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.

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

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

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

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

Assessment of left ventricular systolic function by echocardiography.

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.

Clinical utility of automated assessment of left ventricular ejection fraction using artificial intelligence-assisted border detection.

BACKGROUND: Ejection fraction (EF) calculated from 2-dimensional echocardiography provides important prognostic and therapeutic information in patients with heart disease. However, quantification of EF requires planimetry and is time-consuming. As a result, visual assessment is frequently used but is subjective and requires extensive experience. New computer software to assess EF automatically is now available and could be used routinely in busy digital laboratories (>15,000 studies per year) and in core laboratories running large clinical trials. We tested Siemens AutoEF software (Siemens Medical Solutions, Erlangen, Germany) to determine whether it correlated with visual estimates of EF, manual planimetry, and cardiac magnetic resonance (CMR). METHODS: Siemens AutoEF is based on learned patterns and artificial intelligence. An expert and a novice reader assessed EF visually by reviewing transthoracic echocardiograms from consecutive patients. An experienced sonographer quantified EF in all studies using Simpson's method of disks. AutoEF results were compared to CMR. RESULTS: Ninety-two echocardiograms were analyzed. Visual assessment by the expert (R = 0.86) and the novice reader (R = 0.80) correlated more closely with manual planimetry using Simpson's method than did AutoEF (R = 0.64). The correlation between AutoEF and CMR was 0.63, 0.28, and 0.51 for EF, end-diastolic and end-systolic volumes, respectively. CONCLUSION: The discrepancies in EF estimates between AutoEF and manual tracing using Simpson's method and between AutoEF and CMR preclude routine clinical use of AutoEF until it has been validated in a number of large, busy echocardiographic laboratories. Visual assessment of EF, with its strong correlation with quantitative EF, underscores its continued clinical utility.

Abnormalities in 3-Dimensional Left Ventricular Mechanics With Anthracycline Chemotherapy Are Associated With Systolic and Diastolic Dysfunction.

OBJECTIVES: The objective of this study was to evaluate the changes in three-dimensional (3D) speckle-tracking echocardiography-derived measures of mechanics and their associations with systolic and diastolic dysfunction after anthracyclines. BACKGROUND: An improved understanding of the changes in 3D cardiac mechanics with anthracyclines may provide important mechanistic insight and identify new metrics to detect cardiac dysfunction. METHODS: A total of 142 women with breast cancer receiving doxorubicin (240 mg/m2) with or without trastuzumab underwent 3D speckle-tracking echocardiography at standardized intervals prior to, during, and annually after chemotherapy. Left ventricular ejection fraction (LVEF), global circumferential strain (GCS), global longitudinal strain (GLS), principal strain, twist, and torsion were quantified. Linear regression analyses defined the associations between clinical factors and 3D parameters. Linear regression models with cluster robust variance estimators determined the associations between 3D measures and 2-dimensional (2D) LVEF and Doppler-derived E/e' over time. RESULTS: There were significant abnormalities in 3D LVEF, GCS, GLS, and principal strain post-doxorubicin compared with control subjects (p < 0.001). The 3D parameters worsened post-anthracyclines, and only partially recovered to baseline over a median of 2.1 years (interquartile range: 1 to 4 years). Higher blood pressure and body mass index were associated with worse post-anthracycline 3D GCS and GLS, respectively. All 3D measures were associated with 2D LVEF at the same visit; only 3D LVEF, GCS, GLS, and principal strain were associated with 2D LVEF at subsequent visits (p < 0.05). In exploratory analyses, 3D LVEF and GCS were associated with subsequent systolic function independent of their corresponding 2D measures. The 3D LVEF, GCS, principal strain, and twist were significantly associated with concurrent, but not subsequent, E/e'. CONCLUSIONS: Anthracyclines result in early and persistent abnormalities in 3D mechanics. The 3D LVEF and strain measures are associated with concurrent and subsequent systolic dysfunction, and concurrent diastolic dysfunction. Future research is needed to define the mechanisms and clinical relevance of abnormal 3D mechanics.

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.

Sustained reverse left ventricular structural remodeling with cardiac resynchronization at one year is a function of etiology: quantitative Doppler echocardiographic evidence from the Multicenter InSync Randomized Clinical Evaluation (MIRACLE).

BACKGROUND: Cardiac resynchronization therapy (CRT) is an effective therapy for patients with moderate to severe heart failure and prolonged QRS duration. The purpose of this study was to determine whether reverse left ventricular (LV) remodeling and symptomatic benefit from CRT were sustained at 12 months, and if so, in what proportion of patients this occurred. METHODS AND RESULTS: Serial Doppler echocardiograms were obtained at baseline and 6 and 12 months after CRT in 228 patients enrolled in the Multicenter InSync Randomized Clinical Evaluation (MIRACLE) trial. Measurements were made of LV end-diastolic (EDV) and end-systolic (ESV) volumes, ejection fraction, LV mass, severity of mitral regurgitation (MR), peak transmitral velocities during early (E wave) and late (A wave) diastolic filling, and myocardial performance index. At both 6 and 12 months, respectively, CRT was associated with reduced LV EDV (P<0.0001 and P=0.007) and LV ESV (P<0.0001 and P<0.0001), improved ejection fraction (P<0.0001 and P<0.0001), regression of LV mass (P=0.012 and P<0.0001), and reduced MR (P<0.0001 and P<0.0001). LV filling time, transmitral E/A ratio, and myocardial performance index all improved at 12 months compared with baseline (P<0.001, P=0.031, and P<0.0001). Reverse LV remodeling with CRT occurred in more patients at 6 than at 12 months (74% versus 60%, respectively; P<0.05) and was greater in patients with a nonischemic than an ischemic etiology. CONCLUSIONS: Reverse LV remodeling and symptom benefit with CRT are sustained at 12 months in patients with New York Heart Association class III/IV heart failure but occur to a lesser degree in patients with an ischemic versus a nonischemic etiology, most likely owing to the inexorable progression of ischemic disease.

Cardiac mechanics and dysfunction with anthracyclines in the community: results from the PREDICT study.

BACKGROUND: Our objective was to determine the relevance of changes in myocardial mechanics in diagnosing and predicting cancer therapeutics-related cardiac dysfunction (CTRCD) in a community-based population treated with anthracyclines. METHODS: Quantitative measures of cardiac mechanics were derived from 493 echocardiograms in 165 participants enrolled in the PREDICT study (A Multicenter Study in Patients Undergoing AnthRacycline-Based Chemotherapy to Assess the Effectiveness of Using Biomarkers to Detect and Identify Cardiotoxicity and Describe Treatment). Echocardiograms were obtained primarily at baseline (prior to anthracyclines), 6 and 12 months. Predictors included changes in strain; strain rate; indices of contractile function derived from the end-systolic pressure-volume relationship (end-systolic elastance (Eessb) and the left ventricular (LV) volume at an end-systolic pressure of 100 mm Hg (V100)); total arterial load (effective arterial elastance (Ea)) and ventricular-arterial coupling (Ea/Eessb). Logistic regression models determined the diagnostic and prognostic associations of changes in these measures and CTRCD, defined as a LV ejection fraction decline ≥10 to <50%. RESULTS: By 12 months, 31 participants developed CTRCD. Longitudinal and circumferential strain and strain rate, V100, Ea, and Ea/Eessb each demonstrated significant diagnostic associations, with a 1-7% increased odds of CTRCD (p<0.05). Changes in longitudinal strain rate (area under the curve (AUC) 0.719 (95% CI 0.595 to 0.843)), V100 (AUC 0.796 (95% CI 0.686 to 0.903)) and Ea (AUC 0.742 (95% CI 0.632 to 0.852)) from baseline to 6 months were individually predictive of CTRCD at 12 months. CONCLUSIONS: Changes in non-invasively derived measures of myocardial mechanics are diagnostic and predictive of cardiac dysfunction with anthracycline chemotherapy in community populations. Our findings support the non-invasive assessment of measures of myocardial mechanics more broadly in clinical practice and emphasise the role of serial assessments of these measures during and after cardiotoxic cancer therapy. TRIAL REGISTRATION NUMBER: NCT01032278; Pre-results.

Predictors of remodeling in the CRT era: influence of mitral regurgitation, BNP, and gender.

BACKGROUND: We analyzed quantitative echocardiographic data from a large heart failure cohort receiving medical and cardiac resynchronization therapy (CRT) to determine baseline predictors of progressive left ventricular (LV) enlargement. METHODS AND RESULTS: Quantitative echocardiograms were obtained at baseline and after 6 months in 776 outpatients with chronic heart failure who participated in MIRACLE (Multicenter InSync Randomized Clinical Evaluation) and MIRACLE-ICD (Multicenter InSync ICD Randomized Clinical Evaluation). We used multivariable regression to determine clinical, therapeutic, and echocardiographic characteristics that predicted a subsequent change in left ventricular end-diastolic volume (LVEDV). Over 6 months, LVEDV increased in 308 (40%) and decreased in 468 (60%) patients. Baseline mitral regurgitation and levels of plasma brain natriuretic peptide (BNP) independently predicted LV enlargement, whereas CRT predicted a decrease in LVEDV (all P < .01). In all models tested, male gender was an independent risk factor for progressive LV enlargement (P < .0001). CONCLUSION: Men show more prominent LV dilation than women in chronic heart failure despite medical and device therapy. Rates of LV remodeling are influenced further by mitral regurgitation, plasma BNP, and CRT. Future studies should take these clinical factors into account when determining the influence of genetic factors and novel therapies on ventricular remodeling in chronic heart failure.

Left ventricular remodeling and ventricular arrhythmias after myocardial infarction.

BACKGROUND: The relation between left ventricular (LV) remodeling and ventricular arrhythmias after myocardial infarction is poorly documented. We investigated the relations between LV size, hypertrophy, and function and ventricular arrhythmias in 263 patients from the Survival and Ventricular Enlargement (SAVE) study, using quantitative 2D echocardiography and ambulatory ECG monitoring after myocardial infarction. METHODS AND RESULTS: Transthoracic 2D echocardiograms and arrhythmia monitoring were performed at baseline (mean, 11 days) and 1 and 2 years after infarction. LV size, short-axis muscle (mass) area (LVMA), and function were quantified from 2D echocardiograms. The prevalence of ventricular tachycardia (VT) and frequent ventricular ectopy (premature ventricular contractions [PVCs] >10/h) was assessed from ambulatory ECG. VT and PVCs >10/h occurred in 20% and 29% of patients at baseline, in 22% and 35% at 1 year and 23% and 39% at 2 years, respectively. VT and PVCs >10/h at baseline and 1 and 2 years were significantly related to LV size, LVMA, and function. Furthermore, changes in LV size and function from baseline to 2 years predicted both VT and PVCs >10/h. The study was underpowered to detect treatment effect of ACE inhibitors and beta-adrenergic receptor blockers but did not alter the relations between ventricular arrhythmias, LV size, and function. CONCLUSIONS: Quantitative echocardiographic assessment of LV size, LVMA, and function and changes in these measurements over time predict ventricular arrhythmias after infarction. Altered LV architecture and function during postinfarction LV remodeling provide an important substrate for triggering high-grade ventricular arrhythmias.

Ventricular remodeling does not accompany the development of heart failure in diabetic patients after myocardial infarction.

BACKGROUND: Diabetic patients are at increased risk for heart failure (HF) and other adverse events after myocardial infarction (MI). Left ventricular (LV) enlargement after MI is also associated with the same increased risk. We used data from the Survival and Ventricular Enlargement (SAVE) echocardiographic substudy to test the hypothesis that diabetes was associated with increased LV enlargement after MI. METHODS AND RESULTS: Four hundred twelve nondiabetic and 100 diabetic patients underwent echocardiographic assessment at baseline and 3 months, 1 year, and 2 years after MI. HF developed in 30% of diabetic and 17% of nondiabetic patients during follow-up (P<0.001). Baseline LV diastolic size, ejection fraction, and infarct segment length were similar between diabetic and nondiabetic patients. Diabetic patients demonstrated less LV enlargement between baseline and 2 years than nondiabetic patients (0.9+/-11.1 cm2 versus 3.8+/-10.9 cm2, P=0.047). In patients who developed HF, LV diastolic dilatation (10.0+/-12.4 cm2 versus 3.7+/-13.1 cm2, P=0.06) and systolic dilatation (4.6+/-11.8 versus 0.91+/-12.1, P=0.017) were greater in nondiabetic than in diabetic patients. LV dilatation between baseline and 2 years was a predictor of HF in nondiabetic patients, but not in diabetic patients, even after excluding patients with recurrent MI and adjusting for history of hypertension, prior MI, age, treatment group, and smoking. Diabetes modified the relationship between ventricular enlargement and the risk of HF (P=0.011). CONCLUSIONS: The increased incidence of HF after MI in diabetic patients is not explained by a greater propensity for LV remodeling.

Effect of cardiac resynchronization therapy on left ventricular size and function in chronic heart failure.

BACKGROUND: Cardiac resynchronization therapy (CRT) has recently emerged as an effective treatment for patients with moderate to severe systolic heart failure and ventricular dyssynchrony. The purpose of the present study was to determine whether improvements in left ventricular (LV) size and function were associated with CRT. METHODS AND RESULTS: Doppler echocardiograms were obtained at baseline and at 3 and 6 months after therapy in 323 patients enrolled in the Multicenter InSync Randomized Clinical Evaluation (MIRACLE) trial. Of these, 172 patients were randomized to CRT on and 151 patients to CRT off. Measurements were made of LV end-diastolic and end-systolic volumes, ejection fraction, LV mass, severity of mitral regurgitation (MR), peak transmitral velocities during early (E-wave) and late (A-wave) diastolic filling, and the myocardial performance index. At 6 months, CRT was associated with reduced end-diastolic and end-systolic volumes (both P<0.001), reduced LV mass (P<0.01), increased ejection fraction (P<0.001), reduced MR (P<0.001), and improved myocardial performance index (P<0.001) compared with control. beta-Blocker treatment status did not influence the effect of CRT. Improvements with CRT were greater in patients with a nonischemic versus ischemic cause of heart failure. CONCLUSIONS: CRT in patients with moderate-to-severe heart failure who were treated with optimal medical therapy is associated with reverse LV remodeling, improved systolic and diastolic function, and decreased MR. LV remodeling likely contributes to the symptomatic benefits of CRT and may herald improved longer-term survival.

Right ventricular dysfunction and risk of heart failure and mortality after myocardial infarction.

OBJECTIVES: The aim of this study was to determine the prognostic value of right ventricular (RV) function in patients after a myocardial infarction (MI). BACKGROUND: Right ventricular function has been shown to predict exercise capacity, autonomic imbalance and survival in patients with advanced heart failure (HF). METHODS: Two-dimensional echocardiograms were obtained in 416 patients with left ventricular (LV) dysfunction (ejection fraction [LVEF] < or = 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. RESULTS: Right 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). CONCLUSIONS: Right ventricular function is an independent predictor of death and the development of HF in patients with LV dysfunction after MI.

Prognostic use of echocardiography 1 year after a myocardial infarction.

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

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.

Effect of antecedent systemic hypertension on subsequent left ventricular dilation after acute myocardial infarction (from the Survival and Ventricular Enlargement trial).

Whether antecedent systemic hypertension influences the risk of subsequent left ventricular (LV) dilation in patients after an acute myocardial infarction with LV systolic dysfunction is unclear. We assessed echocardiographic evidence of ventricular remodeling from baseline (mean +/- SD 11 +/- 3 days) to 2 years after an acute myocardial infarction in 122 hypertensive (defined as a history of treated hypertension, baseline systolic blood pressure > or =140 or baseline diastolic blood pressure > or =90 mm Hg) and 334 nonhypertensive patients in the Survival and Ventricular Enlargement echocardiographic substudy. Compared with nonhypertensives, baseline heart size, defined as the sum of the average short- and long-axis LV cavity areas, was similar (70.1 +/- 11.9 vs 68.8 +/- 11.2 cm(2), p = 0.33 at end-diastole; 50.1 +/- 11.3 vs 48.8 +/- 10.8 cm(2), p = 0.31 at end-systole), but short-axis LV myocardial area (24.7 +/- 4.3 vs 25.7 +/- 5.0 cm(2), p = 0.043) and wall thickness (1.15 +/- 0.16 vs 1.21 +/- 0.17 cm, p = 0.004) at end-diastole were greater among hypertensives. The myocardial infarct segment lengths were similar in the 2 groups (p = 0.22). Although LV cavity areas increased significantly in the 2 groups from baseline to 2 years (p < or =0.001), the increase was significantly greater in hypertensives than in nonhypertensives (+5.6 +/- 11.5 vs +2.2 +/- 10.7 cm(2), p = 0.005 at end-diastole; +6.23 +/- 12.75 vs +2.94 +/- 11.4 cm(2), p = 0.012 at end-systole). There was no concomitant difference in the change in LV myocardial area or LV wall thickness between the 2 groups (p >0.30). After adjusting for known confounders, antecedent hypertension was associated with a doubling of the risk of LV dilation (50.8% vs 37.7%, odds ratio 2.09, 95% confidence interval 1.27 to 3.45, p = 0.004). This association was not modified by diabetes mellitus, myocardial infarct segment length, or captopril use (all p values for interaction >0.10). We conclude that antecedent hypertension is associated with subsequent LV dilation in patients after acute myocardial infarction with LV systolic dysfunction.

Correction of traumatic tricuspid regurgitation using the double orifice technique.

We present a case of acute traumatic tricuspid regurgitation in a 39-year-old man who was involved in a motor vehicle accident. A large ecchymotic region over the anterior chest wall prompted evaluation by both transthoracic and transesophageal echocardiography which confirmed the valvular injury. At surgery, valvular incompetence was found to be the result of a flail anterior leaflet due to papillary muscle rupture. The valve was successfully repaired using a single stitch double orifice technique in combination with a ring annuloplasty. The valve remains competent 18 months after surgery.

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.

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.