Takotsubo syndrome in COVID-19 era: Is psychological distress the key?

Covid-19 pandemic, starting from Wuhan, China spread all over the world and Italy was one of the most affected countries, especially in Lombardy, where, on February 20, the first confirmed case was detected. Italian Government ordered a national lockdown on the 9 th March 2020, forcing the population to severe restrictive isolation measures. The burden on mental health of the medical emergency related to COVID19 is progressively been revealed. Takotsubo syndrome (TTS), is estimated to represent 1-3% of patients admitted with suspected STEMI, mostly affecting elderly women with emotional stress and/or acute illness preceding the presentation. Comparing patients hospitalised from February to May 2020 with those of the corresponding period in 2019 we observed a significantly increased number of TTS diagnosis in 2020 (11 patients vs 3 in 2019), especially during the first period of lockdown. The only two males were patients with COVID-19 and were the only two who died in hospital. At psychological examination all patients enrolled report to have lived a particularly stressful experience at IES-R in the last year, without presenting the symptoms of a post-traumatic stress disorder. Most patients were positive to the allostatic overload. Only one patient showed a clinical cut-off for HADS and no one for the Fear COVID-19 scale. We finally concluded that subjects with pre-pandemic psychological distress may have experienced additional psychological overload, opening the door to TTS by a series of physiological alterations as the secretion of cortisol and catecholamines, making the subject more vulnerable to the onset of TTS.

COVID-19 With Stress Cardiomyopathy Mortality and Outcomes Among Patients Hospitalized in the United States: A Propensity Matched Analysis Using the National Inpatient Sample Database.

Takotsubo syndrome (stress cardiomyopathy) has become a well-known complication of COVID-19 infections, with limited large-scale studies evaluating outcomes. We used the National Inpatient Sample (NIS) database to compare COVID-19 patients with and without stress cardiomyopathy. A total of 1,659,040 patients were included in the study: COVID-19 with stress cardiomyopathy (n = 1665, 0.1%) and COVID-19 without stress cardiomyopathy (n = 1657, 375, and 99.9%). The primary outcome was in-hospital mortality, with secondary analysis with propensity matching performed to confirm results from traditional multivariate analysis. COVID-19 patients with stress cardiomyopathy had significantly increased in-hospital mortality compared to COVID-19 patients without stress cardiomyopathy (32.8% vs 14.6%, adjusted OR [aOR]: 2.3 [95% CI, 1.2-4.5], P = 0.01) along with significantly increased mechanical ventilation and vasopressor support, hospitalization charge, acute kidney injury requiring hemodialysis, cardiogenic shock, and cardiac arrest. These results emphasize the need for more research to reduce worse outcomes with COVID-19-related stress cardiomyopathy patients.

In-Hospital Outcomes of Takotsubo Cardiomyopathy During the COVID-19 Pandemic: Propensity Matched National Cohort.

Takotsubo Cardiomyopathy (TTS) is an acute reversible left ventricular dysfunction with regional ballooning secondary to various physical or psychological triggers, including COVID-19. The impact of TTS on outcomes in COVID-19 patients is not well studied. The Nationwide in-patient sample database from 2019 to 2020 was utilized to identify TTS patients with and without COVID-19. Clinical Modification (ICD-10-CM) codes U07.1 and I51.81 were used as disease identifiers for COVID-19 and TTS, respectively. Multivariate logistic regression was performed to report adjusted odds ratios (aOR) and propensity score match (PSM) was done to compare outcomes among TTS patients with and without COVID. The primary outcome was in-hospital mortality. A total of 83,215 TTS patients for the period 2019-2020 were included in our study, of which 1665 (2%) had COVID-19. COVID-19 with TTS group had higher adjusted odds of in-hospital mortality (aOR 7.23, PSM 32.7% vs 10.16%, p = <0.001), cardiogenic shock; (aOR 2.32, PSM 16.7% vs 9.5%, P < 0.001) and acute kidney injury; (aOR 2.30, PSM 47.5% vs 33.1%, P< 0.001) compared to TTS without COVID-19. TTS hospitalizations with COVID-19 were associated with longer lengths of stay (12 ± 12 vs 7 ± 9 days) and higher total cost ($47,702 ± $67,940 vs $26,957 ± $44,286) compared to TTS without COVID. TTS with COVID-19 group had a higher proportion of males compared to TTS without COVID-19 group (37.8% vs 18.5%). TTS with COVID-19 group had a greater proportion of non-white race. The proportion of Blacks, Hispanics, and Asian/Pacific Islander was higher in the COVID-19 TTS group compared to TTS without COVID-19 group (12.9% vs 8.4%, 20.4% vs 6.5%, 5 vs 2.2%, respectively). TTS in the setting of COVID-19 illness has worse outcomes in terms of in-hospital mortality, cardiogenic shock, and acute kidney injury. Male sex and non-white race were more likely to be affected by TTS in the setting of COVID-19. The out-of-hospital morbidity and mortality in patients who suffered TTS during COVID-19 illness need further study. Studies are needed to provide mechanistic insights into the interaction between COVID-19 and TTS.

Takotsubo Syndrome during COVID-19 Pandemic in the Veneto Region, Italy.

Background: During the COVID-19 pandemic, the risk of SARS-CoV-2 infection, the public health measures of social distancing, the freedom limitations, quarantine, and the enforced homeworking under the lockdown period, as well as medical causes including COVID-19 infection per se, may have caused major emotional distress, especially in the most vulnerable patients. We aimed to evaluate the variations in the number of admissions due to Takotsubo syndrome (TTS) during the COVID-19 pandemic in the Veneto region. Methods: We retrospectively reviewed and analyzed the number of admissions because of TTS in 13 Divisions of Cardiology located in the Veneto region, the northeastern area of Italy, covering a population of more than 2.5 million inhabitants, during the two major pandemic waves of COVID-19 (the first between 15 March and 30 April 2020 and the second between 15 November and 30 December 2020) that occurred in 2020. Results: In total, 807 acute coronary syndromes were admitted in the 13 enrolling hospitals. Among these, 3.9% had TTS. Compared to the corresponding 2018 and 2019 time periods, we observed a significant increase in the number of TTS cases (+15.6%, p = 0.03 and +12.5%, p = 0.04, comparing 2018 to 2020 and 2019 to 2020, respectively). Geographical distribution of the TTS cases reflected the broad spread of the SARS-CoV-2 infection with a significant direct relationship between TTS incidence and the number of COVID-19 infections according to Pearson's correlation (r = 0.798, p < 0.001). Conclusions: The higher incidence of TTS during the 2020 COVID-19 pandemic waves, especially in the areas that were hit hardest in terms of morbidity and mortality by the SARS-CoV-2 infection, suggest a strong direct and/or indirect role of COVID-19 in the pathogenesis of TTS.

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.

Knowledge domain and emerging trends in Takotsubo cardiomyopathy: a scientometric review based on CiteSpace analysis.

Takotsubo cardiomyopathy (TTC) is often acute with a high mortality rate and is subject to relapse. Meanwhile, its complex pathogenesis has attracted increasing attention. To learn more about TTC, CiteSpace V.5.7 R5W was used in this study to analyze the research status, hot spots, and trends in TTC before 2020. The keywords, co-citation references, as well as country and institution distribution were explored. A total of 2,349 papers were reviewed. The United States, Italy, and Germany were the main countries studying TTC and had good cooperation relationships. The Mayo Clinic topped the institution list, but the rate of inter-institutional cooperation was not high. Research hotspots include disease features, auxiliary diagnostic methods, epidemiology, and pathophysiological mechanisms, and the latest ones are complications related to prognosis, such as cardiovascular abnormalities caused by myocardial infarction and normal or non-obstructive coronary arteries (MINOCA), atrial fibrillation, stroke, cancer, and COVID-19. In conclusion, the research of TTC is in a hot development period. Our research will help clinicians and researchers to better understand TTC and its research status by providing a foundation for research objectives. In doing this, our research will help to provide better scientific management, diagnosis, and treatment for patients with TTC, which will in turn improve the prognosis of this condition.

Stress-Induced Cardiomyopathy-Considerations for Diagnosis and Management during the COVID-19 Pandemic.

The novel coronavirus disease 2019 (COVID-19) is associated with several cardiovascular manifestations including myocardial injury, myocarditis, arrhythmia, and pulmonary embolism. Rare cases of stress-induced cardiomyopathy, or takotsubo syndrome have also been reported during the acute infection, and secondary to stress following lockdown and self-isolation. Diagnosis in the setting of the acute infection is challenging since conventional imaging modalities such as transthoracic echocardiography and coronary angiography should be restricted to minimize physician-patient contact until the patients is tested negative for COVID-19. The use of point of care hand-held ultrasound is appropriate for this purpose. The overall course of the disease seems to be similar to takotsubo in the general population. Physicians should be familiar with the clinical presentation, possible complications, and management of takotsubo during COVID-19 outbreak. Here, we review the special considerations in the diagnosis and management of takotsubo syndrome during the current pandemic.

Emergency cardiac imaging for coronavirus disease 2019 (COVID-19) in practice: a case of takotsubo stress cardiomyopathy.

BACKGROUND: Cardiovascular complications of severe acute respiratory distress syndrome coronavirus 2 (SARS-CoV2) are known to be associated with poor outcome. A small number of case series and reports have described cases of myocarditis and ischaemic events, however, knowledge on the aetiology of acute cardiac failure in SARS-CoV2 remains limited. We describe the occurrence and risk stratification imaging correlates of 'takotsubo' stress cardiomyopathy presenting in a patient with Coronavirus Disease 2019 (COVID-19) in the intensive care unit. An intubated 53-year old patient with COVID19 suffered acute haemodynamic collapse in the intensive care unit, and was thus investigated with transthoracic echocardiography (TTE), 12-lead electrocardiograms (ECG) and serial troponins and blood tests, and eventually coronary angiography due to clinical suspicion of ischaemic aetiology. Echocardiography revealed a reduced ejection fraction, with evident extensive apical akinesia spanning multiple coronary territories. Troponins and NT-proBNP were elevated, and ECG revealed ST elevation: coronary angiography was thus performed. This revealed no significant coronary stenosis. Repeat echocardiography performed within the following week revealed a substantial recovery of ejection fraction and wall motion abnormalities. Despite requirement of a prolonged ICU stay, the patient now remains clinically stable, and is on spontaneous breathing. CONCLUSION: This case report presents a case of takotsubo stress cardiomyopathy occurring in a critically unwell patient with COVID19 in the intensive care setting. Stress cardiomyopathy may be an acute cardiovascular complication of COVID-19 infection. In the COVID19 critical care setting, urgent bedside echocardiography is an important tool for initial clinical assessment of patients suffering haemodynamic compromise.

Pathophysiology of Takotsubo Cardiomyopathy: Reopened Debate.

Takotsubo cardiomyopathy (TTC), a persistently obscure dysfunctional condition of the left ventricle, is uniquely transient but nevertheless dangerous. It features variable ventricular patterns and is predominant in women. For 30 years, pathophysiologic investigations have progressed only slowly and with inadequate focus. It was initially proposed that sudden-onset spastic obliteration of coronary flow induced myocardial ischemia with residual stunning and thus TTC. Later, it was generally accepted without proof that, in the presence of pain or emotional stress, the dominant mechanism for TTC onset was a catecholamine surge that had a direct, toxic myocardial effect. We think that the manifestations of TTC are more dynamic and complex than can be assumed from catecholamine effects alone. In addition, after reviewing the recent medical literature and considering our own clinical observations, especially on spasm, we theorize that atherosclerotic coronary artery disease modulates and physically opposes obstruction during spasm. This phenomenon may explain the midventricular variant of TTC and the lower incidence of TTC in men. We continue to recommend and perform acetylcholine testing to reproduce TTC and to confirm our theory that coronary spasm is its initial pathophysiologic factor. An improved understanding of TTC is especially important because of the condition's markedly increased incidence during the ongoing COVID-19 pandemic.

Safety measures for COVID-19 do not compromise the outcomes of patients undergoing primary percutaneous coronary intervention: a single center retrospective study.

Coronavirus disease 2019 (COVID-19) is a global pandemic impacting nearly 170 countries/regions and millions of patients worldwide. Patients with acute myocardial infarction (AMI) still need to be treated at percutaneous coronary intervention (PCI) centers with relevant safety measures. This retrospective study was conducted to assess the therapeutic outcomes of PCI performed under the safety measures and normal conditions. AMI patients undergoing PCI between January 24 to April 30, 2020 were performed under safety measures for COVID-19. Patients received pulmonary computed tomography (CT) and underwent PCI in negative pressure ICU. Cardiac catheterization laboratory (CCL) staff and physicians worked with level III personal protection. Demographic and clinical data, such as door-to-balloon (DTB) time, operation time, complications for patients in this period (COVID-19 group) and the same period in 2019 (2019 group) were retrieved and analyzed. COVID-19 and 2019 groups had 37 and 96 patients, respectively. There was no significant difference in age, gender, BMI and comorbidity between the two groups. DTB time and operation time were similar between the two groups (60.0 ± 12.39 vs 58.83 ± 12.85 min, p = 0.636; 61.46 ± 9.91 vs 62.55 ± 10.72 min, p = 0.592). Hospital stay time in COVID-19 group was significantly shorter (6.78 ± 2.14 vs 8.85 ± 2.64 days, p < 0.001). The incidences of malignant arrhythmia and Takotsubo Syndrome in COVID-19 group were higher than 2019 group significantly (16.22% vs 5.21%, p = 0.039; 10.81% vs 1.04% p = 0.008). During hospitalization and 3-month follow-up, the incidence of major adverse cardiovascular events and mortality in the two groups were statistically similar (35.13% vs 14.58%, p = 0.094; 16.22% vs 8.33%, p = 0.184). The risk of major adverse cardiac events (MACE) was associated with cardiogenic shock (OR, 11.53; 95% CI, 2.888-46.036; p = 0.001), malignant arrhythmias (OR, 7.176; 95% CI, 1.893-27.203; p = 0.004) and advanced age (≥ 75 years) (OR, 6.718; 95% CI, 1.738-25.964; p = 0.006). Cardiogenic shock (OR, 17.663; 95% CI, 5.5-56.762; p < 0.001) and malignant arrhythmias (OR, 4.659; 95% CI, 1.481-14.653; p = 0.008) were also associated with death of 3 months. Our analysis showed that safety measures undertaken in this hospital, including screening of COVID-19 infection and use of personal protection equipment for conducting PCI did not compromise the surgical outcome as compared with PCI under normal condition, although there were slight increases in incidence of malignant arrhythmia and Takotsubo Syndrome.

A review of the presentation and outcome of takotsubo cardiomyopathy in COVID-19.

Although the most frequent presentation of the novel Coronavirus disease-2019 (COVID-19) is a respiratory syndrome, cardiac involvement is being increasingly recognized. One such entity is takotsubo cardiomyopathy. We sought to review the various cases of takotsubo cardiomyopathy reported during the COVID-19 pandemic and consolidate the information available on its clinical features, evaluation and treatment. We performed a PubMed search using the MeSH terms "Takotsubo Cardiomyopathy" or "Stress Cardiomyopathy" and "COVID-19", and identified 16 case reports, two case series, and one retrospective cohort study. There was a total of 24 reported patients with COVID-19 infection, who developed takotsubo cardiomyopathy, and two patients without COVID-19 who developed takotsubo cardiomyopathy due to the emotional stress associated with the global pandemic. The mean age of the patients was 67.19 years (SD 15.83) and 16(59.3%) were women. Chest pain was reported in only ten patients (38.46 %) and ST-elevation was seen in 11 patients (42.3%). While most patients had typical takotsubo cardiomyopathy, four patients had inverted(reverse) takotsubo cardiomyopathy, two had bi-ventricular involvement, one had median takotsubo and another had global takotsubo with apical sparing variant. Most patients had a positive outcome with complete or near-complete reversal of cardiac dysfunction at the time of discharge. Five deaths (19.23%) were reported. Takotsubo cardiomyopathy is a rare, but increasingly reported reversible cardiomyopathy that can be seen in patients with COVID-19 infection and the diagnosis must be actively sought for in these patients.

Takotsubo Syndrome and COVID-19: Associations and Implications.

Incidence of cardiovascular complications has increased during the COVID-19 (Coronavirus disease 2019) pandemic, both population-wide and in patients diagnosed with the disease. This increase has presented complications in patient care, leading to increased hospitalizations, adverse outcomes, and medical costs. A condition of interest is takotsubo syndrome, which may be associated with the novel coronavirus. To understand this connection, a narrative review was performed by analyzing primary studies and case reports available. The findings showed increased incidence of takotsubo cardiomyopathy in both the general population and COVID-19 patients. Proposed mechanisms for the linkage include generalized increases in psychological distress, the cytokine storm, increased sympathetic responses in COVID-19 patients, and microvascular dysfunction. Moreover, natural disasters are noted as likely being associated with increases of takotsubo syndrome. As the pandemic continues, treating COVID-19 as a systemic condition is imperative, with the increase in takotsubo syndrome marking a significant impact of the novel coronavirus.

COVID-19: A double threat to takotsubo cardiomyopathy and spontaneous coronary artery dissection?

Coronavirus disease 2019 (COVID-19) is an ongoing pandemic that has affected millions of individuals worldwide. Prior studies suggest that COVID-19 may be associated with an increased risk for various cardiovascular disorders, such as myocardial injury, arrhythmia, acute coronary syndrome, and venous thromboembolism. Early reports of non-COVID-19 patients have described the concurrence of takotsubo cardiomyopathy (TTC) and spontaneous coronary artery dissection (SCAD). However, the interplay between COVID-19, TTC and SCAD has not been well established. We herein propose two sets of two-hit hypotheses for the development of SCAD and TTC in the context of COVID-19. The first two-hit hypothesis explains the development of SCAD, in which TTC-associated formation of vulnerable coronary substrate serves as the first hit (predisposing factor), and COVID-19-associated inflammation and vascular disruption serves as the second hit (precipitating factor). The second two-hit hypothesis is proposed to explain the development of TTC, in which SCAD-associated formation of vulnerable myocardial substrate serves as the first hit, and COVID-19-associated sympathetic overactivity serves as the second hit. Under this conceptual framework, COVID-19 poses a double threat for the development of SCAD (among patients with underlying TTC) as well as TTC (among patients with underlying SCAD), thereby forming a reciprocal causation. This hypothesis provides a rationale for the joint assessment of TTC and SCAD in COVID-19 patients with pertinent cardiovascular manifestations.

Characteristics and outcome of patients with COVID-19 complicated by Takotsubo cardiomyopathy: case series with literature review.

BACKGROUND: Cardiac involvement with COVID-19 is increasingly being recognised. Clinical characteristics and outcomes of patients with COVID-19 complicated by secondary Takotsubo cardiomyopathy (TC) is poorly understood. METHODS: This retrospective case series was conducted between March and April 2020 at four hospitals of Steward Health Care Network of Massachusetts, USA. Seven patients out of 169 who had echocardiogram were identified to have features of TC. Demographic, clinical, laboratory, management and outcome were gathered from their electronic medical records. We also reviewed all the published cases of COVID-19 and TC in the literature to recognise their common clinical characteristics, risk factors and outcomes. RESULTS: In our series of seven patients, three typical, two inverted, one biventricular and one global TC were recognised. Three were females and four were males. The mean age was 71±11 years. In-hospital death was observed in 57% of patients. Patients who belonged to the high-risk group and had high-risk echocardiographic features in our series had a 100% mortality rate. CONCLUSIONS: COVID-19 complicated by TC has a high mortality rate. Early identification of patients with COVID-19 who are at higher risk for developing secondary TC is important for the prevention of complications, and thus improved outcomes.