Long-term follow-up of balloon-expandable valves according to the implantation strategy: insight from the DIRECTAVI trial.

BACKGROUND: Safety and feasibility of transcatheter aortic valve replacement (TAVR) without balloon aortic valvuloplasty (BAV) using the SAPIEN 3 balloon-expandable device has been previously demonstrated. The impact on long-term valve hemodynamic performances and outcomes remains however unknown. We evaluate long-term clinical and hemodynamic results according to the implant strategy (direct TAVR vs BAV pre-TAVR) in patients included in the DIRECTAVI randomized trial (NCT02729519). METHODS: Clinical and echocardiographic follow-up until January 2023 was performed for all patients included in the DIRECTAVI trial since 2016 (n = 228). The primary endpoint was incidence of moderate/severe hemodynamic valve deterioration (HVD), according to the Valve Academic Research defined Consortium-3 criteria (increase in mean gradient ≥10 mmHg resulting in a final mean gradient ≥20 mmHg, or new/worsening aortic regurgitation of 1 grade resulting in ≥ moderate aortic regurgitation). RESULTS: Median follow-up was 3.8 (2.2-4.7) years. Mean age at follow-up was 87 ± 6.7 years. No difference in incidence of HVD in the direct implantation group compared to the BAV group was found (incidence of 1.97 per 100 person-years and 1.45 per 100 person-years, respectively, P = 0.6). Prevalence of predicted prothesis-patient mismatch was low (n = 13 [11.4%] in the direct TAVR group vs n = 15 [13.2%] in BAV group) and similar between both groups (P = .7). Major outcomes including death, stroke, hospitalization for heart failure and pacemaker implantation were similar between both groups, (P = .4, P = .7, P = .3, and P = .3 respectively). CONCLUSION: Direct implantation of the balloon-expandable device in TAVR was not associated with an increased risk of moderate/severe HVD or major outcomes up to 6-year follow-up. These results guarantee wide use of direct balloon-expandable valve implantation, when feasible. CLINICAL TRIALS REGISTRATION NUMBER: NCT05140317.

Identification of Low- versus High-Risk Acute Coronary Syndrome for a Selective ECG Monitoring Strategy.

BACKGROUND: While admission of patients with acute coronary syndromes (ACS) in cardiology intensive care unit (CICU) is usual, in-hospital major outcomes in lower risk patients may be evaluated after early coronary angiography according to the European guidelines. METHODS: Consecutive ACS patients were prospectively included after coronary angiography evaluation within 24 h and percutaneous coronary intervention (PCI), when required. Patients were classified as high- or low-risk according to hemodynamics, rhythmic state, ischemic and bleeding risks. Major in-hospital outcomes were assessed. RESULTS: From January to June 2021, 277 patients were enrolled (62.8% with ST-segment elevation myocardial infarction (STEMI) (n = 174); 37.2% with non-NSTEMI (NSTEMI) (n = 103). PCI was required for 260 patients (93.9%). Seventy-four patients (26.7%) were classified as low-risk (n = 47 NSTEMI; n= 27 STEMI) and 203 patients (73.3%) as high-risk of events. All patients were monitored in CICU. While 38 patients (18.7%) from the high-risk group reached the primary endpoint, mainly related to rhythmic or conduction disorder (n = 24, 11.8%) or unstable hemodynamics (n = 17; 8.4%), only 1 patient (1.3%) in the low-risk group had one major outcome (no fatal bleeding); p < 0.01. The negative predictive value of our patient stratification for the absence of major in-hospital outcome was 100% (CI95%: 100-100%) for STEMI and 97.9% [CI95%: 93.2-100%] for NSTEMI patients. CONCLUSIONS: Stratification of ACS patients after early coronary angiography and most of the time PCI, identify a population with very low risk of in-hospital events (1/4 of all ACS and 1/2 of NSTEMI) who may probably not require ECG monitoring and/or CICU admission. (NCT04378504).

Simplified TAVR Procedure: How Far Is It Possible to Go?

Increasing operators' experience and improvement of the technique have resulted in a drastic reduction in complications following transcatheter aortic valve replacement (TAVR) in patients with lower surgical risk. In parallel, the procedure was considerably simplified, with a routine default approach including local anesthesia in the catheterization laboratory, percutaneous femoral approach, radial artery as the secondary access, prosthesis implantation without predilatation, left ventricle wire pacing and early discharge. Thus, the "simplified" TAVR adopted in most centers nowadays is a real revolution of the technique. However, simplified TAVR must be accompanied upstream by a rigorous selection of patients who can benefit from a minimalist procedure in order to guarantee its safety. The minimalist strategy must not become dogmatic and careful pre-, per- and post-procedural evaluation of patients with well-defined protocols guarantee optimal care following TAVR. This review aims to evaluate the benefits and limits of the simplified TAVR procedure in a current and future vision.

Acute Coronary Syndrome in the Era of SARS-CoV-2 Infection: A Registry of the French Group of Acute Cardiac Care.

BACKGROUND: In this study, we aimed to report clinical characteristics and outcomes of patients with and without SARS-CoV-2 infection who were referred for acute coronary syndrome (ACS) during the peak of the pandemic in France. METHODS: We included all consecutive patients referred for ST-elevation myocardial infarction (STEMI) or non-STEMI (NSTEMI) during the first 3 weeks of April 2020 in 5 university hospitals (Paris, south, and north of France), all performing primary percutaneous coronary intervention. RESULTS: The study included 237 patients (67 ± 14 years old; 69% male), 116 (49%) with STEMI and 121 (51%) with NSTEMI. The prevalence of SARS-CoV-2-associated ACS was 11% (n = 26) and 11 patients had severe hypoxemia on presentation (mechanical ventilation or nasal oxygen > 6 L/min). Patients were comparable regarding medical history and risk factors, except a higher prevalence of diabetes mellitus in SARS-CoV-2 patients (53.8% vs 25.6%; P = 0.003). In SARS-CoV-2 patients, cardiac arrest on admission was more frequent (26.9% vs 6.6%; P < 0.001). The presence of significant coronary artery disease and culprit artery occlusion in SARS-CoV-2 patients respectively, was 92% and 69.4% for those with STEMI, and 50% and 15.5% for those with NSTEMI. Percutaneous coronary intervention was performed in the same percentage of STEMI (84.6%) and NSTEMI (84.8%) patients, regardless of SARS-CoV-2 infection, but no-reflow (19.2% vs 3.3%; P < 0.001) was greater in SARS-CoV-2 patients. In-hospital death occurred in 7 SARS-CoV-2 patients (5 from cardiac cause) and was higher compared with noninfected patients (26.9% vs 6.2%; P < 0.001). CONCLUSIONS: In this registry, ACS in SARS-CoV-2 patients presented with high a percentage of cardiac arrest on admission, high incidence of no-reflow, and high in-hospital mortality.

CONTEXTE: Notre étude avait pour but d'établir les caractéristiques cliniques et les résultats de patients infectés ou non par le SRAS-CoV-2 qui ont été orientés en raison d'un syndrome coronarien aigu (SCA) pendant la phase aiguë de la pandémie en France. MÉTHODOLOGIE: Nous avons inclus dans l'étude tous les patients consécutifs qui ont présenté un infarctus du myocarde avec sus-décalage du segment ST (STEMI) ou sans sus-décalage du segment ST (NSTEMI) au cours des 3 premières semaines d'avril 2020 et qui ont été orientés vers 5 hôpitaux universitaires (situés à Paris, ainsi que dans le sud et le nord de la France), tous en mesure de réaliser des interventions co-ronariennes percutanées primaires. RÉSULTATS: L'étude comprenait 237 patients (âge : 67 ± 14 ans; proportion d'hommes : 69 %); 116 (49 %) présentaient un STEMI et 121 (51 %), un NSTEMI. La prévalence d'un SCA associé à une infection par le SRAS-CoV-2 s'établissait à 11 % (n = 26), et 11 patients étaient en hypoxémie grave (nécessitant une ventilation artificielle ou l'administration d'oxygène par voie nasale à un débit de plus de 6 l/min) à leur arrivée. Les patients présentaient des antécédents médicaux et des facteurs de risque comparables, à l'exception du fait que la prévalence du diabète était plus élevée chez les patients infectés par le SRAS-CoV-2 (53,8 % vs 25,6 %; p = 0,003). Ces derniers avaient plus souvent subi un arrêt cardiaque à leur admission (26,9 % vs 6,6 %; p < 0,001). Chez les patients infectés par le SRAS-CoV-2, une coronaropathie importante et une occlusion de l'artère coupable ont été observées chez respectivement 92 % et 69,4 % des patients présentant un STEMI, et chez 50 % et 15,5 % des patients présentant un NSTEMI. Une intervention coronarienne percutanée a été effectuée dans les mêmes proportions chez les patients subissant un STEMI (84,6 %) que chez ceux présentant un NSTEMI (84,8 %), sans égard à la présence ou à l'absence d'une infection par le SRAS-CoV-2, mais les cas de non-reperfusion (no-reflow) ont été plus fréquents chez les patients infectés que chez les autres patients (19,2 % et 3,3 %, respectivement; p < 0,001). Sept patients infectés par le SRAS-CoV-2 sont morts à l'hôpital (5 de cause cardiaque), ce qui représente un taux de mortalité plus élevé que chez les patients non infectés (26,9 % vs 6,2 %; p < 0,001). CONCLUSIONS: Dans le cadre de cette étude, le SCA survenu chez les patients infectés par le SRAS-CoV-2 était associé à un fort pourcentage d'arrêt cardiaque à l'admission, à une fréquence élevée de cas de non-reperfusion et à un taux élevé de mortalité hospitalière.

Under the skin: Biotransformation of para-aminophenol and para-phenylenediamine in reconstructed human epidermis and human hepatocytes.

We investigated the biotransformation of the oxidative arylamine (AA) hair dye ingredients [14C]-para-aminophenol (PAP) and [14C]-para-phenylenediamine (PPD) in reconstructed human epidermis and human hepatocytes. Human epidermis quantitatively transformed PAP to its N-acetylated derivative (APAP), whereas hepatocytes transformed PAP to sulfate or glucuronic acid conjugates of APAP or PAP as well as free APAP. Epidermis and hepatocytes converted PPD to N-mono- (MAPPD) and N,N'-di-acetylated (DAPPD) derivatives. At higher concentrations of PPD (250-1000 microM), epidermis or hepatocytes produced more of the MAPPD, whereas concentrations below 250 microM and lower favoured formation of the DAPPD metabolite. When compared with epidermis, human hepatocytes had a three-fold or eight-fold greater capacity for generation of MAPPD or DAPPD, respectively. No evidence of transformation of PAP or PPD to N-hydroxylated derivatives was found in epidermis or hepatocytes. Our results suggest that (i) after dermal absorption of PAP or PPD, humans are systemically exposed to acetylated derivatives; (ii) current in vitro skin absorption studies may be inadapated for determination of human systemic exposure to AAs due to reduced or absent metabolic capacity of non-viable skin; (iii) due to qualitative differences between dermal and hepatic metabolism, oral toxicity studies may be unsuited for the hazard assessment of dermal exposure to AAs; and (iv) use of induced rodent liver S9 metabolic activation systems for in vitro genotoxicity studies may produce misleading results on the hazard of human dermal exposure to AAs. In conclusion, our data support the growing evidence that AAs are transformed in human skin and suggest that current practices of safety assessment of AAs should take these findings into account.