Beyond Static Planning: Computational Predictive Modeling to Avoid Coronary Artery Occlusion in TAVR.

BACKGROUND: Coronary artery occlusion (CO) during transcatheter aortic valve replacement (TAVR) is a devastating complication. The objective is to assess the clinical impact of a novel computational predictive modeling algorithm for CO during TAVR planning. METHODS: From January 2020 to December 2022, 116 patients (7.6%) undergoing TAVR evaluation were deemed at increased risk of CO based on traditional criteria. Patients underwent prospective computational modeling (DASI Simulations) to assess risk of CO during TAVR; procedural modifications and clinical results were reviewed retrospectively. RESULTS: Of the 116 patients at risk for CO by traditional methodology, 53 had native aortic stenosis(45.7%), 47 a previous surgical AVR (40.5%), and 16 a prior TAVR (13.8%). Transcatheter valve choice, size, and/or implantation depth was modeled for all patients. Computational modeling predicted an increased risk of CO based in 39/116 (31.9%). Within this sub-cohort, 29 patients proceeded with TAVR. Procedural modifications to augment risk of CO included BASILICA (n=10), chimney coronary stents (n=8), coronary access without stent (n=3). There were no episodes of coronary compromise among patients following TAVR, either for those predicted to be at high risk of CO (with procedural modifications) or predicted low risk (standard TAVR). CONCLUSIONS: Utilization of preoperative simulations for TAVR in patient-specific geometry through computational predictive modeling of CO was an effective enhancement to procedure planning.

Sweet syndrome following the ChAdOx1-S vaccine.

We report a case of vaccine-induced Sweet syndrome in a female patient in her 50s presenting with fevers and a scattered red patchy rash on the lower limbs. Seven days prior, she had received the first dose of AstraZeneca ChAdOx1-S vaccine. A skin biopsy confirmed Sweet syndrome. She did not respond to high doses of prednisolone and required methotrexate therapy to induce remission. This is one of the first reports of Sweet syndrome caused by the ChAdOx1-S vaccine and provides further evidence for vaccine-induced dermatosis. This case demonstrates that methotrexate can induce remission in cases of Sweet syndrome resistant to corticosteroids. This report also describes an approach to the differential diagnosis of patients presenting with a rash, fever and malaise.

5-Year Prospective Evaluation of Mitral Valve-in-Valve, Valve-in-Ring, and Valve-in-MAC Outcomes: MITRAL Trial Final Results.

BACKGROUND: The MITRAL (Mitral Implantation of Transcatheter Valves) trial is the first prospective trial to evaluate the safety and feasibility of balloon-expandable aortic transcatheter heart valves in patients with failed surgical bioprostheses or annuloplasty rings and severe mitral annular calcification treated with mitral valve-in-valve (MViV), valve-in-ring (MViR), or valve-in-mitral annular calcification (ViMAC). OBJECTIVES: The aim of this study was to evaluate 5-year outcomes among these patients. METHODS: A multicenter prospective study was conducted among patients at high surgical risk at 13 U.S. sites. Patients underwent MViV (n = 30), MViR (n = 30), or ViMAC (n = 31) and were followed annually for 5 years. Kansas City Cardiomyopathy Questionnaire scores were obtained at baseline and follow-up visits. Echocardiograms were analyzed at independent core laboratories. RESULTS: A total of 91 patients underwent transcatheter mitral valve replacement (February 2015 to December 2017). The mean age was 74.3 ± 8.9 years. At 5-year follow-up, the lowest all-cause mortality was observed in the MViV group (21.4%), 94.7% of patients were in NYHA functional class I or II, and the mean mitral gradient was 6.6 ± 2.5 mm Hg. The MViR and ViMAC groups had higher all-cause mortality (65.5% and 67.9%), most survivors were in NYHA functional classes I and II (50% and 55.6%), and mean mitral gradients remained stable (5.8 ± 0.1 and 6.7 ± 2.5 mm Hg). Significant improvements in Kansas City Cardiomyopathy Questionnaire scores were observed when all 3 arms were pooled. CONCLUSIONS: MViV, MViR, and ViMAC procedures were associated with sustained improvement of heart failure symptoms and quality of life among survivors at 5 years. Transcatheter heart valve function remained stable in all 3 groups. Patients treated with MViV had excellent survival at 5 years, whereas survival was lower in the MViR and ViMAC groups, consistent with underlying disease severity. Patients with more residual mitral regurgitation had higher mortality.

Machine learning algorithms for population-specific risk score in coronary artery bypass grafting.

BACKGROUND: The aim of this study was to develop a new risk prediction score (NH Score) for patients undergoing coronary artery bypass grafting (CABG) specific to the Indian population and compare it to the Society of Thoracic Surgeon (STS) Score and the EuroSCORE II. METHOD: The baseline features of adult patients who underwent CABG between the years 2015 and 2021 (n = 6703) were taken and split into training data (2015-2020; n = 5561) and validation data (2020-2021; n = 1142). The CatBoost algorithm was trained to predict risk scores (NH score), and the performance was tested on the validation set by Precision-Recall Curve and F1 Score. Model calibration was measured by the Brier Score, Expected Calibration Error and Maximum Calibration Error. RESULTS: The NH score outperformed both the STS and EuroSCORE II for all outcomes. For mortality, the PR AUC for NH Score was (0.463 [95% confidence interval [CI], 0.28-0.64]) compared to 0.113 [95% CI, 0.04-0.22] for the STS score and 0.146 [95% CI, 0.06-0.31] for the EuroSCORE II (p ≪ 0.0001). With respect to morbidity NH Score was superior to the STS score (0.43 [95% CI, 0.33-0.50]) vs. (0.229 [95% CI, 0.18-0.3, p < 0.0001). The observed to the predicted ratio for NH score was superior to the STS Score and similar to EuroSCORE II. NH Score was also more accurate at predicting the risk of prolonged ventilation compared to the STS Score. CONCLUSION: NH score shows an excellent improvement over the performance of STS score and EuroSCORE II for modelling risk predictions for patients undergoing CABG in Indian population. It warrants further validation for larger datasets.

Five-Year Follow-up after Transcatheter Repair of Secondary Mitral Regurgitation.

BACKGROUND: Data from a 5-year follow-up of outcomes after transcatheter edge-to-edge repair of severe mitral regurgitation, as compared with outcomes after maximal doses of guideline-directed medical therapy alone, in patients with heart failure are now available. METHODS: We randomly assigned patients with heart failure and moderate-to-severe or severe secondary mitral regurgitation who remained symptomatic despite the use of maximal doses of guideline-directed medical therapy to undergo transcatheter edge-to-edge repair plus receive medical therapy (device group) or to receive medical therapy alone (control group) at 78 sites in the United States and Canada. The primary effectiveness end point was all hospitalizations for heart failure through 2 years of follow-up. The annualized rate of all hospitalizations for heart failure, all-cause mortality, the risk of death or hospitalization for heart failure, and safety, among other outcomes, were assessed through 5 years. RESULTS: Of the 614 patients enrolled in the trial, 302 were assigned to the device group and 312 to the control group. The annualized rate of hospitalization for heart failure through 5 years was 33.1% per year in the device group and 57.2% per year in the control group (hazard ratio, 0.53; 95% confidence interval [CI], 0.41 to 0.68). All-cause mortality through 5 years was 57.3% in the device group and 67.2% in the control group (hazard ratio, 0.72; 95% CI, 0.58 to 0.89). Death or hospitalization for heart failure within 5 years occurred in 73.6% of the patients in the device group and in 91.5% of those in the control group (hazard ratio, 0.53; 95% CI, 0.44 to 0.64). Device-specific safety events within 5 years occurred in 4 of 293 treated patients (1.4%), with all the events occurring within 30 days after the procedure. CONCLUSIONS: Among patients with heart failure and moderate-to-severe or severe secondary mitral regurgitation who remained symptomatic despite guideline-directed medical therapy, transcatheter edge-to-edge repair of the mitral valve was safe and led to a lower rate of hospitalization for heart failure and lower all-cause mortality through 5 years of follow-up than medical therapy alone. (Funded by Abbott; COAPT ClinicalTrials.gov number, NCT01626079.).

2-Year Outcomes of Transcatheter Mitral Valve Replacement in Patients With Annular Calcification, Rings, and Bioprostheses.

BACKGROUND: The MITRAL (Mitral Implantation of Transcatheter Valves) trial is the first prospective study for valve-in-mitral annular calcification (ViMAC), mitral valve-in-ring (MViR), and mitral valve-in-valve (MViV) using balloon-expandable aortic transcatheter heart valves. Procedural outcomes beyond 1 year are not well described. OBJECTIVES: This study evaluated 2-year outcomes in ViMAC, MViR, and MViV in the MITRAL trial. METHODS: This multicenter prospective study enrolled patients with severe MAC, prior failed mitral annuloplasty ring repair, or prior failed bioprosthetic MV replacement who were at high surgical risk at 13 U.S. sites. RESULTS: Between February 1, 2015, and December 31, 2017, 91 patients were enrolled (31 with ViMAC, 30 with MViR, and 30 with MViV). In the ViMAC group, 2-year all-cause mortality was 39.3%, 66.7% were New York Heart Association (NYHA) functional class I-II, and mean MV gradient was 5.6 ± 2.0 mm Hg. In the MViR group, 2-year all-cause mortality was 50%, 65% were NYHA functional class I-II, and mean MV gradient was 6.5 ± 2.7 mm Hg. In the MViV group, 2-year all-cause mortality was 6.7%, 85% were NYHA functional class I-II, and mean MV gradient was 6.9 ± 2.4 mm Hg. At 2 years, all patients had ≤mild mitral regurgitation and survivors in all 3 arms showed sustained improvement in Kansas City Cardiomyopathy Questionnaire scores compared to baseline. CONCLUSIONS: Use of balloon-expandable aortic transcatheter heart valves in selected patients with severe MAC, failed annuloplasty ring, and bioprosthetic MV dysfunction is associated with improvements in symptoms, quality of life, and stable prosthesis function at 2-year follow-up. Between 1 and 2 years, the MViR group experienced higher mortality rates than the MViV and ViMAC groups.

Effect of preoperative statins on respiratory complications after coronary artery bypass grafting.

OBJECTIVES: Limited data exist on the effect of preoperative statin therapy on postoperative respiratory complications. Machine learning algorithms (MLA) can process large, heterogenous data, and have immensely improved the ability for risk prediction. In this study, we sought to examine the role of preoperative statins on respiratory complications in patients undergoing coronary artery bypass grafting (CABG) using MLA. METHODS: The study population contained the data of patients who underwent CABG between the years 2015 and 2019 (n = 5638). Three hundred and thirty-seven independent variables were recorded and the data was randomly split with stratified sampling into training and testing data with 20% of the data (1113 records) reserved for model testing. Various models including linear models, Random forest, SVM, and XGboost were trained to predict the incidence of postoperative respiratory complications. Forty-seven important features were found to impact model prediction (p ≤ .05) using the global surrogate model method. A conventional multivariable linear regression model was then used to identify predictors of respiratory complications. RESULTS: One thousand three hundred sixty-two (24.5%) patients developed a respiratory complication in our series. The respiratory complication was seen in 561 (29.7%) of the patients who were not on statin compared to only 801 (21.8%) who were on a statin, p < .0001. The area under the curve for receiver operating characteristic curve using statins and respiratory complications was 0.706. Statins showed positive feature importance in all the MLA models. CONCLUSIONS: MLA showed that statins impacted the prediction of respiratory complications in all the models studied. The study confirmed that preoperative statins reduced the risk of respiratory complications by 21%.

Long-term Outcomes of Transcatheter Aortic Valve Replacement With the Lotus Valve vs CoreValve/EvolutR: A Secondary Analysis of the REPRISE III Randomized Clinical Trial.

Importance: Long-term follow-up after transcatheter aortic valve replacement (TAVR) is of interest given that longitudinal data on mortality and durability of transcatheter heart valves are limited. The REPRISE III (Repositionable Percutaneous Replacement of Stenotic Aortic Valve Through Implantation of Lotus Valve System-Randomized Clinical Evaluation) randomized clinical trial compared the mechanically expanded Lotus valve with the self-expanding CoreValve/EvolutR TAVR platforms. Objective: To describe the final 5-year outcomes of the REPRISE III trial. Design, Setting, and Participants: This prespecified secondary analysis assessed the final 5-year clinical, functional, and echocardiographic outcomes of 912 patients from the REPRISE III trial, which was conducted at 55 centers in North America, Europe, and Australia between September 22, 2014, and December 24, 2015. Patients had high risk for aortic stenosis or severe or symptomatic aortic stenosis. Data were analyzed from September 22, 2014, to May 21, 2021. Intervention: Lotus valve or CoreValve/EvolutR TAVR platforms. Main Outcomes and Measures: Valve Academic Research Consortium-2 end points, hemodynamic measures, functional status, and health status were examined through the 5-year follow-up. Results: A total of 912 patients (mean [SD] age, 82.8 [7.3] years; 463 women [50.8%]) were randomized to either the Lotus valve group (n = 607) or CoreValve/EvolutR group (n = 305), with a baseline Society of Thoracic Surgeons risk score of 6.8%. Clinical follow-up data from the REPRISE III trial were available for 581 patients (95.7%) in the Lotus valve group and 285 patients (93.4%) in the CoreValve/EvolutR group. At 5 years, the cumulative event rate for all-cause mortality was 50.9% in the Lotus valve group vs 52.8% in the CoreValve/EvolutR group (P = .59). Disabling stroke was less frequent with the Lotus valve vs CoreValve/EvolutR (cumulative event rates, 8.3% vs 12.2%; P = .04), whereas the cumulative event rates for overall stroke were similar in both groups (14.1% vs 15.3%; P = .38). Insertion of a new permanent pacemaker (38.9% vs 27.3%; P < .001) and detection of prosthetic aortic valve thrombosis (5.8% vs 1.8%; P = .007) were more common in the Lotus valve group than in the CoreValve/EvolutR group. A smaller proportion of patients who received the Lotus valve experienced valve malpositioning (0% vs 2.6%; P < .001) and required the use of a second valve (1.0% vs 3.8%; P < .001) during the procedure compared with those who received the CoreValve/EvolutR. Compared with the Lotus valve group, the CoreValve/EvolutR group had a significantly lower mean (SD) aortic gradient (7.8 [4.2] mm Hg vs 12.6 [6.7] mm Hg; P < .001) and larger valve areas (1.57 [0.56] cm2 vs 1.42 [0.42] cm2; P = .10). After 5 years, the proportion of patients with moderate or greater paravalvular leak was not significantly higher with the CoreValve/EvolutR than with the Lotus valve (1.9% vs 0%; P = .31); however, the proportion of patients with mild paravalvular leak was higher in the CoreValve/EvolutR group compared with the Lotus valve group (23.1% vs 7.8%; P = .006). Long-term, similar improvements in New York Heart Association class and Kansas City Cardiomyopathy Questionnaire score were observed in both groups. Conclusions and Relevance: The REPRISE III trial found that, at 5 years, the clinical outcomes of the Lotus valve were comparable to those of the CoreValve/EvolutR and that the Lotus valve was safe and effective. Trial Registration: ClinicalTrials.gov Identifier: NCT02202434.

Early Experience with the HeartMate Percutaneous Heart Pump from the SHIELD II Trial.

The HeartMate Percutaneous Heart Pump (PHP) is a novel circulatory support catheter delivering a self-expanding 24 French impeller across the aortic valve. The SHIELD II trial compares outcomes among heart failure patients undergoing high-risk percutaneous coronary intervention (HR-PCI) with the PHP versus Impella systems. The trial was halted in 2017 due to device malfunctions. We aimed to describe procedural, hemodynamic, and clinical outcomes among HR-PCI patients treated with PHP as part of the SHIELD II trial roll-in phase. Procedural, hemodynamic, and 90 day outcomes were assessed among patients undergoing HR-PCI with a left ventricular ejection fraction ≤35% and last patent coronary conduit, unprotected left main disease, or significant three vessel disease. The primary endpoint was the 90 day composite of cardiovascular death, myocardial infarction, stroke, repeat revascularization, major bleeding, new/worsening aortic regurgitation, and severe hypotension. Among 75 roll-in phase patients, PHP support duration was 101 ± 53 minutes with 2.5 ± 1.4 coronary lesions treated per patient. Compared with predevice values, the PHP system increased cardiac power and mean arterial pressure. Maximum recorded device flows were 0.4-6.2 L/minute with 26% (n = 19/73) and 9.6% (n = 7/73) of patients achieving peak flows above 3.5 or 5.0 L/minute, respectively. Five PHP device malfunction events (6.7%) were observed. At 90 days, the composite endpoint occurred in 24.3% (18/74) of patients. Early PHP experience demonstrated successful device performance in the majority of enrolled patients; however, unexpected malfunctions led to device revision. Completion of the SHIELD II trial will be required to confirm the safety and efficacy of this iteration of the PHP system in HR-PCI.

Reactivation of IgA vasculitis following COVID-19 vaccination.

A 23-year-old man presented to the acute assessment unit with acute-onset haematuria within 24 hours of receiving his second dose of the Pfizer-BioNTech COVID-19 vaccine. He had been diagnosed with IgA vasculitis 8 months previously. IgA vasculitis is an autoimmune condition characterised by palpable purpura affecting the lower limbs, abdominal pain, arthralgia and renal disease. He was diagnosed with an acute exacerbation of IgA vasculitis and was discharged with oral prednisolone. Reactivation or first presentation of IgA vasculitis is a rare but increasingly recognised complication of COVID-19 vaccination. This is an important new differential in the assessment of patients with haematuria following COVID-19 vaccination.

Sex-Specific Outcomes of Transcatheter Mitral-Valve Repair and Medical Therapy for Mitral Regurgitation in Heart Failure.

OBJECTIVES: This study sought to assess the sex-specific outcomes in patients with heart failure (HF) with 3+ and 4+ secondary mitral regurgitation (SMR) treated with transcatheter mitral valve repair (TMVr) plus guideline-directed medical therapy (GDMT) versus GDMT alone in the COAPT trial. BACKGROUND: The impact of sex in patients with HF and severe SMR treated with TMVr with the MitraClip compared with GDMT alone is unknown. METHODS: Patients were randomized 1:1 to TMVr versus GDMT alone. Two-year outcomes were examined according to sex. RESULTS: Among 614 patients, 221 (36.0%) were women. Women were younger than men and had fewer comorbidities, but reduced quality of life and functional capacity at baseline. In a joint frailty model accounting for the competing risk of death, the 2-year cumulative incidence of the primary endpoint of all HF hospitalizations (HFH) was higher in men compared with women treated with GDMT alone. However, the relative reduction in HFHs with TMVr was greater in men (HR: 0.43; 95% CI: 0.34-0.54) than women (HR: 0.78; 95% CI: 0.57-1.05) (Pinteraction = 0.002). A significant interaction between TMVr versus GDMT alone treatment and time was present for all HFHs in women (HR: 0.57; 95% CI: 0.39-0.84, and HR: 1.39; 95% CI: 0.83-2.33 between 0-1 year and 1-2 years after randomization, respectively, Pinteraction = 0.007) but not in men (HR: 0.48; 95% CI: 0.36-0.64, and HR: 0.33; 95% CI: 0.21-0.51; Pinteraction = 0.16). Female sex was independently associated with a lower adjusted risk of death at 2 years (HR: 0.64; 95% CI: 0.46-0.90; P = 0.011). TMVr consistently reduced 2-year mortality compared with GDMT alone, irrespective of sex (Pinteraction = 0.99). CONCLUSIONS: In the COAPT trial, TMVr with the MitraClip resulted in improved clinical outcomes compared with GDMT alone, irrespective of sex. However, the impact of TMVr in reducing HFH was less pronounced in women compared with men beyond the first year after treatment. (Cardiovascular Outcomes Assessment of the MitraClip Percutaneous Therapy for Heart Failure Patients With Functional Mitral Regurgitation [The COAPT Tria] [COAPT]; NCT01626079).

A randomized evaluation of the TriGuard™ HDH cerebral embolic protection device to Reduce the Impact of Cerebral Embolic LEsions after TransCatheter Aortic Valve ImplanTation: the REFLECT I trial.

AIMS: The REFLECT I trial investigated the safety and effectiveness of the TriGuard™ HDH (TG) cerebral embolic deflection device in patients undergoing transcatheter aortic valve replacement (TAVR). METHODS AND RESULTS: This prospective, multicentre, single-blind, 2:1 randomized (TG vs. no TG) study aimed to enrol up to 375 patients, including up to 90 roll-in patients. The primary combined safety endpoint (VARC-2 defined early safety) at 30 days was compared with a performance goal. The primary efficacy endpoint was a hierarchical composite of (i) all-cause mortality or any stroke at 30 days, (ii) National Institutes of Health Stroke Scale (NIHSS) worsening at 2-5 days or Montreal Cognitive Assessment worsening at 30 days, and (iii) total volume of cerebral ischaemic lesions detected by diffusion-weighted magnetic resonance imaging at 2-5 days. Cumulative scores were compared between treatment groups using the Finkelstein-Schoenfeld method. A total of 258 of the planned, 375 patients (68.8%) were enrolled (54 roll-in and 204 randomized). The primary safety outcome was met compared with the performance goal (21.8% vs. 35%, P < 0.0001). The primary hierarchical efficacy endpoint was not met (mean efficacy score, higher is better: -5.3 ± 99.8 TG vs. 11.8 ± 96.4 control, P = 0.31). Covert central nervous system injury was numerically lower with TG both in-hospital (46.1% vs. 60.3%, P = 0.0698) and at 5 days (61.7 vs. 76.2%, P = 0.054) compared with controls. CONCLUSION: REFLECT I demonstrated that TG cerebral protection during TAVR was safe in comparison with historical TAVR data but did not meet the predefined effectiveness endpoint compared with unprotected TAVR controls.

Prospective Evaluation of Transseptal TMVR for Failed Surgical Bioprostheses: MITRAL Trial Valve-in-Valve Arm 1-Year Outcomes.

OBJECTIVES: The aim of this study was to assess 1-year clinical outcomes among high-risk patients with failed surgical mitral bioprostheses who underwent transseptal mitral valve-in-valve (MViV) with the SAPIEN 3 aortic transcatheter heart valve (THV) in the MITRAL (Mitral Implantation of Transcatheter Valves) trial. BACKGROUND: The MITRAL trial is the first prospective study evaluating transseptal MViV with the SAPIEN 3 aortic THV in high-risk patients with failed surgical mitral bioprostheses. METHODS: High-risk patients with symptomatic moderate to severe or severe mitral regurgitation (MR) or severe mitral stenosis due to failed surgical mitral bioprostheses were prospectively enrolled. The primary safety endpoint was technical success. The primary THV performance endpoint was absence of MR grade ≥2+ or mean mitral valve gradient ≥10 mm Hg (30 days and 1 year). Secondary endpoints included procedural success and all-cause mortality (30 days and 1 year). RESULTS: Thirty patients were enrolled between July 2016 and October 2017 (median age 77.5 years [interquartile range (IQR): 70.3 to 82.8 years], 63.3% women, median Society of Thoracic Surgeons score 9.4% [IQR: 5.8% to 12.0%], 80% in New York Heart Association functional class III or IV). The technical success rate was 100%. The primary performance endpoint in survivors was achieved in 96.6% (28 of 29) at 30 days and 82.8% (24 of 29) at 1 year. Thirty-day all-cause mortality was 3.3% and was unchanged at 1 year. The only death was due to airway obstruction after swallowing several pills simultaneously 29 days post-MViV. At 1-year follow-up, 89.3% of patients were in New York Heart Association functional class I or II, the median mean mitral valve gradient was 6.6 mm Hg (interquartile range: 5.5 to 8.9 mm Hg), and all patients had MR grade ≤1+. CONCLUSIONS: Transseptal MViV in high-risk patients was associated with 100% technical success, low procedural complication rates, and very low mortality at 1 year. The vast majority of patients experienced significant symptom alleviation, and THV performance remained stable at 1 year.

3-Year Outcomes of Transcatheter Mitral Valve Repair in Patients With Heart Failure.

BACKGROUND: In the COAPT (Cardiovascular Outcomes Assessment of the MitraClip Percutaneous Therapy for Heart Failure Patients with Functional Mitral Regurgitation) trial, transcatheter mitral valve repair (TMVr) resulted in fewer heart failure hospitalizations (HFHs) and lower mortality at 24 months in patients with heart failure (HF) with mitral regurgitation (MR) secondary to left ventricular dysfunction compared with guideline-directed medical therapy (GDMT) alone. OBJECTIVES: This study determined if these benefits persisted to 36 months and if control subjects who were allowed to cross over at 24 months derived similar benefit. METHODS: This study randomized 614 patients with HF with moderate-to-severe or severe secondary MR, who remained symptomatic despite maximally tolerated GDMT, to TMVr plus GDMT versus GDMT alone. The primary effectiveness endpoint was all HFHs through 24-month follow-up. Patients have now been followed for 36 months. RESULTS: The annualized rates of HFHs per patient-year were 35.5% with TMVr and 68.8% with GDMT alone (hazard ratio [HR]: 0.49; 95% confidence interval [CI]: 0.37 to 0.63; p < 0.001; number needed to treat (NNT) = 3.0; 95% CI: 2.4 to 4.0). Mortality occurred in 42.8% of the device group versus 55.5% of control group (HR: 0.67; 95% CI: 0.52 to 0.85; p = 0.001; NNT = 7.9; 95% CI: 4.6 to 26.1). Patients who underwent TMVr also had sustained 3-year improvements in MR severity, quality-of-life measures, and functional capacity. Among 58 patients assigned to GDMT alone who crossed over and were treated with TMVr, the subsequent composite rate of mortality or HFH was reduced compared with those who continued on GDMT alone (adjusted HR: 0.43; 95% CI: 0.24 to 0.78; p = 0.006). CONCLUSIONS: Among patients with HF and moderate-to-severe or severe secondary MR who remained symptomatic despite GDMT, TMVr was safe, provided a durable reduction in MR, reduced the rate of HFH, and improved survival, quality of life, and functional capacity compared with GDMT alone through 36 months. Surviving patients who crossed over to device treatment had a prognosis comparable to those originally assigned to transcatheter therapy. (Cardiovascular Outcomes Assessment of the MitraClip Percutaneous Therapy for Heart Failure Patients with Functional Mitral Regurgitation [COAPT]; NCT01626079).

Outcomes of transcatheter mitral valve repair for secondary mitral regurgitation by severity of left ventricular dysfunction.

BACKGROUND: In the COAPT trial, transcatheter mitral valve repair with the MitraClip plus maximally tolerated guideline-directed medical therapy (GDMT) improved clinical outcomes compared with GDMT alone in symptomatic patients with heart failure (HF) and 3+ or 4+ secondary mitral regurgitation (SMR) due to left ventricular (LV) dysfunction. AIMS: In this COAPT substudy, we sought to evaluate two-year outcomes in HF patients with reduced LV ejection fraction (HFrEF; LVEF ≤40%) versus preserved LVEF (HFpEF; LVEF >40%) and in those with severe (LVEF ≤30%) versus moderate (LVEF >30%) LV dysfunction. METHODS: The principal effectiveness outcome was the two-year rate of death from any cause or HF hospitalisations (HFH). Subgroup analysis with interaction testing was performed according to baseline LVEF; 472 patients (82.1%) had HFrEF (mean LVEF 28.0%±6.2%; range 12% to 40%) and 103 (17.9%) had HFpEF (mean LVEF 46.6%±4.9%; range 41% to 65%), while 292 (50.7%) had severely depressed LVEF (LVEF ≤30%; mean LVEF 23.9%±3.8%) and 283 (49.3%) had moderately depressed LVEF (LVEF >30%; mean LVEF 39.0%±6.8%). RESULTS: The two-year rate of death or HFH was 56.7% in patients with HFrEF and 53.4% with HFpEF (HR 1.16, 95% CI: 0.86-1.57, p=0.32). MitraClip reduced the two-year rate of death or HFH in patients with HFrEF (HR 0.50, 95% CI: 0.39-0.65) and HFpEF (HR 0.60, 95% CI: 0.35-1.05), pint=0.55. MitraClip was consistently effective in reducing the individual endpoints of mortality and HFH, improving MR severity, quality of life, and six-minute walk distance in patients with HFrEF, HFpEF, LVEF ≤30%, and LVEF >30%. CONCLUSIONS: In the COAPT trial, among patients with HF and 3+ or 4+ SMR who remained symptomatic despite maximally tolerated GDMT, the MitraClip was consistently effective in improving survival and health status in patients with severe and moderate LV dysfunction and those with preserved LVEF.

Imaging Guidance for Transcatheter Mitral Valve Intervention on Prosthetic Valves, Rings, and Annular Calcification.

Catheter-based interventions to improve mitral valve function are dependent on anatomic and functional information provided by noninvasive imaging to plan, perform, and evaluate each intervention. In this review we highlight the importance of imaging guidance for catheter-based interventions on prosthetic mitral valves, surgical rings, and native valve annular calcification. Both repair and replacement procedures are discussed. We review the general features common to this collection of procedures and discuss specific imaging issues and concerns for each procedure. Figures and intraprocedural videos emphasize central messages using case examples.

Predictors of Clinical Response to Transcatheter Reduction of Secondary Mitral Regurgitation: The COAPT Trial.

BACKGROUND: Transcatheter mitral valve repair with the MitraClip results in marked clinical improvement in some but not all patients with secondary mitral regurgitation (MR) and heart failure (HF). OBJECTIVES: This study sought to evaluate the clinical predictors of a major response to treatment in the COAPT trial. METHODS: Patients with HF and severe MR who were symptomatic on maximally tolerated guideline-directed medical therapy (GDMT) were randomly assigned to MitraClip plus GDMT or GDMT alone. Super-responders were defined as those alive without HF hospitalization and with ≥20-point improvement in the Kansas City Cardiomyopathy Questionnaire overall summary (KCCQ-OS) score at 12 months. Responders were defined as those alive without HF hospitalization and with a 5 to <20-point KCCQ-OS improvement at 12 months. Nonresponders were those who either died, were hospitalized for HF, or had <5-point improvement in KCCQ-OS at 12 months. RESULTS: Among 614 enrolled patients, 41 (6.7%) had missing KCCQ-OS data and could not be classified. At 12 months, there were 79 super-responders (27.2%), 55 responders (19.0%), and 156 nonresponders (53.8%) in the MitraClip arm compared with 29 super-responders (10.2%), 46 responders (16.3%), and 208 nonresponders (73.5%) in the GDMT-alone arm (overall p < 0.0001). Independent baseline predictors of clinical responder status were lower serum creatinine and KCCQ-OS scores and treatment assignment to MitraClip. MR grade and estimated right ventricular systolic pressure at 30 days were improved to a greater degree in super-responders and responders but not in nonresponders. CONCLUSIONS: Baseline predictors of clinical super-responders in patients with HF and severe secondary MR in the COAPT trial were lower serum creatinine, KCCQ-OS score and MitraClip treatment. Improved MR severity and reduced right ventricular systolic pressure at 30 days are associated with a long-term favorable clinical response after transcatheter mitral valve repair. (Cardiovascular Outcomes Assessment of the MitraClip Percutaneous Therapy for Heart Failure Patients With Functional Mitral Regurgitation [COAPT]; NCT01626079).

Clinical Implications of Physical Function and Resilience in Patients Undergoing Transcatheter Aortic Valve Replacement.

Background Gait speed is a reliable measure of physical function and frailty in patients with aortic stenosis undergoing transcatheter aortic valve replacement (TAVR). Slow gait speed pre-TAVR predicts worse clinical outcomes post-TAVR. The consequences of improved versus worsened physical function post-TAVR are unknown. Methods and Results The REPRISE III (Repositionable Percutaneous Replacement of Stenotic Aortic Valve Through Implantation of Lotus Valve System-Randomized Clinical Evaluation) trial randomized high/extreme risk patients to receive a mechanically-expanded or self-expanding transcatheter heart valve. Of 874 patients who underwent TAVR, 576 with complete data at baseline and 1 year were included in this analysis. Slow gait speed in the 5-m walk test was defined as <0.83 m/s. A clinically meaningful improvement (≥0.1 m/s) in gait speed 1 year after TAVR occurred in 39% of patients, 35% exhibited no change, and 26% declined (≥0.1 m/s). Among groups defined by baseline/1-year post-TAVR gait speeds, 1- to 2-year mortality or hospitalization rates were as follows: 6.6% (normal/normal), 8.0% (slow/normal), 20.9% (normal/slow), and 21.5% (slow/slow). After adjustment, slow gait speed at 1 year (regardless of baseline speed) was associated with a 3.5-fold increase in death/hospitalization between 1 and 2 years compared with those with normal baseline/1-year gait speed. Patients whose slow gait speed normalized at 1 year had no increased risk. One-year, but not baseline, gait speed was associated with death or hospitalization between 1 and 2 years (adjusted hazard ratio, 0.83 per 0.1 m/s faster gait; 95% CI, 0.74-0.93, P=0.001). Conclusions Marked heterogeneity exists in the trajectory of physical function after TAVR and this, more than baseline function, has clinical consequences. Identifying and optimizing factors associated with physical resilience after TAVR may improve outcomes. Registration URL: https://www.clini​caltr​ials.gov; Unique identifier: NCT02202434.