Incomplete Recovery From Takotsubo Syndrome Is a Major Determinant of Cardiovascular Mortality.

BACKGROUND: Although there is an apparent rapid and spontaneous recovery of left ventricular ejection fraction (LVEF) in patients with Takotsubo syndrome (TTS), recent studies have demonstrated a long-lasting functional impairment in those patients. The present study sought to evaluate the predictors of incomplete recovery following TTS and its impact on cardiovascular mortality.Methods and Results:Patients with TTS between 2008 and 2018 were retrospectively enrolled at 3 different institutions. After exclusion of in-hospital deaths, 407 patients were split into 2 subgroups according to whether their LVEF was >50% (recovery group; n=341), or ≤50% (incomplete recovery group; n=66) at the chronic phase. Multivariate logistic regression analysis found that LVEF (odds ratio [OR]: 0.94; 95% confidence interval [CI]: 0.91-0.98; P<0.001) and C-reactive protein levels (OR: 1.11; 95% CI: 1.02-1.22; P=0.02) at discharge were independent predictors of incomplete recovery. At a median follow up of 52 days, a higher cardiovascular mortality was evident in the incomplete recovery group (16% vs. 0.6%; P<0.001). CONCLUSIONS: This study demonstrated that incomplete recovery after TTS is characterized by residual systemic inflammation and an increased cardiac mortality at follow up. Altogether, the present study findings determined that patients with persistent inflammation are a high-risk subgroup, and should be targeted in future clinical trials with specific therapies to attenuate inflammation.

Clinical features of patients with acute coronary syndrome during the COVID-19 pandemic.

Although a reduction in hospital admissions of acute coronary syndromes (ACS) patients has been observed globally during the coronavirus disease 2019 (COVID-19) pandemic, clinical features of those patients have not been fully investigated. The aim of the present analysis is to investigate the incidence, clinical presentation, and outcomes of patients with ACS during the COVID-19 pandemic. We performed a retrospective analysis of consecutive patients who were admitted for ACS at our institution between March 1 and April 20, 2020 and compared with the equivalent period in 2019. Admissions for acute myocardial infarction (AMI) reduced by 39.5% in 2020 compared with the equivalent period in 2019. Owing to the emergency medical services (EMS) of our region, all time components of ST-elevated myocardial infarction care were similar during the COVID-19 outbreak as compared with the previous year's dataset. Among the 106 ACS patients in 2020, 7 patients tested positive for COVID-19. Higher incidence of type 2 myocardial infarction (29% vs. 4%, p = 0.0497) and elevated D-dimer levels (5650 µg/l [interquartile range (IQR) 1905-13,625 µg/l] vs. 400 µg/l [IQR 270-1050 µg/l], p = 0.02) were observed in COVID-19 patients. In sum, a significant reduction in admission for AMI was observed during the COVID-19 pandemic. COVID-19 patients were characterized by elevated D-dimer levels on admission, reflecting enhanced COVID-19 related thrombogenicity. The prehospital evaluation by EMS may have played an important role for the timely revascularization for STEMI patients.

Periprocedural Predictors of New-Onset Conduction Abnormalities After Transcatheter Aortic Valve Replacement.

BACKGROUND: New-onset conduction abnormalities (CAs) following transcatheter aortic valve replacement (TAVR) are associated with hospital rehospitalization and long-term mortality, but available predictors are sparse. This study sought to determine clinical predictors of new-onset left bundle branch block (LBBB) and new permanent pacemaker (PPM) implantation in patients undergoing TAVR.Methods and Results:We enrolled 290 patients who received SAPIEN 3 (Edwards Lifesciences, Irvine, CA, USA; n=217) or Evolut R (Medtronic, Minneapolis, MN, USA; n=73) from a prospective registry at Nouvel Hôpital Civil, Strasbourg, France between September 2014 and February 2018. Of 242 patients without pre-existing LBBB, 114 (47%) experienced new-onset LBBB and/or new PPM implantation. A difference between membranous septal length and implantation depth (∆MSID) was the only predictor of CAs for both types of valves. In the multivariate analysis, PR interval and ∆MSID remained as sole predictors of CAs. The risk for adverse clinical events, including all-cause death, myocardial infarction, stroke, and heart failure hospitalization, was higher for patients with CAs as compared with patients without CAs (hazard ratio: 2.10; 95% confidence interval: 1.26 to 3.57; P=0.004). CONCLUSIONS: Computed tomography assessment of membranous septal anatomy and implantation depth predicted CAs after TAVR with new-generation valves. Future studies are required to identify whether adjustment of the implantation depth can reduce the risk of CAs and adverse clinical outcomes.

Left ventricular mechanics in the acute phase of Takotsubo cardiomyopathy: distinctive ballooning patterns translate into different diastolic properties.

Although apical and midventricular Takotsubo cardiomyopathies (TTCs) share common triggers and pathophysiological features, little is known about the potential differences in left ventricular (LV) mechanistic properties between these TTC phenotypes. We sought to investigate whether LV systolic and/or diastolic function, as assessed invasively by left heart catheterization (LHC), differ according to ballooning patterns in the acute phase of TTC. One hundred and fourteen TTC patients were retrospectively identified between January 2009 and December 2015 at the University Hospital of Strasbourg, France. A comprehensive list of LV quantitative parameters was derived from LHC analysis for each patient. We examined 2 groups of patients according to ballooning patterns in the acute phase of TTC: patients with apical ballooning ("Apical group"; n = 76) and those with midventricular ballooning ("Midventricular group"; n = 38). LV minimal diastolic pressure (8.72 ± 6.72 vs. 5.02 ± 6.08 mmHg; p = 0.004), LV end diastolic pressure (23.11 ± 8.32 vs. 18.84 ± 8.06 mmHg; p = 0.01), and LV diastolic stiffness (LV stiffness 1: 0.29 ± 0.23 vs. 18.84 ± 8.06 mmHg/mL; p = 0.04-LV stiffness 2: 0.16 ± 0.08 vs. 0.12 ± 0.05 mmHg/mL; p = 0.005) were significantly higher in patients with apical TTC than in the midventricular group. Concomitantly, these findings were associated with significantly higher BNP levels in the apical group (923.91 ± 1164.53 vs. 418.71 ± 557.75 pg/mL; p = 0.004) than in the midventricular group. In the acute phase of stress cardiomyopathy, the classic apical form of TTC is associated with poorer diastolic function compared to the midventricular ballooning variant, as assessed through direct invasive hemodynamic measurements using LHC.

Impact of Malignancies in the Early and Late Time Course of Takotsubo Cardiomyopathy.

BACKGROUND: Although the relationship between malignancies and catecholamine-induced myocardial stunning remains largely speculative, it has been suggested that the presence of cancer may lower the threshold for stress stimuli and/or may aggravate cardiac adrenoreceptor sensitivity. We sought to investigate whether associations exist between a previous or current diagnosis of malignancy, diagnostic parameters during hospitalization and death in takotsubo. METHODS AND RESULTS: The 154 takotsubo patients were retrospectively identified between May 2008 and December 2014. Previous history of malignancy was identified in 44 patients (28.5%). Cardiac arrest was present at admission in 13 patients (8.4%). Intra-aortic balloon pump was inserted in 16 patients (10.4%). In patients with malignancy, higher B-type natriuretic peptide (BNP), leukocyte and C-reactive protein (CRP) peaks could be observed during the hospital phase. Initial impairment of left ventricular ejection fraction was negatively related to BNP, leukocyte, and CRP peaks. At a median follow-up of 364 days, all-cause death occurred in 41 patients (26.6%) and cardiac death in 12 patients (7.7%). Multivariate Cox regression analysis identified malignancy (hazard ratio 4.77 (1.02-22.17), leukocyte peak and age as independent predictors of cardiac death. Malignancy (2.62 (1.26-5.44), leukocyte peak (1.05 (1.01-1.08) and initial cardiac arrest (6.68 (2.47-18.01) were identified as independent predictors of overall mortality. CONCLUSIONS: In the present takotsubo patients, the prevalence of malignancy was high and may have affected cardiovascular outcomes through the activation of inflammatory and neurohormonal mechanisms. (Circ J 2016; 80: 2192-2198).

COVID-19 promotes endothelial dysfunction and thrombogenicity: role of proinflammatory cytokines/SGLT2 prooxidant pathway.

BACKGROUND: COVID-19 is associated with an increased risk of cardiovascular complications. Although cytokines have a predominant role in endothelium damage, the precise molecular mechanisms are far from being elucidated. OBJECTIVES: The present study hypothesized that inflammation in patients with COVID-19 contributes to endothelial dysfunction through redox-sensitive SGLT2 overexpression and investigated the protective effect of SGLT2 inhibition by empagliflozin. METHODS: Human plasma samples were collected from patients with acute, subacute, and long COVID-19 (n = 100), patients with non-COVID-19 and cardiovascular risk factors (n = 50), and healthy volunteers (n = 25). Porcine coronary artery endothelial cells (ECs) were incubated with plasma (10%). Protein expression levels were determined using Western blot analyses and immunofluorescence staining, mRNA expression by quantitative reverse transcription-polymerase chain reaction, and the level of oxidative stress by dihydroethidium staining. Platelet adhesion, aggregation, and thrombin generation were determined. RESULTS: Increased plasma levels of interleukin (IL)-1ß, IL-6, tumor necrosis factor-α, monocyte chemoattractant protein-1, and soluble intercellular adhesion molecule-1 were observed in patients with COVID-19. Exposure of ECs to COVID-19 plasma with high cytokines levels induced redox-sensitive upregulation of SGLT2 expression via proinflammatory cytokines IL-1ß, IL-6, and tumor necrosis factor-α which, in turn, fueled endothelial dysfunction, senescence, NF-κB activation, inflammation, platelet adhesion and aggregation, von Willebrand factor secretion, and thrombin generation. The stimulatory effect of COVID-19 plasma was blunted by neutralizing antibodies against proinflammatory cytokines and empagliflozin. CONCLUSION: In patients with COVID-19, proinflammatory cytokines induced a redox-sensitive upregulation of SGLT2 expression in ECs, which in turn promoted endothelial injury, senescence, platelet adhesion, aggregation, and thrombin generation. SGLT2 inhibition with empagliflozin appeared as an attractive strategy to restore vascular homeostasis in COVID-19.

Drifting discrete Jovian radio bursts reveal acceleration processes related to Ganymede and the main aurora.

Radio detection at high time-frequency resolutions is a powerful means of remotely studying electron acceleration processes. Radio bursts have characteristics (polarization, drift, periodicity) making them easier to detect than slowly variable emissions. They are not uncommon in solar system planetary magnetospheres, the powerful Jovian "short bursts (S-bursts)" induced by the Io-Jupiter interaction being especially well-documented. Here we present a detection method of drifting radio bursts in terabytes of high resolution time-frequency data, applied to one month of ground-based Jupiter observations. Beyond the expected Io-Jupiter S-bursts, we find decameter S-bursts related to the Ganymede-Jupiter interaction and the main Jovian aurora, revealing ubiquitous Alfvénic electron acceleration in Jupiter's high-latitude regions. Our observations show accelerated electron energies are distributed in two populations, kilo-electron-Volts and hundreds of electron-Volts. This detection technique may help characterizing inaccessible astrophysical sources such as exoplanets.

Determinants and treatments of heart failure after transcatheter aortic valve implantation: moving up a notch.

Transcatheter aortic valve implantation (TAVI) has become an alternative to surgical aortic valve replacement for patients with symptomatic severe aortic stenosis in elderly and comorbid population. Significant improvement in heart function has been observed in patients undergoing TAVI, but numerous patients are readmitted to hospital for heart failure (HF). Moreover, repeat HF hospitalization is strongly associated with an adverse prognosis and increases the financial burden of health care. Although studies have identified pre-existing and post-procedural factors that contribute to HF hospitalization after TAVI, there is a paucity of data regarding optimal post-procedural pharmacological treatments. This review aims to provide an overview of the current understanding of mechanisms, determinants, and potential treatments of HF following TAVI. We first review the pathophysiology of left ventricular (LV) remodelling, coronary microcirculation disorder, and endothelial dysfunction in patients with aortic stenosis and then examine the impact of TAVI on these conditions. We then present evidence of various factors and complications that may interplay with LV remodelling and contribute to HF events after TAVI. Next, we describe the triggers and predictors of early and late HF rehospitalizations following TAVI. Lastly, we discuss the potential of conventional pharmacological treatments, including renin-angiotensin blockers, beta-blockers, and diuretics in TAVI patients. The paper explores the potential of newer drugs, including sodium-glucose co-transporter 2 inhibitors, anti-inflammatory drugs, and ion supplementation. Comprehensive knowledge in this field may aid in recognizing successful existing therapies, developing effective new treatments, and establishing dedicated patient care strategies during follow-up after TAVI.

Combination of Primary Hemostatic Disorders and Atrial Fibrillation Increases Bleeding Events Following Transcatheter Aortic Valve Replacement.

Background Patients with atrial fibrillation (AF) are likely to have a poor prognosis including bleedings following transcatheter aortic valve replacement (TAVR). Closure time of adenosine diphosphate (CT-ADP) is a primary hemostasis point-of-care test and is a predictor of bleeding events following TAVR. We aimed to evaluate the impact of ongoing primary hemostatic disorders on bleeding events in TAVR patients with AF. Methods We enrolled 878 patients from our prospective registry. The primary endpoint was VARC-2 major/life-threatening bleeding complications (MLBCs) at 1 year after TAVR and secondary endpoint was major adverse cardiac and cerebrovascular events (MACCEs) at 1 year, defined as a composite of all-cause death, myocardial infarction, stroke, and heart failure hospitalization. Ongoing primary hemostatic disorder was defined by a postprocedural CT-ADP >180 seconds. Results Patients with AF had a higher incidence of MLBCs (20 vs. 12%, p = 0.002), MACCE (29 vs. 20%, p = 0.002), and all-cause mortality (15 vs. 8%, p = 0.002) within 1 year compared to non-AF patients. When the cohort was split into four subgroups according to AF and CT-ADP >180 seconds, patients with AF and CT-ADP >180 seconds had the highest risk of MLBCs and MACCE. Multivariate Cox regression analysis confirmed that the patients with AF and CT-ADP >180 seconds had 3.9-fold higher risk of MLBCs, whereas those patients were no longer associated with MACCE after the adjustment. Conclusion In TAVR patients, AF with postprocedural CT-ADP >180 seconds was strongly associated with MLBCs following TAVR. Our study suggests that persistent primary hemostatic disorders contribute to a higher risk of bleeding events particularly in AF patients.

Outcomes of patients with active cancer undergoing transcatheter aortic valve replacement.

BACKGROUND: Cardiovascular disease and cancer are the two leading causes of mortality worldwide, and their association presents a therapeutic challenge. Current data regarding the prognosis of active cancer in patients undergoing transcatheter aortic valve replacement are conflicting. AIM: To determine the impact and prognosis of active cancer in transcatheter aortic valve replacement. METHODS: All consecutive patients with severe aortic stenosis treated by transcatheter aortic valve replacement between February 2010 and May 2019 were enrolled in a prospective study. The cohort was divided according to the presence or absence of active cancer at baseline. The primary endpoint was all-cause mortality 1 year after the procedure. RESULTS: A total of 1,125 patients were enrolled: 1,037 (92.2%) without and 88 (7.8%) with active cancer. The most frequent cancers were haematological (36.4%), breast (14.8%) and prostate (14.8%), with 79.5% of patients receiving curative treatment and 17.0% receiving palliative treatment. The 1-year mortality rate was higher in patients with active cancer (27.3% vs. 13.9%; P<0.01), mainly driven by non-cardiovascular causes. An increased cardiovascular mortality rate at 2 years was seen in patients with active cancer (27.5% vs. 15.0%; P=0.03) compared with a similar rate at 1-year follow-up. Active cancer was a strong predictor of 1-year all-cause mortality (hazard ratio 2.46, 95% confidence interval 1.19-4.68; P=0.02). Major/life-threatening bleeding events at 1 year were more frequent in patients with active cancer (P=0.02). CONCLUSIONS: Among patients who undergo transcatheter aortic valve replacement, 1-year all-cause mortality is higher in those with active cancer. We also observed a trend towards increased long-term bleeding events in case of active cancer.

P2Y12 inhibition by clopidogrel increases adverse clinical events after transcatheter aortic valve replacement.

BACKGROUND: Dual antiplatelet therapy (DAPT) has been proposed to explain the increased occurrence of bleeding events after transcatheter aortic valve replacement (TAVR) despite no relevant study exploring the extent of platelet inhibition. In the present study, we sought to assess whether P2Y12 inhibition by clopidogrel impacts clinical outcomes in TAVR patients. METHODS: Patients were enrolled in a prospective registry at Nouvel Hôpital Civil, Strasbourg, France between February 2010 and May 2019. Vasodilator-stimulated phosphoprotein (VASP) flow cytometry test was assessed 24 h after the procedure. Responder to clopidogrel was defined by a platelet reactivity index ≤50%. The primary endpoint was 90-day major adverse cardiac and cerebrovascular events (MACCE), including all-cause death, myocardial infarction, stroke, and heart failure hospitalization. RESULTS: Of the 828 patients with available VASP monitoring, 491 TAVR patients received preprocedural clopidogrel therapy. Responders were identified in 22% (n = 110) and low responders in 78% (n = 381) of patients. By multivariate Cox regression analysis, responders to clopidogrel (hazard ratio [HR]: 2.09; 95% confidence interval [CI]: 1.13 to 3.79: p = 0.02) and previous PCI (HR: 2.16; 95% CI: 1.02 to 4.68; p = 0.04) were identified as independent predictors of 90-day MACCE. The cumulative event-free survival rate at 90-day was significantly lower in the responder group (p = 0.008; log rank test). CONCLUSIONS: In conclusion, appropriate P2Y12 inhibition by clopidogrel is a major determinant of MACCE at 90 days after TAVR. The present data challenge DAPT as a standard therapy during TAVR.

Effective Orifice Area of Balloon-Expandable and Self-Expandable Transcatheter Aortic Valve Prostheses: An Echo Doppler Comparative Study.

Published data on the size-specific effective orifice area (EOA) of transcatheter heart valves (THVs) remain scarce. Here, we sought to investigate the intra-individual changes in EOA and mean transvalvular aortic gradient (MG) of the Sapien 3 (S3), CoreValve (CV), and Evolut R (EVR) prostheses both at short-term and at 1-year follow-up. The study sample consisted of 260 consecutive patients with severe aortic stenosis who underwent transcatheter aortic valve implantation (TAVI). EOAs and MGs were measured with Doppler echocardiography for the following prostheses: S3 23 mm (n = 74; 28.5%), S3 26 mm (n = 67; 25.8%), S3 29 mm (n = 20; 7.7%), CV 23 mm (n = 2; 0.8%), CV 26 mm (n = 15; 5.8%), CV 29 mm (n = 24; 9.2%), CV 31 mm (n = 9; 3.5%), EVR 26 mm (n = 22; 8.5%), and EVR 29 mm (n = 27; 10.4%). Values were obtained at discharge, 1 month, 6 months, and 1 year from implantation. At discharge, EOAs were larger and MGs lower for larger-size prostheses, regardless of being balloon-expandable or self-expandable. In patients with small aortic annulus size, the hemodynamic performances of CV and EVR prostheses were superior to those of S3. However, we did not observe significant differences in terms of all-cause mortality according to THV type or size. Both balloon-expandable and self-expandable new-generation THVs show excellent hemodynamic performances without evidence of very early valve degeneration.

Baseline mean platelet volume is a strong predictor of major and life-threatening bleedings after transcatheter aortic valve replacement.

BACKGROUND: Bleeding following transcatheter aortic valve replacement (TAVR) has important prognostic implications. This study sought to evaluate the impact of baseline mean platelet volume (MPV) on bleeding events after TAVR. METHODS AND RESULTS: Patients undergoing TAVR between February 2010 and May 2019 were included. Low MPV (L-MPV) was defined as MPV ≤10 fL and high MPV (H-MPV) as MPV >10 fL. The primary endpoint was the occurrence of major/life-threatening bleeding complications (MLBCs) at one-year follow-up. Among 1,111 patients, 398 (35.8%) had L-MPV and 713 (64.2%) had H-MPV. The rate of MLBCs at 1 year was higher in L-MPV patients compared with H-MPV patients (22.9% vs. 17.7% respectively, p = 0.034). L-MPV was associated with vascular access-site complications (36.2% vs. 28.9%, p = 0.012), early (<30 days) major bleeding (15.6% vs. 9.4%, p<0.01) and red blood cell transfusion >2 units (23.9% vs. 17.5%, p = 0.01). No impact of baseline MPV on overall death, cardiovascular death and ischemic events (myocardial infarction and stroke) was evidenced. Multivariate analysis using Fine and Gray model identified preprocedural hemoglobin (sHR 0.84, 95%CI [0.75-0.93], p = 0.001), preprocedural L-MPV (sHR 1.64, 95%CI [1.16-2.32], p = 0.005) and closure time adenosine diphosphate post-TAVR (sHR 2.71, 95%CI [1.87-3.95], p<0.001) as predictors of MLBCs. CONCLUSIONS: Preprocedural MPV was identified as an independent predictor of MLBCs one year after TAVR, regardless of the extent of platelet inhibition and primary hemostasis disorders.

Impact of Primary Hemostasis Disorders on Late Major Bleeding Events among Anticoagulated Atrial Fibrillation Patients Treated by TAVR.

BACKGROUND: Bleeding events are among the striking complications following transcatheter aortic valve replacement (TAVR), and bleeding prediction models are crucially warranted. Several studies have highlighted that primary hemostasis disorders secondary to persistent loss of high-molecular-weight (HMW) multimers of the von Willebrand factor (vWF) and assessed by adenosine diphosphate closure time (CT-ADP) may be a strong predictor of late major/life-threatening bleeding complications (MLBCs). Pre-existing atrial fibrillation (AF) is a frequent comorbidity in TAVR patients and potentially associated with increased bleeding events after the procedure. OBJECTIVES: This study evaluated the impact of ongoing primary hemostasis disorders, as assessed by post-procedural CT-ADP > 180 s, on clinical events after TAVR among anticoagulated AF patients. METHODS: An ongoing primary hemostasis disorder was defined by post-procedure CT-ADP > 180 s. Bleeding complications were assessed according to the Valve Academic Research Consortium-2 (VARC-2) criteria. The primary endpoint was the occurrence of late MLBCs at one-year follow-up. The secondary endpoint was a composite of mortality, stroke, myocardial infarction, and rehospitalization for heart failure. RESULTS: In total, 384 TAVR patients were included in the analysis. Of these patients, 57 patients (14.8%) had a prolongated CT-ADP > 180 s. Increased MLBCs were observed in patients with CT-ADP > 180 s (35.1% versus 1.2%; p < 0.0001). Conversely, the occurrence of the composite endpoint did not differ between the groups. Multivariate analysis identified CT-ADP > 180 s (HR 28.93; 95% CI 9.74-85.95; p < 0.0001), bleeding history, paradoxical aortic stenosis (AS), and major vascular complications following TAVR as independent predictors of late MLBCs. CONCLUSION: Among patients with anticoagulated AF, a post-procedural CT-ADP > 180 s was identified as a strong independent predictor of late MLBCs. These findings suggest that persistent primary hemostasis disorders contribute to a higher risk of late bleeding events and should be considered for a tailored, risk-adjusted antithrombotic therapy after TAVR.

Acute kidney injury and acute kidney recovery following Transcatheter Aortic Valve Replacement.

BACKGROUND: Acute kidney injury (AKI) is associated with a dismal prognosis in Transcatheter Aortic Valve replacement (TAVR). Acute kidney recovery (AKR), a phenomenon reverse to AKI has recently been associated with better outcomes. METHODS: Between November 2012 to May 2018, we explored consecutive patients referred to our Heart Valve Center for TAVR. AKI was defined according to the VARC-2 definition. Mirroring the VARC-2 definition of AKI, AKR was defined as a decrease in serum creatinine (≥50%) or ≥25% improvement in GFR up to 72 hours after TAVR. RESULTS: AKI and AKR were respectively observed in 8.3 and 15.7% of the 574 patients included. AKI and AKR patients were associated to more advanced kidney disease at baseline. At a median follow-up of 608 days (range 355-893), AKI and AKR patients experienced an increased cardiovascular mortality compared to unchanged renal function patients (14.6% and 17.8% respectively, vs. 8.1%, CI 95%, p<0.022). Chronic kidney disease, (HR: 3.9; 95% CI 1.7-9.2; p < 0.001) was the strongest independent factor associated with AKI similarly to baseline creatinine level (HR: 1; 95% CI 1 to 1.1 p < 0.001) for AKR. 72-hours post procedural AKR (HR: 2.26; 95% CI 1.14 to 4.88; p = 0.021) was the strongest independent predictor of CV mortality. CONCLUSIONS: Both AKR and AKI negatively impact long term clinical outcomes of patients undergoing TAVR.

Increased susceptibility to SARS-CoV-2 infection in patients with reduced left ventricular ejection fraction.

AIMS: Cardiovascular disease has been recognized as a major determinant of coronavirus disease 2019 (COVID-19) vulnerability and severity. Angiotensin-converting enzyme (ACE) 2 is a functional receptor for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and is up-regulated in patients with heart failure. We sought to examine the potential association between reduced left ventricular ejection fraction (LVEF) and the susceptibility to SARS-CoV-2 infection. METHODS AND RESULTS: Of the 1162 patients with acute coronary syndrome (ACS) who underwent percutaneous coronary intervention between February 2014 and October 2018, we enrolled 889 patients with available clinical follow-up data. Follow-up was conducted by telephone interviews 1 month after the start of the French lockdown which began on 17 March 2020. Patients were divided into two groups according to LVEF <40% (reduced LVEF) (n = 91) or ≥40% (moderately reduced + preserved LVEF) (n = 798). The incidence of COVID-19-related hospitalization or death was significantly higher in the reduced LVEF group as compared with the moderately reduced + preserved LVEF group (9% vs. 1%, P < 0.001). No association was found between discontinuation of ACE-inhibitor or angiotensin-receptor blockers and COVID-19 test positivity. By multivariate logistic regression analysis, reduced LVEF was an independent predictor of COVID-19 hospitalization or death (odds ratio: 6.91, 95% confidence interval: 2.60 to 18.35, P < 0.001). CONCLUSIONS: In a large cohort of patients with previous ACS, reduced LVEF was associated with increased susceptibility to COVID-19. Aggressive COVID-19 testing and therapeutic strategies may be considered for patient with impaired heart function.

Impact of residual inflammation on myocardial recovery and cardiovascular outcome in Takotsubo patients.

AIMS: Recent insights have emphasized the importance of myocardial and systemic inflammation in Takotsubo syndrome (TTS). In a large registry of unselected patients, we sought to evaluate whether residual high inflammatory response (RHIR) could impact cardiovascular outcome after TTS. METHODS AND RESULTS: Patients with TTS were retrospectively included between 2008 and 2018 in three general hospitals. Three hundred eighty-five patients with TTS were split into three subgroups, according to tertiles of C-reactive protein (CRP) levels at discharge (CRP <5.2 mg/L, CRP range 5.2 to 19 mg/L, and CRP >19 mg/L). The primary endpoint was the impact of RHIR, defined as CRP >19 mg/L at discharge, on cardiac death or hospitalization for heart failure. Follow up was obtained in 382 patients (99%) after a median of 747 days. RHIR patients were more likely to have a history of cancer or a physical trigger. Left ventricular ejection fraction (LVEF) at admission and at discharge were comparable between groups. By contrast, RHIR was associated with lower LVEF at follow up (61.7% vs. 60.7% vs. 57.9%; P = 0.004) and increased cardiac late mortality (0% vs. 0% vs. 10%; P = 0.001). By multivariate Cox regression analysis, RHIR was an independent predictor of cardiac death or hospitalization for heart failure (hazard ratio: 1.87; 95% confidence interval: 1.08 to 3.25; P = 0.025). CONCLUSIONS: Residual high inflammatory response was associated with impaired LVEF at follow up and was evidenced as an independent factor of cardiovascular events. All together, these findings underline RHIR patients as a high-risk subgroup, to target in future clinical trials with specific therapies to attenuate RHIR.

Impact of Opioid Analgesia and Inhalation Sedation Kalinox on Pain and Radial Artery Spasm during Transradial Coronary Angiography.

With respect to the transfemoral approach, transradial procedures enable a drastic reduction of bleeding events and are associated with a reduction of mortality. Radial artery spasm (RAS) is one of the most common complications and may lead to patient discomfort and procedural failure. Currently, there is no consensus on the optimal sedation protocol to avoid RAS. The aim of this study was to investigate the respective impact of opioids analgesia and inhalation sedation with a 50% nitrous oxide/oxygen premix (Kalinox) on pain and occurrence of RAS during transradial coronary procedures. Consecutive patients undergoing transradial coronary angiography were prospectively enrolled in one, single center observational study (Nouvel Hôpital Civil, Strasbourg, France). Patients received opioids analgesia or inhalation sedation with Kalinox. The primary endpoints of the study were the incidence of a pain scale ≥5/10 and the occurrence of RAS. The secondary endpoints were the incidence of side effects. A total of 325 patients were enrolled (185 in the opioids analgesia group, 140 in the Kalinox group). RAS and pain scale ≥5 rates were not significantly different in the opioids analgesia and Kalinox groups (respectively 13.5% vs. 10.0% and 16.2% vs. 11.4%). Headache was more frequently observed in the Kalinox group (6.4% vs. 0.0%; p = 0.002). By multivariate analysis, female gender, BMI <25 kg/m2, puncture difficulty, the use of plastic needle and 6F sheath were identified as independent predictors of RAS. Procedural inhalation sedation by Kalinox is as safe as opioids analgesia during transradial coronary angiography.