Differences in the Clinical Profile and Outcomes of Typical and Atypical Takotsubo Syndrome: Data From the International Takotsubo Registry.

IMPORTANCE: Apical ballooning is broadly recognized as the classic form of takotsubo syndrome (TTS). Atypical subtypes of TTS also exist, which constitute about 20% of all cases. To date, clinical profile and course of atypical TTS types have rarely been studied. OBJECTIVE: To characterize the clinical profile and outcomes of typical vs atypical types of TTS in a large patient cohort. DESIGN, SETTING, AND PARTICIPANTS: Records of 1750 patients from the International Takotsubo Registry, comprising 26 participating cardiovascular centers in 9 different countries, were reviewed and data on clinical profile and outcomes collected from January 1, 2011, to December 31, 2014. MAIN OUTCOMES AND MEASURES: Clinical characteristics and in-hospital as well as long-term outcomes were assessed. RESULTS: Of 1750 patients diagnosed with TTS between 1998 and 2014, a total of 1430 (81.7%) presented with apical TTS (defined as typical TTS) and 320 (18.3%) with midventricular, basal, or focal TTS (all defined as atypical TTS). Patients with atypical TTS were younger than those with typical TTS (mean [SD], 62.5 [13.3] vs 67.3 [12.9] years; P < .001). Brain natriuretic peptide levels on admission were lower (median factor increase of the upper limit of normal, 4.18 vs 6.59; P = .02) and left ventricular ejection fraction was higher (mean [SD], 43.4% [10.7%] vs 40.6% [12.0%]; P < .001) in patients with atypical than those with typical forms of TTS. ST-segment depression was more prevalent in patients with atypical TTS (31 of 286 [10.8%] vs 90 of 1292 [7.0%]; P = .03), while ST-segment elevation was found more frequently in patients with typical TTS (593 of 1292 [45.9%] vs 97 of 286 [33.9%]; P < .001). Patients with atypical TTS more often had neurologic disorders than those with typical TTS (81 of 274 [29.6%] vs 286 of 1251 [22.9%]; P = .02). While in-hospital mortality was comparable between patients with atypical and typical TTS (10 of 320 [3.1%] vs 62 of 1430 [4.3%]; P = .32), the atypical forms showed a favorable outcome at 1 year (P = .01). However, after adjustment for confounders, only left ventricular ejection fraction less than 45%, atrial fibrillation, and neurologic disease, but not the type of TTS, were independent predictors. After 1 year, patients with both types of TTS showed a similar prognosis at long-term follow-up. CONCLUSIONS AND RELEVANCE: Atypical TTS has different characteristics than typical TTS, including younger age of onset, more frequent ST-segment depression, higher prevalence of neurologic diseases, less pronounced reduction in left ventricular ejection fraction, and lower brain natriuretic peptide values on admission. Outcomes are comparable between patients with both types after adjustment for confounders, suggesting that both should be equally monitored.

Clinical Features and Outcomes of Takotsubo (Stress) Cardiomyopathy.

BACKGROUND: The natural history, management, and outcome of takotsubo (stress) cardiomyopathy are incompletely understood. METHODS: The International Takotsubo Registry, a consortium of 26 centers in Europe and the United States, was established to investigate clinical features, prognostic predictors, and outcome of takotsubo cardiomyopathy. Patients were compared with age- and sex-matched patients who had an acute coronary syndrome. RESULTS: Of 1750 patients with takotsubo cardiomyopathy, 89.8% were women (mean age, 66.8 years). Emotional triggers were not as common as physical triggers (27.7% vs. 36.0%), and 28.5% of patients had no evident trigger. Among patients with takotsubo cardiomyopathy, as compared with an acute coronary syndrome, rates of neurologic or psychiatric disorders were higher (55.8% vs. 25.7%) and the mean left ventricular ejection fraction was markedly lower (40.7±11.2% vs. 51.5±12.3%) (P<0.001 for both comparisons). Rates of severe in-hospital complications including shock and death were similar in the two groups (P=0.93). Physical triggers, acute neurologic or psychiatric diseases, high troponin levels, and a low ejection fraction on admission were independent predictors for in-hospital complications. During long-term follow-up, the rate of major adverse cardiac and cerebrovascular events was 9.9% per patient-year, and the rate of death was 5.6% per patient-year. CONCLUSIONS: Patients with takotsubo cardiomyopathy had a higher prevalence of neurologic or psychiatric disorders than did those with an acute coronary syndrome. This condition represents an acute heart failure syndrome with substantial morbidity and mortality. (Funded by the Mach-Gaensslen Foundation and others; ClinicalTrials.gov number, NCT01947621.).

Feasibility of second-generation bioresorbable vascular scaffold implantation in complex anatomical and clinical scenarios.

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.

Does guideline-adherent therapy improve the outcome for early-onset breast cancer patients?

BACKGROUND AND OBJECTIVE: Guidelines for the treatment of early-onset breast cancer have been proposed in several countries, but to date, their impact on outcomes is unverified. The objective of this study was to evaluate the association between guideline-adherent versus nonadherent treatment and recurrence-free survival (RFS) and overall survival (OAS) in early-onset breast cancer patients. METHODS: A total of 1,778 patients were included in the study, of whom 111 were 35 years or younger and 1,667 were between 36 and 55 years. RFS and OAS were compared between the two groups, with respect to multiple parameters. All survival data were adjusted for tumor characteristics and analyzed with respect to guideline adherence according to the German Step 3 guidelines. RESULTS: Statistically significant differences between the two groups (<35 years, 36-55 years) were observed with regard to breast surgery (p = 0.002) and hormone therapy (p = 0.006). Both groups were treated identically in terms of guideline adherence concerning axillary dissection (p = 0.9), radiation therapy (p = 0.7) and chemotherapy (p = 0.556). Young breast cancer patients whose treatment adhered to guideline recommendations had increased RFS and OAS [RFS: p = 0.030, hazard ratio (HR) 2.95, 95% confidence interval (CI) 1.11-7.83; OAS: p < or = 0.001, HR 2.92, 95% CI 2.01-4.23]. CONCLUSION: Guideline-adherent treatment for early-onset breast cancer patients significantly improves OAS and RFS and should therefore be demanded for all patients.

Effects of guideline adherence in primary breast cancer--a 5-year multi-center cohort study of 3976 patients.

BACKGROUND: The aim of that study was to analyze the impact of German-S3-breast cancer guideline adherence on clinical outcomes. METHODS: A retrospective study analyzed 3976 patients first diagnosed with primary breast cancer according to an S3-guideline-based model that classified patients retrospectively into groups receiving "guideline-adherent and "guideline non-adherent" therapy. RESULTS: There was a significant association between treatment adherence and prolonged recurrence free and overall survival (p = 0.0001). The greater the number of violations in guideline adherence, the lower was overall survival (p = 0.0001). Advanced age at initial diagnosis was additionally associated with a reduction in guideline adherence. The percentage of guideline adherence for the therapeutic modalities BCT, mastectomy, axillary dissection and hormone therapy was greater than 80%. For chemotherapy, the percent of guideline adherence totaled 71.4%. CONCLUSION: Therapies dispensed in adherence with guidelines may improve recurrence-free survival and overall survival in patients with breast cancer.

Comparison of early onset breast cancer patients to older premenopausal breast cancer patients.

BACKGROUND: The objective of this study was to show differences between breast cancer patients < or =35 and >35 years with regard to tumor characteristics and to present the patient-relevant outcomes overall survival (OAS) and recurrence-free survival (RFS). METHODS: We analyzed data from 119 women aged 35 years or younger with breast cancer and compared multiple parameters against breast cancer patients between 36 and 55 (n = 1,097), all pre-menopausal. Data were adjusted for tumor characteristics and therapy. RESULTS: There was no statistically significant difference in tumor size, axillary lymph node involvement, and histological subtypes. On the contrary, grading lymphovascular invasion and receptor negativity showed statistically significant differences. Unadjusted hazard ratio are 2.11 (1.32-3.39) (OAS) and 1.92 (1.35-2.73) (RFS). Multi-adjusted hazard ratio are 2.97 (1.70-5.18) (OAS) and 2.11 (1.42-3.13) (RFS). CONCLUSIONS: In conclusion, young breast cancer patients still have a poor prognosis. Even after adjustment of the data, OAS and RFS showed a worse prognosis. Normal prognostic factors like tumor size, axillary lymph node involvement, and grading can therefore be not the explanation for the more aggressive disease progress within early onset breast cancer patients.

Activation of human alveolar macrophages via P2 receptors: coupling to intracellular Ca2+ increases and cytokine secretion.

Alveolar macrophages play a crucial role in the pathogenesis of inflammatory airway diseases. By the generation and release of different inflammatory mediators they contribute to both recruitment of different leukocytes into the lung and to airway remodeling. A potent stimulus for the release of inflammatory cytokines is ATP, which mediates its cellular effects through the interaction with different membrane receptors, belonging to the P2X and P2Y families. The aim of this study was to characterize the biological properties of purinoceptors in human alveolar macrophages obtained from bronchoalveolar lavages in the context of inflammatory airway diseases. The present study is the first showing that human alveolar macrophages express mRNA for different P2 subtypes, namely P2X(1), P2X(4), P2X(5), P2X(7), P2Y(1), P2Y(2), P2Y(4), P2Y(6), P2Y(11), P2Y(13), and P2Y(14). We also showed that extracellular ATP induced Ca(2+) transients and increased IL-1beta secretion via P2X receptors. Furthermore, extracellular nucleotides inhibited production of IL-12p40 and TNF-alpha, whereas IL-6 secretion was up-regulated. In summary, our data further support the hypothesis that purinoceptors are involved in the pathogenesis of inflammatory lung diseases.