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.

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.

Bedside Renal Doppler Ultrasonography and Acute Kidney Injury after TAVR.

Acute kidney injury (AKI) following transcatheter aortic valve replacement (TAVR) is associated with a dismal prognosis. Elevated renal resistive index (RRI), through renal Doppler ultrasound (RDU) evaluation, has been associated with AKI development and increased systemic arterial stiffness. Our pilot study aimed to investigate the performance of Doppler based RRI to predict AKI and outcomes in TAVR patients. From May 2018 to May 2019, 100 patients with severe aortic stenosis were prospectively enrolled for TAVR and concomitant RDU evaluation at our institution (Nouvel Hôpital Civil, Strasbourg University, France). AKI by serum Creatinine (sCr-AKI) was defined according to the VARC-2 definition and AKI by serum Cystatin C (sCyC-AKI) was defined as an sCyC increase of greater than 15% with baseline value. Concomitant RRI measurements as well as renal and systemic hemodynamic parameters were recorded before, one day, and three days after TAVR. It was found that 10% of patients presented with AKIsCr and AKIsCyC. The whole cohort showed higher baseline RRI values (0.76 ± 0.7) compared to normal known and accepted values. AKIsCyC had significant higher post-procedural RRI one day (Day 1) after TAVR (0.83 ± 0.1 vs. 0.77 ± 0.6, CI 95%, p = 0.005). AUC for AKIsCyC was 0.766 and a RRI cut-off value of ≥ 0.795 had the most optimal sensitivity/specificity (80/62%) combination. By univariate Cox analysis, Mehran Risk Score, higher baseline right atrial pressure at baseline > 0.8 RRI values one day after TAVR (HR 6.5 (95% CI 1.3-32.9; p = 0.021) but not RRI at baseline were significant predictors of AKIsCyC. Importantly, no significant impact of baseline biological parameters, renal or systemic parameters could be demonstrated. Doppler-based RRI can be helpful for the non-invasive assessment of AKI development after TAVR.

Systemic Inflammatory Response Syndrome Is a Major Determinant of Cardiovascular Outcome in Takotsubo Syndrome.

BACKGROUND: Recent insights have emphasized the importance of inflammatory response in takotsubo syndrome (TTS). We sought to evaluate the predictors of systemic inflammatory response syndrome (SIRS) and its impact on cardiovascular mortality after TTS.Methods and Results:The 215 TTS patients were retrospectively included between September 2008 and January 2018. SIRS was diagnosed in 96 patients (44.7%). They had lower left ventricular ejection fraction (LVEF) on admission (34.5% vs. 41.9%; P<0.001) and higher peak brain natriuretic peptide and troponin. At a median follow-up of 518 days, SIRS was associated with increased in-hospital mortality (14.6% vs. 5.0%; P=0.019), overall mortality (29.4% vs. 10.8%; P=0.002), and cardiovascular mortality (10.6% vs. 2.1%; P=0.026). A history of cancer (OR, 3.36; 95% CI: 1.54-7.31; P=0.002) and LVEF <40% at admission (OR, 2.31; 95% CI: 1.16-4.58; P=0.017) were identified as independent predictors of SIRS. On multivariate Cox regression analysis, SIRS (HR, 12.8; 95% CI: 1.58-104; P=0.017), age (HR, 1.09; 95% CI: 1.02-1.16; P=0.01), and LVEF <40% at discharge (HR, 9.88; 95% CI: 2.54-38.4; P=0.001) were independent predictors of cardiovascular death. CONCLUSIONS: SIRS was found in a large proportion of TTS patients and was associated with enhanced myocardial damage and adverse outcome in the acute phase. At long-term follow-up, SIRS remained an independent factor of cardiovascular death.

Impact of Antithrombotic Regimen and Platelet Inhibition Extent on Leaflet Thrombosis Detected by Cardiac MDCT after Transcatheter Aortic Valve Replacement.

The impact of antithrombotic regimen and platelet inhibition extent on subclinical leaflet thrombosis (SLT) detected by cardiac multidetector computed tomography (MDCT) after transcatheter aortic valve replacement (TAVR) is not well established. Hypoattenuation affecting motion (HAM) has been proposed as a surrogate marker of SLT, and is characterized by hypoattenuated leaflet thickening (HALT) and concomitant reduction in leaflet motion (RELM). We sought to investigate (i) the prevalence of HAM and HALT after TAVR detected by MDCT, (ii) the predictors of SLT, (iii) the impact of oral anticoagulant (OAC) and platelet inhibition extent assessed by platelet reactivity index vasodilator stimulated phosphoprotein (PRI-VASP) and closure time adenosine diphosphate (CT-ADP) on SLT. Of 187 consecutive patients who underwent TAVR from 1 August 2017 to 31 March 2018, 90 of them had cardiac CT at relevant follow-up. Clinical, biological, echocardiographic, procedural characteristics and treatments were collected before, at discharge, and 1 year after TAVR. P2Y12 platelet inhibition extent and primary haemostasis disorders were investigated using platelet PRI-VASP and CT-ADP point-of-care assays. Eighty-five post-TAVR CTs out of 90 were ranked for clarity and assessed with sufficient diagnostic quality. HAM was evidenced in 13 patients (15.3%) and HALT in 30 patients (35%). Procedural characteristics, including aortic valve calcium score, annulus size, or procedural heparin regimens, were equivalent between groups. Likewise, no impact of P2Y12 inhibition (PRI-VASP) nor primary haemostasis disorders (CT-ADP) on SLT could be evidenced. No impact of SLT on valve deterioration evaluated by transthoracic echocardiography (TTE) and clinical events could be established at 12 months follow-up. By multivariate analysis, lack of oral anticoagulant therapy at discharge (HR 12.130 CI 95% (1.394-150.582); p = 0.028) and higher haemoglobin levels were evidenced as the sole independent predictors of SLT. In four patients with HAM, MDCT follow-up was obtained after initiation of OAC therapy and showed a complete regression of HAM. SLT was evidenced in a sizeable proportion of patients treated by TAVR and was mainly determined by the lack of oral anticoagulant therapy. Conversely, no impact of platelet inhibition extent on SLT could be evidenced.