Age-Related Differences in Takotsubo Syndrome: Results From the Multicenter GEIST Registry.

BACKGROUND: The role of age in the short- and long-term prognosis of takotsubo syndrome (TTS) is controversial. The aim of the present study was to evaluate age-related differences and prognostic implications among patients with TTS. METHODS AND RESULTS: In total, 2492 consecutive patients with TTS enrolled in an international registry were stratified into 4 groups (<45, 45-64, 65-74, and ≥75 years). The median long-term follow-up was 480 days (interquartile range, 83-1510 days). The primary outcome was all-cause mortality (in-hospital and out-of-hospital mortality). The secondary end point was TTS-related in-hospital complications. Among the 2479 patients, 58 (2.3%) were aged <45 years, 625 (25.1%) were aged 45 to 64 years, 733 (29.4%) were aged 65 to 74 years, and 1063 (42.6%) were aged ≥75 years. Young patients (<45 years) had a higher prevalence of men (from youngest to oldest, 24.1% versus 12.6% versus 9.7% versus 11.4%; P<0.01), physical triggers (46.6% versus 27.5%, 33.9%, and 38.4%; P<0.01), and non-apical forms of TTS (25.9% versus 23.7%, 12.7%, and 9%; P<0.01) than those aged 45 to 64, 65 to 74, and ≥75 years. During hospitalization, young patients experienced a higher rate of in-hospital complications (32.8% versus 23.4%, 27.4%, and 31.9%; P=0.01), but in-hospital mortality was higher in the older group (0%, 1.6%, 2.9%, and 5%; P=0.001). Long-term all-cause mortality was significantly higher in the older cohort (5.6%, 6.4%, 11.3%, and 22.3%; log-rank P<0.001), as was long-term cardiovascular mortality (0%, 0.9%, 1.9%, and 3.2%; log-rank P=0.01). CONCLUSIONS: Young patients with TTS have a typical phenotype characterized by a higher prevalence of male sex, non-apical ballooning patterns, and in-hospital complications. However, in-hospital and long-term mortality are significantly lower in young patients with TTS. REGISTRATION: URL: https://classic.clinicaltrials.gov/ct2/show/NCT04361994. Unique identifier: NCT04361994.

Neurological Disorders in Takotsubo Syndrome: Clinical Phenotypes and Outcomes.

BACKGROUND: Neurological disorders as a risk factor for Takotsubo syndrome (TTS) are not well characterized. The aim of the study was to evaluate TTS-associated neurological phenotypes and outcome. METHODS AND RESULTS: Patients with TTS enrolled in the international multicenter GEIST (German Italian Spanish Takotsubo) registry were analyzed. Prevalence, clinical characteristics, and short- and long-term outcomes of patients with TTS were recorded. A subgroup analysis of the 5 most represented neurological disorders was performed. In total, 400 (17%) of 2301 patients had neurological disorders. The most represented neurological conditions were previous cerebrovascular events (39%), followed by neurodegenerative disorders (30.7%), migraine (10%), epilepsy (9.5%), and brain tumors (5%). During hospitalization, patients with neurological disorders had longer in-hospital stay (8 [interquartile range, 5-12] versus 6 [interquartile range, 5-9] days; P<0.01) and more often experienced in-hospital complications (27% versus 16%; P=0.01) mainly driven by cardiogenic shock and in-hospital death (12% versus 7.6% and 6.5% versus 2.8%, respectively; both P<0.01). Survival analysis showed a higher mortality rate in neurological patients both at 60 days and long-term (8.8% versus 3.4% and 23.5% versus 10.1%, respectively; both P<0.01). Neurological disorder was an independent predictor of both the 60-day and long-term mortality rate (odds ratio, 1.78 [95% CI, 1.07-2.97]; P=0.02; hazard ratio, 1.72 [95% CI, 1.33-2.22]; both P<0.001). Patients with neurodegenerative disorders had the worst prognosis among the neurological disease subgroups, whereas patients with TTS with migraine had a favorable prognosis (long-term mortality rates, 29.2% and 9.7%, respectively). CONCLUSIONS: Neurological disorders identify a high-risk TTS subgroup for enhanced short- and long-term mortality rate. Careful recognition of neurological disorders and phenotype is therefore needed.

Long-Term Functional Limitations on Cardiopulmonary Exercise Testing in Emotion-Triggered Takotsubo Syndrome.

Background: In patients with prior Takotsubo syndrome (TTS), long-lasting functional cardiac limitations were described as compared with normal subjects. Emotion-triggered Takotsubo syndrome (E-TTS) has more favorable outcomes than TTS preceded by a physical trigger or by no identifiable factors. The aim of the present study was to assess long-term cardiac functional limitations in a cohort of asymptomatic E-TTS patients. Methods: We enrolled n = 40 asymptomatic patients with a diagnosis of E-TTS. Cardiopulmonary exercise tests (CPET) were performed at 30 (12-40) months median follow-up from the acute event. A cohort of n = 40 individuals matched for age, sex, body mass index and comorbidities served as control. Results: Despite recovery of left ventricular ejection fraction, patients with prior E-TTS had lower peak VO2 and percentage of predicted peak VO2 (17.8 ± 3.6 vs. 22.1 ± 6.5; p < 0.001 and 75.2 ± 14.1% vs. 100.6 ± 17.1%, p < 0.001), VO2 at anaerobic threshold (AT) (11.5 [10.1-12.9] vs. 14.4 [12.5-18.7]; p < 0.001), peak O2 pulse (9.8 ± 2.5 vs. 12.9 ± 3.5; p < 0.001) and higher VE/VCO2 slope (30.5 ± 3.7 vs. 27.3 ± 3.5; p < 0.001) compared with matched controls. We found no statistically significant differences in heart rate reserve (HRR), respiratory equivalent ratio (RER), mean blood pressure and peak PetCO2 between patients and controls. Conclusions: Despite its favorable outcome, patients with E-TTS in our population were found to have subclinical long-term functional cardiac limitations as compared with a control cohort.

The Efficiency of Attentional Networks in Takostubo Syndrome: A Study With the Attentional Network Task for Interaction.

INTRODUCTION: The role of cardiovascular risk factors in the occurrence and progression of cognitive impairment is relevant in aging studies. In this condition, attention is one of the processes less studied, but preliminary evidence suggests an association between cardiometabolic alterations and attentional decline. Attention is not a unitary process but a set of independent systems (Alerting, Orienting, Executive), which can interact in certain conditions to ensure maximum behavioral efficiency. METHODS: We investigated attentive networks and their interactions in patients with Takostubo syndrome (TTS). In all, 20 participants with TTS and 20 individuals without cardiovascular pathologies performed an Attention-Network Task for Interaction, which assesses attentional networks and their interactions. RESULTS: Patients with TTS showed an atypical orienting effect when compared to the control group. Moreover, only the control group exhibited an interaction between orienting and alerting. CONCLUSION: These findings establish the relevance of brain-heart interaction in identifying attentional impairment as a prodrome of progressively severe cognitive impairment in TTS.

Statin therapy and outcome in Takotsubo syndrome patients: Results from the multicenter international GEIST registry.

BACKGROUND AND AIMS: Several studies have shown that endothelial dysfunction plays a role in the pathogenesis of Takotsubo syndrome (TTS). Given the potential benefit of statin therapy on endothelial dysfunction, we hypothesized that such treatment could improve outcome. Aim of our study was to evaluate clinical characteristics and outcome of TTS patients treated with statin therapy. METHODS: Patients were enrolled in the international multicenter GEIST (GErman Italian Spanish Takotsubo) registry. Demographic data, clinical features and drug therapy at discharge were recorded. Primary study outcome was the occurrence of all-cause death at follow-up. RESULTS: Study population included 2429 consecutive TTS patients: 1293 (53.2%) discharged on statin and 1136 (46.8%) without statin. Patients with statin were older (age 72 ± 11 vs 69 ± 13 years, p < 0.001), with higher prevalence of hypertension (74.3% vs 60.3%, p < 0.001), diabetes (21.1% vs 14.7%, p < 0.001), dyslipidemia (56.1% vs 23.3%, p < 0.001), history of coronary artery disease (13.3% vs 6.3%, p < 0.001) and lower rates of in-hospital complications (14.7% vs 19.3%, p = 0.003). Survival analysis showed similar mortality rates between groups (log rank p = 0.803). At univariable analysis, statin therapy at discharge was not associated with lower mortality (HR: 0.97, 95% CI 0.74-1.26, p = 0.803). At multivariable analysis age (HR: 1.06 95% CI 1.04-1.08, p < 0.001), male sex (HR: 1.83, 95% CI 1.20-2.80, p = 0.005), diabetes (HR: 2.55, 95% CI 1.83-3.54 p < 0.001), malignancies (HR: 2.41, 95% CI 1.68-3.44, p < 0.001) and physical trigger (HR: 2.24, 95% CI 1.62-3.10, p < 0.001) were associated with increased mortality. CONCLUSIONS: Statin therapy after a TTS event was not associated with better prognosis at follow-up.

Smoking influence in Takotsubo syndrome: insights from an international cohort.

Aims: To assess the influence of tobacco on acute and long-term outcomes in Takotsubo syndrome (TTS). Methods: Patients with TTS from the international multicenter German Italian Spanish Takotsubo registry (GEIST) were analyzed. Comparisons between groups were performed within the overall cohort, and an adjusted analysis with 1:1 propensity score matching was conducted. Results: Out of 3,152 patients with TTS, 534 (17%) were current smokers. Smoker TTS patients were younger (63 ± 11 vs. 72 ± 11 years, p < 0.001), less frequently women (78% vs. 90%, p < 0.001), and had a lower prevalence of hypertension (59% vs. 69%, p < 0.01) and diabetes mellitus (16% vs. 20%, p = 0.04), but had a higher prevalence of pulmonary (21% vs. 15%, p < 0.01) and/or psychiatric diseases (17% vs. 12%, p < 0.01). On multivariable analysis, age less than 65 years [OR 3.85, 95% CI (2.86-5)], male gender [OR 2.52, 95% CI (1.75-3.64)], history of pulmonary disease [OR 2.56, 95% CI (1.81-3.61)], coronary artery disease [OR 2.35, 95% CI (1.60-3.46)], and non-apical ballooning form [OR 1.47, 95% CI (1.02-2.13)] were associated with smoking status. Propensity score matching (PSM) 1:1 yielded 329 patients from each group. Smokers had a similar rate of in-hospital complications but longer in-hospital stays (10 vs. 9 days, p = 0.01). During long-term follow-up, there were no differences in mortality rates between smokers and non-smokers (5.6% vs. 6.9% yearly in the overall, p = 0.02, and 6.6%, vs. 7.2% yearly in the matched cohort, p = 0.97). Conclusions: Our findings suggest that smoking may influence the clinical presentation and course of TTS with longer in-hospital stays, but does not independently impact mortality.

Trigger-Associated Clinical Implications and Outcomes in Takotsubo Syndrome: Results From the Multicenter GEIST Registry.

Background Takotsubo syndrome is usually triggered by a stressful event. The type of trigger seems to influence the outcome and should therefore be considered separately. Methods and Results Patients included in the GEIST (German-Italian-Spanish Takotsubo) registry were categorized according to physical trigger (PT), emotional trigger (ET), and no trigger (NT) of Takotsubo syndrome. Clinical characteristics as well as outcome predictors were analyzed. Overall, 2482 patients were included. ET was detected in 910 patients (36.7%), PT in 885 patients (34.4%), and NT was observed in 717 patients (28.9%). Compared with patients with PT or NT, patients with ET were younger, less frequently men, and had a lower prevalence of comorbidities. Adverse in-hospital events (NT: 18.8% versus PT: 27.1% versus ET: 12.1%, P<0.001) and long-term mortality rates (NT: 14.4% versus PT: 21.6% versus ET: 8.5%, P<0.001) were significantly lower in patients with ET. Increasing age (P<0.001), male sex (P=0.007), diabetes (P<0.001), malignancy (P=0.002), and a neurological disorder (P<0.001) were associated with a higher risk of long-term mortality, while chest pain (P=0.035) and treatment with angiotensin-converting enzyme inhibitor/angiotensin receptor blocker (P=0.027) were confirmed as independent predictors for a lower risk of long-term mortality. Conclusions Patients with ET have better clinical conditions and a lower mortality rate. Increasing age, male sex, malignancy, a neurological disorder, chest pain, angiotensin-converting enzyme inhibitor/angiotensin receptor blocker, and diabetes were confirmed as predictors of long-term mortality.

Cardiac Imaging Biomarkers in Chronic Kidney Disease.

Uremic cardiomyopathy (UC), the peculiar cardiac remodeling secondary to the systemic effects of renal dysfunction, is characterized by left ventricular (LV) diffuse fibrosis with hypertrophy (LVH) and stiffness and the development of heart failure and increased rates of cardiovascular mortality. Several imaging modalities can be used to obtain a non-invasive assessment of UC by different imaging biomarkers, which is the focus of the present review. Echocardiography has been largely employed in recent decades, especially for the determination of LVH by 2-dimensional imaging and diastolic dysfunction by pulsed-wave and tissue Doppler, where it retains a robust prognostic value; more recent techniques include parametric assessment of cardiac deformation by speckle tracking echocardiography and the use of 3D-imaging. Cardiac magnetic resonance (CMR) imaging allows a more accurate assessment of cardiac dimensions, including the right heart, and deformation by feature-tracking imaging; however, the most evident added value of CMR remains tissue characterization. T1 mapping demonstrated diffuse fibrosis in CKD patients, increasing with the worsening of renal disease and evident even in early stages of the disease, with few, but emerging, prognostic data. Some studies using T2 mapping highlighted the presence of subtle, diffuse myocardial edema. Finally, computed tomography, though rarely used to specifically assess UC, might provide incidental findings carrying prognostic relevance, including information on cardiac and vascular calcification. In summary, non-invasive cardiovascular imaging provides a wealth of imaging biomarkers for the characterization and risk-stratification of UC; integrating results from different imaging techniques can aid a better understanding of the physiopathology of UC and improve the clinical management of patients with CKD.

Myocardial oedema contributes to interstitial expansion and associates with mechanical and electrocardiographic changes in takotsubo syndrome: a CMR T1 and T2 mapping study.

AIMS: myocardial oedema is largely represented in takotsubo syndrome (TTS) and may contribute to alter the myocardium morphology and function. The aim of the study is to describe relationships between oedema, mechanical, and electrical abnormalities in TTS. METHODS AND RESULTS: the study included n = 32 hospitalized TTS patients and n = 23 controls. Cardiac magnetic resonance (CMR) with tissue mapping and feature tracking was performed with concomitant 12-lead electrocardiogram (ECG) recording. Mean age of TTS was 72 ± 12 years old, 94% women. Compared with controls, patients had higher left ventricular (LV) mass, worse systolic function, higher septal native T1 (1116 ± 73 msec vs. 970 ± 23 msec, P < 0.001), T2 (56 ± 5 msec vs. 46 ± 2 msec, P < 0.001), and extracellular volume (ECV) fraction (32 ± 5% vs. 24 ± 1%, P < 0.001). TTS patients had higher apicobasal gradient of T2 values (12 ± 6 msec vs. 2 ± 6 msec, P < 0.001); basal LV wall displayed higher native T1, T2, and ECV (all P < 0.002) but similar circumferential strain against controls (-23 ± 3% vs. -24 ± 4%, P = 0.351). In the TTS cohort, septal T2 values showed significant correlations with native T1 (r = 0.609, P < 0.001), ECV (r = 0.689, P < 0.001), left ventricular ejection fraction (r = -0.459, P = 0.008) and aVR voltage (r = -0.478, P = 0.009). Negative T-wave voltage and QTc length correlated with apicobasal T2 mapping gradient (r = 0.499, P = 0.007 and r = 0.372, P = 0.047, respectively) but not with other tissue mapping measurements. CONCLUSIONS: CMR T1 and T2 mapping demonstrated increased myocardial water content conditioning interstitial expansion in acute TTS, detected even outside areas of abnormal wall motion. Oedema burden and distribution associated with mechanical and electrocardiographic changes, making it a potential prognostic marker and therapeutic target in TTS.

Impact of intra-aortic balloon counterpulsation on all-cause mortality among patients with Takotsubo syndrome complicated by cardiogenic shock: results from the German-Italian-Spanish (GEIST) registry.

Aims: Takotsubo syndrome (TTS) is an acute and reversible left ventricular dysfunction and can be complicated by cardiogenic shock (CS). However, few data are available on optimal care in TTS complicated by CS. Aim of this study was to evaluate short- and long-term impact of intra-aortic balloon pumping (IABP) on mortality in this setting. Methods and results: In a multi-centre, international registry on TTS, 2248 consecutive patients were enrolled from 38 centres from Germany, Italy, and Spain. Of the 2248 patients, 212 (9.4%) experienced CS. Patients with CS had a higher prevalence of diabetes (27% vs. 19%), male sex (25% vs. 10%), and right ventricular involvement (10% vs. 5%) (P < 0.01 in all cases). Forty-three patients with CS (20% of 212) received IABP within 8 h (interquartile range 4-18) after admission. No differences in terms of age, gender, cardiovascular risk factors, and admission left ventricular ejection fraction were found among patients with and without IABP. There were no significant differences in terms of 30-day mortality (16% vs. 17%, P = 0.98), length of hospitalization (18.9 vs. 16.7 days, P = 0.51), and need of invasive ventilation (35% vs. 41%, P = 0.60) among two groups: 30-day survival was not significantly different even after propensity score adjustment (log-rank P = 0.73). At 42-month follow-up, overall mortality in patients with CS and TTS was 35%, not significantly different between patients receiving IABP and not (37% vs. 35%, P = 0.72). Conclusions: In a large multi-centre observational registry, the use of IABP was not associated with lower mortality rates at short- and long-term follow-up in patients with TTS and CS.

A contemporary update on cancer and takotsubo syndrome.

Takotsubo syndrome (TTS) is characterized by a transient left ventricular systolic dysfunction, burdened by significant acute and long-term mortality and morbidity. The prognosis of TTS, especially in the long-term, is influenced by both non-cardiovascular (non-CV) and CV comorbidities, among which cancer is one of the most common. The presence of a malignancy is proven to be associated with higher mortality in TTS. Moreover, a number of anticancer treatments has been reported to possibly cause TTS as a form of cardiotoxicity, even though clearcut associations are lacking. The aim of this narrative review is to sum up contemporary knowledge on the association of cancer and TTS, addressing unmet needs and practical implications. The importance of a close collaboration between cardiologists and oncologists is herein highlighted, both to allow an adequate management of the acute TTS phase, and to actively and safely return to the oncologic management once the acute setting is resolved.

Characterization of COVID-19-Related Lung Involvement in Patients Undergoing Magnetic Resonance T1 and T2 Mapping Imaging: A Pilot Study.

Tissue characterization by mapping techniques is a recent magnetic resonance imaging (MRI) tool that could aid the tissue characterization of lung parenchyma in coronavirus disease-2019 (COVID-19). The aim of the present study was to compare lung MRI findings, including T1 and T2 mapping, in a group of n = 11 patients with COVID-19 pneumonia who underwent a scheduled cardiac MRI, and a cohort of healthy controls. MRI scout images were used to identify affected and remote lung regions within the patients' cohort and appropriate regions of interest (ROIs) were drawn accordingly. Both lung native T1 and T2 values were significantly higher in the affected areas of patients with COVID-19 as compared to the controls (1375 ms vs. 1201 ms, p = 0.016 and 70 ms vs. 30 ms, p < 0.001, respectively), whereas no significant differences were detected between the remote lung parenchyma of the COVID-19 patients and the controls (both p > 0.05). When a larger ROI was identified, comprising the whole lung parenchyma within the image irrespective of the affected and remote areas, the COVID-19 patients still retained higher native T1 (1278 ms vs. 1149 ms, p = 0.003) and T2 values (38 ms vs. 34 ms, p = 0.04). According to the receiver operator characteristics curves, the T2 value of the affected region retained the higher accuracy for the differentiation of the COVID-19 patients against the controls (area under the curve 0.934, 95% confidence interval 0.826−0.999). These findings, possibly driven by the ability of MRI tissue mapping to detect ongoing inflammation in the lungs of patients with COVID-19, suggest that T1 and T2 mapping of the lung is a feasible approach in this clinical scenario.

Exploring the influence of takotsubo syndrome on oncologic patients' mortality.

It has been reported that patients affected by takotsubo syndrome (TTS) with a concurrent diagnosis of cancer suffer from greater mortality as compared to their non-cancer counterpart. It remains unclear whether TTS worsens the prognosis of cancer patients as well. Aim of this study was to compare outcomes of cancer patients with and without TTS. We combined data from two independent cohorts: one consisted of a prospective multicentre TTS registry; the second cohort consisted of all oncologic patients from two Cardio-Oncology Outpatient Clinics, who did not have cardiovascular conditions at the time of the cardio-oncologic visit. From the TTS registry, we selected patients with cancer (cancer-TTS patients). Next, we matched these patients with those from the cardio-oncologic cohort (cancer non-TTS patients) in a 1:2 fashion by age, sex, and type and cancer staging. Study endpoint was all-cause mortality. Among 318 TTS patients, 42 (13%) had a concurrent diagnosis of cancer. Characteristics of cancer-TTS patients and of the 84 matched cancer non-TTS subjects were comparable with the exception of diabetes mellitus, which was more common in cancer non-TTS patients. All-cause mortality was similar between cancer-TTS and cancer non-TTS patients. At Cox regression analysis TTS was not associated with mortality (OR 1.4, 95% CI 0.6-3.3, p = 0.43). Our findings show that even in the presence of acute heart failure due to TTS, the prognosis of oncologic patients is driven by the malignancy itself. Our results may prove useful for integrated management of cardio-oncologic patients.

Gender-related differences in changes of estimated bleeding risk in patients on dual antiplatelet therapy: the RE-SCORE multicenter prospective registry.

The risk of bleeding as predicted by the PRECISE-DAPT score can vary over time after percutaneous coronary intervention (PCI). We sought to compare the predictive ability of the PRECISE-DAPT score calculated at baseline and reassessed during follow-up in male and female patients undergoing PCI. The RE-SCORE was a multicenter, prospective registry including patients undergoing PCI treated with dual antiplatelet therapy (DAPT) for 1 year. The primary endpoint was Bleeding Academic Research Consortium (BARC) type 2, 3 or 5 bleeding. The PRECISE-DAPT score was determined for each patient at the time of PCI and at 1, 4 and 8-month follow-up visits or before the occurrence of an endpoint event. A total of 480 patients undergoing PCI were included. At baseline, median PRECISE-DAPT score was similar in males (23.2 [IQR 20.1-24.2]) and females (23.4 [IQR 20.2-25.3]; p = .22). During follow-up, an increase in the PRECISE-DAPT occurred significantly more often in females (44%) than in males (23%; p < .001). The discrimination of the PRECISE-DAPT score calculated at baseline was marginal in both males (c-index = 0.59, 95% CI: 0.51-0.65) and females (c-index = 0.55, 95% CI: 0.49-0.60). The discriminative ability of the score reassessed at follow-up was excellent in females (c-index = 0.84; 95% CI: 0.77-0.91) but remained modest in males (c-index = 0.61; 95% CI: 0.55-0.70). The bleeding predictive ability of the PRECISE-DAPT score can vary over time, more commonly in females than males. The discrimination of the score calculated during follow-up appeared improved in females but remained modest in males.Clinical Trial Registration - ClinicalTrials.gov Identifier: NCT03526614.

Heart and Lung Fibrosis in a Patient with COVID-19-Related Myocarditis.

A COVID-19 patient, in whom pneumonia lesions were first detected by chest computed tomography, was further evaluated by cardiac magnetic resonance (CMR) due to a suspected myocarditis. Beyond heart alterations, CMR revealed peculiar features of affected pulmonary areas in T1 mapping sequences and showed a particular distribution of late gadolinium enhancement in the same regions. The noninvasive assessment of the cellular, fluid, or fibrotic content of lung lesions may provide key information about the underlying pathophysiological pathways in the search of a tailored medical therapy and ventilatory support for COVID-19 patients.

Happy Heart Syndrome: Frequency, Characteristics, and Outcome of Takotsubo Syndrome Triggered by Positive Life Events.

BACKGROUND: The association with a preceding stressor is a characteristic feature of takotsubo syndrome (TTS). Negative emotions before TTS are common and led to the popular term "broken heart syndrome." In contrast, pleasant triggers ("happy heart syndrome") are rare and are scarcely investigated. OBJECTIVES: The authors analyzed the frequency, clinical characteristics, and prognostic implications of positive emotional stressors in the multicenter GEIST (GErman-Italian-Spanish Takotsubo) Registry. METHODS: Patients enrolled in the registry were categorized according to their stressors. This analysis compared patients with pleasant emotional events with patients with negative emotional events. RESULTS: Of 2,482 patients in the registry, 910 patients (36.7%) exhibited an emotional trigger consisting of 873 "broken hearts" (95.9%) and 37 "happy hearts" (4.1%). Consequently, the prevalence of pleasant emotional triggers was 1.5% of all TTS cases. Compared with patients with TTS with negative preceding events, patients with happy heart syndrome were more frequently male (18.9% vs 5.0%; P < 0.01) and had a higher prevalence of atypical ballooning patterns (27.0% vs 12.5%; P = 0.01), particularly midventricular ballooning. In-hospital complications, including death, pulmonary edema, cardiogenic shock, or stroke (8.1% vs 12.3%; P = 0.45), and long-term mortality rates (2.7% vs 8.8%; P = 0.20) were similar in "happy hearts" and "broken hearts." CONCLUSIONS: Happy heart syndrome is a rare type of TTS characterized by a higher prevalence of male patients and atypical, nonapical ballooning compared with patients with negative emotional stressors. Despite similar short- and long-term outcomes in our study, additional data are needed to explore whether numerically lower event rates in "happy hearts" would be statistically significant in a larger sample size. (GErman-Italian-Spanish Takotsubo Registry [GEIST Registry]; NCT04361994).

Gender Differences in Takotsubo Syndrome.

BACKGROUND: Male sex in takotsubo syndrome (TTS) has a low incidence and it is still not well characterized. OBJECTIVES: The aim of the present study is to describe TTS sex differences. METHODS: TTS patients enrolled in the international multicenter GEIST (GErman Italian Spanish Takotsubo) registry were analyzed. Comparisons between sexes were performed within the overall cohort and using an adjusted analysis with 1:1 propensity score matching for age, comorbidities, and kind of trigger. RESULTS: In total, 286 (11%) of 2,492 TTS patients were men. Male patients were younger (age 69 ± 13 years vs 71 ± 11 years; P = 0.005), with higher prevalence of comorbid conditions (diabetes mellitus 25% vs 19%; P = 0.01; pulmonary diseases 21% vs 15%; P = 0.006; malignancies 25% vs 13%; P < 0.001) and physical trigger (55 vs 32% P < 0.01). Propensity-score matching yielded 207 patients from each group. After 1:1 propensity matching, male patients had higher rates of cardiogenic shock and in-hospital mortality (16% vs 6% and 8% vs 3%, respectively; both P < 0.05). Long-term mortality rate was 4.3% per patient-year (men 10%, women 3.8%). Survival analysis showed higher mortality rate in men during the acute phase in both cohorts (overall: P < 0.001; matched: P = 0.001); mortality rate after 60 days was higher in men in the overall (P = 0.002) but not in the matched cohort (P = 0.541). Within the overall population, male sex remained independently associated with both in-hospital (OR: 2.26; 95% CI: 1.16-4.40) and long-term mortality (HR: 1.83; 95% CI: 1.32-2.52). CONCLUSIONS: Male TTS is featured by a distinct high-risk phenotype requiring close in-hospital monitoring and long-term follow-up.

Cardiac Magnetic Resonance Imaging in Immune Check-Point Inhibitor Myocarditis: A Systematic Review.

Immune checkpoint inhibitors (ICIs) are a family of anticancer drugs in which the immune response elicited against the tumor may involve other organs, including the heart. Cardiac magnetic resonance (CMR) imaging is increasingly used in the diagnostic work-up of myocardial inflammation; recently, several studies investigated the use of CMR in patients with ICI-myocarditis (ICI-M). The aim of the present systematic review is to summarize the available evidence on CMR findings in ICI-M. We searched electronic databases for relevant publications; after screening, six studies were selected, including 166 patients from five cohorts, and further 86 patients from a sub-analysis that were targeted for a tissue mapping assessment. CMR revealed mostly preserved left ventricular ejection fraction; edema prevalence ranged from 9% to 60%; late gadolinium enhancement (LGE) prevalence ranged from 23% to 83%. T1 and T2 mapping assessment were performed in 108 and 104 patients, respectively. When available, the comparison of CMR with endomyocardial biopsy revealed partial agreement between techniques and was higher for native T1 mapping amongst imaging biomarkers. The prognostic assessment was inconsistently assessed; CMR variables independently associated with the outcome included decreasing LVEF and increasing native T1. In conclusion, CMR findings in ICI-M include myocardial dysfunction, edema and fibrosis, though less evident than in more classic forms of myocarditis; native T1 mapping retained the higher concordance with EMB and significant prognostic value.