Impact of age on the outcomes of Takotsubo syndrome

Background: Takotsubo syndrome (TTS) is a syndrome with ambiguous pathophysiology. Impaired kidney function (KF) seems to impact the outcome of patients with TTS. We hypothesized that KF worsens the outcome among TTS patients and furthermore, TTS patients with concomitant KF experience more adverse events compared to myocardial infarction (MI) patients with concomitant KF. Methods and Results: This retrospective single-center study comprised two groups (cohorts) of patients including patients with TTS and concomitant KF (n = 61, 27.1%) and patients with MI and concomitant KF (n = 164, 72.9%). The clinical outcomes were delineated as short-term outcomes defined as in-hospital adverse events during index hospitalization and long-term outcomes defined as adverse events over five-year clinical follow-ups. All-cause mortality, stroke, cardiopulmonary resuscitation (CPR), life-threatening arrhythmias, need for respiratory support, and cardiogenic shock with subsequent use of inotropic agents during index hospitalization were denoted as in-hospital adverse events. All-cause mortality, rehospitalization due to heart failure, stroke, thromboembolic events, and the recurrence of primary pathology (TTS and MI) were analyzed during five-year follow-ups after index hospitalization. A higher mortality rate was noted among TTS patients with KF compared to TTS without KF. In addition, in-hospital event rates in patients with TTS and concomitant KF compared to MI and concomitant KF were comparable with the exception of a higher rate of respiratory support in TTS patients. The mortality rate was significantly higher among patients with TTS and KF at 4 years (29.5% vs. 15.9%, p = 0.02) and 5 years (34.4% vs. 20.7%, p = 0.03) in comparison to patients with MI and concomitant KF. In contrast, the rate of re-hospitalization related to heart failure was higher at 30 days, and at one-, four-, and five-year follow-ups in patients suffering from MI and KF compared to TTS and concomitant KF. Additionally, the recurrence of MI after 4 and 5 years was higher than the recurrence of TTS (4.9% vs. 15.2%; 4.9% vs. 16.5%). There were no differences in life-threatening arrhythmias and stroke in both groups. Conclusions: Patients with TTS and concomitant KF have higher all-cause mortality when compared to MI and concomitant KF. The mechanisms responsible remain to be determined.

Long-Term Prognosis of Patients With Takotsubo Syndrome

Prognostic Value of Microvascular Resistance at Rest in Patients With Takotsubo Syndrome

Aims As known, Takotsubo Syndrome (TTS) can occur during stressful events that result in sympathetic overactivity. No studies have investigated the sympathetic activity and long-term prognosis in patients with TTS and admission hyperglycaemia vs. normoglycaemia. Moreover, whether hyperglycaemia may serve as a metabolic trigger to unbalance the sympathetic system axis as well as through over-inflammation is not fully understood. To investigate admission hyperglycaemia effects on the sympathetic system and long-term prognosis in Takotsubo syndrome (TTS). Methods and results In this multicentre study, we screened 4783 patients undergoing coronary angiography within the first 72 h of hospitalization for suspected acute coronary syndrome between January 2015 and January 2018. All enrolled patients met the InterTAK diagnostic criteria proposed in the European Society of Cardiology position statement for the diagnosis of TTS. Exclusion criteria encompassed patients with previous myocardial infarction, TTS events, or chronic kidney or liver disease. Patients with TTS were divided into those with hyperglycaemia vs. those with normoglycaemia according to a cutoff admission blood glucose value of 140 mg/dl. Sympathetic activity was assayed by blood values of norepinephrine and 123I-labelled metaiodobenzylguanidine (MIBG) cardiac scintigraphy with late heart-to-mediastinum ratio (H/Mlate) and washout rate (WR), performed in 30 patients who did not present any contraindication to the examination, evaluated at baseline and at follow-up. Similarly, systemic inflammatory markers [C-reactive protein (CRP), white blood cell count (leukocytes and neutrophils), tumour necrosis factor-alpha (TNF-a)] and B-type natriuretic peptide (BNP) were assessed. Prespecified endpoints [heart failure (HF) and all-cause deaths] were assessed at long-term follow-up (12 and 24 months). At hospitalization, TTS patients with hyperglycaemia (N = 28) vs. those with normoglycaemia (M = 48) had significantly higher levels of inflammatory markers and B-type natriuretic peptide and lower left ventricular ejection fraction. Admission glucose values were correlated with norepinephrine levels (R2 = 0.39; P = 0.001). In 30 patients with TTS, 123I-MIBG cardiac scintigraphy showed lower late heart-to-mediastinum ratio values in the acute phase (P < 0.001) and at follow-up (P < 0.001) in those with hyperglycaemia. Patients with hyperglycaemia had higher rates of HF (P < 0.001) and death events (P < 0.05) after 24 months. In multivariate Cox regression analysis, hyperglycaemia (P = 0.008), tumour necrosis factor-alpha (P = 0.001), and norepinephrine (P = 0.035) were independent predictors of HF events. Conclusions Patients with TTS and hyperglycaemia exhibit sympathetic overactivity with a hyperglycaemia-mediated proinflammatory pathway, which could determine a worse prognosis during follow-up.

Background Although the onset of takotsubo syndrome (TTS) may be accompanied by hyponatremia, the clinical relevance and long-term mortality in a group of hyponatremic TTS patients remains poorly elucidated. Purpose We sought to investigate whether hyponatremia identified in TTS patients influenced in-hospital and long-term outcomes in this group of patients. Methods Among 7771 patients with acute myocardial infarction hospitalized between 2012-2019, TTS was diagnosed in 100 patients (1.3%). Hyponatremia on admission was defined as sodium level <135 mmol/L. In-hospital clinical characteristics and the long-term all-cause mortality were assessed in hyponatremic and normonatriemic TTS patients. Results Admission hyponatremia was identified in 14 (14%) of TTS patients. Hyponatremic patients were older (78.5 vs 69 y, P=0.013) and more frequently had history of stroke (7.1 vs 0%, P=0.046) or heart failure (50 vs 12.8%, P=0.001) than normonatriemic patients. Hyponatremic subjects more often demonstrated ST-segment elevation myocardial infarction (78.6 vs 48.8%, P=0.033) and apical TTS type (100 vs 81.4%, P=0.021). During the index hospitalization hyponatremic versus normonatriemic TTS patients showed lower improvement of left ventricular ejection fraction (0 [0-5] vs 10 [0-20]%, P=0.039) and its lower values on discharge (40 [35-45] vs 50 [42-55]%, P=0.032). Within median observation of 53 months higher all-cause mortality was found in hyponatremic versus normonatriemic TTS patients (35.7 vs 15.1%, P=0.038). By Cox proportional hazard regression lower sodium plasma level on admission was identified as an independent predictor of higher long-term mortality (HR 0.919, 95%CI 0.866-0.975, P=0.005). Conclusions Admission hyponatremia observed in every seventh TTS patient was associated with lower in-hospital left ventricular ejection fraction improvement and higher long-term all-cause mortality.

Takotsubo syndrome (TTS), commonly perceived as a benign and reversible condition has received attention due to emerging registry data revealing its prognosis to be comparable to acute coronary syndrome (ACS). Following ACS, a notable subset of patients develops autonomic dysfunction, whith unfavourable prognostic implications. Periodic repolarization dynamics (PRD) and deceleration capacity (DC), derived from ECG signals, are parameters capable of quantifying cardiac autonomic function. In this study, we aimed to assess autonomic dysfunction in patients with TTC in comparison to ST-elevation myocardial infarction (STEMI) patients. Consecutive patients diagnosed with TTS were prospectively recruited into an observational, single-centre cohort study. All patients underwent a 30-minute high-resolution ecg recording. Subsequent recordings were conducted at 4 and 12 months post-acute event. PRD and DC as markers for sympathetic and parasympathetic activity, respectively, were assessed using established methods. The control group comprised patients with STEMI. Statistical comparisons between groups were performed using the Mann-Whitney U-test, with a corrected significance level for multiple testing of α< .017. Between July 2021 and December 2023, 57 patients diagnosed with TTS were recruited (interquartile range [IQR]) 69.0 years (62.0-78.0), 98.3% women. A control group was derived from a pre-existing cohort of STEMI patients, matched through propensity score matching to adjust for age and sex (median age [IQR]: 69.0 [59.0-76.0] years, 98.3% women). At baseline, there was no significant difference in PRD between TTS patients and controls (median [IQR]: TTS: 5.28deg² [3.43-9.93], STEMI: 4.40deg² [2.24-7.21]; p = .04). However, at 4 months post-acute event, PRD was notably higher in TTS patients compared to controls (median [IQR]: TTS: 5.20deg² [2.71-8.17], STEMI: 2.63deg² [1.86-4.92]; p = .011). Interestingly, at 12-month follow-up, PRD in TTS patients did not differ from that of controls (median [IQR]: TTS: 4.55deg² [2.89-8.40], STEMI: 4.15deg² [2.42-6.85]; p = .68). Regarding DC, no significant differences were observed between TTS and STEMI patients at any time point (baseline: median [IQR]: TTS: 3.95 ms [2.27-5.51], STEMI: 3.52 ms [2.30-7.24], p = .51; 4 months: median [IQR]: TTS: 6.63 ms [4.59-8.64], STEMI: 7.41 ms [4.63-9.25], p = .39; 12 months: median [IQR]: TTS: 4.98 ms [4.19-6.67], STEMI: 7.48 ms [4.92-10.28], p = .17). Patients with TTS show substantial signs of cardiac autonomic dysfunction, similar or even higher than acute STEMI patients. This dysfunction persists even up to 4 months after the acute event, whereas STEMI patients show recovery of autonomic function in this 4 month period. DC remained consistent between TTS and STEMI patients across all time points. Further research elucidating the long-term implications of these autonomic alterations is warranted to refine risk stratification and therapeutic strategies in TTS management.

The recent change in terminology from nonalcoholic fatty liver disease (NAFLD) to metabolic dysfunction-associated fatty liver disease (MAFLD) and metabolic dysfunction-associated steatotic liver disease (MASLD) highlights the link between hepatic steatosis and metabolic dysfunction, taking out the stigmata of alcohol. We compared the effects of NAFLD and MAFLD definitions on the risk of overall and cardiovascular (CV) mortality, liver-related events (LRE), nonfatal CV events (CVE), chronic kidney disease (CKD), and extra-hepatic cancers (EHC). We systematically searched four large electronic databases for cohort studies (published through August 2023) that simultaneously used NAFLD and MAFLD definitions for examining the risk of mortality and adverse CV, renal, or oncological outcomes associated with both definitions. In total, 21 eligible cohort studies were identified. Meta-analysis was performed using random-effects modelling. Compared with those with NAFLD, individuals with MAFLD had significantly higher rates of overall mortality (random-effect OR 1.12, 95% CI 1.04-1.21, p = .004) and CV mortality (random-effect OR 1.15, 95% CI 1.04-1.26, p = .004), and a marginal trend towards higher rates of developing CKD (random-effect OR 1.06, 95% CI 1.00-1.12, p = .058) and EHC events (random-effect OR 1.11, 95% CI 1.00-1.23, p = .052). We found no significant differences in the risk LREs and nonfatal CVE between MAFLD and NAFLD. Meta-regression analyses identified male sex and metabolic comorbidities as the strongest risk factors related to the risk of adverse clinical outcomes in MAFLD compared to NAFLD. Individuals with MAFLD have higher rates of overall and CV mortality and higher rates of developing CKD and EHC events than those with NAFLD, possibly due to the dysmetabolic risk profile related to MAFLD.

Spontaneous coronary artery dissection (SCAD) and Takotsubo syndrome (TTS) constitute two relatively common nonatherosclerotic causes of acute coronary syndrome particularly frequent in women. This study sought to compare the baseline clinical and angiographic characteristics and in-hospital outcomes of patients from two large prospective registries on SCAD and TTS (the prospective nation-wide Spanish SCAD Registry and a prospective single-center TTS registry). A total of 318 SCAD and 106 TTS consecutive patients were included. Most patients in both groups (88%) were women. Patients in the TTS group were older [74 (interquartile range, IQR 67-81) vs. 53 years-old (IQR 47-60), P < 0.001] and presented a higher prevalence of cardiovascular risk factors. Precipitating triggers were more frequent in TTS (56% vs. 42%, P = 0.009) but emotional stress was more common in the SCAD group (25% vs. 15%, P = 0.037). TTS patients showed a reduced release of cardiac biomarkers but had more severe left ventricular dysfunction (ejection fraction <50%: 73% vs. 12%, P < 0.001). In-hospital major adverse cardiovascular events occurred more frequently in TTS patients (12% vs. 4.7%, P < 0.001). Notably, TTS patients showed more frequently congestive heart failure (10% vs. 0.6%, P < 0.001), atrial fibrillation (11% vs. 1%, P < 0.001) and had a higher all-cause in-hospital mortality (5.7% vs. 1.3%, P = 0.032). TTS patients are older and present a higher prevalence of some cardiovascular risk factors than patients with SCAD. TTS is linked to a worse in-hospital prognosis with higher mortality.

Cardiac troponin levels are elevated in Takotsubo syndrome (TTS) with significant overlap to acute myocardial infarction (MI). Long and intact cardiac troponin T (cTnT) forms are typical for MI. This study sought to assess whether the fragmentation composition of cTnT release in TTS differs from MI. The concentration of long molecular forms of cTnT (long cTnT) was measured with a novel upconversion luminescence immunoassay and total cTnT with a commercial high-sensitivity cTnT assay in 24 TTS patients and in 84 Type 1 MI patients. The ratio of long to total cTnT (troponin ratio) was determined as a measure of cTnT fragmentation. Troponin ratio was lower in TTS patients [0.13 (0.10-0.20) vs. 0.62 (0.29-0.96), P < 0.001]. In the receiver operating characteristic curve analyses, troponin ratio showed a better predictive power than total cTnT in discriminating TTS and MI patients {area under the curve [AUC] 0.869 [95% confidence interval (CI) 0.789-0.948] vs. 0.766 [95% CI 0.677-0.855], P = 0.047}. When restricting the analysis to patients with total cTnT below 1200 ng/L (maximal value in TTS patients), the respective AUC values for total cTnT and troponin ratio were 0.599 (95% CI 0.465-0.732) and 0.816 (95% CI 0.712-0.921) (P = 0.003). At a cut-off point of 0.12, troponin ratio correctly identified 95% of MI patients and 50% of TTS patients. In contrast to Type 1 MI, only a small fraction of circulating cTnT in TTS exists in intact or long molecular forms. This clear difference in troponin composition could be of diagnostic value when evaluating patients with cTnT elevations and suspicion of TTS. URL: https://www.clinicaltrials.gov; Unique identifier: NCT04465591.

Background: Takotsubo Syndrome (TTS) is characterized by transient reduction in left ventricular function with in the absence of obstructive coronary artery disease. Clinical presentation often mimics acute myocardial infarction (AMI). Patients with TTS have comparable long-term mortality with AMI patients. However, data on the burden of heart failure (HF) readmissions in patients with TTS are scarce. Methods: This retrospective analysis utilized the US Nationwide Readmission Database for the years 2012-2019 to identify hospitalizations for TTS or AMI. The primary outcome of interest was 6-month readmission due to HF. Secondary outcomes included in-hospital mortality. Results: There were 30,926 hospitalizations with TTS and 2,535,025 hospitalizations with AMI. The proportion of women was 90% among TTS patients and 37.7% among AMI patients (p&lt;0.001). Overall comorbidities were similar between the two groups, but in-hospital mortality during index admission was higher in the AMI arm (6.5% vs 1.5% in TTS, p &lt;0.01) accompanied with increased in-hospital complications. All-cause readmission rates were lower among TTS than among AMI patients (21.9% vs. 29.4%; p &lt;0.01). HF readmissions were also lower among TTS than AMI patients (3.7% vs. 6.7%; p &lt;0.01). After propensity matching, all-cause readmission rate remained lower among TTS than among AMI patients (21.9% vs. 27.9%; p &lt;0.01). HF hospital readmissions rates were also lower among TTS patients (3.7% vs 5.7%; p &lt;0.01). Independent predictors of HF readmission in TTS population included comorbidities such as diabetes mellitus, atrial fibrillation, chronic kidney disease, peripheral vascular disease, and chronic pulmonary disease. Conclusion A substantial proportion of patients (&gt;20%) with TTS suffer a hospital readmission within 6 months, although less than 5% are readmitted with HF. Compared with AMI, all-cause and HF readmission rates are lower in TTS patients.

Prevalence and long-term prognostic impact of malignancy in patients with Takotsubo syndrome.

Takotsubo syndrome (TTS) patients have a higher mortality rate than the general population. Our study was conducted to determine the short- and long-term outcome of TTS patients associated with a significantly compromised mitral annular plane systolic excursion (MAPSE) on hospital admission. Our institutional database constituted a collective of 53 patients diagnosed with TTS between 2003 and 2016. The patients were classified into two groups based on the MAPSE, with those presenting with an MAPSE <1 cm on admission categorized into one group (n = 20, 38%) and those presenting with MAPSE ≥1 cm (n = 33, 62%) categorized into another group. Preliminary results indicated that patients with an MAPSE < 1 cm had a greater risk of developing thromboembolic events. The long-term mortality was significantly higher in TTS patients with an MAPSE < 1 cm. In the multivariate Cox regression analysis, cardiogenic shock (hazard ratio 3.5; 95% confidence interval: 1.2-10.7; P = 0.02) and MAPSE < 1 cm (hazard ratio 5.1; 95% confidence interval: 1.3-19.2; P = 0.01) figured as independent predictors of the mortality. Although the short-term mortality rates among TTS patients diagnosed with a reduced MAPSE on admission were as similar as without reduced MAPSE, the long-term mortality rates among TTS patients diagnosed with a reduced MAPSE on admission were significantly higher. There is an urgent need for randomized trials, which could help define uniform clinical management strategies for high-risk TTS patients.

Case presentation: A 60-year-old woman presented to the emergency department 2 hours after the onset of severe retrosternal chest pain that started soon after she was told that her son had died in a car accident. A 12-lead ECG demonstrated ST-elevation in the precordial leads (Figure 1), and the plasma troponin T level was elevated at 0.07 ng/mL. A diagnosis of acute ST-elevation myocardial infarction was made, and the patient was admitted for emergency coronary angiography, which revealed normal coronary arteries. The left ventriculogram showed severe systolic dysfunction involving the mid and apical segments (Data Supplement Movie I). Figure 1. Twelve-lead ECG demonstrating ST-segment elevation in precordial leads. Physicians have long been aware of the possible association between stress and cardiovascular events. Awareness has increased of a distinct cardiac syndrome that was originally described in the Japanese population and was called Takotsubo cardiomyopathy, named after the octopus-trapping pot with a round bottom and narrow neck that resembles the left ventriculogram during systole in these patients.1,2 Other names used to describe the condition include apical ballooning syndrome (ABS), broken heart syndrome, and stress or ampulla cardiomyopathy. The precise incidence of ABS is unknown, but it may account for 1% to 2% of patients who present with an acute myocardial infarction.3 The majority of patients have a clinical presentation that is indistinguishable from an acute coronary syndrome. Most present with chest pain at rest, although some patients have dyspnea alone as their initial presenting symptom. Rarely, patients present with syncope or an out-of-hospital cardiac arrest.4 ABS appears to occur almost exclusively in postmenopausal women; however, a few cases have been reported in younger women and males.4 The patients are usually hemodynamically stable, but clinical findings of mild-to-moderate congestive heart failure …

BackgroundTakotsubo syndrome (TTS) and acute coronary syndrome (ACS) patients have a similar mortality rate. In this study, we sought to determine the short- and long-term outcome of TTS patients as compared to ACS patients both treated with beta-blockers.ObjectivesIn the present study we described the data of 5 years of follow up of 103 TTS and 422 ACS patients both treated with beta-blockers.MethodsData from TTS patients were included retrospectively and prospectively, ACS patients were included retrospectively. All retrospectively included patients have been followed up for 5 years. The end point in this study was the occurrence of death.ResultsTTS affected significantly more women (87.4%) than ACS (34.6%) (p < 0.01). TTS patients suffered significantly more often from thromboembolic events (14.6% versus 2.1%; p < 0.01) and cardiogenic shock (11.9% versus 3.6%; p < 0.01) than the ACS group. TTS patients had a significantly higher long-term mortality (within 5 years) as compared to ACS patients (17.5% versus 3.6%) (p < 0.01). Patients of the TTS group compared to the ACS group did not benefit from combination of beta-blockers and ACE-inhibitors in terms of long-term mortality (p < 0.01). As we compare TTS patients who were treated with beta-blockers and ACE-inhibitors versus single use of beta-blockers there was no difference in long-term mortality (p = 0.918).ConclusionTTS patients had a significantly higher long-term mortality (within 5 years) than patients with an ACS.

A systematic review and meta-analysis were performed to analyse the differences in clinical profiles between takotsubo syndrome (TTS) and acute coronary syndrome (ACS) patients and to consolidate the evidence regarding the mortality predictors in TTS patients. Literature search of PubMed, EMBASE and the Cochrane Central Register was made, and 55 studies with a total of 66,653 TTS patients were included. Compared with ACS subjects, TTS subjects had significantly lower left ventricle ejection fraction (LVEF) values on admission; however, cardiovascular risks were fewer and the recovery LVEF was notably higher at both discharge and follow-up in TTS patients than in ACS patients (all P < 0.05). No significant differences were observed either in-hospital mortality or long-term mortality between the two groups (both P > 0.05). Acute renal failure and malignancies were independent predictors of all-cause in-hospital mortality in TTS patients (both P < 0.05). Male sex (HR = 0.565, 95% CI 0.253-0.876, P < 0.001, I2 = 0.00%), advanced age (HR = 0.054, 95% CI 0.041 to 0.067, P < 0.001, I2 = 0.00%), shock (HR = 1.382. 95% CI 1.050 to 1.714, P < 0.001, I2 = 0.00%) and initial LVEF < 35% (HR = 0.962, 95% CI 0.948 to 0.977, P < 0.001, I2 = 16.8%) were associated with an increased risk of long-time mortality in TTS patients. In conclusion, TTS has significantly different clinical characteristics than ACS. However, the in-hospital and long-term overall mortality rates are not trivial for TTS patients, and some presenting features (underlying diseases, male sex, advanced age, low LVEF and shock) were significantly associated with all-cause mortality.