Comparison of Incidence and Prognostic Impact of Ischemic, Major Bleeding and Heart Failure Events in Patients With Chronic Coronary Syndrome: Insights From the CORONOR Registry.

BACKGROUND: Evaluation of the residual risk in patient with chronic coronary syndrome is challenging in daily practice. Several types of events (myocardial infarction, ischemic stroke, bleeding, and heart failure [HF]) may occur, and their impact on subsequent mortality is unclear in the era of modern evidence-based pharmacotherapy. METHODS: CORONOR (Suivi d'une cohorte de patients Coronariens stables en région Nord-pas-de-Calais) is a prospective multicenter cohort that enrolled 4184 consecutive unselected outpatients with chronic coronary syndrome. We analyzed the incidence, correlates, and impact of ischemic events (a composite of myocardial infarction and ischemic stroke), major bleeding (Bleeding Academic Research Consortium 3 or higher), and hospitalization for HF on subsequent patient mortality. RESULTS: During follow-up (median, 4.9 years), 677 patients (16.5%) died. The 5-year cumulative incidences (death as competing event) of ischemic events, major bleeding, and HF hospitalization were 6.3% (5.6%-7.1%), 3.1% (2.5%-3.6%), and 8.1% (7.3%-9%), respectively. Ischemic events, major bleeding, and HF hospitalization were each associated with all-cause mortality. Major bleeding and hospitalization for HF were associated with the highest mortality rates in the postevent period (42.4%/y and 34.7%/y, respectively) compared with incident ischemic events (13.1%/y). The age- and sex-adjusted hazard ratios for all-cause mortality were 3.57 (95% CI, 2.77-4.61), 9.88 (95% CI, 7.55-12.93), and 8.60 (95% CI, 7.15-10.35) for ischemic events, major bleeding, and hospitalization for HF, respectively (all P<0.001). CONCLUSIONS: Hospitalization for HF has become both the most frequent and one of the most ominous events among patients with chronic coronary syndrome. Although less frequent, major bleeding is strongly associated with worse patient survival. Secondary prevention should not be limited to preventing ischemic events. Minimizing bleeding and preventing HF may be at least as important.

Feasibility and prognostic significance of ventricular-arterial coupling after myocardial infarction: the RIGID-MI cohort.

AIMS: The clinical significance and feasibility of the recently described non-invasive parameters exploring ventricular-arterial coupling (VAC) remain uncertain. This study aimed to assess VAC parameters for prognostic stratification in stable patients with left ventricular ejection fraction (LVEF) ≥40% following myocardial infarction (MI). METHODS AND RESULTS: Between 2018 and 2021, patients with LVEF ≥40% were evaluated 1 month following MI using transthoracic echocardiography (TTE) and arterial tonometry at rest and after a handgrip test. VAC was studied via the ratio between arterial elastance (Ea) and end-systolic LV elastance (Ees) and between pulse wave velocity (PWV) and global longitudinal strain (GLS). Patients were followed for major adverse cardiovascular events (MACE): all-cause death, acute heart failure, stroke, AMI, and urgent cardiovascular hospitalization. Among the 374 patients included, Ea/Ees and PWV/GLS were obtained at rest for 354 (95%) and 253 patients (68%), respectively. Isometric exercise was workable in 335 patients (85%). During a median follow-up of 32 months (interquartile range: 16-42), 41 (11%) MACE occurred. Patients presenting MACE were significantly older and had a higher prevalence of peripheral arterial disease, lower GLS, higher Ea, PWV, and PWV/GLS ratio. The Ea/Ees ratio and standard TTE parameters during isometric exercise were not associated with MACE. After adjustment, the PWV/GLS ratio was the only VAC parameter independently associated with outcome. Receiver operating characteristic curve analysis identified a PWV/GLS ratio >0.70 (Youden's index = 0.37) as the best threshold to identify patients developing MACE: hazard ratio (95% confidence interval) = 2.2 (1.14-4.27), P = 0.02. CONCLUSION: The PWV/GLS ratio, assessed 1 month after MI, identifies a group of patients at higher risk of MACE providing additional value on top of conventional non-invasive parameters.

Impact of Pre-Existing History of Heart Failure on Patient Profile, Therapeutic Management, and Prognosis in Cardiogenic Shock: Insights from the FRENSHOCK Registry.

There is a large heterogeneity among patients presenting with cardiogenic shock (CS). It is crucial to better apprehend this heterogeneity in order to adapt treatments and improve prognoses in these severe patients. Notably, the presence (or absence) of a pre-existing history of chronic heart failure (CHF) at time of CS onset may be a significant part of this heterogeneity, and data focusing on this aspect are lacking. We aimed to compare CS patients with new-onset HF to those with worsening CHF in the multicenter FRENSHOCK registry. Altogether, 772 CS patients were prospectively included: 433 with a previous history of CHF and 339 without. Worsening CHF patients were older (68 +/− 13.4 vs. 62.7 +/− 16.2, p < 0.001) and had a greater burden of extra-cardiac comorbidities. At admission, acute myocardial infarction was predominantly observed in the new-onset HF group (49.9% vs. 25.6%, p < 0.001). When focusing on hemodynamic parameters, worsening CHF patients showed more congestion and higher ventricular filling pressures. Worsening CHF patients experienced higher in-hospital all-cause mortality (31.3% vs. 24.2%, p = 0.029). Our results emphasize the great heterogeneity of the patients presenting with CS. Worsening CHF patients had higher risk profiles, and this translated to a 30% increase in in-hospital all-cause mortality. The heterogeneity of this population prompts us to better determine the phenotype of CS patients to adapt their management.

Clinical significance of myocardial work parameters after acute myocardial infarction.

Aims: To investigate the additional prognostic value of myocardial work (MW) parameters following acute myocardial infarction (AMI). Methods and results: Between 2018 and 2020, 244 patients admitted in the cardiac intensive care unit in Lille University Hospital for AMI were included. One-month following AMI, comprehensive transthoracic echocardiography (TTE) was performed to assess parameters of myocardial function. Patients were then followed for major events (ME): cardiovascular death, heart failure, and unplanned coronary revascularization. At 1-month, half of the population was symptomatic (NYHA ≥ II), and medical therapy was almost optimized (angiotensin-converting enzyme inhibitor/angiotensin 2 receptor blocker in 95.5%, beta-blockers in 96.3%, DAPT in 94.7%, and statins in 97.1%). After a median follow-up of 681 (interquartile range: 538-840) days, ME occurred in 26 patients (10.7%). Patients presenting ME were older (65.5 ± 14.2 vs. 58.1 ± 12.1years, P = 0.005) with a higher prevalence of hypertension (65.4 vs. 36.2%, P = 0.004), more impaired left ventricular (LV) function as assessed by LV ejection fraction (P = 0.07), global longitudinal strain (P = 0.03), or MW parameters [P = 0.01 for global work efficiency (GWE)], and greater LV and left atrium dilatations (P = 0.06 for left ventricular end-diastolic volume index and P = 0.03 for left atrial volume index). After adjustment, GWE was the only TTE parameter independently associated with long-term occurrence of ME (P = 0.02). A GWE value <91% was selected to identify patients at higher ME risk (hazard ratio: 95% confidence interval) = 2.94 (1.36-6.35), P = 0.0041). Conclusion: Lower GWE at 1 month after AMI is independently associated with higher ME rates. A GWE <91% can improve the post-AMI patient risk stratification.

Cerebral Microbleeds During Transcatheter Aortic Valve Replacement: A Prospective Magnetic Resonance Imaging Cohort.

BACKGROUND: Cerebral microbleeds (CMBs) have been observed in healthy elderly people undergoing systematic brain magnetic resonance imaging. The potential role of acute triggers on the appearance of CMBs remains unknown. We aimed to describe the incidence of new CMBs after transcatheter aortic valve replacement (TAVR) and to identify clinical and procedural factors associated with new CMBs including hemostatic measures and anticoagulation management. METHODS: We evaluated a prospective cohort of patients with symptomatic aortic stenosis referred for TAVR for CMBs (METHYSTROKE [Identification of Epigenetic Risk Factors for Ischemic Complication During the TAVR Procedure in the Elderly]). Standardized neurologic assessment, brain magnetic resonance imaging, and analysis of hemostatic measures including von Willebrand factor were performed before and after TAVR. Numbers and location of microbleeds on preprocedural magnetic resonance imaging and of new microbleeds on postprocedural magnetic resonance imaging were reported by 2 independent neuroradiologists blinded to clinical data. Measures associated with new microbleeds and postprocedural outcome including neurologic functional outcome at 6 months were also examined. RESULTS: A total of 84 patients (47% men, 80.9±5.7 years of age) were included. On preprocedural magnetic resonance imaging, 22 patients (26% [95% CI, 17%-37%]) had at least 1 microbleed. After TAVR, new microbleeds were observed in 19 (23% [95% CI, 14%-33%]) patients. The occurrence of new microbleeds was independent of the presence of microbleeds at baseline and of diffusion-weighted imaging hypersignals. In univariable analysis, a previous history of bleeding (P=0.01), a higher total dose of heparin (P=0.02), a prolonged procedure (P=0.03), absence of protamine reversion (P=0.04), higher final activated partial thromboplastin time (P=0.05), lower final von Willebrand factor high-molecular-weight:multimer ratio (P=0.007), and lower final closure time with adenosine-diphosphate (P=0.02) were associated with the occurrence of new postprocedural microbleeds. In multivariable analysis, a prolonged procedure (odds ratio, 1.22 [95% CI, 1.03-1.73] for every 5 minutes of fluoroscopy time; P=0.02) and postprocedural acquired von Willebrand factor defect (odds ratio, 1.42 [95% CI, 1.08-1.89] for every lower 0.1 unit of high-molecular-weight:multimer ratio; P=0.004) were independently associated with the occurrence of new postprocedural microbleeds. New CMBs were not associated with changes in neurologic functional outcome or quality of life at 6 months. CONCLUSIONS: One out of 4 patients undergoing TAVR has CMBs before the procedure and 1 out of 4 patients develops new CMBs. Procedural or antithrombotic management and persistence of acquired von Willebrand factor defect were associated with the occurrence of new CMBs. REGISTRATION: URL: https://www. CLINICALTRIALS: gov; Unique identifier: NCT02972008.

Myocardial Infarction incidence during national lockdown in two French provinces unevenly affected by COVID-19 outbreak: An observational study.

BACKGROUND: A reduction of admission for MI has been reported in most countries affected by COVID-19. No clear explanation has been provided. METHODS: To report the incidence of myocardial infarction (MI) admission during COVID-19 pandemic and in particular during national lockdown in two unequally affected French provinces (10-million inhabitants) with a different media strategy, and to describe the magnitude of MI incidence changes relative to the incidence of COVID-19-related deaths. A longitudinal study to collect all MIs from January 1 until May 17, 2020 (study period) and from the identical time period in 2019 (control period) was conducted in all centers with PCI-facilities in northern "Hauts-de-France" province and western "Pays-de-la-Loire" Province. The incidence of COVID-19 fatalities was also collected. FINDINGS: In "Hauts-de-France", during lockdown (March 18-May 10), 1500 COVID-19-related deaths were observed. A 23% decrease in MI-IR (IRR=0.77;95%CI:0.71-0.84, p<0.001) was observed for a loss of 272 MIs (95%CI:-363,-181), representing 18% of COVID-19-related deaths. In "Pays-de-la-Loire", 382 COVID-19-related deaths were observed. A 19% decrease in MI-IR (IRR=0.81; 95%CI=0.73-0.90, p<0.001) was observed for a loss of 138 MIs (95%CI:-210,-66), representing 36% of COVID-19-related deaths. While in "Hauts-de-France" the MI decline started before lockdown and recovered 3 weeks before its end, in "Pays-de-la-Loire", it started after lockdown and recovered only by its end. In-hospital mortality of MI patients was increased during lockdown in both provinces (5.0% vs 3.4%, p=0.02). INTERPRETATION: It highlights one of the potential collateral damages of COVID-19 outbreak on cardiovascular health with a dramatic reduction of MI incidence. It advocates for a careful and weighted communication strategy in pandemic crises. FUNDING: The study was conducted without external funding.

Balloon aortic valvuloplasty for severe aortic stenosis before urgent non-cardiac surgery.

BACKGROUND: Balloon aortic valvuloplasty (BAV) has been proposed as a therapeutic option in patients suffering from severe aortic stenosis (SAS) who need urgent non-cardiac surgery (NCS). Whether this strategy is better than medical therapy in this very specific population is unknown. AIMS: We aimed to evaluate the clinical benefit of an invasive strategy (IS) with preoperative BAV in patients with SAS requiring urgent NCS. METHODS: From 2011 to 2019, a registry conducted in two centres included 133 patients with SAS undergoing urgent NCS, of whom 93 underwent preoperative BAV (IS) and 40 a conservative strategy (CS) without BAV. All analyses were adjusted for confounding using inverse probability of treatment weighting (IPTW) (10 clinical and anatomical variables). RESULTS: The primary outcome was MACE at one-month follow-up after NCS including mortality, heart failure, and other cardiovascular outcomes. In patients managed conservatively, occurrence of MACE was 20.0% (n=8) and death was 10.0% (n=4) at 1 month. In patients undergoing BAV, the occurrence of MACE was 20.4% (n=19) and death was 5.4% (n=5) at 1 month. Among patients undergoing conservative management, all events were observed after NCS while, in patients undergoing BAV, 12.9% (n=12) had events between BAV and NCS including 3 deaths, and 7.5% (n=7) had events after NCS including 2 deaths. In IPTW propensity analyses, the incidence of the primary outcome (20.4% vs 20.0%; OR 0.93, 95% CI: 0.38-2.29) and three-month survival (89.2% vs 90.0%; IPTW-adjusted HR 0.90, 95% CI: 0.31-2.60) were similar in both groups. CONCLUSIONS: Patients with SAS managed conservatively before urgent NCS are at high risk of events. A systematic invasive strategy using BAV does not provide a significant improvement in clinical outcome.

Fatal Enterovirus-related Myocarditis in a Patient with Devic's Syndrome Treated with Rituximab.

Enteroviruses are a frequent source of infection and among the most common central nervous system viral pathogens. Enteroviruses - in particular, the Coxsackie B viruses - are a known cause of myocarditis. Rituximab is a genetically engineered chimeric anti-CD20 monoclonal antibody. Many reports in the literature suggest a higher risk of infection following repeated rituximab therapy, including viral infection. However, observations of enterovirus-related myocarditis in the context of rituximab treatment are scarce. The authors describe the case of a patient with neuromyelitis optica spectrum disorder who developed severe and fatal enterovirus-related myocarditis after rituximab therapy with a difficult differential diagnosis of autoimmune or giant-cell myocarditis. This case highlights the importance of complete diagnostic workup in difficult cases of myocarditis, including endomyocardial biopsies.

Feasibility and safety of transfemoral transcatheter aortic valve implantation performed with a percutaneous coronary intervention-like approach.

BACKGROUND: Transfemoral percutaneous transcatheter aortic valve implantation (TF-TAVI) is a safe, reproducible and established procedure, mainly performed under local anaesthesia, which is mostly administered and monitored by a dedicated anaesthesia team (regular approach). Our centre has developed a standardized pathway of care, and eligible patients are selected for a minimalist TF-TAVI, entirely managed by operators without the presence of the anaesthesia team in the operating room, like most interventional coronary procedures ("percutaneous coronary intervention-like" approach [PCI approach]). AIM: To compare the safety and efficacy of TF-TAVI performed with the PCI approach versus the regular approach. METHODS: The analysis population comprised all patients who underwent TF-TAVI with the PCI or regular approach in our institution from November 2016 to July 2019. The two co-primary endpoints were early safety composite and early efficacy composite at 30days as defined by the Valve Academic Research Consortium-2. The PCI (n=137) and Regular (n=221) approaches were compared using the propensity score based method of inverse probability of treatment weighting. RESULTS: No differences were observed after comparison of TAVI performed with the PCI or regular approach regarding the composite safety endpoint (7.3% vs. 11.3%; odds ratio 0.63, 95% confidence interval 0.37 to 1.07; P=0.086) or the composite efficacy endpoint (4.4% vs. 6.3%; odds ratio 0.78, 95% confidence interval 0.41 to 1.49; P=0.45). CONCLUSIONS: This study suggests that the efficacy and safety of TF-TAVI entirely managed by a PCI approach for selected patients are not different to those when TF-TAVI is performed with the attendance of a full anaesthesia care team. The PCI approach appears to be a safe and efficient clinical pathway, providing an appropriate and rational utilization of anaesthesiology resources, and could be used for the majority of TF-TAVI procedures.

Transcatheter Aortic Valve Replacement in Bicuspid Aortic Valve Stenosis.

After 15 years of successive randomized, controlled trials, indications for transcatheter aortic valve replacement (TAVR) are rapidly expanding. In the coming years, this procedure could become the first line treatment for patients with a symptomatic severe aortic stenosis and a tricuspid aortic valve anatomy. However, randomized, controlled trials have excluded bicuspid aortic valve (BAV), which is the most frequent congenital heart disease occurring in 1% to 2% of the total population and representing at least 25% of patients 80 years of age or older referred for aortic valve replacement. The use of a less invasive transcatheter therapy in this elderly population became rapidly attractive, and approximately 10% of patients currently undergoing TAVR have a BAV. The U.S. Food and Drug Administration and the "European Conformity" have approved TAVR for low-risk patients regardless of the aortic valve anatomy whereas international guidelines recommend surgical replacement in BAV populations. Given this progressive expansion of TAVR toward younger and lower-risk patients, heart teams are encountering BAV patients more frequently, while the ability of this therapy to treat such a challenging anatomy remains uncertain. This review will address the singularity of BAV anatomy and associated technical challenges for the TAVR procedure. We will examine and summarize available clinical evidence and highlight critical knowledge gaps regarding TAVR utilization in BAV patients. We will provide a comprehensive overview of the role of computed tomography scans in the diagnosis, and classification of BAV and TAVR procedure planning. Overall, we will offer an integrated framework for understanding the current role of TAVR in the treatment of bicuspid aortic stenosis and for guiding physicians in clinical decision-making.

IMPELLA® or Extracorporeal Membrane Oxygenation for Left Ventricular Dominant Refractory Cardiogenic Shock.

Mechanical circulatory support (MCS) devices are effective tools in managing refractory cardiogenic shock (CS). Data comparing veno-arterial extracorporeal membrane oxygenation (VA-ECMO) and IMPELLA® are however scarce. We aimed to assess outcomes of patients implanted with these two devices and eligible to both systems. From 2004 to 2020, we retrospectively analyzed 128 patients who underwent VA-ECMO or IMPELLA® in our institution for refractory left ventricle (LV) dominant CS. All patients were eligible to both systems: 97 patients were first implanted with VA-ECMO and 31 with IMPELLA®. The primary endpoint was 30-day all-cause death. VA-ECMO patients were younger (52 vs. 59.4, p = 0.006) and had a higher lactate level at baseline than those in the IMPELLA® group (6.84 vs. 3.03 mmol/L, p < 0.001). Duration of MCS was similar between groups (9.4 days vs. 6 days in the VA-ECMO and IMPELLA® groups respectively, p = 0.077). In unadjusted analysis, no significant difference was observed between groups in 30-day mortality: 43.3% vs. 58.1% in the VA-ECMO and IMPELLA® groups, respectively (p = 0.152). After adjustment, VA-ECMO was associated with a significant reduction in 30-day mortality (HR = 0.25, p = 0.004). A higher rate of MCS escalation was observed in the IMPELLA® group: 32.3% vs. 10.3% (p = 0.003). In patients eligible to either VA-ECMO or IMPELLA® for LV dominant refractory CS, VA-ECMO was associated with improved survival rate and a lower need for escalation.

Ultrasound Guidance to Reduce Vascular and Bleeding Complications of Percutaneous Transfemoral Transcatheter Aortic Valve Replacement: A Propensity Score-Matched Comparison.

Background Ultrasound (US) guidance provides the unique opportunity to control the puncture zone of the artery during transfemoral transcatheter aortic valve replacement and may decrease major vascular complications (VC) and life-threatening or major bleeding complications. This study aimed to evaluate the clinical impact of US guidance using a propensity score-matched comparison. Methods and Results US guidance was implemented as the default approach for all transfemoral transcatheter aortic valve replacement cases in our institution in June 2013. We defined 3 groups of consecutive patients according to the method of puncture (fluoroscopic/US guidance) and the use of a transcatheter heart valve. Patients in the US-guided second-generation group (Sapien XT [Edwards Lifesciences, Irvine, CA], Corevalve [Medtronic, Dublin, Ireland]) were successfully 1:1 matched with patients in the fluoroscope-guided second-generation group (n=95) with propensity score matching. In a second analysis we described the consecutive patients of the US-guided third-generation group (Evolut-R [Medtronic], Sapien 3 [Edwards Lifesciences], n=308). All vascular and bleeding complications were reduced in the US-guided second-generation group compared with the fluoroscope-guided second-generation group: VC (16.8% versus 6.3%; P=0.023); life-threatening or major bleeding (22.1% versus 6%; P=0.004); and VC related to vascular access (12.6% versus 4.2%; P=0.052). In the US-guided third-generation group the rates of major VC and life-threatening or major bleeding were 3.2% (95% CI, 1.6% to 5.9%) and 3.6% (95% CI, 1.8% to 6.3%). In the overall population (n=546), life-threatening or major bleeding was associated with a 1.7-fold increased mortality risk (P=0.02). Conclusions We demonstrated that US guidance effectively reduced VC and bleeding complications for transfemoral transcatheter aortic valve replacement and should be considered the standard puncture method. Registration URL: http://www.clinicaltrials.gov. Unique identifier: NCT02628509.

von Willebrand Factor and Management of Heart Valve Disease: JACC Review Topic of the Week.

For decades, numerous observations have shown an intimate relationship between von Willebrand factor (VWF) multimer profile and heart valve diseases (HVD). The current knowledge of the unique biophysical properties of VWF helps us to understand the longstanding observations concerning the bleeding complications in patients with severe HVD. Not only does the analysis of the VWF multimer profile provide an excellent evaluation of HVD severity, it is also a strong predictor of clinical events. Also of importance, VWF responds within minutes to any significant change in hemodynamic valve status, making it an accurate marker of the quality of surgical and transcatheter therapeutic interventions. The authors provide in this review a practical, comprehensive, and evidence-based framework of the concept of VWF as a biomarker in HVD, advocating for its implementation into the clinical decision-making process besides usual clinical and imaging evaluation. They also delineate critical knowledge gaps and research priorities to definitely validate this concept.

Real-Time Monitoring of von Willebrand Factor in the Catheterization Laboratory: The Seatbelt of Mini-Invasive Transcatheter Aortic Valve Replacement?

Significant paravalvular regurgitation (PVR) remains a relatively frequent (4% to 9%) and deleterious complication of transcatheter aortic valve replacement (TAVR), even with the latest generation of bioprosthesis. Although mini-invasive TAVR without general anesthesia or transesophageal echocardiography (TEE) is progressively becoming the predominant approach, identification and grading of PVR in the catheterization laboratory remain an important and challenging clinical issue. The authors discuss how a recently reported blood biomarker reflecting the von Willebrand factor activity, that is, the closure time with adenosine diphosphate, can be successfully applied during the TAVR procedure to detect and monitor PVR in real time, with an excellent negative predictive value. This point-of-care testing performed directly in the catheterization laboratory may improve the diagnosis of PVR and rationalize the decision of whether or not to perform corrective measures. They further discuss how such a test could be a substitute for the multimodal approach combining TEE, hemodynamics, and cine-angiography, and help to secure the transition to the mini-invasive approach and facilitate the expanding indications of less invasive procedures to lower-risk patients without jeopardizing procedural and clinical outcomes.