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.

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.

[Heart rate disorders in patients with Tako-tsubo syndrome]. / Trastornos del ritmo cardiaco en pacientes con síndrome de Tako-tsubo.

OBJECTIVES: This study sought to evaluate the incidence, prognosis and treatment of heart rhythm disorders (HRD) in Tako-tsubo syndrome (TTS). BACKGROUND: TTS is associated with HRD. The HRD prognostic value is not well characterized in TTS yet. METHODS: The HRD of patients included in the National Registry of Tako-tsubo syndrome, admitted between 2002 and 2018 and coming from 38 hospitals throughout the country, was analyzed. We analyzed any heart rhythm disorder in patients presented before admission, at admission and in long-term follow-up. RESULTS: All types of HRD were described in 259 (23.5%) cases, from a cohort of 1,097 consecutive patients with TTS. HRD was more associated with diabetes mellitus, smoking, hyperuricemia, sleep apnea, anemia with a worse LVEF on admission. The most frequent HRD was a new onset of atrial fibrillation. During hospitalization, patients with HRD showed more complications such as shock on admission, major bleeding, acute renal failure, and combined infections. At follow-up, they presented higher mortality and more major adverse cardiac events, but with a non-significant correlation. CONCLUSIONS: The incidence of HRD in patients with TTS is not infrequent. TTS, when associated with HRD, presents more complications and a worse prognosis both in hospital and in the long term.

Long-term prognostic impact of beta-blockers in patients with Takotsubo syndrome: Results from the RETAKO Registry.

BACKGROUND: No evidence-based therapy has yet been established for Takotsubo syndrome (TTS). Given the putative harmful effects of catecholamines in patients with TTS, beta-blockers may potentially decrease the intensity of the detrimental cardiac effects in those patients. OBJECTIVE: The purpose of this study was to assess the impact of beta-blocker therapy on long-term mortality and TTS recurrence. METHODS: The cohort study used the national Spanish Registry on TakoTsubo Syndrome (RETAKO). A total of 970 TTS post-discharge survivors, without pheochromocytoma, left ventricular outflow tract obstruction, sustained ventricular arrhythmias, and significant bradyarrhythmias, between January 1, 2003, and July 31, 2018, were assessed. Cox regression analysis and inverse probability weighting (IPW) propensity score analysis were used to evaluate the association between beta-blocker therapy and survival free of TTS recurrence. RESULTS: From 970 TTS patients, 582 (60.0%) received beta-blockers. During a mean follow-up of 2.5±3.3 years, there were 87 deaths (3.6 per 100 patients/year) and 29 TTS recurrences (1.2 per 100 patient/year). There was no significant difference in follow-up mortality or TTS recurrence in unadjusted and adjusted Cox analysis (hazard ratio [HR] 0.86, 95% confidence interval [CI] 0.59-1.27, and 0.95, 95% CI 0.57-1.13, respectively). After weighting and adjusting by IPW, differences in one-year survival free of TTS recurrence between patients treated and untreated with beta-blockers were not found (average treatment effect -0.01, 95% CI -0.07 to 0.04; p=0.621). CONCLUSIONS: In this observational nationwide study from Spain, there was no significant association between beta-blocker therapy and follow-up survival free of TTS recurrence.

Clinical presentation, therapeutic approach, and outcome of young patients admitted for COVID-19, with respect to the elderly counterpart.

There is limited information on the presenting characteristics, prognosis, and therapeutic approaches of young patients hospitalized for coronavirus disease 2019 (COVID-19). We sought to investigate the baseline characteristics, in-hospital treatment, and outcomes of a wide cohort < 65 years admitted for COVID-19. Using the international multicenter HOPE-COVID-19 registry, we evaluated the baseline characteristics, clinical presentation, therapeutic approach, and prognosis of patients < 65 years discharged (deceased or alive) after hospital admission for COVID-19, also compared with the elderly counterpart. Of the included 5746 patients, 2676 were < 65 and 3070 ≥ 65 years. All risk factors and several parameters suggestive of worse clinical presentation augmented through increasing age classes. In-hospital mortality rates were 6.8% and 32.1% in the younger and older cohort, respectively (p < 0.001). Among young patients, mortality, access to ICU and treatment with IMVwere positively correlated with age. Contrariwise, over 65 years of age this trend was broken so that only the association between age and mortality was persistent, while the rates of access to ICU and IMV started to decline. Younger patients also recognized specific predictors of case fatality, such as obesity and gender. Age negatively impacts on mortality, access to ICU and treatment with IMV in patients < 65 years. In elderly patients only case fatality rate keeps augmenting in a stepwise manner through increasing age categories, while therapeutic approaches become more conservative. Besides age, obesity, gender, history of cancer, and severe dyspnea, tachypnea, chest X-ray bilateral abnormalities, abnormal level of creatinine and leucocyte among admission parameters seem to play a central role in the outcome of patients younger than 65 years.

Takotsubo syndrome and cancer, clinical and prognostic implications, insights of RETAKO. / Implicaciones clínicas y pronósticas en síndrome de Takotsubo y cáncer: percepciones del registro RETAKO.

BACKGROUND AND OBJECTIVES: A relationship between neoplasms and Takotsubo syndrome (TS) has been postulated. Our goal was to determine its prevalence in patients with TS, compare the clinical profile of TS with or without cancer and study its long-term evolution. MATERIALS AND METHODS: The oncological situation of patients included in the National Registry on TAKOtsubo syndrome (RETAKO), admitted between 2002 and 2019, provided by 38 hospitals throughout the country is analysed. Any history of malignancy or tumour, even benign, that received chemotherapy, radiotherapy or specific surgery, current or past, was considered. RESULTS: Any type of neoplasm was described in 129 (11.8%), within a cohort of 1,097 patients with TS. The cohort of patients with neoplasm, with a lower percentage of women (79.1 vs. 88.3%; P=.003), showed a non-significant tendency at an older age, hyperuricaemia, sleep apnoea and lower LVEF on admission, with a similar cardiovascular risk factor profile, but more chronic anaemia and immunosuppression. The most common neoplasm was breast cancer. During their hospital stay, the cancer patients suffered more complications, highlighting heart failure/shock, acute renal failure and a trend towards combined infections. On follow-up, they presented higher mortality and more combined MACE events, with a non-significant trend in the occurrence of cardiovascular recurrences or readmissions. CONCLUSIONS: The prevalence of neoplasms in patients with TS is high. The clinical presentation is different in relation to patients who do not have neoplasms and they probably represent a risk factor for a worse hospital and long term prognosis.

Cintilografia de perfusão miocárdica e comprometimento cardíaco na fase indeterminada da doença de chagas / Myocardial perfusion imaging and cardiac involvement in the indeterminate phase of chagas disease

FUNDAMENTO: A cintilografia de perfusão miocárdica (CPM) tem sido utilizada na avaliação da cardiopatia chagásica. OBJETIVO: Investigar o valor da CPM com tomografia computadorizada por emissão de fóton único (gated-SPECT) para detectar comprometimento cardíaco precoce em pacientes chagásicos na fase indeterminada, que apresentam anomalias de movimento segmentar detectadas por exame de imagem por Doppler tecidual (IDT) strain derivada. MÉTODOS: Foram incluídos 40 indivíduos (idade média: 25 ± 2 anos, 50% homens) de uma área endêmica da doença de Chagas e com diagnóstico sorológico positivo. Todos foram submetidos à CPM com gated-SPECT de 2 dias (repouso e estresse) e ecocardiografia. RESULTADOS: Trinta indivíduos (75%) apresentaram resultados normais. Em três casos (8%), a CPM apresentou resultado ligeiramente anormal e em sete foi ambígua. Em todos os casos com defeitos reversíveis, os segmentos afetados foram coincidentes com aqueles com anomalias de movimento. Foi encontrada redução na fração de ejeção ventricular esquerda (FEVE) > 5% (ΔLVEF% < -5) pós-estresse em 11 dos 40 indivíduos (28%). Tanto o desvio padrão fasederivado como a largura da banda do histograma mostraram diferença significativa entre o pós-estresse e a fase de repouso. Em ambos os casos, houve ligeira dessincronia em repouso normalizado no pós-estresse. CONCLUSÃO: Uma abordagem estresse-repouso com gated-SPECT é válida para detectar alterações miocárdicas precoces, bem como dessincronia intraventricular na fase indeterminada da doença de Chagas em pacientes com anomalias no movimento segmentar previamente detectadas pela IDT strain derivada.

BACKGROUND: Myocardial perfusion imaging (MPI) has been used in the assessment of chagasic heart disease. OBJECTIVE: To investigate the value of gated-single photon emission computed tomography (gated-SPECT) MPI to detect early cardiac involvement in chagasic patients in the indeterminate phase, who present segmental motion abnormalities detected by tissue Doppler imaging (TDI)-derived strain. METHODS: Forty individuals (mean age: 25±2 years, 50% males) from an endemic area of Chagas disease and with positive serologic diagnosis, were included. All underwent gated-SPECT two-day (stress-rest) MPI and echocardiography. RESULTS: Thirty individuals (75%) showed a normal scan. In three cases (8%) the MPI was slightly abnormal, and in seven it was equivocal. In all cases with reversible defects, the affected segments were coincident with those with motion abnormalities. A post-stress left ventricular ejection fraction (LVEF) reduction > 5% (ΔLVEF < -5%) was found in 11 out of 40 individuals (28%). Both the phase-derived standard deviation and the histogram bandwidth showed a significant difference between post-stress and rest. In both cases there was a slight dyssynchrony at rest which normalized at post-stress. CONCLUSIONS: A stress-rest gated-SPECT is a valid approach to detect early myocardial alterations, as well as intraventricular dyssynchrony in the indeterminate phase of Chagas disease in patients with segmental motion abnormalities previously detected by TDI-derived strain.