Clinical and Hemodynamic Improvement in Pulmonary Hypertension After Switching to Sacubitril/Valsartan in Patients With Heart Failure With Preserved Ejection Fraction.

ABSTRACT: Patients with heart failure with preserved ejection fraction (HFpEF) and pulmonary hypertension have poor survival, and established medical therapies for both conditions are not available. In this retrospective study of 69 patients with HFpEF and either isolated postcapillary pulmonary hypertension (IpcPH, n = 53) or combined postcapillary and precapillary pulmonary hypertension (CpcPH, n = 16), we investigated the effects of sacubitril/valsartan on pulmonary hypertension measured using right heart catheterization at baseline (ie, presacubitril/valsartan) and 99 (94-123) days after switching to sacubitril/valsartan. After switching to sacubitril/valsartan, right heart catheterization showed significantly lower pulmonary artery pressures (systolic/diastolic/mean) in both patient groups compared with presacubitril/valsartan [IpcPH: 44 (38-52)/15 (12-19)/28 (22-33) mm Hg vs. 47 (40-55)/18 (15-23)/31 (26-35) mm Hg, P < 0.01; CpcPH: 54 (43-57)/18 (12-23)/34 (30-36) mm Hg vs. 61 (50-79)/24 (19-30)/40 (31-53) mm Hg, P < 0.05]. The median sacubitril/valsartan dose at follow-up was 24/26 (24/26-49/51) mg twice daily in both patients with IpcPH and CpcPH. Clinically, the New York Heart Association functional class improved by at least 1 class in 32 of 69 patients ( P < 0.01). In conclusion, sacubitril/valsartan therapy improves pulmonary hypertension in patients with HFpEF and either IpcPH or CpcPH. Further prospective randomized trials are needed for confirmation of our results.

Machine learning-based prediction of in-hospital death for patients with takotsubo syndrome: The InterTAK-ML model.

AIMS: Takotsubo syndrome (TTS) is associated with a substantial rate of adverse events. We sought to design a machine learning (ML)-based model to predict the risk of in-hospital death and to perform a clustering of TTS patients to identify different risk profiles. METHODS AND RESULTS: A ridge logistic regression-based ML model for predicting in-hospital death was developed on 3482 TTS patients from the International Takotsubo (InterTAK) Registry, randomly split in a train and an internal validation cohort (75% and 25% of the sample size, respectively) and evaluated in an external validation cohort (1037 patients). Thirty-one clinically relevant variables were included in the prediction model. Model performance represented the primary endpoint and was assessed according to area under the curve (AUC), sensitivity and specificity. As secondary endpoint, a K-medoids clustering algorithm was designed to stratify patients into phenotypic groups based on the 10 most relevant features emerging from the main model. The overall incidence of in-hospital death was 5.2%. The InterTAK-ML model showed an AUC of 0.89 (0.85-0.92), a sensitivity of 0.85 (0.78-0.95) and a specificity of 0.76 (0.74-0.79) in the internal validation cohort and an AUC of 0.82 (0.73-0.91), a sensitivity of 0.74 (0.61-0.87) and a specificity of 0.79 (0.77-0.81) in the external cohort for in-hospital death prediction. By exploiting the 10 variables showing the highest feature importance, TTS patients were clustered into six groups associated with different risks of in-hospital death (28.8% vs. 15.5% vs. 5.4% vs. 1.0.8% vs. 0.5%) which were consistent also in the external cohort. CONCLUSION: A ML-based approach for the identification of TTS patients at risk of adverse short-term prognosis is feasible and effective. The InterTAK-ML model showed unprecedented discriminative capability for the prediction of in-hospital death.

Final 3-Year Outcomes of a Randomized Trial Comparing a Self-Expanding to a Balloon-Expandable Transcatheter Aortic Valve.

BACKGROUND: In the SCOPE I trial (Safety and Efficacy of the Symetis ACURATE Neo/TF Compared to the Edwards SAPIEN 3 Bioprosthesis), transcatheter aortic valve implantation with the self-expanding ACURATE neo (NEO) did not meet noninferiority compared with the balloon-expandable SAPIEN 3 (S3) device regarding a composite end point at 30 days due to higher rates of prosthetic valve regurgitation and acute kidney injury. Data on long-term durability of NEO are scarce. Here, we report whether early differences between NEO and S3 translate into differences in clinical outcomes or bioprosthetic valve failure 3 years after transcatheter aortic valve implantation. METHODS: Patients with severe aortic stenosis were randomized to transfemoral transcatheter aortic valve implantation with NEO or S3 at 20 European centers. Clinical outcomes at 3 years are compared using Cox proportional or Fine-Gray subdistribution hazard models by intention-to-treat. Bioprosthetic valve failure is reported for the valve-implant cohort. RESULTS: Among 739 patients, 84 of 372 patients (24.3%) had died in the NEO and 85 of 367 (25%) in the S3 group at 3 years. Comparing NEO with S3, the 3-year rates of all-cause death (hazard ratio, 0.98 [95% CI, 0.73-1.33]), stroke (subhazard ratio, 1.04 [95% CI, 0.56-1.92]), and hospitalization for congestive heart failure (subhazard ratio, 0.74 [95% CI, 0.51-1.07]) were similar between the groups. Aortic valve reinterventions were required in 4 NEO and 3 S3 patients (subhazard ratio, 1.32 [95% CI, 0.30-5.85]). New York Heart Association functional class ≤II was observed in 84% (NEO) and 85% (S3), respectively. Mean gradients remained lower after NEO at 3 years (8 versus 12 mm Hg; P<0.001). CONCLUSIONS: Early differences between NEO and S3 did not translate into significant differences in clinical outcomes or bioprosthetic valve failure throughout 3 years. REGISTRATION: URL: https://clinicaltrials.gov, Unique identifier: NCT03011346.

The COORDINATE Pilot Study: Impact of a Transcatheter Aortic Valve Coordinator Program on Hospital and Patient Outcomes.

The transcatheter aortic valve implantation (TAVI) treatment pathway is complex, leading to procedure-related delays. Dedicated TAVI coordinators can improve pathway efficiency. COORDINATE was a pilot observational prospective registry at three German centers that enrolled consecutive elective patients with severe aortic stenosis undergoing TAVI to investigate the impact a TAVI coordinator program. Pathway parameters and clinical outcomes were assessed before (control group) and after TAVI coordinator program implementation (intervention phase). The number of repeated diagnostics remained unchanged after implementation. Patients with separate hospitalizations for screening and TAVI had long delays, which increased after implementation (65 days pre- vs. 103 days post-implementation); hospitalizations combining these were more efficient. The mean time between TAVI and hospital discharge remained constant. Nurse (p = 0.001) and medical technician (p = 0.008) working hours decreased. Patient satisfaction increased, and more consistent/intensive contact between patients and staff was reported. TAVI coordinators provided more post-TAVI support, including discharge management. No adverse effects on post-procedure or 30-day outcomes were seen. This pilot suggests that TAVI coordinator programs may improve aspects of the TAVI pathway, including post-TAVI care and patient satisfaction, without compromising safety. These findings will be further investigated in the BENCHMARK registry.

Modern gold standard of cardiac output measurement - A simplified bedside measurement of individual oxygen uptake in the cath lab.

OBJECTIVES: Cardiac output (CO) measurements employing the direct Fick principle represent the gold standard in right-sided heart catheterization (RHC). The current widespread approach in hemodynamic workup however uses the indirect Fick principle with assumed values for oxygen uptake (VO2) leading to incorrect CO values in up to 25% of patients. We have tested a contemporary breath-by-breath gas analyzer that allows precise real-time measurements of VO2 with appropriate time and effort to serve the direct Fick principle. METHODS: By means of a small and mobile metabolic cart assembled with widely used components of a standard spiroergometer, we performed bedside measurements of individual VO2. In 33 unselected, consecutive patients with various indications for RHC we compared CO values derived from indirect vs. direct Fick calculations. RESULTS: In 28 of the 33 patients, VO2 measurements were completed with a plausible dataset within a median of 3.2 (interquartile range 2.8-6.2) min. In nine of the 28 patients, CO values based on measured VO2 values differed by more than 20% from CO calculations based on assumed VO2 values with value deviations scattering over a broad range in both directions (maximally +52% to minimally -46%). CONCLUSIONS: The bedside measurement of VO2 for gold standard CO determination is technically feasible within a few min and can thus be easily included in any RHC protocol. As modern therapy for numerus indications demand a precise upfront measurement of hemodynamics, our method might help to correctly identify patients for costly therapies.

Ethnic comparison in takotsubo syndrome: novel insights from the International Takotsubo Registry.

BACKGROUND: Ethnic disparities have been reported in cardiovascular disease. However, ethnic disparities in takotsubo syndrome (TTS) remain elusive. This study assessed differences in clinical characteristics between Japanese and European TTS patients and determined the impact of ethnicity on in-hospital outcomes. METHODS: TTS patients in Japan were enrolled from 10 hospitals and TTS patients in Europe were enrolled from 32 hospitals participating in the International Takotsubo Registry. Clinical characteristics and in-hospital outcomes were compared between Japanese and European patients. RESULTS: A total of 503 Japanese and 1670 European patients were included. Japanese patients were older (72.6 ± 11.4 years vs. 68.0 ± 12.0 years; p < 0.001) and more likely to be male (18.5 vs. 8.4%; p < 0.001) than European TTS patients. Physical triggering factors were more common (45.5 vs. 32.0%; p < 0.001), and emotional triggers less common (17.5 vs. 31.5%; p < 0.001), in Japanese patients than in European patients. Japanese patients were more likely to experience cardiogenic shock during the acute phase (15.5 vs. 9.0%; p < 0.001) and had a higher in-hospital mortality (8.2 vs. 3.2%; p < 0.001). However, ethnicity itself did not appear to have an impact on in-hospital mortality. Machine learning approach revealed that the presence of physical stressors was the most important prognostic factor in both Japanese and European TTS patients. CONCLUSION: Differences in clinical characteristics and in-hospital outcomes between Japanese and European TTS patients exist. Ethnicity does not impact the outcome in TTS patients. The worse in-hospital outcome in Japanese patients, is mainly driven by the higher prevalence of physical triggers. TRIAL REGISTRATION: URL: https://www.clinicaltrials.gov ; Unique Identifier: NCT01947621.

Outcomes after transcatheter valve-in-valve implantation using a balloon-expandable Edwards Sapien valve in patients with degenerated Freestyle aortic bioprosthesis.

BACKGROUND: Transcatheter aortic valve-in-valve implantation (ViV TAVI) in degenerated Medtronic Freestyle aortic bioprosthesis (FSB) has been reported as being technically challenging. This study sought to evaluate procedural data and outcomes after ViV TAVI using a balloon-expandable Edwards valve in patients with failed FSB. METHODS: Between August 2014 and December 2020, twenty-seven consecutive patients underwent ViV TAVI for symptomatic FSB failure at our institution using a Sapien XT (n=1) and Sapien 3 (n=26) valve, respectively. Endpoints were defined according to the Valve Academic Research Consortium-2 (VARC-2) criteria and were retrospectively analyzed. RESULTS: Mean patient age was 75.7±8.2 years (female n=5, male n=22); Society of Thoracic Surgeons Predicted Risk of Mortality score was 7.3%±6.2%. ViV implantation with correct positioning of the Edwards Sapien valve within the FSB was successful in all cases. Intraprocedural transesophageal echocardiography revealed none/trace paravalvular regurgitation in twenty-five patients (92.6%), mild paravalvular regurgitation was present in two patients (7.4%). Neither of the patients had a mean gradient ≥20.0 mmHg excluding significant patient-prosthesis mismatch. Three early deaths (≤thirty days) occurred resulting in a device success rate of 88.8%. One-year and three-year survival rates for patients alive beyond day thirty after ViV TAVI were 95.8% and 70.0%, respectively. CONCLUSIONS: ViV TAVI with Edwards Sapien valves lead to acceptable functional results in high-risk patients with degenerated FSB but early complications must be considered particularly during hospital stay.

Reduction of Pulmonary Hypertension After Transition to Sacubitril/Valsartan in Patients With Heart Failure With Preserved Ejection Fraction.

Objectives: Although the PARAGON-HF trial failed to reach its primary endpoint, subgroups of patients with heart failure with preserved ejection fraction (HFpEF) still appear to benefit from Sacubitril/Valsartan therapy. As HFpEF patients with pulmonary hypertension display a specifically high mortality and morbidity, we evaluated the effect of Sacubitril/Valsartan in this subgroup of HFpEF patients. Methods: In this retrospective case-series of 18 patients with HFpEF and pulmonary hypertension, right heart catheterisation (RHC) for determination of invasive pulmonary pressure were performed at baseline (pre-Sacubitril/Valsartan) and 99 (71-156) days after transition from angiotensin-converting enzyme inhibitors and angiotensin receptor blockers to Sacubitril/Valsartan (post-Sacubitril/Valsartan). Results are given as median and interquartile range. Results: After conversion to Sacubitril/Valsartan, RHC showed significantly reduced pulmonary artery pressure (PAP) and mean pulmonary capillary wedge pressure (PCWP) compared to pre-Sacubitril/Valsartan [PAP systolic/diastolic/mean 44 (38-55)/15 (11-20)/27 (23-33) mm Hg vs. 51 (41-82)/22 (13-29)/33 (28-52) mm Hg, p < 0.05 and p < 0.01, respectively; PCWP 16 (12-20) mm Hg vs. 22 (15-27) mm Hg, p < 0.05]. Median Sacubitril/Valsartan dosage was 24/26 mg BID (24/26 BID-49/51 mg BID). Clinically, New York Heart Association functional class improved in 12 of the 18 patients (p < 0.01) after conversion to Sacubitril/Valsartan. Echocardiographic parameters of left ventricular function and cardiovascular co-medication did not differ markedly between pre- and post-Sacubitril/Valsartan. Conclusion: Sacubitril/Valsartan therapy is associated with an improvement of pulmonary hypertension in HFpEF patients.

Impact of Atrial Fibrillation on Outcome in Takotsubo Syndrome: Data From the International Takotsubo Registry.

Background Atrial fibrillation (AF) is a major risk factor for mortality. The prevalence, clinical correlates, and prognostic impact of AF in Takotsubo syndrome (TTS) have not yet been investigated in a large patient cohort. This study aimed to investigate the prevalence, clinical correlates, and prognostic impact of AF in patients with TTS. Methods and Results Patients with TTS were enrolled from the International Takotsubo Registry, which is a multinational network with 26 participating centers in Europe and the United States. Patients were dichotomized according to the presence or absence of AF at the time of admission. Of 1584 patients with TTS, 112 (7.1%) had AF. The mean age was higher (P<0.001), and there were fewer women (P=0.046) in the AF than in the non-AF group. Left ventricular ejection fraction was significantly lower (P=0.001), and cardiogenic shock was more often observed (P<0.001) in the AF group. Both in-hospital (P<0.001) and long-term mortality (P<0.001) were higher in the AF group. Multivariable Cox regression analysis revealed that AF was independently associated with higher long-term mortality (hazard ratio, 2.31; 95% CI, 1.50-3.55; P<0.001). Among patients with AF on admission, 42% had no known history of AF before the acute TTS event, and such patients had comparable in-hospital and long-term outcomes compared with those with a history of AF. Conclusions In patients presenting with TTS, AF on admission is significantly associated with increased in-hospital and long-term mortality rates. Whether antiarrhythmics and/or cardioversion are beneficial in TTS with AF should thus be tested in a future trial. Registration URL: https://www.clinicaltrials.gov; Unique identifier: NCT01947621.

"Brass Knuckle"-Like Right Coronary Artery.

A 60-year-old asymptomatic woman was admitted to hospital for an invasive evaluation of a patent foramen ovale and a suspected formation within the right atrium. Transthoracic and transesophageal echocardiography excluded both, but instead unveiled a huge "brass knuckle"-like ectasia of the right coronary artery meandering down the lateral wall of the right atrium. Coronary anomalies are common and mostly discovered incidentally. Thus, diagnostic and therapeutic approaches should be guided by the clinical scenario of the patient.

Prognostic impact of acute pulmonary triggers in patients with takotsubo syndrome: new insights from the International Takotsubo Registry.

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.

Transcatheter valve-in-valve implantation versus surgical redo aortic root replacement in patients with degenerated freestyle aortic bioprosthesis.

BACKGROUND: Transcatheter aortic valve-in-valve implantation (ViV TAVI) represents a new treatment option for patients with degenerated aortic bioprosthesis. Comparative data to redo surgical aortic valve replacement (redo SAVR) are limited. OBJECTIVE: We investigated feasibility and outcome of ViV TAVI versus redo SAVR in patients with symptomatic degenerated Medtronic Freestyle aortic bioprosthesis (FSB). METHODS: Between January 2002 and February 2020, 25 patients with failed FSB underwent ViV TAVI and 10 patients with failed FSB underwent redo SAVR. Endpoints were defined according to the Valve Academic Research Consortium-2 (VARC-2) criteria. RESULTS: Age and logistic EuroSCORE II were higher in patients with ViV TAVI (75.4 ± 1.7 vs. 62.9 ± 5.1 years, p = .019; 11.5 ± 1.6 vs. 5.6 ± 5.6%, p = .007). Valve implantation was successful in all cases. Mean transvalvular pressure gradients were significantly lower in patients with redo SAVR than ViV TAVI (7.6 ± 1.0 vs. 10.3 ± 0.8 mmHg, p = .037). Aortic valve regurgitation was absent in 91% and 100% of patients with ViV TAVI and redo SAVR, respectively. Thirty-day mortality rates were 12% in the ViV TAVI cohort versus 0% in the redo SAVR cohort (p = .542). Within the first year after hospital discharge, one patient after ViV TAVI had redo surgical intervention. CONCLUSIONS: ViV TAVI and redo SAVR lead to excellent functional results in patients with degenerated FSB. Post-procedural early complications must be considered particularly in patients with ViV TAVI because of higher clinical risk profiles.

Kidney injury as post-interventional complication of TAVI.

Transcatheter aortic valve implantation (TAVI) is an accepted treatment approach of aortic stenosis. In the beginning, this technique was executed in high-risk patients only. Today, intermediate-risk patients are also amenable for TAVI, as long as the transfemoral approach is chosen. Numerous predictors have been identified that could lead to periprocedural complications and are defined by patient co-morbidities as well as being inherent to the technical approach. Although vascular complications and postinterventional paravalvular regurgitation have been minimized over the past years by revised technologies and techniques, there is a prevailing individual risk brought about by the specific pathophysiology of the cardiorenal syndrome.

Coexistence and outcome of coronary artery disease in Takotsubo syndrome.

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.

Age-Related Variations in Takotsubo Syndrome.

BACKGROUND: Takotsubo syndrome (TTS) occurs predominantly in post-menopausal women but is also found in younger patients. OBJECTIVES: This study aimed to investigate age-related differences in TTS. METHODS: Patients diagnosed with TTS and enrolled in the International Takotsubo Registry between January 2011 and February 2017 were included in this analysis and were stratified by age (younger: ≤50 years, middle-age: 51 to 74 years, elderly: ≥75 years). Baseline characteristics, hospital course, as well as short- and long-term mortality were compared among groups. RESULTS: Of 2,098 TTS patients, 242 (11.5%) patients were ≤50 years of age, 1,194 (56.9%) were 51 to 74 years of age, and 662 (31.6%) were ≥75 years of age. Younger patients were more often men (12.4% vs. 10.9% vs. 6.3%; p = 0.002) and had an increased prevalence of acute neurological (16.3% vs. 8.4% vs. 8.8%; p = 0.001) or psychiatric disorders (14.1% vs. 10.3% vs. 5.6%; p < 0.001) compared with middle-aged and elderly TTS patients. Furthermore, younger patients had more often cardiogenic shock (15.3% vs. 9.1% vs. 8.1%; p = 0.004) and had a numerically higher in-hospital mortality (6.6% vs. 3.6% vs. 5.1%; p = 0.07). At multivariable analysis, younger (odds ratio: 1.60; 95% confidence interval: 0.86 to 3.01; p = 0.14) and older age (odds ratio: 1.09; 95% confidence interval: 0.66 to 1.80; p = 0.75) were not independently associated with in-hospital mortality using the middle-aged group as a reference. There were no differences in 60-day mortality rates among groups. CONCLUSIONS: A substantial proportion of TTS patients are younger than 50 years of age. TTS is associated with severe complications requiring intensive care, particularly in younger patients.

Impact of aspirin on takotsubo syndrome: a propensity score-based analysis of the InterTAK Registry.

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.

Intraventricular Thrombus Formation and Embolism in Takotsubo Syndrome: Insights From the International Takotsubo Registry.

OBJECTIVE: Takotsubo syndrome (TTS) is characterized by acute left ventricular dysfunction, which can contribute to intraventricular thrombus and embolism. Still, prevalence and clinical impact of thrombus formation and embolic events on outcome of TTS patients remain unclear. This study aimed to investigate clinical features and outcomes of patients with and without intraventricular thrombus or embolism. Additionally, factors associated with thrombus formation or embolism, as well as predictors for mortality, were identified. Approach and Results: TTS patients enrolled in the International Takotsubo Registry at 28 centers in Australia, Europe, and the United States were dichotomized according to the occurrence/absence of intraventricular thrombus or embolism. Patients with intraventricular thrombus or embolism were defined as the ThrombEmb group. Of 1676 TTS patients, 56 (3.3%) patients developed intraventricular thrombus and/or embolism following TTS diagnosis (median time interval, 2.0 days [range, 0-38 days]). Patients in the ThrombEmb group had a different clinical profile including lower left ventricular ejection fraction, higher prevalence of the apical type, elevated levels of troponin and inflammatory markers, and higher prevalence of vascular disease. In a Firth bias-reduced penalized-likelihood logistic regression model apical type, left ventricular ejection fraction ≤30%, previous vascular disease, and a white blood cell count on admission >10×103 cells/µL emerged as independent predictors for thrombus formation or embolism. CONCLUSIONS: Intraventricular thrombus or embolism occur in 3.3% of patients in the acute phase of TTS. A simple risk score including clinical parameters associated with intraventricular thrombus formation or embolism identifies patients at increased risk. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifier: NCT01947621.

Clinical Predictors and Prognostic Impact of Recovery of Wall Motion Abnormalities in Takotsubo Syndrome: Results From the International Takotsubo Registry.

Background Left ventricular (LV) recovery in takotsubo syndrome (TTS) occurs over a wide-ranging interval, varying from hours to weeks. We sought to investigate the clinical predictors and prognostic impact of recovery time for TTS patients. Methods and Results TTS patients from the International Takotsubo Registry were included in this study. Cut-off for early LV recovery was determined to be 10 days after the acute event. Multivariable logistic regression was used to assess factors associated with the absence of early recovery. In-hospital outcomes and 1-year mortality were compared for patients with versus without early recovery. We analyzed 406 patients with comprehensive and serial imaging data regarding time to recovery. Of these, 191 (47.0%) had early LV recovery and 215 (53.0%) demonstrated late LV improvement. Patients without early recovery were more often male (12.6% versus 5.2%; P=0.011) and presented more frequently with typical TTS (76.3% versus 67.0%, P=0.040). Cardiac and inflammatory markers were higher in patients without early recovery than in those with early recovery. Patients without early recovery showed unfavorable 1-year outcome compared with patients with early recovery (P=0.003). On multiple logistic regression, male sex, LV ejection fraction <45%, and acute neurologic disorders were associated with the absence of early recovery. Conclusions TTS patients without early LV recovery have different clinical characteristics and less favorable 1-year outcome compared with patients with early recovery. The factors associated with the absence of early recovery included male sex, reduced LV ejection fraction, and acute neurologic events. Clinical Trial Registration URL: http://www.clinicaltrials.gov. Unique identifier: NCT01947621.