Percutaneous repair of moderate-to-severe or severe functional mitral regurgitation in patients with symptomatic heart failure: Baseline characteristics of patients in the RESHAPE-HF2 trial and comparison to COAPT and MITRA-FR trials.

AIM: The RESHAPE-HF2 trial is designed to assess the efficacy and safety of the MitraClip device system for the treatment of clinically important functional mitral regurgitation (FMR) in patients with heart failure (HF). This report describes the baseline characteristics of patients enrolled in the RESHAPE-HF2 trial compared to those enrolled in the COAPT and MITRA-FR trials. METHODS AND RESULTS: The RESHAPE-HF2 study is an investigator-initiated, prospective, randomized, multicentre trial including patients with symptomatic HF, a left ventricular ejection fraction (LVEF) between 20% and 50% with moderate-to-severe or severe FMR, for whom isolated mitral valve surgery was not recommended. Patients were randomized 1:1 to a strategy of delivering or withholding MitraClip. Of 506 patients randomized, the mean age of the patients was 70 ± 10 years, and 99 of them (20%) were women. The median EuroSCORE II was 5.3 (2.8-9.0) and median plasma N-terminal pro-B-type natriuretic peptide (NT-proBNP) was 2745 (1407-5385) pg/ml. Most patients were prescribed beta-blockers (96%), diuretics (96%), angiotensin-converting enzyme inhibitors/angiotensin receptor blockers/angiotensin receptor-neprilysin inhibitors (82%) and mineralocorticoid receptor antagonists (82%). The use of sodium-glucose cotransporter 2 inhibitors was rare (7%). Cardiac resynchronization therapy (CRT) devices had been previously implanted in 29% of patients. Mean LVEF, left ventricular end-diastolic volume and effective regurgitant orifice area (EROA) were 31 ± 8%, 211 ± 76 ml and 0.25 ± 0.08 cm2, respectively, whereas 44% of patients had mitral regurgitation severity of grade 4+. Compared to patients enrolled in COAPT and MITRA-FR, those enrolled in RESHAPE-HF2 were less likely to have mitral regurgitation grade 4+ and, on average, HAD lower EROA, and plasma NT-proBNP and higher estimated glomerular filtration rate, but otherwise had similar age, comorbidities, CRT therapy and LVEF. CONCLUSION: Patients enrolled in RESHAPE-HF2 represent a third distinct population where MitraClip was tested in, that is one mainly comprising of patients with moderate-to-severe FMR instead of only severe FMR, as enrolled in the COAPT and MITRA-FR trials. The results of RESHAPE-HF2 will provide crucial insights regarding broader application of the transcatheter edge-to-edge repair procedure in clinical practice.

Aortic valve replacement for aortic stenosis: Influence of centre volume on TAVR adoption rates and outcomes in France.

BACKGROUND: Transcatheter (TAVR) has supplanted surgical (SAVR) aortic valve replacement (AVR). AIM: To evaluate whether adoption of this technology has varied according to centre volume at the nationwide level. METHODS: From an administrative hospital-discharge database, we collected data on all AVRs performed in France between 2007 and 2019. Centres were divided into terciles based on the annual number of SAVRs performed in 2007-2009 ("before TAVR era"). RESULTS: A total of 192,773 AVRs (134,662 SAVRs and 58,111 TAVRs) were performed in 47 centres. The annual number of AVRs and TAVRs increased significantly and linearly in low-volume (<152 SAVRs/year; median 106, interquartile range [IQR] 75-129), middle-volume (152-219 SAVRs/year; median 197, IQR 172-212) and high-volume (>219 SAVRs/year; median 303, IQR 268-513) terciles, but to a greater degree in the latter (+14, +16 and +24 AVRs/centre/year and +16, +19 and +31 TAVRs/centre/year, respectively; PANCOVA<0.001). Charlson Comorbidity Index and in-hospital death rates declined from 2010 to 2019 in all terciles (all Ptrend<0.05). In 2017-2019, after adjusting for age, sex and Charlson Comorbidity Index, there was a trend toward lower death rates in the high-volume tercile (P=0.06) for SAVR, whereas death rates were similar for TAVR irrespective of tercile (P=0.27). Similar results were obtained when terciles were defined based on number of interventions performed in the last instead of the first 3years. Importantly, even centres in the lowest-volume tercile performed a relatively high number of interventions (150 TAVRs/year/centre). CONCLUSIONS: In a centralized public healthcare system, the total number of AVRs increased linearly between 2007 and 2019, mostly due to an increase in TAVR, irrespective of centre volume. Progressive declines in patient risk profiles and death rates were observed in all terciles; in 2017-2019 death rates were similar in all terciles, although lower in high-volume centres for SAVR.

Tricuspid regurgitation: Frequency, clinical presentation, management and outcome among patients with severe left-sided valvular heart disease in Europe. Insights from the ESC-EORP Valvular Heart Disease II survey.

AIMS: Tricuspid regurgitation (TR) is commonly observed in patients with severe left-sided valvular heart disease (VHD). This study sought to assess TR frequency, management and outcome in this population. METHODS AND RESULTS: Among 6883 patients with severe native left-sided VHD or previous left-sided valvular intervention enrolled in the EURObservational Research Programme prospective VHD II survey, moderate or severe TR was very frequent in patients with severe mitral VHD (30% when mitral stenosis, 36% when mitral regurgitation [MR]), especially in patients with secondary MR (46%), and rare in patients with severe aortic VHD (4% when aortic stenosis, 3% when aortic regurgitation). An increase in TR grade was associated with a more severe clinical presentation and a poorer 6-month survival (p < 0.0001). Rates of concomitant tricuspid valve (TV) intervention at the time of left-sided heart valve surgery were high at the time of mitral valve surgery (50% when mitral stenosis, 41% when MR). Concordance between class I indications (patients with severe TR) for concomitant TV surgery at the time of left-sided valvular heart surgery according to guidelines and real-practice decision-making was very good (88% overall, 95% in patients operated on for MR). CONCLUSION: In this large international prospective survey among patients with severe left-sided VHD, moderate/severe TR was frequent in patients with mitral valve disease and was associated with a poorer outcome as TR grade increased. In patients with severe TR, compliance to guidelines for class I indications for concomitant TV surgery at the time of left-sided heart valve surgery was very good.

Impact of the coronavirus disease 2019 pandemic on aortic valve replacement and outcomes in France.

BACKGROUND: The coronavirus disease of 2019 (COVID-19) pandemic lockdowns limited access to medical care. The impact on surgical (SAVR) and transcatheter (TAVR) aortic valve replacement (AVR) has been poorly described. AIM: We sought to evaluate the impact of the COVID-19 pandemic on the number and modalities of AVR, patient demographics and in-hospital outcomes at the nationwide level. METHODS: Using the French nationwide administrative hospital discharge database, we compared projected numbers and proportions of AVR and hospital outcomes, obtained using linear regressions derived from 2015-2019 trends, with those observed in 2020. RESULTS: In 2020, 21,382 AVRs were performed (13,051 TAVRs, 5706 isolated SAVRs and 2625 SAVRs combined with other cardiac surgery). Compared with the 2020 projected number of AVRs (24,586, 95% confidence interval [CI] 23,525-25,646), TAVRs (14,866, 95% CI 14,164-15,568), isolated SAVRs (6652, 95% CI 6203-7100) and SAVRs combined with other cardiac surgery (3069, 95% CI 2822-3315), there were reductions of 13.0%, 12.2%, 14.2% and 14.5%, respectively. These trends were similar regardless of sex or age. In 2020, the mean age, Charlson Comorbidity Index and hospital admission duration continued to decline, and the proportion of females remained constant, following 2015-2019 trends. Overall, 2020 in-hospital mortality was higher than projected (2.0% observed vs. 1.7% projected; 95% CI 1.5-1.9%), with no increased pacemaker implantation, but more acute kidney injury and cerebrovascular accidents in some surgical subsets. CONCLUSIONS: During the COVID-19 pandemic, fewer TAVR and SAVR procedures were performed, with increased in-hospital mortality and periprocedural complications. Extended follow-up will be important to establish the long-term effect of the COVID-19 pandemic on patient management and outcomes.

Association of Age and Sex With Use of Transcatheter Aortic Valve Replacement in France.

BACKGROUND: Current guidelines recommend selecting surgical aortic valve replacement (SAVR) or transcatheter aortic valve replacement (TAVR) based on age, comorbidities, and surgical risk. Nevertheless, reports from the United States suggest a rapid expansion of TAVR in young patients. OBJECTIVES: The authors sought to evaluate the trends in TAVR uptake at a nationwide level in France according to age and sex. METHODS: Using a nationwide administrative database, we evaluated age- and sex-related trends in TAVR uptake, patient demographics, and in-hospital outcomes between 2015 and 2020. RESULTS: A total of 107,397 patients (44.0% female) underwent an isolated aortic valve replacement (AVR) (59.1% TAVR, 40.9% SAVR). In patients <65 years of age, the proportion of TAVR increased by 63.2% (P < 0.001) from 2015 to 2020 but remained uncommon at 11.1% of all AVR by 2020 (12.4% in females, 10.6% in males) while TAVR was the dominant modality in patients ≥65 years of age. In patients undergoing TAVR, the Charlson comorbidity index (CCI) (P = 0.119 for trend) and in-hospital mortality (P = 0.740 for trend) remained unchanged in patients <65 years of age but declined in those ≥65 years of age irrespective of sex (all P < 0.001 for trends). Females were older (P < 0.001), had lower CCI (P < 0.001), were more likely to undergo TAVR (P < 0.001), and experienced higher in-hospital mortality (TAVR, P = 0.015; SAVR, P < 0.001) that persisted despite adjustment for age and CCI. CONCLUSIONS: In France, the use of TAVR remained uncommon in young patients, predominantly restricted to those at high risk. Important sex differences were observed in patent demographics, selection of AVR modality, and patient outcomes. Additional research evaluating the long-term impact of TAVR use in young patients and prospective data evaluating sex differences in AVR modality selection and outcomes are needed.

Acute heart failure and valvular heart disease: A scientific statement of the Heart Failure Association, the Association for Acute CardioVascular Care and the European Association of Percutaneous Cardiovascular Interventions of the European Society of Cardiology.

Acute heart failure (AHF) represents a broad spectrum of disease states, resulting from the interaction between an acute precipitant and a patient's underlying cardiac substrate and comorbidities. Valvular heart disease (VHD) is frequently associated with AHF. AHF may result from several precipitants that add an acute haemodynamic stress superimposed on a chronic valvular lesion or may occur as a consequence of a new significant valvular lesion. Regardless of the mechanism, clinical presentation may vary from acute decompensated heart failure to cardiogenic shock. Assessing the severity of VHD as well as the correlation between VHD severity and symptoms may be difficult in patients with AHF because of the rapid variation in loading conditions, concomitant destabilization of the associated comorbidities and the presence of combined valvular lesions. Evidence-based interventions targeting VHD in settings of AHF have yet to be identified, as patients with severe VHD are often excluded from randomized trials in AHF, so results from these trials do not generalize to those with VHD. Furthermore, there are not rigorously conducted randomized controlled trials in the setting of VHD and AHF, most of the data coming from observational studies. Thus, distinct to chronic settings, current guidelines are very elusive when patients with severe VHD present with AHF, and a clear-cut strategy could not be yet defined. Given the paucity of evidence in this subset of AHF patients, the aim of this scientific statement is to describe the epidemiology, pathophysiology, and overall treatment approach for patients with VHD who present with AHF.

Unmet needs in valvular heart disease.

Valvular heart disease (VHD) is the next epidemic in the cardiovascular field, affecting millions of people worldwide and having a major impact on health care systems. With aging of the population, the incidence and prevalence of VHD will continue to increase. However, VHD has not received the attention it deserves from both the public and policymakers. Despite important advances in the pathophysiology, natural history, management, and treatment of VHD including the development of transcatheter therapies, VHD remains underdiagnosed, identified late, and often undertreated with inequality in access to care and treatment options, and there is no medication that can prevent disease progression. The present review article discusses these gaps in the management of VHD and potential actions to undertake to improve the outcome of patients with VHD.

Impact of procedural success on clinical outcome after MitraClip: Results from the MITRA-FR trial.

BACKGROUND: Differences in procedural success rates have been proposed to explain the divergent results between the MITRA-FR trial (Percutaneous Repair with the MitraClip Device for Severe Functional/Secondary Mitral Regurgitation) and the COAPT trial (Cardiovascular Outcomes Assessment of the MitraClip Percutaneous Therapy for Heart Failure Patients with Functional Mitral Regurgitation). AIM: To examine whether MITRA-FR patients who had successful clip implantation achieved a better outcome than the control group. METHODS: Based on the per protocol population of MITRA-FR, we compared the outcome in 71 patients in whom optimal clip implantation was achieved (group 1: mitral regurgitation grade ≤ 1 + at discharge) with that in 23 patients with non-optimal clip implantation (group 2: mitral regurgitation grade ≥ 2 + at discharge) and that in 137 patients in the control group (group 3). The primary endpoint was all-cause death or unplanned hospitalization for heart failure at 24 months. RESULTS: Event-free survival was not different across the groups (42±6% in group 1, 30±10% in group 2 and 31±4% in group 3; log-rank P=0.32). In multivariable analyses, after adjustment for age, sex, rhythm, aetiology, left ventricular ejection fraction and mitral regurgitation severity, group was not associated with variations in outcome: using Group 3 as reference, hazard ratio 0.86, 95% confidence interval 0.58-1.27 (P=0.43) in group 1; and hazard ratio 0.98 95% confidence interval 0.54-1.76 (P=0.94) in group 2. CONCLUSIONS: The clinical outcome of patients in whom optimal procedural result was achieved at discharge was not different compared with the control group. Our results do not support the hypothesis that the differences in rates of residual mitral regurgitation at discharge between MITRA-FR and COAPT explain the divergent results between the two trials.

Trends in aortic valve replacement for aortic stenosis: a French nationwide study.

AIMS: Transcatheter aortic valve replacement (TAVR) as an alternative to surgical aortic valve replacement (SAVR) has profoundly changed the management of patients with aortic valve stenosis (AS). Large unbiased nationwide data regarding TAVR implementation, impact on SAVR and their respective outcomes are scarce. METHODS AND RESULTS: Based on a French administrative hospital-discharge database, we collected data on all consecutive aortic valve replacements (AVRs) performed in France for AS between 2007 and 2019 [106 253 isolated SAVR (49%), 46 514 combined SAVR (21%), and 65 651 TAVR (30%)]. The number of AVR linearly increased between 2007 and 2019 (from 10 892 to 23 109, P for trend < 0.0001) due to a marked increase in TAVR (from 253 to 13 030, P for trend < 0.0001), while SAVR increased up to 2013 and then declined (10 892 in 2007, 12 699 in 2013, and 10 079 in 2019). The Charlson index decreased linearly for TAVR, but in two steps for SAVR (2011 and 2017). In-hospital mortality rates of both SAVR and TAVR declined (both P for trend < 0.0001) and were similar or lower for TAVR than for isolated SAVR in patients 75 years or above in the last 3 years (2017-19). Complication rates of TAVR also declined but permanent pacemaker rates remained high and length of stay substantial (16.7% and median 6 days, respectively, in 2017-19). CONCLUSION: The number of AVR has doubled in a decade and TAVR has become the dominant form of AVR in 2018. The improvement in patient profiles seems to have anticipated the demonstrated benefit of TAVR in intermediate and low-risk patients. In patients 75 years or older, TAVR should be considered as the first option. We also highlight two important areas for improvement, the high permanent pacemaker rates, and the long length of stay even in the contemporary era. Our results may have major implications for clinical practice and policymakers.

EURObservational Research Programme: a bibliometric assessment of its scientific output.

AIMS: Given the lack of reliable observational data, a network of volunteer centres, and standardized methodological procedures, the European Society of Cardiology EURObservational Research Programme (EORP) was set up to provide a better understanding of real-world cardiovascular care and outcomes. We aimed to evaluate the scientific impact of EORP using a bibliometric approach. METHODS AND RESULTS: We collected data for each individual publication and for each individual journal with at least one EORP publication. Bibliometric indicators evaluating research performance were categorized into those evaluating EORP publications (publication-based indicators) and those assessing the journals where those papers were published (journal-based indicators). During the first ∼11 years since its inception, we found that EORP produced 189 publications, with most published in journals in the first quartile (60.9%) or the second quartile (33.5%) of the Web of Science Journal Citation Report. The total number of citations to EORP publications was 9630 (average citation per publication of 51, h-index of 54, and 29 EORP publications with ≥100 citations). Of EORP publications, 20 had an Altmetric Attention Score >50 and 9 had a score >100. A total of 52 EORP papers have been cited 65 times in ESC Clinical Practice Guidelines between 2013 and 2021. CONCLUSION: EORP registries have contributed to impactful scientific knowledge. The high-quality metrics highlight the relevance of the EORP international cardiovascular registries to the academic community. Efforts are needed to support this, and other programmes aimed at delivering real-world evidence from independent patient data of cardiovascular care and outcomes across multiple geographies.

Characteristics, management, and outcomes of patients with multiple native valvular heart disease: a substudy of the EURObservational Research Programme Valvular Heart Disease II Survey.

AIMS: To assess the characteristics, management, and survival of patients with multiple native valvular heart disease (VHD). METHODS AND RESULTS: Among the 5087 patients with ≥1 severe left-sided native VHD included in the EURObservational VHD II Survey (maximum 3-month recruitment period per centre between January and August 2017 with a 6-month follow-up), 3571 had a single left-sided VHD (Group A, 70.2%), 363 had one severe left-sided VHD with moderate VHD of the other ipsilateral valve (Group B, 7.1%), and 1153 patients (22.7%) had ≥2 severe native VHDs (left-sided and/or tricuspid regurgitation, Group C). Patients with multiple VHD (Groups B and C) were more often women, had greater congestive heart failure (CHF) and comorbidity, higher left atrial volumes and pulmonary pressures, and lower ejection fraction than Group A patients (all P ≤ 0.01). During the index hospitalization, 36.7% of Group A (n = 1312), 26.7% of Group B (n = 97), and 32.7% of Group C (n = 377) underwent valvular intervention (P < 0.001). Six-month survival was better for Group A than for Group B or C (both P < 0.001), even after adjustment for age, sex, body mass index, and Charlson index [hazard ratio (HR) 95% confidence interval (CI) 1.62 (1.10-2.38) vs. Group B and HR 95% CI 1.72 (1.32-2.25) vs. Group C]. Groups B and C had more CHF at 6 months than Group A (both P < 0.001). Factors associated with mortality in Group C were age, CHF, and comorbidity (all P < 0.010). CONCLUSION: Multiple VHD is common, encountered in nearly 30% of patients with left-sided native VHD, and associated with greater cardiac damage and leads to higher mortality and more heart failure at 6 months than single VHD, yet with lower rates of surgery.

Multi-modality imaging assessment of native valvular regurgitation: an EACVI and ESC council of valvular heart disease position paper.

Valvular regurgitation represents an important cause of cardiovascular morbidity and mortality. Imaging is pivotal in the evaluation of native valve regurgitation and echocardiography is the primary imaging modality for this purpose. The imaging assessment of valvular regurgitation should integrate quantification of the regurgitation, assessment of the valve anatomy and function, and the consequences of valvular disease on cardiac chambers. In clinical practice, the management of patients with valvular regurgitation largely relies on the results of imaging. It is crucial to provide standards that aim at establishing a baseline list of measurements to be performed when assessing native valve regurgitation. The present document aims to present clinical guidance for the multi-modality imaging assessment of native valvular regurgitation.