Marco Ferlini

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).

High-dose erythropoietin in patients with acute myocardial infarction: A pilot, randomised, placebo-controlled study

BACKGROUND Mortality and morbidity after acute myocardial infarction (AMI) remain high even when myocardial reperfusion is successful. Erythropoietin (EPO) protects against experimental MI. METHODS The aim of this single-centre study was to investigate the effects of short-term high-dose erythropoietin on peripheral blood cells (PBCs) and infarct size in 30 patients with a first uncomplicated AMI undergoing percutaneous coronary intervention (PCI) who were randomly assigned to treatment with EPO (33 × 10(3)IU before PCI, and 24 and 48 h after admission), or placebo. We considered short-term CD34+ cell mobilisation, quantitative PBC gene expression in the apoptotic, angiogenic and inflammatory pathways, and enzymatically estimated infarct size. Echocardiographic and cardiac magnetic resonance studies were performed in the acute phase and six months later. RESULTS CD34+ cell mobilisation 72 h after admission was greater in the EPO-treated patient group (93 cells/μl [36-217] vs 22 cells/μl [6-51]; p = 0.002), who also showed higher expression of the anti-apoptotic AKT and NFkB, the pro-angiogenic VEGFR-2, and the EPO-R genes, and lower expression of the pro-apoptotic CASP3 and TP53 and pro-inflammatory IL12a genes. Moreover, they showed smaller infarct size (30% reduction in CK-MB release; p = 0.025), and a favourable pattern of left ventricular remodelling. CONCLUSIONS Short-term high-dose EPO administration in patients with AMI treated by PCI and standard anti-platelet therapy increases the levels of circulating CD34+ cells, shifts PBC gene expression towards anti-apoptotic, pro-angiogenic and anti-inflammatory pathways, and decreases infarct size. The clinical relevance of these results needs to be confirmed in specifically tailored trials.

Myocardial infarction in the young: a sex-based comparison.

A relative paucity of information concerns the natural history, clinical features and coronary anatomy in young patients with acute myocardial infarction. In particular, there is a dearth of data relating to sex differences in young patients. The objective was to evaluate whether or not there are correlations between the clinical characteristics and the extent and localization of coronary artery lesions in young men compared with young women. The study population consisted of 1646 young patients (87% men, 13% women; mean age 39±5 years) with a first acute myocardial infarction admitted to one of the 125 coronary care units of Italy in a period of 3 years. Clinical data were collected. All patients underwent coronary angiography during hospitalization. Smoking, hypercholesterolemia and obesity were significantly more prevalent in men than in women; physical inactivity was significantly more prevalent among women. Hemodynamically significant coronary stenosis occurred in 82% of patients and were more frequent in men than in women (P<0.05). Women more frequently had single-vessel disease and no coronary lesions at all (58 vs. 47% and 24 vs. 9% women vs. men respectively, both P<0.05). Men more frequently had multivessel disease (38 vs. 13%, P<0.05). Significant stenosis mainly affected the left anterior descending artery (52%) with no gender-related difference; men more likely had lesions of the left circumflex or right coronary artery (P<0.05). In conclusion, young patients with a first acute myocardial infarction risk factors profile and extent of coronary artery lesions were significantly different between sexes.

Evaluating the safety of very short-term (10 days) dual antiplatelet therapy after Genous™ bio-engineered R stent™ implantation: the multicentre pilot Genous trial.

AIMS Percutaneous coronary stenting is synonymous with dual antiplatelet therapy, ranging from four weeks to lifelong. However, even short-term (four weeks) therapy with aspirin and thienopyridines is occasionally contraindicated. No study has ever appraised very short-term dual antiplatelet therapy after stenting. We thus aimed to exploit the pro-healing features of the Genous™ Bio-engineered R stent™ (Genous) (OrbusNeich Medical Technologies, Hong Kong, Peoples Republic of China) and evaluate the safety of a 10-day dual antiplatelet regimen after its implantation in up to 50 patients. METHODS AND RESULTS Forty-nine consecutive patients with de novo lesions located in vessels able to receive a 2.5 mm Genous stent were included. After stenting, they received lifelong aspirin plus clopidogrel for 10 days. The primary endpoint of the study was sudden cardiac death, myocardial infarction or angiographic evidence of stent thrombosis ascribable to the study stent. Almost 70% of patients effectively discontinued clopidogrel nine to 11 days after stenting. At three-month clinical follow-up, no patient had died or reached the primary endpoint (95%; confidence interval 0-7.3%). Repeat revascularisation occurred instead in three (6.1%[2.1-16.5%]), with target lesion revascularisation in two (4.1%[1.1-13.7%]). CONCLUSIONS Even very short-term dual antiplatelet therapy seems safe after coronary stenting with Genous in de novo coronary artery lesions located in secondary branch vessels. This preliminary exploratory study gives some support to planning a large trial to test the hypothesis of short dual antiplatelet therapy following Genous stent implantation.

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

Antiplatelet therapy and outcome in patients undergoing surgery following coronary stenting: Results of the surgery after stenting registry

The aim of the present study was to define the feasibility and clinical impact of complying with national consensus recommendations on perioperative management of antiplatelet therapy in patients with coronary stents undergoing cardiac and noncardiac surgery.

Flecainide as first-line treatment for supraventricular tachycardia in newborns.

Background Flecainide for the treatment of supraventricular tachycardia (SVT) in newborns is still controversial because of its potentially severe proarrhythmic effects. Methods and results Between January 2004 and December 2006, we used flecainide to treat 20 consecutive newborns (15 males) with paroxysmal SVT without any structural heart disease. Their age at hospitalization was 11.5 ± 11.1 days. The intravenous administration of flecainide (1 mg/kg) effectively restored sinus rhythm in all the patients. Once stable sinus rhythm had been restored, the drug was administered orally at a dose of 2 mg/kg/day twice daily, which was uptitrated as the patients gained weight. The patients were followed up for up to 24 months with clinical evaluations, baseline ECG and 24-h Holter monitoring every 3 months. There were neither deaths nor any episodes of heart failure or sustained ventricular tachycardia during follow-up. SVT were completely controlled in 17 patients (85%), with an oral dose of 3.35 ± 1.35 mg/kg/day of flecainide; in the remaining three patients with refractory arrhythmias, propranolol was added for optimal treatment. No significant increase in the duration of QRS (70 ± 1.09 vs. 63.8 ± 1.87 ms, P = NS) or any significant QTc prolongation (413 ± 7.4 vs. 412.6 ± 8.01 ms, P = NS) was observed. One patient developed an incomplete right bundle branch block promptly reverted by reducing the dose. Conclusion This preliminary experience indicates that flecainide is well tolerated and effective as first-line treatment for paroxysmal SVT in newborns without structural heart disease.

Percutaneous Coronary Aneurysm Obliteration Using a Novel Pericardium-Covered Stent

![Figure][1] ![Figure][1] [![Graphic][3] ][3] Baseline Angiography Selective angiography of right coronary artery showing the giant aneurysm. ![Figure][1] [![Graphic][4] ][4] Stent Implantation Deployment of the first covered stent. ![Figure][1] [![

Outcome of coronary lesions with deferred revascularization due to negative fractional flow reserve in subjects with acute coronary syndrome

OBJECTIVE Revascularization of functionally non-significant stenoses in patients with stable coronary artery disease can safely be deferred as rate of adverse cardiovascular events is low. It is not clear whether fractional flow reserve (FFR) is just as accurate in acute coronary syndromes (ACS). The aim of this study is to assess the outcome of coronary lesions whose revascularization was deferred based on negative FFR values in subjects with ACS. METHODS Patients with acute coronary syndrome and showing at least one coronary stenosis whose revascularization was deferred based on FFR value >0.80 were included in the study. The primary endpoint of the study was the rate of target lesion failure (TLF), a composite of cardiac events (cardiac death, myocardial infarction and any coronary revascularization) related to the initially deferred stenosis at three-year follow-up. RESULTS A total of 319 patients (237 male), mean age 68 [59-74] years and 355 coronary lesions with deferred revascularization based on negative FFR values (0.88±0.05) were selected. The rate of TLF was 6% at 1-year, 9% at 2-year and 12% at 3-year follow-up. TLF was driven by a new acute coronary syndrome in 75% of cases. The median time interval from FFR assessment to TLF was 457 [138-868] days. CONCLUSIONS In patients with acute coronary syndrome, the rate of TLF of the initially deferred coronary stenoses is 12% at 3-year follow-up and TLF occurred because of a new ACS in three quarters of cases.

Use of sirolimus-eluting stents for treatment of in-stent restenosis: long-term follow-up.

Objectives The aims of this study were to assess (i) the feasibility, safety and efficacy of sirolimus-eluting stents (SESs) in treating in-stent restenosis (ISR), (ii) the risk factors for recurrent ISR, and (iii) the long-term major adverse cardiac events (MACE). Methods Between May 2002 and April 2004, 100 consecutive patients with evidence of myocardial ischaemia and 112 ISRs in native coronary arteries were treated using SESs. We evaluated the rate of procedural and clinical success, the incidence of in-hospital and long-term MACE, the recurrence rate of ISR after 6–8 months, and the risk factors for recurrent ISR and follow-up MACE. Results Forty-five percent of the lesions were directly stented. After stent implantation, the minimal lumen diameter increased from 0.51 ± 0.32 to 2.50 ± 0.32 mm in the stents and to 2.30 ± 0.35 mm in the lesions (acute gain 1.99 ± 0.37 mm). The procedural success rate was 99%. The clinical success rate was 88%. MACE occurred in 2.0% of patients during hospitalisation and in 12.8% after a median follow-up of 15.1 months (interquartile range 8.4–19.7). The recurrence rate of ISR was 11.8% after a median follow-up of 7.7 months (interquartile range 7.4–8.4). The risk for recurrent ISR was significantly higher in patients with diabetes or hypertension, in those aged more than 65 years and in female patients, as well as in the lesions with a small minimal lumen diameter. Three-vessel disease and age were risk factors for MACE. Conclusions This study confirms the feasibility, safety and effectiveness of using SESs to treat ISR, and identifies a risk profile for recurrent ISR and MACE.