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Objective: Takotsubo syndrome (TTS) is characterized by transient left ventricular dysfunction, often elevated myocardial enzymes, and electrocardiographic changes. Previous studies suggested that an overstimulation of the sympathetic nervous system might cause TTS. However, the pathogenesis of TTS is largely unknown. Therefore, we investigated physiological stress reactivity with a standardized stress test in monozygotic twin sisters, only one of whom had experienced TTS. Methods: The 60-year-old Caucasian monozygotic twins, one with and one without a previous episode of TTS, were recruited in the Department of Cardiology at the University Hospital Zurich, Switzerland. We applied the Trier Social Stress Test (TSST) to investigate stress reactivity six weeks after the TTS. Hemodynamic measures (heart rate (HR), blood pressure (BP)), heart rate variability (HRV), plasma norepinephrine and epinephrine and salivary cortisol levels were collected immediately before and after the TSST, and 15, 45, and 90 min after TSST. The monozygotic twins differed in their hemodynamic stress response with the TTS twin showing blunted HR and BP reactivity and vagal withdrawal beyond the acute phase of stress. In contrast, the TTS twin showed a higher catecholamine and cortisol stress response with a steady increase in norepinephrine during the recovery period from stress compared to her non-TTS twin sister. Conclusion: Large studies applying a case-control design are needed to confirm blunted hemodynamic reactivity, increased catecholamine reactivity, vagal withdrawal, and increased cortisol reactivity to stress in TTS. This may advance the knowledge of psychophysiological mechanisms in TTS. [ABSTRACT FROM AUTHOR]

Background Takotsubo syndrome (TTS) is an acute heart failure syndrome characterized by transient left ventricular dysfunction, increased myocardial biomarkers, and electrocardiographic changes. Symptoms of TTS are similar to those of acute coronary syndromes, but there is often no significant coronary stenosis. Although emotional and physical stressors are often reported as having triggered TTS, the pathogenesis is largely unknown. To address this issue, we comprehensively characterized a monozygous pair of twin sisters, one of whom experienced TTS. Case summary The 60-year-old Caucasian monozygotic female twins with and without TTS were examined at the University Hospital Zurich in Switzerland. The twins completed questionnaires and clinical interviews assessing several sociopsychological factors. The twin sister with TTS exhibited higher levels of anxiety, vital exhaustion, social inhibition, and alexithymia, and lower levels of quality of and meaning in life. She was given the diagnoses of social phobia, adjustment disorder, specific anxiety disorder, obsessive–compulsive personality disorder, and an accentuated anxiety-avoidant personality disorder. Additionally, the twin with TTS experienced more—and also more severe—stressors involving life-threatening and dangerous situations over the life course. Discussion These monozygous female twins with and without TTS differed in several notable aspects of their psychological functioning, psychiatric status, personality, and lifetime stressor exposure. The results thus highlight several factors, besides genetic components, that may play an important role in the pathogenesis of TTS. Looking forward, larger studies using experimental and longitudinal designs are needed to elucidate the role that psychosocial factors play in TTS. [ABSTRACT FROM AUTHOR]

Aims Clinical presentation of takotsubo syndrome (TTS) mimics acute coronary syndrome (ACS) and does not allow differentiation. We aimed to develop a clinical score to estimate the probability of TTS and to distinguish TTS from ACS in the acute stage. Methods and results Patients with TTS were recruited from the International Takotsubo Registry (www.takotsubo-registry.com) and ACS patients from the leading hospital in Zurich. A multiple logistic regression for the presence of TTS was performed in a derivation cohort (TTS, n = 218; ACS, n = 436). The best model was selected and formed a score (InterTAK Diagnostic Score) with seven variables, and each was assigned a score value: female sex 25, emotional trigger 24, physical trigger 13, absence of ST-segment depression (except in lead aVR) 12, psychiatric disorders 11, neurologic disorders 9, and QTc prolongation 6 points. The area under the curve (AUC) for the resulting score was 0.971 [95% confidence interval (CI) 0.96–0.98] and using a cut-off value of 40 score points, sensitivity was 89% and specificity 91%. When patients with a score of ≥50 were diagnosed as TTS, nearly 95% of TTS patients were correctly diagnosed. When patients with a score ≤31 were diagnosed as ACS, ∼95% of ACS patients were diagnosed correctly. The score was subsequently validated in an independent validation cohort (TTS, n = 173; ACS, n = 226), resulting in a score AUC of 0.901 (95% CI 0.87–0.93). Conclusion The InterTAK Diagnostic Score estimates the probability of the presence of TTS and is able to distinguish TTS from ACS with a high sensitivity and specificity. [ABSTRACT FROM AUTHOR]

Objective To assess safety up to 1 year of follow-up associated with prasugrel and clopidogrel use in a prospective cohort of patients with acute coronary syndromes (ACS). Methods Between 2009 and 2012, 2286 patients invasively managed for ACS were enrolled in the multicentre Swiss ACS Bleeding Cohort, among whom 2148 patients received either prasugrel or clopidogrel according to current guidelines. Patients with ST-elevation myocardial infarction (STEMI) preferentially received prasugrel, while those with non-STEMI, a history of stroke or transient ischaemic attack, age ≥75 years, or weight <60 kg received clopidogrel or reduced dose of prasugrel to comply with the prasugrel label. Results After adjustment using propensity scores, the primary end point of clinically relevant bleeding events (defined as the composite of Bleeding Academic Research Consortium, BARC, type 3, 4 or 5 bleeding) at 1 year, occurred at a similar rate in both patient groups (prasugrel/clopidogrel: 3.8%/5.5%). Stratified analyses in subgroups including patients with STEMI yielded a similar safety profile. After adjusting for baseline variables, no relevant differences in major adverse cardiovascular and cerebrovascular events were observed at 1 year (prasugrel/clopidogrel: cardiac death 2.6%/4.2%, myocardial infarction 2.7%/3.8%, revascularisation 5.9%/6.7%, stroke 1.0%/1.6%). Of note, this study was not designed to compare efficacy between prasugrel and clopidogrel. Conclusions In this large prospective ACS cohort, patients treated with prasugrel according to current guidelines (ie, in patients without cerebrovascular disease, old age or underweight) had a similar safety profile compared with patients treated with clopidogrel. [ABSTRACT FROM AUTHOR]

Treatment of Heavily Calcified Coronary Lesions Abstract. In Switzerland and other industrialized nations, coronary heart disease (CHD) is the most common cause of death in adulthood. CHD is a chronic disease in which stenoses of the epicardial coronary arteries usually cause a deficit in blood supply to the heart muscle tissue, which can lead to chest pain, myocardial infarction, heart failure or cardiac arrhythmia and ultimately to significant morbidity and mortality. Since the first percutaneous coronary intervention (PCI) on 16th September 1977 at the University Hospital of Zurich by Andreas Grüntzig, the field of interventional cardiology has seen remarkable progress in the treatment of coronary artery disease, especially with the development and evolution of coronary stents. Nonetheless, calcified coronary stenoses pose a challenge in everyday interventional practice because they prevent stent implantation or correct expansion or are associated with a higher rate of complications. Unfortunately, to date, there are no established interventions to prevent calcification of the coronary arteries. However, there are some therapeutic approaches that allow PCI in calcified vessels, and these are the focus of this work.

Aim: Cystatin C, neutrophil gelatinase-associated lipocalin and galectin-3 have emerged as biomarker candidates to predict cardiovascular outcomes and mortality in the general population as well as in patients with coronary artery or renal disease. However, their predictive role and clinical utility in patients with acute coronary syndromes alone or in combination beyond currently used risk scores remains to be determined., Methods and Results: Cystatin C, neutrophil gelatinase-associated lipocalin, and galectin-3 were measured in plasmas of 1832 patients at the time of presentation with acute coronary syndromes requiring percutaneous coronary intervention or coronary artery bypass grafting. The primary outcomes were major adverse cardiac and cerebrovascular events (defined as the composite of all-cause mortality, cerebrovascular events, any repeat revascularization or myocardial infarction) and all-cause mortality after 1 year and occurred in 192 (10.5%) and 78 (4.3%) of patients, respectively. All three biomarkers were increased in those with major adverse cardiac and cerebrovascular events compared with those without ( p <0.001). However, only galectin-3 (all-cause mortality: hazard ratio=1.027 (95% confidence interval (1.011-1.043); p =0.001), major adverse cardiac and cerebrovascular events: hazard ratio=1.025 (95% confidence interval (1.012-1.037); p <0.001)) but not cystatin C nor neutrophil gelatinase-associated lipocalin emerged as independent predictors of both major adverse cardiac and cerebrovascular events and death. The risks were particularly high in the highest quartile of galectin-3. The integration of galectin-3 into the global registry of acute coronary events (GRACE) score improved the prediction of major adverse cardiac and cerebrovascular events and all-cause mortality significantly. The areas under the receiver operator characteristics curves increased from 0.6701 to 0.6932 for major adverse cardiac and cerebrovascular events ( p =0.0474) and from 0.804 to 0.8199 for all-cause mortality ( p =0.0197). Finally, we applied net reclassification improvement index using different cut-offs for major adverse cardiac and cerebrovascular events which showed negative results (for the cut-offs of 5% and 15%, net reclassification improvement index 0.028, p =0.586, for the cut-offs of 10% and 20%, net reclassification improvement index 0.072, p =0.1132 and for the cut-offs of 10% and 30% the net reclassification improvement index is 0.0843, p =0.077)., Conclusion: In acute coronary syndromes patients, galectin-3 has moderate prognostic accuracy, provides statistically significant incremental value in some, but not all models, and that the magnitude of any improvement would seem of questionable clinical value.

Background Left ventricular (LV) recovery in takotsubo syndrome (TTS) occurs over a wide-ranging interval, varying from hours to weeks. We sought to investigate the clinical predictors and prognostic impact of recovery time for TTS patients. Methods and Results TTS patients from the International Takotsubo Registry were included in this study. Cut-off for early LV recovery was determined to be 10 days after the acute event. Multivariable logistic regression was used to assess factors associated with the absence of early recovery. In-hospital outcomes and 1-year mortality were compared for patients with versus without early recovery. We analyzed 406 patients with comprehensive and serial imaging data regarding time to recovery. Of these, 191 (47.0%) had early LV recovery and 215 (53.0%) demonstrated late LV improvement. Patients without early recovery were more often male (12.6% versus 5.2%; P =0.011) and presented more frequently with typical TTS (76.3% versus 67.0%, P =0.040). Cardiac and inflammatory markers were higher in patients without early recovery than in those with early recovery. Patients without early recovery showed unfavorable 1-year outcome compared with patients with early recovery ( P =0.003). On multiple logistic regression, male sex, LV ejection fraction <45%, and acute neurologic disorders were associated with the absence of early recovery. Conclusions TTS patients without early LV recovery have different clinical characteristics and less favorable 1-year outcome compared with patients with early recovery. The factors associated with the absence of early recovery included male sex, reduced LV ejection fraction, and acute neurologic events. Clinical Trial Registration URL: http://www.clinicaltrials.gov. Unique identifier: NCT01947621.

Background: Hyperglycemia in the setting of an acute coronary syndrome (ACS) impacts short term outcomes, but little is known about longer term effects. We therefore designed this study to firstly determine the association between hyperglycemia and short term and longer term outcomes in patients presenting with ACS and secondly evaluate the prognostic role of diabetes, body mass index (BMI) and the novel biomarker Cyr61 on outcomes., Methods: The prospective Special Program University Medicine-Acute Coronary Syndrome (SPUM-ACS) cohort enrolled 2168 patients with ACS between December 2009 and October 2012, of which 2034 underwent PCI (93.8%). Patients were followed up for 12 months. Events were independently adjudicated by three experienced cardiologists. Participants were recruited from four tertiary hospitals in Switzerland: Zurich, Geneva, Lausanne and Bern. Participants presenting with acute coronary syndromes and who underwent coronary angiography were included in the analysis. Patients were grouped according to history of diabetes (or HbA1c greater than 6%), baseline blood sugar level (BSL; < 6, 6-11.1 and > 11.1 mmol/L) and body mass index (BMI). The primary outcome was major adverse cardiac events (MACE) which was a composite of myocardial infarction, stroke and all-cause death. Secondary outcomes included the individual components of the primary endpoint, revascularisations, bleeding events (BARC classification) and cerebrovascular events (ischaemic or haemorrhagic stroke or TIA)., Results: Patients with hyperglycemia, i.e. BSL ≥ 11.1 mmol/L, had higher levels of C-reactive protein (CRP), white blood cell count (WBC), creatinine kinase (CK), higher heart rates and lower left ventricular ejection fraction (LVEF) and increased N-terminal pro-brain natriuretic peptide. At 30 days and 12 months, those with BSL ≥ 11.1 mmol/L had more MACE and death compared to those with BSL < 6.0 mmol/L or 6.0-11.1 mmol/L (HR-ratio 4.78 and 6.6; p < 0.001). The novel biomarker Cyr61 strongly associated with high BSL and STEMI and was independently associated with 1 year outcomes (HR 2.22; 95% CI 1.33-3.72; Tertile 3 vs. Tertile 1)., Conclusions and Relevance: In this large, prospective, independently adjudicated cohort of in all comers ACS patients undergoing PCI, both a history of diabetes and elevated entry glucose was associated with inflammation and increased risk of MACE both at short and long-term. The mediators might involve increased sympathetic activation, inflammation and ischemia as reflected by elevated Cyr61 levels leading to larger levels of troponin and lower LVEF. Trial registration Clinical Trial Registration Number: NCT01000701. Registered October 23, 2009.

Aims: The aim of the present study was to analyze gender disparities in a large cohort of acute coronary syndrome (ACS) patients from the Zurich Acute Coronary Syndrome (Z-ACS) Registry., Methods: Gender disparities in ACS were examined. The primary endpoint included in-hospital death rate, and the secondary endpoint major adverse cardiac and cerebrovascular events (MACCEs) at 30-day follow-up. Furthermore, independent predictors for MACCEs and death were identified., Results: In total, 2612 patients with ACS were identified. Out of these, 23% were women. The mean age was higher in women (68.6 ± 12.2; P < 0.001). Troponin-T on admission (1.33 ± 4.64 vs. 1.19 ± 3.04 μg/l; P = 0.002) and N-terminal of the prohormone brain natriuretic peptide on admission (3456.2 ± 7286.7 vs. 1665.6 ± 4800.6 ng/l; P < 0.001) were higher in women compared with men. Single-vessel disease was more common in women (44.9 vs. 39.7%; P = 0.023) and, conversely, multivessel disease was more prevalent in male patients as compared with their female counterparts (59.4 vs. 54.4%; P = 0.029). At discharge, men were more likely prescribed statins (89.4 vs. 85.2%; P = 0.004). Overall mortality and MACCEs were similar for both genders. In women, peak creatine kinase and peak C-reactive protein emerged as independent predictors for MACCEs and SBP on admission, and maximal C-reactive protein and use of glycoprotein IIb/IIIa inhibitors (GPIIb/IIIa) as strong independent predictors for in-hospital death., Conclusion: The present results suggest a closing gap in short-term outcome and improvement in cardiac care between women and men. Nonetheless, differences in treatment strategies continue to exist, particularly pertaining to statin regimens at discharge, which might potentially have a powerful impact on long-term outcomes and gender disparities.

Background: Bioresorbable vascular scaffolds (BVS) have become an emerging tool to treat coronary artery disease. However, the current use of BVS is still widely restricted to stable patients and non-complex lesions. In real-world practice patients are far more complex than those with simple type A lesions and the extended use of BVS to complex lesions and high-risk patients needs to be evaluated. Therefore, we sought to investigate the feasibility and performance of BVS in a broad spectrum of patients., Methods: 106 patients underwent in total 193 BVS implantations. We assessed the device-related (cardiac death, target vessel myocardial infarction, ischemia-driven target lesion revascularization) and patient-related (all-cause death, any reinfarction and any revascularization) composite outcomes., Results: 90 % of patients (n = 95) had at least one of the following characteristics: >65 years (35 %), ACS (42 %), tortuous vessels (13 %), calcified (17 %) or thrombotic lesions (12 %), lesions defined as AHA type B2/C (42 %), bifurcations (16 %), chronic total occlusions (9 %) or restenosis (14 %). There was no evidence of significant edge dissection, huge thrombus load or incidence of scaffold dislodgement or scaffold disruption in optical coherence tomography pullbacks. Out of 10,157 struts evaluated within 1,117 cross-sections, 302 were classified as malapposed (2.9 %). During a mean follow-up of 147 ± 119 days the rate of device-related events was 2.0 %, whereas patient-related composite events occurred in 6.1 %., Conclusions: Our results strongly suggest that BVS implantation is feasible in a wide spectrum of patients and complex anatomy of coronary lesions. Long-term outcome of BVS should be further investigated in unrestricted settings in randomized controlled trials.