Mitral transcatheter edge-to-edge repair vs. isolated mitral surgery for severe mitral regurgitation: a French nationwide study.

BACKGROUND AND AIMS: Mitral valve surgery and, more recently, mitral transcatheter edge-to-edge repair (TEER) are the two treatments of severe mitral regurgitation in eligible patients. Clinical comparison of both therapies remains limited by the number of patients analysed. The objective of this study was to analyse the outcomes of mitral TEER vs. isolated mitral valve surgery at a nationwide level in France. METHODS: Based on the French administrative hospital discharge database, the study collected information for all consecutive patients treated for mitral regurgitation with isolated TEER or isolated mitral valve surgery between 2012 and 2022. Propensity score matching was used for the analysis of outcomes. RESULTS: A total of 57 030 patients were found in the database. After matching on baseline characteristics, 2160 patients were analysed in each arm. At 3-year follow-up, TEER was associated with significantly lower incidence of cardiovascular death (hazard ratio 0.685, 95% confidence interval 0.563-0.832; P = .0001), pacemaker implantation, and stroke. Non-cardiovascular death (hazard ratio 1.562, 95% confidence interval 1.238-1.971; P = .0002), recurrent pulmonary oedema, and cardiac arrest were more frequent after TEER. No significant differences between the two groups were observed regarding all-cause death (hazard ratio 0.967, 95% confidence interval 0.835-1.118; P = .65), endocarditis, major bleeding, atrial fibrillation, and myocardial infarction. CONCLUSIONS: Our results suggest that TEER for severe mitral regurgitation was associated with lower cardiovascular mortality than mitral surgery at long-term follow-up. Pacemaker implantation and stroke were less frequently observed after TEER.

Assessment of epidemiology and outcomes of adult patients with kidney-limited thrombotic microangiopathies.

Thrombotic microangiopathies (TMA) are usually associated with hematological features (RH-TMA). The epidemiology of TMA limited to kidneys (RL-TMA) is unclear Therefore, patients with TMA and native kidney biopsies were identified during 2009-2022 in 20 French hospitals and results evaluated. RL-TMA was present in 341/757 (45%) patients and associated with lower creatinine levels (median 184 vs 346 µmol/L) than RH-TMA. RL-TMA resulted from virtually all identified causes, more frequently from anti-VEGF treatment and hematological malignancies but less frequently from shigatoxin-associated hemolytic uremic syndrome (HUS), systemic sclerosis, gemcitabine and bacterial infection, and even less frequently when three or more causes/triggers were combined (RL-TMA: 5%; RH-TMA: 12%). RL-TMA was associated with significantly lower major cardiovascular events (10% vs 20%), kidney replacement therapy (23% vs 43%) and death (12% vs 20%) than RH-TMA during follow-up (median 28 months). Atypical HUS (aHUS) was found in 326 patients (RL-TMA: 43%, RH-TMA: 44%). Among the 69 patients with proven complement-mediated aHUS, eculizumab (anti-C5 therapy) was used in 43 (62%) (RL-TMA: 35%; RH-TMA: 71%). Among the 257 other patients with aHUS, including 51% with RL-TMA, eculizumab was used in 29 but with unclear effects of this treatment. Thus, RL-TMA represents a very high proportion of patients with TMA and results from virtually all known causes of TMA and includes 25% of patients with complement-mediated aHUS. Adverse outcomes of RL-TMA are lower compared to RH-TMA but remain significant. Anti-C5 therapy was rarely used in RL-TMA, even in proven complement-mediated aHUS, and its effects remain to be assessed.

Incidence of stroke, subsequent clinical outcomes and health care resource utilization in people with type 2 diabetes: a real-world database study in France: "INSIST" study.

BACKGROUND: People with type 2 diabetes (T2D) are at elevated risk of cardiovascular disease (CVD) including stroke, yet existing real-world evidence (RWE) on the clinical and economic burden of stroke in this population is limited. The aim of this cohort study was to evaluate the clinical and economic burden of stroke among people with T2D in France. METHODS: We conducted a retrospective RWE study using data from the nationally representative subset of the French Système National des Données de Santé (SNDS) database. We assessed the incidence of stroke requiring hospitalization between 2012 and 2018 among T2D patients. Subsequent clinical outcomes including CVD, stroke recurrence, and mortality were estimated overall and according to stroke subtype (ischemic versus hemorrhagic). We also examined the treatment patterns for glucose-lowering agents and CVD agents, health care resource utilization and medical costs. RESULTS: Among 45,331 people with T2D without baseline history of stroke, 2090 (4.6%) had an incident stroke requiring hospitalization. The incidence of ischemic stroke per 1000 person-years was 4.9-times higher than hemorrhagic stroke (6.80 [95% confidence interval (CI) 6.47-7.15] versus 1.38 [1.24-1.54]). During a median follow-up of 2.4 years (interquartile range 0.6; 4.4) from date of index stroke, the rate of CVD, stroke recurrence and mortality per 1000 person-years was higher among hemorrhagic stroke patients than ischemic stroke patients (CVD 130.9 [107.7-159.0] versus 126.4 [117.2-136.4]; stroke recurrence: 86.7 [66.4-113.4] versus 66.5 [59.2-74.6]; mortality 291.5 [259.1-327.9] versus 144.1 [134.3-154.6]). These differences were not statistically significant, except for mortality (adjusted hazard ratio 1.95 [95% CI 1.66-2.92]). The proportion of patients prescribed glucagon-like peptide-1 receptor agonists increased from 4.2% at baseline to 6.6% during follow-up. The proportion of patients prescribed antihypertensives and statins only increased slightly following incident stroke (antihypertensives: 70.9% pre-stroke versus 76.7% post-stroke; statins: 24.1% pre-stroke versus 30.0% post-stroke). Overall, 68.8% of patients had a subsequent hospitalization. Median total medical costs were €12,199 (6846; 22,378). CONCLUSIONS: The high burden of stroke among people with T2D, along with the low proportion of patients receiving recommended treatments as per clinical guidelines, necessitates a strengthened and multidisciplinary approach to the CVD prevention and management in people with T2D.

Epilepsy and the risk of adverse cardiovascular events: A nationwide cohort study.

BACKGROUND AND PURPOSE: Epilepsy is associated with higher morbidity and mortality compared to people without epilepsy. We performed a retrospective cross-sectional and longitudinal cohort study to evaluate cardiovascular comorbidity and incident vascular events in people with epilepsy (PWE). METHODS: Data were extracted from the French Hospital National Database. PWE (n = 682,349) who were hospitalized between January 2014 and December 2022 were matched on age, sex, and year of hospitalization with 682,349 patients without epilepsy. Follow-up was conducted from the date of first hospitalization with epilepsy until the date of each outcome or date of last news in the absence of the outcome. Primary outcome was the incidence of all-cause death, cardiovascular death, myocardial infarction, hospitalization for heart failure, ischaemic stroke (IS), new onset atrial fibrillation, sustained ventricular tachycardia or fibrillation (VT/VF), and cardiac arrest. RESULTS: A diagnosis of epilepsy was associated with higher numbers of cardiovascular risk factors and adverse cardiovascular events compared to controls. People with epilepsy had a higher incidence of all-cause death (incidence rate ratio [IRR] = 2.69, 95% confidence interval [CI] = 2.67-2.72), cardiovascular death (IRR = 2.16, 95% CI = 2.11-2.20), heart failure (IRR = 1.26, 95% CI = 1.25-1.28), IS (IRR = 2.08, 95% CI = 2.04-2.13), VT/VF (IRR = 1.10, 95% CI = 1.04-1.16), and cardiac arrest (IRR = 2.12, 95% CI = 2.04-2.20). When accounting for all-cause death as a competing risk, subdistribution hazard ratios for ischaemic stroke of 1.59 (95% CI = 1.55-1.63) and for cardiac arrest of 1.73 (95% CI = 1.58-1.89) demonstrated higher risk in PWE. CONCLUSIONS: The prevalence and incident rates of cardiovascular outcomes were significantly higher in PWE. Targeting cardiovascular health could help reduce excess morbidity and mortality in PWE.

Impact of gender in patients with device-related thrombosis after left atrial appendage closure - A sub-analysis from the multicenter EUROC-DRT-registry.

BACKGROUND: Device-related thrombosis (DRT) is a common finding after left atrial appendage closure (LAAC) and is associated with worse outcomes. As women are underrepresented in clinical studies, further understanding of sex differences in DRT patients is warranted. METHODS AND RESULTS: This sub-analysis from the EUROC-DRT-registry compromises 176 patients with diagnosis of DRT after LAAC. Women, who accounted for 34.7% (61/176) of patients, were older (78.0 ± 6.7 vs. 74.9 ± 9.1 years, p = .06) with lower rates of comorbidities. While DRT was detected significantly later in women (173 ± 267 vs. 127 ± 192 days, p = .01), anticoagulation therapy was escalated similarly, mainly with initiation of novel oral anticoagulant (NOAC), vitamin K antagonist (VKA) or heparin. DRT resolution was achieved in 67.5% (27/40) of women and in 75.0% (54/72) of men (p = .40). In the remaining cases, an intensification/switch of anticoagulation was conducted in 50.% (9/18) of men and in 41.7% (5/12) of women. Final resolution was achieved in 72.5% (29/40) cases in women, and in 81.9% (59/72) cases in men (p = .24). Women were followed-up for a similar time as men (779 ± 520 vs. 908 ± 687 days, p = .51). Kaplan-Meier analysis revealed no difference in mortality rates in women (Hazard Ratio [HR]: 1.73, 95%-Confidence interval [95%-CI]: .68-4.37, p = .25) and no differences in stroke (HR: .83, 95%-CI: .30-2.32, p = .72) within 2 years after LAAC. CONCLUSION: Evaluation of risk factors and outcome revealed no differences between men and women, with DRT in women being diagnosed significantly later. Women should be monitored closely to assess for DRT formation/resolution. Treatment strategies appear to be equally effective.

The Role of the Wearable Defibrillator in Heart Failure.

PURPOSE OF REVIEW: Wearable cardioverter defibrillators (WCDs) have been developed as a temporary measure for protecting patients at risk for sudden cardiac death that do not meet the indication for implantable cardioverter defibrillator (ICD), most notably in the early stages of heart failure with reduced ejection fraction before reassessment of their left ventricular ejection fraction. In this review, we report available evidence in the literature and guidelines regarding WCD use in order to try to define the role WCDs may have in heart failure. RECENT FINDINGS: In the last decade, most observational studies found WCDs to be both safe and effective in terminating ventricular arrhythmias in various indications, mostly centered around heart failure with reduced ejection fraction. The only available randomized controlled trial using WCD did not however show a benefit on patients' survival. Hence, recent guidelines only recommended its use in limited indications. Recent data also suggest a possible interest of WCD in monitoring patients, a finding that may prove useful in the context of new-onset heart failure. Data regarding WCD benefit is scarce, and definitive conclusions on its utility are hard to draw. In the context of heart failure, and particularly new-onset heart failure, WCD might find a role in a global comprehensive management of the disease, both acting as an educational tool, a monitoring tool, and, most importantly, a safe and effective tool in preventing sudden cardiac death. The low level of evidence however invites caution, and the decision of prescribing a WCD needs to be individualized and thoroughly discussed with the patient whose compliance is key with this device.

A worldwide survey on incidence, management, and prognosis of oesophageal fistula formation following atrial fibrillation catheter ablation: the POTTER-AF study.

AIMS: Oesophageal fistula represents a rare but dreadful complication of atrial fibrillation catheter ablation. Data on its incidence, management, and outcome are sparse. METHODS AND RESULTS: This international multicentre registry investigates the characteristics of oesophageal fistulae after treatment of atrial fibrillation by catheter ablation. A total of 553 729 catheter ablation procedures (radiofrequency: 62.9%, cryoballoon: 36.2%, other modalities: 0.9%) were performed, at 214 centres in 35 countries. In 78 centres 138 patients [0.025%, radiofrequency: 0.038%, cryoballoon: 0.0015% (P < 0.0001)] were diagnosed with an oesophageal fistula. Peri-procedural data were available for 118 patients (85.5%). Following catheter ablation, the median time to symptoms and the median time to diagnosis were 18 (7.75, 25; range: 0-60) days and 21 (15, 29.5; range: 2-63) days, respectively. The median time from symptom onset to oesophageal fistula diagnosis was 3 (1, 9; range: 0-42) days. The most common initial symptom was fever (59.3%). The diagnosis was established by chest computed tomography in 80.2% of patients. Oesophageal surgery was performed in 47.4% and direct endoscopic treatment in 19.8% and conservative treatment in 32.8% of patients. The overall mortality was 65.8%. Mortality following surgical (51.9%) or endoscopic treatment (56.5%) was significantly lower as compared to conservative management (89.5%) [odds ratio 7.463 (2.414, 23.072) P < 0.001]. CONCLUSION: Oesophageal fistula after catheter ablation of atrial fibrillation is rare and occurs mostly with the use of radiofrequency energy rather than cryoenergy. Mortality without surgical or endoscopic intervention is exceedingly high.

Heart failure with preserved ejection fraction and atrial fibrillation: recent advances and open questions.

Atrial fibrillation (AF) and heart failure (HF) are frequently associated and can be caused or exacerbated by each other through different mechanisms. AF is particularly common in patients with heart failure with preserved ejection fraction (HFpEF) defined as left ventricular ejection fraction (LVEF) ≥ 50%, with a prevalence ranging around 40-60%.In two recent trials, treatment with SGLT2 inhibitors resulted in a lower risk of worsening heart failure or cardiovascular death than placebo in patients with HFpEF, and SGLT2 inhibitors similarly improved prognosis whether patients had AF or not at enrolment. Analyses for subgroups of interest of patients with HFpEF likely to be at higher risk of AF (particularly those with older age or obesity) similarly indicated a consistent benefit with SGLT2 inhibitors. That subgroup in patients with HFpEF is those with a history of previous HF with LVEF ≤ 40%. The EAST-AFNET 4 trial indicated that early rhythm-control therapy was associated with a lower risk of adverse cardiovascular outcomes than usual care among patients with recent AF and cardiovascular conditions, including those with HF. In patients with AF and HF included in the CABANA trial, catheter ablation produced marked improvements in survival, freedom from AF recurrence, and quality of life compared to drug therapy. When strategies aiming at rhythm control eventually fail in patients with AF and HFpEF, a strategy of rate control with atrioventricular junction ablation and cardiac resynchronisation should be discussed since it may also reduce all-cause mortality.Finally, and in conclusion, considering that patients with AF and HFpEF may have a variety of cardiovascular and non-cardiovascular additional comorbidities, they are among those likely to have the highest clinical benefit being adherent to a holistic and integrated care management of AF following the ABC (Atrial Fibrillation Better Care) pathway.

Prevalence, risk factors and outcomes of cardiac disease in cystic fibrosis: a multinational retrospective cohort study.

BACKGROUND: Although people living with cystic fibrosis (PwCF) often have some risk factors for cardiovascular disease, including diabetes and chronic inflammation, little is known about the long-term cardiac risk in this condition. We aimed to determine the characteristics, rates and outcomes for cardiac disease in CF. METHODS: We looked at rates and outcomes for cardiac disease in 5649 adult PwCF in the UK CF Registry and 6265 adult PwCF in TriNetX (a global federated database of electronic healthcare record data). We used propensity matching to compare risk of major adverse cardiac events (MACE) (myocardial infarction, left-sided heart failure and atrial fibrillation) in PwCF against matched non-CF comparators in the general population and other inflammatory diseases. RESULTS: PwCF had a high prevalence of diabetes but low rates of hypertension and obesity. Some cardiac risk factors (age, diabetes and hypertension) were associated with MACE, but relationships between disease-specific risk factors (lung function and intravenous antibiotic days) were also observed. In propensity score-matched analyses, PwCF had higher risk of MACE than matched general population comparators (hazard ratio (HR) 1.65, 95% CI 1.40-1.95; p<0.001) and an equivalent or higher relative risk compared with other inflammatory conditions considered "high risk" for cardiovascular disease, including systemic lupus erythematosus (HR 0.95, 95% CI 0.82-1.09; p=0.44), rheumatoid arthritis (HR 1.21, 95% CI 1.00-1.48; p<0.001) and HIV (HR 0.93, 95% CI 0.82-1.06; p=0.29). CONCLUSIONS: PwCF are at increased risk of adverse cardiac disease events. Future work should focus on defining determinants of cardiovascular risk such that appropriate risk stratification can be employed.

Prediction of early death after atrial fibrillation diagnosis using a machine learning approach: A French nationwide cohort study.

AIMS: Atrial fibrillation is associated with important mortality but the usual clinical risk factor based scores only modestly predict mortality. This study aimed to develop machine learning models for the prediction of death occurrence within the year following atrial fibrillation diagnosis and compare predictive ability against usual clinical risk scores. METHODS AND RESULTS: We used a nationwide cohort of 2,435,541 newly diagnosed atrial fibrillation patients seen in French hospitals from 2011 to 2019. Three machine learning models were trained to predict mortality within the first year using a training set (70% of the cohort). The best model was selected to be evaluated and compared with previously published scores on the validation set (30% of the cohort). Discrimination of the best model was evaluated using the C index. Within the first year following atrial fibrillation diagnosis, 342,005 patients (14.4%) died after a period of 83 (SD 98) days (median 37 [10-129]). The best machine learning model selected was a deep neural network with a C index of 0.785 (95% CI, 0.781-0.789) on the validation set. Compared to clinical risk scores, the selected model was superior to the CHA2DS2-VASc and HAS-BLED risk scores and superior to dedicated scores such as Charlson Comorbidity Index and Hospital Frailty Risk Score to predict death within the year following atrial fibrillation diagnosis (C indexes: 0.597; 0.562; 0.643; 0.626 respectively. P < .0001). CONCLUSION: Machine learning algorithms predict early death after atrial fibrillation diagnosis and may help clinicians to better risk stratify atrial fibrillation patients at high risk of mortality.

Incident heart failure, arrhythmias and cardiovascular outcomes with sodium-glucose cotransporter 2 (SGLT2) inhibitor use in patients with diabetes: Insights from a global federated electronic medical record database.

AIM: To investigate the impact of sodium-glucose cotransporter 2 (SGLT2) inhibitors on the risk of incident heart failure and adverse cardiovascular outcomes. METHODS: All patients with diabetes who were registered between January 2018 and December 2019 were identified from a federated electronic medical record database (TriNetX) and followed up for 2 years. A 1:1 propensity-score matching (PSM) analysis was performed to balance the SGLT2 inhibitor and non-SGLT2 inhibitor cohorts. The primary outcome was incident heart failure. Secondary outcomes included all-cause mortality, cardiac arrest, ventricular tachycardia/ventricular fibrillation (VT/VF), incident atrial fibrillation (AF), ischaemic stroke/transient ischaemic attack (TIA), composite of arterial and venous thrombotic events, and composite of incident VT/VF and cardiac arrest. RESULTS: A total of 131 189 and 2 692 985 patients were treated with and without SGLT2 inhibitors, respectively. After PSM, 131 188 patients remained in each group. The risk of incident heart failure was significantly lower in the SGLT2 inhibitor cohort compared to the non-SGLT2 inhibitor cohort (hazard ratio [HR] 0.70, 95% confidence interval [CI] 0.68-0.73). SGLT2 inhibitor use was also associated with a significantly lower risk of all-cause mortality (HR 0.61, 95% CI 0.58-0.64), cardiac arrest (HR 0.70, 95% CI 0.63-0.78), incident AF (HR 0.81, 95% CI 0.76-0.84), ischaemic stroke/TIA (HR 0.90, 95% CI 0.88-0.93), composite of arterial and venous thrombotic events (HR 0.90, 95% CI 0.88-0.92), and composite of incident VT/VF and cardiac arrest (HR 0.76, 95% CI 0.71-0.81). There were no significant differences for VT/VF (HR 0.94, 95% CI 0.88-1.00). CONCLUSION: Use of SGLT2 inhibitors was associated with a significant reduction in the risk of incident heart failure and adverse cardiovascular outcomes but not ventricular arrhythmias.

Contemporary management of atrial fibrillation and the predicted vs. absolute risk of ischaemic stroke despite treatment: a report from ESC-EHRA EORP-AF Long-Term General Registry.

BACKGROUND: Risk stratification in patients with atrial fibrillation (AF) is important to facilitate guideline-directed therapies. The Calculator of Absolute Stroke Risk (CARS) scheme enables an individualized estimation of 1-year absolute risk of stroke in AF. We aimed to investigate the predicted and absolute risks of ischaemic stroke, and evaluate whether CARS (and CHA2DS2-VASc score) may be useful for identifying high risk patients with AF despite contemporary treatment. METHODS: We utilized the EORP-AF General Long-Term Registry which prospectively enrolled patients with AF from 250 centres across 27 participating European countries. Patients with sufficient data to determine CARS and CHA2DS2-VASc score, and reported outcomes of ischaemic stroke were included in this analysis. The primary outcome of ischaemic stroke was recorded over a 2-year follow-up period. RESULTS: A total of 9444 patients were included (mean age 69.1 [±11.4] years; 3776 [40.0%] females). There was a high uptake (87.9%) of anticoagulation therapy, predominantly with vitamin K antagonist (50.0%). Over a mean follow-up period of 24 months, there were a total of 101 (1.1%) ischaemic stroke events. In the entire cohort, the median CARS and absolute annual risks of ischaemic stroke were 2.60 (IQR 1.60-4.00) and 0.53% (95%CI 0.43-0.64%), respectively. There was no statistical difference between the predictive performance of CARS and CHA2DS2-VASc score (0.621 [95%CI 0.563-0.678] vs. 0.626 [95%CI 0.573-0.680], P = 0.725). CONCLUSION: Contemporary management of AF was associated with a low risk of ischaemic stroke. CARS and CHA2DS2-VASc score may be useful to identify high risk patients despite treatment who may benefit from more aggressive treatment and follow-up.

Incidence of clinical atrial fibrillation and related complications using a screening algorithm at a nationwide level.

AIMS: In a recent position paper, the European Heart Rhythm Association (EHRA) proposed an algorithm for the screening and management of arrhythmias using digital devices. In patients with prior stroke, a systematic screening approach for atrial fibrillation (AF) should always be implemented, preferably immediately after the event. Patients with increasing age and with specific cardiovascular or non-cardiovascular comorbidities are also deemed to be at higher risk. From a large nationwide database, the aim was to analyse AF incidence rates derived from this new EHRA algorithm. METHODS AND RESULTS: Using the French administrative hospital discharge database, all patients hospitalized in 2012 without a history of AF, and with at least a 5-year follow-up (FU) (or if they died earlier), were included. The yearly incidence of AF was calculated in each subgroup defined by the algorithm proposed by EHRA based on a history of previous stroke, increasing age, and eight comorbidities identified via International Classification of Diseases 10th Revision codes. Out of the 4526 104 patients included (mean age 58.9 ± 18.9 years, 64.5% women), 1% had a history of stroke. Among those with no history of stroke, 18% were aged 65-74 years and 21% were ≥75 years. During FU, 327 012 patients had an incidence of AF (yearly incidence 1.86% in the overall population). Implementation of the EHRA algorithm divided the population into six risk groups: patients with a history of stroke (group 1); patients > 75 years (group 2); patients aged 65-74 years with or without comorbidity (groups 3a and 3b); and patients < 65 years with or without comorbidity (groups 4a and 4b). The yearly incidences of AF were 4.58% per year (group 2), 6.21% per year (group 2), 3.50% per year (group 3a), 2.01% per year (group 3b), 1.23% per year (group 4a), and 0.35% per year (group 4b). In patients aged < 65 years, the annual incidence of AF increased progressively according to the number of comorbidities from 0.35% (no comorbidities) to 9.08% (eight comorbidities). For those aged 65-75 years, the same trend was observed, i.e. increasing from 2.01% (no comorbidities) to 11.47% (eight comorbidities). CONCLUSION: These findings at a nationwide scale confirm the relevance of the subgroups in the EHRA algorithm for identifying a higher risk of AF incidence, showing that older patients (>75 years, regardless of comorbidities) have a higher incidence of AF than those with prior ischaemic stroke. Further studies are needed to evaluate the usefulness of algorithm-based risk stratification strategies for AF screening and the impact of screening on major cardiovascular event rates.

EHRA expert consensus document on the management of arrhythmias in frailty syndrome, endorsed by the Heart Rhythm Society (HRS), Asia Pacific Heart Rhythm Society (APHRS), Latin America Heart Rhythm Society (LAHRS), and Cardiac Arrhythmia Society of Southern Africa (CASSA).

There is an increasing proportion of the general population surviving to old age with significant chronic disease, multi-morbidity, and disability. The prevalence of pre-frail state and frailty syndrome increases exponentially with advancing age and is associated with greater morbidity, disability, hospitalization, institutionalization, mortality, and health care resource use. Frailty represents a global problem, making early identification, evaluation, and treatment to prevent the cascade of events leading from functional decline to disability and death, one of the challenges of geriatric and general medicine. Cardiac arrhythmias are common in advancing age, chronic illness, and frailty and include a broad spectrum of rhythm and conduction abnormalities. However, no systematic studies or recommendations on the management of arrhythmias are available specifically for the elderly and frail population, and the uptake of many effective antiarrhythmic therapies in these patients remains the slowest. This European Heart Rhythm Association (EHRA) consensus document focuses on the biology of frailty, common comorbidities, and methods of assessing frailty, in respect to a specific issue of arrhythmias and conduction disease, provide evidence base advice on the management of arrhythmias in patients with frailty syndrome, and identifies knowledge gaps and directions for future research.

Ischemic Stroke in Patients With Hypertrophic Cardiomyopathy According to Presence or Absence of Atrial Fibrillation.

BACKGROUND AND PURPOSE: Patients with hypertrophic cardiomyopathy (HCM) have high risk of ischemic stroke (IS), especially if atrial fibrillation (AF) is present. Improvements in risk stratification are needed to help identify those patients with HCM at higher risk of stroke, whether AF is present or not. METHODS: This French longitudinal cohort study from the database covering hospital care from 2010 to 2019 analyzed adults hospitalized with isolated HCM. A logistic regression model was used to construct a French HCM score, which was compared with the HCM Risk-CVA and CHA2DS2-VASc scores using c-indexes and calibration analysis. RESULTS: In 32 206 patients with isolated HCM, 12 498 (38.8%) had AF, and 2489 (7.7%) sustained an IS during follow-up. AF in patients with HCM was independently associated with a higher risk for death (hazard ratio, 1.129 [95% CI, 1.088-1.172]), cardiovascular death (hazard ratio, 1.254 [95% CI, 1.177-1.337]), IS (hazard ratio, 1.210 [95% CI, 1.111-1.317]), and other major cardiovascular events. Independent predictors of IS in HCM were older age, heart failure, AF, prior IS, smoking and poor nutrition (all P<0.05). For the HCM Risk-CVA score, CHA2DS2-VASc score and a French HCM score, all c-indexes were 0.65 to 0.70, with good calibration. Among patients with AF, the CHA2DS2-VASc score had marginal improvement over the HCM Risk-CVA score but was less predictive compared with the French HCM score (P=0.001). In patients without AF, both HCM Risk-CVA score and the French HCM score had significantly better prediction compared with CHA2DS2-VASc (both P<0.0001). Decision curve analysis demonstrated that the French HCM score had the best clinical usefulness of the 3 tested risk scores. CONCLUSIONS: Patients with HCM have a high prevalence of AF and a significant risk of IS, and the presence of AF in patients with HCM was independently associated with worse outcomes. A simple French HCM score shows good prediction of IS in patients with HCM and clinical usefulness, with good calibration.

Clinical complexity and impact of the ABC (Atrial fibrillation Better Care) pathway in patients with atrial fibrillation: a report from the ESC-EHRA EURObservational Research Programme in AF General Long-Term Registry.

BACKGROUND: Clinical complexity is increasingly prevalent among patients with atrial fibrillation (AF). The 'Atrial fibrillation Better Care' (ABC) pathway approach has been proposed to streamline a more holistic and integrated approach to AF care; however, there are limited data on its usefulness among clinically complex patients. We aim to determine the impact of ABC pathway in a contemporary cohort of clinically complex AF patients. METHODS: From the ESC-EHRA EORP-AF General Long-Term Registry, we analysed clinically complex AF patients, defined as the presence of frailty, multimorbidity and/or polypharmacy. A K-medoids cluster analysis was performed to identify different groups of clinical complexity. The impact of an ABC-adherent approach on major outcomes was analysed through Cox-regression analyses and delay of event (DoE) analyses. RESULTS: Among 9966 AF patients included, 8289 (83.1%) were clinically complex. Adherence to the ABC pathway in the clinically complex group reduced the risk of all-cause death (adjusted HR [aHR]: 0.72, 95%CI 0.58-0.91), major adverse cardiovascular events (MACEs; aHR: 0.68, 95%CI 0.52-0.87) and composite outcome (aHR: 0.70, 95%CI: 0.58-0.85). Adherence to the ABC pathway was associated with a significant reduction in the risk of death (aHR: 0.74, 95%CI 0.56-0.98) and composite outcome (aHR: 0.76, 95%CI 0.60-0.96) also in the high-complexity cluster; similar trends were observed for MACEs. In DoE analyses, an ABC-adherent approach resulted in significant gains in event-free survival for all the outcomes investigated in clinically complex patients. Based on absolute risk reduction at 1 year of follow-up, the number needed to treat for ABC pathway adherence was 24 for all-cause death, 31 for MACEs and 20 for the composite outcome. CONCLUSIONS: An ABC-adherent approach reduces the risk of major outcomes in clinically complex AF patients. Ensuring adherence to the ABC pathway is essential to improve clinical outcomes among clinically complex AF patients.

Breast cancer and incident cardiovascular events: A systematic analysis at the nationwide level.

BACKGROUND: Breast cancer (BC) is one of the most common cancers worldwide, and the treatments are frequently cardiotoxic. Whether BC is associated with a higher risk of cardiovascular events is a matter of debate. We evaluated the associations among BC and incident cardiovascular events in a contemporary population. METHODS: All female patients discharged from French hospitals in 2013 with at least 5 years of follow-up and without a history of major adverse cardiovascular event (myocardial infarction [MI], heart failure [HF], ischaemic stroke or all-cause death, and MACE-HF, which includes cardiovascular death, MI, ischaemic stroke or HF) or cancer (except BC) were identified. After propensity score matching, patients with BC were matched 1:1 with patients with no BC. Hazard ratios (HRs) for cardiovascular events during follow-up were adjusted on age, sex and smoking status at baseline. RESULTS: 1,795,759 patients were included, among whom 64,480 (4.3%) had history of BC. During a mean follow-up of 5.1 years, matched female patients with BC had a higher risk of all-cause death (HR 3.55, 95% confidence interval [CI]: 3.47-3.64), new-onset HF (HR 1.08, 95% CI 1.04-1.11), major bleeding (HR 1.43, 95% CI 1.36-1.49), MACE-HF (HR 1.07, 95% CI 1.04-1.11) and net adverse clinical events (NACE) including all-cause death, MI, ischaemic stroke, HF or major bleeding (HR 2.53, 95% CI 2.48-2.58) compared with those with no BC. By contrast, risks were not higher for cardiovascular death (HR 0.94, 95% CI 0.88-1.00) and were lower for MI (HR 0.81, 95% CI 0.75-0.88) and ischaemic stroke (HR 0.85, 95% CI 0.79-1.11). CONCLUSIONS: In a large and contemporary analysis of female patients seen in French hospitals, women with history of breast cancer had a higher risk of all-cause mortality, new-onset heart failure and major bleeding compared to a matched cohort of women without breast cancer. In contrast, they have a reduced risk of cardiovascular mortality, MI and stroke.

Impact of renal impairment on atrial fibrillation: ESC-EHRA EORP-AF Long-Term General Registry.

BACKGROUND: Atrial fibrillation (AF) and renal impairment share a bidirectional relationship with important pathophysiological interactions. We evaluated the impact of renal impairment in a contemporary cohort of patients with AF. METHODS: We utilised the ESC-EHRA EORP-AF Long-Term General Registry. Outcomes were analysed according to renal function by CKD-EPI equation. The primary endpoint was a composite of thromboembolism, major bleeding, acute coronary syndrome and all-cause death. Secondary endpoints were each of these separately including ischaemic stroke, haemorrhagic event, intracranial haemorrhage, cardiovascular death and hospital admission. RESULTS: A total of 9306 patients were included. The distribution of patients with no, mild, moderate and severe renal impairment at baseline were 16.9%, 49.3%, 30% and 3.8%, respectively. AF patients with impaired renal function were older, more likely to be females, had worse cardiac imaging parameters and multiple comorbidities. Among patients with an indication for anticoagulation, prescription of these agents was reduced in those with severe renal impairment, p < .001. Over 24 months, impaired renal function was associated with significantly greater incidence of the primary composite outcome and all secondary outcomes. Multivariable Cox regression analysis demonstrated an inverse relationship between eGFR and the primary outcome (HR 1.07 [95% CI, 1.01-1.14] per 10 ml/min/1.73 m2 decrease), that was most notable in patients with eGFR <30 ml/min/1.73 m2 (HR 2.21 [95% CI, 1.23-3.99] compared to eGFR ≥90 ml/min/1.73 m2 ). CONCLUSION: A significant proportion of patients with AF suffer from concomitant renal impairment which impacts their overall management. Furthermore, renal impairment is an independent predictor of major adverse events including thromboembolism, major bleeding, acute coronary syndrome and all-cause death in patients with AF.

Impact of malignancy on outcomes in European patients with atrial fibrillation: A report from the ESC-EHRA EURObservational research programme in atrial fibrillation general long-term registry.

BACKGROUND: The management of patients with atrial fibrillation (AF) and malignancy is challenging given the paucity of evidence supporting their appropriate clinical management. PURPOSE: To evaluate the outcomes of patients with active or prior malignancy in a contemporary cohort of European AF patients. METHODS: Patients enrolled in the EURObservational Research Programme in AF General Long-Term Registry were categorized into 3 categories: No Malignancy (NoMal), Prior Malignancy (PriorMal) and Active Malignancy (ActiveMal). The primary outcomes were all-cause death and the composite outcome MACE. RESULTS: A total of 10 383 patients were analysed. Of these, 9597 (92.4%) were NoMal patients, 577 (5.6%) PriorMal and 209 (2%) ActiveMal. Lack of any antithrombotic treatment was more prevalent in ActiveMal patients (12.4%) as compared to other groups (5.0% vs 6.3% for PriorMal and NoMal, p < .001). After a median follow-up of 730 days, there were 982 (9.5%) deaths and 950 (9.7%) MACE events. ActiveMal was independently associated with a higher risk for all-cause death (HR 2.90, 95% CI 2.23-3.76) and MACE (HR 1.54, 95% CI 1.03-2.31), as well as any haemorrhagic events and major bleeding (OR 2.42, 95% CI 1.49-3.91 and OR 4.18, 95% CI 2.49-7.01, respectively). Use of oral anticoagulants was not significantly associated with a higher risk for all-cause death or bleeding in ActiveMal patients. CONCLUSIONS: In a large contemporary cohort of AF patients, active malignancy was independently associated with all-cause death, MACE and haemorrhagic events. Use of anticoagulants was not associated with a higher risk of all-cause death in patients with active malignancies.

Valve-in-valve transcatheter aortic valve replacement or re-surgical aortic valve replacement in degenerated bioprostheses: A systematic review and meta-analysis of short and midterm results.

INTRODUCTION: Despite limited to short and midterm outcomes, valve-in-valve (ViV) transcatheter aortic valve implantation (TAVI) has emerged as a valid alternative to re-surgical aortic valve replacement (re-SAVR) for high- and intermediate-risk patients with degenerated surgical bioprosthesis. METHODS: All studies comparing multivariate adjustment between ViV TAVI and re-SAVR were screened. The primary end-points were all-cause and cardiovascular (CV) mortality at 30 days and at Midterm follow-up. Short-term complications were the secondary endpoints. RESULTS: We obtained data from 11 studies, encompassing 8570 patients, 4224 undergoing ViV TAVI, and 4346 re-SAVR. Four studies included intermediate-risk patients and seven high-risk patients. 30-day all-cause and CV mortality were significantly lower in ViV (odds ratio [OR] 0.43, 95% confidence intervals [CIs] 0.29-0.64 and OR 0.44, 0.26-0.73 respectively), while after a mean follow-up of 717 (180-1825) days, there was no difference between the two groups (OR 1.04, 0.87-1.25 and OR 1.05, 0.78-1.43, respectively). The risk of stroke (OR 1.03, 0.59-1.82), MI (OR 0.70, 0.34-1.44), major vascular complications (OR 0.92, 0.50-1.67), and permanent pacemaker implantation (OR 0.67, 0.36-1.25) at 30 days did not differ, while major bleedings and new-onset atrial fibrillation were significantly lower in ViV patients (OR 0.41, 0.25-0.67 and OR 0.23, 0.12-0.42, respectively, all 95% CIs). CONCLUSIONS: In high- and intermediate-risk patients with degenerated surgical bioprostheses, ViV TAVI is associated with reduced short-term mortality, compared with re-SAVR. Nevertheless, no differences were found in all-cause and CV mortality at midterm follow-up. PROSPERO CRD42021226488.