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Aim: To evaluate the long-term outcome of patients with Takotsubo syndrome (TTS) and severely reduced left ventricular ejection fraction (LVEF ≤ 35%) at presentation.Methods and Results: The study population included 326 patients (mean age 69.5 ± 10.7 years, 28 male) with TTS enrolled in the Takotsubo Italian Network, divided into two groups according to LVEF (≤ 35%, n = 131; > 35%, n = 195), as assessed by transthoracic echocardiography at hospital admission. In-hospital events were recorded in both groups. At long-term follow-up (median 26.5 months, interquartile range 18-33), composite major adverse cardiac events (MACE: cardiac death, acute myocardial infarction, heart failure, and TTS recurrence) and rehospitalization were investigated. Compared to patients with LVEF > 35%, patients with LVEF ≤ 35% were older (71.2 ± 10.8 vs. 68.4 ± 10.6 years; P = 0.026) and experienced more frequently cardiogenic shock (16% vs. 4.6%; P < 0.001), acute heart failure (28.2% vs. 12.8%; P = 0.001), and intra-aortic balloon pump support (11.5% vs. 2.6%; P = 0.001) in the acute phase. At long-term follow-up, higher rates of composite MACE (25.2% vs. 10.8%; P = 0.001) and rehospitalization for cardiac causes (26% vs. 13.3%; P = 0.004) were observed in these patients. LVEF ≤ 35% at admission [hazard ratio (HR) 2.184, 95% confidence interval (CI) 1.231-3.872; P = 0.008] and age (HR 1.041, 95% CI 1.011-1.073; P = 0.006) were independent predictors of MACE. Patients with LVEF ≤ 35% also had a significant lower freedom from composite MACE during long-term follow-up (χ2 = 11.551, P = 0.001).Conclusion: Left ventricular ejection fraction ≤ 35% at presentation is a key parameter to identify TTS patients at higher risk not only in the acute phase but also at long-term follow-up. [ABSTRACT FROM AUTHOR]

Aortic dissection ( AD) is the most common life-threatening disease involving the aorta. It is rarely associated with systemic disorders such as Autosomal Dominant Polycystic Kidney Disease ( ADPKD), a genetic syndrome characterized by cystic degeneration of kidneys, possible presence of cysts in other organs and extra-renal manifestations, including cardiovascular disorders. We performed a systematic literature search focused on the occurrence of AD associated with ADPKD (25 cases identified), and reported two cases from our experience. We selected data on sex, age, family history of ADPKD and/or AD, habitus, hypertension, renal function, presence of hepatic/pancreatic/splenic cysts, clinical presentation of AD, AD type according to the Stanford classification, treatment and outcome. Furthermore we compared this dataset with the data of the overall population with AD from the International Registry of Acute Aortic Dissection ( IRAD). Stanford A type AD was documented in 62% of patients. As expected, the initial manifestation of AD was most commonly chest and back pain (80%). The mean age of AD occurrence appears significantly reduced in ADPKD patients compared to the general population with AD (49 ± 12 vs 62 ± 14, P < 0.001). Of note, our analysis shows a remarkably higher frequency of hypertension (90%) compared to the overall AD population (75%), although not significantly ( P = 0.133). AD should be always ruled out in ADPKD subjects with chest and back pain symptoms, despite them being young and at lower risk. A careful preventive monitoring as well as an optimal blood pressure control may reduce the risk of AD and improve the outcome of these patients. [ABSTRACT FROM AUTHOR]

Objectives To determine whether type 2 diabetes mellitus and hyperglycemia on admission should be considered independent predictors of mortality in elderly adults with acute coronary syndrome (ACS). Design Prospective cohort study. Setting Twenty-three hospitals in Italy. Participants Individuals aged 75 and older with non- ST-elevation ACS ( NSTEACS) (mean age 82, 47% female) (N = 645). Measurements Diabetic status and blood glucose levels were assessed on admission. Hyperglycemia was defined as glucose greater than 140 mg/dL. Multivariable Cox proportional hazard regression was used to assess the potential confounding effect of major covariates on the association between diabetic status, admission glucose, and 1-year mortality. Results A history of diabetes mellitus was found in 231 participants (35.8%), whereas 257 (39.8%) had hyperglycemia. Hyperglycemia was found in 171 participants with diabetes mellitus (70%) and 86 (21%) without diabetes mellitus. Participants with diabetes mellitus were significantly ( P < .05) more likely to have had prior myocardial infarction and stroke and had lower ejection fraction and blood hemoglobin. Hyperglycemia was associated with lower ( P < .05) ejection fraction and estimated glomerular filtration rate ( eGFR). Diabetic status and hyperglycemia were associated with greater 1-year mortality according to univariate analysis (54 participants with diabetes mellitus died (23.4%), versus 66 (15.9%) without diabetes mellitus (hazard ratio (HR) = 1.5 95% confidence interval (CI) = 1.0-2.1), and 60 participants with hyperglycemia died (23.3%), versus 60 (15.5%) without hyperglycemia (HR=1.6; 95% CI = 1.1-2.2), but this association was not statistically significant after adjustment for ejection fraction, age, blood hemoglobin, and eGFR. Conclusion In elderly adults with NSTEACS, diabetes mellitus and hyperglycemia on admission are associated with higher mortality, mostly because of preexisting cardiovascular and renal damage. [ABSTRACT FROM AUTHOR]

Aims: Several studies have shown that muscle mass loss is an important pathogenic issue in heart failure (HF). Atrogin-1 is a F-box protein selectively expressed in cardiac and skeletal muscle tissue, which plays a pivotal role in muscle wasting regulation. The aim of this study was to investigate the expression of Atrogin-1 and the molecular pathway involved in Atrogin-1 regulation in human HF. Methods and Results: Cardiac tissue from patients with HF (HF group: n=10) or with normal left ventricular function (control group: n=9) was studied by western blot and real time-PCR analysis. Linear regression analysis between patients left ventricular ejection fraction (LVEF) and Atrogin1 or its regulator Forkhead box O 3a (Foxo3a) myocardial expression was performed to test correlations between protein expression and LVEF. Western blot analysis revealed that the myocardial expression of Atrogin-1 in the HF group was 2.5-fold increased compared with controls (P=0.007). Accordingly, Atrogin-1 mRNA was 1.5 higher than in controls (P=0.003). The expression of Foxo3a and its up-stream regulator AKT were also measured. Western blot analysis demonstrated in the HF group a 2.56-fold reduction of AKT phosphorylation and a 3.32-fold increase of Foxo3a as compared with controls (P=0.002 and P=0.001, respectively). Finally, linear regression showed a significant relationship between Foxo3a or Atrogin-1 expression and LVEF (R=0.976, P<0.0001 and R=0.895, P=0.003, respectively). Conclusion: Our results suggest that in human HF, the activity of AKT decreases, with activation of Foxo3a and induction of Atrogin-1, thereby leading to a molecular state that favours heart muscle loss and left ventricular dysfunction. [ABSTRACT FROM AUTHOR]

We studied the role of α1-adrenergic receptors (AR) in ischemia-induced neoangiogenesis (NeoA) in vivo in 12-week-old rats in which the right common femoral artery was removed and in vitro in cultured rat endothelial cells (EC). We investigated the effects of 14 days' administration of the α1-AR antagonist doxazosin (DOXA, 0.06 mg/kg/d, n=16) or saline (CTRL, n=6) by means of peritoneum-implanted osmotic minipumps. Laser Doppler analysis and digital angiography TIMI Frame Count showed an improvement in perfusion of the ischemic hind limb of the DOXA vs CTRL group. Similarly, dyed microsphere perfusion and histologic evaluation confirmed the beneficial effects of DOXA on NeoA. In vitro, we verified by RT-PCR the expression of α1-AR in EC. DOXA (10-7M; 24 h) increased EC proliferation in response to fetal bovine serum (FBS, 5%) and enhanced FBS-induced ERK and Rb activation. Our findings support a beneficial role for α1-AR blockade in ischemia-induced NeoA and on EC proliferation. [ABSTRACT FROM AUTHOR]

Background: The CHA 2 DS 2 -VASc score predicts stroke in patients with atrial fibrillation and has been reported to have a prognostic role even in acute coronary syndrome patients. The Takotsubo syndrome is a condition that mimics acute coronary syndrome and may present several complications including stroke. We sought to assess the ability of CHA 2 DS 2 -VASc score to predict adverse events in Takotsubo syndrome patients., Methods and Results: Overall, 371 Takotsubo syndrome patients were enrolled in a prospective registry. Patients were divided into 3 groups according to the CHA 2 DS 2 -VASc score: Group A (≤1), B (2-3), and C (≥4). The median CHA 2 DS 2 -VASc score was 3 (interquartile range: 2-4). Overall, 9%, 42%, and 49% were included in Group A, B, and C, respectively. Follow-up length was 26±20 months. The mortality rate was 6%, 7%, and 17% in Group A, B, and C, respectively ( P =0.011). The stroke rate was 3% and not different among the 3 groups. Estimated major adverse cardiac and cerebrovascular events (the composite of death, myocardial infarction, and stroke) rates in the 3 groups were 6%, 9%, and 17% in Group A, B, and C, respectively ( P =0.033). The CHA 2 DS 2 -VASc score resulted as a predictor of major adverse cardiac and cerebrovascular events (odds ratio 2.1, 95% confidence interval, 1.2-3.6; P =0.01) and all-cause mortality (odds ratio 1.5, 95% confidence interval, 1.2-1.9; P =0.001)., Conclusions: In Takotsubo syndrome, the CHA 2 DS 2 -VASc score allows prediction of cardiovascular events and mortality at long-term follow-up., (© 2017 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley.)