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.

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.

Diagnosis and Management of Spontaneously Recanalized Coronary Thrombus Guided by Optical Coherence Tomography　- Lessons From the French "Lotus Root" Registry.

BACKGROUND: Spontaneous reanalyzed coronary thrombus (SRCT) has been reported in autopsy series, but little is known about SRCT, and it is potentially under-diagnosed in clinical practice.Methods and Results:SRCT identified on OCT were included in a French multicenter series, the Lotus Root French Registry. A total of 34 SRCT were identified on OCT in 33 patients (23 male; median age, 56 years; IQR, 52-65 years); 23/33 patients (70%) presented with angina pectoris and/or dyspnea. Three angiographic aspects were distinguished retrospectively: braided, pseudo-dissected, and hazy. Stenosis severity on quantitative coronary analysis varied between 11% and 100% (median, 45%), whereas the reduction in lumen area on OCT varied between 20% and 92% (median, 68%). A typical "lotus root" aspect was confirmed on OCT, consisting of multiple circular concave-edged channels of varying size, numbering between 3 and 12 depending on the slice, separated by smooth-edged septa of high luminosity without posterior attenuation. OCT also served to guide treatment, with stenting in 91% of cases. During the 17-month follow-up 91% of patients had excellent evolution. One death and 3 ACS events occurred. CONCLUSIONS: In this large SRCT cohort, angiography had limited diagnostic value whereas OCT could be used to define disease characteristics and guide treatment of lesions inducing angina pectoris and/or silent myocardial ischemia. OCT-guided management was associated with good prognosis.

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.

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.

Pericardial effusion in patients with COVID-19: case series.

BACKGROUND: SARS-coronavirus-2 [coronavirus disease 2019 (COVID-19)] infection is a public health issue affecting millions of people. It started in Wuhan in China in December 2019 spreading rapidly worldwide. CASE SUMMARY: Three patients aged 51-84 developed a pericarditis related to COVID-19, associated for two of them with a myocarditis. Case 1 was a COVID-19 cardiac tamponade without myocarditis, confirmed by a positive chest computed tomography (CT) scan. Case 2 showed a COVID-19 myopericarditis, confirmed by a positive chest CT scan and a SARS-coronavirus-2 positive swab. Case 3 was a cardiac tamponade due to COVID-19 pericarditis, with a positive polymerase chain reaction on pericardial fluid. They were all treated by colchicine and their condition improved rapidly. DISCUSSION: Presumably rare, we reported three cases of pericardial effusions (PEs) occurring in a single cardiology centre. There is a higher incidence of COVID-19-related cardiac diseases such as pericarditis that can manifest as a minimal PE to a cardiac tamponade, which should result in a higher awareness of cardiologists. A systematic measure of the high-sensitivity troponin kinetic in patients affected by COVID-19 could be interesting in order to screen for potential myocarditis. Any unexplained haemodynamic failure or increased cardiac biomarkers should make the medical team search for myopericarditis by a transthoracic echocardiography.

Paradoxical Increase of Stroke in Patients with Defect of High Molecular Weight Multimers of the von Willebrand Factors following Transcatheter Aortic Valve Replacement.

BACKGROUND: Stroke is a major cause of disability after transcatheter aortic valve replacement (TAVR) and stroke prediction models and data are crucially needed. Following TAVR, high molecular weight (HMW) multimers defect of von Willebrand factor (VWF) as assessed by closure time of adenosine diphosphate (CT-ADP) value > 180 seconds is an independent predictor of bleeding events. This study sought to identify predictors of ischemic neurological events in patients who underwent TAVR and the specific impact of HMW multimers defect of VWF. METHODS: Patients were prospectively enrolled between November 2012 and May 2018 at our institution. The CT-ADP, a point-of-care measure of hemostasis, was assessed the day before and 24 hours after the procedures. The rate of ischemic stroke and transient ischemic attack (TIA) was recorded up to 30 days after the procedures. RESULTS: Of 565 TAVR patients, ischemic stroke/TIA was observed in 21 (3.7%) patients within 30 days. Ischemic stroke/TIA was associated with major/life-threatening bleeding complications (MLBCs) (9 [43%] vs. 88 [16%], p = 0.002) and postprocedure CT-ADP > 180 seconds (10 [48%] vs. 116 [21%], p = 0.01). By multivariate analysis, MLBCs (odds ratio [OR]: 3.58; 95% confidence interval [CI]: 1.45-8.84; p = 0.006) and postprocedure CT-ADP > 180 seconds (OR: 3.38; 95% CI: 1.38-8.25; p = 0.008) were evidenced as independent predictors of ischemic stroke/TIA. CONCLUSION: MLBCs and CT-ADP > 180 seconds were identified as predictors for ischemic stroke or TIA. The present study suggests that the defects of HMW multimers of the VWFs may contribute not only to bleeding events but also to thrombotic events.

Does Transcatheter Aortic Valve Replacement Modulate the Kinetic of Superoxide Anion Generation?

Reactive oxygen species (ROS) are central bioenergetic markers linked to aortic stenosis (AS) development and severity. We sought to evaluate the time course and impact of ROS assessed by plasmatic superoxide anion (SA) among patients undergoing transcatheter aortic valve replacement (TAVR). Among 106 patients, SA significantly decreased after TAVR. Dropped values were measured 10 min after TAVR (0.590 ± 0.181 vs. 0.648 ± 0.193; p < 0.001) and persistent at 3 days (0.611 ± 0.0.228 vs. 0.646 ± 0.199; p = 0.033) and 30 days follow-up (0.572 ± 0.207 vs. 0.639 ± 0.199; p = 0.005). Increased baseline SA (>75 percentile) was continuously associated with higher postprocedural SA values 10 min after valve expansion (p < 0.001), at 3 days (p < 0.001) and 30 days (p < 0.001). Higher baseline SA was linked to higher inflammatory response assessed by higher C-reactive protein values at day 1 and day 3. The composite endpoint of all-cause mortality and/or stroke and/or pacemaker implantation and/or significant paravalvular aortic regurgitation ≥mild at 30 days did not differ significantly according to SA baseline values (p = 0.055). This is the first report identifying a decrease in oxidative stress level after TAVR. Our observation leads to the hypothesis that oxidative stress biomarkers may survive the journey from bench to bedside in AS and TAVR and become new biomarkers with both diagnostic and prognostic values. Antioxid. Redox Signal. 31, 420-426.

Primary Hemostatic Disorders and Late Major Bleeding After Transcatheter Aortic Valve Replacement.

BACKGROUND: Periprocedural and late (>30 days) bleedings represent major complications after transcatheter aortic valve replacement and have been identified as potential areas for improved patient care. OBJECTIVES: The authors sought to evaluate the impact of ongoing primary hemostasis disorders on late major/life-threatening bleeding complications (MLBCs). METHODS: Bleedings were assessed according to the VARC-2 (Valve Academic Research Consortium-2) criteria. Closure time of adenosine diphosphate (CT-ADP), a surrogate marker of high molecular weight von Willebrand multimers proteolysis was assessed 24 h after the procedure. Ongoing primary hemostasis disorder was defined by a CT-ADP >180 s. RESULTS: Among 372 patients who survived at 30 days, MLBCs occurred in 42 patients (11.3%) at a median follow-up of 383 days (interquartile range: 188 to 574 days). MLBCs were mainly of gastrointestinal origin (42.8%) and were associated with increased overall mortality (hazard ratio [HR]: 5.66; 95% confidence interval [CI]: 3.10 to 10.31; p < 0.001) and cardiac mortality (HR: 11.62; 95% CI: 4.59 to 29.37; p < 0.001). A 2.5-fold elevation of MLBCs could be evidenced in patients with a CT-ADP > 180 s (27.4% vs. 11.5%; p < 0.001). Multivariate regression analysis identified paravalvular leak (PVL) (HR: 6.31; 95% CI: 3.43 to 11.60; p < 0.0001) and CT-ADP > 180 s (HR: 3.08; 95% CI: 1.62 to 5.81; p = 0.0005) as predictor of MLBCs. CONCLUSIONS: MLBCs after transcatheter aortic valve replacement are frequent and associated with an increased morbidity and mortality. PVL and CT-ADP >180 s were identified as strong predictors for MLBCs. These findings strongly suggest that persistent HMW defects contribute to enhanced bleeding risk in patients with residual PVL.

CT-ADP Point-of-Care Assay Predicts 30-Day Paravalvular Aortic Regurgitation and Bleeding Events following Transcatheter Aortic Valve Replacement.

BACKGROUND: Paravalvular aortic regurgitation (PVAR) remains a frequent postprocedural concern following transcatheter aortic valve replacement (TAVR). Persistence of flow turbulence results in the cleavage of high-molecular-weight von Willebrand multimers, primary haemostasis dysfunction and may favour bleedings. Recent data have emphasized the value of a point-of-care measure of von Willebrand factor-dependent platelet function (closure time [CT] adenosine diphosphate [ADP]) in the monitoring of immediate PVAR. This study examined whether CT-ADP could detect PVAR at 30 days and bleeding complications following TAVR. METHODS: CT-ADP was assessed at baseline and the day after the procedure. At 30 days, significant PVAR was defined as a circumferential extent of regurgitation more than 10% by transthoracic echocardiography. Events at follow-up were assessed according to the Valve Academic Research Consortium-2 consensus classification. RESULTS: Significant PVAR was diagnosed in 44 out of 219 patients (20.1%). Important reduction of CT-ADP could be found in patients without PVAR, contrasting with the lack of CT-ADP improvement in significant PVAR patients. By multivariate analysis, CT-ADP > 180 seconds (hazard ratio [HR]: 5.1, 95% confidence interval [CI]: 2.5-10.6; p < 0.001) and a self-expandable valve were the sole independent predictors of 30-day PVAR. At follow-up, postprocedural CT-ADP >180 seconds was identified as an independent predictor of major/life-threatening bleeding (HR: 1.7, 95% CI [1.0-3.1]; p = 0.049). Major/life-threatening bleedings were at their highest levels in patients with postprocedural CT-ADP > 180 seconds (35.2 vs. 18.8%; p = 0.013). CONCLUSION: Postprocedural CT-ADP > 180 seconds is an independent predictor of significant PVAR 30 days after TAVR and may independently contribute to major/life-threatening bleedings.

Radial versus femoral access for coronary angiography and intervention is associated with lower patient radiation exposure in high-radial-volume centres: Insights from the RAY'ACT-1 study.

BACKGROUND: Literature suggests that radial access is associated with higher radiation doses than femoral access. AIMS: To compare patient radiation exposure during coronary angiography (CA) and percutaneous coronary intervention (PCI) with radial versus femoral access. METHODS: RAY'ACT is a nationwide, multicentre, French survey evaluating patient radiation in interventional cardiology. Variables of patient exposure from 21,675 CAs and 17,109 PCIs performed at 44 centres during 2010 were analysed retrospectively. RESULTS: Radial access was used in 71% of CAs and 69% of PCIs. Although median fluoroscopy times were longer for radial versus femoral access (CA, 3.8 vs 3.5minutes [P<0.001]; PCI, 10.4 vs 10.1minutes [P=0.001]), the Kerma-area product (KAP) was lower with radial access (CA, 26.8 vs 28.1Gy·cm2; PCI, 55.6 vs 59.4Gy·cm2; both P=0.001). Differences in KAP remained significant in the multivariable analysis (P<0.01), and in a propensity score-matched analysis (P=0.01). A significant interaction was found between KAP and the percentage of procedures with radial access by centre (P<0.001). KAP was higher by radial versus femoral access in low-radial-volume centres, and lower in high-radial-volume centres. Radiation protection techniques, such as the use of low frame rates (7.5 frame/s), were used more frequently in high-radial-volume radial centres. CONCLUSIONS: In this multicentre study, radial access was associated with lower radiation doses to patient than femoral access in high-radial-volume centres. Provided that radioprotection methods are implemented, radial access could be associated with lower patient radiation exposure.

Radiation Doses to Patients in Interventional Coronary Procedures-Estimation of Updated National Reference Levels by Dose Audit.

The objective of this study was to estimate the French national updated reference levels (RLs) for coronary angiography (CA) and percutaneous coronary intervention (PCI) by a dose audit from a large data set of unselected procedures and in standard-sized patients. Kerma-area product (PKA), air kerma at interventional point (Ka,r), fluoroscopy time (FT), and the number of registered frames (NFs) and runs (NRs) were collected from 51 229 CAs and 42 222 PCIs performed over a 12-month period at 61 French hospitals. RLs estimated by the 75th percentile in CAs and PCIs performed in unselected patients were 36 and 78 Gy.cm² for PKA, 498 and 1285 mGy for Ka,r, 6 and 15 min for FT, and 566 and 960 for NF, respectively. These values were consistent with the RLs calculated in standard-sized patients. The large difference in dose between sexes leads us to propose specific RLs in males and females. The results suggest a trend for a time-course reduction in RLs for interventional coronary procedures.

Management of Takotsubo cardiomyopathy in non-academic hospitals in France: The Observational French SyndromEs of TakoTsubo (OFSETT) study.

BACKGROUND: Takotsubo cardiomyopathy (TTC) is a rare condition characterized by a sudden temporary weakening of the heart. TTC can mimic acute myocardial infarction and is associated with a minimal release of myocardial biomarkers in the absence of obstructive coronary artery disease. AIMS: To provide an extensive description of patients admitted to hospital for TTC throughout France and to study the management and outcomes of these patients. METHODS: In 14 non-academic hospitals, we collected clinical, electrocardiographic, biological, psychological and therapeutic data in patients with a diagnosis of TTC according to the Mayo Clinic criteria. RESULTS: Of 117 patients, 91.5% were women, mean ± SD age was 71.4 ± 12.1 years and the prevalence of risk factors was high (hypertension: 57.9%, dyslipidaemia: 33.0%, diabetes: 11.5%, obesity: 11.5%). The most common initial symptoms were chest pain (80.5%) and dyspnoea (24.1%). A triggering psychological event was detected in 64.3% of patients. ST-segment elevation was found in 41.7% of patients and T-wave inversion in 71.6%. Anterior leads were most frequently associated with ST-segment elevation, whereas T-wave inversion was more commonly associated with lateral leads, and Q-waves with septal leads. The ratio of peak B-type natriuretic peptide (BNP) or N-terminal prohormone BNP (NT-proBNP) level to peak troponin level was 1.01. No deaths occurred during the hospital phase. After 1 year of follow-up, 3 of 109 (2.8%) patients with available data died, including one cardiovascular death. Rehospitalizations occurred in 17.4% of patients: 2.8% due to acute heart failure and 14.7% due to non-cardiovascular causes. There was no recurrence of TTC. CONCLUSIONS: This observational study of TTC included primarily women with atherosclerotic risk factors and mental stress. T-wave inversion was more common than ST-segment elevation. There were few adverse cardiovascular outcomes in these patients after 1-year follow-up.