Expanding the Spectrum of TEER Suitability: Evidence From the EXPAND G4 Post Approval Study

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Background Septal reduction techniques play a pivotal role in mitigating morbidity and mortality among patients with obstructive hypertrophic cardiomyopathy (oHCM). While trans-apical intramyocardial septal radiofrequency ablation (PIMSRA or LIWEN procedure) has shown promise in reducing left ventricular outflow tract (LVOT) gradients and improving symptoms in oHCM patients, it is associated with complications such as cardiac tamponade and atrioventricular block. Objective This study introduces a novel approach for transcatheter radiofrequency ablation of hypertrophic septum via femoral access, utilizing the DragonFire Transcatheter Myocardial Puncture and Radiofrequency Ablation System. We aim to evaluate its safety and medium-term outcomes in patients with oHCM. Methods A prospective, single-center, single-arm study of tf-PIMSRA was conducted in patients with drug-refractory oHCM. Ten patients were enrolled and underwent the procedure under the guidance of transesophageal echocardiography. The primary outcome was 30-day major adverse clinical events, with secondary outcomes including 90-day improvements in outflow obstruction and quality of life. Results All patients, with an average age of 57±10 years, including 4 males, underwent the procedure successfully without any complications, including major adverse clinical events or conduction abnormalities. The average duration of the procedure was 125.2±34.6 minutes, with an average ablation time of 38.69±18.29 minutes and ablation energy of 3.60±1.49KJ. At 90-day follow-up, significant reductions were observed in peak LVOT gradients (resting gradient: from 82.00 [56.00] mmHg to 14.00 [6.25] mmHg; p < 0.001; provoked gradient: from 102.00 [76.25] mmHg to 33.00 [16.50] mmHg; p = 0.002), and interventricular septum thickness (from 22.00 [19.00] mm to 17.00 [15.00] mm; p = 0.002). These improvements were associated with enhancements in NYHA functional classification (from 3.00 [2.75] to 1.00 [1.00]; p < 0.0001), Kansas City Cardiomyopathy Questionnaire scores (from 59.00 [44.50] to 80.00 [77.25]; p < 0.02), 6-minute walk distance (from 441 [400] m to 480 [465] m; p < 0.01), and pro B-type natriuretic peptide levels (from 1738.00 [1113.25] pg/ml to 252.00 [200.00] pg/ml; p = 0.002). All patients achieved New York Heart Association functional class I or II at follow-up. Conclusions Transfemoral PIMSRA appears to be a safe and effective procedure for relieving LVOT obstruction and symptoms in patients with drug-refractory oHCM. These findings support further investigation through randomized clinical trials comparing it with established septal reduction therapies.Patient-Level Outcomes for the trans-fem

Patients with tricuspid regurgitation (TR) are at high risk for morbidity and mortality, with poorer outcomes associated with increasing TR severity. Tricuspid transcatheter edge-to-edge repair (T-TEER) has emerged as a promising treatment option. TriCLASP is a prospective, single-arm, European post-market study evaluating the safety and effectiveness of T-TEER with the PASCAL system to treat patients with ≥severe TR. The TriCLASP study enrolled 300 patients to evaluate the safety and performance of T-TEER. Major adverse events (MAE), reduction in TR grade, and clinical, functional, and quality-of-life outcomes were assessed at 1 year. Enrolled patients had a mean age of 80.1 years, 52.0% were female, and 75.8% had ≥severe TR. Tricuspid regurgitation was reduced to ≤moderate in 87.7% of patients (p<0.001). The composite MAE rate was 1.7% at 30 days and 12.7% at 1 year. Kaplan-Meier estimates for survival and freedom from heart failure hospitalisation (HFH) were 88.3±1.9% and 83.2±2.3%, respectively. Annualised HFH rates decreased by 72.2% in the 12 months pre- versus post-procedure (p<0.001). Significant functional and quality-of-life improvements were observed from baseline to 1 year, including 74.5% of patients in New York Heart Association Class I/II, a 29.4-metre increase in the 6-minute walk distance, and an 8.3-point increase in the Kansas City Cardiomyopathy Questionnaire score (p<0.001). The 1-year results of the TriCLASP study confirm the safety and effectiveness of T-TEER with the PASCAL system in patients with ≥severe TR. Patients experienced significant TR reduction, low mortality, high freedom from HFH, and significant improvements in symptoms, functional capacity, and quality of life.

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Background Impaired health status as measured by standardized tools such as Kansas City Cardiomyopathy Questionnaire (KCCQ), Duke Activity Status Index (DASI) and six-minute walk test (6MWT) has been shown to predict hospitalization and mortality in patients with chronic heart failure. However, prognostic implications of these measurements in response to guideline-directed medical therapy for heart failure with reduced ejection fraction (HFrEF) remained to be elucidated. Purpose We hypothesized that impaired health status were predictive of persistently elevated N-terminal pro-B-type natriuretic peptide (NT-proBNP) after 6 and 12 months of therapeutic optimization in HFrEF. Methods Data on the GUIDE-IT trial that included protocolized HFrEF drug titration were analyzed. Patients who did not have NT-proBNP at 12 months were excluded. KCCQ overall and clinical summary scores, and DASI scores at baseline and 6 months were calculated. Six-minute walk test (6MWT) distance at baseline were also available. Response to medical therapy was defined as having NT-proBNP at 12 months of less than 1,000 pg/mL. Median value of each measurement was used as a cutoff. Multivariate logistic regression analysis was used to determine independent associations between different QOL scores and NT-proBNP response after adjustment for age, comorbidities, baseline EF, NYHA functional class, and NT-proBNP. Results There were 193 (43%) responders. Compared with those who responded to the medical therapy, non-responders were older, and more likely to have comorbidities including coronary artery disease, stroke, PAD, AF, hypertension, COPD, DM, CKD, and dyslipidemia, as well as lower EF, NHYA functional class and higher baseline NT-proBNP. After adjustment for baseline characteristics, lower KCCQ (either overall or summary) scores at baseline and 6 months, and lower DASI scores at 6 months (but not baseline) were independently associated with lower likelihood of response to GDMT (Table). In contrast, baseline 6MWT distance did not predict non-response to GDMT after adjustments. Conclusions Only impaired baseline KCCQ scores were predictive of persistently elevated NT-proBNP, while lower KCCQ and DASI scores at 6 month were predictive of persistently elevated NT-proBNP. Funding Acknowledgement Type of funding sources: None. Health Status Score below Median and ORs

Real-World Outcomes of Fourth-Generation Mitral Transcatheter Repair: 30-Day Results From EXPAND G4

Patient-reported and morbidity-mortality endpoints: can one have the best of both worlds?

BackgroundStem cell therapy is the transplantation of human cells to aid the healing of damaged or wounded tissues and cells. Only a few small-scale trials have been conducted to investigate stem cell therapy for non-ischemic dilated cardiomyopathy (DCM). We aimed to perform a systematic review and meta-analysis to assess the efficacy and safety of stem cell therapy for DCM.MethodsA comprehensive search of the databases of PubMed, Embase, Web of Science Core Collection, Cochrane Library, and ProQuest was conducted from their inception to June 30, 2024, to access randomized controlled trials (RCTs) that were centered on stem cell therapy for DCM. The primary outcome was left ventricular ejection fraction (LVEF), and the secondary outcomes included left ventricular end-diastolic dimension (LVEDD), left ventricular end-diastolic volume (LVEDV), 6-min walk test (6MWT), NYHA functional classification, quality of life (QoL) such as Minnesota Living with Heart Failure Questionnaire (MLHFQ) and Kansas City Cardiomyopathy Questionnaire (KCCQ), N-terminal pro-brain natriuretic peptide (NT-proBNP), and VO2 peak. Moreover, major adverse cardiovascular events (MACEs) were also recorded. The Cochrane risk-of-bias assessment tool was used to evaluate the quality of the included RCTs, and the certainty of the evidence was assessed using the GRADE method. Sensitivity analysis was taken into consideration to determine the stability of the results. This review was registered with PROSPERO (CRD42024568912).ResultsEleven RCTs involving 637 participants were included in the quantitative analysis. The results indicated that there was a significant increase in mean LVEF (MD = 4.84, 95% CI 3.25–6.42, P < 0.00001) and considerable decrease in LVEDV (MD = − 29.51, 95% CI − 58.07 to − 0.95, P = 0.04) and NT-proBNP (MD = − 737.55, 95% CI − 904.28 to − 570.82, P < 0.00001) in DCM patients treated with stem cell therapy compared with controls. Stem cell therapy was also related to the improvement in functional capacity, as evaluated by 6MWT (MD = 44.32, 95% CI 34.70 − 53.94, P < 0.00001) and NYHA functional classification (MD = − 0.63, 95% CI − 0.96 to − 0.30, P = 0.0002). It also had positive effects on improving QoL, including significantly decreasing MLHFQ score (MD = − 16.60, 95% CI − 26.57 to − 6.63, P = 0.001) and increasing the KCCQ score (MD = 14.76, 95% CI 7.76 − 21.76, P < 0.0001). No significant differences were observed in LVEDD, VO2 peak, and MACEs between the two groups. The GRADE analysis revealed that the evidence was graded from low to moderate. Sensitivity analysis of the results suggested that the results were stable.ConclusionThe systematic review and meta-analysis indicates that stem cell therapy may be an effective and safe approach to improve cardiac function and quality of life in DCM patients. Nevertheless, given the limitations of existing studies, larger well-designed RCTs are required to confirm and support our findings.

The effect of MitraClip implantation on left ventricular (LV) remodelling has been shown to be highly variable. The present study wants to assess patterns of LV remodelling and its relationship with outcome. Serial echocardiography before, 1 and 6 months after MitraClip implantation was performed in 79 pts with severe mitral regurgitation (MR) (age 74 ± 10 years, New York Heart Association III/IV 80%, LV ejection fraction 38 ± 13%, logistic EuroSCORE 21 ± 15, and functional MR 81%). LV reverse/adverse remodelling was defined as a >15% decrease/>10% increase in LV end-diastolic volume (LVEDV), respectively. Patients were followed over a period of 32 ± 16 months with all-cause mortality as the primary endpoint. A sustained (6 month) reduction of MR ≤ 2 post-MitraClip implantation was observed in 83% of patients. The average decrease in LVEDV 6 months after intervention was 13% ± 16%. Reverse remodelling at 6 months occurred in 40 patients (51%), and adverse remodelling occurred in 6 patients (8%). Patients with adverse remodelling showed a 38% increase of LVEDV at 1 month vs. no early change in LVEDV in patients with reverse remodelling. During follow-up, a total of 25 patients (32%) died. Patients with adverse remodelling died more frequently than patients with reverse remodelling [67% vs. 27%, adjusted odds ratio of 5.6 (95% CI 1.5-21)]. The majority of patients undergoing MitraClip implantation for severe MR showed LV reverse remodelling. However, there was a small group in whom afterload mismatch resulted in sustained adverse remodelling with subsequent high mortality.

Association Between Disease-specific Health-related Quality of Life and All-cause Mortality in Patients with Heart Failure: A Meta-analysis

Many patients with atrial functional mitral regurgitation are not suitable candidates for surgery or transcatheter repair. For transcatheter mitral valve replacement, a common contraindication is the risk of left ventricular outflow tract obstruction, particularly in patients with atrial functional mitral regurgitation, who have characteristically small left ventricles. Herein, we examine the outcomes of transcatheter mitral valve replacement using the AltaValve system, which employs atrial fixation thus minimizing left ventricular outflow tract obstruction risk. Patients with severe, symptomatic mitral regurgitation who were treated in the AltaValve early feasibility study or on the basis of a compassionate use exemption. The definition of atrial functional mitral regurgitation required the presence of: (1) severe mitral regurgitation; (2) atrial fibrillation; (3) normal left ventricular size; (4) left ventricular ejection fraction ≥50%; and (5) absence of organic mitral disease. Procedural outcomes, 30-day survival, and echo findings are reported. Fourteen patients (71% women, mean age 77.9 years, Society of Thoracic Surgeons Predicted Risk of Mortality score 5.4%) were treated, including 11 via transseptal delivery and 3 via a transapical approach. Technical success and mitral regurgitation reduction from severe to none/trace were achieved in all cases. There were no cases of left ventricular outflow tract obstruction. All-cause mortality at 30 days was 14% (2/14). Class III/IV New York Heart Association status was reduced from 79% at baseline to 0% at 30 days. At 30 days, 11 of 12 surviving patients had an available echocardiogram; mitral regurgitation severity was trace/none in 90.9% (10/11) and mild in 9.1% (1/11). The AltaValve system shows promising early procedural and clinical results for the unique anatomy of patients with atrial functional mitral regurgitation. Long-term clinical studies to demonstrate the benefit of this system are warranted.

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Mitral transcatheter edge-to-edge repair (TEER) is approved for patients with severe functional mitral regurgitation (FMR) beyond optimal medical therapy (OMT). We aimed to assess TEER's efficacy beyond OMT in patients with severe FMR. A systematic review and meta-analysis were conducted, including randomized controlled trials from PubMed, Cochrane, Scopus, and EMBASE up to September 2024. heart failure hospitalization (HFH); secondary outcomes: cardiovascular (CV) mortality, all-cause mortality, and Kansas City Cardiomyopathy Questionnaire (KCCQ) scores. Time-to-event data from Kaplan-Meier curves were reconstructed for individual patient data. Three studies (1423 patients) were included. TEER significantly reduced HFH (RR 0.73, 95% CI 0.58-0.92, p < 0.01) and CV mortality (RR 0.79, 95% CI 0.66-0.95, p = 0.01), and improved KCCQ scores (mean difference 14.32, 95% CI 10.85-17.80, p < 0.01) compared to OMT. No significant difference was found for all-cause mortality (RR 0.80, 95% CI 0.63-1.02, p = 0.07). Prognostic meta-analysis showed a 34% reduced risk of HFH (HR 0.66, 95% CI 0.45-0.96, p = 0.03), but no effect on all-cause or CV mortality. Reconstructed Kaplan-Meier analysis confirmed a 34% reduced risk of HFH (HR 0.65, p < 0.001), with effect attenuation after 15 months in landmark analysis (HR 0.64, p = 0.07). RMST analysis showed a 2.9-month longer HFH-free survival with TEER (p < 0.01). In patients with FMR, TEER significantly reduces HFH, improves functional status, and lowers CV mortality at 24 months but does not significantly affect all-cause mortality. The device group experienced a modest, but significant, 2.9-month longer HFH-free survival compared to the control group. However, the reduction in HFH showed attenuation beyond 15 months.

Off-Pump Transapical Implantation of Artificial Neo-Chordae to Correct Mitral Regurgitation: The TACT Trial (Transapical Artificial Chordae Tendinae) Proof of Concept

Percutaneous valve repair of functional mitral regurgitation: aiming at optimal and durable results.