Szeged, Hungary
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Jaguszewski M.,University of Zürich | Radovanovic D.,University of Zürich | Nallamothu B.K.,University of Michigan | Luscher T.F.,University of Zürich | And 6 more authors.
EuroIntervention | Year: 2013

Aims: We examined what type of STEMI patients are more likely to undergo multivessel PCI (MPCI) in a "real-world" setting and whether MPCI leads to worse or better outcomes compared with single-vessel PCI (SPCI) after stratifying patients by risk. Methods and results: Among STEMI patients enrolled in the Swiss AMIS Plus registry between 2005 and 2012 (n=12,000), 4,941 were identified with multivessel disease. We then stratified patients based on MPCI use and their risk. High-risk patients were identified a priori as those with: 1) left main (LM) involvement (lesions, n=263); 2) out-of-hospital cardiac arrest; or 3) Killip class III/IV. Logistic regression models examined for predictors of MPCI use and the association between MPCI and in-hospital mortality. Three thousand eight hundred and thirty-three (77.6%) patients underwent SPCI and 1,108 (22.4%) underwent MPCI. Rates of MPCI were greater among high-risk patients for each of the three categories: 8.6% vs. 5.9% for out-of-hospital cardiac arrest (p<0.01); 12.3% vs. 6.2% for Killip III/IV (p<0.001); and 14.5% vs. 2.7% for LM involvement (p<0.001). Overall, in-hospital mortality after MPCI was higher when compared with SPCI (7.3% vs. 4.4%; p<0.001). However, this result was not present when patients were stratified by risk: in-hospital mortality for MPCI vs. SPCI was 2.0% vs. 2.0% (p=1.00) in low-risk patients and 22.2% vs. 21.7% (p=1.00) in high-risk patients. Conclusions: High-risk patients are more likely to undergo MPCI. Furthermore, MPCI does not appear to be associated with higher mortality after stratifying patients based on their risk. © Europa Digital & Publishing 2013.

Radovanovic D.,University of Zürich | Seifert B.,University of Zürich | Eberli F.R.,Stadtspital Triemli | Rickli H.,Kantonsspital St. Gallen | And 3 more authors.
Heart | Year: 2014

Objective This study aimed to assess the impact of individual comorbid conditions as well as the weight assignment, predictive properties and discriminating power of the Charlson Comorbidity Index (CCI) on outcome in patients with acute coronary syndrome (ACS). Methods A prospective multicentre observational study (AMIS Plus Registry) from 69 Swiss hospitals with 29 620 ACS patients enrolled from 2002 to 2012. The main outcome measures were in-hospital and 1-year follow-up mortality. Results Of the patients, 27% were female (age 72.1 ±12.6 years) and 73% were male (64.2±12.9 years). 46.8% had comorbidities and they were less likely to receive guideline-recommended drug therapy and reperfusion. Heart failure (adjusted OR 1.88; 95% CI 1.57 to 2.25), metastatic tumours (OR 2.25; 95% CI 1.60 to 3.19), renal diseases (OR 1.84; 95% CI 1.60 to 2.11) and diabetes (OR 1.35; 95% CI 1.19 to 1.54) were strong predictors of in-hospital mortality. In this population, CCI weighted the history of prior myocardial infarction higher (1 instead of -0.4, 95% CI -1.2 to 0.3 points) but heart failure (1 instead of 3.7, 95% CI 2.6 to 4.7) and renal disease (2 instead of 3.5, 95% CI 2.7 to 4.4) lower than the benchmark, where all comorbidities, age and gender were used as predictors. However, the model with CCI and age has an identical discrimination to this benchmark (areas under the receiver operating characteristic curves were both 0.76). Conclusions Comorbidities greatly influenced clinical presentation, therapies received and the outcome of patients admitted with ACS. Heart failure, diabetes, renal disease or metastatic tumours had a major impact on mortality. CCI seems to be an appropriate prognostic indicator for in-hospital and 1-year outcomes in ACS patients. Identifier NCT01305785.

Erne P.,AMIS Plus | Erne P.,University of Zürich | Bertel O.,Cardiology Center | Urban P.,La Tour Hospital | And 3 more authors.
European Journal of Internal Medicine | Year: 2015

Abstract Background There are few studies on patients suffering acute myocardial infarction (AMI) when already in hospital for other reasons; therefore, this study aimed to compare patients with in-hospital-onset AMI admitted for either medical or surgical reasons versus patients with outpatient-onset AMI. Methods Patients enrolled in the AMIS Plus registry from 2002 to 2014 were analyzed. The main endpoint was in-hospital mortality. Results Among 35,394 AMI patients, 356 (1%) had inpatient-onset AMI following hospital admission due to other pathologies (surgical 175, non-surgical 181). These patients were older (74 vs. 66 years; P < 0.001), more often female (35% vs. 27%; P < 0.001), had less frequently ST-elevation myocardial infarction (35.5% vs. 55.5%; P < 0.001), but higher risk profiles: hypertension (83% vs. 62%; P < 0.001), diabetes (28% vs. 20%; P = 0.001), known coronary artery disease (54% vs. 35%; P < 0.001), and more comorbidities (Charlson Comorbidity Index above 1 in 51% vs. 22%; P < 0.001) than those with outpatient-onset AMI. Percutaneous coronary intervention was less frequently applied (OR 0.45; 95% CI 0.36-0.57), and they were less likely to be treated with aspirin (OR 0.43; 95% CI 0.37-0.59), P2Y12 blockers (OR 0.42; 0.34-0.52) or statins (OR 0.51; 95% CI 0.41-0.63). Crude mortality was higher (14.3% vs. 5.5%; P < 0.001) and inpatient-onset AMI was an independent predictor of in-hospital mortality (OR 2.35; 95% CI 1.63-3.39; P < 0.001). Conclusions Patients with in-hospital-onset AMI were at greater risk of death than those with outpatient-onset AMI. More work is needed to improve the identification of hospitalized patients at risk of AMI in order to provide the appropriate management. © 2015 European Federation of Internal Medicine.

Alho I.,Cardiology Center | Alho I.,Institute Medicina Molecular | Costa L.,Institute Medicina Molecular | Costa L.,Hospital Of Santa Maria | And 2 more authors.
PLoS ONE | Year: 2013

Low molecular weight protein tyrosine phosphatase (LMW-PTP) has been associated with cell proliferation control through dephosphorylation and inactivation of growth factor receptors such as PDGF-R and EphA2, and with cellular adhesion and migration through p190RhoGap and RhoA. We aim to clarify the role of two main LMW-PTP isoforms in breast cancer tumorigenesis. We used a siRNA-mediated loss-of-function in MDA-MB-435 breast cancer cell line to study the role of the two main LMW-PTP isoforms, fast and slow, in breast cancer tumorigenesis and migration. Our results show that the siRNAs directed against total LMW-PTP and LMW-PTP slow isoform enhanced cell motility in an invasive breast cancer cell line, MDA-MB-435, with no changes in the proliferation and invasive potential of cells. The total LMW-PTP knockdown caused a more pronounced increase of cell migration. Suppression of total LMW-PTP decreased RhoA activation and suppression of the LMW-PTP slow isoform caused a small but significant increase in RhoA activation. We propose that the increase or decrease in RhoA activation induces changes in stress fibers formation and consequently alter the adhesive and migratory potential of cells. These findings suggest that the two main isoforms of LMW-PTP may act differentially, with the fast isoform having a more prominent role in tumor cell migration. In addition, our results highlight functional specificity among LMW-PTP isoforms, suggesting hitherto unknown roles for these proteins in breast cancer biology. Novel therapeutic approaches targeting LMW-PTP, considering the expression of these two isoforms and not LMW-PTP as a whole, should be investigated. © 2013 Alho et al.

Alho I.,Cardiology Center | Alho I.,Institute Medicina Molecular | Costa L.,Institute Medicina Molecular | Costa L.,Hospital Of Santa Maria | And 2 more authors.
Tumor Biology | Year: 2013

Protein tyrosine phosphorylation is a crucial cellular event that is involved in the most important processes of cellular metabolism. Low-molecular-weight protein tyrosine phosphatase (LMW-PTP) is a tyrosine phosphatase that presents two active distinct isoforms and is regulated through cysteine oxidation and tyrosine phosphorylation. This enzyme has been linked to tumorigenesis, but its role is considered controversial: it may be considered oncogenic or anti-oncogenic depending on its interaction with different substrates. Furthermore, recent studies have demonstrated that LMW-PTP is involved in epithelial cell migration, a characteristic of tumor cells. This fact strengthens the importance of this enzyme in the oncogenic process and opens new avenues for future research. The study of LMW-PTP and its pathways may enhance therapeutic strategies that target tyrosine phosphorylation and its substrates. In this review, we try to clarify the importance of this protein in carcinogenesis through the analysis of LMW-PTP interaction with different substrates. © 2013 International Society of Oncology and BioMarkers (ISOBM).

Erne P.,University of Zürich | Erne P.,Cardiovasc Schweiz AG | Radovanovic D.,University of Zürich | Schoenenberger A.W.,University of Bern | And 4 more authors.
Journal of Hypertension | Year: 2015

Objective: The role of hypertension and its impact on outcome in patients with acute coronary syndrome (ACS) is still debated. This study aimed to compare the outcomes of hypertensive and nonhypertensive ACS patients. Methods: Using data of ACS patients enrolled in the Acute Myocardial Infarction in Switzerland Plus Registry from 1997 to 2013, characteristics at presentation and outcomes in hospital and after 1 year were analyzed. Hypertension was defined as previously diagnosed and treated by a physician. The primary endpoint was mortality. Data were analyzed using multiple logistic regressions. Results: Among 41 771 ACS patients, 16 855 (40.4%) were without and 24 916 (59.6%) with preexisting hypertension. Patients with preexisting hypertension had a more favorable in-hospital outcome [odds ratio (OR) inhospital mortality 0.82, 95% confidence interval (CI) 0.73-0.93; P=0.022]. The independent predictors of inhospital mortality for patients with preexisting hypertension were age, Killip class greater than 2, Charlson Comorbidity Index greater than 1, no pretreatment with statins and lower admission systemic blood pressure. Preexisting hypertension was not an independent predictor of 1-year mortality in the subgroup of patients (n=7801) followed: OR 1.07, 95% CI 0.78-1.47; P=0.68. Independent predictors of mortality 1 year after discharge for the 4796 patients with preexisting hypertension were age, male sex and comorbidities. Angiotensin-converting enzyme inhibitors or angiotensin II receptor antagonists and statins prescribed at discharge improved the outcomes. Conclusion: Outcome of ACS patients with preexisting hypertension was associated with an improved in-hospital prognosis after adjustment for their higher baseline risk. However, this effect was not long-lasting and does not necessarily mean a causal relationship exists. Short-term and long-term management of patients with hypertension admitted with ACS could be further improved. Copyright © 2015 Wolters Kluwer Health, Inc. All rights reserved.

Kovari B.,University of Szeged | Donko V.,University of Szeged | Piukovics K.,Cardiology Center
Lege Artis Medicinae | Year: 2016

INTRODUCTION - Myelofibrosis is a type of chronic myeloproliferative neoplasia frequently associated with extramedullary hematopoiesis. This latter process usually affects the spleen and the liver, and should be designated as nonhepatosplenic extramedullary hematopoiesis if it involves other organs. Nonhepatosplenic extramedullary hematopoiesis is reported to be more common in patients who had splenectomy. CASE REPORT - A 66-year-old woman with 5-year history of myelofibrosis was hospitalized eight month prior to death due to increasing abdominal effusion, abdominal discomfort and dyspnea. Three years before death, splenectomy was performed. The abdominal imaging studies disclosed a circumscribed tumorous mass in the pancreas, with enlargement of the peripancreatic lymph nodes. The lesion interpreted as pancreatic cancer progressed and the patient died. Post mortem histological evaluation confirmed the abdominal mass to represent myeloid metaplasia of the retroperitoneal fat tissue. CONCLUSIONS - Besides the possibility of a secondary primary tumor, the discovery of a novel mass lesion in patients with myelofibrosis should raise the suspicion of extramedullary hematopoiesis, especially when the patient had splenectomy.

PubMed | Mount Sinai School of Medicine, Sengupta Hospital and Research Institute, Cardiology Center and Medicity
Type: | Journal: The international journal of cardiovascular imaging | Year: 2016

The goal of this study was to evaluate the impact of pregnancy and labor on left ventricular (LV) myocardial mechanics using speckle tracking echocardiography (STE). Pregnancy is characterized by profound hormonal and hemodynamic alterations that directly or indirectly influence cardiac structure and function. However, the impact of these changes on left ventricular (LV) myocardial contractile function has not been fully elucidated. In this prospective, longitudinal study, 35 pregnant women underwent serial clinical and echocardiographic evaluation during each trimester and at labor. Two dimensional STE was performed to measure global LV longitudinal, circumferential and radial strain (GLS, GCS and GRS, respectively). Similar data obtained from 20 nulliparous, age-matched women were used as control. All strain values during pregnancy were adjusted for age and hemodynamic parameters. There was a progressive increase in heart rate, systolic and diastolic blood pressure, cardiac output and LV stroke-work during pregnancy. LV end-diastolic and end-systolic volumes also increased progressively but LV ejection fraction remained unaltered, except for slight reduction during the second trimester. Compared to the controls, GLS and GCS were reduced in the first trimester itself (GLS -22.395.43% vs. -18.660.64%, P 0.0002; GCS -20.843.20 vs. -17.880.09, P<0.001) and remained so throughout the pregnancy and labor. In contrast, GRS showed an increase during pregnancy which peaked during the second trimester (24.180.39% vs. 18.068.14% in controls, P<0.001). Alterations in loading conditions during pregnancy are associated with counterbalancing changes in the myocardial mechanics. LV longitudinal and circumferential strain are reduced whereas radial strain is increased. These counterbalancing changes serve to maintain overall LV ejection performance within a normal range and enable the maternal heart to meet the hemodynamic demands of pregnancy and labor.

ST elevation myocardial infarction (STEMI) patients treated by primary percutaneous coronary intervention (PCI) are at higher risk of acute kidney injury (AKI) than patients undergoing PCI in stable clinical conditions. This fact suggests that mechanisms other than contrast nephrotoxicity are involved.To evaluate the incidence, risk factors, and consequences of AKI in patients undergoing primary PCI for STEMI in current daily practice.Analysis of all consecutive patients who underwent primary PCI over a one-year period. AKI was defined as an increase in serum creatinine 50% or 26.5 mol/L (AKIN criteria) from the baseline within 48 h.A total of 202 patients were included. AKI occurred in 25 (12.4%) subjects. Baseline characteristics and in-hospital complications of the patients with and without AKI did not differ significantly except for age (69 13 vs. 62 12; p = 0.003), female gender (48.0% vs. 26.6%; p = 0.035), hypertension (88.0% vs. 62.7%; p = 0.013), left ventricular ejection fraction (40% 12% vs. 49% 14%; p = 0.002), cardiogenic shock (44.0% vs. 5.1%; p < 0.0001), use of intravenous diuretics (76.0% vs. 26.0%; p < 0.0001), ventricular arrhythmias (24.0% vs. 3.4%; p = 0.001), and in-hospital mortality (24.0% vs. 3.4%; p = 0.001). In multivariate analysis heart failure remained the only independent correlate of AKI.AKI was an frequent and serious complication of STEMI in patients treated by primary PCI. Heart failure was the strongest predictor of AKI. Other risk factors including contrast medium volume, baseline renal function, diabetes, and age failed to predict AKI.

PubMed | Hospital Of Santa Cruz, Azienda Ospedaliera Ordine Mauriziano, Interventional Cardiology, Policlinico S. Marco and 11 more.
Type: Comparative Study | Journal: JACC. Cardiovascular interventions | Year: 2016

This study sought to investigate the ischemic and bleeding outcomes of patients fulfilling high bleeding risk (HBR) criteria who were randomized to zotarolimus-eluting Endeavor Sprint stent (E-ZES) or bare-metal stent (BMS) implantation followed by an abbreviated dual antiplatelet therapy (DAPT) duration for stable or unstable coronary artery disease.DES instead of BMS use remains controversial in HBR patients, in whom long-term DAPT poses safety concerns.The ZEUS (Zotarolimus-Eluting Endeavor Sprint Stent in Uncertain DES Candidates) is a multinational, randomized single-blinded trial that randomized among others, in a stratified manner, 828 patients fulfilling pre-defined clinical or biochemical HBR criteria-including advanced age, indication to oral anticoagulants or other pro-hemorrhagic medications, history of bleeding and known anemia-to receive E-ZES or BMS followed by a protocol-mandated 30-day DAPT regimen. The primary endpoint of the study was the 12-month major adverse cardiovascular event rate, consisting of death, myocardial infarction, or target vessel revascularization.Compared with patients without, those with 1 or more HBR criteria had worse outcomes, owing to higher ischemic and bleeding risks. Among HBR patients, major adverse cardiovascular events occurred in 22.6% of the E-ZES and 29% of the BMS patients (hazard ratio: 0.75; 95% confidence interval: 0.57 to 0.98; p = 0.033), driven by lower myocardial infarction (3.5% vs. 10.4%; p < 0.001) and target vessel revascularization (5.9% vs. 11.4%; p = 0.005) rates in the E-ZES arm. The composite of definite or probable stent thrombosis was significantly reduced in E-ZES recipients, whereas bleeding events did not differ between stent groups.Among HBR patients with stable or unstable coronary artery disease, E-ZES implantation provides superior efficacy and safety as compared with conventional BMS. (Zotarolimus-Eluting Endeavor Sprint Stent in Uncertain DES Candidates [ZEUS]; NCT01385319).

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