Extracellular Vesicles to Predict Outcomes After Transcatheter Aortic Valve Implantation - a Prospective, Multicenter Cohort Study.

INTRODUCTION: Transcatheter aortic valve implantation (TAVI) is an established treatment for aortic stenosis (AS) in patients at intermediate and high surgical risk. Circulating extracellular vesicles (EVs) are nanoparticles involved in cardiovascular diseases. We aimed to (i) determine the effect of TAVI on plasma concentrations of five EV subtypes and (ii) evaluate the predictive value of EVs for post-TAVI outcomes. METHODS: Blood samples were collected 1 day before TAVI and at hospital discharge. Concentrations of EVs were evaluated using flow cytometry. RESULTS: Concentration of leukocytes EVs decreased after TAVI, compared to the measurement before (p = 0.008). Among 123 patients discharged from the hospital, 19.5% experienced MACCE during the median of 10.3 months. Increased pre-TAVI concentration of phosphatidylserine-exposing EVs was an independent predictor of MACCE in multivariable analysis (OR 5.313, 95% CI 1.164-24.258, p = 0.031). CONCLUSIONS: Patients with increased pre-TAVI concentration of procoagulant, PS-exposing EVs have over fivefold higher odds of adverse outcomes.

Transcatheter Intervention for Inoperable Tricuspid Surgical Prosthesis Dysfunction: Minimally Invasive Approach to Mitigate Heart Failure.

What is the efficacy and safety of transcatheter tricuspid valve-in-valve implantation for patients with inoperable tricuspid surgical prosthesis dysfunction? Thirty-day mortality after greatly effective transcatheter treatment is 2 times less than the estimated surgical risk.

Gender differences in the development of heart failure after acute coronary syndrome: Insight from the CORALYS registry.

BACKGROUND: Impact of gender on heart remodeling after acute coronary syndrome (ACS) and consequently on development of heart failure (HF) remains to be elucidated. METHODS: CORALYS is a multicenter, retrospective, observational registry enrolling consecutive patients admitted for ACS and treated with percutaneous coronary intervention. HF hospitalization was the primary endpoint while all-cause mortality and the composite endpoint of incidence of first HF hospitalization and cardiovascular mortality were the secondary ones. RESULTS: Among 14,699 patients enrolled in CORALYS registry, 4578 (31%) were women and 10,121 (69%) males. Women were older, had more frequently hypertension and diabetes and less frequently smoking habit. History of myocardial infarction (MI), STEMI at admission and multivessel disease were less common in women. After median follow up of 2.9 ± 1.8 years, women had higher incidence of primary and secondary endpoints and female sex was an independent predictor of HF hospitalization (HR 1.26;1.05-1.50; p = 0.011) and cardiovascular death/HF hospitalization (HR 1.18;1.02-1.37; p = 0.022). At multivariable analysis women and men share as predictors of HF diabetes, history of cancer, chronic kidney disease, atrial fibrillation, complete revascularization and left ventricular ejection fraction. Chronic obstructive pulmonary disease (HR 2.34;1.70-3.22, p < 0.001) and diuretics treatment (HR 1.61;1.27-2.04, p < 0.001) were predictor of HF in men, while history of previous MI (HR 1.46;1.08-1.97, p = 0.015) and treatment with inhibitors of renin-angiotensin system (HR 0.69;0,49-0.96 all 95% CI, p = 0.030) in women. CONCLUSIONS: Women are at increased risk of HF after ACS and gender seems to be an outcome-modifier of the relationship between a variable and primary outcome.

1-Year Outcomes Following Transfemoral Transseptal Transcatheter Mitral Valve Replacement: The HighLife TSMVR Feasibility Study.

BACKGROUND: A significant number of patients with severe mitral regurgitation (MR) are not suitable for either surgical or transcatheter edge-to-edge repair because of high surgical risk or inappropriate mitral valve anatomy. OBJECTIVES: The aim of this study was to evaluate the HighLife Trans-Septal Mitral Valve Replacement (TSMVR) system in patients with symptomatic MR and high surgical risk. METHODS: This prospective, multicenter, nonrandomized feasibility study evaluated the safety and performance of the HighLife TSMVR system in patients with moderate to severe or severe symptomatic MR during 1-year follow-up. Echocardiographic data were assessed at an independent core laboratory. RESULTS: A total of 30 patients (mean age 75.6 years, 27% women, median Society of Thoracic Surgeons score 5.5%) with severe MR (90% with secondary MR, median left ventricular ejection fraction 43%) were treated at 13 sites. In 27 of the 30 patients, the HighLife TSMVR system was implanted successfully (technical success rate 90%). Device success at 30 days was 83%. After 1 year, 5 patients (17%) had died. None of the patients who underwent implantation required mitral valve reintervention. All patients who underwent implantation had no or trace (78%) or mild (22%) MR, the mean gradient of the HighLife valve was 5.1 mm Hg, and there were no signs of left ventricular outflow tract obstruction (mean gradient 2.0 mm Hg). CONCLUSIONS: The 1-year results from the HighLife TSMVR feasibility study demonstrate a high technical success rate, excellent valve function, no left ventricular outflow tract obstruction, and no need for mitral valve reintervention. Additional patient outcomes and longer follow-up are needed to confirm these findings. (Expanded Study of the HighLife 28mm Trans-Septal Trans-Catheter Mitral Valve in Patients With Moderate-Severe or Severe Mitral Regurgitation and at High Surgical Risk; NCT04029363).

Safety and efficacy of percutaneous atrial appendage closure followed by antiplatelet therapy in a high-risk population: single-center experience with a WATCHMAN device.

Introduction: In our everyday practice we encounter many patients with non-valvular atrial fibrillation with either a contraindication to oral anticoagulation or with its inefficiency. Aim: To investigate whether left atrial appendage closure (LAAC) followed by post-procedure antiplatelet therapy is safe and efficient in a high-risk population. Material and methods: Ninety-one (48 males) consecutive patients with non-valvular atrial fibrillation (NVAF) underwent an LAAC procedure using a first-generation WATCHMAN 2.5 device followed by antiplatelet therapy. Clinical and transesophageal echocardiography data were collected at baseline and at the follow-up visit. Results: The median (IQR) CHA2DS2-VASc score was 5 (4.0-6.0) and the HAS-BLED score was 3 (3.0-4.0); the mean (SD) age was 74.4 (8.4). A bleeding history was observed in 89% of patients and 24.2% of patients had a history of stroke or transient ischemic attack (TIA). The procedure was successful in 98.9%. Post-procedure therapy was dual antiplatelet therapy in 85 patients; 3 patients received single antiplatelet therapy and the therapy was maintained until the follow-up visit. Peri-procedural complications were tamponade (3.3%), pericardial effusion (2.2%) and two deaths (2.2%) with no bleeding or vascular complications. The median follow-up was 67 (52.75-84.75) days. Primary safety endpoint (bleeding BARC type 3 or more, tamponade, pericardial effusion, and device embolization) and primary efficacy endpoint (stroke or TIA, hemorrhagic stroke, peripheral embolism, cardiovascular (CV) and non-CV death) were observed in 2 and 4 patients, respectively. Conclusions: The LAAC procedure followed by antiplatelet therapy seems to be safe and efficient in the high-risk population. Further studies in this field are required.

Long-term mortality after transcatheter aortic valve implantation for aortic stenosis in immunosuppression-treated patients: a propensity-matched multicentre retrospective registry-based analysis.

Introduction: Data regarding patients with a previous medical record of immunosuppression treatment who have undergone transcatheter aortic valve implantation (TAVI) are limited and extremely inconclusive. Available studies are mostly short term observations; thus there is a lack of evidence on efficacy and safety of TAVI in this specific group of patients. Aim: To compare the in-hospital and long-term outcomes between patients with or without a medical history of immunosuppressive treatment undergoing TAVI for aortic valve stenosis (AS). Material and methods: We conducted a retrospective registry-based analysis including patients undergoing TAVI for AS at 5 centres between January 2009 and August 2017. The primary endpoint was long-term all-cause mortality. Secondary endpoints comprised major vascular complications, life-threatening or disabling bleeding, stroke and new pacemaker implantation. Results: Of 1451 consecutive patients who underwent TAVI, two propensity-matched groups including 25 patients with a history of immunosuppression and 75 patients without it were analysed. No differences between groups in all-cause mortality were found in a median follow-up time of 2.7 years following TAVI (p = 0.465; HR = 0.73; 95% CI: 0.30-1.77). The rate of major vascular complications (4.0% vs. 5.3%) was similar in the two groups (p = 1.000). There were no statistically significant differences in the composite endpoint combining life-threatening or disabling bleeding, major vascular complications, stroke and new pacemaker implantation (40.0% vs. 20.0%, p = 0.218). Conclusions: Patients who had undergone TAVI for AS had similar long-term mortality regardless of whether they had a previous medical record of immunosuppression. Procedural complication rates were comparable between the groups.

Impact of previous coronary artery revascularization on outcomes in patients undergoing transcatheter aortic valve implantation.

Introduction: Coexistence of coronary artery disease (CAD) in patients with severe aortic stenosis (AS) referred for transcatheter aortic valve implantation (TAVI) raises questions regarding the safety and efficacy of TAVI in this subset of patients. Aim: To evaluate the impact of previous coronary revascularization in terms of percutaneous coronary intervention (PCI) or coronary artery bypass grafting (CABG) on clinical outcomes after TAVI. Material and methods: A total of 507 consecutive patients who underwent TAVI were divided into: non-revascularization (NR), post-PCI and post-CABG groups. The endpoints were established according to VARC-2 definitions. Results: Patients with previous coronary revascularization (36.7% of the population) were younger, more often male and their EuroSCORE II risk evaluation was significantly higher (NR 7.9% vs. post-PCI 8.0% vs. post-CABG 20.5%, p < 0.0001). Patients after PCI or CABG prior to TAVI had similar 30-day all-cause mortality rates as those without coronary revascularization at baseline (NR vs. post-PCI vs. post-CABG: 8.1% vs. 5.5% vs. 6.8%, respectively; p = 0.6). There were no differences in 12-month all-cause mortality rates between groups (NR vs. post-PCI vs. post-CABG: 15.3% vs. 14.2% vs. 16.9%, respectively; log-rank p = 0.67). In the Cox proportional-hazards regression model, acute kidney injury stage 2-3 (HR = 3.7, 95% CI: 2.14-6.33; p < 0.001) and post-TAVI stroke (HR = 3.5, 95% CI: 1.57-7.8; p = 0.002) were independently correlated with 1-year mortality. Conclusions: TAVI seems to be a safe and effective procedure for the treatment of severe AS in patients with previous coronary revascularization.

Forecasting the Risk of Heart Failure Hospitalization After Acute Coronary Syndromes: the CORALYS HF Score.

The present study aimed to identify patients at a higher risk of hospitalization for heart failure (HF) in a population of patients with acute coronary syndrome (ACS) treated with percutaneous coronary revascularization without a history of HF or reduced left ventricular (LV) ejection fraction before the index admission. We performed a Cox regression multivariable analysis with competitive risk and machine learning models on the incideNce and predictOrs of heaRt fAiLure After Acute coronarY Syndrome (CORALYS) registry (NCT04895176), an international and multicenter study including consecutive patients admitted for ACS in 16 European Centers from 2015 to 2020. Of 14,699 patients, 593 (4.0%) were admitted for the development of HF up to 1 year after the index ACS presentation. A total of 2 different data sets were randomly created, 1 for the derivative cohort including 11,626 patients (80%) and 1 for the validation cohort including 3,073 patients (20%). On the Cox regression multivariable analysis, several variables were associated with the risk of HF hospitalization, with reduced renal function, complete revascularization, and LV ejection fraction as the most relevant ones. The area under the curve at 1 year was 0.75 (0.72 to 0.78) in the derivative cohort, whereas on validation, it was 0.72 (0.67 to 0.77). The machine learning analysis showed a slightly inferior performance. In conclusion, in a large cohort of patients with ACS without a history of HF or LV dysfunction before the index event, the CORALYS HF score identified patients at a higher risk of hospitalization for HF using variables easily accessible at discharge. Further approaches to tackle HF development in this high-risk subset of patients are needed.

Impact of Complete Revascularization on Development of Heart Failure in Patients With Acute Coronary Syndrome and Multivessel Disease: A Subanalysis of the CORALYS Registry.

Background The impact of complete revascularization (CR) on the development of heart failure (HF) in patients with acute coronary syndrome and multivessel coronary artery disease undergoing percutaneous coronary intervention remains to be elucidated. Methods and Results Consecutive patients with acute coronary syndrome with multivessel coronary artery disease from the CORALYS (Incidence and Predictors of Heart Failure After Acute Coronary Syndrome) registry were included. Incidence of first hospitalization for HF or cardiovascular death was the primary end point. Patients were stratified according to completeness of coronary revascularization. Of 14 699 patients in the CORALYS registry, 5054 presented with multivessel disease. One thousand four hundred seventy-three (29.2%) underwent CR, while 3581 (70.8%) did not. Over 5 years follow-up, CR was associated with a reduced incidence of the primary end point (adjusted hazard ratio [HR], 0.66 [95% CI, 0.51-0.85]), first HF hospitalization (adjusted HR, 0.67 [95% CI, 0.49-0.90]) along with all-cause death and cardiovascular death alone (adjusted HR, 0.74 [95% CI, 0.56-0.97] and HR, 0.56 [95% CI, 0.38-0.84], respectively). The results were consistent in the propensity-score matching population and in inverse probability treatment weighting analysis. The benefit of CR was consistent across acute coronary syndrome presentations (HR, 0.59 [95% CI, 0.39-0.89] for ST-segment elevation myocardial infarction and HR, 0.71 [95% CI, 0.50-0.99] for non-ST-elevation acute coronary syndrome) and in patients with left ventricular ejection fraction >40% (HR, 0.52 [95% CI, 0.37-0.72]), while no benefit was observed in patients with left ventricular ejection fraction ≤40% (HR, 0.77 [95% CI, 0.37-1.10], P for interaction 0.04). Conclusions CR after acute coronary syndrome reduced the risk of first hospitalization for HF and cardiovascular death, as well as first HF hospitalization, and cardiovascular and overall death both in patients with ST-segment elevation myocardial infarction and non-ST-elevation acute coronary syndrome. Registration URL: https://www.clinicaltrials.gov; Unique identifier: NCT04895176.

Optimal medical therapy improves outcomes in patients with diabetes mellitus and acute myocardial infarction.

AIMS: We aimed to explored the association between the use of optimal medical therapy (OMT) in patients with myocardial infarction (AMI) and diabetes mellitus (DM) and clinical outcomes. METHODS: Bleeding complications in a Multicenter registry of patients discharged with diagnosis of Acute Coronary Syndrome (BleeMACS) is an international registry that enrolled participants with acute coronary syndrome followed up for at least 1 year across 15 centers from 2003 to 2014. Baseline characteristics and endpoints were analyzed. RESULTS: Among 3095 (23.2%) patients with AMI and DM, 1898 (61.3%) received OMT at hospital discharge. OMT was associated with significantly reduced mortality (4.3% vs. 10.8%, p < 0.001), re-AMI (4.4% vs. 8.1%, p < 0.001), and composite endpoint of death/re-AMI (8.0% vs. 17.6%, p < 0.001). No difference was observed among regions. Propensity score matching confirmed that OMT significantly associated with lower mortality. After adjusting for confounding variables, OMT, drug-eluting stents, and complete revascularization were independent protective factors of 1-year mortality, whereas left ventricular ejection fraction and age were risk factors. CONCLUSIONS: Guideline-recommended OMT was prescribed at suboptimal frequencies with geographic variations in this worldwide cohort. OMT can improve long-term clinical outcomes in patients with DM and AMI. CLINICAL TRIAL REGISTRATION: NCT02466854 June 9, 2015.

Valve-in-valve transcatheter transfemoral mitral valve implantation (ViV-TMVI): Characteristics and early results from nationwide registry.

BACKGROUND: Valve-in-valve transcatheter transfemoral mitral valve implantation (ViV-TMVI) is an emerging treatment alternative to reoperation in high surgical risk patients with a failed mitral bioprostheses. AIM: To describe characteristics and evaluate 30-day outcomes of ViV-TMVI in the Polish population. METHODS: Nationwide registry was initiated to collect data of all patients with failed mitral bioprosthesis undergoing ViV-TMVI in Poland. This study presents 30-days clinical and echocardiographic follow-up. RESULTS: Overall, 27 ViV-TMVI were performed in 8 centers until May 2022 (85% since 2020). Mean (standard deviation [SD]) age was 73 (11.6) years with the median (interquartile range [IQR]) STS score of 5.3% (4.3%-14.3%). Mean (SD) time between surgical implantation and ViV-TMVI was 8.2 (3.2) years. Failed Hancock II (29%) and Perimount Magna (22%) were most frequently treated. Mechanisms of failure were equally often pure mitral regurgitation or stenosis (both 37%) with mixed etiology in 26%. Balloon-expandable Sapien 3/Ultra were used in all but 1 patient. Technical success was 96.3% (1 patient required additional prosthesis). Mean (SD) transvalvular mitral gradient reached 6.7 (2.2) mm Hg and mitral valve area was 1.8 (0.4) cm². None of the patients had moderate or severe mitral regurgitation with only 14.8% graded as mild. In 92.6% device success (2 patients had mean gradient ≥10 mm Hg) and in 85.6% procedural success was present. There were no deaths, cerebrovascular events or need for mitral valve surgery during 30-day follow-up. CONCLUSIONS: In short-term observation ViV-TMVI is safe and effective alternative for patients with failed mitral bioprosthesis at high surgical risk of re-operation. Longer observations on larger sample are warranted.

Impact of Enterococci vs. Staphylococci Induced Infective Endocarditis after Transcatheter Aortic Valve Implantation.

BACKGROUND: The two most common organisms found in infective endocarditis following transcatheter aortic valve implantation (TAVI-IE) are enterococci (EC-IE) and staphylococci (SC-IE). We aimed to compare clinical characteristics and outcomes of patients with EC-IE and SC-IE. METHODS: TAVI-IE patients from 2007 to 2021 were included in this analysis. The 1-year mortality was the primary outcome measure of this retrospective multi-center analysis. RESULTS: Out of 163 patients, 53 (32.5%) EC-IE and 69 (42.3%) SC-IE patients were included. Subjects were comparable with regard to age, sex, and clinically relevant baseline comorbidities. Symptoms at admission were not significantly different between groups, except for a lower risk for presenting with septic shock in EC-IE than SC-IE. Treatment was performed in 78% by antibiotics alone and in 22% of patients by surgery and antibiotics, with no significant differences between groups. The rate of any complication, in particular heart failure, renal failure, and septic shock during treatment for IE, was lower in EC-IE compared with SC-IE (p < 0.05). In-hospital (EC-IE: 36% vs. SC-IE: 56%, p = 0.035) and 1-year mortality (EC-IE: 51% vs. SC-IE: 70%, p = 0.009) were significantly lower in EC-IE compared with SC-IE. CONCLUSIONS: EC-IE, compared with SC-IE, was associated with a lower morbidity and mortality. However, absolute numbers are high, a finding that should trigger further research in appropriate perioperative antibiotic management and improvement of early IE diagnosis in the case of clinical suspicion.

Machine learning for prediction of all-cause mortality after transcatheter aortic valve implantation.

AIMS: Prediction of adverse events in mid-term follow-up after transcatheter aortic valve implantation (TAVI) is challenging. We sought to develop and validate a machine learning model for prediction of 1-year all-cause mortality in patients who underwent TAVI and were discharged following the index procedure. METHODS AND RESULTS: The model was developed on data of patients who underwent TAVI at a high-volume centre between January 2013 and March 2019. Machine learning by extreme gradient boosting was trained and tested with repeated 10-fold hold-out testing using 34 pre- and 25 peri-procedural clinical variables. External validation was performed on unseen data from two other independent high-volume TAVI centres. Six hundred four patients (43% men, 81 ± 5 years old, EuroSCORE II 4.8 [3.0-6.3]%) in the derivation and 823 patients (46% men, 82 ± 5 years old, EuroSCORE II 4.7 [2.9-6.0]%) in the validation cohort underwent TAVI and were discharged home following the index procedure. Over the 12 months of follow-up, 68 (11%) and 95 (12%) subjects died in the derivation and validation cohorts, respectively. In external validation, the machine learning model had an area under the receiver-operator curve of 0.82 (0.78-0.87) for prediction of 1-year all-cause mortality following hospital discharge after TAVI, which was superior to pre- and peri-procedural clinical variables including age 0.52 (0.46-0.59) and the EuroSCORE II 0.57 (0.51-0.64), P < 0.001 for a difference. CONCLUSION: Machine learning based on readily available clinical data allows accurate prediction of 1-year all-cause mortality following a successful TAVI.

Nationwide experience with transcarotid transcatheter aortic valve implantation: Insights from the POL-CAROTID registry.

BACKGROUND: The carotid artery is an alternative access route for transcatheter aortic valve implantation (TAVI), especially useful in patients unsuitable for traditional access routes including transfemoral (TF), subclavian, transapical, and aortic. AIMS: To investigate the feasibility and safety of transcarotid (TC) access for TAVI in comparison to the TF approach in a multicenter setting. METHODS: A total of 41 patients, treated between December 2014 and December 2018, were retrospectively reported to the Polish Registry of Common Carotid Artery Access for TAVI (POL-CAROTID). The median follow-up time was 619 (365-944) days, and Valve Academic Research Consortium-2 (VARC-2) definitions were applied. Clinical outcomes were compared with 41 propensity-matched TF-TAVI patients. RESULTS: The mean (standard deviation [SD]) patients' age was 78.0 (7.2) years, and 29 patients (70.7%) were men. Prohibitive iliofemoral anatomy and/or obesity (46.3%) and/or the presence of a stent graft in the abdominal aorta (31.7%) were the most common indications for TC-TAVI. Device success for TC-TAVI was comparable with the matched TF-TAVI group (90.2% vs. 95.3%, respectively, P = 0.396), and no periprocedural mortality was observed. Moreover, early safety was similar between the two groups (92.7% vs. 95.3%, respectively, log-rank P = 0.658) with only 1 case of non-disabling stroke during the first month after TC-TAVI. Consequently, no cerebrovascular events were observed in the mid-term, and the clinical efficacy of TC-TAVI corresponded well with TF-TAVI (90.2% vs. 92.7%, respectively, log-rank P = 0.716). A total of 4 (9.8%) deaths were noted in the TC-TAVI cohort in comparison to 3 (7.3%) in the TF-TAVI group. CONCLUSIONS: The results of the study indicated that the first cohort of Polish patients with implantations of second-generation transcarotid transcatheter heart valves had a similar prognosis to TF-TAVI with regard to safety and feasibility. TC access may be considered an optimal alternative for patients in whom the TF approach is precluded.