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ObjectivesThis study was conducted to test the hypothesis that cardiac micro-ribonucleic acid (miR) profiling in severe heart failure patients at the time of ventricular assist device (VAD) placement would differentiate those who remained VAD-dependent from those with subsequent left ventricular (LV) recovery.BackgroundThe relationship of myocardial miR expression to ventricular recovery is unknown.MethodsWe studied 28 patients with nonischemic cardiomyopathy requiring VAD support consisting of test and validation cohorts from 2 institutions: 14 with subsequent LV recovery and VAD removal and 14 clinically matched VAD-dependent patients. Apical core myocardium was studied for expression of 376 miRs by polymerase chain reaction (PCR) array and real-time-PCR methods. Samples from 7 nonfailing hearts were used in confirmatory studies.ResultsBy PCR array, 10 miRs were differentially expressed between LV recovery and VAD-dependent patients in the test cohort. The real-time PCR confirmed lower expression in LV recovery patients for 4 miRs (15b, −1.5-fold; 23a, −2.2-fold; 26a, −1.4-fold; and 195, −1.8-fold; all p < 0.04 vs. VAD dependent). The validation cohort similarly showed lower miRs expression in LV recovery patients (23a, −1.8-fold; and 195, −1.5-fold; both p < 0.03). Furthermore, miR 23a and 195 expression in nonfailing hearts was similar to LV recovery patients (both p < 0.04 vs. VAD dependent). The LV recovery patients also had significantly smaller cardiomyocytes by quantitative histology in both cohorts.ConclusionsLower cardiac expression of miRs 23a and 195 and smaller cardiomyocyte size at the time of VAD placement were associated with subsequent LV functional recovery. Differential expression of miRs at VAD placement may provide markers to assess recovery potential.

Background Most current indices of synchrony quantify left ventricular (LV) contraction pattern in terms of a single, global (integrated) measure. We report the development and physiological relevance of a novel method to quantify LV segmental contraction synchrony.

Objectives We sought to determine clinical and demographic predictors of recovery of left ventricular function for subjects with recent onset cardiomyopathy (ROCM). Background Although ROCM is a frequent reason for consultation and transplantation referral, its prognosis and natural history on contemporary therapy are unknown. Methods In the multicenter IMAC (Intervention in Myocarditis and Acute Cardiomyopathy)-2 study, subjects with a left ventricular ejection fraction (LVEF) of ≤0.40, fewer than 6 months of symptom duration, and an evaluation consistent with idiopathic dilated cardiomyopathy or myocarditis were enrolled. LVEF was reassessed at 6 months, and subjects were followed up for 4 years. LVEF and event-free survival were compared by race, sex, and clinical phenotype. Results The cohort of 373 persons was 38% female and 21% black, with a mean age of 45 ± 14 years. At entry, 91% were receiving angiotensin-converting enzyme inhibitors or angiotensin receptor blockers and 82% were receiving beta-blockers, which increased to 92% and 94% at 6 months. LVEF was 0.24 ± 0.08 at entry and 0.40 ± 0.12 at 6 months (mean increase: 17 ± 13 ejection fraction units). Transplant-free survival at 1, 2, and 4 years was 94%, 92%, and 88%, respectively; survival free of heart failure hospitalization was 88%, 82%, and 78%, respectively. In analyses adjusted for sex, baseline LVEF, and blood pressure, LVEF at 6 months was significantly lower in blacks than in nonblacks (p = 0.02). Left ventricular end-diastolic diameter at presentation was the strongest predictor of LVEF at 6 months (p Conclusions Outcomes in ROCM are favorable but differ by race. Left ventricular end-diastolic diameter by transthoracic echo at presentation was most predictive of subsequent myocardial recovery. (Genetic Modulation of Left Ventricular Recovery in Recent Onset Cardiomyopathy; NCT00575211 )

Although there is little debate over the fact that cardiac resynchronization therapy (CRT) can benefit the majority of patients selected with routine indications, the precise mechanism for improvement may be considered controversial. Among patients selected with New York Heart Association functional class III or IV symptoms, left ventricular ejection fraction ≤ 35% and electrocardiographic QRS widening of at least 120-130 ms, approximately 60-80% of patients improved depending on the definition of response used. Although a reasonable assumption is that electrocardiographic QRS widening is a surrogate for delays in regional ventricular mechanical activation, a large volume of data has demonstrated that there is a subset of patients with widened QRS complexes who have no significant mechanical dyssynchrony. The reason for dissociation of electrical dispersion and mechanical dyssynchrony is unknown presently, but many studies have demonstrated the association of dyssynchrony with favorable outcome following CRT. Perhaps more importantly, several imaging studies (principally by echocardiography) have shown the lack of baseline mechanical dyssynchrony to be as a marker for a less favorable outcome after CRT. Recently, the lack of dyssynchrony before CRT has been shown to be associated with a significantly lower long-term probability of freedom from death, heart transplantation, or left ventricular assist device placement. As further mechanistic evidence for the relationship of mechanical dyssynchrony and LV functional response to CRT, it has been suggested that patients who failed to improve their tissue Doppler measures of dyssynchrony after CRT have a lower chance of reverse remodeling. This topic has been muddled by technical difficulties in measurement of mechanical dyssynchrony by all imaging approaches, the confounding variable of scar in ischemic disease, and the widely variable definitions of response used by different investigators. However, the weight of evidence from a pathophysiological basis to the recent long-term patient outcome data strongly support the notion that resynchronization is the principle mechanism of benefit from CRT.

Objectives The purpose of this study was to evaluate mechanical dyssynchrony in patients with acute onset cardiomyopathy with narrow QRS interval, and its association with improvements in left ventricular (LV) function. Background LV dyssynchrony has been usually studied in patients with chronic heart failure and wide QRS in the context of cardiac resynchronization therapy. Methods We studied 201 patients enrolled in the IMAC-2 (Inflammatory Mediators in Acute Cardiomyopathy) trial with recent onset nonischemic cardiomyopathy and ejection fraction Results Although mean QRS was narrow (98 ± 21 ms), 108 (54%) acute cardiomyopathy patients had significant LV dyssynchrony at presentation: opposing wall delay 89 ± 51 ms, versus 35 ± 11 ms in controls, and 12-site standard deviation 43 ± 23, versus 24 ± 8 ms in controls (p Conclusions Mechanical dyssynchrony was observed in a significant number of patients with acute onset cardiomyopathy, despite having a narrow QRS interval. Resolution of dyssynchrony associated with improvements in LV function occurred in the large majority of these patients.

Resynchronizing Pacemaker-Dependent Patients. Introduction: Right ventricular (RV) pacing engenders left ventricular (LV) dyssynchrony and may diminish LV systolic function, promote adverse cardiac remodeling, and foster heart failure (HF). This process may be reversible in some pacemaker-dependent patients upgraded to cardiac resynchronization therapy (CRT). We examined the clinical characteristics of pacemaker-dependent patients who exhibit hyperresponse (i.e., normalization of LV function) with CRT upgrade. Methods and Results: We identified 51 chronically RV-paced patients with no coronary artery disease, LV ejection fraction (EF) ≤ 35%, and severe HF symptoms who were upgraded to CRT-defibrillators (CRT-D). Echocardiograms were performed before and ≥6 months after CRT. Patients with follow-up LVEF ≥ 50% were deemed hyperresponders. Clinical outcomes of death, cardiac transplant, mechanical circulatory support, and HF hospitalizations were assessed. Fifteen patients were CRT hyperresponders; all demonstrated ≥15% relative LV end-systolic volume decrease. Hyperresponders had smaller baseline LV dimensions and shorter known cardiomyopathy duration than nonhyperresponders (P < 0.01). The best predictors of hyperresponse using receiver operating characteristic analysis were LV end-systolic dimension

The benefit of cardiac resynchronization therapy (CRT) for most heart failure (HF) patients with low ejection fraction (EF) and widened QRS is undisputed. Mortality and HF hospitalization are reduced, and multiple measures of cardiac function are improved. It remains of clinical importance that

Cardiac resynchronization therapy (CRT) is believed to benefit patients by primarily correcting heterogeneity in regional ventricular mechanical contraction, known as dyssynchrony. Although many symptomatic heart failure patients with depressed left ventricular ejection fraction and widened electrocardiographic QRS complexes have clinical improvement from CRT, a significant subset of approximately one-third do not seem to respond. Because the degree of mechanical dyssynchrony may be widely variable, interest has remained high to attempt to improve patient selection for CRT using cardiac imaging as a means to quantify dyssynchrony. This article will review the principal echocardiographic methods of dyssynchrony analysis by tissue Doppler imaging, (opposing wall delay, 12-site standard deviation or Yu index, and longitudinal strain), routine pulsed-Doppler (interventricular mechanical delay, pre-ejection delay and filling time ratio), and speckle tracking (including radial, circumferential, and longitudinal strain). In addition, dyssynchrony analysis by cardiac magnetic resonance imaging is introduced as a potential alternative technique. The technical features, strengths and limitations, and clinical evidence for these methods are discussed, including a practical clinical approach.

Biventricular pacing or cardiac resynchronization therapy (CRT) has been a considerable advance in the therapy of chronic heart failure. However, it is clear that not all patients benefit either in terms of symptoms or cardiac function, and some may be worsened by CRT. In this review, we consider the arguments, both clinical and economical, in favour of improved selection of patients for CRT other than those in current guidelines. It also seems clear that the fundamental mechanism of CRT is correction of dyssynchrony, and we review the various methodologies available to detect dyssynchrony. Other factors are probably also important in determining outcomes such as lead position, the extent and form of myocardial damage, optimizing pacemaker performance, and clinical expertise. The potential costs of inappropriate CRT implantation are high to our patients and to the health economy, and it behooves the cardiology community to develop better selection criteria. The current guidelines can and should be improved.

International audience; INTRODUCTION: Current guidelines recommend cardiac resynchronisation therapy (CRT) in patients with severe symptomatic heart failure, depressed left ventricular (LV) systolic function and a wide QRS complex (>or=120 ms). However, patients with heart failure having a narrow QRS complex might also benefit from CRT. DESIGN SETTING PATIENTS INTERVENTIONS: During the Predictors of Response to Cardiac Resynchronisation Therapy (PROSPECT) trial, 41 patients were enrolled in a 'narrow' QRS sub-study. These patients had a QRS complex

Background Some studies suggest that right ventricular (RV) pacing has an adverse impact on left ventricular ejection fraction (LVEF), particularly in subjects with preexisting left ventricular (LV) dysfunction, and that direct LV pacing may be relatively protective. Interactions between pacing site and LVEF remain unclear. Objective The purpose of this study was to examine the relative impact of RV and LV pacing on LVEF by serial study during a period in which LV dysfunction, induced by tachypacing, was introduced and then resolved. Methods In each of five dogs, RV, LV, and simultaneous RV and LV (BiV) pacing modes were compared to native ventricular activation (1) prior to tachypacing (baseline), (2) weekly during a 5-week continuous tachypacing period, and (3) weekly during a 3-week post-tachypacing recovery period. At each evaluation, LVEF and LV contraction synchrony were assessed during each pacing mode. Results The decrease in LVEF during the tachypacing period was more pronounced during RV pacing than during native activation or LV or BiV pacing. The magnitude of this effect correlated with a diminishment in LV contraction synchrony that was not observed during native activation or LV or BiV pacing. During the post-tachypacing period, gradual reversal of these changes toward baseline was observed. Conclusion Compared to native activation, RV pacing worsens LVEF in a manner proportional to the severity of preexisting LV dysfunction, attributable to reduced LV contraction synchrony. In comparison, both LV and BiV pacing preserve LVEF and contraction synchrony.

Section Editor: Thomas H. Marwick, MBBS, PHD cardiac resynchronization therapy (crt) may provide a dramatic improvement of symptom status and outcome in many patients with heart failure. Unfortunately, the use of current selection criteria is associated with a failure to respond on symptomatic or

ObjectivesThe goals of this study were to compare patterns of mechanical activation in patients with chronic right ventricular (RV) pacing with those with left bundle branch block (LBBB) using 2-dimensional and novel 3-dimensional speckle tracking, and to compare ejection fraction (EF) response and long-term survival after cardiac resynchronization therapy (CRT).BackgroundSeveral randomized CRT trials have excluded patients with chronic RV pacing, and current guidelines for CRT include patients with intrinsically widened QRS, typically LBBB.MethodsWe studied 308 patients who were referred for CRT: 227 had LBBB, 81 were RV paced. Dyssynchrony was assessed by tissue Doppler, routine pulsed Doppler, and 2-dimensional speckle-tracking radial strain. 3D strain was assessed using speckle tracking from a pyramidal dataset in a subset of 57 patients for mechanical activation mapping. Survival after CRT was compared with survival in a group of 46 patients with attempted, but failed, CRT.ResultsPatients with chronic RV pacing and LBBB had similar intraventricular dyssynchrony, with opposing wall delays by tissue Doppler of 82 ± 45 ms versus 87 ± 63 ms and anteroseptum-to-posterior delays by speckle tracking of 225 ± 142 ms, versus 211 ± 107 ms, respectively. RV-paced patients, however, had greater interventricular dyssynchrony: 44 ± 24 ms versus 35 ± 21 ms (p < 0.01), which correlated with their greater QRS duration (p < 0.001). Sites of latest mechanical activation were most often posterior or lateral in both groups, but RV-paced patients had sites of earliest activation more often from the inferior-septum and apex (p < 0.05). EF response was similar in RV-paced and LBBB groups, and survival free from transplantation or mechanical support after CRT was similarly favorable as compared with failed CRT patients over 5 years (p < 0.01).ConclusionsRV-paced patients, when compared with LBBB patients, had similar dyssynchronous patterns of mechanical activation and greater interventricular dyssynchrony. Importantly, RV-paced patients had similar EF response and long-term outcome as those with LBBB, which supports their candidacy for CRT.

Lung transplantation is important therapeutic option for scleroderma patients with end stage lung disease. The means to determine long term prognosis after transplantation remains unclear. We studied 59 scleroderma patients before lung transplantation with routine and speckle tracking echo. A

Pulmonary arterial hypertension (PAH) is a devastating disease with variable progression. Prediction of risk remains challenging. We hypothesized that quantification of RA function by strain echocardiography has prognostic value. We studied 151 patients with pre-capillary primary PAH by speckle

Subarachnoid hemorrhage (SAH) can be associated with an acute stress cardiac injury. A reverse takotsubo pattern with apical sparing has been described, but not clearly understood. From our prospective study (R01NR04221), 221 patients with acute aneurysmal SAH had a strain echo on 2.3 days from

Left atrial (LA) function is important in heart failure. LA strain is a novel method to quantify LA function. We hypothesized that LA strain has prognostic significance in peripartum cardiomyopathy (PPCM). We studied 100 PPCM patients in the multicenter Pregnancy Associated Cardiomyopathy study [LV

Previous methods to quantify dyssynchrony could not determine regional 3-dimensional (3-D) strain. We hypothesized that a novel 3-D speckle tracking strain imaging system can quantify left ventricular (LV) dyssynchrony and site of latest mechanical activation. We studied 64 subjects; 54 patients with heart failure were referred for cardiac resynchronization therapy (CRT) with an ejection fraction 25 +/- 6% and QRS interval 165 +/- 29 ms and 10 healthy volunteer controls. The 3-D speckle tracking system determined radial strain using a 16-segment model from a pyramidal 3-D dataset. Dyssynchrony was quantified as maximal opposing wall delay and SD in time to peak strain. The 3-D analysis was compared to standard 2-dimensional (2-D) strain datasets and site of 3-D latest mechanical activation, not possible by 2D was quantified. As expected, dyssynchrony in patients on CRT was significantly greater than in controls (maximal opposing wall delay 316 +/- 112 vs 59 +/- 12 ms and SD 124 +/- 48 vs 28 +/- 11 ms, p0.001 vs normal). The 3-D opposing wall delay was closely correlated with 3-D 16-segment SD (r = 0.95) and 2-D mid-LV strain (r = 0.83) and SD (r = 0.85, all p values0.001). The 3-D site of the latest mechanical activation was most commonly midposterior (26%), basal posterior (22%), midlateral (20%), and basal lateral (17%). Eleven patients studied after CRT demonstrated improvements in 3-D synchrony (300 +/- 124 to 94 +/- 37 ms) and ejection fraction (24 +/- 6% to 31 +/- 7%, p0.05). In conclusion, 3-D speckle tracking can successfully quantify 3-D dyssynchrony and site the latest mechanical activation. This approach may play a clinical role in management of patients on CRT.

Background and Purpose— Cardiac injury persistence after aneurysmal subarachnoid hemorrhage (aSAH) is not well described. We hypothesized that post-aSAH cardiac injury, detected by elevated cardiac troponin I (cTnI), is related to aSAH severity and associated with electrocardiographic and structural echocardiographic abnormalities that are persistent. Methods— Prospective longitudinal study was conducted of patients with aSAH with Fisher grade ≥2 and/or Hunt/Hess grade ≥3. Serum cTnI was collected on Days 1 to 5; cohort dichotomized into peak cTnI ≥0.3 ng/mL (elevated) or cTnI Results— Of 204 subjects, 31% had cTnI ≥0.3 ng/mL. cTnI ≥0.3 ng/mL was incrementally related to aSAH severity by admission symptoms (Hunt/Hess P =0.001) and blood load (Fisher P =0.028). More patients with cTnI ≥0.3 ng/mL had prolonged QTc on early (63% versus 30%, P P =0.024). On Holter monitoring, more patients with cTnI ≥0.3 ng/mL had ventricular tachycardia/fibrillation (22% versus 9%, P =0.018) but not atrial fibrillation/flutter ( P =0.241). Cardiac troponin I ≥0.3 ng/mL was associated with both early ejection fraction P P Conclusions— Cardiac injury is incrementally worse with increasing aSAH severity and associated with persistent QTc prolongation and ventricular arrhythmias. Regional wall motion abnormalities and depressed ejection fraction persist to some degree in the majority of those affected.

Background Although several echocardiographic approaches exist to quantify mechanical dyssynchrony, the comparative ability of different manufacturers' speckle-tracking software programs to predict response to cardiac resynchronization therapy (CRT) is unknown. Methods Eighty-four patients with heart failure referred for CRT were studied (mean age, 64 ± 12 years; mean ejection fraction [EF], 26 ± 7%; mean QRS duration, 157 ± 26 ms). Dyssynchrony was assessed using the same midventricular short-axis digital cine loop for each patient with 3 different offline speckle-tracking strain analysis programs: software A, speckle-tracking two-dimensional strain; software B, velocity vector imaging strain; and software C, speckle-tracking strain. Significant dyssynchrony was defined as an anterior septum–to–posterior wall delay ≥130 ms. Follow-up was available for 57 patients (mean, 7 ± 4 months). Response to CRT was defined as an EF increase ≥15%. Results Variability between software results was observed when patients had large degrees of dyssynchrony (≥200 ms), with limits of agreement from 123 to 214 ms. However, close agreement for identifying patients with significant dyssynchrony was observed: 91% for software A versus B, 96% for software A versus C, and 93% for software B versus C. Importantly, the 3 software approaches' ability to predict EF outcome had similar sensitivities, specificities, and areas under receiver operating characteristic curves: 0.87, 0.86, and 0.86, respectively. Conclusions Radial strain dyssynchrony analyses by 3 different speckle-tracking software programs were similarly able to predict EF response to CRT. Although variability in absolute values of dyssynchrony was observed, there was close agreement for determining the presence or absence of significant dyssynchrony. Speckle-tracking echocardiography has potential as a means to quantify dyssynchrony in a multicenter clinical trial or clinical practice.

Over the past decade, cardiac resynchronization therapy (CRT) has changed the treatment of patients with end-stage, drug-refractory heart failure. Evidence of 8 large trials (including 4,017 patients) ([1–8][1]) and numerous small studies have demonstrated the benefit of CRT on heart failure

There is still no standardized measure of left ventricular (LV) dyssynchrony or definition of response in candidates of cardiac resynchronization therapy (CRT). Recipients of CRT underwent echocardiographic assessment of LV dyssynchrony before and immediately after implantation of a CRT device. Patients were followed for 6 months postimplantation. A total of 44 patients (64 +/- 12 years, 30 men, and 26 with ischemic cardiomyopathy) were included in this analysis. There was a significant decrease in both radial (304 +/- 137 vs 121 +/- 85 ms, p0.001) and longitudinal (143 +/- 104 vs 95 +/- 43 ms, p = 0.02) measures of LV dyssynchrony immediately after CRT. The immediate post-CRT change in radial (r = -0.43, p = 0.015) but not longitudinal (r = -0.09, p = 0.61) LV dyssynchrony correlated with a significant improvement in the physical component of the quality-of-life score 6 months after CRT. Although a higher baseline longitudinal (p = 0.05) or radial (p = 0.025) LV dyssynchrony predicted aor=1 improvement in New York Heart Association classification of heart failure 6 months after CRT, acute changes in neither radial (p = 0.71) nor longitudinal (p = 0.89) LV dyssynchrony were predictive of any improved echocardiographic outcomes in follow-up. Concordance between clinical and echocardiographic response to CRT was documented in 72% of patients. In conclusion, both longitudinal and radial measures of LV dyssynchrony improve after CRT. The change in longitudinal but not radial measures of LV dyssynchrony correlates with improved physical quality-of-life score in intermediate term follow-up.

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.

Although cardiac resynchronization therapy (CRT) has been of unquestioned therapeutic benefit to many patients with heart failure identified by a widened QRS complex on an electrocardiogram, many patients do not respond favorably. Several studies using echocardiographic methods to measure abnormalities of mechanical activation, known as dyssynchrony, have been proposed to improve patient selection for CRT. Many single-center studies from institutions with special expertise have demonstrated the feasibility of echocardiographic dyssynchrony to potentially assist with patient selection. However, the PROSPECT trial, a recent large multicenter study, highlighted the technical challenges in echocardiographic dyssynchrony analysis in mainstream clinical practice. Accordingly, a uniform clinical approach has not been established, and refinements of echocardiographic approaches and methods are constantly evolving. This article reviews current echocardiographic methods to quantify ventricular dyssynchrony, their strengths and limitations, and the proposed and potential expanding clinical applications.

This study extracted hemodynamic information from echocardiogram to complement the left ventricle ejection fraction and the stroke volume for cardiac evaluation and diagnosis. The dynamic characteristics of irregular wall motions can be analyzed by kinetic energy fluxes transferred from the left ventricle to the blood flow. A set of cardiac indices is developed for quantification and classification of echocardiogram for clinical application. The pumping characteristics can be further quantified through the work done by pressure and viscous stresses of the ventricle.

ObjectivesThe purpose of this study was to test the hypothesis that a combined echocardiographic assessment of longitudinal dyssynchrony by tissue Doppler imaging (TDI) and radial dyssynchrony by speckle-tracking strain may predict left ventricular (LV) functional response to cardiac resynchronization therapy (CRT).BackgroundMechanical LV dyssynchrony is associated with response to CRT; however, complex patterns may exist.MethodsWe studied 190 heart failure patients (ejection fraction [EF] 23 ± 6%, QRS duration 168 ± 27 ms) before and after CRT. Longitudinal dyssynchrony was assessed by color TDI for time to peak velocity (2 sites in all and 12 sites in a subgroup of 67). Radial dyssynchrony was assessed by speckle-tracking radial strain. The LV response was defined as ≥15% increase in EF.ResultsOne hundred seventy-six patients (93%) had technically sufficient baseline and follow-up data available. Overall, 34% were EF nonresponders at 6 ± 3 months after CRT. When both longitudinal dyssynchrony by 2-site TDI (≥60 ms) and radial dyssynchrony (≥130 ms) were positive, 95% of patients had an EF response; when both were negative, 21% had an EF response (p < 0.001 vs. both positive). The EF response rate was lowest (10%) when dyssynchrony was negative using 12-site TDI and radial strain (p < 0.001 vs. both positive). When either longitudinal or radial dyssynchrony was positive (but not both), 59% had an EF response. Combined longitudinal and radial dyssynchrony predicted EF response with 88% sensitivity and 80% specificity, which was significantly better than either technique alone (p < 0.0001).ConclusionsCombined patterns of longitudinal and radial dyssynchrony can be predictive of LV functional response after CRT.

Objectives Speckle-tracking strain analysis was used to assess the effects of permanent right ventricular (RV) pacing on the heterogeneity in timing of regional wall strain and left ventricular (LV) dyssynchrony. Background Recent studies have shown detrimental effects of RV pacing, possibly related to the induction of LV dyssynchrony. Methods Fifty-eight patients treated with His bundle ablation and pacemaker implantation were studied. To assess the effect of RV pacing on time-to-peak radial strain of different LV segments, we applied speckle-tracking analysis to standard LV short-axis images. In addition, New York Heart Association (NYHA) functional class, LV volumes, and systolic function were assessed at baseline and after long-term RV pacing. Results At baseline, similar time-to-peak strain for the 6 segments was observed (mean 371 ± 114 ms). In contrast, after a mean of 3.8 ± 2.0 years of RV pacing, there was a marked heterogeneity in time-to-peak strain of the 6 segments. In 33 patients (57%), LV dyssynchrony, represented by a time difference ≥130 ms between the time-to-peak strain of the (antero)septal and the posterolateral segments, was present. In these patients, a deterioration of LV systolic function and NYHA functional class was observed. In 11 patients, an “upgrade” of the conventional pacemaker to a biventricular pacemaker resulted in partial reversal of the detrimental effects of RV pacing. Conclusions Speckle-tracking analysis revealed that permanent RV pacing induced heterogeneity in time-to-peak strain, resulting in LV dyssynchrony in 57% of patients, associated with deterioration of LV systolic function and NYHA functional class. Biventricular pacing may reverse these adverse effects of RV pacing.

ObjectivesWe sought to test the hypothesis that a novel 2-dimensional echocardiographic image analysis system using artificial intelligence-learned pattern recognition can rapidly and reproducibly calculate ejection fraction (EF).BackgroundEchocardiographic EF by manual tracing is time consuming, and visual assessment is inherently subjective.MethodsWe studied 218 patients (72 female), including 165 with abnormal left ventricular (LV) function. Auto EF incorporated a database trained on >10,000 human EF tracings to automatically locate and track the LV endocardium from routine grayscale digital cineloops and calculate EF in 15 s. Auto EF results were independently compared with manually traced biplane Simpson’s rule, visual EF, and magnetic resonance imaging (MRI) in a subset.ResultsAuto EF was possible in 200 (92%) of consecutive patients, of which 77% were completely automated and 23% required manual editing. Auto EF correlated well with manual EF (r = 0.98; 6% limits of agreement) and required less time per patient (48 ± 26 s vs. 102 ± 21 s; p < 0.01). Auto EF correlated well with visual EF by expert readers (r = 0.96; p < 0.001), but interobserver variability was greater (3.4 ± 2.9% vs. 9.8 ± 5.7%, respectively; p < 0.001). Visual EF was less accurate by novice readers (r = 0.82; 19% limits of agreement) and improved with trainee-operated Auto EF (r = 0.96; 7% limits of agreement). Auto EF also correlated with MRI EF (n = 21) (r = 0.95; 12% limits of agreement), but underestimated absolute volumes (r = 0.95; bias of −36 ± 27 ml overall).ConclusionsAuto EF can automatically calculate EF similarly to results by manual biplane Simpson’s rule and MRI, with less variability than visual EF, and has clinical potential.

Introduction: Heart failure (HF) patients have an increased risk for ventricular arrhythmias (VA) and in particular patients with ischemic cardiomyopathy (ICM) have a worse prognosis after cardiac resynchronization therapy with defibrillator (CRT-D) compared with non-ischemic patients. Hypothesis: We hypothesize that global longitudinal strain (GLS) at baseline has the ability to identify ICM patients at higher risk for VA after CRT-D. Methods: We prospectively studied 175 consecutive HF patients implanted with CRT-D from a single center. All of them had class II-IV HF symptoms, LV ejection fraction (≤35%), QRS≥120 ms. GLS was measured from the three standard apical views and presented as absolute values. Outcome event was defined as VA (anti-tachycardia pacing or appropriate shock) after CRT in the first 2 years of follow-up. Results: Of 175 patients aged 65±11 years, 135 (77%) were male and 115 (66%) had ICM. They suffered 34 (19%) VA events over 2 years. Mean GLS of the population was 8.1±3.0. GLS (< 6.5%) was associated with VA events after CRT-D with a sensitivity of 70% and specificity of 56%. A cutoff of GLS Conclusions: Low GLS (

Background: Peripartum cardiomyopathy (PPCM) is a rare disease with variable but potentially devastating consequences. The prognostic importance of alterations in LV diastolic function is unclear. Methods: Pregnancy Associated Cardiomyopathy cohort was a prospective study of 100 PPCM women from 30 centers presenting with LV ejection fraction (EF) < 45% within 2 months of delivery. Baseline data were mitral inflow E-wave, A-wave, E/A ratio, E deceleration time (DT), tissue Doppler septal and lateral annular velocities and biplane LA volume index. There were 90 PPCM patients and 21 female controls (8 healthy postpartum and 13 non-pregnant) with diastolic data. LV recovery was defined as LVEF ≥ 50% at 1 year. Outcome events were predefined as death, heart transplant or LV assist device (LVAD). Results: PPCM patients were aged 30±6 years with EF 35±9% at presentation. At 1 year, 84 patients had follow-up data: 63 patients (75%) had LV recovery (EF ≥50%) and 11 patients (13%) had either LVEF ≤35% or a major event (4 LVADs and 2 deaths). Elevated filling pressures (E/A≥2 and DT Conclusions: In PPCM patients, echo-Doppler measures of diastolic function at presentation provide important prognostic information regarding LV recovery and clinical outcomes.

Background— Response to cardiac resynchronization therapy is most favorable in patients with heart failure with QRS duration ≥150 ms and left bundle branch block and less predictable in those with QRS width 120 to 149 ms or non–left bundle branch block. Methods and Results— We studied 205 patients with heart failure referred for cardiac resynchronization therapy with QRS ≥120 ms and ejection fraction ≤35%. We tested the hypothesis that contractile function using speckle-tracking echocardiographic global circumferential strain (GCS) from 2 short-axis views and global longitudinal strain (GLS) from 3 apical views add prognostic value to electrocardiographic criteria. There were 112 patients (55%) with GLS >−9% and 136 patients (66%) with GCS >−9%. During 4 years, 81 patients reached the combined primary end point (death, circulatory support, or transplant) and 120 reached the secondary end point (heart failure hospitalization or death). Both GLS >−9% and GCS >−9% were associated with increased risk of unfavorable events as follows: for the primary end point (hazard ratio=2.91; 95% confidence interval, 1.88–4.49; P P P P P =0.014 and P =0.002 for the primary end point and P =0.049 and P =0.001 for the secondary end point. Global strain measures had additive prognostic value to routine clinical or electrocardiographic parameters ( P Conclusions— Baseline GCS and GLS were significantly associated with long-term outcome after cardiac resynchronization therapy and had additive prognostic value to routine clinical and electrocardiographic selection criteria for cardiac resynchronization therapy.

Background— Peripartum cardiomyopathy has variable disease progression and left ventricular (LV) recovery. We hypothesized that baseline right ventricular (RV) size and function are associated with LV recovery and outcome. Methods and Results— Investigations of Pregnancy-Associated Cardiomyopathy was a prospective 30-center study of 100 peripartum cardiomyopathy women with LV ejection fraction (LVEF) Conclusions— Peripartum cardiomyopathy patients had a high incidence of LV recovery, but a significant minority had persistent LV dysfunction or a major clinical event by 1 year. RV function per echocardiographic fractional area change at presentation was associated with subsequent LV recovery and clinical outcomes and thus is prognostically important.

Background— Left ventricular (LV) mechanical discoordination, often referred to as dyssynchrony, is often observed in patients with heart failure regardless of QRS duration. We hypothesized that different myocardial substrates for LV mechanical discoordination exist from (1) electromechanical activation delay, (2) regional differences in contractility, or (3) regional scar and that we could differentiate electromechanical substrates responsive to cardiac resynchronization therapy (CRT) from unresponsive non–electrical substrates. Methods and Results— First, we used computer simulations to characterize mechanical discoordination patterns arising from electromechanical and non–electrical substrates and accordingly devise the novel systolic stretch index (SSI), as the sum of posterolateral systolic prestretch and septal systolic rebound stretch. Second, 191 patients with heart failure (QRS duration ≥120 ms; LV ejection fraction ≤35%) had baseline SSI quantified by automated echocardiographic radial strain analysis. Patients with SSI≥9.7% had significantly less heart failure hospitalizations or deaths 2 years after CRT (hazard ratio, 0.32; 95% confidence interval, 0.19–0.53; P P P =0.004) and less deaths, transplants, or LV assist devices (hazard ratio, 0.27; 95% confidence interval, 0.12–0.60; P =0.001). Conclusions— Computer simulations differentiated patterns of LV mechanical discoordination caused by electromechanical substrates responsive to CRT from those related to regional hypocontractility or scar unresponsive to CRT. The novel SSI identified patients who benefited more favorably from CRT, including those with intermediate electrocardiographic criteria, where CRT response is less certain by ECG alone.

This editorial refers to ‘Reduced appropriate implantable cardioverter defibrillator therapy after cardiac synchronization therapy-induced left ventricular function recovery: a meta-analysis and systematic review’, by N. Chatterjee et al ., doi:10.1093/eurheartj/ehv373. The term ‘remodelling’ was first used >30 years ago to describe pathological left ventricular (LV) structural and functional changes occurring after myocardial infarction.1 LV remodelling was subsequently adopted to describe the complex interplay of molecular, myocyte, fibroblast, and interstitial mechanisms influenced by haemodynamic load, neurohormonal activation, and inflammatory signalling. Clinically, LV remodelling is assessed by measuring increases in LV volumes and reductions in ejection fraction (EF).2 Reverse remodelling may then be defined as the process by which an injured left ventricle may return towards normal. Reverse remodelling may occur spontaneously, such as in acute non-ischaemic cardiomyopathy,3 or in response to a therapeutic intervention. Therapy associated with reverse remodelling may be pharmacological, such as renin–angiotensin–aldosterone system inhibition and beta-adrenergic receptor blockade, or device-based, such as cardiac resynchronization therapy (CRT) and mechanical circulatory support. The effects of CRT on LV reverse remodelling have been of particular interest because the precise mechanisms remain unclear, CRT response has been variable, and associated risks of ventricular arrhythmias have been uncertain. In this issue, Chatterjee et al . report an interesting meta-analysis focused on patients with LV reverse remodelling after CRT-defibrillator (CRT-D) therapy.4 Their objective …

Expression of different cytokines and growth factors after myocardial injury has been associated with fibroplasia and dilatation versus reverse remodeling and myocardial repair. Specifically, the proinflammatory/fibrotic mediators: interleukin (IL)-6, epidermal growth factor, and fibroblast growth factor (FGF)-2 cause fibroplasia, whereas reparative cytokines including: IL-1α, IL-1β, IL-4, and IL-13 can limit fibrosis. In appropriate patients, cardiac resynchronization therapy (CRT) reverses cardiomyopathy and improves outcome. However, a significant proportion will not respond to this therapy. We conducted this study to assess the association of proinflammatory/fibrotic and/or reparative immune response mediators at baseline with outcome after CRT. In the multicenter RISK study, plasma samples were collected prospectively before CRT implantation. Plasma IL-6, epidermal growth factor, FGF-2, IL-1α, IL-1β, IL-4, and IL-13 were evaluated by Luminex technology. The primary outcome was predefined as freedom from heart failure hospitalization or death and a decrease in echocardiographic end-systolic volume of >15% at 12 months. To determine associations with the outcome, multivariate logistic regression models including baseline clinical characteristics and the specific cytokines and growth factors were constructed. On multivariate analysis of 257 patients, detectable reparative cytokine IL-13 was significantly associated with the primary outcome (odds ratio 3.79; 95% CI 2.10 to 6.82, p

Aims Patients with recent onset non-ischaemic cardiomyopathy have a variable clinical course with respect to recovery of left ventricular ejection fraction (LVEF). The aim of this study was to understand whether temporal changes in diastolic function (DF) are associated with clinical outcomes independent of LVEF recovery. Methods and results The Intervention in Myocarditis and Acute Cardiomyopathy (IMAC)-2 study was a prospective, multicentre trial investigating myocardial recovery in subjects with symptoms onset of

AIMS: In EchoCRT, a randomized trial evaluating the effect of cardiac resynchronization therapy (CRT) in patients with a QRS duration of METHODS AND RESULTS: The main EchoCRT trial was prematurely terminated due to futility. For the current subgroup analysis we compared data for CRT-ON vs. -OFF in patients with QRS < 120 (n = 661) and QRS 120-130 ms (n = 139). On uni- and multivariable analyses, no significant interaction was observed between the two groups and randomized treatment for the primary or any of the secondary endpoints. On multivariable analysis, a higher risk for the primary endpoint was observed in patients with a QRS duration of 120-130 ms randomized to CRT-ON vs. CRT-OFF (hazard ratio 2.18, 95% CI 1.02-4.65; P = 0.044). However, no statistically significant interaction, compared with patients with QRS < 120 ms randomized to CRT-ON vs. CRT-OFF, was noted (P-interaction = 0.160).CONCLUSIONS: In this pre-specified subgroup analysis of EchoCRT, no benefit of CRT was evident in patients with a QRS duration of 120-130 ms. These data further question the usefulness of CRT in this patient population.

BACKGROUND: Tissue Doppler cross-correlation analysis has been shown to be associated with long-term survival after cardiac resynchronization defibrillator therapy (CRT-D). Its association with ventricular arrhythmia (VA) is unknown.METHODS: From two centers 151 CRT-D patients (New York Heart Association functional classes II-IV, ejection fraction ≤ 35%, and QRS duration ≥ 120 msec) were prospectively included. Tissue Doppler cross-correlation analysis of myocardial acceleration curves from the basal segments in the apical views both at baseline and 6 months after CRT-D implantation was performed. Patients were divided into four subgroups on the basis of dyssynchrony at baseline and follow-up after CRT-D. Outcome events were predefined as appropriate antitachycardia pacing, shock, or death over 2 years.RESULTS: Mechanical dyssynchrony was present in 97 patients (64%) at baseline. At follow-up, 42 of these 97 patients (43%) had persistent dyssynchrony. Furthermore, among 54 patients with no dyssynchrony at baseline, 15 (28%) had onset of new dyssynchrony after CRT-D. In comparison with the group with reduced dyssynchrony, patients with persistent dyssynchrony after CRT-D were associated with a substantially increased risk for VA (hazard ratio [HR], 4.4; 95% CI, 1.2-16.3; P = .03) and VA or death (HR, 4.0; 95% CI, 1.7-9.6; P = .002) after adjusting for other covariates. Similarly, patients with new dyssynchrony had increased risk for VA (HR, 10.6; 95% CI, 2.8-40.4; P = .001) and VA or death (HR, 5.0; 95% CI, 1.8-13.5; P = .002).CONCLUSIONS: Persistent and new mechanical dyssynchrony after CRT-D was associated with subsequent complex VA. Dyssynchrony after CRT-D is a marker of poor prognosis.

Background— Adverse right ventricular (RV) remodeling has significant prognostic and therapeutic implications to patients with pulmonary hypertension (PH). However, differentiating RV adaption from adverse remodeling associated with poor outcomes is difficult. We hypothesized that novel 3-dimensional (3D) wall motion tracking echocardiography can differentiate morphological features of RV adaption from adverse remodeling heralding an unfavorable short-term prognosis in patients with PH. Methods and Results— We studied 112 subjects: 92 patients with PH and 20 normal controls with 3D wall motion tracking for RV end-systolic volume index (ESVi), RV ejection fraction (EF), and RV global area strain. Patients with PH also had invasive hemodynamic measurements. Pressure–volume relations classified patients with PH into 3 groups, such as RV adapted, RV adapted–remodeled, and RV adverse–remodeled. The predefined combined end point was PH-related hospitalization, death, or lung surgery (lung transplantation or pulmonary endarterectomy) during 6 months. The 92 patients with PH had significantly larger RV volumes, lower RVEF and global area strain than normal controls as expected. Patients with PH classified as RV adapted (ESVi, ≤ 72 mL/m 2 ) had a more favorable clinical outcome than those classified as RV adapted–remodeled (ESVi, 73–113 mL/m 2 ) or RV adverse–remodeled (ESVi, ≥ 114 mL/m 2 ): hazard ratio, 0.15; 95% confidence intervals, 0.07 to 0.39; P ≥ 114 mL/m 2 ) had worse short-term outcome than the RV adapted–remodeled patients: hazard ratio, 2.2; 95% confidence interval, 0.91 to 5.39; P =0.04. Conclusions— Quantitative 3D echocardiography in patients with PH demonstrated morphological subsets of RV adaption and remodeling associated with clinical outcomes.

Aims Very elderly patients have not been well-represented in the randomized trials that established the benefits of cardiac resynchronization therapy (CRT) in heart failure (HF) patients. We therefore compared clinical outcomes in CRT-defibrillator (CRT-D) recipients ≥80 and

To determine concordance between speckle tracking echo and myocardial SPECT for the determination of the latest activated LV segment. Out of 187 patients enrolled in the Speckle Tracking Assisted Resynchronization Therapy for Electrode Region trial, 54 had both echo and SPECT at baseline, of whom

Background QRS duration and morphology are known established predictors of cardiac resynchronisation therapy (CRT) response, whereas mechanical dyssynchrony is not. Our aim was to determine if mechanical dyssynchrony provides independent prognostic information on CRT response. Methods We studied 369 consecutive patients with heart failure (HF) with low ejection fraction (EF) and widened QRS receiving CRT. Radial dyssynchrony (septal-posterior radial peak strain delay ≥130 ms by speckle tracking) assessment was possible in 318 patients (86%). Associations with left ventricular end-systolic volume (LVESV) changes were examined using linear regression, and clinical outcomes analysed using Cox regression adjusted for multiple established outcome correlates. Results Patients with radial dyssynchrony before CRT (64%) had greater improvements in EF (8.8±9.4 vs 6.1±9.7 units, p=0.04) and LVESV (−30±41 vs −10±30 mL, p

Background: Wide QRS complexes are associated with left ventricular (LV) dyssynchrony, but an optimal site of LV pacing has not been established. Hypothesis: We hypothesized that concordance between the sites of LV pacing and of latest LV mechanical activation during cardiac resynchronization therapy (CRT) is associated with more favorable acute echocardiographic changes. Methods: An analysis of 28 consecutive patients (64 ± 15 years, 46% male, 52% ischemic heart disease, LV ejection fraction 0.24 ± 0.07, QRS 163 ± 22 ms, New York Heart Association > 3 93%) implanted with biventricular (BIV) defibrillators was performed. Sites of latest LV activation were determined by tissue Doppler imaging (TDI) and speckle tracking (ST). The site of LV pacing was determined by fluoroscopy in two views. A concordance score (0-5) was created to describe the proximity of the pacing site to the site of the latest mechanical activation. Results: Compared with the worst concordance score, a perfect score was associated with shorter QRS width with LV (187 ± 40 vs. 246 ± 8 ms, p = 0.048) and BIV (134 ± 19 ms vs. 179 ± 39 ms, p = 0.05) but not with right ventricular pacing. A perfect concordance score was also associated with a greater acute reduction in LV volumes in systole (42 ± 36 ms 16 ± 22 ms, p = 0.068) and diastole (47 ± 37 vs. 8 ± 31 ml, p = 0.043) 24 h after CRT device implantation. Conclusions: A high concordance is associated with shorter QRS width with LV and BIV pacing and greater acute reduction in LV volumes. The effect of concordance on the intermediate and long-term response to BIV pacing deserves further evaluation.