Quantitation of myocardial 99mTc-HMDP uptake with new SPECT/CT cadmium zinc telluride (CZT) camera in patients with transthyretin-related cardiac amyloidosis: Ready for clinical use?

BACKGROUND: The aim of this study was to investigate the feasibility of assessing absolute myocardial 99mTc-HMDP uptake in patients with suspected cardiac ATTR using SUV with a whole-body CZT SPECT-CT camera (DNM670CZT). METHODS: Fifteen patients with suspected cardiac ATTR (Perugini ≥ 2) underwent a conventional 99mTc-HMDP planar imaging and a thoracic SPECT/CT using a DNM 670CZT. A control group consisted of 15 patients with negative scintigraphy (Perugini < 2). SUVmax (mg·L-1) and percentage of injected dose (%ID) were calculated in a cardiac volume of interest (VOI) encompassing the left ventricle. VOIs were also placed in the lung, the right pectoris major, and the sternum. A heart-to-lung SUVmax ratio (HLR) was calculated. RESULTS: All ATTR patients demonstrated an increased cardiac HMDP SUVmax (12.2 ± 3.7 mg·L-1) vs controls (3.5 ± 1.2, P < .0001). Percentage of ID, pectoral uptake and HLR were significantly higher in the ATTR group (1.1 ± 0.3 vs 0.15 ± 0.8, P < .0001; 1.5 ± 0.3 vs 0.9 ± 0.3, P < .0001; 9.7 ± 3 vs 4.3 ± 2.2, P < .0001). Bone uptake was not statistically different between the two groups. CONCLUSION: This study demonstrated the feasibility of quantitative 99mTc-HMDP SUVmax measurement using a whole-body SPECT/CT CZT camera in patients with suspected cardiac ATTR.

Assessment of left ventricular size and function by 3-dimensional transthoracic echocardiography: Impact of the echocardiography platform and analysis software.

BACKGROUND: Whether echocardiography platform and analysis software impact left ventricular (LV) volumes, ejection fraction (EF), and stroke volume (SV) by transthoracic tridimensional echocardiography (3DE) has not yet been assessed. Hence, our aim was to compare 3DE LV end-diastolic and end-systolic volumes (EDV and ESV), LVEF, and SV obtained with echocardiography platform from 2 different manufacturers. METHODS: 3DE was performed in 84 patients (65% of screened consecutive patients), with equipment from 2 different manufacturers, with subsequent off-line postprocessing to obtain parameters of LV function and size (Philips QLAB 3DQ and General Electric EchoPAC 4D autoLVQ). Twenty-five patients with clinical indication for cardiac magnetic resonance imaging served as a validation subgroup. RESULTS: LVEDV and LVESV from 2 vendors were highly correlated (r = 0.93), but compared with 4D autoLVQ, the use of Qlab 3DQ resulted in lower LVEDV and LVESV (bias: 11 mL, limits of agreement: -25 to +47 and bias: 6 mL, limits of agreement: -22 to +34, respectively). The agreement between LVEF values of each software was poor (intraclass correlation coefficient 0.62) despite no or minimal bias. SVs were also lower with Qlab 3DQ advanced compared with 4D autoLVQ, and both were poorly correlated (r = 0.66). Consistently, the underestimation of LVEDV, LVESV, and SV by 3DE compared with cardiac magnetic resonance imaging was more pronounced with Philips QLAB 3DQ advanced than with 4D autoLVQ. CONCLUSIONS: The echocardiography platform and analysis software significantly affect the values of LV parameters obtained by 3DE. Intervendor standardization and improvements in 3DE modalities are needed to broaden the use of LV parameters obtained by 3DE in clinical practice.

Quantitative assessment of aortic regurgitation by Doppler echocardiography: Usefulness of the comparison of aortic and pulmonary flows.

AIMS: Patients with significant (3+/4+) aortic regurgitation (AR) require careful monitoring or valve surgery. We sought to evaluate the diagnostic performance of aortic and pulmonary flow comparison in identifying patients with significant AR, by echocardiography. METHOD: Two hundred forty-six patients with more than trivial AR were prospectively enrolled from three centers. Aortic regurgitation (AR) severity was assessed by an expert using the currently recommended integrative approach. Aortic and pulmonary flows were independently assessed by another investigator to calculate the regurgitant fraction (RF), the aortic to pulmonary flow ratio (Qao/Qp) and the aortic to pulmonary velocity-time integral (VTIao/VTIp) ratio. The control group consisted of 195 patients without AR. RESULTS: A significant correlation was observed between AR grading and RF (r = .82, P < .0001) and Qao/Qp (r = .81, P < .0001), but the correlation was modest for VTIao/VTIp ratio (r = .63; P < .0001). The accuracy of RF and Qao/Qp ratio to identify patients with significant AR was excellent (0.96 and 0.95, respectively), but was significantly lower for VTIao/VTIp ratio at 0.82. A RF > 40% indicated grade 3 or 4 AR with a sensitivity of 83% and a specificity of 93%. A Qao/Qp ratio > 1.6 indicated grade 3 or 4 AR with a sensitivity of 88% and a specificity of 89%. The VTIao/VTIp ratio was not helpful in identifying patients with significant AR, as a wide overlap was found between 1+/2+ and 3+/4+ patients. CONCLUSION: Regurgitant fraction (RF) and Qao/Qp are helpful in identifying significant AR. The assessment of Doppler aortic/pulmonary flow should be incorporated in the comprehensive evaluation of AR.

Is mechanical dyssynchrony a therapeutic target in heart failure with preserved ejection fraction?

BACKGROUND: Previous studies have found a high frequency of mechanical dyssynchrony in patients with heart failure (HF) with preserved ejection fraction (HFpEF), hence suggesting that cardiac resynchronization therapy (CRT) may be considered in HFpEF. The present study was designed to compare the amount of mechanical dyssynchrony between HFpEF patients and (1) HF with reduced EF (HFrEF) patients with an indication for CRT (HFrEF-CRT(+)) group, (2) HFrEF patients with QRS duration < 120 ms (HFrEF-QRS < 120 ms) group, and (3) hypertensive controls (HTN). METHODS: Electrical (ECG) and mechanical dyssynchrony (atrio-ventricular dyssynchrony, interventricular dyssynchrony, intraventricular dyssynchrony) were assessed using conventional, tissue Doppler, and Speckle Tracking strain echocardiography in 40 HFpEF patients, 40 age- and sex-matched HTN controls, 40 HFrEF-QRS < 120 ms patients, and 40 HFrEF-CRT(+) patients. RESULTS: The frequency of left bundle branch block was low in HFpEF patients (5%) and similar to HTN controls (5%, P = 0.85). Indices of dyssynchrony were similar between HFpEF and HTN patients or HFrEF-QRS < 120 ms patients. In contrast, most indices of dyssynchrony differed between HFpEF and HFrEF-CRT(+) patients. The principal components analysis on the entire cohort of 160 patients yielded 2 homogeneous groups of patients in terms of dyssynchrony, the first comprising HFrEF-CRT(+) patients and the second comprising HTN, HFrEF-QRS < 120 ms and HFpEF patients. CONCLUSIONS: Mechanical dyssynchrony in HFpEF does not differ from that of patients with HTN or patients with HFrEF and a narrow QRS. This data raises concerns regarding the role of dyssynchrony in the pathophysiology of HFpEF and thereby the potential usage of CRT in HFpEF.

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.

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).

Cardiac resynchronization therapy as rescue therapy in end-stage heart failure: illustration by three-dimensional speckle tracking strain echocardiography.

We report the case of a 73-year-old man admitted for refractory heart failure following implantation of a dual-chamber pacemaker. Three-dimensional (3D) echocardiography with speckle tracking area strain identified severe left ventricular (LV) dysfunction and LV dyssynchrony following right ventricular pacing. As the patient's clinical condition rapidly worsened despite optimal medical treatment, a cardiac resynchronization therapy (CRT) pacemaker was successfully implanted as rescue therapy. Symptoms rapidly regressed and echocardiographic assessment following CRT demonstrated an immediate improvement in LV systolic function, confirmed at 9-month follow-up with evidence of reverse remodeling. New imaging technologies such as 3D echocardiography with speckle tracking area strain may help to identify and follow up patients who will benefit from CRT as rescue therapy.

Clinical and echocardiographic correlates of plasma B-type natriuretic peptide levels in patients with aortic valve stenosis and normal left ventricular ejection fraction.

BACKGROUND: Several studies suggest that BNP testing may help define the timing of aortic valve surgery in patients with aortic valve stenosis (AVS) prior onset of overt LV systolic dysfunction. The aim of this study was to identify clinical and echocardiographic correlates of plasma BNP levels in a large cohort of patients with AVS and preserved LV ejection fraction. METHOD AND RESULTS: One hundred thirty-five consecutive patients were prospectively included in the present study (Mean age 73 ± 13 years old, 66 (49%) male). Eighty-nine patients (66%) had severe AVS (aortic valve area <0.6 cm(2) /m(2) BSA). Plasma BNP levels, clinical and comprehensive Doppler echocardiography evaluation was performed in all patients. Independent clinical correlates of plasma BNP levels (R(2) = 0.19) were older age (P < 0.0001) and presence of AVS symptoms (P = 0.004). Independent echocardiographic correlates of plasma BNP levels (R(2) = 0.38) were E/Ea ratio (P = 0.01), LV mass index (P = 0.018), left atrial surface (P < 0.0001) and systolic pulmonary artery pressure (sPAP; P = 0.004). Overall, independent correlates of plasma BNP levels (R(2) = 0.47) were older age (P = 0.001), known coronary artery disease (P = 0.047), increased LV mass index (P = 0.001), left atrial enlargement (P = 0.002), and increased sPAP (P = 0.003). CONCLUSIONS: In patients with AVS and normal LV ejection fraction, plasma BNP predominantly reflects the clinical and echocardiographic consequences of afterload burden imposed on the left ventricle rather than the severity of valve stenosis, per se.

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.

Relationship Between the Ratio of Acceleration Time/Ejection Time and Mortality in Patients With High-Gradient Severe Aortic Stenosis.

Background The ratio of acceleration time/ejection time (AT/ET) is a simple and reproducible echocardiographic parameter that integrates aortic stenosis severity and its consequences on the left ventricle. No study has specifically assessed the prognostic impact of AT/ET on outcome in patients with high-gradient severe aortic stenosis (SAS) and no or mild symptoms. We sought to evaluate the relationship between AT/ET and mortality and determine the best predictive AT/ET cutoff value in these patients. Methods and Results A total of 353 patients (median age, 79 years; 46% women) with high-gradient (mean pressure gradient ≥40 mm Hg and/or aortic peak jet velocity ≥4 m/s) SAS, left ventricular ejection fraction ≥50%, and no or mild symptoms were studied. The impact of AT/ET ≤0.35 or >0.35 on all-cause mortality was retrospectively studied. During a median follow-up of 39 (25th-75th percentile, 23-62) months, 70 patients died. AT/ET >0.35 was associated with a considerable increased mortality risk after adjustment for established prognostic factors in SAS under medical and/or surgical management (adjusted hazard ratio [HR], 2.54; 95% CI, 1.47-4.37; P<0.001) or conservative management (adjusted HR, 3.29; 95% CI, 1.70-6.39; P<0.001). Moreover, AT/ET >0.35 improved the predictive performance of models including established risk factors in SAS with better global model fit, reclassification, and discrimination. After propensity matching, increased mortality risk persisted when AT/ET >0.35 (adjusted HR, 2.10; 95% CI, 1.12-3.90; P<0.001). Conclusions AT/ET >0.35 is a strong predictor of outcome in patients with SAS and no or only mild symptoms and identifies a subgroup of patients at higher risk of death who may derive benefit from earlier aortic valve replacement.

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.

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.

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.

Clinical Significance of Ejection Dynamics Parameters in Patients with Aortic Stenosis: An Outcome Study.

BACKGROUND: Ejection dynamics parameters are useful in assessing prosthetic valve obstruction, but very limited data are available in the setting of native aortic stenosis (AS). The aim of this study was to evaluate and compare the prognostic value of acceleration time (AT) and the ratio of AT to ejection time (ET) in patients with AS. METHODS: AT and AT/ET were prospectively measured in 456 patients with AS (aortic valve area < 1.3 cm2; mean aortic valve area, 0.85 ± 0.24 cm2). The relationships between AT/ET, AT, and mortality during follow-up were studied. RESULTS: During a median follow-up period of 35 months (interquartile range, 33-37 months), 124 patients died. After adjustment for variables of prognostic importance, including mean pressure gradient, stroke volume index, and aortic valve replacement as a time-dependent covariate, patients in the highest tertiles of both AT/ET (>0.36) and AT (>112 msec) were at high risk for overall mortality (adjusted hazard ratios, 2.44 [95% CI, 1.46-4.08; P = .001] and 1.78 [95% CI, 1.06-2.98; P = .029], respectively) compared with those in the lowest tertiles of AT/ET and AT, while survival was similar for the other tertiles (P = NS for all). Compared with patients with AT/ET ≤ 0.36, an increased risk for overall mortality was observed in patients with AT/ET > 0.36 (adjusted hazard ratio, 2.51; 95% CI, 1.66-3.78; P < .0001), while the risk for mortality was not significantly increased in patients with AT > 112 msec compared with those with AT ≤ 112 msec. Adding AT/ET > 0.36 to a multivariate model including classical variables of prognostic importance, including mean pressure gradient and stroke volume index, improved predictive performance in terms of overall mortality, with improved global model fit, reclassification, and better discrimination. CONCLUSIONS: Among ejection dynamics parameters in patients with AS, AT/ET is strongly associated with excess risk for death during follow-up. AT/ET should be considered in the multiparametric echocardiographic prognostic assessment of patients with AS in clinical practice.

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.

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.

Relationship between exercise pressure gradient and haemodynamic progression of aortic stenosis.

BACKGROUND AND AIMS: We hypothesized that large exercise-induced increases in aortic mean pressure gradient can predict haemodynamic progression during follow-up in asymptomatic patients with aortic stenosis. METHODS: We retrospectively identified patients with asymptomatic moderate or severe aortic stenosis (aortic valve area<1.5cm2 or<1cm2) and normal ejection fraction, who underwent an exercise stress echocardiography at baseline with a normal exercise test and a resting echocardiography during follow-up. The relationship between exercise-induced increase in aortic mean pressure gradient and annualised changes in resting mean pressure gradient during follow-up was investigated. RESULTS: Fifty-five patients (mean age 66±15 years; 45% severe aortic stenosis) were included. Aortic mean pressure gradient significantly increased from rest to peak exercise (P<0.001). During a median follow-up of 1.6 [1.1-3.2] years, resting mean pressure gradient increased from 35±13mmHg to 48±16mmHg, P<0.0001. Median annualised change in resting mean pressure gradient during follow-up was 5 [2-11] mmHg. Exercise-induced increase in aortic mean pressure gradient did correlate with annualised changes in mean pressure gradient during follow-up (r=0.35, P=0.01). Hemodynamic progression of aortic stenosis was faster in patients with large exercise-induced increase in aortic mean pressure gradient (≥20mmHg) as compared to those with exercise-induced increase in aortic mean pressure gradient<20mmHg (median annualised increase in mean pressure gradient 19 [6-28] vs. 4 [2-10] mmHg/y respectively, P=0.002). Similar results were found in the subgroup of 30 patients with moderate aortic stenosis. CONCLUSION: Large exercise-induced increases in aortic mean pressure gradient correlate with haemodynamic progression of stenosis during follow-up in patients with asymptomatic aortic stenosis. Further studies are needed to fully establish the role of ESE in the decision-making process in comparison to other prognostic markers in asymptomatic patients with aortic stenosis.

Clinical significance of septal deformation patterns in heart failure patients receiving cardiac resynchronization therapy.

AIMS: Specific septal motion related to dyssynchrony is strongly linked to reverse remodelling, in patients with systolic heart failure (HF) receiving cardiac resynchronization therapy (CRT). We aimed to investigate the relationship between septal deformation patterns studied by longitudinal speckle tracking and clinical outcome following CRT. METHODS AND RESULTS: A total of 284 CRT candidates from two centres (HF NYHA classes II-IV, ejection fraction < 35%, QRS ≥ 120 ms) were prospectively included. Longitudinal strain of the septum in the apical four-chamber view determined three patterns of septal contraction. The endpoints were overall mortality, cardiovascular mortality, and hospitalization for HF. Compared with patterns 1 or 2, pattern 3 was associated with an increased risk for both overall and cardiovascular mortality [hazard ratio (HR) = 3.78, 95% confidence interval (CI): 1.85-7.75, P < 0.001 and HR = 3.84, 95% CI: 1.45-10.16, P = 0.007, respectively] and HF hospitalization (HR = 4.41, 95% CI: 2.18-8.90, P < 0.001). Addition of septal patterns to multivariable models, including baseline QRS width and presence of left bundle branch block, improved risk prediction, and discrimination. In patients with intermediate QRS duration (120-150 ms), pattern 3 remained associated with a worse outcome than pattern 1 or 2 (P < 0.05 for all endpoints). CONCLUSION: The identification of septal deformation patterns provides important prognostic information in CRT candidates in addition to ordinary clinical, electrocardiographic, and echocardiographic predictors of outcome in HF patients. This parameter may be particularly useful in patients with intermediate QRS duration in whom the benefit of CRT remains uncertain.

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.

Prognostic value of left ventricular reverse remodeling and performance improvement after cardiac resynchronization therapy: A prospective study.

BACKGROUND: The present study was designed to evaluate the respective value of left ventricular (LV) reverse remodeling (changes in LV end-systolic volume relative to baseline (ΔLVESV)) or LV performance improvement (ΔLV ejection fraction (ΔLVEF) or ΔGlobal longitudinal strain (GLS)) to predict long-term outcome in a prospective cohort of consecutive patients receiving routine cardiac resynchronization therapy (CRT). METHODS: One hundred and seventy heart failure patients (NYHA classes II-IV, LVEF ≤ 35%, QRS width ≥ 120 ms) underwent echocardiography before and 9 months after CRT. The relationships between ΔLVESV, ΔLVEF, ΔGLS and outcome (all-cause mortality and/or CHF hospitalization, overall mortality, cardiovascular mortality, CHF hospitalization) were investigated. RESULTS: During a median follow-up of 32 months, 20 patients died and 27 were hospitalized for heart failure. ΔLVESV, ΔLVEF or ΔGLS were significantly associated with all-cause mortality or CHF hospitalization (adjusted hazard's ratio (HR) per standard deviation 0.58 (0.43-0.77), 0.39 (0.27-0.57) or 0.55 (0.37-0.83) respectively, all p < 0.01) and all other endpoints (all p < 0.01). Patients with ΔLVESV≥15%, ΔLVEF ≥ 10% and ΔGLS ≥ 1% had a reduced risk of mortality or CHF hospitalization (adjusted HR=0.25 (0.12-0.51), p < 0.001, adjusted HR = 0.26 (0.13-0.54), p < 0.001 and adjusted HR 0.38 (0.19-0.75), p = 0.006 respectively). Overall performance of multivariate models was better using ΔLVESV or ΔLVEF compared with ΔGLS. Interobserver agreement was excellent for ΔLVESV (Intraclass correlation coefficient - ICC-0.91) and ΔGLS (ICC 0.90) but modest for ΔLVEF (ICC 0.76) in a sample of 20 patients from the study population. CONCLUSIONS: LV reverse remodeling assessed by ΔLVESV is a strong and reproducible predictor of outcome following CRT. Compared with ΔLVESV, ΔLVEF and ΔGLS have important shortcomings: poorer reproducibility or lower predictive value.