Bax, Jeroen J.

Abstract Aims Acute pulmonary disorders are known physical triggers of takotsubo syndrome (TTS). This study aimed to investigate prevalence of acute pulmonary triggers in patients with TTS and their impact on outcomes. Methods and results Patients with TTS were enrolled from the International Takotsubo Registry and screened for triggering factors and comorbidities. Patients were categorized into three groups (acute pulmonary trigger, chronic lung disease, and no lung disease) to compare clinical characteristics and outcomes. Of the 1670 included patients with TTS, 123 (7%) were identified with an acute pulmonary trigger, and 194 (12%) had a known history of chronic lung disease. The incidence of cardiogenic shock was highest in patients with an acute pulmonary trigger compared with those with chronic lung disease or without lung disease (17% vs. 10% vs. 9%, P = 0.017). In-hospital mortality was also higher in patients with an acute pulmonary trigger than in the other two groups, although not significantly (5.7% vs. 1.5% vs. 4.2%, P = 0.13). Survival analysis demonstrated that patients with an acute pulmonary trigger had the worst long-term outcome (P = 0.002). The presence of an acute pulmonary trigger was independently associated with worse long-term mortality (hazard ratio 2.12, 95% confidence interval 1.33–3.38; P = 0.002). Conclusions The present study demonstrates that TTS is related to acute pulmonary triggers in 7% of all TTS patients, which accounts for 21% of patients with physical triggers. The presence of acute pulmonary trigger is associated with a severe in-hospital course and a worse long-term outcome.

Abstract This International Consensus Classification and Nomenclature for the congenital bicuspid aortic valve condition recognizes 3 types of bicuspid valves: 1. The fused type (right-left cusp fusion, right-non-coronary cusp fusion and left-non-coronary cusp fusion phenotypes); 2. The 2-sinus type (latero-lateral and antero-posterior phenotypes); and 3. The partial-fusion (forme fruste) type. The presence of raphe and the symmetry of the fused type phenotypes are critical aspects to describe. The International Consensus also recognizes 3 types of bicuspid valve-associated aortopathy: 1. The ascending phenotype; 2. The root phenotype; and 3. Extended phenotypes.

Abstract This International evidence-based nomenclature and classification consensus on the congenital bicuspid aortic valve and its aortopathy recognizes 3 types of bicuspid aortic valve: 1. Fused type, with 3 phenotypes: right-left cusp fusion, right-non cusp fusion and left-non cusp fusion; 2. 2-sinus type with 2 phenotypes: Latero-lateral and antero-posterior; and 3. Partial-fusion or forme fruste. This consensus recognizes 3 bicuspid-aortopathy types: 1. Ascending phenotype; root phenotype; and 3. extended phenotypes.

Abstract Background While the presence left ventricular (LV) remodelling after ST-segment elevation myocardial infarction (STEMI) is known to worsen prognosis, the impact of progressive vs. stable LV remodelling on outcome has not been established. Purpose To investigate the impact of progressive LV remodelling on outcome in STEMI patients who were treated with primary percutaneous coronary intervention (PCI) and optimal pharmacotherapy. Methods Baseline, 3-, 6- and 12-month echocardiograms were analysed. Early LV remodelling (ER) was defined as a ≥20% increase in LV end-diastolic volume (EDV) during the first 3 months post-STEMI, and mid-term remodelling (MTR) as ≥20% LVEDV change by 6 months. Progressive LV remodelling was defined according to spline curve analyses: ≥0% LVEDV increase by 6 months (i.e. further increase after 3 months) for ER, and ≥20% by 12 months (i.e. an additional increase after 6 months) for MTR. The impact of progressive LV remodelling on outcome was evaluated with a Log rank test. Results 589 STEMI patients (mean age 61±12 years, 78% male) who demonstrated LV remodelling in the first 6 months post-infarct, were analysed: 408 (69%) ER and 181 (31%) MTR. Progressive LV remodelling occurred in 146 (36%) ER and in 12 (7%) MTR. After a median follow-up of 90 (IQR 64–117) months, 39 (10%) ER were hospitalised for heart failure. 25 (14%) MTR remodellers died after a median follow-up of 86 (IQR 66–112) months. Progressive LV remodelling in ER led to a higher rate of heart failure hospitalisation (P=0.017 vs. non-progressive ER, Fig. 1A) but no mortality difference (P=0.10 vs. non-progressive ER). In contrast, MTR with progressive LV remodelling experienced worse survival (P=0.01 vs. non-progressive MTR, Fig. 1B) but no increase in heart failure hospitalisation (P=0.65 vs. non-progressive MTR). Conclusions Progressive LV remodelling causes an increased risk of heart failure in ER post-infarct, vs. higher mortality in MTR. These two patterns of progressive, post-infarct LV remodelling possibly represent different underlying pathophysiological mechanisms: i.e. evolution of true post-infarct remodelling in ER, vs. natural history of established heart failure in MTR. Figure 1 Funding Acknowledgement Type of funding source: None

Abstract Transcatheter aortic valve replacement (TAVR) has grown exponentially worldwide in the last decade. Due to the higher bleeding risks associated with oral anticoagulation and in patients undergoing TAVR, antiplatelet therapy is currently considered first-line antithrombotic treatment after TAVR. Recent studies suggest that some patients can develop subclinical transcatheter heart valve (THV) thrombosis after the procedure, whereby thrombus forms on the leaflets that can be a precursor to leaflet dysfunction. Compared with echocardiography, multidetector computed tomography is more sensitive at detecting THV thrombosis. Transcatheter heart valve thrombosis can occur while on dual antiplatelet therapy with aspirin and thienopyridine but significantly less with anticoagulation. This review summarizes the incidence and diagnostic criteria for THV thrombosis and discusses the pathophysiological mechanisms that may lead to thrombus formation, its natural history, potential clinical implications and treatment for these patients.

Abstract Aims More evidence is needed to quantify the association between tricuspid regurgitation (TR) and mortality in patients with heart failure (HF). Methods and results Between 2008–2017, using the Optum longitudinal database, a patient-level database that integrates multiple US-based electronic health and claim records from several health care providers, we identified 435 679 patients with new HF diagnosis and both an assessment of the left ventricular ejection fraction and at least 1 year of history. TR was graded as mild, moderate or severe and classified as prevalent (at the time of the initial HF diagnosis) or incident (subsequent new cases thereafter). For prevalent TR, the analysis was performed using a Cox proportional hazards model with adjustment for patient covariates. Incident TR was modelled as a time-updated covariate, as were other non-fatal events during follow-up. Prevalence of mild, moderate and severe TR at baseline was 10.1%, 5.1% and 1.4%, respectively. Over a median follow-up of 1.5 years, 121 273 patients (27.8%) died and prevalent TR was independently associated with survival. Compared to patients with no TR at baseline, the adjusted hazard ratios for mortality were 0.99 [95% confidence interval (CI) 0.97–1.01], 1.17 (95% CI 1.14–1.20) and 1.34 (95% CI 1.28–1.39) for mild, moderate and severe TR, respectively. In the 363 270 patients free from TR at baseline, incident TR (at least mild, at least moderate, or severe) developed during follow-up in 12.1%, 5.1% and 1.1%, respectively. Adjusted mortality hazard ratios for such new cases were 1.48 (95% CI 1.44–1.52), 1.92 (95% CI 1.86–1.99) and 2.44 (95% CI 2.32–2.57), respectively. Findings were consistent across all patient subgroups based on age, gender, rhythm, associated comorbidities, prior cardiac surgery, B-type natriuretic peptide/N-terminal pro-B-type natriuretic peptide, and left ventricular ejection fraction. Conclusions In this large contemporary patient-level database of almost half-million US patients with HF, TR was associated with a marked increases in mortality risk overall and in all subgroups. Future randomized controlled trials will evaluate the impact of TR correction on clinical outcomes and the causal relationship between TR and mortality.

Abstract Aims Takotsubo syndrome (TTS) is an acute heart failure syndrome, which shares many features with acute coronary syndrome (ACS). Although TTS was initially described with angiographically normal coronary arteries, smaller studies recently indicated a potential coexistence of coronary artery disease (CAD) in TTS patients. This study aimed to determine the coexistence, features, and prognostic role of CAD in a large cohort of patients with TTS. Methods and results Coronary anatomy and CAD were studied in patients diagnosed with TTS. Inclusion criteria were compliance with the International Takotsubo Diagnostic Criteria for TTS, and availability of original coronary angiographies with ventriculography performed during the acute phase. Exclusion criteria were missing views, poor quality of angiography loops, and angiography without ventriculography. A total of 1016 TTS patients were studied. Of those, 23.0% had obstructive CAD, 41.2% had non-obstructive CAD, and 35.7% had angiographically normal coronary arteries. A total of 47 patients (4.6%) underwent percutaneous coronary intervention, and 3 patients had acute and 8 had chronic coronary artery occlusion concomitant with TTS, respectively. The presence of CAD was associated with increased incidence of shock, ventilation, and death from any cause. After adjusting for confounders, the presence of obstructive CAD was associated with mortality at 30 days. Takotsubo syndrome patients with obstructive CAD were at comparable risk for shock and death and nearly at twice the risk for ventilation compared to an age- and sex-matched ACS cohort. Conclusions Coronary artery disease frequently coexists in TTS patients, presents with the whole spectrum of coronary pathology including acute coronary occlusion, and is associated with adverse outcome. Trial registration ClinicalTrials.gov number: NCT01947621.

Abstract Aims Left ventricular (LV) remodelling after ST-segment elevation myocardial infarction (STEMI) worsens outcome. The effect of sex on LV post-infarct remodelling is unknown. We therefore investigated the sex distribution and long-term prognosis of LV post-infarct remodelling after STEMI in the contemporary era of primary percutaneous coronary intervention (PCI) and optimal pharmacotherapy. Methods and results Data were obtained from an ongoing primary PCI STEMI registry. LV remodelling was defined as ≥20% increase in LV end-diastolic volume at either 3, 6, or 12 months post-infarct, and LV remodelling impact on outcome was evaluated with a log-rank test. A total population of 1995 STEMI patients were analysed (mean age 60 ± 12 years): 1527 (77%) men and 468 (23%) women. The mean age of male patients was 60±11 versus 63±13 years for women (P < 0.001). A total of 953 (48%) patients experienced LV remodelling in the first 12 months of follow-up, and it was equally frequent amongst men (n = 729, 48%) and women (n = 224, 48%). After a median follow-up of 94 (interquartile range 69–119) months, 225 patients died: 171 (11%) men and 54 (12%) women. No survival difference was seen between remodellers and non-remodellers in the male (P = 0.113) and female (P = 0.920) groups. Conclusion LV post-infarct remodelling incidence, as well as long-term survival of LV remodellers and non-remodellers, was similar in men and women who were treated with primary PCI and optimal pharmacotherapy post-STEMI.

Abstract Aims The aim of the present study was to investigate the impact of aspirin on prognosis in takotsubo syndrome (TTS). Methods and results Patients from the International Takotsubo (InterTAK) Registry were categorized into two groups based on aspirin prescription at discharge. A comparison of clinical outcomes between groups was performed using an adjusted analysis with propensity score (PS) stratification; results from the unadjusted analysis were also reported to note the effect of the PS adjustment. Major adverse cardiac and cerebrovascular events (MACCE: a composite of death, myocardial infarction, TTS recurrence, stroke or transient ischaemic attack) were assessed at 30-day and 5-year follow-up. A total of 1533 TTS patients with known status regarding aspirin prescription at discharge were included. According to the adjusted analysis based on PS stratification, aspirin was not associated with a lower hazard of MACCE at 30-day [hazard ratio (HR) 1.24, 95% confidence interval (CI) 0.50–3.04, P = 0.64] or 5-year follow-up (HR 1.11, 95% CI 0.78–1.58, P = 0.58). These results were confirmed by sensitivity analyses performed with alternative PS-based methods, i.e. covariate adjustment and inverse probability of treatment weighting. Conclusion In the present study, no association was found between aspirin use in TTS patients and a reduced risk of MACCE at 30-day and 5-year follow-up. These findings should be confirmed in adequately powered randomized controlled trials. ClinicalTrials.gov Identifier: NCT01947621.