Cardiac troponin elevation and mortality in takotsubo syndrome: New insights from the international takotsubo registry.

BACKGROUND: The clinical relevance of cardiac troponin (cTn) elevation in takotsubo syndrome (TTS) remains uncertain. The present study sought to investigate the role of cardiac troponin (cTn) elevations in mortality prediction of patients with Takotsubo syndrome (TTS). METHODS: Patients enrolled in the International Takotsubo (InterTAK) Registry from January 2011 to February 2020 with available data on peak cTn levels were included in the analysis. Peak cTn levels during the index hospitalization were used to define clinically relevant myocardial injury. The threshold at which clinically relevant myocardial injury drives mortality at 1 year was identified using restricted cubic spline analysis. RESULTS: Out of 2'938 patients, 222 (7.6%) patients died during 1-year follow-up. A more than 28.8-fold increase of cTn above the upper reference limit was identified as threshold for clinically relevant myocardial injury. The presence of clinically relevant myocardial injury was significantly associated with an increased risk of mortality at 5 years (adjusted HR 1.58, 95% CI 1.18-2.12, p =.002). Clinically relevant myocardial injury was related to an increased 5-year mortality risk in patients with apical TTS (adjusted HR 1.57, 95% CI 1.21-2.03, p =.001), in presence of physical stressors (adjusted HR 1.60, 95% CI 1.22-2.11, p =.001), and in absence of emotional stressors (adjusted HR 1.49, 95% CI, 1.17-1.89, p =.001). CONCLUSION: This study for the first time determined a troponin threshold for the identification of TTS patients at excess risk of mortality. These findings advance risk stratification in TTS and assist in identifying patients in need for close monitoring and follow-up.

Temporal Trends in Takotsubo Syndrome: Results From the International Takotsubo Registry.

BACKGROUND: The perception of takotsubo syndrome (TTS) has evolved significantly over the years, primarily driven by increased recognition of acute complications and mortality. OBJECTIVES: This study aimed to explore temporal trends in demographic patterns, risk factors, clinical presentations, and outcomes in patients with TTS. METHODS: Patients diagnosed with TTS between 2004 and 2021 were enrolled from the InterTAK (International Takotsubo) registry. To assess temporal trends, patients were divided into 6 groups, each corresponding to a 3-year interval within the study period. RESULTS: Overall, 3,957 patients were included in the study. There was a significant demographic transition, with the proportion of male patients rising from 10% to 15% (P = 0.003). Although apical TTS remained the most common form, the diagnosis of midventricular TTS increased from 18% to 28% (P = 0.018). The prevalence of physical triggers increased from 39% to 58% over the years (P < 0.001). There was a significant increase in 60-day mortality over the years (P < 0.001). However, a landmark analysis excluding patients who died within the first 60 days showed no differences in 1-year mortality (P = 0.150). CONCLUSIONS: This study of temporal trends in TTS highlights a transition in patients demographic with a growing prevalence among men, increasing recognition of midventricular TTS type, and increased short-term mortality and rates of cardiogenic shock in recent years. This transition aligns with the rising prevalence of physical triggers, as expression of increased recognition of TTS in association with acute comorbidities.

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.

Challenges and Burdens in the Coronary Artery Disease Care Pathway for Patients Undergoing Percutaneous Coronary Intervention: A Contemporary Narrative Review.

Clinical and economic burdens exist within the coronary artery disease (CAD) care pathway despite advances in diagnosis and treatment and the increasing utilization of percutaneous coronary intervention (PCI). However, research presenting a comprehensive assessment of the challenges across this pathway is scarce. This contemporary review identifies relevant studies related to inefficiencies in the diagnosis, treatment, and management of CAD, including clinician, patient, and economic burdens. Studies demonstrating the benefits of integration and automation within the catheterization laboratory and across the CAD care pathway were also included. Most studies were published in the last 5-10 years and focused on North America and Europe. The review demonstrated multiple potentially avoidable inefficiencies, with a focus on access, appropriate use, conduct, and follow-up related to PCI. Inefficiencies included misdiagnosis, delays in emergency care, suboptimal testing, longer procedure times, risk of recurrent cardiac events, incomplete treatment, and challenges accessing and adhering to post-acute care. Across the CAD pathway, this review revealed that high clinician burnout, complex technologies, radiation, and contrast media exposure, amongst others, negatively impact workflow and patient care. Potential solutions include greater integration and interoperability between technologies and systems, improved standardization, and increased automation to reduce burdens in CAD and improve patient outcomes.

Electrophysiology lab efficiency comparison between cryoballoon and point-by-point radiofrequency ablation: a German sub-analysis of the FREEZE Cohort study.

BACKGROUND: Pulmonary vein isolation (PVI) is recommended to treat paroxysmal and persistent atrial fibrillation (AF). This analysis aimed to assess the hospital efficiency of single-shot cryoballoon ablation (CBA) and point-by-point radiofrequency ablation (RFA). METHODS: The discrete event simulation used PVI procedure times from the FREEZE Cohort study to establish the electrophysiology (EP) lab occupancy time. 1000 EP lab days were simulated according to an illustrative German hospital, including 3 PVI cases per day using CBA at one site and RFA at the other. RESULTS: The analysis included 1560 CBA patients and 1344 RFA patients from the FREEZE Cohort. Some baseline patients' characteristics were different between groups (age, AF type, and some concomitant diseases), without being statistically associated to ablation procedure time. Mean procedure time was 122.2 ± 39.4 min for CBA and 160.3 ± 53.5 min for RFA (p < 0.0001). RFA was associated with a more than five-fold increase of cumulative overtime compared to CBA over the simulated period (1285 h with RFA and 253 h with CBA). 70.7% of RFA lab days included overtime versus 25.7% for CBA. CBA was associated with more days with an additional hour at the end of the EP lab shift compared to RFA (47.8% vs 11.5% days with one hour left, respectively). CONCLUSION: CBA is faster and more predictable than point-by-point RFA, and enables improvements in EP lab efficiency, including: fewer cumulative overtime hours, more days where overtime is avoided and more days with remaining time for the staff or for any EP lab usage. Clinical trial registration NCT01360008 (first registration 25/05/2011).

Prognostic relevance of gradual weight changes on long-term mortality in chronic heart failure.

BACKGROUND AND AIMS: While obesity has been linked to better ouctomes (the obesity paradox), cachexia is associated with higher mortality in patients with heart failure with reduced ejection fraction (HFrEF). As opposed to overt cachexia, little is known about the prognostic impact of gradual, long-term weight changes in stable HFrEF. METHODS AND RESULTS: We included ambulatory patients with clinically stable chronic HFrEF on individually optimized treatment. Next to other clinical and functional parameters, changes in body weight over the past one (n = 733, group 1) or two (n = 636, group 2) years were recorded. Four-year mortality was analysed with respect to baseline BMI and changes in body weight or BMI using fractional polynomials. In addition, outcome was stratified by BMI categories (18.5-25 kg/m2: normal weight, >25-30 kg/m2: overweight, >30 kg/m2: obesity). An obesity paradox was present in both groups, with overweight and obese patients having the best prognosis. In both groups, a gradual weight gain of 5% was associated with the lowest mortality, whereas mortality steadily increases with increasing weight loss. Excessive weight gain >10% was also related to higher mortality. Stratification by baseline BMI categories revealed that weight loss was most detrimental in normal weight patients, whereas the prognostic impact of weight change was weaker in obese patients. CONCLUSION: In patients with chronic HFrEF, gradual weight loss is associated with steadily increasing mortality, whereas a weight gain of 5% is related to the best prognosis. Prevention of any inappropriate weight loss might be a therapeutic goal in HFrEF patient care.

Transcatheter Closure of Large Atrial Septal Defects in Adults.

OBJECTIVE: To examine the outcomes of percutaneous closure of large atrial septal defects (ASDs) (≥25 mm). BACKGROUND: Data on long-term results after closure of large ASDs are limited. METHODS: We reviewed the records of 275 consecutive patients who underwent transcatheter closure of large (≥25 mm) ASDs from January 1999 until December 2016 in our center. The most common indication for closure was a large left-to-right shunt. Follow-up (FU) was performed at regular intervals thereafter. Results after closure of ASDs with diameters of 25-30 mm, >30-35 mm and >35 mm were compared. RESULTS: Percutaneous closure was technically successful in 99.6%. Mean FU time was 4.8 years (0-15.5 years). Peri-operative (30-day) adverse events occurred in 20.4% and included death in 0.7% (one unrelated to the procedure and one of unknown cause), device erosion in 0.7%, device embolization in 2.9%, pericardial effusion in 5.5%, air embolism in 0.4%, new onset atrial fibrillation in 10.5%, transient supraventricular tachycardia in 0.4% and fever in 0.7%. Late (>30 days after the procedure) atrial fibrillation occurred in 5.8%. There was one device erosion >15 years after the implantation treated successfully surgically. Complete defect closure was achieved in 95.6%. CONCLUSION: Device closure of large ASDs is feasible, safe and effective with high technical success and low risk of serious periprocedural complications. Nevertheless, in very large defects (>40 mm), both options, surgery and percutaneous closure should be considered. Device or procedural long-term adverse events are rare.

Renal effects of guideline-directed medical therapies in heart failure: a consensus document from the Heart Failure Association of the European Society of Cardiology.

Novel pharmacologic treatment options reduce mortality and morbidity in a cost-effective manner in patients with heart failure (HF). Undisputedly, the effective implementation of these agents is an essential element of good clinical practice, which is endorsed by the European Society of Cardiology (ESC) guidelines on acute and chronic HF. Yet, physicians struggle to implement these therapies as they have to balance the true and/or perceived risks versus their substantial benefits in clinical practice. Any worsening of biomarkers of renal function is often perceived as being disadvantageous and is in clinical practice one of the most common reasons for ineffective drug implementation. However, even in this context, they clearly reduce mortality and morbidity in HF with reduced ejection fraction (HFrEF) patients, even in patients with poor renal function. Furthermore these agents are also beneficial in HF with mildly reduced ejection fraction (HFmrEF) and sodium-glucose cotransporter 2 (SGLT2) inhibitors more recently demonstrated a beneficial effect in HF with preserved ejection fraction (HFpEF). The emerge of several new classes (angiotensin receptor-neprilysin inhibitor [ARNI], SGLT2 inhibitors, vericiguat, omecamtiv mecarbil) and the recommendation by the 2021 ESC guidelines for the diagnosis and treatment of acute and chronic HF of early initiation and titration of quadruple disease-modifying therapies (ARNI/angiotensin-converting enzyme inhibitor + beta-blocker + mineralocorticoid receptor antagonist and SGLT2 inhibitor) in HFrEF increases the likelihood of treatment-induced changes in renal function. This may be (incorrectly) perceived as deleterious, resulting in inertia of starting and uptitrating these lifesaving therapies. Therefore, the objective of this consensus document is to provide advice of the effect HF drugs on renal function.

Impact of HAS-BLED Score on outcome after percutaneous left atrial appendage closure: insights from the German Left Atrial Appendage Occluder Registry LAARGE.

AIM: Percutaneous left atrial appendage (LAA) closure has been established as alternative stroke prophylaxis in patients with non-valvular atrial fibrillation (AF) and high bleeding risk. However, little is known regarding the outcome after LAA closure depending on the HAS-BLED score. METHODS: A sub-analysis of the prospective, multicenter, Left-Atrium-Appendage Occluder Register-GErmany (LAARGE) registry was performed assessing three different groups with respect to the HAS-BLED score (0-2 [group 1] vs. 3-4 [group 2] vs. 5-7 [group 3]). RESULTS: A total of 633 patients at 38 centers were enrolled. Of them, 9% (n = 59) were in group 1, 63% (n = 400) in group 2 and 28% (n = 174) in group 3. The Kaplan-Meier estimated 1-year composite of death, stroke and systemic embolism was 3.4% in group 1 vs. 10.4% in group 2 vs. 20.1% in group 3, respectively (p log-rank < 0.001). The difference was driven by death since stroke and systemic embolism did not show a significant difference between the groups. The rate of major bleeding at 1 year was 0% vs. 0% vs. 2.4%, respectively (p = 0.016). CONCLUSION: The present data show that patients had similarly low rates of ischemic complications 1 year after LAA closure irrespective of the baseline bleeding risk. Higher HAS-BLED scores were associated with increased mortality due to higher age and more severe comorbidity of these patients.

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.

Mutation status and postresection survival of patients with non-small cell lung cancer brain metastasis: implications of biomarker-driven therapy.

OBJECTIVE: Non-small cell lung cancer (NSCLC) is the most common primary tumor to develop brain metastasis. Prognostic markers are needed to better determine survival after neurosurgical resection of intracranial disease. Given the importance of mutation subtyping in determining systemic therapy and overall prognosis of NSCLC, the authors examined the prognostic value of mutation status for postresection survival of patients with NSCLC brain metastasis. METHODS: The authors retrospectively analyzed all cases of NSCLC brain metastasis with available molecular testing data that were resected by a single surgeon at a single academic center from January 2009 to February 2019. Mutation status, demographic characteristics, clinical factors, and treatments were analyzed. Association between predictive variables and overall survival after neurosurgery was determined with Cox regression. RESULTS: Of the included patients (n = 84), 40% were male, 76% were smokers, the mean ± SD Karnofsky Performance Status was 85 ± 14, and the mean ± SD age at surgery was 63 ± 11 years. In total, 23%, 26%, and 4% of patients had EGFR, KRAS, and ALK/ROS1 alterations, respectively. On multivariate analysis, survival of patients with EGFR (HR 0.495, p = 0.0672) and KRAS (HR 1.380, p = 0.3617) mutations were not significantly different from survival of patients with wild-type (WT) tumor. However, the subgroup of patients with EGFR mutation who also received tyrosine kinase inhibitor (TKI) therapy had significantly prolonged survival (HR 0.421, p = 0.0471). In addition, postoperative stereotactic radiosurgery (HR 0.409, p = 0.0177) and resected tumor diameter < 3 cm (HR 0.431, p = 0.0146) were also significantly associated with prolonged survival, but Graded Prognostic Assessment score ≤ 1.0 (HR 2.269, p = 0.0364) was significantly associated with shortened survival. CONCLUSIONS: Patients with EGFR mutation who receive TKI therapy may have better survival after resection of brain metastasis than patients with WT tumor. These results may inform counseling and decision-making regarding the appropriateness of resection of NSCLC brain metastasis.

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.

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.