Economic value and cost-effectiveness of biventricular versus right ventricular pacing: results from the BLOCK-HF study.

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.

Echocardiography Core Laboratory Reproducibility of Cardiac Safety Assessments in Cardio-Oncology.

BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

Racial/Ethnic Differences in Left Ventricular Structure and Function in Chronic Kidney Disease: The Chronic Renal Insufficiency Cohort.

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.

Left Ventricular Architecture, Long-Term Reverse Remodeling, and Clinical Outcome in Mild Heart Failure With Cardiac Resynchronization: Results From the REVERSE Trial.

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 <40%, and QRS duration >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 < 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 index >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).

Dietary therapy in heart failure with preserved ejection fraction and/or left ventricular diastolic dysfunction in patients with metabolic syndrome.

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.

The Impact of the PR Interval in Patients Receiving Cardiac Resynchronization Therapy: Results From the REVERSE Study.

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 (hazard ratio [HR]: 0.34) and 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).

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.

Improvement in Clinical Outcomes With Biventricular Versus Right Ventricular Pacing: The BLOCK HF Study.

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).

Effects of Cardiac Resynchronization Therapy on Cardiac Remodeling and Contractile Function: Results From Resynchronization Reverses Remodeling in Systolic Left Ventricular Dysfunction (REVERSE).

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 Resynchronization 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<0.01). There were no consistent effects on end-systolic elastance, stroke work, preload recruitable stroke work, or ventricular-arterial coupling. In the active cardiac resynchronization therapy population, baseline measures of arterial load were associated with the clinical composite score (odds ratio 1.30, 95% 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: NCT00271154.

Ventricular assist devices for treatment of acute heart failure and chronic heart failure.

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.

Left Ventricular Reverse Remodeling With Biventricular Versus Right Ventricular Pacing in Patients With Atrioventricular Block and Heart Failure in the BLOCK HF Trial.

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.

The effect of reverse remodeling on long-term survival in mildly symptomatic patients with heart failure receiving cardiac resynchronization therapy: results of the REVERSE study.

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.

Strain improves risk prediction beyond ejection fraction in chronic systolic heart failure.

BACKGROUND: The utility of longitudinal, circumferential, and radial strain and strain rate in determining prognosis in chronic heart failure is not well established. METHODS AND RESULTS: In 416 patients with chronic systolic heart failure, we performed speckle-tracking analyses of left ventricular longitudinal, circumferential, and radial strain and strain rate on archived echocardiography images (30 frames per second). Cox regression models were used to determine the associations between strain and strain rate and risk of all-cause mortality, cardiac transplantation, and ventricular-assist device placement. The area under the time-dependent ROC curve (AUC) was also calculated at 1 year and 5 years. Over a maximum follow-up of 8.9 years, there were 138 events (33.2%). In unadjusted models, all strain and strain rate parameters were associated with adverse outcomes (P<0.001). In multivariable models, all parameters with the exception of radial strain rate (P=0.11) remained independently associated, with patients in the lowest tertile of strain or strain rate parameter having a ≈ 2-fold increased risk of adverse outcomes compared with the reference group (P<0.05). Addition of strain to ejection fraction (EF) led to a significantly improved AUC at 1 year (0.697 versus 0.633, P=0.032) and 5 years (0.700 versus 0.638, P=0.001). In contrast, strain rate did not provide incremental prognostic value to EF alone. CONCLUSIONS: Longitudinal and circumferential strain and strain rate, and radial strain are associated with chronic heart failure prognosis. Strain provides incremental value to EF in the prediction of adverse outcomes, and with additional study may be a clinically relevant prognostic tool.

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.

Impact of ejection fraction on the clinical response to cardiac resynchronization therapy in mild heart failure.

BACKGROUND: Current guidelines recommend cardiac resynchronization therapy (CRT) in mild heart failure (HF) patients with QRS prolongation and ejection fraction (EF) ≤30%. To assess the effect of CRT in less severe systolic dysfunction, outcomes in the REsynchronization reVErses Remodeling in Systolic left vEntricular dysfunction (REVERSE) study were evaluated in which patients with left ventricular (LV) ejection fraction (LVEF) >30% were included. METHODS AND RESULTS: The results of patients with baseline EF >30% (n=177) and those with EF ≤30% (n=431), as determined by a blinded core laboratory, were compared. In the LVEF >30% subgroup, there was a trend for improvement in the clinical composite response with CRT ON versus CRT OFF (P=0.06) and significant reductions in LV end systolic volume index (-6.7 ± 21.1 versus 2.1 ± 17.6 mL/m(2); P=0.01) and LV mass (-20.6 ± 50.5 versus 5.0 ± 42.4 g; P=0.04) after 12 months. The time to death or first HF hospitalization was significantly prolonged with CRT (hazard ratio, 0.26; P=0.012). In the LVEF <30% subgroup, significant improvements in clinical composite response (P=0.02), reverse remodeling parameters, and time to death or first HF hospitalization (hazard ratio, 0.58; P=0.047) were observed. After adjusting for important covariates, the CRT ON assignment remained independently associated with improved time to death or first HF hospitalization (hazard ratio, 0.54; P=0.035), whereas there was no significant interaction with LVEF. CONCLUSIONS: Among subjects with mild HF, QRS prolongation, and LVEF >30%, CRT produced reverse remodeling and similar clinical benefit compared with subjects with more severe LV systolic dysfunction. CLINICAL TRIAL REGISTRATION- URL: http://www.clinicaltrials.gov. Unique identifier: NCT00271154.

Ventricular-arterial coupling, remodeling, and prognosis in chronic heart failure.

OBJECTIVES: The objective of this study was to compare the physiological determinants of ejection fraction (EF)-ventricular size, contractile function, and ventricular-arterial (VA) interaction-and their associations with clinical outcomes in chronic heart failure (HF). BACKGROUND: EF is a potent predictor of HF outcomes, but represents a complex summary measure that integrates several components including left ventricular size, contractile function, and VA coupling. The relative importance of each of these parameters in determining prognosis is unknown. METHODS: In 466 participants with chronic systolic HF, we derived quantitative echocardiographic measures of EF: cardiac size (end-diastolic volume [EDV]); contractile function (the end-systolic pressure volume relationship slope [Eessb] and intercept [V0]); and VA coupling (arterial elastance [Ea]/Eessb). We determined the association between these parameters and the following adverse outcomes: 1) the combined endpoint of death, cardiac transplantation, or ventricular assist device (VAD) placement; and 2) cardiac hospitalization. RESULTS: Over a median follow-up of 3.4 years, there were 76 deaths, 52 transplantations, 14 VAD placements, and 684 cardiac hospitalizations. EF was independently associated with death, transplantation, and VAD placement (adjusted hazard ratio [HR]: 3.0; 95% confidence interval [CI]: 1.8 to 5.0 comparing third and first tertiles), as were EDV (HR: 2.6; 95% CI: 1.5 to 4.2); V0 (HR: 3.6; 95% CI: 2.1 to 6.1); and Ea/Eessb (HR: 2.1; 95% CI: 1.3 to 3.3). EDV, V0, and Ea/Eessb were also associated with risk of cardiac hospitalization. Eessb was not significantly associated with any adverse outcomes in adjusted analyses. CONCLUSIONS: Left ventricular size, V0, and VA coupling are associated with prognosis in systolic HF, but end-systolic elastance (Eessb) is not. Assessment of VA coupling via Ea/Eessb is an additional noninvasively derived metric that can be used to gauge prognosis in human HF.

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.

Early and late systolic wall stress differentially relate to myocardial contraction and relaxation in middle-aged adults: the Asklepios study.

Experimental studies implicate late systolic load as a determinant of impaired left-ventricular relaxation. We aimed to assess the relationship between the myocardial loading sequence and left-ventricular contraction and relaxation. Time-resolved central pressure and time-resolved left-ventricular geometry were measured with carotid tonometry and speckle-tracking echocardiography, respectively, for computation of time-resolved ejection-phase myocardial wall stress (EP-MWS) among 1214 middle-aged adults without manifest cardiovascular disease from the general population. Early diastolic annular velocity and systolic annular velocities were measured with tissue Doppler imaging, and segment-averaged longitudinal strain was measured with speckle-tracking echocardiography. After adjustment for age, sex, and potential confounders, late EP-MWS was negatively associated with early diastolic mitral annular velocity (standardized ß=-0.25; P<0.0001) and mitral inflow propagation velocity (standardized ß=-0.13; P=0.02). In contrast, early EP-MWS was positively associated with early diastolic mitral annular velocity (standardized ß=0.18; P<0.0001) and mitral inflow propagation velocity (standardized ß=0.22; P<0.0001). A higher late EP-MWS predicted a lower systolic mitral annular velocity (standardized ß=-0.31; P<0.0001) and lesser myocardial longitudinal strain (standardized ß=0.32; P<0.0001), whereas a higher early EP-MWS was associated with a higher systolic mitral annular velocity (standardized ß=0.16; P=0.002) and greater longitudinal strain (standardized ß=-0.24; P=0.002). The loading sequence remained independently associated with early diastolic mitral annular velocity after adjustment for systolic mitral annular velocity or systolic longitudinal strain. In the context of available experimental data, our findings support the role of the myocardial loading sequence as a determinant of left-ventricular systolic and diastolic function. A loading sequence characterized by prominent late systolic wall stress was associated with lower longitudinal systolic function and diastolic relaxation.