Additive Prognostic Value of Left Ventricular Dispersion and Deformation in Patients With Severe Aortic Stenosis.

BACKGROUND: Speckle tracking strain echocardiography allows one to visualize the timing of maximum regional strain and quantifies left ventricular-mechanical dispersion (LV-MD). Whether LV-MD and LV-global longitudinal strain (LV-GLS) provide similar or complementary information in mortality risk stratification in patients with severe aortic stenosis (SAS) remains unknown. OBJECTIVES: The authors hypothesized that LV mechanical dyssynchrony assessed by LV-MD is associated with an increased risk of mortality and provides additional prognostic information on top of LV-GLS in patients with SAS. METHODS: A total of 364 patients with SAS (aortic valve area indexed ≤0.6 cm2/m2 and/or aortic valve area ≤1 cm2), LV ejection fraction ≥50% and no or mild symptoms were enrolled. The endpoint was overall mortality. RESULTS: During a median follow-up period of 41 months, 149 patients died. After adjustment, LV-MD ≥68 ms was significantly associated with an increased risk of mortality (adjusted HR: 1.41; 95% CI: 1.01-1.96; P = 0.044). Adding LV-MD ≥68 ms to a multivariable Cox regression model including LV-GLS ≥-15% improved predictive performance in terms of overall mortality, with improved global model fit, reclassification, and better discrimination. Patients with both criteria had an important increase in mortality compared to patients with none or one criterion (adjusted HR: 2.02; 95% CI: 1.34-3.03; P = 0.001). Interobserver reproducibility of LV-MD was good with an intraclass correlation coefficient of 0.90 (95% CI: 0.72-0.97). CONCLUSIONS: LV-MD is a reproducible parameter independently associated with an increased risk of mortality in SAS. Increased LV-MD associated with depressed LV-GLS identifies a subgroup of patients with an increased mortality risk. Whether early aortic valve replacement improves the outcome of these patients deserves further studies.

Dyssynchrony and Response to Cardiac Resynchronization Therapy in Heart Failure Patients With Unfavorable Electrical Characteristics.

BACKGROUND: Among heart failure (HF) patients undergoing cardiac resynchronization therapy (CRT), those with unfavorable electrical characteristics (UEC) are less frequently CRT responders. OBJECTIVES: In this study, the authors sought to evaluate the relationship between preprocedural echocardiographic parameters of electromechanical dyssynchrony (EMD) and outcome following CRT. METHODS: Among 551 patients receiving CRT, 121 with UEC, defined as atypical left bundle branch, presence of right bundle branch block, or unspecified intraventricular conduction disturbance, were enrolled. Indices of EMD were presence of septal flash, apical rocking, septal deformation patterns, and global wasted work (GWW), determined with the use of speckle-tracking strain echocardiography. Endpoints were response to CRT, defined as a relative decrease in left ventricular end-systolic volume ≥15% at 9-month postoperative follow-up, and all-cause death or HF hospitalization during follow-up. RESULTS: Among the 121 patients, 68 (56%) were CRT responders. In multivariate analysis, GWW ≥200 mm Hg% (adjusted odds ratio [aOR]: 4.17 [95% CI: 1.33-14.56]; P = 0.0182) and longitudinal strain septal contraction patterns 1 and 2 (aOR: 10.05 [95% CI: 2.82-43.97]; P < 0.001) were associated with CRT response. During a 46-month follow-up (IQR: 42-55 months), survival free from death or HF hospitalization increased with the number of positive criteria (87% for 2, 59% for 1, and 27% for 0). After adjustment for established predictors of outcome in patients receiving CRT, absence of either of the 2 criteria remained associated with a considerable increased risk of death and/or HF hospitalization (adjusted HR: 4.83 [95% CI: 1.84-12.68]; P = 0.001). CONCLUSIONS: In patients with UEC, echocardiographic assessment of EMD may help to select patients who will derive benefit from CRT. (Echocardiography in Cardiac Resynchronization Therapy [Echo-CRT]; NCT02986633).

Impact of left atrial and diastolic ventricular dysfunction on mortality in patients with aortic stenosis.

BACKGROUND: Diastolic dysfunction (DD) is common in severe aortic stenosis (AS) and preserved left ventricular ejection fraction (LVEF≥50%). AIM: To determine the impact of American Society of Echocardiography/European Association of Cardiovascular Imaging-recommended DD grading and left atrial strain on mortality in a cohort of patients with severe AS and preserved LVEF. METHODS: We studied patients with severe AS (aortic valve area indexed<0.6 cm2/m2 and/or aortic valve area<1cm2), LVEF≥50% and no or mild AS-related symptoms. The endpoint was all-cause mortality. RESULTS: A total of 387 patients (median age 76years; 53% women) were studied. During a median follow-up of 57 (interquartile range 37; 83) months, 158 patients died. After adjustment for prognostic factors, patients with grade II or III DD had an increased mortality risk versus patients with grade I DD (adjusted hazard ratio (aHR) 1.62, 95% confidence interval (CI) 1.11-2.38; P=0.013; aHR 4.73, 95% CI 2.49-8.99; P<0.001; respectively). Adding peak atrial longitudinal strain (PALS)≤14% to a multivariable model including DD grade improved predictive performance, with better global model fit, reclassification and discrimination. Patients with grade III DD or grade II DD+PALS≤14% displayed an increased mortality risk versus patients with grade I DD+PALS>14% (aHR 4.17, 95% CI 2.46-7.06; P<0.0001). Those with grade I DD+PALS≤14% or grade II DD+PALS>14% were at intermediate risk (aHR 1.63, 95% CI 1.07-2.49; P=0.024). CONCLUSIONS: Our results demonstrate the strong relationship between DD and mortality in patients with severe AS and preserved LVEF. Patients with grade III or grade II DD and impaired PALS are at very high risk. These data demonstrate the importance of a comprehensive assessment of diastolic function in patients with severe AS.

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.

Balloon aortic valvuloplasty for severe aortic stenosis before urgent non-cardiac surgery.

BACKGROUND: Balloon aortic valvuloplasty (BAV) has been proposed as a therapeutic option in patients suffering from severe aortic stenosis (SAS) who need urgent non-cardiac surgery (NCS). Whether this strategy is better than medical therapy in this very specific population is unknown. AIMS: We aimed to evaluate the clinical benefit of an invasive strategy (IS) with preoperative BAV in patients with SAS requiring urgent NCS. METHODS: From 2011 to 2019, a registry conducted in two centres included 133 patients with SAS undergoing urgent NCS, of whom 93 underwent preoperative BAV (IS) and 40 a conservative strategy (CS) without BAV. All analyses were adjusted for confounding using inverse probability of treatment weighting (IPTW) (10 clinical and anatomical variables). RESULTS: The primary outcome was MACE at one-month follow-up after NCS including mortality, heart failure, and other cardiovascular outcomes. In patients managed conservatively, occurrence of MACE was 20.0% (n=8) and death was 10.0% (n=4) at 1 month. In patients undergoing BAV, the occurrence of MACE was 20.4% (n=19) and death was 5.4% (n=5) at 1 month. Among patients undergoing conservative management, all events were observed after NCS while, in patients undergoing BAV, 12.9% (n=12) had events between BAV and NCS including 3 deaths, and 7.5% (n=7) had events after NCS including 2 deaths. In IPTW propensity analyses, the incidence of the primary outcome (20.4% vs 20.0%; OR 0.93, 95% CI: 0.38-2.29) and three-month survival (89.2% vs 90.0%; IPTW-adjusted HR 0.90, 95% CI: 0.31-2.60) were similar in both groups. CONCLUSIONS: Patients with SAS managed conservatively before urgent NCS are at high risk of events. A systematic invasive strategy using BAV does not provide a significant improvement in clinical outcome.

Clinical and prognostic implications of phenomapping in patients with heart failure receiving cardiac resynchronization therapy.

BACKGROUND: Despite having an indication for cardiac resynchronization therapy according to current guidelines, patients with heart failure with reduced ejection fraction who receive cardiac resynchronization therapy do not consistently derive benefit from it. AIM: To determine whether unsupervised clustering analysis (phenomapping) can identify distinct phenogroups of patients with differential outcomes among cardiac resynchronization therapy recipients from routine clinical practice. METHODS: We used unsupervised hierarchical cluster analysis of phenotypic data after data reduction (55 clinical, biological and echocardiographic variables) to define new phenogroups among 328 patients with heart failure with reduced ejection fraction from routine clinical practice enrolled before cardiac resynchronization therapy. Clinical outcomes and cardiac resynchronization therapy response rate were studied according to phenogroups. RESULTS: Although all patients met the recommended criteria for cardiac resynchronization therapy implantation, phenomapping analysis classified study participants into four phenogroups that differed distinctively in clinical, biological, electrocardiographic and echocardiographic characteristics and outcomes. Patients from phenogroups 1 and 2 had the most improved outcome in terms of mortality, associated with cardiac resynchronization therapy response rates of 81% and 78%, respectively. In contrast, patients from phenogroups 3 and 4 had cardiac resynchronization therapy response rates of 39% and 59%, respectively, and the worst outcome, with a considerably increased risk of mortality compared with patients from phenogroup 1 (hazard ratio 3.23, 95% confidence interval 1.9-5.5 and hazard ratio 2.49, 95% confidence interval 1.38-4.50, respectively). CONCLUSIONS: Among patients with heart failure with reduced ejection fraction with an indication for cardiac resynchronization therapy from routine clinical practice, phenomapping identifies subgroups of patients with differential clinical, biological and echocardiographic features strongly linked to divergent outcomes and responses to cardiac resynchronization therapy. This approach may help to identify patients who will derive most benefit from cardiac resynchronization therapy in "individualized" clinical practice.

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.

Clinical significance of energy loss index in patients with low-gradient severe aortic stenosis and preserved ejection fraction.

AIMS: We hypothesized that among patients with low-gradient severe aortic stenosis (AS) and preserved left ventricular ejection fraction (LVEF), reclassification of AS severity as moderate by pressure recovery adjusted indexed aortic valve area (AVAi) = energy loss index (ELI), may identify a subgroup of patients with a better outcome. METHODS AND RESULTS: Three hundred and seventy-nine patients with low-gradient AS (defined by AVAi ≤ 0.6 cm2/m2 and mean aortic pressure gradient < 40 mmHg) and preserved LVEF ≥50% were studied. Reclassification as moderate AS by ELI was defined as AVAi ≤0.6 cm2/m2 but with an ELI >0.6 cm2/m2. Cardiac events [cardiac mortality and/or need for aortic valve replacement (AVR)] during follow-up were studied. One hundred and forty-eight patients (39%) were reclassified as moderate AS by ELI. Reclassification as moderate AS was independently associated with decreased body surface area, normal flow status, decreased left ventricular mass index, and left atrial volume index (all P < 0.05). After adjustment for variables of prognostic interest, reclassification as moderate AS by ELI was associated with a considerable reduction of risk of cardiac events {adjusted hazard ratio (HR) 0.49 [95% confidence interval (CI) 0.33-0.72]; P < 0.001}, need for AVR [adjusted HR 0.52 (95% CI 0.34-0.81); P = 0.004], and cardiac mortality [adjusted HR 0.46 (95% CI 0.22-0.98); P = 0.044]. CONCLUSION: In patients with low-gradient severe AS and preserved LVEF, calculation of ELI permits to reclassify almost 40% of patients as having moderate AS. These reclassified patients have a considerable reduction of the risk of cardiac events during follow-up. Calculation of ELI is useful for decision-making in patients with low-gradient severe AS and preserved ejection fraction.

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.

Impact of Increased Right Atrial Size on Long-Term Mortality in Patients With Heart Failure Receiving Cardiac Resynchronization Therapy.

The ability to visualize the right atrium (RA) by echocardiography allows a quantitative, highly reproducible assessment of the RA volume (RAV). The aim of this study is to evaluate the relation between RAV and long-term mortality in a prospective cohort of heart failure and reduced ejection fraction patients in sinus rhythm receiving cardiac resynchronization therapy. 172 patients were included. The right atrium volume index (RAVI) was calculated using Simpson's method from the apical four-chamber view and indexed to body surface area. The relation between RAVI and mortality during follow up was studied. Median follow up was 68 months (interquartile range 62 to 73 months). Mean RAVI was 27 ± 14 mL/m² (IQR 22 to 33 mL/m²). Cumulative 5-year all-cause mortality was 22 ± 6% in patients with RAVI ≤ 19 mL/m², 24 ± 6% for RAVI 19 to 29 mL/m² and 58 ± 7% for RAVI >29 mL/m² (p for trend <0.001). After adjustment on clinical and echocardiographic predictors of outcome including indices of right ventricular function, there was a significant increase in overall mortality risk with increasing RAVI (adjusted hazard ratio 1.02 [95% confidence interval, 1.00 to 1.03], per 1 mL/m2 increment; p = 0.042). Patients in the highest tertile (RAVI >29 mL/m²) had significantly greater risk of death compared with those with RAVI ≤29 mL/m² (adjusted hazard ratio 2.01 [95% confidence interval, 1.15 to 3.50]; p = 0.014). In conclusion, RA enlargement is a powerful and highly reproducible independent predictor of long-term mortality in patients with heart failure and reduced ejection fraction in sinus rhythm receiving cardiac resynchronization therapy.

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.