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Objectives This study sought to evaluate the impact of baseline PR interval on cardiac resynchronization therapy (CRT) outcomes in the REVERSE (Resynchronization Reverses Remodeling in Systolic Left Ventricular Dysfunction) study. Background The baseline electrocardiogram has important prognostic value to determine response to CRT. Specifically, QRS duration and morphology are strong predictors of response and outcomes; however, the prognostic importance of the PR interval is less clear. Methods REVERSE was a double-blinded, randomized study of CRT in mild heart failure (HF). The primary endpoint was the analysis of patients in sinus rhythm (n = 582) of the time-to–first HF hospitalization or death during the 2-year randomized period of the trial. In addition, the long-term impact of PR interval was assessed in the cohort actively on CRT during the pre-planned 5-year follow-up. Subjects were analyzed by PR interval, grouped by the median (180 ms) in 20-ms bins or as a continuous variable depending on the analysis performed. Secondary endpoints included the clinical composite score and echocardiographic measures of reverse remodeling. Results During the randomized phase of the study, CRT had similar effectiveness for both PR 180 ms (HR: 0.57) subgroups (interaction p = 0.33). Similar results were observed when PR interval was grouped in 20-ms bins or treated as a continuous variable. In multivariable analysis of the long-term follow-up, left bundle branch block morphology, New York Heart Association functional class, HF etiology, and QRS duration, but not PR interval, predicted HF hospitalization or death. Conclusions Baseline PR interval does not affect clinical outcomes or reverse remodeling with CRT in mild HF. (Resynchronization Reverses Remodeling in Systolic Left Ventricular Dysfunction [REVERSE]; NCT00271154)

Objectives This study sought to determine the effects of abnormal left ventricular (LV) architecture on cardiac remodeling and clinical outcomes in mild heart failure (HF). Background Cardiac resynchronization therapy (CRT) is an established treatment for HF that improves survival in part by favorably remodeling LV architecture. LV shape is a dynamic component of LV architecture on which contractile function depends. Methods Transthoracic 2-dimensional echocardiography was used to quantify changes in LV architecture over 5 years of follow-up of patients with mild HF from the REVERSE study. REVERSE was a prospective study of patients with large hearts (LV end-diastolic dimension ≥55 mm), LV ejection fraction 120 ms randomly assigned to CRT-ON (n = 419) and CRT-OFF (n = 191). CRT-OFF patients were excluded from this analysis. LV dimensions, volumes, mass index, and LV ejection fraction were calculated. LV architecture was assessed using the sphericity index, as follows: (LV end-diastolic volume)/(4/3 × π × r3) × 100%. Results LV architecture improved over time and demonstrated significant associations between LV shape, age, sex, and echocardiography metrics. Changes in LV architecture were strongly correlated with changes in LV end-systolic volume index and LV end-diastolic volume index (both p 15% occurred in more than two-thirds of patients, which indicates considerable reverse remodeling. Conclusions We demonstrated that change in LV architecture in patients with mild HF with CRT is associated with structural and functional remodeling. Mean LV filling pressure was elevated, and the inability to lower it was an additional predictor of HF hospitalization or death. (Resynchronization Reverses Remodeling in Systolic Left Ventricular Dysfunction [REVERSE]; NCT00271154)

Aims: The Biventricular vs Right Ventricular Pacing in Heart Failure Patients with Atrioventricular Block (BLOCK-HF) demonstrated that biventricular (BiV) pacing resulted in better clinical and structural outcomes compared to right ventricular (RV) pacing in patients with atrioventricular (AV) block and reduced left ventricular ejection fraction (LVEF; ≤50%). This study investigated the cost-effectiveness of BiV vs RV pacing in the patient population enrolled in the BLOCK-HF trial. Methods: All-cause mortality, New York Heart Association (NYHA) Class distribution over time, and NYHA-specific heart failure (HF)-related healthcare utilization rates were predicted using statistical models based on BLOCK-HF patient data. A proportion-in-state model calculated cost-effectiveness from the Medicare payer perspective. Results: The predicted patient survival was 6.78 years with RV and 7.52 years with BiV pacing, a 10.9% increase over lifetime. BiV pacing resulted in 0.41 more quality-adjusted life years (QALYs) compared to RV pacing, at an additional cost of $12,537. The “base-case” incremental cost-effectiveness ratio (ICER) was $30,860/QALY gained. Within the clinical sub-groups, the highest observed ICER was $43,687 (NYHA Class I). Patients receiving combined BiV pacing and defibrillation (BiV-D) devices were projected to benefit more (0.84 years gained) than BiV pacemaker (BiV-P) recipients (0.49 years gained), compared to dual-chamber pacemakers. Conclusions: BiV pacing in AV block patients improves survival and attenuates HF progression compared to RV pacing. ICERs were consistently below the US acceptability threshold ($50,000/QALY). From a US Medicare perspective, the additional up-front cost associated with offering BiV pacing to the BLOCK-HF patient population appears justified.

Background Sustained right ventricular (RV) apical pacing may lead to deterioration in ventricular function and an increased risk of heart failure, especially in patients with pre-existing systolic dysfunction. The BLOCK HF (Biventricular Versus Right Ventricular Pacing in Heart Failure Patients With Atrioventricular Block) trial demonstrated that biventricular-paced patients had a reduced incidence of a composite endpoint of death, heart failure–related urgent care, and adverse left ventricular remodeling. Objectives In a pre-specified analysis, this study examined clinical outcomes, including clinical composite score, quality of life (QOL), and change in New York Heart Association (NYHA) functional classification. Methods The BLOCK HF trial randomized patients with atrioventricular block, NYHA symptom class I to III heart failure, and left ventricular ejection fraction ≤50% to biventricular or RV pacing. NYHA functional classification, QOL, and clinical composite score were assessed at 6, 12, 18, and 24 months. Bayesian statistical methods were used, with the pre-specified metric of benefit being a posterior probability ≥0.95. Results Patients with biventricular pacing showed greater improvement in NYHA functional class at 12 months, with 19% improved, 61% unchanged, and 17% worsened, compared with 12%/62%/23% in the RV arm. QOL was improved through 12 months. At 6 months, clinical composite score was improved/unchanged/worsened in 53%/24%/24% in the biventricular arm compared with 39%/33%/28% in the RV arm. This improvement in clinical composite score was sustained through 24 months. Conclusions For patients with atrioventricular block and systolic dysfunction, biventricular pacing not only reduces the risk of mortality/morbidity, but also leads to better clinical outcomes, including improved QOL and heart failure status, compared with RV pacing. (Biventricular Versus Right Ventricular Pacing in Heart Failure Patients With Atrioventricular Block [BLOCK HF]; NCT00267098 )

Despite therapeutic advances that improve longevity and quality of life, heart failure (HF) remains a relentless disease. At the end stage of HF, patients may become eligible for mechanical circulatory support (MCS) for the indications of stabilising acute cardiogenic shock or for chronic HF management. MCS use is growing rapidly in the USA and some countries of the European Union, especially in transplant-ineligible patients. In others, it remains largely a tool to stabilise patients until heart transplant. MCS comprises a heterogeneous group of temporary and durable devices which augment or replace the pumping function of one or both ventricles, with postimplant 2 year survival rivalling that of transplant in selected, lower-risk patients. In transplant-eligible and non-transplant-eligible patients, improvement in end-organ perfusion, functional capacity and quality of life have been noted. Even for optimal candidates, however, there are a host of potential complications that require constant vigilance of a coordinated care team. Recently, there has been official recognition of the importance of palliative care expertise in advance care planning preimplant and management of patients with ventricular assist devices at the end of their lives.

Background— Biventricular pacing in heart failure (HF) improves survival, relieves symptoms, and attenuates left ventricular (LV) remodeling. However, little is known about biventricular pacing in HF patients with atrioventricular block because they are typically excluded from biventricular trials. Methods and Results— The Biventricular versus Right Ventricular Pacing in Heart Failure Patients with Atrioventricular Block (BLOCK HF) trial randomized patients with atrioventricular block, New York Heart Association symptom classes I to III HF, and LV ejection fraction ≤50% to biventricular or right ventricular pacing. Doppler echocardiograms were obtained at randomization (after 30 to 60 days of right ventricular pacing postimplant) and every 6 months through 24 months. Data analysis comparing changes in 10 prespecified echo parameters over time was conducted using a Bayesian design. LV end systolic volume index was also evaluated as a predictor of mortality/morbidity. Of 691 randomized subjects, 624 had paired Doppler echocardiogram data for ≥1 analyses at 6, 12, 18, or 24 months. Biventricular pacing significantly reduced LV volume indices and intraventricular mechanical delay, and improved LV ejection fraction, consistent with LV reverse remodeling. These parameters showed little change with right ventricular pacing alone, indicating no systematic reverse remodeling with right ventricular pacing. LV end systolic volume index was predictive of mortality/morbidity; the estimated risk increased up to 1% for every 1 mL/m 2 increase in LV end systolic volume index. Conclusions— LV end systolic volume index is a significant predictor of mortality/morbidity in this population. Cardiac structure and function are improved with biventricular pacing for patients with atrioventricular block and LV systolic dysfunction. Clinical Trial Registration— URL: http://www.clinicaltrials.gov . Unique identifier: NCT00267098.

BACKGROUND Chronic kidney disease (CKD) is associated with increased risk of cardiovascular disease (CVD) and it is especially common among Blacks. Left ventricular hypertrophy (LVH) is an important subclinical marker of CVD, but there are limited data on racial variation in left ventricular structure and function among persons with CKD. METHODS In a cross-sectional analysis of the Chronic Renal Insufficiency Cohort Study, we compared the prevalence of different types of left ventricular remodeling (concentric hypertrophy, eccentric hypertrophy, and concentric remodeling) by race/ethnicity. We used multinomial logistic regression to test whether race/ethnicity associated with different types of left ventricular remodeling independently of potential confounding factors. RESULTS We identified 1,164 non-Hispanic Black and 1,155 non-Hispanic White participants who completed Year 1 visits with echocardiograms that had sufficient data to categorize left ventricular geometry type. Compared to non-Hispanic Whites, non-Hispanic Blacks had higher mean left ventricular mass index (54.7 ± 14.6 vs. 47.4 ± 12.2 g/m2.7; P < 0.0001) and prevalence of concentric LVH (45.8% vs. 24.9%). In addition to higher systolic blood pressure and treatment with >3 antihypertensive medications, Black race/ethnicity was independently associated with higher odds of concentric LVH compared to White race/ethnicity (odds ratio: 2.73; 95% confidence interval: 2.02, 3.69). CONCLUSION In a large, diverse cohort with CKD, we found significant differences in left ventricular mass and hypertrophic morphology between non-Hispanic Blacks and Whites. Future studies will evaluate whether higher prevalence of LVH contribute to racial/ethnic disparities in cardiovascular outcomes among CKD patients.

Arrhythmia in Adults with Single Ventricles 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

Background— There is growing evidence to support an important role for vitamin D and related hormones, parathyroid hormone and fibroblast growth factor 23 (FGF23), on cardiac remodeling in chronic kidney disease. Our objective was to determine the relationships between vitamin D and cardiac remodeling in chronic kidney disease and the effects of parathyroid hormone and FGF23 on these associations. Methods and Results— In 1431 participants from the Chronic Renal Insufficiency Cohort study, we measured 25-hydroxyvitamin D (25(OH)D), 1,25-dihyroxyvitamin D (1,25(OH) 2 D), FGF23, and parathyroid hormone and performed quantitative echocardiography. Using linear regression methods, we determined significant negative interactions between 25(OH)D and FGF23 on left ventricular (LV) mass ( P =0.016), end-diastolic volume ( P =0.029), and end-systolic volumes ( P =0.021). In participants with an FGF23 level greater than the median of 123.5 RU/mL, each doubling of 25(OH)D was associated with a 2.5% (95% confidence interval, −4.8, −0.2) lower LV mass. This association was less pronounced with FGF23 levels less than the median (0.4%; 95% confidence interval, −1.9, 2.7). Conversely, in participants with deficient 25(OH)D levels P 2 D and LV mass and volumes ( P Conclusions— We identified significant interactions among 25(OH)D, 1,25(OH) 2 D, and FGF23 on cardiac remodeling. Increased LV mass and cavity dilatation were observed with low 25(OH)D and high FGF23. Our findings suggest that consideration of both hormones is crucial to understanding the role of either in cardiac remodeling, and may have important therapeutic implications.

Right ventricular pacing restores an adequate heart rate in patients with atrioventricular block, but high percentages of right ventricular apical pacing may promote left ventricular systolic dysfunction. We evaluated whether biventricular pacing might reduce mortality, morbidity, and adverse left ventricular remodeling in such patients.We enrolled patients who had indications for pacing with atrioventricular block; New York Heart Association (NYHA) class I, II, or III heart failure; and a left ventricular ejection fraction of 50% or less. Patients received a cardiac-resynchronization pacemaker or implantable cardioverter-defibrillator (ICD) (the latter if the patient had an indication for defibrillation therapy) and were randomly assigned to standard right ventricular pacing or biventricular pacing. The primary outcome was the time to death from any cause, an urgent care visit for heart failure that required intravenous therapy, or a 15% or more increase in the left ventricular end-systolic volume index.Of 918 patients enrolled, 691 underwent randomization and were followed for an average of 37 months. The primary outcome occurred in 190 of 342 patients (55.6%) in the right-ventricular-pacing group, as compared with 160 of 349 (45.8%) in the biventricular-pacing group. Patients randomly assigned to biventricular pacing had a significantly lower incidence of the primary outcome over time than did those assigned to right ventricular pacing (hazard ratio, 0.74; 95% credible interval, 0.60 to 0.90); results were similar in the pacemaker and ICD groups. Left ventricular lead-related complications occurred in 6.4% of patients.Biventricular pacing was superior to conventional right ventricular pacing in patients with atrioventricular block and left ventricular systolic dysfunction with NYHA class I, II, or III heart failure. (Funded by Medtronic; BLOCK HF ClinicalTrials.gov number, NCT00267098.).

This study sought to evaluate the impact of baseline PR interval on cardiac resynchronization therapy (CRT) outcomes in the REVERSE (Resynchronization Reverses Remodeling in Systolic Left Ventricular Dysfunction) study.The baseline electrocardiogram has important prognostic value to determine response to CRT. Specifically, QRS duration and morphology are strong predictors of response and outcomes; however, the prognostic importance of the PR interval is less clear.REVERSE was a double-blinded, randomized study of CRT in mild heart failure (HF). The primary endpoint was the analysis of patients in sinus rhythm (n = 582) of the time-to-first HF hospitalization or death during the 2-year randomized period of the trial. In addition, the long-term impact of PR interval was assessed in the cohort actively on CRT during the pre-planned 5-year follow-up. Subjects were analyzed by PR interval, grouped by the median (180 ms) in 20-ms bins or as a continuous variable depending on the analysis performed. Secondary endpoints included the clinical composite score and echocardiographic measures of reverse remodeling.During the randomized phase of the study, CRT had similar effectiveness for both PR 180 ms (hazard ratio [HR]: 0.34) and PR180 ms (HR: 0.57) subgroups (interaction p = 0.33). Similar results were observed when PR interval was grouped in 20-ms bins or treated as a continuous variable. In multivariable analysis of the long-term follow-up, left bundle branch block morphology, New York Heart Association functional class, HF etiology, and QRS duration, but not PR interval, predicted HF hospitalization or death.Baseline PR interval does not affect clinical outcomes or reverse remodeling with CRT in mild HF. (Resynchronization Reverses Remodeling in Systolic Left Ventricular Dysfunction [REVERSE]; NCT00271154).

This study sought to determine the effects of abnormal left ventricular (LV) architecture on cardiac remodeling and clinical outcomes in mild heart failure (HF).Cardiac resynchronization therapy (CRT) is an established treatment for HF that improves survival in part by favorably remodeling LV architecture. LV shape is a dynamic component of LV architecture on which contractile function depends.Transthoracic 2-dimensional echocardiography was used to quantify changes in LV architecture over 5 years of follow-up of patients with mild HF from the REVERSE study. REVERSE was a prospective study of patients with large hearts (LV end-diastolic dimension ≥55 mm), LV ejection fraction 40%, and QRS duration120 ms randomly assigned to CRT-ON (n = 419) and CRT-OFF (n = 191). CRT-OFF patients were excluded from this analysis. LV dimensions, volumes, mass index, and LV ejection fraction were calculated. LV architecture was assessed using the sphericity index, as follows: (LV end-diastolic volume)/(4/3 × π × rLV architecture improved over time and demonstrated significant associations between LV shape, age, sex, and echocardiography metrics. Changes in LV architecture were strongly correlated with changes in LV end-systolic volume index and LV end-diastolic volume index (both p 0.0001). Sphericity index emerged as a predictor of death and HF hospitalization in spite of the low adverse event rate. A decrease in LV end-systolic volume index15% occurred in more than two-thirds of patients, which indicates considerable reverse remodeling.We demonstrated that change in LV architecture in patients with mild HF with CRT is associated with structural and functional remodeling. Mean LV filling pressure was elevated, and the inability to lower it was an additional predictor of HF hospitalization or death. (Resynchronization Reverses Remodeling in Systolic Left Ventricular Dysfunction [REVERSE]; NCT00271154).

Background Heart failure is an ongoing epidemic of left ventricular (LV) dilatation and/or dysfunction due to the increasing prevalence of predisposing risk factors such as age, physical inactivity, (abdominal) obesity, and type-2-diabetes. Approximately half of these patients have diastolic heart failure (HFpEF). The prognosis of HFpEF is comparable to that of systolic heart failure, but without any known effective treatment. Diastolic dysfunction A biomathematically corrected diagnostic approach is presented that quantifies diastolic dysfunction via the predominant age dependency of LV diastolic function and unmasks (metabolic) risk factors, that are independent of age and, therefore, potential targets for therapy. Patients with HFpEF have reduced cardiac energy reserve that is frequently caused by insulin resistance. Consequently, HFpEF and/or LV diastolic dysfunction may be regarded as a cardiac manifestation of the metabolic syndrome (MetS). Dietary therapy Accordingly, a causal therapy for metabolically induced dysfunction aims at normalizing insulin sensitivity by improving postprandial glucose and lipid metabolism. The respective treatments include 1) weight loss induced by dietary energy restriction that is often not sustained long-term and 2) independent of weight loss, focus on carbohydrate modification in exchange for an increase in protein and fat, ideally combined with an aerobic exercise program. Hence, beneficial effects of different macronutrient compositions in the dietary therapy of the underlying MetS are discussed together with the most recently available publications and meta-analyses. Conclusion Modulation/restriction of carbohydrate intake normalizes postprandial hyperglycemic and insulinemic peaks and has been shown to improve all manifestations of the MetS and also to reduce cardiovascular risk.

Aims Chronic kidney disease (CKD) is a risk factor for left ventricular hypertrophy (LVH) and heart failure. We evaluated the effect of CKD on left ventricular (LV) remodelling among patients with mild heart failure. Methods and results REVERSE was a randomized, controlled trial evaluating cardiac resynchronization therapy (CRT) in patients with New York Heart Association (NYHA) class I/II heart failure. CKD was defined as an estimated glomerular filtration rate (eGFR)

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.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.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.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.

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.

Although Friedreich ataxia (FA) is associated with cardiomyopathy, the severity and evolution of cardiac disease is poorly understood. To identify factors predicting cardiomyopathy in FA, we assessed echocardiograms from a large heterogenous cohort and their relation to disease traits. The most recent echocardiograms from 173 subjects with FA were analyzed in a core laboratory to determine their relation to disease duration, subject age, age of onset, functional disability score, and GAA repeat length. Mean age of the cohort was 19.7 years, mean age of disease onset was 10.6 years, and mean shorter GAA length was 681 repeats. Echocardiograms collectively illustrated systolic dysfunction, diastolic dysfunction, and hypertrophy. Measurements of hypertrophy correlated moderately with each other (r = 0.39 to 0.79) but not with measurements of diastolic dysfunction (r0.35). Diastolic measurements correlated poorly with each other, although 26% of the cohort had multiple diastolic abnormalities. The most common diastolic dysfunction classification was pseudonormalization. Classification of diastolic dysfunction was predicted by GAA repeat length but not by age or gender. Ejection fraction was below normal in 20% of the cohort. In linear regression analysis, increasing age predicted decreasing ejection fraction. Functional disability score, a measurement of neurologic ability, did not predict any echocardiographic measurements. In conclusion, hypertrophy and diastolic and systolic dysfunctions occur in FA and are substantially independent; diastolic dysfunction is the most common abnormality with most patients having an assigned diastolic dysfunction class of pseudonormalization.

Chronic kidney disease (CKD) is a public health epidemic that increases risk of death due to cardiovascular disease. Left ventricular hypertrophy (LVH) is an important mechanism of cardiovascular disease in individuals with CKD. Elevated levels of FGF23 have been linked to greater risks of LVH and mortality in patients with CKD, but whether these risks represent causal effects of FGF23 is unknown. Here, we report that elevated FGF23 levels are independently associated with LVH in a large, racially diverse CKD cohort. FGF23 caused pathological hypertrophy of isolated rat cardiomyocytes via FGF receptor-dependent activation of the calcineurin-NFAT signaling pathway, but this effect was independent of klotho, the coreceptor for FGF23 in the kidney and parathyroid glands. Intramyocardial or intravenous injection of FGF23 in wild-type mice resulted in LVH, and klotho-deficient mice demonstrated elevated FGF23 levels and LVH. In an established animal model of CKD, treatment with an FGF-receptor blocker attenuated LVH, although no change in blood pressure was observed. These results unveil a klotho-independent, causal role for FGF23 in the pathogenesis of LVH and suggest that chronically elevated FGF23 levels contribute directly to high rates of LVH and mortality in individuals with CKD.

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. (Echocardiography 2011;28:767-773)

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.

Blood pressure (BP) reduction to 140/90 mm Hg or lower using renin-angiotensin-system blockers reportedly provides the greatest left ventricular (LV) mass regression; β-blockers have less effect. This study examined whether combination antihypertensive therapy would provide greater benefit. With a double-blind, parallel-group design, the effects of 3 different combinations, carvedilol controlled-release (CR)/lisinopril, atenolol/lisinopril, and lisinopril, on left ventricular mass index (LVMI) were assessed by MRI after 12 months. Patients were treated to achieve guideline-recommended BP (

Our objective was to determine the gender differences in the relation between the echocardiographic parameters of cardiac remodeling and clinical outcomes in patients with chronic stable angina. The baseline ejection fraction (EF), end-diastolic volume, and end-systolic volume were assessed in 7,016 patients in the study "A Coronary disease Trial Investigating Outcomes with Nifedipine gastrointestinal therapeutic system" (ACTION). All-cause and cardiac mortality and incident heart failure were determined after a median of 5.0 years. Cox proportional hazard models were fit to determine the effect of gender on the relation between the echocardiographic parameters and clinical outcomes (interaction p

The aim of this study was to investigate the ability of transthoracic echocardiography (TTE) to detect vegetations and the relationship between blood cultures and transesophageal echocardiography (TEE).Five hundred eleven TTE and TEE pairs performed to evaluate endocarditis were retrospectively analyzed. Vegetation on TTE, prosthetic valve, change in regurgitation, and blood cultures were correlated with vegetation on TEE.TTE detected 45% of vegetations seen on TEE. There was no difference for prosthetic valves. Prosthetic valves (odds ratio, 1.7; P = .03) and increased regurgitation (odds ratio, 1.7; P = .01) were associated with vegetations on TEE; staphylococcal bacteremia and fungemia were not. Negative blood cultures were associated with negative results on TEE (P.0001), but 27% of patients with prosthetic valves had culture-negative endocarditis or nonbacterial thrombotic endocarditis, and 6% had abscesses missed by TTE.This study demonstrates a limited capacity of TTE to detect vegetations. TEE may be an appropriate initial study to evaluate prosthetic valves. TEE for culture-negative endocarditis deserves further study.

As the potential for cancer therapy-related cardiac dysfunction is increasingly recognized, there is a need for the standardization of echocardiographic measurements and cut points to guide treatment. The aim of this study was to determine the reproducibility of cardiac safety assessments across two academic echocardiography core laboratories (ECLs) at the University of Pennsylvania and the Duke Clinical Research Institute.To harmonize the application of guideline-recommended measurement conventions, the ECLs conducted multiple training sessions to align measurement practices for traditional and emerging assessments of left ventricular (LV) function. Subsequently, 25 echocardiograms taken from patients with breast cancer treated with doxorubicin with or without trastuzumab were independently analyzed by each laboratory. Agreement was determined by the proportion (coverage probability [CP]) of all pairwise comparisons between readers that were within a prespecified minimum acceptable difference. Persistent differences in measurement techniques between laboratories triggered retraining and reassessment of reproducibility.There was robust reproducibility within each ECL but differences between ECLs on calculated LV ejection fraction and mitral inflow velocities (all CPs 0.80); four-chamber global longitudinal strain bordered acceptable reproducibility (CP = 0.805). Calculated LV ejection fraction and four-chamber global longitudinal strain were sensitive to small but systematic interlaboratory differences in endocardial border definition that influenced measured LV volumes and the speckle-tracking region of interest, respectively. On repeat analyses, reproducibility for mitral velocities (CP = 0.940-0.990) was improved after incorporating multiple-beat measurements and homogeneous image selection. Reproducibility for four-chamber global longitudinal strain was unchanged after efforts to develop consensus between ECLs on endocardial border determinations were limited primarily by a lack of established reference standards.High-quality quantitative echocardiographic research is feasible but requires a commitment to reproducibility, adherence to guideline recommendations, and the time, care, and attention to detail to establish agreement on measurement conventions. These findings have important implications for research design and clinical care.

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 ≤ 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 (β = 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 (β = −17.85; P < 0.0001) during handgrip, Zc during handgrip (β = −150; P < 0.0001), and the change in the timing of wave reflections during handgrip (β = −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.

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 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.

Echocardiography serves an extremely important role in the diagnosis and management of patients with heart failure. The various stages of structural and functional changes that constitute progressive left ventricle remodeling have all been characterized by two-dimensional echocardiography. In addition, echocardiography has defined the transition from compensated hypertrophy to left ventricle dilatation and progression to end-stage heart failure. Echocardiography has also played an important role in clinical heart failure trials of beta-adrenergic blocking agents and angiotensin-converting enzyme inhibitors and angiotensin receptor blockers and demonstrated their efficacy in heart failure.

The response to cardiopulmonary exercise (CPX) in patients with heart failure (HF) with normal left ventricular (LV) ejection fractions (EFs) is not well characterized. To determine if CPX testing could distinguish between patients with HF with normal EFs (>50%; i.e., diastolic HF) and those with decreased EFs (> or =50%; i.e., systolic HF), CPX responses were compared between 185 patients with systolic HF (79% men, mean age 62.6 +/- 10.9 years) and 43 with diastolic HF (54% men, mean age 67.4 +/- 9.8 years) enrolled in a phase II multicenter clinical trial. All patients were evaluated with echocardiography and a standardized CPX test as part of the trial. CPX variables, including oxygen uptake at peak exercise (peak VO(2)) and the slope of the ventilation/carbon dioxide production ratio (VE/VCO(2)), were determined and analyzed by core laboratory personnel. Echocardiographic measurements included the LV EF, the E/A ratio, filling time, cavity volumes, right ventricular function, and mitral regurgitation. Patients in the diastolic HF group tended to be older (p

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 ≤35%, QRS ≥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 ≥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 ≥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 ≤0.62. There was large variability in the analysis of the dyssynchrony parameters. Conclusion— 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.

Remodeling reflects the structural and functional deterioration that occurs in heart failure. Indices of remodeling constitute an important marker of the severity of heart failure, and reverse remodeling is an accepted goal in the treatment of heart failure. Cardiac resynchronization therapy (CRT) has been shown to reverse the remodeling process by improving ventricular size, shape, and mass and reducing mitral regurgitation in the short and long term. Diastolic function, right ventricular size, and atria exhibit reverse remodeling. Trials of medical therapy for heart failure strongly link remodeling indices with outcomes, and emerging data suggest that remodeling indices may be among the most accurate predictors of long-term morbidity and mortality in heart failure patients with CRT devices. This review discusses remodeling and focuses on the evidence for CRT-induced reverse remodeling.

Background Intravenous agitated saline injection during transthoracic echocardiography assists in the detection of right to left intracardiac and intrapulmonary shunts. Whether digital echocardiography offers comparable sensitivity and specificity to analog tape recording to assess shunts is unknown. Technical differences between methods could lead to significant differences in shunt detection. Methods Agitated saline was injected intravenously at rest and with Valsalva in 189 consecutive patient studies (406 injections). Echocardiographers assessed presence and degree of left ventricle contrast on simultaneously recorded analog tape and digital echocardiography images in blinded fashion. Results Digital echocardiography had low overall sensitivity (rest 0.50, valsalva 0.63, late 0.39) compared to analog tape. Longer clip lengths improved sensitivity for detection of late contrast passage (rest 0.50, valsalva 0.67, late 0.46). Conclusion Digital echocardiography saline contrast studies have poor sensitivity for assessment of intracardiac shunts versus analog tape, and increasing clip length only modestly increases sensitivity. Joint Photographic Experts Group digital compression losses may be an important cause of failure to detect intracardiac shunts, including patent foramen ovale.

In the last decade, we have witnessed an extraordinary development of new cardiac imaging techniques. Some are already in routine use while other promising techniques, such as 3D and intracardiac echocardiography, are still taking their first steps in clinical applications and have not yet revealed all their potential. Heart failure surgery is also evolving rapidly toward less-invasive procedures with the introduction of video-assisted robotic valve repair/replacement surgery, percutaneous delivery of epicardial restraint devices, mitral edge-to-edge clips, coronary sinus mitral annuloplasty rings, and stem cell therapy. These rapid developments are challenging for the imager and the surgeon and mandate a close collaboration between the two disciplines to minimize surgical risk and improve the outcome of patients who have heart failure.

Sustained right ventricular (RV) apical pacing may lead to deterioration in ventricular function and an increased risk of heart failure, especially in patients with pre-existing systolic dysfunction. The BLOCK HF (Biventricular Versus Right Ventricular Pacing in Heart Failure Patients With Atrioventricular Block) trial demonstrated that biventricular-paced patients had a reduced incidence of a composite endpoint of death, heart failure-related urgent care, and adverse left ventricular remodeling.In a pre-specified analysis, this study examined clinical outcomes, including clinical composite score, quality of life (QOL), and change in New York Heart Association (NYHA) functional classification.The BLOCK HF trial randomized patients with atrioventricular block, NYHA symptom class I to III heart failure, and left ventricular ejection fraction ≤50% to biventricular or RV pacing. NYHA functional classification, QOL, and clinical composite score were assessed at 6, 12, 18, and 24 months. Bayesian statistical methods were used, with the pre-specified metric of benefit being a posterior probability ≥0.95.Patients with biventricular pacing showed greater improvement in NYHA functional class at 12 months, with 19% improved, 61% unchanged, and 17% worsened, compared with 12%/62%/23% in the RV arm. QOL was improved through 12 months. At 6 months, clinical composite score was improved/unchanged/worsened in 53%/24%/24% in the biventricular arm compared with 39%/33%/28% in the RV arm. This improvement in clinical composite score was sustained through 24 months.For patients with atrioventricular block and systolic dysfunction, biventricular pacing not only reduces the risk of mortality/morbidity, but also leads to better clinical outcomes, including improved QOL and heart failure status, compared with RV pacing. (Biventricular Versus Right Ventricular Pacing in Heart Failure Patients With Atrioventricular Block [BLOCK HF]; NCT00267098).

Background Cardiac resynchronization therapy results in improved ejection fraction in patients with heart failure. We sought to determine whether these effects were mediated by changes in contractility, afterload, or volumes. Methods and Results In 610 patients with New York Heart Association class I/ II heart failure from the Re synchronization Reverses Remodeling in Systolic Left Ventricular Dysfunction ( REVERSE ) study, we performed detailed quantitative echocardiography assessment prior to and following cardiac resynchronization therapy. We derived measures of contractility (the slope [end‐systolic elastance] and the volume intercept of the end‐systolic pressure–volume relationship, stroke work, and preload recruitable stroke work), measures of arterial load and ventricular–arterial coupling, and measures of chamber size (volume intercept, end‐systolic and end‐diastolic volumes). At 6 and 12 months, cardiac resynchronization therapy was associated with a reduction in the volume intercept and end‐systolic and end‐diastolic volumes ( P CI 1.04 to 1.63, P =0.02). The volume intercept was associated with mortality (hazard ratio 1.90, 95% CI 1.01 to 3.59, P =0.047) and more modestly with the combined end point of mortality or heart failure hospitalization (hazard ratio 1.48, 95% CI 0.8 to 2.25, P =0.06). In contrast, end‐systolic elastance, stroke work, preload recruitable stroke work, and ventricular–arterial coupling were not associated with any outcomes. Conclusion In patients with NYHA Class I/ II heart failure, cardiac resynchronization therapy exerts favorable changes in left ventricular end‐systolic and end‐diastolic volumes and the volume intercept. The volume intercept may be useful to gain insight into prognosis in heart failure. Clinical Trial Registration URL : https://www.clinicaltrials.gov/ . Unique identifier: NCT 00271154.

International audience; Background Cardiac resynchronization therapy (CRT) reduces mortality, improves functional status, and induces reverse left ventricular remodeling in selected populations with heart failure (HF). The magnitude of reverse remodeling predicts survival with many HF medical therapies. However, there are few studies assessing the effect of remodeling on long-term survival with CRT. Objective The purpose of this study was to assess the effect of CRT-induced reverse remodeling on long-term survival in patients with mildly symptomatic heart failure. Methods The REsynchronization reVErses Remodeling in Systolic Left vEntricular Dysfunction trial was a multicenter, double-blind, randomized trial of CRT in patients with mild HF. Long-term follow-up of 5 years was preplanned. The present analysis was restricted to the 353 patients who were randomized to the CRT ON group with paired echocardiographic studies at baseline and 6 months postimplantation. The left ventricular end-systolic volume index (LVESVi) was measured in the core laboratory and was an independently powered end point of the REsynchronization reVErses Remodeling in Systolic Left vEntricular Dysfunction trial. Results A 68% reduction in mortality was observed in patients with ≥15% decrease in LVESVi compared to the rest of the patients (P = .0004). Multivariable analysis showed that the change in LVESVi was a strong independent predictor (P = .0002), with a 14% reduction in mortality for every 10% decrease in LVESVi. Other remodeling parameters such as left ventricular end-diastolic volume index and ejection fraction had a similar association with mortality. Conclusion The change in left ventricular end-systolic volume after 6 months of CRT is a strong independent predictor of long-term survival in mild HF

Patients at high risk for hypertension may require several therapeutic agents to lower their blood pressure to guideline-recommended targets. Some antihypertensive agents are more effective than others in protecting against cardiovascular morbidity and mortality. Numerous beta-blocking agents have been approved by the US Food and Drug Administration (FDA) for the treatment of hypertension. Previous trials have demonstrated that although all beta-blockers effectively reduce blood pressure, there are differences in how they affect various metabolic factors. In 2 trials, a novel controlled-release (CR) formulation of carvedilol will be tested against other selective beta-blockers to determine whether differences exist in their individual effects on cardiovascular risk factors. These will be the first head-to-head trials using carvedilol CR to determine whether the differing pharmacologic actions among beta-blockers result in varying effects on cardiovascular risk factors.

Congenital supravalvular aortic stenosis (SVAS) is a rare cause of congenital left ventricular outflow obstruction and pressure overload, with a diffuse form that often extends into the aortic arch, and can be associated with stenoses in other vascular territories. Knowledge of the extent of disease involvement can be complementary to medical management or critically important prior to surgical intervention. We report a case of diffuse SVAS and demonstrate the utility of ECG-gated multidetector computed tomography (CT) as a comprehensive diagnostic tool in evaluating such patients.

Quantification of cardiac chamber size, ventricular mass and function ranks among the most clinically important and most frequently requested tasks of echocardiography. Over the last decades, echocardiographic methods and techniques have improved and expanded dramatically, due to the introduction of higher frequency transducers, harmonic imaging, fully digital machines, left-sided contrast agents, and other technological advancements. Furthermore, echocardiography due to its portability and versatility is now used in emergency rooms, operating rooms, and intensive care units. Standardization of measurements in echocardiography has been inconsistent and less successful, compared to other imaging techniques and consequently, echocardiographic measurements are sometimes perceived as less reliable. Therefore, the American Society of Echocardiography, working together with the European Association of Echocardiography, a branch of the European Society of Cardiology, has critically reviewed the literature and updated the recommendations for quantifying cardiac chambers using echocardiography. This document reviews the technical aspects on how to perform quantitative chamber measurements of morphology and function, which is a component of every complete echocardiographic examination.

Left ventricular (LV) and right ventricular (RV) function are known predictors of morbidity and mortality after an acute myocardial infarction (MI). However, the prognostic use of a late evaluation of cardiac function after an MI remains unclear.We analyzed echocardiograms obtained 1 year after MI in patients with LV dysfunction at baseline (ejection fraction [EF]or = 40%) from 291 patients enrolled in the SAVE echocardiographic substudy who did not develop heart failure (HF) or a recurrent MI during this first year. Left ventricular EF and RV fractional area change were assessed.After a median follow-up of 22 months after the 1-year echocardiogram, a low LVEF (30%) at 1 year was associated with an increased risk of death and/or HF (hazards ratio [HR] 2.7, 95% CI 1.3-5.3). Presence of RV dysfunction was also associated with an increased risk of death (HR 8.9, 95% CI 3.5-22.1), development of HF (HR 7.1, 95% CI 3.4-15.0), and the composite end point of death or HF (HR 7.6, 95% CI 4.1-14.2). In multivariate analyses, both low LVEF and RV dysfunction remained independently predictive of the composite end point of death or HF. Patients with biventricular dysfunction were at the greatest risk of death and/or HF (HR 19.4, 95% CI 8.2-46.0) in follow-up.In a stable population of survivors of MI, impaired LV and RV function at 1 year after MI are independently and additively predictive of increased risk of HF or death.

Objectives The aim of this study was to determine echocardiographic predictors of outcome in patients with advanced heart failure (HF) due to severe left ventricular (LV) systolic dysfunction in the Beta-blocker Evaluation of Survival Trial (BEST). Background Previous studies indicate that echocardiographic measurements of LV size and function, mitral deceleration time, and mitral regurgitation (MR) predict adverse outcomes in HF. However, complete quantitative echocardiograms evaluating all of these parameters have not been reported in a prospective randomized clinical trial in the era of modern HF therapy. Methods Complete echocardiograms were performed in 336 patients at 26 sites and analyzed by a core laboratory. A Cox proportional-hazards regression model was used to determine which echocardiographic variables predicted the primary end point of death or the secondary end point of death, HF hospitalization, or transplant. Significant variables were then entered into a multivariable model adjusted for clinical and demographic covariates. Results On multivariable analysis adjusted for clinical covariates, only LV end-diastolic volume index predicted death (events = 75), with a cut point of 120 ml/m 2 . Three echocardiographic variables predicted the combined end point of death (events = 75), HF hospitalization (events = 97), and transplant (events = 9): LV end-diastolic volume index, mitral deceleration time, and the vena contracta width of MR. Optimal cut points for these variables were 120 ml/m 2 , 150 ms, and 0.4 cm, respectively. Conclusions Echocardiographic predictors of outcome in advanced HF include LV end-diastolic volume index, mitral deceleration time, and vena contracta width. These variables indicate that LV remodeling, increased LV stiffness, and MR are independent predictors of outcome in patients with advanced HF.

Background Friedreich ataxia is an autosomal recessive neurodegenerative disorder characterized by ataxia of all four limbs, dysarthria, areflexia, and cardiomyopathy. At present, baseline values of cardiac troponin I are unknown among Friedreich ataxia subjects. Methods In this study, we evaluated baseline plasma cardiac troponin I levels among a cross-sectional cohort of 49 pediatric and adult Friedreich ataxia subjects without active arrhythmia, chest pain or features of acute coronary syndrome at the time of sampling. We also reviewed baseline electrocardiograms from 45 of these subjects. Results Troponin I values were elevated above the 99th percentile population cutoff in 46.9% of all subjects, with 16.3% of asymptomatic subjects having levels typically seen during an acute myocardial infarction. In logistic regression models, younger age and an earlier disease onset predicted higher serum cardiac troponin I values. Only weak correlations were seen between cardiac troponin I values and echocardiogram parameters, including ejection fraction. Additionally, 82.2% of subjects also had abnormal baseline electrocardiograms. Conclusion The present study demonstrates that both abnormal electrocardiograms and elevated serum cardiac troponin I values may be common baseline characteristics seen in Friedreich ataxia subjects. Further longitudinal studies will allow for a better understanding of the cause and prognostic implications of elevated levels, as well as the clinical utility of serum cardiac troponin I testing in Friedreich ataxia.

Cardiac resynchronization therapy (CRT) has been proposed as an alternative treatment in patients with severe, drug-refractory heart failure. The clinical results are promising, and improvement in symptoms, exercise capacity, and systolic left ventricular (LV) function have been demonstrated after CRT, accompanied by a reduction in hospitalization and a superior survival as compared with optimized medical therapy alone. However, 20% to 30% of patients do not respond to CRT. Currently, patients are selected mainly on electrocardiogram criteria (wide QRS complex, left bundle branch block configuration). In view of the 20% to 30% of nonresponders, additional selection criteria are needed. Echocardiography (and, in particular, tissue Doppler imaging) may allow further identification of potential responders to CRT, based on assessment of inter- and intraventricular dyssynchrony. In addition, echocardiography may allow optimal LV lead positioning and follow-up after CRT. In the current review, the different echocardiographic approaches to predict response to CRT are discussed. In addition, the use of echocardiography to guide LV lead positioning and follow-up after CRT are addressed.

previously documented. The majority of benign NCFs were simple hepatic cysts, while approximately half of the indeterminate and worrisome NCFs consisted of pleural effusions and ascites. The majority of these latter patients had a referral diagnosis of heart failure. There were comparatively few NCFs overall. Small prior TTE studies that focused on NCFs in pre-operative or intensive care patients showed a similarly low prevalence of NCFs. 3-5 However, there was a consistent major shortfall in the detection of NCFs by TTE as compared to MRI and CT. The magnitude of these discrepancies is difficult to reconcile but is most likely related to the standardized cross-sectional nature of CT and MRI with much more extensive systematic tomographic imaging of extracardiac structures. Furthermore, pulmonary pathology that is so easily visualized by CT and MRI is not demonstrable with TTE because of ultrasound attenuation in lung tissue. Importantly, in their review of a randomly selected subset of 300 patients for detection of additional NCFs from the parasternal long axis, apical 4-chamber and apical two chamber views, the authors identified an additional 2%, none of which seriously altered patient management.

Little is known about the distribution of cardiac sources of embolism among African-Americans with cryptogenic cerebrovascular events. We compared the prevalence of potential cardiac sources of embolism between black and white patients referred to our laboratory for transesophageal echocardiographic (TEE) evaluation of unexplained stroke or transient ischemic attack. Records were reviewed to exclude subjects with high-risk cardiac or vascular disorders likely to explain the index event. Of 297 patients satisfying the inclusion criteria, 196 were white and 87 black. Potential cardioembolic sources were significantly less common in blacks than in whites (adjusted odds ratio [OR], 0.44; 95% confidence interval [CI] 0.26 to 0.75), and related largely to the difference in prevalence of interatrial communication (OR 0.40; 95% CI 0.21 to 0.74). In contrast, African-Americans had a higher prevalence of left ventricular (LV) hypertrophy (OR 3.50; 95% CI 1.97 to 6.22), and particularly, moderate or severe hypertrophy (OR 4.03; 95% CI 1.88 to 9.65) compared with whites. In conclusion, in African-Americans with unexplained cerebrovascular events, the yield of TEE for potential cardioembolic sources, and especially interatrial communication, is lower than in their white counterparts. African-Americans exhibit a substantially higher prevalence of LV hypertrophy, which may be a marker for a higher burden of subclinical cerebrovascular disease involved in the pathogenesis of cryptogenic cerebral ischemia in this population.

Background: Extensive left ventricular (LV) dilatation after myocardial infarction (MI) is associated with increased heart failure risk. Aims: To investigate whether the power to demonstrate the relation between LV dilatation and heart failure depends on the method applied to predict LV dilatation after MI. Methods: A random-effects model and ANOVA model for repeated measurements (MANOVA) were applied to predict LV volume index during I year for 298 post-MI patients. Spearman correlation coefficients (r) were calculated and Cox regression analysis was used to calculate risk ratio's (RR). Results: LV volume indices were more accurately predicted by a random-effects model than by a MANOVA model (systolic/diastolic respectively r=0.93/0.91 vs. r=0.67/0.64). Furthermore, patients with high LV volume index as predicted by the random-effects model, had significantly increased heart failure risk (systolic RR 2.04 (95% CL 1.31 to 3.17; P=0.001), diastolic RR 1.80 (95% Cl: 1.16 to 2.78; P=0.007). Using the same data, MANOVA failed to demonstrate this relation significantly (systolic RR 1.77 (95% CL 0.79 to 3.98; P=0.16), diastolic RR 1.49 (95% Cl: 0.68 to 3.30; P=0.31). Conclusion: When analyzing repeated measurement data, random-effect models are more powerful in detecting clinical relations than are MANOVA models, especially in the presence of missing values. (C) 2002 European Society of Cardiology. Published by Elsevier Science B.V. All rights reserved.

Pulmonary artery systolic pressure (PASP) was examined in relationship to age, body mass index (BMI), the effects of comorbid disease, and standard echocardiographic measurements of cardiac chamber size, left ventricular filling patterns, and left ventricular systolic function in 5 large cohorts presenting with a primary problem of obesity. For subjects with a measurable PASP, means (± SD) across cohorts for age ranged from 46.0 ± 11.2 to 54.1 ± 12.8 years, for BMI from 26.0 ± 4.4 to 37.2 ± 6.1 kg/m 2 , and PASP (n = 1515) from 29.9 ± 7.7 to 33.8 ± 7.8 mm Hg. PASP 30 mm Hg or greater occurred in 46% to 66% of subjects and 35 mm Hg or greater in 16% to 36%. Age and BMI were the most significant correlates of PASP. Increased PASP was also significantly associated with systemic hypertension and a history of cardiovascular disease. The mean PASP in obese individuals is higher than previously reported with nearly one third having a PASP of 35 mm Hg or greater. Clinical interpretation of PASP should include BMI, age, blood pressure, and presence of cardiovascular disease. (J Am Soc Echocardiogr 2002;15:454-62.)

ObjectivesThe aim of this study was to determine the prognostic value of right ventricular (RV) function in patients after a myocardial infarction (MI).BackgroundRight ventricular function has been shown to predict exercise capacity, autonomic imbalance and survival in patients with advanced heart failure (HF).MethodsTwo-dimensional echocardiograms were obtained in 416 patients with left ventricular (LV) dysfunction (ejection fraction [LVEF] ≤40%) from the Survival And Ventricular Enlargement (SAVE) echocardiographic substudy (mean 11.1 ± 3.2 days post infarction). Right ventricular function from the apical four-chamber view, assessed as the percent change in the cavity area from end diastole to end systole (fractional area change [FAC]), was related to clinical outcome.ResultsRight ventricular function correlated only weakly with the LVEF (r = 0.12, p = 0.013). On univariate analyses, the RV FAC was a predictor of mortality, cardiovascular mortality and HF (p < 0.0001 for all) but not recurrent MI. After adjusting for age, gender, diabetes mellitus, hypertension, previous MI, LVEF, infarct size, cigarette smoking and treatment assignment, RV function remained an independent predictor of total mortality, cardiovascular mortality and HF. Each 5% decrease in the RV FAC was associated with a 16% increased odds of cardiovascular mortality (95% confidence interval 4.3% to 29.2%; p = 0.006).ConclusionsRight ventricular function is an independent predictor of death and the development of HF in patients with LV dysfunction after MI.