Left atrial to coronary sinus shunting for treatment of heart failure with mildly reduced or preserved ejection fraction: The ALT FLOW Early Feasibility Study 1-year results.

AIMS: Patients with heart failure and mildly reduced or preserved ejection fraction have limited therapeutic options. The ALT-FLOW Early Feasibility Study evaluated safety, haemodynamics and outcomes for the APTURE transcatheter shunt system, a novel left atrium to coronary sinus shunt in these patients. METHODS AND RESULTS: Safety and shunt implantation success was evaluated for all 116 enrolled patients. An analysis population of implanted patients with a left ventricular ejection fraction (LVEF) >40% (n = 95) was chosen to assess efficacy via paired comparison between baseline and follow-up haemodynamic (3 and 6 months), and echocardiographic, clinical and functional outcomes (6 months and 1 year). Health status and quality of life outcomes were assessed using the Kansas City Cardiomyopathy Questionnaire overall summary score (KCCQ-OSS). The primary safety endpoint, major adverse cardiac, cerebral, and renal events, and reintervention through 30 days, occurred in 3/116 patients (2.6%). All implanted shunts were patent at 1 year. In patients with LVEF >40%, the mean (95% confidence interval) reduction in exercise pulmonary capillary wedge pressure (PCWP) at 20 W was -5.7 (-8.6, -2.9) mmHg at 6 months (p < 0.001). At baseline, 8% had New York Heart Association class I-II status and improved to 68% at 1 year (p < 0.001). KCCQ-OSS at baseline was 39 (35, 43) and improved at 6 months and 1 year by 25 (20-30) and 27 (22-32) points, respectively (both p < 0.0001). No adverse changes in haemodynamic and echocardiographic indices of right heart function were observed at 1 year. Overall, the reduction in PCWP at 20 W and improvement in KCCQ-OSS in multiple subgroups were consistent with those observed for the entire population. CONCLUSIONS: In patients with heart failure and LVEF >40%, the APTURE shunt demonstrated an acceptable safety profile with significant sustained improvements in haemodynamic and patient-centred outcomes, underscoring the need for further evaluation of the APTURE shunt in a randomized trial.

The relationship between mitral regurgitant severity, symptoms, and exercise capacity in primary degenerative mitral regurgitation.

Although it is assumed that more severe MR is associated with a greater burden of symptoms and lower exercise capacity, the relationship between symptoms, exercise capacity, and mitral regurgitant severity has not been well studied. We prospectively studied 67 (63 ± 11 years, 72% male) patients with at least mild degenerative MR and left ventricular ejection fraction ≥ 50% who underwent stress echocardiography, CMR, and evaluation with the Kansas City Cardiomyopathy questionnaire (KCCQ). Symptoms and exercise capacity were evaluated in the context of MR severity. Patients reporting dyspnea had lower KCCQ symptom scores (79 ± 23 vs. 96 ± 9, p = 0.01) and achieved lower percentage of age and gender predicted METs (114 ± 37 vs. 152 ± 43%, p < 0.001) compared to those without dyspnea. There was no significant difference in MR volume between those with vs. without dyspnea by CMR (43 ± 26 ml vs. 51 ± 28 ml, p = 0.3) or echocardiography (64 ± 28 vs. 73 ± 41ml, p = 0.4). Those with severe MR by CMR had similar KCCQ symptom scores (96 ± 10 vs. 89 ± 17, p = 0.04) and percentage of age and gender predicted METs (148 ± 42 vs. 133 ± 47%, p = 0.2) to those without severe MR. Those with severe MR by echocardiography had similar KCCQ symptom score (93 ± 15 vs. 89 ± 16, p = 0.3) and percentage of age and gender predicted METs (138 ± 43 vs. 153 ± 46%, p = 0.2) to those without severe MR. Patients with degenerative MR assessed by CMR and stress echocardiography, there was no relationship between MR severity and either symptoms or exercise capacity. These findings highlight the disconnect between symptoms and the severity of MR and challenge the assumption that correcting MR can be counted on to improve symptom status in patients with degenerative MR.

Left Atrial to Coronary Sinus Shunting for Treatment of Symptomatic Heart Failure.

BACKGROUND: Heart failure (HF) is associated with both mortality and a significant decline in health status. Interatrial shunting is increasingly being investigated as a novel therapeutic option. OBJECTIVES: The ALT FLOW Early Feasibility Study was designed to evaluate the safety of the Edwards left atrial to coronary sinus APTURE Transcatheter Shunt System in patients with symptomatic HF. METHODS: A total of 18 centers enrolled patients with symptomatic HF with a pulmonary capillary wedge pressure >15 mm Hg at rest or 25 mm Hg during exercise. RESULTS: Between May 2018 and September 2022, 87 patients underwent attempted APTURE shunt implantation. Mean age was 71 years, and 53% were male. At baseline, mean left ventricular ejection fraction was 59% with 90% of the patients being in NYHA functional class III. Device success was achieved in 78 patients (90%), with no device occlusions or associated adverse events identified after implantation. The primary safety outcome occurred in only 2 patients (2.3%) at 30 days. At 6 months, health status improved: 67% of participants achieved NYHA functional class I to II status, with a 23-point improvement (P < 0.0001; 95% CI: 17-29 points) in the Kansas City Cardiomyopathy Questionnaire overall summary score. Also at 6 months, 20-W exercise pulmonary capillary wedge pressure was 7 mm Hg lower (P < 0.0001; 95% CI: -11 to -4 mm Hg) without change in right atrial pressure or other right heart function indices. CONCLUSIONS: In this single-arm experience, the APTURE Transcatheter Shunt System in patients with symptomatic HF was observed to be safe and resulted in reduction in pulmonary capillary wedge pressure and clinically meaningful improvements in HF symptoms and quality of life indices.

American Society of Echocardiography Algorithm for Degenerative Mitral Regurgitation: Comparison With CMR.

OBJECTIVES: The purpose of this study was to compare the American Society of Echocardiography (ASE) algorithm for assessing mitral regurgitation (MR) to cardiac magnetic resonance (CMR) and left ventricular (LV) remodeling following mitral intervention. BACKGROUND: The ASE recommends integrating multiple echocardiographic parameters for assessing MR. The ASE guidelines include an algorithm that weighs the parameters and highlights those considered indicative of definitely mild or definitely severe MR. METHODS: We prospectively enrolled 152 (age 62 ± 13 years; 59% male) patients with degenerative MR who underwent ASE algorithm-guided echocardiographic and CMR grading of MR severity. Using the ASE algorithm, patients were graded as definitely mild, grade I, grade II, grade III, grade IV, or definitely severe MR. CMR MR volume was graded as mild (<30 mL), grade II moderate (30-44 mL), grade III moderate (45-59 mL), or severe (≥60 mL). A subgroup of 63 patients underwent successful mitral intervention, of whom 48 had postintervention CMR. RESULTS: Only 52% of patients with definitely severe MR by the ASE algorithm had severe MR by CMR, and 10% had mild MR by CMR. There was an increase in post mitral intervention LV reverse remodeling with worsening MR severity using CMR (P < 0.0001) but not the ASE algorithm (P = 0.07). Severe MR by CMR was an independent predictor of post mitral intervention LV reverse remodeling and definitely severe MR by the ASE algorithm was not. CONCLUSIONS: In patients with degenerative MR, agreement between CMR and the ASE algorithm was suboptimal. Severe MR by CMR was an independent predictor of post mitral intervention LV reverse remodeling, whereas definitely severe MR by the ASE algorithm was not. These findings suggest an important role for CMR in surgical decision making in degenerative MR. (Comparison Study of Echocardiography and Cardiovascular Magnetic Resonance Imaging in the Assessment of Mitral and Aortic Regurgitation; NCT04038879).

Characterization of Primary Mitral Regurgitation With Flail Leaflet and/or Wall-Impinging Flow.

BACKGROUND: Echocardiography guidelines note that a flail leaflet is a specific criterion for severe mitral regurgitation (MR) and that regurgitant severity is underestimated in wall-impinging jets (Coanda effect). Both findings are often considered to be pathognomonic of severe MR. OBJECTIVES: In this study, the authors sought to determine the association of flail leaflet and Coanda effect with MR severity quantified by means of cardiac magnetic resonance (CMR). METHODS: The authors enrolled 158 consecutive patients with primary MR according to echocardiography and CMR. The presence of a flail leaflet or Coanda was determined for each patient. CMR regurgitant volume (RV) and regurgitant fraction (RF) were quantified for all patients. RESULTS: There were 55 patients (35%) with a flail leaflet, 52 (33%) with Coanda, and 22 (14%) with a flail leaflet and Coanda. The mean CMR mitral RV and RF progressively increased in patients without a Coanda or flail, a Coanda, a flail, or a Coanda and a flail (RV: 28 ± 21 mL vs 43 ± 23 mL vs 58 ± 29 mL vs 64 ± 25 mL [P < 0.001]; RF: 25% ± 16% vs 34% ± 14% vs 41% ± 12% vs 45% ± 12% [P < 0.001]). With the use of CMR RV, 35%, 46%, and 59% of patients had severe MR with the presence of a Coanda, flail leaflet, or both, respectively. With the use of CMR RF, 25%, 31%, and 40% of patients had severe MR with the presence of a Coanda, flail leaflet, or both, respectively. CONCLUSIONS: While the presence of a flail leaflet and Coanda effect on echocardiography are associated with higher regurgitant volumes and fractions, they are frequently not associated with severe MR as assessed by means of CMR. (Comparison Study of Echocardiography and Cardiovascular Magnetic Resonance Imaging in the Assessment of Mitral and Aortic Regurgitation; NCT04038879).

Concordance and Discordance of Echocardiographic Parameters Recommended for Assessing the Severity of Mitral Regurgitation.

BACKGROUND: The American College of Cardiology/American Heart Association and American Society of Echocardiography guidelines recommend assessing several echocardiographic parameters when evaluating mitral regurgitation (MR) severity. These parameters can be discordant, making the assessment of MR challenging. The degree to which echocardiographic parameters of MR severity are concordant is not well studied. METHODS: We enrolled 159 patients in a prospective multicenter study. Eight parameters were included in this analysis: proximal isovelocity surface area (PISA)-derived regurgitant volume, PISA-derived effective regurgitant orifice area, vena contracta, color Doppler jet/left atrial area, left atrial volume index, left ventricular end-diastolic volume index, peak E wave, and the presence of pulmonary vein systolic reversal. Each echocardiographic parameter was determined to represent severe or nonsevere MR according to the American Society of Echocardiography guidelines. A concordance score was calculated as [Formula: see text] so that a higher score reflects greater concordance. There was no discordance when all the echocardiographic parameters agreed and high discordance when 3 or 4 parameters were discordant. RESULTS: The mean concordance score was 75±14% for the entire cohort. There were 9 (6%) patients with complete agreement of all parameters and 61 (38%) with high discordance. There was greater discordance in patients with severe MR but no difference between primary versus secondary or central versus eccentric jets. There was an improvement in concordance when only considering PISA-based regurgitant volume, PISA-based effective regurgitant orifice area, and vena contracta with agreement in 68% of patients. CONCLUSIONS: There was limited concordance between the echocardiographic parameters of MR severity, and the discordance was worse with more severe MR. Concordance improved when considering only 3 quantitative measures of vena contracta and PISA-based effective regurgitant orifice area and regurgitant volume. These findings highlight the challenges facing echocardiographers when assessing the severity of MR and emphasize the difficulty of using an integrated approach that incorporates multiple components. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT04038879.

The Effect of Systolic Variation of Mitral Regurgitation on Discordance Between Noninvasive Imaging Modalities.

OBJECTIVES: This study sought to assess the impact of systolic variation of mitral regurgitation (MR) has on discordance between echocardiography and magnetic resonance imaging (MRI). BACKGROUND: Studies have shown discordance between echocardiography and MRI when assessing the severity of MR. Contributing factors to this discordance may include the systolic variation of MR and the use of the color Doppler jet at a single point in time as the basis of many echocardiographic methods. METHODS: This analysis included 117 patients (62 ± 14 years of age; 58% male) with MR who underwent echocardiographic and MRI evaluation. Discordance was defined as the difference between the grades of MR (mild, moderate, or severe) by MRI and echocardiography. For each patient, 2 echocardiographic methods, the continuous wave time index and the color Doppler time index, and 1 MRI method, the systolic variation score (SVS), were measured to quantify systolic variation of MR. RESULTS: There was absolute agreement between echocardiography and MRI in 47 (40%) patients, a 1-grade difference in 54 (46%) patients, and a 2-grade difference in 16 (14%) patients. Only the SVS significantly differed between patients with and without discordance (0.60 ± 0.23 vs. 0.47 ± 0.21; p = 0.003). On receiver-operating characteristic analysis SVS had moderate predictive power of discordance (area under the curve: 0.67; p = 0.003), with an SVS of 53 having a sensitivity of 61% and a specificity of 65% to predict discordance. CONCLUSIONS: Discordance between MRI and echocardiographic assessment of MR severity is associated with systolic variation of MR as quantified by MRI using the SVS. Continuous wave Doppler and the presence of color Doppler were not correlated with discordance. This study highlights an advantage of MRI. Namely, it does not rely on a single point in time to determine MR severity. Because systolic variation had only moderate sensitivity and specificity for predicting discordance, other factors are also responsible for the discordance between the 2 techniques.

A Comparative Assessment of Echocardiographic Parameters for Determining Primary Mitral Regurgitation Severity Using Magnetic Resonance Imaging as a Reference Standard.

BACKGROUND: The American Society of Echocardiography (ASE) guidelines suggest the use of several echocardiographic methods to assess mitral regurgitation severity using an integrated approach, without guidance as to the weighting of each parameter. The purpose of this multicenter prospective study was to evaluate the recommended echocardiographic parameters against a reference modality and develop and validate a weighting for each echocardiographic measure of mitral regurgitation severity. METHODS: This study included 112 patients who underwent evaluation with echocardiography and magnetic resonance imaging (MRI). Echocardiographic parameters recommended by the ASE were included and compared with MRI-derived regurgitant volume (MRI-RV). RESULTS: Echocardiographic parameters that correlated best with MRI-RV were proximal isovelocity surface area (PISA) radius (r = 0.65, P < .0001), PISA-derived effective regurgitant orifice area (r = 0.65, P < .0001), left ventricular end-diastolic volume (r = 0.56, P < .0001), and PISA-derived regurgitant volume (r = 0.52, P < .0001). In the linear regression models PISA-derived effective regurgitant orifice area, PISA-derived regurgitant volume, left ventricular end-diastolic volume, and the presence of a flail leaflet independently predicted MRI-RV. CONCLUSION: Echocardiographic parameters of mitral regurgitation as recommended by the ASE had moderate correlations with MRI-RV. The best predictors of MRI-RV were PISA-derived effective regurgitant orifice area, PISA-derived regurgitant volume, left ventricular end-diastolic volume, and the presence of a flail leaflet, suggesting that these parameters should be weighted more heavily than other echocardiographic parameters in the application of the ASE-recommended integrated approach.