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Ejection fraction (EF) is still widely used to categorize heart failure (HF) patients but has limitations. Global longitudinal strain (GLS) has emerged as a new prognosticator in HF, independent of EF.We investigated the incremental predictive benefit of GLS over different risk profiles as identified by automated cluster analysis of simple echocardiographic parameters.In 797 HFrEF patients (age 66 ± 12y; mean EF 30 ± 7%), unsupervised cluster analysis of 10 routine echocardiographic variables (without GLS) was performed. Median follow-up was 37 months. End-point was all-cause mortality. Association between risk profiles, GLS, and mortality was assessed by Cox proportional-hazard modeling with interaction term. Cluster analysis allocated patients to 3 different risk phenogroups (PG): PG-1 (mild diastolic dysfunction [DD], moderate systolic dysfunction, no pulmonary hypertension, normal right ventricular [RV] function); PG-2 (moderate DD, mild pulmonary hypertension, normal RV function); PG-3 (severe DD, advanced systolic dysfunction, pulmonary hypertension, RV dysfunction). Compared to PG-1, PG-2 and PG-3 showed increased adjusted-hazard ratio (1.71; 95% CI:1.05-2.77, P = 0.30; and 2.58; 95% CI:1.50-4.44, P 0.001, respectively). GLS was independently associated with outcome in the whole population (adjusted-HR: 1.11; 95% CI: 1.05-1.17, P = 0.001); however, profile membership modified the relationship between GLS and outcome which was no longer significant in PG-3 (P for interaction = 0.003).Within HFrEF populations, clustering of routine echocardiography parameters can automatically identify patients with different risk profiles; further assessment by GLS may be useful for patients with not advanced disease.

Background Patients with heart failure undergoing cardiac resynchronization therapy with or without defibrillator function may exhibit recovery of left ventricular ejection fraction (LVEF) during follow-up. Mechanical dispersion (MD; the SD of time to peak longitudinal strain by two-dimensional speckle-tracking echocardiography) is a known predictor of life-threatening ventricular arrhythmias (VAs). Relationships among LVEF recovery, changes in MD, and incidence of VA are still not extensively investigated. Methods In this retrospective study, recipients of cardiac resynchronization therapy defibrillation (n = 183) or implantable cardioverter-defibrillators only (n = 87) underwent conventional and speckle-tracking echocardiography, both at baseline and after 10 to 12 months, and were followed clinically. Both a ≥10% increase in LVEF and a final LVEF > 35% defined echocardiographic response (EchoResp). Reduction in MD ≥10 msec defined MD response (MDResp). Risk for appropriate implantable cardioverter-defibrillator therapy for VAs was assessed using a multivariable Cox hazard model. Results The prevalence of EchoResp+ and MDResp+ was 39% and 46%, respectively. During follow-up (49.8 ± 33.5 months), 74 VA events occurred. The incidence rate (per 100 patient-years) of VAs was lowest in the EchoResp+/MDResp+ group (1.66%; 95% CI, 0.69%-3.99%), highest in the EchoResp−/MDResp− group (12.8%; 95% CI, 9.53%-17.2%; P 71.4 msec) was associated with VAs independent of whether final LVEF was below or above the guideline-reported cutoff of 35% (P Conclusions Among ICD recipients, improvements in both left ventricular function and MD are associated with reduced risk for VAs. In patients whose follow-up LVEFs improved to >35%, risk for VAs, although substantially decreased, remained elevated in the presence of still elevated MD.

Aims: In patients with heart failure with reduced ejection fraction (HFrEF), an association between left atrial (LA) dilatation and dysfunction is expected, but the degree of coexistence of the two abnormalities and their relative prognostic role is not known. Methods and results: A total of 626 HFrEF patients formed the study population. All of them underwent a comprehensive echocardiographic evaluation. LA maximal volume was indexed to body surface area (LAVi); LA function was assessed using strain analysis during the reservoir phase: peak atrial longitudinal strain (PALS) analysis. Study primary endpoint was overall mortality or hospitalization for worsening heart failure. Four groups of patients were included in this study according to LAVi (≤34 or >34 mL/m2 ) and PALS (≤23% or >23%); 61 (10%) patients had normal LA volume and function (Group 1), 58 (9%) had LA dilatation but normal function (Group 2), 100 (16%) had normal volume but abnormal function (Group 3), and 407 (65%) had enlarged left atrium and abnormal function (Group 4). PALS was associated with primary endpoint in patients with both normal-size [Groups 1 and 3: hazard ratio (HR) 0.92, 95% confidence interval (CI) 0.88-0.96; P = 0.0006] and dilated left atria (Groups 2 and 4: HR 0.93, 95% CI 0.91-0.96; P < 0.0001). In contrast, LAVi was associated with the primary endpoint in patients with abnormal LA function (Groups 3 and 4: HR 1.018, 95% CI 1.011-1.024; P < 0.00001) but not in those with normal PALS (Groups 1 and 2: HR 1.023, 95% CI 0.99-1.057; P = 0.1). Conclusions: Left atrial dilatation and dysfunction frequently but not invariably coexist. PALS emerged as a significant prognostic parameter in HFrEF even in the absence of LA dilation.

AIMS A compromised tricuspid annular plane systolic excursion (TAPSE) is associated with worse survival in patients with chronic heart failure with reduced ejection fraction (HFrEF). However, it is not known whether a reversible abnormal TAPSE at follow-up predicts survival. Our aim was to evaluate whether a reversible abnormal TAPSE is associated with a better survival in patients with chronic HFrEF. METHODS AND RESULTS A complete echocardiography was performed in 706 patients with chronic HFrEF (LVEF ≤45%) at baseline and after 6 ± 3 months. Right ventricular (RV) systolic function was evaluated using TAPSE. The study endpoint was all-cause mortality. At baseline, TAPSE was severely reduced (≤14 mm) in 89 (13%) patients, and slightly reduced (>14 but

Background Left atrial (LA) volume is a marker of cardiac remodeling and prognosis in heart failure (HF) with reduced ejection fraction (EF), but LA function is rarely measured or characterized. We investigated determinants and prognostic impact of LA reservoir function in patients with HF with reduced EF. Methods and Results In 405 patients with stable HF with reduced EF (EF, ≤40%) in sinus rhythm, we assessed LA reservoir function by both LA total EF (by phasic volume changes) and peak atrial longitudinal strain (PALS; by speckle tracking echocardiography); LA functional index was also calculated. During follow-up (median, 30 months; Q1–Q3, 13–52), 139 patients (34%) reached the composite end point (all-cause death/HF hospitalization). Median PALS was 15.5% (interquartile range, 11.2–20.6). By univariable analysis, all LA function parameters significantly predicted outcome ( P P =0.030). Adding PALS to a base model, including age, sex, LA volume, EF, E/E′ ratio, and global longitudinal strain, provided incremental predictive value (continuous net reclassification improvement, 0.449; P =0.0009). Conclusions In HF with reduced EF, assessment of LA reservoir function by PALS allows powerful prognostication, independently of LA volume and left ventricular longitudinal contraction.

Global right ventricular (RV) longitudinal strain (RVGLS) and free wall RV longitudinal strain (RVFWS) have both been advocated as sensitive tools to evaluate RV function and predict prognosis in patients with heart failure and reduced ejection fraction (HFrEF). However, because the interventricular septum is an integral part of the left ventricle (LV) also, RVGLS might be influenced by LV dysfunction. Thus, we compared the prognostic performance of either RV strain parameter in HFrEF patients, also taking into account the degree of LV systolic dysfunction.In 288 prospectively enrolled outpatients with stable HFrEF, RVGLS and RVFWS were assessed by speckle-tracking and LV systolic function by global longitudinal strain and LV ejection fraction. Patients were followed up for 30.2 ± 23.0 months; the primary endpoint was all-cause death/heart failure-related hospitalization. Prognostic performance was assessed by C-statistic and net reclassification improvement.There were 95 events during follow-up. By univariable analysis, both RVGLS (hazard ratio × 1 SD, 1.60; 95% CI, 1.29-1.99; P .0001) and RVFWS (hazard ratio × 1 SD, 1.82; 95% CI, 1.45-2.29; P .0001) were associated with outcome, and both remained significant after correction for EMPHASIS risk score, New York Heart Association class, natriuretic peptides, and therapy. However, after further correction for LV systolic function parameters, only RVFWS remained significantly associated with outcome (P .01). A basic prediction model was improved by adding RVFWS (net reclassification improvement 0.390; P .05), but not RVGLS.Although both RVGLS and RVFWS have prognostic value, RVFWS better predicts outcome in HFrEF patients, mainly because it is less influenced by LV longitudinal dysfunction.

We compared the follow-up data on loop diuretic use and renal function, as assessed by serum creatinine levels, and the estimated glomerular filtration rate (eGFR), of two groups of consecutive ambulatory HF patients: 1) the clinically-guided group, in which management was clinically driven based on the institutional protocol of the HF Unit of the Cardiovascular and Thoracic Department of Pisa (standard of care) and 2) the echo and B-type natriuretic peptide (BNP) guided group (patients conforming to the protocol of the Network Labs Ultrasound (NEBULA) in HF Study Group: Pisa, Perugia, Pavia; Verona, Auckland, and Veruno), in which therapy was delivered according to the serial assessment of BNP and echocardiography. Patients whose follow-up was based on standard of care had a significant higher prevalence of worsening renal function, that was likely related to higher diuretic dosages, whilst, a better management of renal function was observed in the echo-BNP-guided group. The data is related to “Echo and natriuretic peptide guided therapy improves outcome and reduces worsening renal function in systolic heart failure: An observational study of 1137 outpatients” (A. Simioniuc, E. Carluccio, S. Ghio, A. Rossi, P. Biagioli, G. Reboldi, G.G. Galeotti, F. Lu, C. Zara, G. Whalley, P.G. Temporelli, F.L. Dini, 2016; K.J. Harjai, H.K. Dinshaw, E. Nunez, M. Shah, H. Thompson, T. Turgut, H.O. Ventura, 1999; A. Ahmed, A. Husain, T.E. Love, G. Gambassi, L.J. Dell׳Italia, G.S. Francis, M. Gheorghiade, R.M. Allman, S. Meleth, R.C. Bourge, 2006) [1–3].

Background— In heart failure (HF) with reduced ejection fraction, right ventricular (RV) impairment, as defined by reduced tricuspid annular plane systolic excursion, is a predictor of poor outcome. However, peak longitudinal strain of RV free wall (RVFWS) has been recently proposed as a more accurate and sensitive tool to evaluate RV function. Accordingly, we investigated whether RVFWS could help refine prognosis of patients with HF with reduced ejection fraction in whom tricuspid annular plane systolic excursion is still preserved. Methods and Results— A total of 200 patients with HF with reduced ejection fraction (age, 66±11 years; ejection fraction, 30±7%) with preserved tricuspid annular plane systolic excursion (>16 mm) underwent RV function assessment using speckle-tracking echocardiography to measure peak RVFWS. After a median follow-up period of 28 months, 62 (31%) patients reached the primary composite end point of all-cause death/HF rehospitalization. Median RVFWS was −19.3% (interquartile range, −23.3% to −15.0%). By lasso-penalized Cox-hazard model, RVFWS was an independent predictor of outcome, along with Eplerenone in Mild Patients Hospitalization and Survival Study in Heart Failure-HF score, Echo-HF score, and severe mitral regurgitation. The best cutoff value of RVFWS for prediction of outcome was −15.3% (area under the curve, 0.68; P P P Conclusions— In patients with HF with reduced ejection fraction with preserved tricuspid annular plane systolic excursion, RV free-wall strain provides incremental prognostic information and improved risk stratification.

Background Increased red blood cell distribution width (RDW) has been associated with poor outcome after cardiac resynchronization therapy (CRT). However, whether baseline RDW, and its serial changes after CRT implant, have incremental prognostic value is unknown. Methods and results In 148 consecutive patients (age, 68±9years; 122 men) undergoing CRT, RDW was assessed before and 3months after implant. Patients were categorized according to baseline RDW (≤14.5% vs >14.5%); and as "stable", "decreased", "increased", relative to post-implant changes. Primary end-point was a composite of death/HF hospitalization during follow-up (median 21months). A reduction in left ventricular (LV) end-systolic volume by ≥15% at 6-month identified LV reverse remodeling. By multivariable logistic regression analysis "increased" (OR:0.22, 95%CI: 0.07-0.69, P =0.010) and "stable-high" RDW at follow-up (OR: 0.39, 95%CI: 0.17–0.89, P =0.027) showed a lower likelihood to develop LV reverse remodeling, while baseline RDW was no longer predictive of LV remodeling. During follow-up, there were 57 events. Baseline RDW>14.5% (HR: 2.24, 95%CI: 1.05–4.77, P =0.036), "increased" (HR: 2.55, 95% CI: 1.09–5.97, P =0.030) and "stable-high" RDW (HR: 2.95, 95% CI: 1.45–5.99, P =0.003) independently predicted outcome after adjusting for functional improvement after CRT, radial dyssynchrony, BNP, creatinine clearance, and left atrial volume index. However, integrated discrimination improvement and net reclassification improvement were not statistically significant when both baseline RDW and its changes were added to a base predictive model. Conclusion Increased and stable-high values of RDW were independently associated with both LV reverse remodeling and outcome after CRT; however, RDW did not show any incremental predictive value.

Background: Myocardial performance index (MPI), or Tei index, is an indicator of systolic and diastolic myocardial function. MPI increases in case of cardiac dysfunction; however, whether reversal of left ventricular dysfunction is also reflected by concomitant improvement (i.e., decrease) of MPI is unknown. Methods: Fifty-two patients with chronic ischemic cardiomyopathy and viable myocardium by dobutamine stress echocardiography were studied by echocardiography before and more than 4 months after cardiac revascularization. Patients were in optimal medical therapy, which remained unchanged following revascularization. Results: At baseline, ejection fraction (EF: 32 ± 6%) and wall motion score index (WMSI: 2.37 ± 0.32) were impaired, and MPI averaged 0.71 ± 0.19. Revascularization markedly improved EF (44 ± 10%, P < 0.0001) and WMSI (1.77 ± 0.44, P < 0.0001). MPI also improved (0.59 ± 0.26, P < 0.0001), and its decrease was significantly correlated with the improvement in EF (r =−0.68, P < 0.0001) and to the extent of viable myocardium (r =−0.45, P = 0.0007). Responders to revascularization (≥5% increase in EF at follow-up, n = 40% and 77%) achieved a significant improvement in MPI at follow-up in contrast with nonresponders (−23 ± 25% vs. 0.02 ± 0.18%, P = 0.001). Improvement in MPI was largely driven by a significant reduction in isovolumic contraction time (P < 0.001) with consequent prolongation of the ejection phase. Conclusion: In patients with chronic ischemic cardiomyopathy, MPI improves along with recovery of function, reflecting the intrinsic improvement of viable segments induced by revascularization. (Echocardiography 2012;29:298-306)

We read with great interest the paper by Asami et al. [(1)][1] regarding the association between right ventricular (RV) dysfunction and cardiovascular death after transcatheter aortic valve replacement. In their elegant study, RV function was pre-operatively assessed by measuring fractional area

Myocardial reflectivity, as assessed by calibrated integrated backscatter (cIB) analysis, is a non-invasive surrogate for the amount of left ventricular (LV) fibrosis. The aim of this study was to assess the myocardial reflectivity pattern in patients with heart failure and preserved ejection fraction (HFpEF), and to evaluate its relationship with longitudinal systolic deformation of LV by 2D-speckle tracking echocardiography, and degree of diastolic dysfunction. Transthoracic echocardiography, myocardial Doppler-derived systolic (Sm) and early diastolic velocity (E'), global longitudinal strain (GLS), and tissue characterization by cIB, were obtained in 86 subjects, 46 with HFpEF, and 40 controls. GLS was significantly impaired in HFpEF patients (-15.4 ± 3.5 % vs -21.5 ± 2.9 % in controls; P

Objectives The purpose of this study was to investigate whether post-ischemic left ventricular (LV) remodeling might be induced by regional contractile dysfunction per se (i.e., in the absence of transmural necrosis) and whether this phenomenon is potentially reversible after contractile recovery. Background Formation of extensive scar tissue is thought to be chiefly responsible for post-infarction LV remodeling; however, myocardial necrosis also causes loss of contractility. We investigated LV geometry and shape in a setting in which contractile dysfunction occurs in the presence of preserved myocyte viability, and thus it is potentially reversible. Methods In 42 patients with chronically dysfunctional myocardium, we evaluated (by two-dimensional echocardiography) LV global and regional function, volumes, and sphericity index (SI), at baseline and 8 ± 3 months after coronary revascularization. Myocardial viability before revascularization was evaluated by dobutamine echocardiography. Results At baseline, regional and global function were depressed and LV dilation was present. Revascularization was followed by recovery of ejection fraction (from 33 ± 6% to 45 ± 10%, p Conclusions Hibernating myocardium is associated with major alterations in LV volumes and shape, which significantly revert after revascularization. Thus, chronic dyssynergy per se is sufficient to induce ischemic LV remodeling in patients.

Aims Although many transthoracic echocardiographic (TTE) measurements have been shown to predict outcome in heart failure (HF), whether incremental risk prediction is afforded by their combination is unknown. We developed a simple echocardiographic risk score of mortality in HF patients. Methods and results We performed TTE in 747 systolic HF patients followed-up for 34 ± 23 months. The Cox hazard model was used to evaluate the association between 14 TTE parameters and death. The Echo Heart Failure Score (EHFS) was derived by assigning the value of 1 to each independent predictor when present, and 0 when it was absent, and then by summing the number. The 3-year risk prediction improvement was tested by adding the EHFS to a model containing clinical predictors, and by calculating the C index and net reclassification improvement (NRI). Five baseline TTE variables (end-systolic volume index, left atrial volume index, mitral E-wave deceleration time, tricuspid annular peak systolic excursion, and pulmonary artery systolic pressure) remained independent predictors of mortality. The mortality rate (per 100 patients/year) significantly increased with EHFS ranging from 0 to 5 (EHFS = 0, 2.7%; 1, 5.2%; 2, 10.1%; 3, 13.7%, 4, 29.7%; 5, 36.9%; P < 0.0001). Patients with EHFS ≥3 had a mortality hazard ratio of 3.58 (95% confidence interval 2.74–4.78) compared with EHFS

ObjectivesThe aim of this study was to evaluate whether, in patients with evidence of both electrical and mechanical left ventricular (LV) dyssynchrony, extensive LV dilation would affect response to cardiac resynchronization therapy (CRT).BackgroundCardiac resynchronization therapy is effective in heart failure patients with LV dysfunction and wide QRS complex. However, many patients still fail to respond. We hypothesized that presence of extensive LV dilation might prevent response to CRT, despite LV mechanical dyssynchrony.MethodsWe studied 78 heart failure patients (68 ± 9 years of age, 77% men) with both electrical (QRS width >120 ms) and mechanical intraventricular dyssynchrony (by tissue Doppler imaging and/or left lateral wall post-systolic contraction). Echocardiographic evaluation was performed at baseline and 6 to 8 months after CRT. As an indication of LV remodeling, end-diastolic volume index and end-systolic volume index (ESVI) and sphericity index were measured. Long-term (40 ± 23 months) clinical follow-up (events: cardiac death and hospital admission for heart failure) was also obtained.ResultsAt follow-up after CRT, in the overall population, ejection fraction increased from 26 ± 6% to 35 ± 11% (p < 0.0001), whereas end-diastolic volume index (from 144 ± 43 ml/m2 to 119 ± 55 ml/m2), ESVI (from 108 ± 37 ml/m2 to 82 ± 49 ml/m2, p < 0.0001 for both), and sphericity index (from 0.60 ± 0.22 to 0.53 ± 0.15, p = 0.0036) all significantly decreased. By multiple linear regression analysis, after controlling for confounding factors, change in LV ejection fraction at follow-up resulted independently and negatively associated with baseline ESVI (p = 0.001), with much lower improvement after implant in the highest tertile of baseline ESVI. During follow-up, 31 patients (39.7%) had a cardiac event. By Cox regression model, baseline ESVI was the most powerful predictor of events, with event-rate/year increasing with increasing tertiles of ESVI (6.3%, 10.1%, and 23.8%, respectively, p < 0.05).ConclusionsIn this nonrandomized, open-label clinical study, despite intraventricular electrical and mechanical dyssynchrony, extensive LV remodeling at baseline negatively impacted CRT results in terms of LV function improvement and incidence of cardiac events at follow-up.

In patients with ischaemic left ventricular (LV) dysfunction and viable myocardium, revascularization improves systolic function. Diastolic dysfunction is also present in such patients; however, whether revascularization improves diastolic function also is largely unknown. Methods Twenty-six patients with chronic ischaemic cardiomyopathy (ejection fraction (EF) 32+6%, wall motion score index (WMSI) 2.45+0.33) and viable myocardium (low-dose dobutamine echocardiography) were examined at baseline and � 4 months after revascularization. Diastolic function was assessed by transmitral pulsed-wave Doppler and tissue Doppler imaging (TDI) at the mitral annulus. Results At baseline, 62% of patients showed non-restrictive filling (non-RF) pattern, and 38% restrictive filling (RF) pattern. After revascularization, along with improvement in systolic function (EF 43+10%, WMSI 1.78+0.47, P ¼ 0.0002 for both), diastolic filling improved in most patients, with only three patients still exhibiting RF pattern (P ¼ 0.016); fur- thermore, E 0 velocity increased (32+42%, P ¼ 0.0028) and E/E 0 decreased (219+31%, P ¼ 0.0378) compared with baseline. Left ventricular filling pressure also decreased, from 17.5+6.8 to 13.1+6.5 mmHg (P ¼ 0.005). Improvement of diastolic function by TDI was related to the extent of viability at baseline (P ¼ 0.0098) and to LV reverse remodelling after revascularization (P ¼ 0.0092). Conclusion In patients with ischaemic cardiomyopathy, LV diastolic filling may largely improve after revascularization. Improve- ment of diastolic dysfunction is related to the amount of viable tissue and it may represent an additional advantage of revascularizing dyssinergic but viable myocardium.

Increased dispersion of the QT interval has been observed during pacing or exercise stress testing in patients with coronary artery disease (CAD). It has not been established whether this phenomenon is a consequence of ischemia. Therefore, we sought to evaluate whether dipyridamole-induced myocardial ischemia, as directly detected by echocardiographic monitoring of regional contractile function, would affect QT dispersion. Twenty-four patients with nonsignificant and 34 patients with significant CAD but no previous myocardial infarction underwent dipyridamole stress echocardiography while not taking medications. QT dispersion was measured on a 12-lead electrocardiogram at baseline and at various times after dipyridamole infusion. Dipyridamole infusion did not influence QT dispersion in patients without CAD. QT dispersion was similarly unaffected in patients with CAD in whom dipyridamole did not induce wall motion abnormalities. In contrast, in patients with positive dipyridamole stress test findings, QT dispersion increased from 60 +/- 17 ms at baseline to 94 +/- 25 ms during peak infusion (p0.0001), with a time course mirroring that of development of contractile abnormalities. QT dispersion returned to 63 +/- 25 ms upon relief of ischemia by administration of aminophylline. The increase in QT dispersion was significantly related to the extent of contractile dysfunction induced by dipyridamole. Although ST-segment depression occurred in only 40% of patients with positive dipyridamole stress test findings, 88% of such patients had an increase in QT dispersion. Analysis of the receiver-operating characteristic curve showed that a QT dispersion increase ofor =20 ms identified positive findings for dipyridamole stress echocardiography with 68% sensitivity and 91% specificity. Thus, QT dispersion is acutely affected by myocardial ischemia induced by the administration of dipyridamole. Measurement of QT dispersion may improve detection of stress-induced ischemia on surface electrocardiograms.