Performance of Purpose-Built vs Off-Label Transcatheter Devices for Aortic Regurgitation: The PURPOSE Study.

BACKGROUND: Severe pure aortic regurgitation (AR) carries a high mortality and morbidity risk, and it is often undertreated because of the inherent surgical risk. Transcatheter heart valves (THVs) have been used off-label in this setting with overall suboptimal results. The dedicated "purpose-built" Jena Valve Trilogy (JVT, JenaValve Technology) showed an encouraging performance, although it has never been compared to other THVs. OBJECTIVES: The aim of our study was to assess the performance of the latest iteration of THVs used off-label in comparison to the purpose-built JVT in inoperable patients with severe AR. METHODS: We performed a multicenter, retrospective registry with 18 participating centers worldwide collecting data on inoperable patients with severe AR of the native valve. A bicuspid aortic valve was the main exclusion criterion. The primary endpoints were technical and device success, 1-year all-cause mortality, and the composite of 1-year mortality and the heart failure rehospitalization rate. RESULTS: Overall, 256 patients were enrolled. THVs used off-label were used in 168 cases (66%), whereas JVT was used in 88 (34%). JVT had higher technical (81% vs 98%; P < 0.001) and device success rates (73% vs 95%; P < 0.001), primarily driven by significantly lower incidences of THV embolization (15% vs 1.1%; P < 0.001), the need for a second valve (11% vs 1.1%; P = 0.004), and moderate residual AR (10% vs 1.1%; P = 0.007). The permanent pacemaker implantation rate was comparable and elevated for both groups (22% vs 24%; P = 0.70). Finally, no significant difference was observed at the 1-year follow-up in terms of mortality (HR: 0.99; P = 0.980) and the composite endpoint (HR: 1.5; P = 0.355). CONCLUSIONS: The JVT platform has a better acute performance than other THVs when used off-label for inoperable patients with severe AR. A longer follow-up is conceivably needed to detect a possible impact on prognosis.

Impact of extra-mitral valve cardiac involvement in patients with primary mitral regurgitation undergoing transcatheter edge-to-edge repair.

BACKGROUND: In the context of primary mitral regurgitation (PMR), the selection of patients for transcatheter edge-to-edge repair (TEER) does not include a systematic assessment of PMR-associated cardiac remodelling. AIMS: We aimed to investigate the epidemiology and prognostic significance of different phenotypes of extra-mitral valve (MV) cardiac involvement in a large series of patients with PMR referred for TEER. METHODS: The study included 654 patients from the multicentre Italian GIOTTO registry, stratified into groups according to extra-mitral valve (MV) cardiac involvement. The primary endpoint was all-cause death at 2-year follow-up. RESULTS: Patients with no cardiac involvement (NI; n=58), left heart involvement (LHI; n=343) and right heart involvement (RHI; n=253) were analysed. Acute technical success was achieved in 98% of patients. Kaplan-Meier curve analysis revealed significantly worse survival in patients with LHI and RHI (p=0.041). On multivariate Cox regression analysis, extra-MV cardiac involvement, haemoglobin level and technical success were independent predictors of the primary endpoint occurrence. CONCLUSIONS: Grading cardiac involvement may help refine risk stratification, since at least 1 group of extra-MV cardiac involvement represents in itself a negative predictor of midterm outcome.

Prognostic Significance of Flail Mitral Leaflet in Transcatheter Edge-to-Edge Repair for Primary Mitral Regurgitation.

Despite the growing experience with MitraClip in the broad spectrum of mitral regurgitation (MR), limited data are available regarding the independent prognostic role on survival of different mitral regurgitation etiology subtypes. We sought to evaluate the impact of flail leaflet etiology in a large series of patients with primary MR (PMR) who underwent MitraClip treatment. The study included 588 patients with significant PMR from the multicenter GIOTTO (Italian Society of Interventional Cardiology [GIse] registry Of Transcatheter treatment of mitral valve regurgitaTiOn), stratified into 2 groups according to MR etiology: flail+ (n = 300) and flail- (n = 288). The primary end point was a composite of cardiac death and first rehospitalization for heart failure (HF). To account for the baseline differences, patients were propensity score-matched 1:1. Flail leaflet etiology was present in about a half of the patients. Acute technical success was achieved in 98% of the overall cohort, with no significant differences between the study groups (p = 0.789). At the 2-year Kaplan-Meier analysis, the primary end point occurred in 13% of flail+ patients compared with 23% in flail- (p = 0.009). The flail+ group presented lower rates of both cardiac death and rehospitalization for HF, whereas a similar overall death rate was observed between the groups. A multivariate Cox regression analysis identified flail leaflet etiology as an independent predictor of favorable outcome in terms of the primary end point (hazard ratio 0.141, 95% confidence interval 0.049 to 0.401, p <0.001). After propensity score matching, flail+ patients had confirmed lower rates of cardiac mortality and rehospitalization for HF but similar rates of overall death. In conclusion, flail leaflet-related etiology was common in patients with PMR who underwent MitraClip treatment and was an independent predictor of midterm favorable clinical outcomes.

Concomitant Transcatheter Edge-to-Edge Treatment of Secondary Tricuspid and Mitral Regurgitation: An Expert Opinion.

Secondary (functional) tricuspid regurgitation (sTR) is common in patients with mitral regurgitation (MR). Because combined valvular heart disease affects long-term survival, in comparison with isolated MR or tricuspid regurgitation, it is essential to offer patients adequate treatment. Despite considerable experience, no conclusive data are yet available on the prognostic impact of concomitant tricuspid valve surgery at the time of mitral valve surgery. Emerging transcatheter treatments offer the opportunity to treat both conditions (MR and sTR) simultaneously or in a stepwise fashion. This review provides a clinical overview on available data regarding the rationale for treatment of sTR in patients with relevant MR undergoing mitral transcatheter edge-to-edge repair, focusing on clinical and anatomical selection criteria.

Derivation and Validation of a Clinical Risk Score for COAPT-Ineligible Patients Who Underwent Transcatheter Edge-to-Edge Repair.

Up to half of real-world patients with secondary mitral regurgitation who underwent transcatheter edge-to-edge repair (TEER) do not meet the highly selective COAPT (Cardiovascular Outcomes Assessment of the MitraClip Percutaneous Therapy for Heart Failure Patients with Functional Mitral Regurgitation) criteria. No randomized trials or standardized and validated tools exist to evaluate the risk: benefit ratio of TEER in this specific population. We sought to derive and externally validate a clinical risk score to predict the risk of death or heart failure (HF) hospitalization for COAPT-ineligible patients who underwent TEER (CITE score). The study population consisted of patients with secondary mitral regurgitation having at least 1 exclusion criterion of the COAPT trial. The derivation cohort included 489 patients from the GIOTTO (GIse registry of Transcatheter treatment of Mitral Valve regurgitaTiOn) registry. Cox proportional hazards regression was used to identify predictors of 2-year death/HF hospitalization and develop a numerical risk score. The predictive performance was assessed in the derivation cohort and validated in 268 patients from the MiZüBr (Milan-Zürich-Brescia) registry. The CITE score (hemodynamic instability, left ventricular impairment, New York Heart Association class III/IV, peripheral artery disease, atrial fibrillation, brain natriuretic peptide, and hemoglobin) showed a c-index for 2-year death or HF hospitalization of 0.70 (95% confidence interval [CI] 0.67 to 0.73) in the derivation cohort, and 0.68 (95% CI 0.64 to 0.73) in the validation cohort. A cutoff of <12 points was selected to identify patients at lower risk of adverse outcomes, hazard ratio of 0.35 (95% CI 0.26 to 0.46). In conclusion, the CITE score is a simple 7-item tool for the prediction of death or HF hospitalization at 2 years after TEER in COAPT-ineligible patients. The score may support clinical decision-making by identifying those patients who, even if excluded from clinical trials, can still benefit from TEER.

First-in-Human Treatment of Severe Tricuspid Regurgitation Using a Novel Cross-Caval Heterotopic Device.

A 79-year-old woman, previously surgically treated for mitral and aortic valve replacement, experienced recurrent torrential tricuspid regurgitation after 2 transcatheter edge-to-edge repair procedures. Heart team assessment deemed the patient high risk for redo surgery and excluded transcatheter edge-to-edge repair and orthotopic replacement. The patient was then scheduled for a novel cross-caval device implantation.

Effect of Chronic Kidney Disease on 5-Year Outcome in Patients With Heart Failure and Secondary Mitral Regurgitation Undergoing Percutaneous MitraClip Insertion.

Chronic kidney disease (CKD) is strongly related to outcomes in cardiovascular diseases. Limited data are available regarding the independent prognostic role of CKD after transcatheter mitral valve repair with MitraClip. We sought to evaluate the real impact of CKD in a large series of patients with heart failure (HF) and secondary mitral regurgitation (SMR) who underwent MitraClip treatment. The study included 565 patients with severe SMR from a multicenter international registry. Patients were stratified into 3 groups according to estimated glomerular filtration rate (eGFR) assessment before MitraClip implantation: normal eGFR (≥60 ml/min/1.73 m2) (n = 196), mild-to-moderate CKD (30 to 59 ml/min/1.73 m2) (n = 267), and severe CKD (<30 ml/min/1.73 m2) (n = 102). The primary end point was a composite of overall death and the first rehospitalization for HF, the secondary end points were overall death, cardiac death, and first rehospitalization for HF. CKD was present in about 2/3 of patients. At 5-year Kaplan-Meier analysis, primary clinical end point occurred in 60% of patients with normal eGFR, compared with 73% cases in patients with mild-to-moderate CKD and 91% in patients with severe CKD (p <0.001). Long-term overall death rate significantly decreased with increasing eGFR, and cardiac death and rehospitalization for HF rates. Multivariate Cox regression analysis identified severe CKD as the strongest independent predictor of adverse outcome (hazard ratio 2.136, 95% confidence interval 1.164 to 3.918, p = 0.014). In conclusion, CKD affected about 2/3 of patients who underwent MitraClip treatment for severe SMR, and it was a strong and independent predictor of 5-year adverse outcomes.

Transcatheter edge-to-edge mitral valve repair in atrial functional mitral regurgitation: insights from the multi-center MITRA-TUNE registry.

BACKGROUND: A-FMR is considered a specific sub-type of secondary MR in patients with atrial fibrillation (AF) and preserved left ventricle ejection fraction (LVEF). Aim of the study was to investigate the acute and mid-term outcomes of transcatheter edge-to-edge mitral valve repair (TMVr) with the MitraClip in atrial functional mitral regurgitation (A-FMR). METHODS: The study included patients with A-FMR and concomitant AF who underwent to the MitraClip at 7 Italian Centers. Aim of the study was to assess the safety, efficacy and mid-term cardiovascular outcomes. RESULTS: After reviewing 1153 patients with FMR treated with TMVr from 2009 to 2021, 87 patients (median age 81 years, 61% female) with A-FMR were identified. Technical success was achieved in 97%, 30-day device success in 83% and 30-day procedural success in 80%. All-cause death at 30-day was 5%. Estimated two-year freedom from all-cause death and cardiac death was 60% and 77%, respectively, whereas freedom from all-cause death/heart failure hospitalization was 55%. Residual MR ≤ 2+ was encountered in 89% (n = 47/53) and improvement in NYHA class I/II in 79% (n = 48/61). Post-procedural MR ≥ 2+ (HR 5.400, CI 1.371-21.268) and inter-commissural annular diameter ≥ 35 mm (HR 4.159, CI 1.057-16.363) were independent predictors of all-cause death/heart failure hospitalization during the follow-up. Positive reverse remodeling of left atrium and mitral annular dimensions occurred after TMVr during the follow-up. CONCLUSIONS: MitraClip resulted to be a safe and effective option to treat A-FMR in elderly patients.

Transcatheter Edge-to-Edge Repair in COAPT-Ineligible Patients: Incidence and Predictors of 2-Year Good Outcome.

BACKGROUND: COAPT-trial entry criteria are useful to identify patients with better outcomes after transcatheter edge-to-edge repair (TEER). However, up to one-half of real-world patients with secondary mitral regurgitation (SMR) undergoing TEER do not meet these highly selective criteria and no study has formally investigated them. The aim of this study was to evaluate the predictors of good outcome after TEER in COAPT-ineligible patients. METHODS: All consecutive patients with SMR and heart failure (HF) treated with MitraClip at 3 European centres were retrospectively screened. The presence of at least 1 COAPT exclusion criterion was used to define a COAPT-ineligible profile, allowing the inclusion in the study population. Freedom from all-cause death or HF hospitalisation was evaluated at 2-year follow-up (primary end point). RESULTS: A total of 305 patients (47%) had a COAPT-ineligible profile. An overall 58% rate of all-cause death or HF hospitalisation was detected at 2 years. Patients with a single COAPT exclusion criterion experienced fewer adverse events than those with multiple criteria (55% vs 69%). At multivariable Cox regression analysis, New York Heart Association functional class II, younger age (< 75 years), lower serum creatinine (< 2 mg/dL), lower left ventricular end-diastolic volume (< 240 mL), and the absence of hemodynamic instability, atrial fibrillation, and chronic obstructive pulmonary disease were independently associated with good outcome. CONCLUSIONS: In this real-world series of patients with SMR undergoing TEER, a COAPT-ineligible profile was common. The presence of only 1 COAPT exclusion criterion or the absence of hemodynamic instability were associated with the most favourable outcomes.

Prognostic significance of right ventricle to pulmonary artery coupling in patients with mitral regurgitation treated with the MitraClip system.

OBJECTIVES: To evaluate the prognostic impact of baseline tricuspid annular plane systolic excursion/pulmonary artery systolic pressure (TAPSE/PASP) ratio, as an expression of the right ventricle-pulmonary artery (RV-PA) coupling, in patients with mitral regurgitation (MR) treated with the MitraClip. BACKGROUND: Impaired RV to PA coupling is considered a marker of RV dysfunction. METHODS: From February 2016 to February 2020, a total of 165 patients were evaluated and stratified in two groups according to a prespecified value of TAPSE/PASP ratio ≤ 0.36. RESULTS: The median patients' age was 79 (men: 62.4%). Sixty-three patients (38.1%) presented TAPSE/PASP ≤ 0.36 and were then compared with patients with TAPSE/PASP > 0.36. Functional MR etiology was more frequent in TAPSE/PASP ≤ 0.36 (71.4%; p = 0.046). Acute technical success was achieved in 92.7% of the population, without any significant difference between the two groups of study and with sustained results at 30-day (device success: 85.5%; procedural success: 84.8%). On multivariate Cox regression analysis, after correction for body mass index, chronic kidney disease and left ventricle ejection fraction ≥30% but <50%, TAPSE/PASP ≤ 0.36 remained a sustained predictor of mortality and hospitalization for heart failure at one year after MitraClip (hazard ratio: 3.87; 95% confidence interval: 1.83-8.22; p ≤ 0.001). Kaplan-Meier all-cause mortality and heart failure hospitalization rates at one year were consequently higher in patients with TAPSE/PASP ≤ 0.36 (39.4% vs. 14.8%; log-rank p ≤ 0.001). CONCLUSION: Baseline TAPSE/PASP ratio seems independently associated with all-cause mortality and heart failure hospitalization after MitraClip both in functional and degenerative MR.

Pre-admission acetylsalicylic acid therapy and impact on in-hospital outcome in COVID-19 patients: The ASA-CARE study.

BACKGROUND: Patients with coronavirus disease 2019 (COVID-19) exhibit high thrombotic risk. The evidence on a potential independent prognostic role of antiplatelet treatment in those patients is limited. The aim of the study was to evaluate the prognostic impact of pre-admission low-dose acetylsalicylic acid (ASA) in a wide series of hospitalized patients with COVID-19. METHODS: This cohort study included 984 COVID-19 patients stratified according to ASA intake before hospitalization: ASA+ (n = 253) and ASA- (n = 731). Patients were included in ASA+ group if they received it daily in the 7 days before admission. 213 (83%) were on ASA 100 mg daily. Primary endpoint was a composite of in-hospital death and/or need for respiratory support upgrade, secondary endpoints were in-hospital death and need for respiratory support upgrade. RESULTS: Mean age was 72 [62; 81] with 69% of male patients. ASA+ patients were significantly older, with higher prevalence of comorbidities. No significant differences regarding the degree of respiratory dysfunction were observed. At 30-day Kaplan-Meier analysis, ASA+ patients had higher survival free from the primary endpoint and need for respiratory support upgrade, conversely in-hospital death did not significantly differ between groups. At multivariate analysis ASA intake was independently associated with a lower probability of reaching primary endpoint (HR 0.697, 95% C.I. 0.525-0.924; p = 0.012). CONCLUSIONS: In COVID-19 patients undergoing hospitalization, pre-admission treatment with ASA is associated with better in-hospital outcome, mainly driven by less respiratory support upgrade.

Infection, Infectious Agents and Vascular Disease.

BACKGROUND: Infectious agents may be involved in the pathogenesis of vascular disease and related complications. The aim of this review is to analyze the most relevant information on the common infections related to vascular disease, discussing the main pathophysiological mechanisms. METHODS: In the current review, the most important evidence on the issue of infections and vascular disease is searched on Medline, Scopus, and ScienceDirect database. RESULTS: Among infectious agents, herpesviruses, parvovirus B19, hepatitis viruses, human immunodeficiency virus, severe acute respiratory syndrome coronavirus 2, treponema pallidum, mycobacterium tuberculosis, pseudomonas aeruginosa, staphylococcus aureus, and candida albicans seem to particularly related to vascular disease. CONCLUSION: Infectious agents may affect vessel's homeostasis and functionality, both on the arterial and venous side, by means of several pathophysiological mechanisms such as dysregulation in vasomotor function, thromboembolic complications, initiation and progression of atherosclerosis, alteration of perivascular adipose tissue, recruiting inflammatory cells and molecules.

Prognostic Value of Pre-operative Atrial Fibrillation in Patients With Secondary Mitral Regurgitation Undergoing MitraClip Implantation.

Limited data are available regarding the independent prognostic role of preoperative atrial fibrillation (AF) after transcatheter mitral valve repair with MitraClip. We sought to evaluate the impact of preoperative AF in patients with heart failure (HF) and concomitant secondary mitral regurgitation (MR) after MitraClip treatment. The study included 605 patients with significant secondary MR from a multicenter international registry. Patients were stratified into 2 groups according to the presence or absence of preoperative AF. Primary end point was 5-year overall death, secondary end points were 5-year cardiac death and first re-hospitalization for HF. To account for baseline differences, patients were propensity score matched 1:1. The overall prevalence of preoperative AF was 44%. At 5-year Kaplan-Meier analysis, compared with patients without AF, those with AF had significantly more adverse events in term of overall death (67% vs 43%; HR 1.84, log-rank p <0.001) and cardiac death (56% vs 29%; HR 2.11, log-rank p <0.001) and re-hospitalization for HF (63% vs 52%; HR 1.33, log-rank p = 0.048). Multivariate analysis identified AF as independent predictor of worse outcome in term of primary end point (HR 1.729, 95% C.I. 1.060 to 2.821; p = 0.028). After propensity score matching, patients with AF had higher rates of death and cardiac mortality but similar rates of re-hospitalization for HF. In conclusion, in patients with HF undergoing MitraClip treatment for secondary MR, preoperative AF is common and an unfavourable predictor of 5-year death and cardiac death. However, AF did not affect the frequency of re-hospitalization for HF.

Mid-Term Clinical Outcomes Following Percutaneous Mitral Valve Edge-to-Edge Repair.

BACKGROUND: Approximately 50% of patients with severe mitral regurgitation (MR) referred for surgery have prohibitive surgical risk. MitraClip (Abbott Vascular) is an alternative therapy option in these patients. The aim of this study is to evaluate mid-term outcome in patients who underwent MitraClip implantation. METHODS: All consecutive patients with ≥2+ MR and high risk for conventional surgical therapy who underwent MitraClip implantation at our unit were included in the analysis. The primary endpoint was all-cause mortality and secondary endpoint was heart failure rehospitalization. RESULTS: From October 2008 to December 2016, a total of 162 patients underwent MitraClip procedure at our unit. The mean follow-up duration was 819.8 ± 671.1 days. Acute procedural success was achieved in 141 of 162 patients (87.0%) and was not significantly different between primary and secondary MR patients (P=.09). Mortality rates were 14.4%, 28.7%, 38.7%, and 49.3% at 1 year, 2 years, 3 years, and 5 years, respectively. Rehospitalization rates for heart failure were 21.7%, 34.3%, 44.2%, and 56.6% at 1 year, 2 years, 3 years, and 5 years, respectively. At follow-up, patients exhibited significant improvement in New York Heart Association functional classification (P<.001). On multivariate analysis, baseline left ventricular ejection fraction (LVEF) <30% (odds ratio, 6.62) and baseline MR severity (odds ratio, 3.40) were the strongest predictors of mortality. Primary MR (odds ratio, 0.20) was associated with lower risk of mortality compared with secondary MR. CONCLUSIONS: Treatment of MR with MitraClip results in significant symptomatic improvement with excellent short-term results. However, 5-year mortality was 49.3%; baseline LVEF <30% and MR severity are the strongest predictors of mortality, while primary MR was a predictor for lower risk of mortality when compared with secondary MR.