Clinical Outcomes With Transcatheter Edge-to-Edge Repair in Atrial Functional MR From the EXPAND Study.

BACKGROUND: Although transcatheter edge-to-edge repair (TEER) has been shown to improve clinical outcomes and improve quality of life in patients with symptomatic secondary mitral regurgitation (SMR) and left ventricular dysfunction, its effect in patients with atrial SMR (aSMR) has not been well described. OBJECTIVES: The aim of this study was to assess the safety, echocardiographic outcomes, and clinical effectiveness of TEER for aSMR. METHODS: Patients with aSMR in the prospective, observational, multicenter EXPAND (A Contemporary, Prospective, Multi-Center Study Evaluating Real-World Experience of Performance and Safety for the Next Generation of MitraClip Devices) study were identified by an echocardiography core laboratory. Follow-up occurred at discharge, 30 days, and 1 year. Key endpoints included mitral regurgitation (MR) severity, functional class, heart failure hospitalizations, mortality, and 30-day major adverse events. RESULTS: Among 1,041 patients enrolled in EXPAND, 835 patients had evaluable echocardiograms at baseline. Of these, 53 patients had aSMR and 360 had ventricular SMR (vSMR). In the aSMR cohort, TEER resulted in a significant reduction in MR through 1 year (MR grade ≤2 in 100.0%), significantly increased 1-year Kansas City Cardiomyopathy Questionnaire score (+26.6 ± 30.5 points; P < 0.0001), and improved functional class from baseline, similar to the effects among patients with vSMR (MR grade ≤2 in 99.5% at 1 year, 1-year increase in Kansas City Cardiomyopathy Questionnaire score 21.23 ± 24.92 points). Major adverse events at 30 days and leaflet adverse events at 1 year were infrequent in both groups. CONCLUSIONS: In a prospective, real-world, global registry, TEER for aSMR was associated with significant MR reduction and improvement in quality of life and functional class, similar to patients with vSMR. This suggests that TEER may provide clinical benefit in patients with atrial fibrillation with SMR in the setting of heart failure with preserved ejection fraction. (The MitraClip® EXPAND Study of the Next Generation of MitraClip® Devices; NCT03502811).

Right ventricular dysfunction predicts outcome after transcatheter mitral valve repair for primary mitral valve regurgitation.

AIMS: Right ventricular dysfunction (RVD), as expressed by right ventricular to pulmonary artery coupling, has recently been identified as a strong outcome predictor in patients undergoing mitral valve edge-to-edge repair (M-TEER) for secondary mitral regurgitation (MR). The aim of this study was to define RVD in patients undergoing M-TEER for primary MR (PMR) and to evaluate its impact on procedural MR reduction, symptomatic development and 2-year all-cause mortality. METHODS AND RESULTS: This multicentre study included patients undergoing M-TEER for symptomatic PMR at nine international centres. The study cohort was divided into a derivation (DC) and validation cohort (VC) for calculation and validation of the best discriminatory value for RVD. A total of 648 PMR patients were included in the study. DC and VC were comparable regarding procedural success and outcomes at follow-up. Sensitivity analysis identified RVD as an independent predictor for 2-year mortality in the DC (hazard ratio [HR] 2.37, 95% confidence interval [CI] 1.47-3.81, p < 0.001), which was confirmed in the VC (HR 2.06, 95% CI 1.36-3.13, p < 0.001). Procedural success (MR ≤2+) and symptomatic improvement at follow-up (New York Heart Association [NYHA] class ≤II) were lower in PMR patients with RVD (MR ≤2+: 82% vs. 93%, p = 0.002; NYHA class ≤II: 57.3% vs. 66.5%, p = 0.09 for with vs. without RVD). In all PMR patients, the presence of RVD significantly impaired 2-year survival after M-TEER (HR 2.23, 95% CI 1.63-3.05, p < 0.001). CONCLUSIONS: Mitral valve edge-to-edge repair is an effective treatment option for PMR patients. The presence of RVD is associated with less MR reduction, less symptomatic improvement and increased 2-year mortality. Accordingly, RVD might be included into pre-procedural prognostic considerations.

Impact of Residual Mitral Regurgitation on Survival After Transcatheter Edge-to-Edge Repair for Secondary Mitral Regurgitation.

OBJECTIVES: The aim of this study was to assess the impact of residual mitral regurgitation (resMR) on mortality with respect to left ventricular dilatation (LV-Dil) or right ventricular dysfunction (RV-Dys) in patients with secondary mitral regurgitation (SMR) who underwent mitral valve transcatheter edge-to-edge repair (TEER). BACKGROUND: The presence of LV-Dil and RV-Dys correlates with advanced stages of heart failure in SMR patients, which may impact the outcome after TEER. METHODS: SMR patients in a European multicenter registry were evaluated. Investigated outcomes were 2-year all-cause mortality and improvement in New York Heart Association functional class with respect to MR reduction, LV-Dil (defined as LV end-diastolic volume ≥159 ml), and RV-Dys (defined as tricuspid annular plane systolic excursion-to-systolic pulmonary artery pressure ratio of <0.274 mm/mm Hg). RESULTS: Among 809 included patients, resMR ≤1+ was achieved in 546 (67%) patients. Overall estimated 2-year mortality rate was 32%. Post-procedural resMR was significantly associated with mortality (p = 0.031). Although the improvement in New York Heart Association functional class persisted regardless of either LV-Dil or RV-Dys, the beneficial treatment effect of resMR ≤1+ on 2-year mortality was observed only in patients without LV-Dil and RV-Dys (hazard ratio: 1.75; 95% confidence interval: 1.03 to 3.00). CONCLUSIONS: Achieving optimal MR reduction by TEER is associated with improved survival in SMR patients, especially if the progress in heart failure is not too advanced. In SMR patients with advanced stages of heart failure, as evidenced by LV-Dil or RV-Dys, the treatment effect of TEER on symptomatic improvement is maintained, but the survival benefit appears to be reduced.

Sex-Related Clinical Characteristics and Outcomes of Patients Undergoing Transcatheter Edge-to-Edge Repair for Secondary Mitral Regurgitation.

OBJECTIVES: The authors sought to assess sex-based differences in characteristics and outcomes of patients undergoing transcatheter edge-to-edge mitral valve repair (TMVR) for secondary mitral regurgitation (SMR). BACKGROUND: Subgroup analysis from the COAPT (Cardiovascular Outcomes Assessment of the MitraClip Percutaneous Therapy for Heart Failure Patients with Functional Mitral Regurgitation) trial indicated potential sex-related differences in outcomes after TMVR. The impact of sex on results after TMVR in a real-world setting is unknown. METHODS: The authors assessed clinical outcomes and echocardiographic parameters in women and men undergoing TMVR for SMR between 2008 and 2018 who were included in the large, international, multicenter real-world EuroSMR registry (European Registry of Transcatheter Repair for Secondary Mitral Regurgitation). RESULTS: A total of 1,233 patients, including 445 women (36%) and 788 men (64%), were analyzed. Although women were significantly older and had fewer comorbidities than men, TMVR was equally effective in women and men (mitral regurgitation [MR] grade ≤2+ at discharge: 93.2% vs. 94.6% for women vs. men; p = 0.35). All-cause mortality at 1 year (17.9% vs. 18.9%, adjusted hazard ratio: 0.806; p = 0.46) and at 2-year follow-up (26.5% vs. 26.4%, adjusted hazard ratio: 0.757; p = 0.26) were similar in women versus men after multivariate regression analysis. Durability of MR reduction, improvement in symptoms, quality of life, and functional capacity did also not differ during follow-up. CONCLUSIONS: Results from the EuroSMR registry confirmed effective and similar MR reduction with TMVR in women and men. There were no sex-related differences in clinical outcomes up to 2 years of follow-up.

Impact of effective regurgitant orifice area on outcome of secondary mitral regurgitation transcatheter repair.

OBJECTIVES: To assess the value of effective regurgitant orifice (ERO) in predicting outcome after edge-to-edge transcatheter mitral valve repair (TMVR) for secondary mitral regurgitation (SMR) and identify the optimal cut-off for patients' selection. METHODS: Using the EuroSMR (European Registry of Transcatheter Repair for Secondary Mitral Regurgitation) registry, that included patients undergoing edge-to-edge TMVR for SMR between November 2008 and January 2019 in 8 experienced European centres, we assessed the optimal ERO threshold associated with mortality in SMR patients undergoing TMVR, and compared characteristics and outcomes of patients according to baseline ERO. RESULTS: Among 1062 patients with severe SMR and ERO quantification by proximal isovelocity surface area method in the registry, ERO was < 0.3 cm2 in 575 patients (54.1%), who were more symptomatic at baseline (NYHA class ≥ III: 91.4% vs. 86.9%, for ERO < vs. ≥ 0.3 cm2; P = 0.004). There was no difference in all-cause mortality at 2-year follow-up according to baseline ERO (28.3% vs. 30.0% for ERO < vs. ≥ 0.3 cm2, P = 0.585). Both patient groups demonstrated significant improvement of at least one NYHA class (61.7% and 73.8%, P = 0.002), resulting in a prevalence of NYHA class ≤ II at 1-year follow-up of 60.0% and 67.4% for ERO < vs. ≥ 0.3 cm2, respectively (P = 0.05). CONCLUSION: All-cause mortality at 2 years after TMVR does not differ if baseline ERO is < or ≥ 0.3 cm2, and both groups exhibit relevant clinical improvements. Accordingly, TMVR should not be withheld from patients with ERO < 0.3 cm2 who remain symptomatic despite optimal medical treatment, if TMVR appropriateness was determined by experienced teams in dedicated valve centres.

Shear Wave Elastography Using High-Frame-Rate Imaging in the Follow-Up of Heart Transplantation Recipients.

OBJECTIVES: The purpose of this study was to investigate whether propagation velocities of naturally occurring shear waves (SWs) at mitral valve closure (MVC) increase with the degree of diffuse myocardial injury (DMI) and with invasively determined LV filling pressures as a reflection of an increase in myocardial stiffness in heart transplantation (HTx) recipients. BACKGROUND: After orthotopic HTx, allografts undergo DMI that contributes to functional impairment, especially to increased passive myocardial stiffness, which is an important pathophysiological determinant of left ventricular (LV) diastolic dysfunction. Echocardiographic SW elastography is an emerging approach for measuring myocardial stiffness in vivo. Natural SWs occur after mechanical excitation of the myocardium, for example, after MVC, and their propagation velocity is directly related to myocardial stiffness, thus providing an opportunity to assess myocardial stiffness at end-diastole. METHODS: A total of 52 HTx recipients who underwent right heart catheterization (all) and cardiac magnetic resonance (CMR) (n = 23) during their annual check-up were prospectively enrolled. Echocardiographic SW elastography was performed in parasternal long axis views of the LV using an experimental scanner at 1,135 ± 270 frames per second. The degree of DMI was quantified with T1 mapping. RESULTS: SW velocity at MVC correlated best with native myocardial T1 values (r = 0.75; p < 0.0001) and was the best noninvasive parameter that correlated with pulmonary capillary wedge pressures (PCWP) (r = 0.54; p < 0.001). Standard echocardiographic parameters of LV diastolic function correlated poorly with both native T1 and PCWP values. CONCLUSIONS: End-diastolic SW propagation velocities, as measure of myocardial stiffness, showed a good correlation with CMR-defined diffuse myocardial injury and with invasively determined LV filling pressures in patients with HTx. Thus, these findings suggest that SW elastography has the potential to become a valuable noninvasive method for the assessment of diastolic myocardial properties in HTx recipients.

Value of Echocardiographic Right Ventricular and Pulmonary Pressure Assessment in Predicting Transcatheter Tricuspid Repair Outcome.

OBJECTIVES: The aim of this study was to assess the value of echocardiographic right ventricular (RV) and systolic pulmonary artery pressure (sPAP) assessment in predicting transcatheter tricuspid edge-to-edge valve repair (TTVR) outcome. BACKGROUND: RV dysfunction and pulmonary hypertension are associated with poor prognosis and are systematically sought during tricuspid regurgitation evaluation. The value of echocardiographic assessment in predicting TTVR outcome is unknown. METHODS: Data were taken from the TriValve (Transcatheter Tricuspid Valve Therapies) registry, which includes patients undergoing TTVR at 14 European and North American centers. The primary outcome was 1-year survival free from hospitalization for heart failure, and secondary outcomes were 1-year survival and absence of hospital admission for heart failure at 1 year. RESULTS: Overall, 249 patients underwent TTVR between June 2015 and 2018 (mean tricuspid annular plane systolic excursion [TAPSE] 15.8 ± 15.3 mm, mean sPAP 43.6 ± 16.0 mm Hg). Tricuspid regurgitation grade ≥3+ was found in 96.8% of patients at baseline and 29.4% at final follow-up; 95.6% were in New York Heart Association functional class III or IV initially, compared with 34.3% at follow-up (p < 0.05). Final New York Heart Association functional class did not differ among TAPSE and sPAP quartiles, even when both low TAPSE and high sPAP were present. Rates of 1-year survival and survival free from hospitalization for heart failure were 83.9% and 78.7%, respectively, without significant differences according to baseline echocardiographic RV characteristics (TAPSE, fractional area change, and end-diastolic area) and sPAP (p > 0.05 for all). CONCLUSIONS: TTVR provides clinical improvement, with 1-year survival free from hospital readmission >75% in patients with severe tricuspid regurgitation. Conventional echocardiographic parameters used to assess RV function and sPAP did not predict clinical outcome after TTVR.

1-Year Outcomes After Edge-to-Edge Valve Repair for Symptomatic Tricuspid Regurgitation: Results From the TriValve Registry.

OBJECTIVES: The purpose of this study was to evaluate procedural and 1-year clinical and echocardiographic outcomes of patients treated with tricuspid edge-to-edge repair. BACKGROUND: Transcatheter edge-to-edge repair has been successfully performed in selected patients with symptomatic tricuspid regurgitation (TR) and high risk for surgery, but outcome data are sparse. METHODS: This analysis of the multicenter international TriValve (Transcatheter Tricuspid Valve Therapies) registry included 249 patients with severe TR treated with edge-to-edge repair in compassionate and/or off-label use. Clinical and echocardiographic outcomes were prospectively collected and retrospectively analyzed. RESULTS: In 249 patients (mean age 77 ± 9 years; European System for Cardiac Operative Risk Evaluation II score 6.4% [interquartile range: 3.9% to 13.9%]), a successful procedure with TR reduction to grade ≤2+ was achieved in 77% by placement of 2 ± 1 tricuspid clips. Concomitant treatment of severe TR and mitral regurgitation was performed in 52% of patients. At 1-year follow-up, significant and durable improvements in TR severity (TR ≤2+ in 72% of patients) and New York Heart Association functional class (≤II in 69% of patients) were observed. All-cause mortality was 20%, and the combined rate of mortality and unplanned hospitalization for heart failure was 35%. Predictors of procedural failure included effective regurgitant orifice area, tricuspid coaptation gap, tricuspid tenting area, and absence of central or anteroseptal TR jet location. Predictors of 1-year mortality were procedural failure, worsening kidney function, and absence of sinus rhythm. CONCLUSIONS: Transcatheter tricuspid edge-to-edge repair can achieve TR reduction at 1 year, resulting in significant clinical improvement. Predictors of procedural failure and 1-year mortality identified here may help select patients who will benefit most from this therapy.

Prognostic value of preprocedural 6-min walk test in patients undergoing transcatheter mitral valve repair-insights from the German transcatheter mitral valve interventions registry.

AIMS: The 6-min walk test (6 MWT) has been established as an important tool for functional assessment in heart failure patients. However, its prognostic impact on the outcome in subjects with mitral regurgitation undergoing transcatheter mitral valve repair is unknown. METHODS: This present work represents a sub-analysis of the German, prospective, multicenter, Transcatheter Mitral Valve Interventions (TRAMI) registry. Of the main study cohort (n = 828) 326 patients underwent 6 MWT prior to the procedure. Patients were assigned to two groups depending on the preprocedural 6 MWT distance using the median (< 200 m [group 1] vs. ≥ 200 m [group 2]). RESULTS: No differences regarding procedural success (97 vs. 96%; p = 0.71) and 30-day mortality (3 vs. 4%; p = 0.96) were observed between the groups. With regards to 1-year outcome, patients with a walking distance < 200 m had higher all-cause mortality (26 vs. 14%; p = 0.013) as compared to those with a 6 MWT distance 200 m. After adjustment of baseline risk factors, 6 MWT distance < 200 m still showed a strong trend towards increased 1-year all-cause mortality (HR 1.63, 95% confidence interval 0.96-2.76; p = 0.071). CONCLUSIONS: In the present study preprocedural 6 MWT distance < 200 m showed a strong trend towards increased 1-year mortality in patients undergoing MitraClip implantation.

Catheter ablation of atrial fibrillation facilitated by preprocedural three-dimensional transesophageal echocardiography: Long-term outcome.

AIM: To evaluate the long-term outcome of catheter ablation of atrial fibrillation (AF) facilitated by preprocedural three-dimensional (3-D) transesophageal echocardiography. METHODS: In 50 patients, 3D transesophageal echocardiography (3D TEE) was performed immediately prior to an ablation procedure (paroxysmal AF: 30 patients, persistent AF: 20 patients). The images were available throughout the ablation procedure. Two different ablation strategies were used. In most of the patients with paroxysmal AF, the cryoablation technique was used (Arctic Front Balloon, CryoCath Technologies/Medtronic; group A2). In the other patients, a circumferential pulmonary vein ablation was performed using the CARTO system [Biosense Webster; group A1 (paroxysmal AF), group B (persistent AF)]. Success rates and complication rates were analysed at 4-year follow-up. RESULTS: A 3D TEE could be performed successfully in all patients prior to the ablation procedure and all four pulmonary vein ostia could be evaluated in 84% of patients. The image quality was excellent in the majority of patients and several variations of the pulmonary vein anatomy could be visualized precisely (e.g., common pulmonary vein ostia, accessory pulmonary veins, varying diameter of the left atrial appendage and its distance to the left superior pulmonary vein). All ablation procedures could be performed as planned and almost all pulmonary veins could be isolated successfully. At 48-mo follow-up, 68.0% of all patients were free from an arrhythmia recurrence (group A1: 72.7%, group A2: 73.7%, group B: 60.0%). There were no major complications. CONCLUSION: 3D TEE provides an excellent overview over the left atrial anatomy prior to AF ablation procedures and these procedures are associated with a favourable long-term outcome.

Comparison of transcatheter aortic valve implantation with the newest-generation Sapien 3 vs. Direct Flow Medical valve in a single center cohort.

BACKGROUND: The latest generation transcatheter heart valves including Edwards Sapien 3 (ES3) and Direct Flow Medical (DFM) were designed to allow precise implantation at the intended position and to minimize prosthesis dysfunction as well as procedural complications. Our aim was to compare short-term functional and clinical outcomes of these 2 transcatheter aortic valve systems. METHODS: Of 174 patients undergoing transfemoral transcatheter aortic valve implantation (TAVI) at our institution between August 2013 and June 2015, 113 were treated with ES3 and 61 with DFM. Device success, residual aortic regurgitation and early safety endpoints were defined according to the updated VARC-2 criteria and prespecified as primary endpoints. RESULTS: Patients treated with ES3 had a significantly higher rate of procedural success (ES3 94% vs. DFM 79%, p=0.005), mainly driven by lower postprocedural gradients (ES3 8.6±0.5mmHg vs. DFM 14.6±1.4mmHg by invasive recordings; p=0.00012) and no incidence of more than mild aortic regurgitation. The occurrence of safety endpoints at 30days was low and comparable in the DFM vs. ES3 group (ES3 88% vs. DFM 95% of patients without endpoints, p=0.26). No significant differences were observed in 30day mortality, stroke or the incidence of new permanent pacemaker implantation. CONCLUSIONS: These single-center experience data show a higher rate of device success for ES3 treated patients, while 30day safety outcome was similar in both groups. Long-term follow-up and larger scale multicenter experience will have to assess possible effects of these observations on long-term clinical outcomes.

Transcatheter aortic valve implantation with the new-generation Evolut R™: Comparison with CoreValve® in a single center cohort.

BACKGROUND: The Medtronic Evolut R (EVR) is a novel transcatheter heart valve designed to allow precise implantation at the intended position and to minimize prosthesis dysfunction as well as procedural complications. Our aim was to compare short-term functional and clinical outcomes of the new EVR with the established Medtronic CoreValve (CV) system. METHODS AND RESULTS: Of 151 patients undergoing transfemoral transcatheter aortic valve implantation with a self-expanding valve at our institution between January 2013 and January 2016, 86 were treated with EVR and 65 with CV. Patients treated with EVR had a significantly lower rate of more-than-mild aortic regurgitation and a higher rate of device success. Recapture maneuvers to optimize valve deployment were performed in 22.1% of the EVR procedures. Transvalvular post-procedural gradients were slightly higher in the EVR group, while no differences were observed in the incidence of safety endpoints at 30 days, vascular complications, or need for permanent pacemaker implantation following asystole or complete atrioventricular block. CONCLUSIONS: These initial single-center experience data on the short-term outcomes after EVR valve implantation show a substantially reduced rate of more-than-mild paravalvular regurgitation and higher device success, while 30-day safety outcomes were similar to the CV system. Clinical outcome data from long-term follow-up and larger scale multicenter experience are now necessary.

Rationale and design of the RE-LATED AF--AFNET 7 trial: REsolution of Left atrial-Appendage Thrombus--Effects of Dabigatran in patients with Atrial Fibrillation.

BACKGROUND: Dabigatran etexilate, a direct thrombin inhibitor and non-vitamin K antagonist oral anticoagulant (NOAC), has been shown to effectively prevent thromboembolic events in patients with non-valvular atrial fibrillation (AF). However, there is a paucity of data on the antithrombotic efficacy and safety of dabigatran in the resolution of left atrial appendage (LAA) thrombi in AF patients. OBJECTIVE: The primary objective of the RE-LATED AF trial is to assess whether dabigatran results in a faster complete LAA thrombus resolution as compared to vitamin K antagonist phenprocoumon. Secondary objectives are to assess the impact of dabigatran on complete LAA thrombus resolution rate within 6 weeks of treatment and change in LAA thrombus volume under treatment. Furthermore, this study aims to assess and compare safety and tolerability of dabigatran vs. phenprocoumon. METHODS: The study is designed as a prospective, randomized, open-label, controlled, explorative, blinded endpoint (PROBE) trial. Patients with AF and left atrial appendage thrombus confirmed by transoesophageal echocardiography (TEE) will be randomized to receive either dabigatran (150 mg bid) or phenprocoumon (INR 2-3) for the resolution of LAA thrombus formation for at least 21 days. Thrombus resolution will be determined by TEE 3 weeks after treatment initiation and subsequently at weeks 4 and 6, if the LAA thrombus has not been resolved before. A total of 110 patients are planned to be randomized. CONCLUSION: This is the first prospective, multicentre, randomized controlled clinical trial investigating safety and efficacy of a NOAC for the resolution of LAA thrombi in patients with non-valvular AF.

Analysis of left ventricular volumes and function: a multicenter comparison of cardiac magnetic resonance imaging, cine ventriculography, and unenhanced and contrast-enhanced two-dimensional and three-dimensional echocardiography.

BACKGROUND: Contrast echocardiography improves accuracy and reduces interreader variability on left ventricular (LV) functional analyses in the setting of two-dimensional (2D) echocardiography. The need for contrast imaging using three-dimensional (3D) echocardiography is less defined. The aim of this multicenter study was to define the accuracy and interreader agreement of unenhanced and contrast-enhanced 2D and 3D echocardiography for the assessment of LV volumes and ejection fraction (EF). METHODS: A multicenter, open-label study was conducted including 63 patients, using intrasubject comparisons to assess the agreement of unenhanced and contrast-enhanced 2D and 3D echocardiography as well as calibrated biplane cine ventriculography with cardiac magnetic resonance for the determination of LV volumes and EF. Each of the imaging techniques used to define LV function was assessed by two independent, off-site readers unaware of the results of the other imaging techniques. RESULTS: LV end-systolic and end-diastolic volumes were underestimated by 2D and 3D unenhanced echocardiography compared with cardiac magnetic resonance. Contrast enhancement resulted in similar significant increases in LV volumes on 2D and 3D echocardiography. The mean percentage of interreader variability for LV EF was reduced from 14.3% (95% confidence interval [CI], 11.7%-16.8%) for unenhanced 2D echocardiography and 14.3% (95% CI, 9.7%-18.9%) for unenhanced 3D echocardiography to 8.0% (95% CI, 6.3%-9.7%; P < .001) for contrast-enhanced 2D echocardiography and 7.4% (95% CI, 5.7%-9.1%; P < .01) for contrast-enhanced 3D echocardiography and thus to a similar level as for cardiac magnetic resonance (7.9%; 95% CI, 5.4%-10.5%). A similar effect was observed for interreader variability for LV volumes. CONCLUSIONS: Contrast administration on 3D echocardiography results in improved determination of LV volumes and reduced interreader variability. The use of 3D echocardiography requires contrast application as much as 2D echocardiography to reduce interreader variability for volumes and EF.

Comparison of two- and three-dimensional unenhanced and contrast-enhanced echocardiographies versus cineventriculography versus cardiac magnetic resonance for determination of left ventricular function.

Contrast enhancement has been shown to improve detection of regional wall motion abnormalities (RWMA) in 2-dimensional (2D) echocardiography. This study determined the use of contrast enhancement in the setting of 3-dimensional (3D) echocardiography for definition of left ventricular RWMA compared with 2D echocardiography, cineventriculography, and cardiac magnetic resonance (CMR). In 63 patients, unenhanced and contrast-enhanced (SonoVue; Bracco Imaging S.p.A., Milan, Italy) 2D and 3D echocardiographies, CMR, and cineventriculography were performed. Hypokinesia in ≥1 segment defined the presence of RWMA. Interreader agreement (IRA) between 2 blinded off-site readers on presence of RWMA was determined within each imaging technique. Intermethod agreement among imaging techniques was analyzed. A standard of truth for the presence of RWMA was obtained by an independent expert panel decision. IRA on presence of RWMA expressed as Cohen's κ coefficient was 0.27 for unenhanced 3D echocardiography, 0.40 for unenhanced 2D echocardiography, 0.57 for CMR, and 0.51 for cineventriculography. The use of contrast increased IRA on RWMA to 0.42 for 3D echocardiography and to 0.56 for 2D echocardiography. Agreement with CMR on RWMA increased for 3D echocardiography when contrast enhancement was used (κ 0.40 vs 0.22 for unenhanced 3D echocardiography). Similarly, agreement of 2D echocardiography with CMR on RWMA increased with contrast enhancement (κ 0.50 vs 0.32). Accuracy to detect expert panel-defined RWMA was highest for CMR (84%) followed by 2D contrast echocardiography (78%) and 3D contrast echocardiography (76%). It was lesser for 2D and 3D unenhanced echocardiographies. In conclusion, analysis of RWMA is characterized by considerable interreader variability even using high-quality imaging techniques. IRA on RWMA is lower with 3D echocardiography compared with 2D echocardiography. IRA on RWMA and accuracy to detect panel-defined RWMA improve with contrast enhancement irrespective of the 2D or 3D echocardiography use.

Comparison of sulfur hexafluoride microbubble (SonoVue)-enhanced myocardial contrast echocardiography with gated single-photon emission computed tomography for detection of significant coronary artery disease: a large European multicenter study.

OBJECTIVES: The purpose of this study was to compare sulfur hexafluoride microbubble (SonoVue)-enhanced myocardial contrast echocardiography (MCE) with single-photon emission computed tomography (SPECT) relative to coronary angiography (CA) for assessment of coronary artery disease (CAD). BACKGROUND: Small-scale studies have shown that myocardial perfusion assessed by SonoVue-enhanced MCE is a viable alternative to SPECT for CAD assessment. However, large multicenter studies are lacking. METHODS: Patients referred for myocardial ischemia testing at 34 centers underwent rest/vasodilator SonoVue-enhanced flash-replenishment MCE, standard (99m)Tc-labeled electrocardiography-gated SPECT, and quantitative CA within 1 month. Myocardial ischemia assessments by 3 independent, blinded readers for MCE and 3 readers for SPECT were collapsed into 1 diagnosis per patient per technique and were compared to CA (reference standard) read by 1 independent blinded reader. RESULTS: Of 628 enrolled patients who received SonoVue (71% males; mean age: 64 years; >1 cardiovascular [CV] risk factor in 99% of patients) 516 patients underwent all 3 examinations, of whom 161 (31.2%) had ≥70% stenosis (131 had single-vessel disease [SVD]; 30 had multivessel disease), and 310 (60.1%) had ≥50% stenosis. Higher sensitivity was obtained with MCE than with SPECT (75.2% vs. 49.1%, respectively; p < 0.0001), although specificity was lower (52.4% vs. 80.6%, respectively; p < 0.0001) for ≥70% stenosis. Similar findings were obtained for patients with ≥50% stenosis. Sensitivity levels for detection of SVD and proximal disease for ≥70% stenosis were higher for MCE (72.5% vs. 42.7%, respectively; p < 0.0001; 80% vs. 58%, respectively; p = 0.005, respectively). CONCLUSIONS: SonoVue-enhanced MCE demonstrated superior sensitivity but lower specificity for detection of CAD compared to SPECT in a population with a high incidence of CV risk factors and intermediate-high prevalence of CAD. (A phase III study to compare SonoVue® enhanced myocardial echocardiography [MCE] to single photon emission computerized tomography [ECG-GATED SPECT], at rest and at peak of low-dose Dipyridamole stress test, in the assessment of significant coronary artery disease [CAD] in patients with suspect or known CAD using Coronary Angiography as Gold Standard-SonoVue MCE vs SPECT; EUCTR2007-003492-39-GR).

Prognostication of post-infarct chronic heart failure: superiority of clinical assessment vs. cardiopulmonary and left ventricular function analysis.

BACKGROUND: Prognostication of congestive heart failure post-myocardial infarction (MI) is important for decision making. We sought of a head-to-head comparison between the prognostic implication of clinical, cardiopulmonary, and left ventricular (LV) function assessment. METHODS: Retrospectively, 100 consecutive post-MI patients (MI history 1418+/-1668 days ago) were stratified by NYHA functional classification system, cardiopulmonary exercise testing (CPX) [oxygen consumption at maximal exercise (VO(2max)) and at the anaerobic threshold (VO(2AT)) resulting in the Weber classification], and LV function analysis by M-mode and two-dimensional echocardiography [LV end-diastolic and -systolic diameter index (LVDDI and LVSDI), shortening fraction (%D), and LV end-diastolic and -systolic volume index (EDVI and ESVI), LV ejection fraction (EF)]. Patients were controlled by phone call 1470+/-607 days later. RESULTS: There was only a modest correlation between NYHA and Weber classes (r=0.402) and no correlation between VO(2max) and ESVI (r=0.080) nor between NYHA and ESVI (r=0.174). Several parameters (ESVI, LVDDI, LVSDI, %D) could discriminate NYHA classes to a higher significance (p=0.05; 0.0008; 0.0002; 0.04) than the Weber classes (n.s.; p=0.03; n.s.; n.s.). The following parameters could significantly differentiate quartiles in a log-rank analysis (Kaplan-Meier survival curves): NYHA classes (p=0.0001), Weber classes (p=0.069), EDVI (p=0.004), ESVI (p=0.0001), EF (p=0.002), LVDDI (p=0.002), LVSDI (p<0.001) and %D (p<0.001). Multivariate analysis isolated the following three parameters implying decreasing, independent prognostic information: NYHA classes (p=0.001), ESVI (p=0.003), and Weber classes (p=0.040). CONCLUSIONS: In post-MI patients the thorough clinical assessment according the NYHA functional classification system implies higher prognostic information than more objective measures. This should be considered especially in primary care and should lessen the dependence on costly and expertise-dependent technical investigations.

Analysis of myocardial perfusion or myocardial function for detection of regional myocardial abnormalities. An echocardiographic multicenter comparison study using myocardial contrast echocardiography and 2D echocardiography.

BACKGROUND: Echocardiography based myocardial perfusion imaging and regional wall motion analysis are used for evaluation of coronary artery disease and regional myocardial abnormalities. AIM: This study sought to compare myocardial contrast echocardiography (MCE) and 2D echocardiography with regard to interobserver variability and detection of regional myocardial abnormalities. METHODS: In 70 patients evenly distributed between three ejection fraction groups based on biplane cineventriculography ( > 55%, 35-55%, < 35%), unenhanced and contrast enhanced 2D echocardiography and myocardial contrast echocardiography (MCE; SonoVue; Bracco) were performed. Regional wall motion and myocardial perfusion were assessed referring to a 16 segment model. Interobserver agreement (IOA) among 2 readers was determined within each imaging modality. To define a standard of truth for the presence of segmental myocardial disease an independent expert-panel decision was obtained based on clinical data, ECG, coronary angiography and blinded information from the imaging modalities. RESULTS: Regional wall motion assessment was possible in 98.1% of segments using contrast enhanced 2D echocardiography and in 87.2% using unenhanced 2D echocardiography (p < 0.001), while perfusion assessment was possible in 90.1% of segments (p < 0.001). IOA on presence of any regional wall motion abnormality expressed as Kappa coefficient was 0.71 (95% CI 0.53-0.89) for contrast enhanced echocardiography and 0.37 (95% CI 0.14-0.59) for unenhanced echocardiography. IOA on presence of any perfusion abnormality was 0.53 (95% CI 0.34-0.73). For MCE there was high IOA for the apical segments (kappa = 0.57) and lower IOA for the basal segments (kappa=0.14), while no such gradient was found for the IOA on wall motion abnormalities. Mean accuracy to detect expert-panel defined myocardial abnormalities was 80.6% for unenhanced echocardiography, 85.0% for contrast enhanced 2D echocardiography and 80.6% for MCE. CONCLUSIONS: MCE is inferior to contrast enhanced 2D echocardiography with regard to visibility of all LV segments and appears slightly inferior with regards to IOA, while both are superior to unenhanced 2D echocardiography. The methods demonstrated high accuracy in detection of panel defined regional myocardial abnormalities.

Analysis of regional left ventricular function by cineventriculography, cardiac magnetic resonance imaging, and unenhanced and contrast-enhanced echocardiography: a multicenter comparison of methods.

OBJECTIVES: To define the use of cineventriculography, cardiac magnetic resonance imaging (cMRI), and unenhanced and contrast-enhanced echocardiography for detection of left ventricular (LV) regional wall motion abnormalities (RWMA). BACKGROUND: Detection of RWMA is integral to the evaluation of LV function. METHODS: In 100 patients, cineventriculography and unenhanced and contrast-enhanced echocardiography were performed. Fifty-six of the patients underwent additional cMRI. RWMA were assessed referring to a 16-segment model for cMRI, unenhanced and contrast echocardiography. Cineventriculography was evaluated on a 7-segment model. Hypokinesia in one or more segments defined presence of RWMA. Interobserver agreement among three readers was determined within each imaging modality. Intermethod agreement between imaging modalities was analyzed. A standard of truth for the presence of RWMA was obtained by an independent expert panel decision (EPD) based on clinical data, electrocardiogram, coronary angiography, and blinded information from the imaging modalities. RESULTS: Sixty-seven patients were found to have an RWMA by EPD. Interobserver agreement expressed as kappa coefficient was 0.41 (range 0.37 to 0.44) for unenhanced echocardiography, 0.43 (range 0.29 to 0.79) for cMRT, 0.56 (range 0.44 to 0.70) for cineventriculography, and 0.77 (range 0.71 to 0.88) for contrast echocardiography. Contrast enhancement compared to unenhanced echocardiography improved agreement of echocardiography related to cMRI (kappa 0.46 vs. 0.29) and related to cineventriculography (kappa 0.59 vs. 0.28). Accuracy to detect EPD-defined RWMA was highest for contrast echocardiography, followed by cMRI, unenhanced echocardiography, and cineventriculography. CONCLUSIONS: Analysis of RWMA is characterized by considerable interobserver variability even using high-quality imaging modalities. Interobserver agreement on RWMA and accuracy to detect panel-defined RWMA is good using contrast echocardiography.