Infliximab Limits Injury in Myocardial Infarction.

BACKGROUND: The purpose of this study was to investigate a therapeutic approach targeting the inflammatory response and consequent remodeling from ischemic myocardial injury. METHODS AND RESULTS: Coronary thrombus aspirates were collected from patients at the time of ST-segment-elevation myocardial infarction and subjected to array-based proteome analysis. Clinically indistinguishable at myocardial infarction (MI), patients were stratified into vulnerable and resilient on the basis of 1-year left ventricular ejection fraction and death. Network analysis from coronary aspirates revealed prioritization of tumor necrosis factor-α signaling in patients with worse clinical outcomes. Infliximab, a tumor necrosis factor-α inhibitor, was infused intravenously at reperfusion in a porcine MI model to assess whether infliximab-mediated immune modulation impacts post-MI injury. At 3 days after MI (n=7), infliximab infusion increased proregenerative M2 macrophages in the myocardial border zone as quantified by immunofluorescence (24.1%±23.3% in infliximab versus 9.29%±8.7% in sham; P<0.01). Concomitantly, immunoassays of coronary sinus samples quantified lower troponin I levels (41.72±7.34 pg/mL versus 58.11±10.75 pg/mL; P<0.05) and secreted protein analysis revealed upregulation of injury-modifying interleukin-2, -4, -10, -12, and -18 cytokines in the infliximab-treated cohort. At 4 weeks (n=12), infliximab treatment resulted in significant protective influence, improving left ventricular ejection fraction (53.9%±5.4% versus 36.2%±5.3%; P<0.001) and reducing scar size (8.31%±10.9% versus 17.41%±12.5%; P<0.05). CONCLUSIONS: Profiling of coronary thrombus aspirates in patients with ST-segment-elevation MI revealed highest association for tumor necrosis factor-α in injury risk. Infliximab-mediated immune modulation offers an actionable pathway to alter MI-induced inflammatory response, preserving contractility and limiting adverse structural remodeling.

Contemporary 1-Year Outcomes of Mitral Valve-in-Ring With Balloon-Expandable Aortic Transcatheter Valves in the U.S.

BACKGROUND: Adequate valve performance after surgical mitral valve repair with an annuloplasty ring is not always sustained over time. The risk of repeat mitral valve surgery may be high in these patients. Transcatheter mitral valve-in-ring (MViR) is emerging as an alternative for high-risk patients. OBJECTIVES: The authors sought to assess contemporary outcomes of MViR using third-generation balloon-expandable aortic transcatheter heart valves. METHODS: Patients who underwent MViR and were enrolled in the STDS/ACC TVT (Society of Thoracic Surgeons/American College of Cardiology Transcatheter Valve Therapy) Registry between August 2015 and December 2022 were analyzed. RESULTS: A total of 820 patients underwent MViR at 236 sites, mean age was 72.2 ± 10.4 years, 50.9% were female, mean STS score was 8.2% ± 6.9%, and most (78%) were in NYHA functional class III to IV. Mean left ventricular ejection fraction was 47.8% ± 14.2%, mean mitral gradient was 8.9 ± 7.0 mm Hg, and 75.5% had ≥ moderate mitral regurgitation. Access was transseptal in 93.9% with 88% technical success. All-cause mortality at 30 days was 8.3%, and at 1 year, 22.4%, with a reintervention rate of 9.1%. At 1-year follow-up, 75.6% were NYHA functional class I to II, Kansas City Cardiomyopathy Questionnaire score increased by 25.9 ± 29.1 points, mean mitral valve gradient was 8.4 ± 3.4 mm Hg, and 91.7% had ≤ mild mitral regurgitation. CONCLUSIONS: MViR with third-generation balloon-expandable aortic transcatheter heart valves is associated with a significant reduction in mitral regurgitation and improvement in symptoms at 1 year, but with elevated valvular gradients and a high reintervention rate. MViR is a reasonable alternative for high-risk patients unable undergo surgery who have appropriate anatomy for the procedure. (STS/ACC TVT Registry Mitral Module [TMVR]; NCT02245763).

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.

Emerging Approaches to Management of Left Ventricular Outflow Obstruction Risk in Transcatheter Mitral Valve Replacement.

An increasing number of patients with mitral valve disease are high risk for surgery and in need of less invasive treatments including transcatheter mitral valve replacement (TMVR). Left ventricular outflow tract (LVOT) obstruction is a predictor of poor outcome after TMVR, and its risk can be accurately predicted using cardiac computed tomography analysis. Novel treatment strategies that have shown efficacy in reducing risk of LVOT obstruction after TMVR include pre-emptive alcohol septal ablation, radiofrequency ablation, and anterior leaflet electrosurgical laceration. This review describes recent advances in the management of LVOT obstruction risk after TMVR, provides a new management algorithm, and explores forthcoming studies that will further advance the field.

Genetic-Guided Oral P2Y12 Inhibitor Selection and Cumulative Ischemic Events After Percutaneous Coronary Intervention.

BACKGROUND: Genetic-guided P2Y12 inhibitor selection has been proposed to reduce ischemic events by identifying CYP2C19 loss-of-function (LOF) carriers at increased risk with clopidogrel treatment after percutaneous coronary intervention (PCI). A prespecified analysis of TAILOR-PCI (Tailored Antiplatelet Therapy Following PCI) evaluated the effect of genetic-guided P2Y12 inhibitor therapy on cumulative ischemic and bleeding events. OBJECTIVES: Here, the authors detail a prespecified analysis of cumulative endpoints. The primary endpoint was cumulative incidence rate of ischemic events at 12 months. Cumulative incidence of major and minor bleeding was a secondary endpoint. Cox proportional hazards models as adapted by Wei, Lin, and Weissfeld were used to estimate the effect of this strategy on all observed events. METHODS: The TAILOR-PCI trial was a prospective trial including 5,302 post-PCI patients with acute and stable coronary artery disease (CAD) who were randomized to genetic-guided P2Y12 inhibitor or conventional clopidogrel therapy. In the genetic-guided group, LOF carriers were prescribed ticagrelor, whereas noncarriers received clopidogrel. TAILOR-PCI's primary analysis was time to first event in LOF carriers. RESULTS: Among 5,276 patients (median age 62 years; 25% women; 82% acute CAD; 18% stable CAD), 1,849 were LOF carriers (903 genetic-guided; 946 conventional therapy). The cumulative primary endpoint was significantly reduced in the genetic-guided group compared with the conventional therapy (HR: 0.61; 95% CI: 0.41-0.89; P = 0.011) with no significant difference in cumulative incidence of major or minor bleeding (HR: 1.36; 95% CI: 0.67-2.76; P = 0.39). CONCLUSIONS: Among CYP2C19 LOF carriers undergoing PCI, a genetic-guided strategy resulted in a statistically significant reduction in cumulative ischemic events without a significant difference in bleeding. (Tailored Antiplatelet Therapy Following PCI [TAILOR-PCI]; NCT01742117).

Predictors of hemodynamic response to mitral transcatheter edge-to-edge repair.

BACKGROUND: Improvement in left atrial pressure (LAP) during transcatheter edge-to-edge repair (TEER) is associated with improved outcomes. We sought to investigate the predictors of optimal hemodynamic response to TEER. METHODS: We identified patients who underwent TEER at Mayo Clinic between May 2014 and February 2022. Patients with missing LAP data, an aborted procedure, and those undergoing a concomitant tricuspid TEER were excluded. We performed a logistic regression analysis to identify predictors of optimal hemodynamic response to TEER (defined as LAP ≤ 15 mmHg). RESULTS: A total of 473 patients were included (Mean age 78.5 ± 9.4 years, 67.2% males). Overall, 195 (41.2%) achieved an optimal hemodynamic response after TEER. Patients who did not achieve an optimal response had higher baseline LAP (20.0 [17-25] vs. 15.0 [12-18] mmHg, p < 0.001), higher prevalence of AF (68.3% vs. 55.9%, p = 0.006), functional MR (47.5% vs. 35.9%, p = 0.009), annular calcification (41% vs. 29.2%, p = 0.02), lower left ventricular EF (55% vs. 58%, p = 0.02), and more frequent postprocedural severe MR (11.9% vs. 5.1%, p = 0.02) and elevated mitral gradient >5 mmHg (30.6% vs. 14.4%, p < 0.001). In the multivariate logistic regression analysis, AF (OR = 0.58; 95% CI = 0.35-0.96; p = 0.03), baseline LAP (OR = 0.80; 95% CI = 0.75-0.84; p < 0.001) and postprocedural mitral gradient <5 mmHg (OR = 0.35; 95% CI = 0.19-0.65; p < 0.001), were independent predictors of achieving an optimal hemodynamic response. In the multivariate model, residual MR was not independently associated with optimal hemodynamic response. CONCLUSIONS: Optimal hemodynamic response is achieved in 4 in 10 patients undergoing TEER. AF, higher baseline LAP, and higher postprocedural mitral gradient were negative predictors of optimal hemodynamic response after TEER.

Risks of Right Heart Catheterization and Right Ventricular Biopsy: A 12-year, Single-Center Experience.

OBJECTIVE: To study the incidence of complications when undergoing right heart catheterization (RHC) and right ventricular biopsy (RVB). METHODS: Complications following RHC and RVB are not well reported. We studied the incidence of death, myocardial infarction, stroke, unplanned bypass, pneumothorax, hemorrhage, hemoptysis, heart valve repair/replacement, pulmonary artery perforation, ventricular arrhythmias, pericardiocentesis, complete heart block, and deep vein thrombosis (primary endpoint) following these procedures. We also adjudicated the severity of tricuspid regurgitation and causes of in-hospital death following RHC. Diagnostic RHC procedures, RVB, multiple right heart procedures alone or combined with left heart catheterization, and complications from January 1, 2002, through December 31, 2013, were identified using the clinical scheduling system and electronic records at Mayo Clinic, Rochester, Minnesota. International Classification of Diseases, Ninth Revision billing codes were used. Registration was queried to identify all-cause mortality. All clinical events and echocardiograms for worsening tricuspid regurgitation were reviewed and adjudicated. RESULTS: A total of 17,696 procedures were identified. Procedures were categorized into those undergoing RHC (n=5556), RVB (n=3846), multiple right heart catheterization (n=776), and combined right and left heart catheterization procedures (n=7518). Primary endpoint was seen in 21.6 and 20.8 of 10,000 procedures for RHC and RVB, respectively. There were 190 (1.1%) deaths during hospital admission and none was related to the procedure. CONCLUSION: Complications following diagnostic RHC and RVB are seen in 21.6 and 20.8 procedures, respectively, of 10,000 procedures and all deaths were secondary to acute illness.

The interaction of forced expiratory volume in 1 s and N-terminal pro-B-type natriuretic peptide with outcomes after transcatheter aortic valve replacement.

OBJECTIVES: Low forced expiratory volume in 1 s (FEV1) and elevated N-terminal pro-B-type natriuretic peptide (NT-Pro-BNP) have been individually associated with poor outcomes after transcatheter aortic valve replacement (TAVR). We hypothesized a combination of the 2 would provide prognostic indication after TAVR. METHODS: We categorized 871 patients who received TAVR from 2008 to 2018 into 4 groups according to baseline FEV1 (<60% or ≥60% predicted) and NT-Pro-BNP (<1601 or ≥1601 pg/ml): group A (n = 312, high FEV1, low NT-Pro-BNP), group B (n = 275, high FEV1, high NT-Pro-BNP), group C (n = 123 low FEV1, low NT-Pro-BNP) and group D (n = 161, low FEV1, high NT-Pro-BNP). The primary end point was survival at 1 and 5 years. RESULTS: Patients in group A had more severe aortic stenosis and achieved the best long-term survival at 1 [93% (95% CI: 90-96)] and 5 [45.3% (95% CI: 35.4-58)] years. Low FEV1 and high NT-Pro-BNP (group D) patients had more severe symptoms, higher Society of Thoracic Surgeons predicted risk of operative mortality, lower ejection fraction and aortic valve gradient at baseline. Patients in group D had the worst survival at 1 [76% (95% CI: 69-83)] and 5 years [13.1% (95% CI: 7-25)], hazard ratio compared to group A: 2.29 (95% CI: 1.6-3.2, P < 0.001) with 25.7% of patients in New York Heart Association class III-IV. Patients in groups B and C had intermediate outcomes. CONCLUSIONS: The combination of FEV1 and NT-Pro-BNP stratifies patients into 4 groups with distinct risk profiles and clinical outcomes. Patients with low FEV1 and high NT-Pro-BNP have increased comorbidities, poor functional outcomes and decreased long-term survival after TAVR.

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.

Safety and Efficacy of CYP2C19 Genotype-Guided Escalation of P2Y12 Inhibitor Therapy After Percutaneous Coronary Intervention in Chronic Kidney Disease: a Post Hoc Analysis of the TAILOR-PCI Study.

PURPOSE: Chronic kidney disease (CKD) is a risk factor for ischemic and bleeding events with dual antiplatelet therapy after percutaneous coronary intervention (PCI). Whether the presence of CYP2C19 loss of function (LOF) alleles modifies this risk, and whether a genotype-guided (GG) escalation of P2Y12 inhibitor therapy post PCI is safe in this population is unclear. METHODS: This was a post hoc analysis of randomized patients in TAILOR PCI. Patients were divided into two groups based on estimated glomerular filtration rate (eGFR) threshold of < 60 ml/min/1.73 m2 for CKD (n = 539) and non-CKD (n = 4276). The aggregate of cardiovascular death, stroke, myocardial infarction, stent thrombosis, and severe recurrent coronary ischemia at 12-months post-PCI was assessed as the primary endpoint. Secondary endpoint was major or minor bleeding. RESULTS: Mean (standard deviation) eGFR among patients with CKD was 49.5 (8.4) ml/min/1.72 m2. Among all patients, there was no significant interaction between randomized strategy and CKD status for any endpoint. Among LOF carriers, the interaction between randomized strategy and CKD status on composite ischemic outcome was not significant (p = 0.2). GG strategy was not associated with an increased risk of bleeding in either CKD group. CONCLUSIONS: In this exploratory analysis, escalation of P2Y12 inhibitor therapy following a GG strategy did not reduce the primary outcome in CKD. However, P2Y12 inhibitor escalation following a GG strategy was not associated with increased bleeding risk in CKD. Larger studies in CKD are needed. CLINICAL TRIAL REGISTRATION: https://clinicaltrials.gov/ct2/show/NCT01742117?term=TAILOR-PCI&draw=2&rank=1 . NCT01742117.

Preemptive Septal Radiofrequency Ablation to Prevent Left Ventricular Outflow Tract Obstruction With Transcatheter Mitral Valve Replacement: A Case Series.

BACKGROUND: Left ventricular outflow tract obstruction may occur following transcatheter mitral valve replacement in the setting of mitral annular calcification. METHODS: We present a case series whereby preemptive septal radiofrequency ablation (RADIO-TMVR) was used to augment the left ventricular outflow tract for transcatheter mitral valve replacement in 4 patients at risk for left ventricular outflow tract obstruction despite alcohol septal ablation. RESULTS: All patients were female, average age of 74.9 (68.8-80.4) years. Baseline ejection fraction was 71% (63%-75%). Mean mitral valve area was 1.28 (range, 1.0-1.59) cm2. Mean mitral valve gradient at rest was 9.5 (range, 7-11) mm Hg. New York Heart Association symptoms were III to IV at baseline. Patients underwent preemptive septal radiofrequency ablation to prevent left ventricular outflow tract obstruction with transcatheter mitral valve replacement a range between 69 and 154 days after alcohol septal ablation. Procedural time was 384 (337-424) minutes with a fluoroscopic time of 31 (14-71) minutes. Radiofrequency ablation time was 132 (100-175) minutes. As anticipated, 3 patients developed complete heart block and underwent pacemaker implantation, whereas 1 had a preexisting pacemaker. One patient developed groin hematoma and heart failure exacerbation. There were no peri-procedural deaths. Preemptive septal radiofrequency ablation to prevent left ventricular outflow tract obstruction with transcatheter mitral valve replacement resulted in septal end-diastolic wall thickness reduction compared with baseline (28.6%, 30.4%, 30.3%, and 11.1%) and following alcohol septal ablation (23.1%, 12%, 8.5%). Valve replacement in the setting of mitral annular calcification was performed in all patients 89 (range, 38-45) days after preemptive septal radiofrequency ablation to prevent left ventricular outflow tract obstruction with transcatheter mitral valve replacement. Two patients had concomitant laceration of the anterior mitral leaflet to further augment the neo-left ventricular outflow tract. Postprocedure, New York Heart Association symptoms improved to class I (3 patients) and class II (1 patient). CONCLUSIONS: In at-risk individuals, preemptive septal radiofrequency ablation may be an effective strategy at preventing left ventricular outflow tract obstruction with transcatheter mitral valve replacement.

Mitral Valve Surgery for Persistent or Recurrent Mitral Regurgitation After Transcatheter Edge-to-Edge Repair Is Associated With Improved Survival.

Background The management of severe mitral regurgitation (MR) after transcatheter edge-to-edge repair (TEER) remains a clinical conundrum. Considering the growing volume of TEER, more outcomes data for mitral surgery in this cohort are needed. Methods and Results Symptomatic patients with persistent or recurrent severe MR after TEER evaluated between May 2014 and June 2021 were included. The primary outcome was all-cause mortality in patients who were treated with surgery versus medical therapy. The Kaplan-Meier and Cox regression methods were used to report risk-adjusted survival analyses. Among the 142 included patients, 44 (31.0%) underwent mitral surgery. Patients who underwent surgery were younger than those treated medically (74.1±8.9 versus 78.6±10.5 years, P=0.01). Major comorbidities were similar except obesity, sleep apnea, left ventricular dimensions, and ejection fraction. Society of Thoracic Surgeons Predicted Risk of Operative Mortality was 9.0±4.7 versus 7.9±4.9 in the surgical versus medical therapy groups, respectively, P=0.22. Time from TEER to detection of severe MR was similar in both groups (median [interquartile range] 97.5 [39.5-384] versus 93.5 [40-389] days in the surgical versus medical groups, respectively [P>0.05]). In the surgical group, valve replacement was performed in all patients. Operative mortality was 4.5% (observed/expected ratio 0.55), and major complications were uncommon. After risk-adjustment, surgery was associated with significantly lower all-cause mortality (adjusted hazard ratio, 0.33 [95% CI, 0.12-0.92], P=0.001) compared with medial therapy. Conclusions Compared with medical therapy, mitral surgery in patients with severe persistent or recurrent MR after TEER is associated with lower mortality despite the high-risk profile of these patients. Patients with severe MR after TEER should be considered for surgery at a referral mitral surgical center.

Patient Onboarding and Engagement to Build a Digital Study After Enrollment in a Clinical Trial (TAILOR-PCI Digital Study): Intervention Study.

BACKGROUND: The Tailored Antiplatelet Initiation to Lessen Outcomes Due to Decreased Clopidogrel Response After Percutaneous Coronary Intervention (TAILOR-PCI) Digital Study is a novel proof-of-concept study that evaluated the feasibility of extending the TAILOR-PCI randomized controlled trial (RCT) follow-up period by using a remote digital platform. OBJECTIVE: The aim of this study is to describe patients' onboarding, engagement, and results in a digital study after enrollment in an RCT. METHODS: In this intervention study, previously enrolled TAILOR-PCI patients in the United States and Canada within 24 months of randomization were invited by letter to download the study app. Those who did not respond to the letter were contacted by phone to survey the reasons for nonparticipation. A direct-to-patient digital research platform (the Eureka Research Platform) was used to onboard patients, obtain consent, and administer activities in the digital study. The patients were asked to complete health-related surveys and digitally provide follow-up data. Our primary end points were the consent rate, the duration of participation, and the monthly activity completion rate in the digital study. The hypothesis being tested was formulated before data collection began. RESULTS: After the parent trial was completed, letters were mailed to 907 eligible patients (representing 18.8% [907/4837] of total enrolled in the RCT) within 15.6 (SD 5.2) months of randomization across 24 sites. Among the 907 patients invited, 290 (32%) visited the study website and 110 (12.1%) consented-40.9% (45/110) after the letter, 33.6% (37/110) after the first phone call, and 25.5% (28/110) after the second call. Among the 47.4% (409/862) of patients who responded, 41.8% (171/409) declined to participate because of a lack of time, 31.2% (128/409) declined because of the lack of a smartphone, and 11.5% (47/409) declined because of difficulty understanding what was expected of them in the study. Patients who consented were older (aged 65.3 vs 62.5 years; P=.006) and had a lower prevalence of diabetes (19% vs 30%; P=.02) or tobacco use (6.4% vs 24.8%; P<.001). A greater proportion had bachelor's degrees (47.2% vs 25.7%; P<.001) and were more computer literate (90.5% vs 62.3% of daily internet use; P<.001) than those who did not consent. The average completion rate of the 920 available monthly electronic visits was 64.9% (SD 7.6%); there was no decrease in this rate throughout the study duration. CONCLUSIONS: Extended follow-up after enrollment in an RCT by using a digital study was technically feasible but was limited because of the inability to contact most eligible patients or a lack of time or access to a smartphone. Among the enrolled patients, most completed the required electronic visits. Enhanced recruitment methods, such as the introduction of a digital study at the time of RCT consent, smartphone provision, and robust study support for onboarding, should be explored further. TRIAL REGISTRATION: Clinicaltrails.gov NCT01742117; https://clinicaltrials.gov/ct2/show/NCT01742117.

Invasive Hemodynamic Predictors of Survival in Patients With Mitral Stenosis Secondary to Mitral Annular Calcification.

Background The aim of this study was to establish prognostic hemodynamic parameters in patients with mitral stenosis secondary to mitral annular calcification. Methods and Results A retrospective cohort of 105 patients undergoing transseptal catheterization for hemodynamic evaluation of mitral annular calcification-related mitral stenosis between 2004 and 2020 was studied. Mitral valve gradient (MVG) and mitral valve area (MVA; calculated by the Gorlin formula) were measured using direct left atrial and left ventricular pressures. The median age of the patients was 70.3 years (58.4-76.7 years), and 53.3% were women. The median MVA was 1.7 cm2 (1.3-2.3 cm2) and MVG was 7.3 mm Hg (5.3-10.3 mm Hg); left ventricular end-diastolic pressure was 17.6±28.3 mm Hg. During a median of 2.1 years (0.7-4.5 years), there were 63 deaths; 1- and 5-year survival were 76% and 40%, respectively. There was no association between left ventricular end-diastolic pressure and survival. After adjusting for age and comorbidities, both MVA (hazard ratio [HR], 0.50 per cm2; 95% CI, 0.34-0.73) and MVG (HR, 1.1 per mm Hg; 95% CI, 1.05-1.20) were independent predictors of death. Atrial fibrillation was also independently associated with mortality. When added to a combined model, MVA remained associated with death (HR, 0.51 per cm2; 95% CI, 0.33-0.79) while MVG was not. Conclusions In patients with mitral annular calcification-related mitral stenosis, survival was poor. MVA and MVG were independently associated with death, but MVA was a better predictor of outcomes.

Outcomes of Radial Versus Femoral Access in Patients With Severe Aortic Stenosis Undergoing Percutaneous Coronary Intervention Prior to Transcatheter Aortic Valve Replacement.

BACKGROUND: The safety and feasibility of radial access in patients undergoing percutaneous coronary intervention (PCI) prior to transcatheter aortic valve replacement (TAVR) has not been studied. METHODS: This study included consecutive patients who underwent PCI within 30 days before TAVR at Mayo Clinic. Vascular access was left to the discretion of the operator. Baseline demographics, procedural data, PCI outcomes, and subsequent transfemoral TAVR outcomes were extracted from patient charts. RESULTS: A total of 331 patients were included in this study, with 107 patients undergoing PCI via radial access (rPCI), and 224 via femoral access (fPCI). Mean age was 80.6 years and 35.6% were females (35.5% rPCI vs 35.3% fPCI). More patients in the fPCI group had previous coronary artery bypass graft surgery (13.1% rPCI vs 34.4% fPCI; P<.001). Fluoroscopy time (13.36 minutes vs 18.86 minutes; P<.001) and contrast use (115 mL vs 140 mL; P<.01) were lower in the rPCI group than in the fPCI group. Crossover rate from radial to femoral was 6.5%. There were more access-site hematomas in the fPCI group (2.8% rPCI vs 14.3% fPCI; P<.001), with no statistically significant rate of other access-related complications. There was no difference in stroke, myocardial infarction, cardiac arrest, or unplanned surgery. There was no difference in bleeding or stroke between both groups during subsequent transfemoral TAVR. CONCLUSION: Radial access for pre-TAVR PCI is feasible and safe and is associated with a lower rate of access-site hematoma. This study supports the increased use of transradial access for pre-TAVR PCI.

The impact of pulmonary hypertension on outcomes of transcatheter mitral valve replacement in mitral annular calcification.

OBJECTIVES: To assess the impact of pulmonary hypertension (PH) on outcomes of patients with severe mitral annular calcification (MAC) undergoing transcatheter mitral valve replacement (TMVR). BACKGROUND: PH is associated with poor outcomes after mitral valve surgery. Whether the presence of PH in patients with MAC undergoing (TMVR) is associated with poor outcomes, is unknown. METHODS: Retrospective evaluation of 116 patients from 51 centers in 11 countries who underwent TMVR with valve in mitral annular calcification (ViMAC) using balloon-expandable aortic transcatheter valves (THVs) from September 2012 to March 2017. Pulmonary artery systolic blood pressure (PASP) by echocardiogram was available in 90 patients. The subjects were stratified based on PASP: No PH = PASP ≤35 mmHg (n = 11); mild to moderate PH = PASP 36-49 mmHg (n = 21) and severe PH = PASP ≥50 mmHg (n = 58). Clinical, procedural, and echocardiographic outcomes were assessed. RESULTS: Mean age was 72.7 (±12.8) years, 59 (65.6%) were female, Society of Thoracic Surgeons score was 15.8 + 11.8% and 90.0% where in New York Heart Association (NYHA) class III-IV. There was no significant difference in all-cause mortality at 30 days (no PH = 27.3%, mild-moderate PH = 19.0%, severe PH = 31.6%; p = 0.55) or at 1 year (no PH = 54.5%, mild-moderate PH = 38.1%, severe PH = 56.1%; p = 0.36). No difference in adverse events, NYHA class or amount of residual mitral regurgitation at 1 year were observed between the groups. CONCLUSION: This study suggests that the presence of PH in patients with predominantly mitral stenosis with MAC undergoing TMVR does not impact mortality or adverse events. Further studies are needed to fully understand the effect of PH in this group of patients.

Five-year outcomes of transcatheter mitral valve implantation and redo surgery for mitral prosthesis degeneration.

BACKGROUND: Transcatheter mitral valve replacement (TMVR) has emerged as a feasible alternative to redo surgical mitral valve replacement (SMVR) in patients with degenerated mitral prostheses, with limited comparative data. METHODS: We compared mid-term outcomes in patients with degenerated mitral valve prostheses treated with TMVR or redo SMVR. The primary endpoint was survival at 5 years of follow-up. RESULTS: From 2014 to 2020, 215 patients presented with degenerated mitral valve prostheses. Of whom 86 (40%) were treated with TMVR (75[87%] valve-in-valve and 11[13%] valve-in-ring), while 129 patients (60%) underwent SMVR. The TMVR cohort was older (p < 0.0001), more symptomatic (p = 0.0003) and had more chronic lung disease (p = 0.02), worse renal function (p = 0.02) and higher right ventricular systolic pressures (p < 0.0001). Thirty-day mortality was lower with TMVR versus SMVR (2.4% vs. 10.2%, OR4.69 [95% CI 1.25-30.5], p = 0.04) with probability of mortality at 1, 2, and 5 years being 14.7% versus 17.5%, 24.5% versus 20.7%, and 49.9% versus 34.0%, respectively. Mode of prosthesis degeneration, baseline hemodynamics, and valve selection did not appreciably impact outcomes. CONCLUSIONS: TMVR for degenerated mitral prostheses is associated with better early survival compared to SMVR despite a greater burden of comorbidities. In contrast, 5 year survival rates appear more favorable with SMVR, which may reflect the lower baseline risk of this population. Clinical, hemodynamic, and echocardiographic follow-up support the mid-term durability of TMVR for degenerated mitral prostheses. Further dedicated studies, however, are required to optimize outcomes in this challenging patient cohort and to navigate the choice of approach for each individual patient.

Impact of mitral intervention on outcomes of patients with mitral valve dysfunction and annulus calcification.

OBJECTIVES: To compare all-cause mortality in patients with mitral annulus calcification (MAC) and severe mitral valve dysfunction (MVD) who received standard mitral intervention versus no intervention. BACKGROUND: Patients with MAC often have high surgical risk due to advanced age, comorbidities, and technical challenges related to calcium. The impact of a mitral intervention on outcomes of patients with MAC and severe MVD is not well known. METHODS: Retrospective review of patients with MAC by transthoracic echocardiography (TTE) in 2015 at a single institution. Patients with severe mitral stenosis (MS) or regurgitation (MR) were analyzed and stratified into two groups: surgical or transcatheter intervention performed <1 year after the index TTE, and no or later intervention. The primary endpoint was all-cause mortality. RESULTS: Of 5502 patients with MAC, 357 had severe MVD (MS = 27%, MR = 73%). Of those, 108 underwent mitral intervention (surgery = 87; transcatheter = 21). They were younger (73 ± 11 vs. 76 ± 11 years, p < 0.01) and less frequently had cardiovascular diseases compared with no-intervention. Frequency in women was similar (45% vs. 50%, p = 0.44). During median follow-up of 3.2 years, the intervention group had higher estimated survival than those without intervention (80% vs. 72% at 1 year and 55% vs. 35% at 4 year, p < 0.01). Adjusted for age, eGFR, LVEF < 50%, and pulmonary hypertension, mitral intervention was an independent predictor of lower mortality (hazard ratio = 0.66, 95% confidence interval 0.43-0.99, p = 0.046). CONCLUSION: Patients with MAC and severe MVD who underwent mitral intervention <1 year from index TTE had lower mortality than those without intervention. Mitral intervention was independently associated with lower mortality.

Transcatheter mitral valve replacement for degenerated mitral bioprostheses: a systematic review.

BACKGROUND: Treatment of degenerated mitral bioprostheses with transcatheter mitral valve-in-valve (MVIV) implantation is increasingly used. The goal of this review was to evaluate the one-year outcomes of this therapy using the most recent evidence. METHODS: A MEDLINE, Cochrane database and SCOPUS search was performed of published observational studies involving patients undergoing transcatheter MVIV for degenerated bioprosthesis to determine procedural success, thirty-day and one-year survival. RESULTS: A total of 2,684 patients undergoing transcatheter MVIV were identified from five studies with mean age of 73-75 years, 57-63% female and Society for Thoracic Surgery (STS) risk score ranging from 9-13%. Procedural technical success ranged from 94-98%, with 1-3% rates of periprocedural death, 0-2% stroke and 1-5% risk of left ventricular outflow tract (LVOT) obstruction. Thirty-day post-procedure mean mitral prosthetic gradient ranged from 6-7 mmHg and residual mitral regurgitation was mild or less in 96-100% of patients. Thirty-day survival and one-year survival ranged from 93-97% and 83-89% respectively. CONCLUSIONS: Transcatheter MVIV is an effective treatment for structural degeneration of biologic mitral valve replacement with low complication rates and favorable one-year outcomes. Accordingly, MVIV should be considered as a reasonable alternative to re-do surgical mitral valve replacement in high risk patients with comorbidities. Further study of long-term outcomes of this treatment is needed.