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.

Clinical characteristics and outcomes of patients with takotsubo syndrome versus spontaneous coronary artery dissection.

BACKGROUND: Takotsubo syndrome (TTS) and spontaneous coronary artery dissection (SCAD) are now increasingly recognized. Both conditions predominantly affect females; however, the exact pathophysiology remains unclear. Large multi-center databases can help elucidate the underlying mechanism and optimize treatments to improve outcomes by allowing us to compare features and outcomes of patients with TTS and patients with SCAD. METHODS: Takotsubo syndrome patients were enrolled from the International Takotsubo Registry and compared to SCAD patients from the Canadian Spontaneous Coronary Artery Dissection Cohort Study. In total 2098 TTS patients and 750 SCAD patients were included in the present study. RESULTS: More than 85% of patients in both groups were females. TTS patients were older compared to SCAD patients. Physical triggers were more common in TTS patients, while emotional triggers and non-identifiable triggering events were more common in SCAD patients. Left ventricular ejection fraction was more impaired in TTS compared to SCAD. TTS patients had more major cardiovascular risk factors, while SCAD patients had a higher rate of migraines and anxiety disorders than TTS patients. Thirty-day mortality was significantly higher in TTS patients, while 30-day stroke rates were comparable between groups. CONCLUSIONS: These findings suggest that women are at higher risk for TTS and SCAD compared to men, which should be considered in the differential diagnosis of those presenting with acute coronary syndrome. Additionally, emotional stressors play a significant role in triggering events particularly in younger women suffering from SCAD. The present findings may help clinicians better differentiate these two entities and aid in the appropriate risk stratification, diagnosis, and management. TRIAL REGISTRATION: ClinicalTrials.gov no. NCT01947621.

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.

Coronary Artery Aneurysm in Kawasaki Disease: Coronary CT Angiography through the Lens of Pathophysiology and Differential Diagnosis.

Kawasaki disease (KD) is an inflammatory autoimmune vasculitis affecting the coronary arteries of very young patients, which can result in coronary artery aneurysms (CAAs) with lifelong manifestations. Accurate identification and assessment of CAAs in the acute phase and sequentially during the chronic phase of KD is fundamental to the treatment plan for these patients. The differential diagnosis of CAA includes atherosclerosis, other vasculitic processes, connective tissue disorders, fistulas, mycotic aneurysms, and procedural sequelae. Understanding of the initial pathophysiology and evolutionary arterial changes is important to interpretation of imaging findings. There are multiple applicable imaging modalities, each with its own strengths, limitations, and role at various stages of the disease process. Coronary CT angiography is useful for evaluation of CAAs as it provides assessment of the entire coronary tree, CAA size, structure, wall, and lumen characteristics and visualization of other cardiothoracic vasculature. Knowledge of the natural history of KD, the spectrum of other conditions that can cause CAA, and the strengths and limitations of cardiovascular imaging are all important factors in imaging decisions and interpretation. Keywords: Pediatrics, Coronary Arteries, Angiography, Cardiac © RSNA, 2021.

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.

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.

Left Atrial Appendage Mechanical Exclusion: Procedural Planning Using Cardiovascular Computed Tomographic Angiography.

Left atrial appendage (LAA) mechanical exclusion is being investigated for nonpharmacologic stroke risk reduction in selected patients with atrial fibrillation. There are multiple potential approaches in various stages of development and clinical application, each of which depends on specific cardiothoracic anatomic characteristics for optimal performance. Multiple imaging modalities can be utilized for application of this technology, with transesophageal echocardiography used for intraprocedural guidance. Cardiovascular computed tomographic angiography can act as a virtual patient avatar, allowing for the assessment of cardiac structures in the context of surrounding cardiac, coronary vascular, thoracic vascular, and visceral and skeletal anatomy, aiding preprocedural decision-making, planning, and follow-up. Although transesophageal echocardiography is used for intraprocedural guidance, computed tomographic angiography may be a useful adjunct for preprocedure assessment of LAA sizing and anatomic obstacles or contraindications to deployment, aiding in the assessment of optimal approaches. Potential approaches to LAA exclusion include endovascular occlusion, epicardial ligation, primary minimally invasive intercostal thoracotomy with thoracoscopic LAA ligation or appendectomy, and minimally invasive or open closure as part of cardiothoracic surgery for other indications. The goals of these procedures are complete isolation or exclusion of the entire appendage without leaving a residual appendage stump or residual flow with avoidance of acute or chronic damage to surrounding cardiovascular structures. The cardiovascular imager plays an important role in the preprocedural and postprocedural assessment of the patient undergoing LAA exclusion.

Acute dilated cardiomyopathy in the setting of catastrophic antiphospholipid syndrome and thrombotic microangiopathy: A case series and review.

Catastrophic antiphospholipid antibody syndrome (CAPS) is a rare form of antiphospholipid syndrome, an autoimmune condition characterized by vascular thromboses, pregnancy loss, and antiphospholipid (aPL) antibodies. Diagnosis of CAPS relies on thrombosis of at least three different organs systems over 1 week, histopathological evidence of small vessel occlusion, and high aPL antibody titers. In a subset of precipitating circumstances, activation or disruption of endothelial cells in the microvasculature may occur along with cardiomyopathy. We present two cases of CAPS-associated dilated cardiomyopathy at our institution, focusing on disease management, pathophysiology, and treatment. These patients were of Southeastern Asian descent, raising the possibility of genetic polymorphisms contributing to the development of cardiomyopathy. Both met CAPS criteria and both demonstrated clinicopathologic thrombotic microangiopathy (TMA) and complement activation and developed severe dilated cardiomyopathy with shock. Complement activation plays an important role in the development of CAPS and may be important in the pathogenesis of CAPS-associated cardiomyopathy. Clinical suspicion for TMA as a pathophysiologic mechanism of unexplained heart failure in CAPS is important and increased awareness of cardiac side effects is necessary so that early treatment can be initiated to halt further cardiac and systemic complications.

Ventricular asystole in a CRT-D device. What is the mechanism?

We present a case of an 89-year-old man with a left ventricular assist device and cardiac resynchronization therapy device (CRT-D) who presented with multiple presyncopal events. On the night of admission, telemetry revealed a 13-s pause with appropriately timed pacing spikes but with failure to capture, followed by intermittent ventricular contraction with different QRS morphology. What was the mechanism for his ventricular asystole?

Cardiovascular Computed Tomographic Angiography as a Virtual Patient Avatar for Individualized Surgical Planning of Complex Anomalous Coronary Artery Anatomy.

Cardiovascular computed tomographic angiography (CCTA) 3-D thoracic reconstruction can serve as a "virtual patient avatar" providing surgical views for approach to complex anomalous coronary artery anatomy. Images demonstrated a single coronary artery ostium arising from the right aortic sinus with trifurcation into a prepulmonic left anterior descending coronary artery (LAD), an interarterial circumflex with a subsequent intraseptal course, and normal course of the right coronary artery. Virtual 3-D CCTA reconstructions were important to planning an incisional plane for surgical correction.

Late onset cardiac cirrhosis and portal hypertensive ascites after atrial fibrillation ablation.

Pulmonary vein stenosis is a potential complication following catheter ablation of atrial fibrillation (AF). We report the case of a patient with refractory ascites late after multiple catheter ablation procedures for AF. This is the first case report of portal hypertensive ascites due to acquired multiple pulmonary vein stenoses resulting in pulmonary hypertension (PH) and cardiac cirrhosis late after AF ablation. Despite extensive surgical reconstruction of the affected pulmonary veins, the patient has PH and right heart failure with persistent ascites and lower extremity edema.

A Case of Myocarditis and Near-Lethal Arrhythmia Associated With Interleukin-2 Therapy.

We present a case of a 48-year-old female who developed myocarditis and near fatal arrhythmias during high dose Il-2 therapy for metastatic renal cancer. On day 5 of therapy, the patient developed sudden onset chest pain, elevated cardiac enzymes and ST segment changes on EKG. Coronary angiogram was normal, however echocardiogram showed reduced ejection fraction and hemodynamic measurements showed elevated bilateral elevated filling pressures. The patient then developed episodes of recurrent ventricular arrhythmia, precipitated by bradycardia and PVC, requiring defibrillation and temporary pacemaker placement. Endomycardial biopsy was nonspecific showing fibrosis with subsequent cardiac MRI showed evidence of myocardial edema, consistent with Il-2 induced myocarditis in the setting of no prior cardiac history. After the discontinuation of Il-2 therapy, the patient displayed clinical improvement as well as improved ejection fraction. This case brings attention to the cardiac toxicities associated with high dose Il-2 therapy including potentially lethal arrhythmias and highlights the importance of careful cardiac screening prior to initiation of treatment.

Virtual medicine: Utilization of the advanced cardiac imaging patient avatar for procedural planning and facilitation.

Advances in imaging technology have led to a paradigm shift from planning of cardiovascular procedures and surgeries requiring the actual patient in a "brick and mortar" hospital to utilization of the digitalized patient in the virtual hospital. Cardiovascular computed tomographic angiography (CCTA) and cardiovascular magnetic resonance (CMR) digitalized 3-D patient representation of individual patient anatomy and physiology serves as an avatar allowing for virtual delineation of the most optimal approaches to cardiovascular procedures and surgeries prior to actual hospitalization. Pre-hospitalization reconstruction and analysis of anatomy and pathophysiology previously only accessible during the actual procedure could potentially limit the intrinsic risks related to time in the operating room, cardiac procedural laboratory and overall hospital environment. Although applications are specific to areas of cardiovascular specialty focus, there are unifying themes related to the utilization of technologies. The virtual patient avatar computer can also be used for procedural planning, computational modeling of anatomy, simulation of predicted therapeutic result, printing of 3-D models, and augmentation of real time procedural performance. Examples of the above techniques are at various stages of development for application to the spectrum of cardiovascular disease processes, including percutaneous, surgical and hybrid minimally invasive interventions. A multidisciplinary approach within medicine and engineering is necessary for creation of robust algorithms for maximal utilization of the virtual patient avatar in the digital medical center. Utilization of the virtual advanced cardiac imaging patient avatar will play an important role in the virtual health care system. Although there has been a rapid proliferation of early data, advanced imaging applications require further assessment and validation of accuracy, reproducibility, standardization, safety, efficacy, quality, cost effectiveness, and overall value to medical care.