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.

Prospective 1-year results of atrial fibrillation ablation using the pentaspline pulsed field ablation catheter: The initial French experience.

BACKGROUND: Pulsed field ablation has recently emerged as an interesting non-thermal energy for atrial fibrillation ablation. At a time of rapid spread of this technology, there is still a lack of prospective real-life data. AIM: To describe multicentre prospective safety and 1-year efficacy data in three of the first French centres to use pulsed field ablation. METHODS: All consecutive patients undergoing a first pulsed field ablation were included prospectively. The primary outcome was freedom from documented atrial arrhythmia. The safety endpoint was a composite of major adverse events. Univariate and multivariable analyses, including patient and procedural characteristics, were performed to identify factors predictive of recurrence. RESULTS: Between May 2021 and June 2022, 311 patients were included (paroxysmal atrial fibrillation in 53%, persistent atrial fibrillation in 35% and long-standing persistent atrial fibrillation in 11%). Additional non-pulmonary vein pulsed field ablation applications were performed in 104/311 patients. One-year freedom from arrhythmia recurrence was 77.6% in the overall population and was significantly higher in patients with paroxysmal atrial fibrillation (88.4%) compared with patients with persistent atrial fibrillation (69.7%; P<0.001) and those with long-standing persistent atrial fibrillation (49.0%; P<0.001). The major complication rate was 2.6% (tamponade in four patients, stroke in two patients and coronary spasm in one patient). Besides the usual predictors of recurrences (left atrium size, CHA2DS2-VASc score, type of atrial fibrillation), the presence of atrial fibrillation at procedure start was independently associated with arrhythmia recurrence (hazard ratio: 2.04, 95% confidence interval: 1.10-3.77). CONCLUSION: In this prospective multicentre real-world study, pulsed field ablation for atrial fibrillation ablation seems to be associated with a good safety profile and rather favourable acute and 1-year success rates.

Reducing length of stay after transfemoral transcatheter aortic valve implantation: the FAST-TAVI II trial.

BACKGROUND AND AIMS: The length of stay (LOS) after transcatheter aortic valve implantation (TAVI) remains extremely variable whereas early discharge has been shown to be feasible and safe. The study objective was to evaluate the efficacy and safety of an intervention aimed at reducing LOS after transfemoral TAVI. METHODS: FAST-TAVI II is a prospective, multicentre, cluster, randomized, controlled study including patients with severe symptomatic aortic stenosis, who had transfemoral TAVI. The intervention consisted in a dedicated training programme to implement 10 quality of care measures to reduce LOS with an implementation phase of eight weeks. The primary endpoint was the proportion of patients discharged early within 3 days. Secondary endpoints included: LOS, 30-day mortality and 30-day incidence of readmission for cardiovascular events. RESULTS: During the study period, 969 patients were enrolled in the intervention group and 860 patients in the control group. Mean age was 81.9 ± 6.6 years and mean EuroSCORE II was 4.4 ± 4.5%. Early discharge was achieved in 563 (58.1%) patients in the intervention group vs. 364 (42.3%) patients in the control group (P < .0001). Median LOS was significantly reduced in the intervention group compared to the control group [3 (IQR: 3) vs. 4 days (IQR: 3), P < .0001]. Thirty-day mortality was low and similar in the two groups (0.5% vs. 0.9%, P = .30), as were 30-day readmissions (4.6% vs. 2.8%, P = .28). CONCLUSIONS: The intervention was simple and fast to implement, and was effective and safe to reduce LOS and increase the proportion of patients discharged early after TAVI (NCT04503655).

Pentaspline Pulsed Field Ablation Catheter Versus Cryoballoon for Atrial Fibrillation Ablation: Results From a Prospective Comparative Study.

BACKGROUND: Cryoballoon ablation is currently the gold standard technique for single-shot pulmonary vein isolation (PVI). Pulsed field ablation (PFA) has recently emerged as an interesting nonthermal alternative energy for PVI. The purpose of our study was to evaluate the safety and long-term efficacy of PVI using the pentaspline PFA catheter in comparison to cryoballoon ablation. METHODS AND RESULTS: Between January 2021 and December 2022, we included all consecutive patients of our center in whom a first PVI-only procedure was performed using PFA or cryoballoon. The choice of the energy was based on patients' preference between general anesthesia (PFA) and local anesthesia (cryoballoon). The primary end point was freedom from documented atrial arrhythmia recurrence after a 3-month blanking period. A total of 301 patients (paroxysmal atrial fibrillation in 220 patients) underwent a first PVI procedure performed using PFA (n=151) or cryoballoon (n=150). Complete short-term PVI was obtained in 144 of 150 patients (96%) in the cryoballoon group and in all patients of the PFA group (P=0.01). Procedure duration was significantly longer in the cryoballoon group. Transient and persistent phrenic nerve injuries were observed in the cryoballoon group only (13/150 and 2/150, respectively). One-year freedom from atrial arrhythmia was significantly higher in the PFA group compared with the cryoballoon group (87.9% versus 77.7%; adjusted hazard ratio, 0.53 [95% CI, 0.30-0.96]; P=0.037). CONCLUSIONS: This prospective, comparative, real-life study suggested that PFA could overcome safety limitations of cryoballoon with optimal effectiveness. Randomized controlled studies are required to further investigate the potential superiority of PFA over cryoballoon.

Patterns of aortic valve replacement in Europe and adoption by sex.

OBJECTIVE: Management of patients with severe aortic stenosis (AS) may differ according to the patient sex. This study aimed to describe patterns of aortic valve replacement (AVR) for severe AS across Europe, including stratification by sex. METHODS: Procedure volume data for surgical aortic valve replacement (SAVR) and transcatheter aortic valve implantation (TAVI) for six years (2015-2020) were extracted from national databases for Austria, Czech Republic, Denmark, England, Finland, France, Germany, Norway, Poland, Spain, Sweden, and Switzerland and stratified by sex. Patients per million population (PPM) undergoing AVR per year were calculated using population estimates from Eurostat. RESULTS: Between 2015 and 2019, AVR procedures grew at an average annual rate of 3.9%. In 2020, the average total PPM undergoing AVR across all countries was 339, with 51% of procedures being TAVI and 49% SAVR. AVR PPM varied widely between countries, with the highest and lowest in Germany and Poland, respectively. The average total PPM was higher for men than women (423 vs. 258), but a higher proportion of women (62%) than men (44%) received TAVI. The proportion of TAVI among total AVR procedures increased with age, with an overall average of 96% of men and 98% of women aged ≥85 years receiving TAVI; however, adoption of TAVI varied by country. CONCLUSIONS: The analysis of temporal trends in the adoption of TAVI vs. SAVR across Europe showed significant variations. Despite the higher use of TAVI vs. SAVR in women, overall rates of AV intervention in women were lower compared to men.

Clinical effects of permanent pacemaker implantation after transcatheter aortic valve implantation: Insights from the nationwide FRANCE-TAVI registry.

BACKGROUND: The influence of permanent pacemaker implantation upon outcomes after transcatheter aortic valve implantation (TAVI) remains controversial. AIMS: To evaluate the impact of permanent pacemaker implantation after TAVI on short- and long-term mortality, and on the risk of hospitalization for heart failure. METHODS: Data from the large FRANCE-TAVI registry, linked to the French national health single-payer claims database, were analysed to compare 30-day and long-term mortality rates and hospitalization for heart failure rates among patients with versus without permanent pacemaker implantation after TAVI. Multivariable regressions were performed to adjust for confounders. RESULTS: A total of 36,549 patients (mean age 82.6years; 51.6% female) who underwent TAVI from 2013 to 2019 were included in the present analysis. Among them, 6999 (19.1%) received permanent pacemaker implantation during the index hospitalization, whereas 232 (0.6%) underwent permanent pacemaker implantation between hospital discharge and 30days after TAVI, at a median of 11 (interquartile range: 7-18) days. In-hospital permanent pacemaker implantation was not associated with an increased risk of death between discharge and 30days (adjusted odds ratio: 0.91, 95% confidence interval: 0.64-1.29). At 5years, the incidence of all-cause death was higher among patients with versus without permanent pacemaker implantation within 30days of the procedure (adjusted hazard ratio: 1.13, 95% confidence interval: 1.07-1.19). Permanent pacemaker implantation within 30days of TAVI was also associated with a higher 5-year rate of hospitalization for heart failure (adjusted subhazard ratio: 1.17, 95% confidence interval: 1.11-1.23). CONCLUSIONS: Permanent pacemaker implantation after TAVI is associated with an increased risk of long-term hospitalization for heart failure and all-cause mortality. Further research to mitigate the risk of postprocedural permanent pacemaker implantation is needed as TAVI indications expand to lower-risk patients.

Device innovation in cardiovascular medicine: a report from the European Society of Cardiology Cardiovascular Round Table.

Research performed in Europe has driven cardiovascular device innovation. This includes, but is not limited to, percutaneous coronary intervention, cardiac imaging, transcatheter heart valve implantation, and device therapy of cardiac arrhythmias and heart failure. An important part of future medical progress involves the evolution of medical technology and the ongoing development of artificial intelligence and machine learning. There is a need to foster an environment conducive to medical technology development and validation so that Europe can continue to play a major role in device innovation while providing high standards of safety. This paper summarizes viewpoints on the topic of device innovation in cardiovascular medicine at the European Society of Cardiology Cardiovascular Round Table, a strategic forum for high-level dialogue to discuss issues related to the future of cardiovascular health in Europe. Devices are developed and improved through an iterative process throughout their lifecycle. Early feasibility studies demonstrate proof of concept and help to optimize the design of a device. If successful, this should ideally be followed by randomized clinical trials comparing novel devices vs. accepted standards of care when available and the collection of post-market real-world evidence through registries. Unfortunately, standardized procedures for feasibility studies across various device categories have not yet been implemented in Europe. Cardiovascular imaging can be used to diagnose and characterize patients for interventions to improve procedural results and to monitor devices long term after implantation. Randomized clinical trials often use cardiac imaging-based inclusion criteria, while less frequently trials randomize patients to compare the diagnostic or prognostic value of different modalities. Applications using machine learning are increasingly important, but specific regulatory standards and pathways remain in development in both Europe and the USA. Standards are also needed for smart devices and digital technologies that support device-driven biomonitoring. Changes in device regulation introduced by the European Union aim to improve clinical evidence, transparency, and safety, but they may impact the speed of innovation, access, and availability. Device development programmes including dialogue on unmet needs and advice on study designs must be driven by a community of physicians, trialists, patients, regulators, payers, and industry to ensure that patients have access to innovative care.

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.

Impact of Prosthesis-Patient Mismatch After Transcatheter Aortic Valve Replacement.

BACKGROUND: Data on the long-term impact of prosthesis-patient mismatch (PPM) on outcomes after transcatheter aortic valve replacement (TAVR) remain sparse. We therefore aimed to investigate the incidence, predictive factors, and long-term prognostic impact of PPM on bioprosthesis durability and mortality. METHODS: This was a single-centre retrospective study including 2117 patients who underwent TAVR for aortic stenosis from 2002 to 2022. Moderate PPM was defined by indexed effective orifice area (iEOA) > 0.65 and ≤ 0.85 cm2/m2 (> 0.55 and ≤ 0.70 cm2/m2 if BMI ≥ 30 kg/m2) and severe PPM by an iEOA ≤ 0.65 cm2/m2 (≤ 0.55 cm2/m2 If BMI ≥ 30 kg/m2). RESULTS: There were 351 patients (16.6%) with PPM, including 39 patients (1.8%) with severe PPM and 312 patients (14.7%) with moderate PPM. The mean follow-up duration was 31.2 ± 26.5 months. Factors independently associated with the occurrence of PPM were body surface area (odds ratio [OR] 3.32, 95% confidence interval [CI] 1.32-8.35; P = 0.01), valve-in-valve TAVR (OR 6.12, 95% CI 2.29-16.08; P < 0.001), small annulus (OR 2.42, 95% CI 1.41-4.07; P = 0.001), and the use of a balloon-expandable valve (OR 4.17, 95% CI 2.17-8.33; P < 0.001). PPM was associated with increased risk of mortality (hazard ratio [HR] 1.3, 95% CI 1.1-1.5, P = 0.004) and valve thrombosis (HR 4.2, 95% CI 1.4-12.6, P = 0.01), and a trend towards increased risk of structural valve deterioration (HR 1.7, 95% CI 0.9-2.9; P = 0.08). CONCLUSIONS: The results of this study suggest that PPM has a negative long-term impact on outcomes after TAVR. These findings emphasise the importance of preventing PPM.

Infective Endocarditis After Transcatheter Versus Surgical Aortic Valve Replacement.

BACKGROUND: Scarce data are available comparing infective endocarditis (IE) following surgical aortic valve replacement (SAVR) and transcatheter aortic valve replacement (TAVR). This study aimed to compare the clinical presentation, microbiological profile, management, and outcomes of IE after SAVR versus TAVR. METHODS: Data were collected from the "Infectious Endocarditis after TAVR International" (enrollment from 2005 to 2020) and the "International Collaboration on Endocarditis" (enrollment from 2000 to 2012) registries. Only patients with an IE affecting the aortic valve prosthesis were included. A 1:1 paired matching approach was used to compare patients with TAVR and SAVR. RESULTS: A total of 1688 patients were included. Of them, 602 (35.7%) had a surgical bioprosthesis (SB), 666 (39.5%) a mechanical prosthesis, 70 (4.2%) a homograft, and 350 (20.7%) a transcatheter heart valve. In the SAVR versus TAVR matched population, the rate of new moderate or severe aortic regurgitation was higher in the SB group (43.4% vs 13.5%; P < .001), and fewer vegetations were diagnosed in the SB group (62.5% vs 82%; P < .001). Patients with an SB had a higher rate of perivalvular extension (47.9% vs 27%; P < .001) and Staphylococcus aureus was less common in this group (13.4% vs 22%; P = .033). Despite a higher rate of surgery in patients with SB (44.4% vs 27.3%; P < .001), 1-year mortality was similar (SB: 46.5%; TAVR: 44.8%; log-rank P = .697). CONCLUSIONS: Clinical presentation, type of causative microorganism, and treatment differed between patients with an IE located on SB compared with TAVR. Despite these differences, both groups exhibited high and similar mortality at 1-year follow-up.

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.

Patterns of Aortic Valve Replacement in Europe: Adoption by Age.

INTRODUCTION: The management of patients with severe aortic stenosis may differ according to patients' age. The aim of this analysis was to describe patterns of aortic valve replacement (AVR) use in European countries stratified by age. METHODS: Procedure volume data for AVR, including surgical aortic valve replacement (sAVR) and transcatheter aortic valve implantation (TAVI), for the years 2015-2020 were obtained from national databases for twelve European countries (Austria, the Czech Republic, Denmark, England, Finland, France, Germany, Norway, Poland, Spain, Sweden, and Switzerland). Procedure volumes were reported by patient age (<50 years, 5-year age groups between 50 and 85 years, and ≥85 years). Patients per million (PPM) population undergoing AVR each year were calculated using population estimates from Eurostat. RESULTS: AVR PPM varied widely between countries, from 508 PPM in Germany to 174 PPM in Poland in 2020. TAVI rates ranged from 61% in Switzerland and Finland to 25% in Poland. AVR PPM increased with age to a peak at 80-84 years, after which it decreased again. AVR procedures increased from 2015 to 2019 at an average annual rate of 3.9%. AVR increased more substantially in people aged ≥80 years than in younger age groups; these older age groups accounted for 30% of all AVR procedures in 2015 and 35% in 2019. TAVI accounted for an increasing proportion of all AVR procedures as patient age increased; an overall average of 96% of males and 98% of females aged ≥85 years received TAVI as the treatment modality, although adoption of TAVI differed between countries. CONCLUSIONS: There is considerable variation in the rates of AVR use and the adoption of TAVI versus sAVR between European countries. The use of TAVI has increased in recent years, particularly for older patients.

Very long-term outcomes after acute myocardial infarction in young men and women: Insights from the FAST-MI program.

AIMS: Conflicting data exists about long-term outcomes in young women and men experiencing acute myocardial infarction (AMI). METHODS: The FAST-MI program consists of three nationwide French surveys carried out 5years apart from 2005 to 2015, including consecutive patients with AMI over a 1-month period with up to 10-year follow-up. The present analysis focused on adults≤50 yo according to their gender. RESULTS: Women accounted for 17.5% (335) of the 1912 patients under 50 yo and had a similar age as men (43.9±5.1 vs. 43.9±5.5years, P=0.92). They received less percutaneous coronary interventions (PCI) than men (85.9% vs. 91.3%, P=0.005), even in ST-elevation myocardial infarction (83.6% vs. 93.5%, P<0.001). Recommended secondary prevention medications were less frequently prescribed at discharge in women (40.6% vs. 52.8%, P<0.001), a trend that persisted in 2015 (59.1% vs. 72.8% in 2015, P<0.001). Still, ten-year survival was similar in men (90.5%) and women (92.3%) (crude HR: 0.86 [95% CI: 0.55-1.35], P=0.52, adjusted HR: 0.63 [95% CI: 0.38-1.07], P=0.09); similar results were found for ten-year survival among hospital survivors (91.2% in men vs. 93.7% in women, adjusted HR: 0.87 [95% CI: 0.45-1.66], P=0.66). Of the 1684 patients alive at hospital discharge with morbidity follow-up≥6months available, death, AMI or stroke at 8years occurred in 12.9% men and 11.2% in women (adjusted HR: 0.90 [95% CI: 0.60-1.33], P=0.59). CONCLUSIONS: Young women with AMI undergo less cardiac interventions and are less often prescribed secondary prevention treatment than men, even when significant coronary artery disease is present, but keep a similar long-term prognosis after AMI. Optimal management of these young patients, regardless of gender, is necessary to ensure best outcomes after this major cardiovascular event.

Is excessive ventricular irregularity predictive of rehospitalization in patients with permanent AF and HFpEF?

AIMS: There are currently limited therapeutic approaches for patients with heart failure with preserved ejection fraction (HFpEF) who have developed permanent atrial fibrillation (AF). We aimed to analyse the impact of ventricular irregularity on heart failure rehospitalization in patients with permanent AF and HFpEF. METHODS AND RESULTS: All 24 h ambulatory Holter monitoring performed in our centre within a month after a first heart failure hospitalization were screened. Patients with HFpEF and permanent AF were included in the retrospective analysis. The following parameters of ventricular irregularity were calculated over the 24 h recording period: standard deviation of all RR intervals (SDNN), coefficient of variation of SDNN (CV-SDNN = SDNN/mean RR), root of the mean squared differences of successive RR intervals (RMSSD), and percentage of consecutive RR intervals with difference over 50 ms (pNN50). The primary endpoint was rehospitalization for acute heart failure (HFrH). From 2010 to 2021, 51/216 screened patients were included. During a median follow-up of 3.13 years, 29/51 patients reached the primary endpoint. HFrH patients had higher SDNN (205 ± 65 vs. 154 ± 46 ms; P < 0.01), CV-SDNN (26 ± 8% vs. 19 ± 5%, P < 0.01), RMSSD (182 ± 47 vs. 138 ± 65 ms, P = 0.013), and pNN50 (76 ± 9 vs. 58 ± 26, P < 0.001) when compared with patients with no HFrH. In multivariate analysis, all those parameters remained significantly associated with HFrH. CONCLUSIONS: In this pilot study, we found some evidences for a deleterious impact of excessive ventricular irregularity on HFrH in AF patients with HFpEF. Those new findings could pave the way for new prognosis and therapeutic approaches in this patients' population.

Subtotal Nephrectomy Associated with a High-Phosphate Diet in Rats Mimics the Development of Calcified Aortic Valve Disease Associated with Chronic Renal Failure.

Introduction. This study addressed the hypothesis that subtotal nephrectomy associated with a high-phosphorus diet (5/6Nx + P) in rats represents a suitable animal model to mimic the cardiovascular consequences of chronic kidney disease (CKD) including calcified aortic valve disease (CAVD). Indeed, the latter contributes to the high morbidity and mortality of CKD patients and sorely lacks preclinical models for pathophysiological and pharmacological studies. Methods. Renal and cardiovascular function and structure were compared between sham-operated and 5/6 Nx rats + P 10 to 12 weeks after surgery. Results. As expected, 11 weeks after surgery, 5/6Nx + P rats developed CKD as demonstrated by their increase in plasma creatinine and urea nitrogen and decrease in glomerular filtration rate, estimated by using fluorescein-isothiocyanate-labelled sinistrin, anemia, polyuria, and polydipsia compared to sham-operated animals on a normal-phosphorus diet. At the vascular level, 5/6Nx + P rats had an increase in the calcium content of the aorta; a decrease in mesenteric artery dilatation in response to a stepwise increase in flow, illustrating the vascular dysfunction; and an increase in blood pressure. Moreover, immunohistology showed a marked deposition of hydroxyapatite crystals in the aortic valve of 5/6Nx + P rats. Echocardiography demonstrated that this was associated with a decrease in aortic valve cusp separation and an increase in aortic valve mean pressure gradient and in peak aortic valve velocity. Left-ventricular diastolic and systolic dysfunction as well as fibrosis were also present in 5/6Nx + P rats. Conclusion. This study demonstrates that 5/6Nx + P recapitulates the cardiovascular consequences observed in humans with CKD. In particular, the initiation of CAVD was shown, highlighting the interest of this animal model to study the mechanisms involved in the development of aortic stenosis and test new therapeutic strategies at an early stage of the disease.