Evaluation of the specificity of the 2023 European Society of Cardiology classification for infective endocarditis.

BACKGROUND: The 2023 Duke-ISCVID and 2023 ESC classifications have recently issued independent diagnostic criteria for infective endocarditis (IE), updating the 2015 ESC criteria. OBJECTIVES: The specificity of the 2023 ESC criteria should be evaluated and compared to the two other classifications in IE suspected patients. METHODS: We retrospectively collected the characteristics of patients hospitalised in Bichat University Hospital, in 2021, who had been evaluated for suspicion of IE, and in whom IE diagnosis was finally rejected. All were classified by 2015 ESC, 2023 Duke-ISCVID, and 2023 ESC. RESULTS: In total 130 patients were analysed. Mean age was 62 years, 64.6% were male, 30.0% had prosthetic cardiac valve or valve repair, 16.2% had cardiac implanted electronic device, and 23.1% other cardiac conditions. Overall, 2, 5 and 5 patients were falsely classified as definite IE with the 2015 ESC, 2023 Duke-ISCVID and 2023 ESC criteria, respectively. The corresponding specificities were 99% (95% CI [94%; 100%], 96% (95% CI [91%; 99%]), and 96% (95% CI [91%; 99%]). CONCLUSION: The 2023 ESC and the 2023 Duke-ISCVID criteria are highly specific, although slightly less than the 2015 ESC criteria, for ruling out the diagnosis of definite IE.HIGHLIGHTS2023 Duke-ISCVID and 2023 ESC criteria are recently issued diagnostic classifications2023 ESC criteria have an excellent specificity, equivalent to the 2023 Duke-ISCVID one2023 ESC criteria and the 2023 Duke-ISCVID are less specific than the 2015 ESC criteriaSpecificities were quite similar according to the nature of the cardiac valve (native or prosthetic valve) or the duration of antibiotic therapy.

Diagnostic Yield of Exome Sequencing in Early-Onset Hypertensive Nephropathy in Adults.

INTRODUCTION: Hypertensive nephrosclerosis (HN) ranks as one of the most frequent causes of chronic kidney disease (CKD), but its very existence has repeatedly been called into question, especially in young adults. Its diagnostic framework is established chiefly on non-specific clinical criteria, and its defining histopathological set of features is in fact shared by numerous other conditions. Genetic testing based on exome sequencing (ES) has emerged as a comprehensive tool to detect Mendelian diseases in timely fashion in nephrology, with a significant number of re-established diagnoses. The aim of this study was to investigate the diagnostic yield of ES in patients with a clinical diagnosis of hypertensive nephropathy. METHOD: Since September 2018, ES has been readily available as part of the routine diagnostic work-up in our institution. The indication of ES includes hypertensive nephropathy of early onset (i.e., <45 years old). We retrospectively collected the ES data performed in the context of hypertensive nephropathy in our institution between September 2018 and February 2021. RESULTS: A total of 128 patients were sequenced in the context of hypertensive nephropathy with early onset. The chief indications of ES were an early onset of CKD (47%), family history of kidney disease (8%), or both (18%). We detected diagnostic variants in 19 of the 128 patients (15%), encompassing a total of 13 different monogenic disorders. The diagnostic yield of ES was lower in patients of African ancestry (diagnostic yield of 7 vs. 30% in non-African ancestry patients, p < 0.001). CONCLUSIONS: The high diagnostic yield of ES (15%) in a population of patients thought to have HN casts further doubts on the validity of the existing diagnosis criteria, including histological criteria, supposed to characterize the condition. This was especially true in patients with no African ancestry, where ES positivity reached 30%.

Sex differences and outcomes in surgical infective endocarditis.

BACKGROUND: Cardiac surgery for infective endocarditis (IE) is associated with significant hospital mortality, and female sex may be associated with worse outcomes. However, the impact of sex on the presenting characteristics, management, and outcomes of patients operated on for acute infective endocarditis (IE) has not been adequately studied. OBJECTIVES: The goal of our study was to analyse differences in management and outcome of IE between women and men who undergo surgery. METHODS: Clinical data of 717 patients undergoing cardiac surgery for IE between December 2005 and December 2019 were prospectively collected. Sex-related postoperative outcomes including in-hospital mortality were recorded. Univariable and multivariable analyses were performed to identify potential sex-related determinant of in-hospital mortality. RESULTS: In all, 532 male patients (74.2%) and 185 female patients (25.8%) underwent surgery for IE. At baseline, women had more frequent mitral regurgitation with 63 patients (34.1%) than men with 135 patients (25.4%) (P = 0.002). Female sex was associated with higher in-hospital mortality (23.2% versus 17.3%, P = 0.049). However, multivariable analysis revealed age (P < 0.01), antibiotics < 7 days before surgery (P = 0.01) and staphylococcal IE (P < 0.01) but not female sex (P = 0.99) as independent determinants of hospital mortality. CONCLUSIONS: In this study of patients operated-on for IE, female sex was associated with more severe manifestations of IE and significantly higher in-hospital mortality. However, after multivariable analysis, initial presentation, but not sex, seemed to determine clinical outcomes.

Evaluation of the Specificity of the 2023 Duke-International Society of Cardiovascular Infectious Diseases Classification for Infective Endocarditis.

BACKGROUND: The 2023 Duke-ISCVID (International Society of Cardiovascular Infectious Diseases) classification is a new diagnostic tool for infective endocarditis, updating the 2000 modified Duke and the 2015 European Society for Cardiology (ESC) classifications. In comparison, its sensitivity is higher; however, its specificity remains to be evaluated and compared to that of the 2 other classifications in endocarditis suspected patients. METHODS: We retrospectively collected the characteristics of patients hospitalized in Bichat University's Hospital, Paris, in 2021, who had been evaluated for clinical suspicion of endocarditis, have had at least a transthoracic echocardiography, 2 pairs of blood cultures, 3-month follow-up and in whom endocarditis diagnosis was finally rejected. All patients were classified by 2000 modified Duke, 2015 ESC and 2023 Duke-ISCVID, as though the endocarditis diagnosis had not been rejected. RESULTS: In total, 130 patients' charts were analyzed. Mean age was 62 years, 84 (64.6%) were male, 39 (30.0%) had prosthetic cardiac valve or valve repair, 21 (16.2%) cardiac implanted electronic device, and 30 (23.1%) other cardiac conditions. Overall, 5, 2, and 5 patients were falsely classified as definite endocarditis with the 2000 modified Duke, 2015 ESC, and 2023 Duke-ISCVID classifications, respectively. The corresponding specificities were 96.2% (95% confidence interval [CI] [90.8%, 98.6%]), 98.5% (95% CI [93.9%, 99.7%]), and 96.2% (95% CI [90.8%, 98.6%]). The rates of possible endocarditis were of 38%, 35%, and 35% in the 3 classifications, respectively. CONCLUSIONS: The 2023 Duke-ISCVID classification is highly specific for ruling out the diagnosis of definite infective endocarditis in patients who had been evaluated for IE.

Comparison of Direct Oral Anticoagulants vs Vitamin K Antagonists After Transcatheter Mitral Valve Replacement.

BACKGROUND: There is currently no established recommendation for antithrombotic treatment following transcatheter mitral valve replacement (TMVR). However, based on the analogy with surgical mitral bioprosthesis, vitamin K antagonists (VKAs) are predominantly used. OBJECTIVES: The purpose of this study was to compare bleeding and thrombotic events associated with direct oral anticoagulants (DOACs) or VKAs in a prospective cohort of TMVR patients. METHODS: We enrolled consecutive patients who underwent transseptal TMVR using a SAPIEN family prosthesis at our center between 2011 and 2023. The primary outcome was the occurrence of bleeding. VKAs were administered to patients until October 2019, after which DOACs were prescribed. The median follow-up was 4.7 months (Q1-Q3: 2.6-6.7 months). RESULTS: A total of 156 patients were included. The mean age was 65 ± 18.5 years, and 103 patients (66%) were women. The median EuroSCORE II was 7.48% (Q1-Q3: 3.80%-12.97%). Of the participants, 20.5% received DOACs and 79.5% were treated with VKAs. The primary outcome was observed in 50 (40%) patients in the VKA group and 3 (9%) patients in the DOAC group (adjusted HR: 0.21; 95% CI: 0.06-0.74; P = 0.02). Treatment with DOAC was associated with a shorter length of hospital stay. No significant differences were found in terms of thrombotic events, major vascular complications, stroke, or death. CONCLUSIONS: The use of DOACs after TMVR, compared with VKAs, appears to reduce the risk of bleeding complications and decrease the length of hospital stay for patients, without a significant increase in the risk of thrombotic events.

Transcatheter Mitral Valve Replacement Using Transcatheter Aortic Valve or Dedicated Devices: Current Evidence and Future Prospects.

Transcatheter mitral valve replacement (TMVR) is a novel and evolving field dedicated to addressing the therapeutic challenges posed by patients at high surgical risk with mitral valve disease. TMVR can be categorized into two distinct fields based on the type of device and its specific indications: TMVR with transcatheter aortic valves (TAV) and TMVR with dedicated devices. Similar to aortic stenosis, TMVR with TAV requires a rigid support structure to secure the valve in place. As a result, it is indicated for patients with failing bioprothesis or surgical rings or mitral valve disease associated with severe mitral annular calcification (MAC), which furnishes the necessary foundation for valve anchoring. While TMVR with TAV has shown promising outcomes in valve-in-valve procedures, its effectiveness remains more contentious in valve-in-ring or valve-in-MAC procedures. Conversely, TMVR with dedicated devices seeks to address native mitral regurgitation, whether accompanied by MAC or not, providing an alternative to Transcatheter Edge-to-Edge Repair (TEER) when TEER is not feasible or expected to yield unsatisfactory results. This emerging field is gradually surmounting technical challenges, including anchoring a valve in a non-calcified annulus and transitioning from the transapical route to the transeptal approach. Numerous devices are presently undergoing clinical trials. This review aims to furnish an overview of the supporting evidence for TMVR using TAV in each specific indication (valve-in-valve, valve-in-ring, valve-in-MAC). Subsequently, we will discuss the anticipated benefits of TMVR with dedicated devices over TEER, summarize the characteristics and clinical results of TMVR systems currently under investigation, and outline future prospects in this field.

Management and outcomes of carcinoid heart disease with liver metastases of midgut neuroendocrine tumours.

OBJECTIVE: Despite recent advances in surgical and interventional techniques, knowledge on the management of carcinoid heart disease (CHD) remains limited. In a cohort of patients with liver metastases of midgut neuroendocrine tumours (NETs), we aimed to describe the perioperative management and short-term outcomes of CHD. METHODS: From January 2003 to June 2022, consecutive patients with liver metastases of midgut NETs and severe CHD (severe valve disease with symptoms and/or right ventricular enlargement) were included at Beaujon and Bichat hospitals. All patients underwent clinical evaluation and echocardiography. RESULTS: Out of 43 (16%) consecutive patients with severe CHD and liver metastases of midgut NETs, 79% presented with right-sided heart failure. Tricuspid valve replacement was performed in 26 (53%) patients including 19 (73%) cases of combined pulmonary valve replacement. The 30-day postoperative mortality rate was high (19%), and preoperative heart failure was associated with worse survival (p=0.02). Epicardial pacemakers were systematically implanted in operated patients and 25% were permanently paced. A postoperative positive right ventricular remodelling was observed (p<0.001). A greater myofibroblastic infiltration was observed in pulmonary versus tricuspid valves (p<0.001), suggesting that they may have been explanted at an earlier stage of the disease than the tricuspid valve, with therefore potential for evolution. CONCLUSIONS: We observed a high postoperative mortality rate and baseline right-sided heart failure was associated with worse outcome. In surviving patients, a positive right ventricular remodelling was observed. Prospective, multicentre studies are warranted to better define the management strategy and to identify biomarkers associated with outcome in CHD.

Effect of alirocumab on cataracts in patients with acute coronary syndromes.

BACKGROUND: Some data suggest that low levels of low-density lipoprotein cholesterol (LDL-C) are associated with risk of cataracts. Proprotein convertase subtilisin-kexin type 9 (PCSK9) inhibitors reduce LDL-C below levels achieved with statins alone. We determined whether the incidence of cataracts was influenced by treatment with the PCSK9 inhibitor alirocumab versus placebo, and whether that incidence was affected by achieved LDL-C levels. METHODS: The ODYSSEY OUTCOMES trial (NCT01663402) compared alirocumab with placebo in 18,924 patients with recent acute coronary syndrome receiving high-intensity or maximum-tolerated statin. Incident cataracts were pre-specified events of interest. In multivariable analysis using propensity score-matching on characteristics including cataract risk factors, incident cataracts were compared in the alirocumab and placebo groups according to LDL-C levels achieved with alirocumab. RESULTS: Over median follow-up of 2.8 years (interquartile range 2.3 - 3.4), the incidence of cataracts was similar with alirocumab (127/9462 [1.3%]) versus placebo (134/9462 [1.4%]); hazard ratio [HR] 0.94, 95% confidence interval [CI] 0.74 - 1.20). In patients treated with alirocumab with ≥ 2 LDL-C values < 25 mg/dL (0.65 mmol/L), the incidence of cataracts was 71/4305 (1.6%), versus 60/4305 (1.4%) in propensity score-matched patients from the placebo group (HR 1.10, CI 95% 0.78 - 1.55). In patients treated with alirocumab with ≥ 2 LDL-C values < 15 mg/dL (0.39 mmol/L), the incidence of cataracts was 13/782 (1.7%), versus 36/2346 (1.5%) in matched patients from the placebo group (HR 1.03, CI 95% 0.54 - 1.94). CONCLUSION: Treatment with alirocumab versus placebo, added to statin, did not influence the incidence of cataracts, even when achieved LDL-C levels on alirocumab were very low. Longer follow-up studies might be necessary to exclude the long-term effects on the incidence or progression of cataracts. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT01663402 .

Carcinoid heart disease in patients with midgut neuroendocrine tumours.

Carcinoid heart disease (CHD) is the main complication of carcinoid syndrome (CS) associated with metastatic small intestine neuroendocrine tumours (NETs). The pathophysiology of CHD is partly understood but vasoactive hormones secreted by NETs, especially serotonin, play a major role, leading to the formation of fibrous plaques. These plaque-like deposits involve the right side of the heart in >90% of cases, particularly the tricuspid and pulmonary valves, which become thickened, retracted and immobile, resulting in regurgitation or stenosis. CHD represents a major diagnostic and therapeutic challenge for patients with NET and CS and is associated with increased risk of morbidity and mortality. CHD often occurs 2-5 years after the diagnosis of metastatic NET, but diagnosis of CHD can be delayed as patients are often asymptomatic for a long time despite severe heart valve involvement. Circulating biomarkers (5HIAA, NT-proBNP) are relevant tools but transthoracic echocardiography is the key examination for diagnosis and follow-up of CHD. However, there is no consensus on the optimal indications and frequency of TTE and biomarker dosing regarding screening and diagnosis. Treatment of CHD is complex and requires a multidisciplinary approach. It relies on antitumour treatment, control of CS and surgical valve replacement in cases of severe CHD. However, cardiac surgery is associated with a high risk of mortality, notably due to perioperative carcinoid crisis and right ventricular dysfunction. Timing of surgery is the most crucial point of CHD management and relies on the case-by-case determination of the optimal compromise between tumour progression, cardiac symptoms and CS control.

Beta-blocker prescription and outcomes in uncomplicated acute myocardial infarction: Insight from the ePARIS registry.

BACKGROUND: Systematic prescription of beta-blockers after myocardial infarction remains an open question in the era of revascularization, especially for patients with uncomplicated myocardial infarction. OBJECTIVE: To evaluate in a real-life registry the proportion of patients with uncomplicated myocardial infarction (preserved left ventricular ejection fraction and no cardiovascular event within the first 6 months), and to report their characteristics, outcomes and beta-blocker use. METHODS: We included 1887 consecutive patients with ST-segment elevation myocardial infarction from the prospective ePARIS registry. Patients were divided into three groups: the "uncomplicated myocardial infarction" group (n=1060), defined by a left ventricular ejection fraction ≥ 40% and a 6-month period free from cardiovascular events; the "complicated myocardial infarction" group (n=366), defined by a left ventricular ejection fraction ≥ 40% and a recurrent cardiovascular event in the first 6 months; and the "left ventricular dysfunction" group (n=461), defined by a left ventricular ejection fraction<40%. RESULTS: During a median follow-up of 2.7 years (interquartile range 1.0-4.9 years), the "uncomplicated myocardial infarction" group was at low mortality risk compared with the "complicated myocardial infarction" group (hazard ratio 0.38, 95% confidence interval 0.25-0.58; P<0.01) and the "left ventricular dysfunction" group (hazard ratio 0.22, 95% confidence interval 0.15-0.32; P<0.01). Beta-blockers were prescribed at discharge predominantly in the "uncomplicated myocardial infarction" group (93%) compared with 87% in the "complicated myocardial infarction" group and 81% in the "left ventricular dysfunction" group. CONCLUSIONS: Beta-blockers are less prescribed in patients who may need them the most. The benefit of beta-blockers-largely prescribed in lower-risk patients-remains to be shown beyond the first 6 months for these patients with no left ventricular dysfunction and no recurrent events.

Interleukin-1ß and Risk of Premature Death in Patients With Myocardial Infarction.

BACKGROUND: Inhibition of the interleukin (IL)-1ß innate immunity pathway is associated with anti-inflammatory effects and a reduced risk of recurrent cardiovascular events in stable patients with previous myocardial infarction (MI) and elevated high-sensitivity C-reactive protein (hs-CRP). OBJECTIVES: This study assessed the association between IL-1ß level with all-cause mortality in patients with acute ST-segment elevation MI who underwent primary percutaneous coronary intervention and the interplay between IL-1ß and hs-CRP concentrations on the risk of premature death. METHODS: IL-1ß concentration was measured in 1,398 patients with ST-segment elevation MI who enrolled in a prospective cohort. Crude and hazard ratios for all-cause and cardiovascular mortality were analyzed at 90 days and 1 year using multivariate Cox proportional regression analysis. Major adverse cardiovascular events (MACEs) were analyzed. RESULTS: IL-1ß concentration measured at admission was associated with all-cause mortality at 90 days (adjusted hazard ratio [adjHR]: 1.47 per 1 SD increase; 95% confidence interval [CI]: 1.16 to 1.87; p < 0.002). The relation was nonlinear, and the highest tertile of IL-1ß was associated with higher mortality rates at 90 days (adjHR: 2.78; 95% CI: 1.61 to 4.79; p = 0.0002) and at 1 year (adjHR: 1.93; 95% CI: 1.21 to 3.06; p = 0.005), regardless of the hs-CRP concentration. Significant relationships were equally observed when considering cardiovascular mortality and MACEs at 90 days (adjHR: 2.42; 95% CI: 1.36 to 4.28; p = 0.002, and adjHR: 2.29; 95% CI: 1.31 to 4.01; p = 0.004, respectively) and at 1 year (adjHR: 2.32; 95% CI: 1.36 to 3.97; p = 0.002, and adjHR: 2.35; 95% CI: 1.39 to 3.96; p = 0.001, respectively). CONCLUSIONS: IL-1ß measured at admission in patients with acute MI was independently associated with the risk of mortality and recurrent MACEs.