Clinical Significance of Global Wasted Work in Patients with Heart Failure Receiving Cardiac Resynchronization Therapy.

BACKGROUND: The relationship between myocardial work assessment using pressure-strain loops by echocardiography before cardiac resynchronization therapy (CRT) and response to CRT has been recently revealed. Among myocardial work parameters, the impact of left ventricular myocardial global wasted work (GWW) on response to CRT and outcome following CRT has been seldom studied. Hence, the authors evaluated the relationship between preprocedural GWW and outcome in a large prospective cohort of patients with heart failure (HF) and reduced ejection fraction receiving CRT. METHODS: The study included 249 patients with HF. Myocardial work indices including GWW were calculated using speckle-tracking strain two-dimensional echocardiography using pressure-strain loops. End points of the study were (1) response to CRT, defined as left ventricular reverse remodeling and/or absence of hospitalization for HF, and (2) all-cause death during follow-up. RESULTS: Median follow-up duration was 48 months (interquartile range, 43-54 months). Median preoperative GWW was 281 mm Hg% (interquartile range, 184-388 mm Hg%). Preoperative GWW was associated with CRT response (area under the curve, 0.74; P < .0001), and a 200 mm Hg% threshold discriminated CRT nonresponders from responders with 85% specificity and 50% sensitivity, even after adjustment for known predictors of CRT response (adjusted odds ratio, 4.03; 95% CI, 1.91-8.68; P < .001). After adjustment for established predictors of outcome in patients with HF with reduced ejection fraction receiving CRT, GWW < 200 mm Hg% remained associated with a relative increased risk for all-cause death compared with GWW ≥ 200 mm Hg% (adjusted hazard ratio, 2.0; 95% CI, 1.1-3.9; P = .0245). Adding GWW to a baseline model including known predictors of outcome in CRT resulted in an improvement of this model (χ2 to improve 4.85, P = .028). The relationship between GWW and CRT response and outcome was stronger in terms of size effect and statistical significance than for other myocardial work indices. CONCLUSIONS: Low preoperative GWW (<200 mm Hg%) is associated with absence of CRT response in CRT candidates and with a relative increased risk for all-cause death. GWW appears to be a promising parameter to improve selection for CRT of patients with HF with reduced ejection fraction.

Prognostic Importance of Left Ventricular Global Longitudinal Strain in Patients with Severe Aortic Stenosis and Preserved Ejection Fraction.

BACKGROUND: Impaired left ventricular (LV) speckle-tracking-derived global longitudinal strain (GLS) magnitude (GLS worse than 14.7%) has been associated with poor outcome in patients with severe aortic stenosis (AS) and preserved LV ejection fraction (EF). OBJECTIVES: To test the hypothesis that GLS magnitude ≤ 15% obtained with vendor-independent speckle-tracking strain software may be able to identify patients with severe AS who are at higher risk of death, despite preserved LVEF and no or mild symptoms. METHODS: GLS was retrospectively obtained in 332 patients with severe AS (aortic valve area indexed [AVAi] < 0.6 cm2/m2), no or mild symptoms, and LVEF ≥ 50%. Absolute values of GLS were collected. Survival analyses were carried out to study the impact of GLS magnitude on all-cause mortality. RESULTS: During a median follow-up period of 42 (37-46) months, 105 patients died. On multivariate analysis, and after adjustment of known clinical and/or echocardiographic predictors of outcome and aortic valve replacement as a time-dependent covariate, GLS magnitude ≤ 15% was independently associated with mortality during follow-up (all P < .01). Adding GLS magnitude ≤ 15% (adjusted hazard ratio = 1.99 [1.17-3.38], P = .011) to a multivariate model including clinical and echocardiographic variables of prognostic importance (aortic valve replacement, aortic valve area, LV stroke volume index < 30 mL/m2, and LVEF<60%) improved the predictive performance with improved global model fit, reclassification, and better discrimination. After propensity score matching (n = 196), increased risk of mortality persisted among patients with GLS magnitude ≤ 15% compared with those with GLS > 15% (hazard ratio = 2.10; 95% confidence interval, 1.20-3.68; P = .009). CONCLUSIONS: In this series of patients with severe AS, no or mild symptoms, and LVEF ≥ 50%, GLS obtained with vendor-independent speckle-tracking strain software was an effective tool to identify patients with a poor outcome. Detection of myocardial dysfunction by identifying GLS magnitude < 15% in patients with severe AS, no or mild symptoms, and LVEF ≥ 50%, can aid in risk assessment.

Prognostic Impact of the Ratio of Acceleration Time to Ejection Time in Patients With Low Gradient Severe Aortic Stenosis and Preserved Ejection Fraction.

The clinical management of patients with low gradient severe aortic stenosis (LG-SAS) and preserved left ventricular ejection fraction (LVEF) remains challenging owing to their heterogeneity. The aim to this study was to evaluate the relation between an ejection dynamic parameter linked to AS severity and outcome, the ratio of acceleration time (AT) to ejection time (ET), in a cohort of patients with LG-SAS and preserved LVEF. Three hundred and fifty-six patients with LG-AS (defined by AVA ≤1 cm² and/or AVAi ≤0.6 cm²/m² and mean aortic pressure gradient <40 mm Hg) and preserved LVEF ≥50% were studied. The relation between AT/ET and all-cause and cardiac mortality during follow-up was studied. Median follow-up was 41 months (interquartile range, 35 to 47 months). Median AT/ET was 0.32 (interquartile range, 0.29 to 0.36). The 5-year estimates of all-cause and cardiac mortality were respectively 57 ± 7%, 36 ± 7% for patients with AT/ET >0.36 versus 43 ± 4%, 16 ± 3% for patients with AT/ET ≤0.36 (p = 0.024 and p <0.001, respectively). After adjustment on known predictors of outcome including aortic valve replacement used as a time-dependent covariate, there was a significant increase in all-cause mortality risk for patients with AT/ET >0.36 (adjusted hazard ratio 2.04 [95% confidence interval, 1.32 to 3.13]; p = 0.001) and cardiac mortality risk (adjusted hazard ratio 2.89 [95% confidence interval, 1.54 to 5.43]; p<0.001) compared with patients with AT/ET ≤0.36. The association of AT/ET >0.36 and all-cause or cardiac mortality risk was consistent in subgroups of patients with LG-SAS and preserved EF. In conclusion, an AT/ET ratio of more than 0.36 is an independent predictor of mortality in patients with LG-SAS and preserved EF.

Clinical Significance of Electromechanical Dyssynchrony and QRS Narrowing in Patients With Heart Failure Receiving Cardiac Resynchronization Therapy.

BACKGROUND: We hypothesized that preoperative electromechanical dyssynchrony amenable to cardiac resynchronization therapy (CRT) and QRS narrowing immediately after CRT are both correlated and have a cumulative impact on response and outcome after CRT. METHODS: A total of 233 CRT candidates (heart failure New York Heart Association classes II-IV, ejection fraction < 35%, QRS ≥ 120 milliseconds, 44% women, 71 ± 11 years old) were prospectively included. Preoperative electromechanical dyssynchrony amenable to CRT was assessed by septal deformation patterns using speckle tracking echocardiography. QRS narrowing was calculated from 12-lead electrocardiograms before and immediately after CRT implantation. The primary endpoint was overall mortality during long-term follow-up. The NTC clinical trial number is NCT02986633. RESULTS: Eighty-seven percent of patients with preoperative electromechanical dyssynchrony experienced QRS narrowing after CRT (118/136), whereas 69% of patients without preoperative electromechanical dyssynchrony (67/97) experienced QRS narrowing after CRT (P < 0.001). By Cox multivariate analysis, both preoperative electromechanical dyssynchrony and lack of postoperative QRS narrowing were independently associated with an increased risk of mortality during follow-up (adjusted hazards ratio [HR] 2.24, 95% confidence interval [CI] 1.43-3.50 and HR 1.90, 95% CI 1.06-3.38, respectively). Compared with patients with preoperative electromechanical dyssynchrony, patients without both electromechanical dyssynchrony and postoperative QRS narrowing experienced a considerable increased risk of mortality during follow-up (adjusted HR 3.70, 95% CI 1.96-6.97). CONCLUSIONS: Lack of postoperative QRS narrowing after CRT is associated with preoperative electromechanical dyssynchrony. Both preoperative electromechanical dyssynchrony and postoperative QRS narrowing have a favourable cumulative impact on outcome after CRT.

Prospective assessment of the frequency of low gradient severe aortic stenosis with preserved left ventricular ejection fraction: Critical impact of aortic flow misalignment and pressure recovery phenomenon.

BACKGROUND: The frequency of paradoxical low-gradient severe aortic stenosis (AS) varies widely across studies. The impact of misalignment of aortic flow and pressure recovery phenomenon on the frequency of low-gradient severe AS with preserved left ventricular ejection fraction (LVEF) has not been evaluated in prospective studies. AIMS: To investigate prospectively the impact of aortic flow misalignment by Doppler and lack of pressure recovery phenomenon correction on the frequency of low-gradient (LG) severe aortic stenosis (AS) with preserved LVEF. METHODS: Aortic jet velocities and mean pressure gradient (MPG) were obtained by interrogating all windows in 68 consecutive patients with normal LVEF and severe AS (aortic valve area [AVA] ≤1cm2) on the basis of the apical imaging window alone (two-dimensional [2D] apical approach). Patients were classified as having LG or high-gradient (HG) AS according to MPG <40mmHg or ≥40mmHg, and normal flow (NF) or low flow (LF) according to stroke volume index >35mL/m2 or ≤35mL/m2, on the basis of the 2D apical approach, the multiview approach (multiple windows evaluation) and AVA corrected for pressure recovery. RESULTS: The proportion of LG severe AS was 57% using the 2D apical approach alone. After the multiview approach and correction for pressure recovery, the proportion of LG severe AS decreased from 57% to 13% (LF-LG severe AS decreased from 23% to 3%; NF-LG severe AS decreased from 34% to 10%). As a result, 25% of patients were reclassified as having HG severe AS (AVA ≤1cm2 and MPG ≥40mmHg) and 19% as having moderate AS. Hence, 77% of patients initially diagnosed with LG severe AS did not have "true" LG severe AS when the multiview approach and the pressure recovery phenomenon correction were used. CONCLUSIONS: Aortic flow misevaluation, resulting from lack of use of multiple windows evaluation and pressure recovery phenomenon correction, accounts for a large proportion of incorrectly graded AS and considerable overestimation of the frequency of LG severe AS with preserved LVEF.

Time course of secondary mitral regurgitation in patients with heart failure receiving cardiac resynchronization therapy: Impact on long-term outcome beyond left ventricular reverse remodelling.

BACKGROUND: The prognostic value of secondary mitral regurgitation (MR) at baseline versus immediately after and several months after cardiac resynchronization therapy (CRT), beyond left ventricular (LV) reverse remodelling, has yet to be investigated. AIM: To evaluate the clinical significance of secondary MR before and at two timepoints after CRT in a large cohort of consecutive patients with heart failure (HF) and reduced LV ejection fraction. METHODS: A total of 198 patients were recruited prospectively into a registry, and underwent echocardiography at baseline and immediately after CRT (on the day of hospital discharge). Echocardiography was also performed 9 months after CRT in 172 patients. The impact of significant secondary MR (≥moderate) on all-cause death, cardiovascular death and hospitalization for HF was studied at each stage. RESULTS: The frequency of significant secondary MR decreased from 23% (n=45) to 8% (n=16) immediately after CRT. Among the 172 patients who underwent echocardiography 9 months after CRT, 17 (10%) had significant secondary MR. During a median follow-up of 48 months, 49 patients died and 36 were hospitalized for HF. Patients with significant secondary MR immediately after or 9 months after CRT had an increased risk of all-cause death, cardiovascular death and hospitalization for HF during follow-up (P<0.05 for all endpoints). After adjustment for LV reverse remodelling, significant secondary MR 9 months after CRT remained associated with an increased risk of all-cause death (adjusted hazard ratio [HR] 3.77; P=0.014), cardiovascular death (adjusted HR 5.36; P=0.037), and hospitalization for HF (adjusted HR 7.33; P=0.001). CONCLUSIONS: Significant secondary MR despite CRT provides important prognostic information beyond LV reverse remodelling. Further studies are needed to evaluate the potential role of new percutaneous procedures for mitral valve repair in improving outcome in these very high-risk patients.

Global longitudinal strain software upgrade: Implications for intervendor consistency and longitudinal imaging studies.

BACKGROUND: Speckle tracking can be used to measure left ventricular global longitudinal strain (GLS). AIMS: To study the effect of speckle tracking software product upgrades on GLS values and intervendor consistency. METHODS: Subjects (patients or healthy volunteers) underwent systematic echocardiography with equipment from Philips and GE, without a change in their position. Off-line post-processing for GLS assessment was performed with the former and most recent upgrades from these two vendors (Philips QLAB 9.0 and 10.2; GE EchoPAC 12.1 and 13.1.1). GLS was obtained in three myocardial layers with EchoPAC 13.1.1. Intersoftware and intervendor consistency was assessed. Interobserver variability was tested in a subset of patients. RESULTS: Among 73 subjects (65 patients and 8 healthy volunteers), absolute values of GLS were higher with QLAB 10.2 compared with 9.0 (intraclass correlation coefficient [ICC]: 0.88; bias: 2.2%). Agreement between EchoPAC 13.1.1 and 12.1 varied by myocardial layer (13.1.1 only): midwall (ICC: 0.95; bias: -1.1%), endocardium (ICC: 0.93; bias: 1.6%) and epicardial (ICC: 0.80; bias: -3.3%). Although GLS was comparable for QLAB 9.0 versus EchoPAC 12.1 (ICC: 0.95; bias: 0.5%), the agreement was lower between QLAB 10.2 and EchoPAC 13.1.1 endocardial (ICC: 0.91; bias: 1.1%), midwall (ICC: 0.73; bias: 3.9%) and epicardial (ICC: 0.54; bias: 6.0%). Interobserver variability of all software products in a subset of 20 patients was excellent (ICC: 0.97-0.99; bias: -0.8 to 1.0%). CONCLUSION: Upgrades of speckle tracking software may be associated with significant changes in GLS values, which could affect intersoftware and intervendor consistency. This finding has important clinical implications for the longitudinal follow-up of patients with speckle tracking echocardiography.

Quantitative Evaluation of Mitral Regurgitation Secondary to Mitral Valve Prolapse by Magnetic Resonance Imaging and Echocardiography.

The present prospective study was designed to evaluate the accuracy of quantitative assessment of mitral regurgitant fraction (MRF) by echocardiography and cardiac magnetic resonance imaging (cMRI) in the modern era using as reference method the blinded multiparametric integrative assessment of mitral regurgitation (MR) severity. 2-Dimensional (2D) and 3-dimensional (3D) MRF by echocardiography (2D echo MRF and 3D echo MRF) were obtained by measuring the difference in left ventricular (LV) total stroke volume (obtained from either 2D or 3D acquisition) and aortic forward stroke volume normalized to LV total stroke volume. MRF was calculated by cMRI using either (1) (LV stroke volume - systolic aortic outflow volume by phase contrast)/LV stroke volume (cMRI MRF [volumetric]) or (2) (mitral inflow volume - systolic aortic outflow volume)/mitral inflow volume (cMRI MRF [phase contrast]). Six patients had 1 + MR, 6 patients had 2 + MR, 12 patients had 3 + MR, and 10 had 4 + MR. A significant correlation was observed between MR grading and 2D echo MRF (r = 0.60, p <0.0001) and 3D echo MRF (r = 0.79, p <0.0001), cMRI MRF (volumetric) (r = 0.87, p <0.0001), and cMRI MRF (phase contrast r = 0.72, p <0.001). The accuracy of MRF for the diagnosis of MR ≥3+ or 4+ was the highest with cMRI MRF (volumetric) (area under the receiver-operating characteristic curve [AUC] = 0.98), followed by 3D echo MRF (AUC = 0.96), 2D echo MRF (AUC = 0.90), and cMRI MRF (phase contrast; AUC = 0.83). In conclusion, MRF by cMRI (volumetric method) and 3D echo MRF had the highest diagnostic value to detect significant MR, whereas the diagnostic value of 2D echo MRF and cMRI MRF (phase contrast) was lower. Hence, the present study suggests that both cMRI (volumetric method) and 3D echo represent best approaches for calculating MRF.