Luigi Oltrona Visconti

Pretreatment with prasugrel in non-ST-segment elevation acute coronary syndromes.

BACKGROUND Although P2Y12 antagonists are effective in patients with non-ST-segment elevation (NSTE) acute coronary syndromes, the effect of the timing of administration--before or after coronary angiography--is not known. We evaluated the effect of administering the P2Y12 antagonist prasugrel at the time of diagnosis versus administering it after the coronary angiography if percutaneous coronary intervention (PCI) was indicated. METHODS We enrolled 4033 patients with NSTE acute coronary syndromes and a positive troponin level who were scheduled to undergo coronary angiography within 2 to 48 hours after randomization. Patients were randomly assigned to receive prasugrel (a 30-mg loading dose) before the angiography (pretreatment group) or placebo (control group). When PCI was indicated, an additional 30 mg of prasugrel was given in the pretreatment group at the time of PCI and 60 mg of prasugrel was given in the control group. RESULTS The rate of the primary efficacy end point, a composite of death from cardiovascular causes, myocardial infarction, stroke, urgent revascularization, or glycoprotein IIb/IIIa inhibitor rescue therapy (glycoprotein IIb/IIIa bailout) through day 7, did not differ significantly between the two groups (hazard ratio with pretreatment, 1.02; 95% confidence interval [CI], 0.84 to 1.25; P=0.81). The rate of the key safety end point of all Thrombolysis in Myocardial Infarction (TIMI) major bleeding episodes, whether related or not related to coronary-artery bypass grafting (CABG), through day 7 was increased with pretreatment (hazard ratio, 1.90; 95% CI, 1.19 to 3.02; P=0.006). The rates of TIMI major bleeding and life-threatening bleeding not related to CABG were increased by a factor of 3 and 6, respectively. Pretreatment did not reduce the rate of the primary outcome among patients undergoing PCI (69% of the patients) but increased the rate of TIMI major bleeding at 7 days. All the results were confirmed at 30 days and in prespecified subgroups. CONCLUSIONS Among patients with NSTE acute coronary syndromes who were scheduled to undergo catheterization, pretreatment with prasugrel did not reduce the rate of major ischemic events up to 30 days but increased the rate of major bleeding complications. (Funded by Daiichi Sankyo and Eli Lilly; ACCOAST ClinicalTrials.gov number, NCT01015287.).

Remote ischemic post-conditioning of the lower limb during primary percutaneous coronary intervention safely reduces enzymatic infarct size in anterior myocardial infarction: A randomized controlled trial

OBJECTIVES This study sought to evaluate whether remote ischemic post-conditioning (RIPC) could reduce enzymatic infarct size in patients with anterior ST-segment elevation myocardial infarction undergoing primary percutaneous coronary intervention (pPCI). BACKGROUND Myocardial reperfusion injury may attenuate the benefit of pPCI. In animal models, RIPC mitigates myocardial reperfusion injury. METHODS One hundred patients with anterior ST-segment elevation myocardial infarction and occluded left anterior descending artery were randomized to pPCI + RIPC (n = 50) or conventional pPCI (n = 50). RIPC consisted of 3 cycles of 5 min/5 min ischemia/reperfusion by cuff inflation/deflation of the lower limb. The primary endpoint was infarct size assessed by the area under the curve of creatinine kinase-myocardial band release (CK-MB). Secondary endpoints included the following: infarct size assessed by cardiac magnetic resonance delayed enhancement volume; T2-weighted edema volume; ST-segment resolution >50%; TIMI (Thrombolysis In Myocardial Infarction) frame count; and myocardial blush grading. RESULTS Four patients (2 RIPC, 2 controls) were excluded due to missing samples of CK-MB. A total of 96 patients were analyzed; median area under the curve CK-MB was 8,814 (interquartile range [IQR]: 5,567 to 11,325) arbitrary units in the RIPC group and 10,065 (IQR: 7,465 to 14,004) arbitrary units in control subjects (relative reduction: 20%, 95% confidence interval: 0.2% to 28.7%; p = 0.043). Seventy-seven patients underwent a cardiac magnetic resonance scan 3 to 5 days after randomization, and 66 patients repeated a second scan after 4 months. T2-weighted edema volume was 37 ± 16 cc in RIPC patients and 47 ± 22 cc in control subjects (p = 0.049). ST-segment resolution >50% was 66% in RIPC and 37% in control subjects (p = 0.015). We observed no significant differences in TIMI frame count, myocardial blush grading, and delayed enhancement volume. CONCLUSIONS In patients with anterior ST-segment elevation myocardial infarction, RIPC at the time of pPCI reduced enzymatic infarct size and was also associated with an improvement of T2-weighted edema volume and ST-segment resolution >50%. (Remote Postconditioning in Patients With Acute Myocardial Infarction Treated by Primary Percutaneous Coronary Intervention [PCI] [RemPostCon]; NCT00865722).

Clinical and prognostic relevance of echocardiographic evaluation of right ventricular geometry in patients with idiopathic pulmonary arterial hypertension.

The aim of the present study was to assess the clinical and prognostic significance of right ventricular (RV) dilation and RV hypertrophy at echocardiography in patients with idiopathic pulmonary arterial hypertension. Echocardiography and right heart catheterization were performed in 72 consecutive patients with idiopathic pulmonary arterial hypertension admitted to our institution. The median follow-up period was 38 months. The patients were grouped according to the median value of RV wall thickness (6.6 mm) and the median value of the RV diameter (36.5 mm). On multivariate analysis, the mean pulmonary artery pressure (p = 0.018) was the only independent predictor of RV wall thickness, and age (p = 0.011) and moderate to severe tricuspid regurgitation (p = 0.027) were the independent predictors of RV diameter. During follow-up, 22 patients died. The death rate was greater in the patients with a RV diameter >36.5 mm than in patients with a RV diameter ≤36.5 mm: 15.9 (95% confidence interval 9.4 to 26.8) vs 6.6 (95% confidence interval 3.3 to 13.2) events per 100-person years (p = 0.0442). In contrast, the death rate was similar in patients with RV wall thickness above or below the median value. However, among the patients with a RV wall thickness >6.6 mm, a RV diameter >36 mm was not associated with a poorer prognosis (p = 0.6837). In conclusion, in patients with idiopathic pulmonary arterial hypertension, a larger RV diameter is a marker of a poor prognosis but a greater RV wall thickness reduces the risk of death associated with a dilated right ventricle.

Long-term follow-up of Tako-Tsubo-like syndrome: a retrospective study of 22 cases.

Objectives To assess the late outcome of the Tako-Tsubo like syndrome in a community hospital in northern Italy. Methods and results We reviewed 2233 patients who were admitted from 2001 to 2006 with diagnosis of acute coronary syndrome. Twenty-two patients (1%) presenting clinical and instrumental characteristics of Tako-Tsubo like syndrome were included in the study and prospectively underwent clinical and echocardiographic follow-up. All patients were women; aged 76 ± 7 years; 82% experienced a stress before the acute episode; 50% reported chest pain and dyspnoea also days before. Mean troponin peak value was 3.6 ± 3.3 μg/l. Mean acute echocardiographic ejection fraction was 40 ± 7%. Eighteen percent of them presented major in-hospital complications. At a mean follow-up time of 27 ± 19 months, 2 patients (9%) died because of ischemic stroke and renal failure, respectively, 14 (63%) were asymptomatic, 1 (5%) declared a paroxysmal episode of atrial fibrillation, and 5 (23%) still lamented dyspnoea or atypical chest pain. In all patients, typical apical ballooning disappeared and an increase in mean ejection fraction to 60 ± 4% was observed. Conclusion After complications are promptly recognized and treated in the acute phase, prognosis of Tako-Tsubo like syndrome appears to be good at long-term follow-up, with a complete recovery of normal left ventricular function.

Epidemiology and patterns of care of patients admitted to Italian Intensive Cardiac Care units: the BLITZ-3 registry.

Background Intensive cardiac care units (ICCUs) have shifted from the observation of patients with myocardial infarction to the care of different acute cardiac diseases. However, few data on such an evolution are available. Methods and results From 7 to 20 April 2008, 6986 consecutive patients admitted to 81% of Italian ICCUs were prospectively enrolled. Patients observed were mainly elderly men (median age 72 years) with several co-morbidities. Most of them were triaged to ICCU from the emergency room, but 15% of admissions were transfer-in from other hospitals. Several diagnostic and therapeutic procedures were applied (78% had echocardiography and 35% coronary angiography) during the ICCU stay [median length 4 days, interquartile range (IQR) 2–5]. The discharge diagnosis was ST-elevation acute coronary syndrome (ACS) in 21%, non-ST-elevation ACS in 31%, acute heart failure (AHF) in 14% and other acute non-ACS, non-AHF cardiac diseases in 34%. Of those with ST-elevation ACS, 60% received reperfusion (15% fibrinolysis and 45% primary percutaneous coronary intervention). The overall in-ICCU crude mortality was 3.3%. Conclusion The BLITZ-3 survey provides a unique snapshot of current epidemiology and patterns of care of patients admitted to ICCUs. Although ACS still remains the most frequent admission diagnosis, the number of non-ACS patients is substantial. However, the correct standard of care for these non-ACS patients has to be defined.

Regional abnormalities of myocardial deformation in patients with hypertrophic cardiomyopathy: correlations with delayed enhancement in cardiac magnetic resonance

Hypertrophic cardiomyopathy (HCM) is a genetic disease histologically characterized by a profound disarray of myocardial fibres and by local fibrosis. We sought to characterize regional left ventricular contractility in HCM patients using deformation analysis and to compare it with the presence or absence of delayed enhancement in cardiac magnetic resonance (CMR).

Positive trend in survival to hospital discharge after out-of-hospital cardiac arrest: a quantitative review of the literature

Background Seven editions of cardiopulmonary resuscitation (CPR) and emergency cardiovascular care guidelines have been published with many changes, in particular, about CPR. Objectives The aim of our study was to evaluate the temporal trend of survival to hospital discharge after out-of-hospital cardiac arrest (OHCA) as a possible effect of guidelines changes. Methods We searched PubMed for observational studies on ‘survival to hospital discharge after OHCA’. Survival to discharge was the primary outcome; prehospital return of spontaneous circulation and survival to hospital admission were our secondary endpoints. All data were analyzed according to the year of inclusion: group 1 before 2000; group 2 between 2000 and 2005; and group 3 after 2005. Mortality rates were compared between groups by means of a group frequency-weighted log-linear model. Results We considered 38 of 201 studies for a total of 156 301 patients. Survival to hospital discharge rate was 5.0% [95% confidence interval (CI) 4.9–5.2) in group 1; 6.1% (95% CI 5.9–6.4) in group 2; and 9.1% (95% CI 8.9–9.4) in group 3 (P < 0.001). A statistically significant decrease in risk of mortality in group 2 vs. group 1 (risk ratio 0.988, 95% CI 0. 985–0.0.992, P < 0.001) and in group 3 vs. group 2 (risk ratio 0.967, 95% CI 0.964–0.971, P < 0.001) was observed. Similar trends were observed for return of spontaneous circulation and survival to hospital admission. Conclusion Survival to hospital discharge after OHCA has significantly improved. Many aspects may influence survival, but surely, the reduction of time and an early and good quality CPR have positively influenced the outcome.

Management of patients with acute coronary syndromes in real-world practice in Italy: an outcome research study focused on the use of ANTithRombotic Agents: the MANTRA registry

Background: Although outcomes of acute coronary syndromes (ACS) have greatly improved, bleeding is still an issue. Thus, this study aims to evaluate in-hospital management and outcomes of unselected patients with ACS focusing on antithrombotic therapies and bleeding. Methods and results: From 22 April 2009 to 29 December 2010, 6394 consecutive Italian patients were prospectively enrolled and followed for 6 months. Most patients (55.3%) had non-ST-elevation (NSTE) ACS. Of the ST-elevation (STE) ACS patients, 79.8% received reperfusion (mainly mechanical). In-hospital and 6-month unadjusted total mortality rates were 4.2 and 7.8% for STE-ACS and 2.5 and 6.4% for NSTE-ACS, respectively. During hospitalization, TIMI major bleeding rate was 1.2% (1.4% STE-ACS and 1.1% NSTE-ACS, respectively) and TIMI minor bleeding was 3.1%. In-hospital and 6-month unadjusted total mortality rates were 3.1 and 6.7% for patients without bleeding, 1.5 and 8.6% for minor bleeding, and 19.0 and 26.6% for TIMI major bleeding, respectively (p<0.0001). Notably, TIMI major bleeding was one of the strongest predictors of the 6-month composite end point (death or reinfarction) (STE-ACS hazard ratio, HR, 2.86, 95% confidence interval, 95% CI, 1.57−5.23; NSTE-ACS HR, 2.71, 95% CI 1.52−4.80). Predictors of in-hospital TIMI major bleeding were weight (odds ratio, OR, 0.97, 95% CI 0.95−0.99), female gender (OR 1.80, 95% CI 1.09−2.96), history of peripheral vasculopathy (OR 2.95, 95% CI 1.83−4.78), switching anticoagulant therapy (OR 2.62, 95% CI 1.36−5.05), intra-aortic balloon pump implantation (OR 4.44, 95% CI 1.85−10.69), and creatinine ≥2 mg/dl on admission (OR 3.68, 95% CI 1.84−7.33). Conclusions: Despite aggressive management, the rate of bleeding remains relatively low in an unselected ACS population. However, major bleeding adversely affects prognosis and physicians should tailor treatments to reduce it.

Remote ischemic postconditioning as a strategy to reduce acute kidney injury during primary PCI: A post-hoc analysis of a randomized trial ☆

Remote ischemic postconditioning as a strategy to reduce acute kidney injury during primary PCI: A post-hoc analysis of a randomized trial☆ Gabriele Crimi ⁎, Marco Ferlini , Fabio Gallo , Maria Pia Sormani , Claudia Raineri , Ezio Bramucci , Gaetano M. De Ferrari , Silvia Pica , Barbara Marinoni , Alessandra Repetto , Arturo Raisaro , Sergio Leonardi , Paolo Rubartelli , Luigi Oltrona Visconti , Maurizio Ferrario a

Pulmonary arterial compliance and exercise capacity after pulmonary endarterectomy.

Patients with chronic thromboembolic pulmonary hypertension (CTEPH), despite successful pulmonary endarterectomy (PEA), can continue to suffer from a limitation in exercise capacity. The objective of this study was to assess whether pulmonary arterial compliance is a predictor of exercise capacity after PEA. Right heart haemodynamics, treadmill incremental exercise test, spirometry, carbon monoxide transfer factor, arterial blood gas and echocardiographic examinations were retrospectively analysed in a population of CTEPH patients who underwent PEA at a single centre. Baseline and 3-month haemodynamic data were available in 296 patients; 5-year follow-up data were available in 68 patients. In a multivariable model the following parameters were found to be independent predictors of exercise capacity after surgery: age, sex, pulmonary arterial compliance, tricuspid annular plane excursion, arterial oxygen tension and carbon monoxide transfer factor (p<0.0001); the model showed good discrimination (Harrell’s c=0.84) and calibration (shrinkage coefficient=0.91). Poor exercise capacity at 3 months was loosely associated with higher death rate during subsequent survival (Harrell’s c=0.61). In conclusion, after successful PEA, reduced pulmonary arterial compliance is an important determinant of exercise capacity in association with the age and sex of the patients, and the extent of recovery of both cardiac and respiratory function. However, exercise capacity does not explain a large proportion of the effect of surgery on subsequent survival. Pulmonary arterial compliance is an important determinant of exercise capacity after pulmonary endarterectomy http://ow.ly/rDj1B