameters. CONCLUSIONS: Given the modest sensitivity and specificity in this multicenter setting despite training and central analysis, no single echocardiographic measure of dyssynchrony may be recommended to improve patient selection for CRT beyond current guidelines. Efforts aimed at reducing variability arising from technical and interpretative factors may improve the predictive power of these echocardiographic parameters in a broad clinical setting.

Heart failure with normal ejection fraction: consideration of mechanisms other than diastolic dysfunction.

More than half of patients with heart failure (HF) have a normal ejection fraction (EF). These patients are typically elderly, are predominantly female, and have a high incidence of multiple comorbid conditions associated with development of ventricular hypertrophy and/or interstitial fibrosis. Thus, the cause of HF has been attributed to diastolic dysfunction. However, the same comorbidities may also impact myocardial systolic, ventricular, vascular, renal, and extracardiovascular properties in ways that can also contribute to symptoms of HF by way of mechanisms not related to diastolic dysfunction. Accordingly, the descriptive term HF with normal EF has been suggested as an alternative to the mechanistic term diastolic HF. In this article, we review the current understanding of nondiastolic mechanisms that may contribute to the HF with normal EF syndrome to highlight potential pathways for research that may lead to new targets for therapy.