[show abstract][hide abstract] ABSTRACT: 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).
Myocardial reperfusion injury may attenuate the benefit of pPCI. In animal models, RIPC mitigates myocardial reperfusion injury.
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.
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.
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).
[show abstract][hide abstract] ABSTRACT: Visceral artery pseudoaneurysms (PA) are a rare complication of abdominal surgery. Their natural history is generally unknown and unpredictable, so a repair is recommended. We report the case of a 77-year-old male with a huge PA of the hepatic artery diagnosed by computed tomography (CT) and treated successfully with percutaneous exclusion using a pericardium-covered stent. A staged CT confirmed the good result of the procedure.
Journal of Cardiovascular Medicine 04/2012; · 2.66 Impact Factor
[show abstract][hide abstract] ABSTRACT: Aim Conflicting evidence exists as to whether the mitral E/E' ratio can be a reliable predictor of the left ventricular end-diastolic pressure (LVEDP). Our aim was to assess the value of the mitral E/E' ratio for the estimation of left ventricular diastolic pressures (LVDP) in patients without heart failure (HF). METHODS AND RESULTS: Echo-Doppler examination and left heart catheterization were carried out in 100 consecutive patients to assess the correlation between echo-Doppler parameters and the LVDP. The E/A ratio showed the best correlation with the pre-a LVDP and the LVEDP, whereas septal and mean E/E' ratios were significantly correlated with pre-a LVDP but not with the LVEDP. No difference in the echo-Doppler parameters was found between patients with normal and elevated LVEDP. Mitral E/E' ratio was significantly higher in patients with an ejection fraction (EF) <50% compared with those with the EF ≥ 50% and in patients with a dilated left ventricular (LV) compared with those with a normal LV. No significant difference in mean LVEDP was found among the three groups with E/E' ratios of <8, 8-15, and >15. The best cut-off values identified by receiver operating characteristic curve analysis for septal, lateral, and mean E/E' had sensitivities of 53, 68, and 54% and specificities of 66, 51, and 69% for identifying a >15 mmHg LVEDP. CONCLUSION: In patients without HF mitral E/E' ratio is influenced by EF and LV volumes and is better correlated with the pre-a LVDP than with the LVEDP. The suboptimal sensitivity and specificity of E/E' for predicting increased LVDP suggest that the mitral E/E' ratio is of limited clinical value in patients without HF.
European heart journal cardiovascular Imaging. 12/2011; 13(7):588-95.
[show abstract][hide abstract] ABSTRACT: The purpose of this study was to test whether the 9p21.3 variant rs1333040 influences the occurrence of new cardiovascular events and coronary atherosclerosis progression after early-onset myocardial infarction.
9p21.3 genetic variants are associated with ischemic heart disease, but it is not known whether they influence prognosis after an acute coronary event.
Within the Italian Genetic Study of Early-onset Myocardial Infarction, we genotyped rs1333040 in 1,508 patients hospitalized for a first myocardial infarction before the age of 45 years who underwent coronary angiography without index event coronary revascularization. They were followed up for major cardiovascular events and angiographic coronary atherosclerosis progression.
Over 16,599 person-years, there were 683 cardiovascular events and 492 primary endpoints: 77 cardiovascular deaths, 223 reoccurrences of myocardial infarction, and 383 coronary artery revascularizations. The rs1333040 genotype had a significant influence (p = 0.01) on the primary endpoint, with an adjusted hazard ratio of 1.19 (95% confidence interval [CI]: 1.08 to 1.37) for heterozygous carriers and 1.41 (95% CI: 1.06 to 1.87) for homozygous carriers. Analysis of the individual components of the primary endpoints provided no significant evidence that the rs1333040 genotype influenced the hazard of cardiovascular death (p = 0.24) or the reoccurrence of myocardial infarction (p = 0.57), but did provide significant evidence that it influenced on the hazard of coronary revascularization, with adjusted heterozygous and homozygous ratios of 1.38 (95% CI: 1.17 to 1.63) and 1.90 (95% CI: 1.36 to 2.65) (p = 0.00015), respectively. It also significantly influenced the angiographic endpoint of coronary atherosclerosis progression (p = 0.002).
In early-onset myocardial infarction, the 9p21.3 variant rs1333040 affects the progression of coronary atherosclerosis and the probability of coronary artery revascularization during long-term follow-up.
Journal of the American College of Cardiology 07/2011; 58(4):426-34. · 14.09 Impact Factor
[show abstract][hide abstract] ABSTRACT: An inherited predisposition is an important factor in the etiology of myocardial infarction (MI) at a young age. However, the extent of the risk for early-onset MI in relatives of young patients is still unclear, due to the paucity of family history data. Hence familial aggregation of early-onset MI was investigated in a cohort of relatives of Italian patients who had survived MI who occurred at the age of 45 or earlier.
In the framework of a case-control study, lifetime data and early-onset MI status for 11,696 relatives of cases and 8897 relatives of controls were collected using a standardized questionnaire.
Occurrence of early-onset MI in females was very uncommon (Kaplan-Meier risk=0.6%, 95% confidence interval (CI): 0.38-0.82%, for female case relatives), and significantly lower than that for male case relatives (5.0%, 95% CI: 4.41-5.56%). The hazard ratio (HR) for case relatives was approximately 3-fold greater than that for control aunts (taken as reference category). Risk for early-onset MI to siblings (HR=1.7, 95% CI: 1.33-2.18) was significantly different from that to parents (HR=0.9, 95% CI: 0.71-1.16). The familial risk ratio λ(R) was 2.6 (95% CI: 2.30-2.89) for case relatives, using control parents as reference population for early-onset MI risk estimates (i.e. 37 per 100,000 in fathers and 7 per 100,000 in mothers).
We evaluated the risk of early-onset MI by category of relatives, obtaining evidence for familial aggregation of the disease in this Italian sample and providing figures for genetic counselling and planning genetic epidemiological studies.
European Journal of Internal Medicine 12/2010; 21(6):511-5. · 2.05 Impact Factor
[show abstract][hide abstract] ABSTRACT: Mortality and morbidity after acute myocardial infarction (AMI) remain high even when myocardial reperfusion is successful. Erythropoietin (EPO) protects against experimental MI.
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.
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.
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.
International journal of cardiology 11/2009; 147(1):124-31. · 7.08 Impact Factor
[show abstract][hide abstract] ABSTRACT: We conducted a genome-wide association study testing single nucleotide polymorphisms (SNPs) and copy number variants (CNVs) for association with early-onset myocardial infarction in 2,967 cases and 3,075 controls. We carried out replication in an independent sample with an effective sample size of up to 19,492. SNPs at nine loci reached genome-wide significance: three are newly identified (21q22 near
[show abstract][hide abstract] ABSTRACT: We conducted a genome-wide association study testing single nucleotide polymorphisms (SNPs) and copy number variants (CNVs) for association with early-onset myocardial infarction in 2,967 cases and 3,075 controls. We carried out replication in an independent sample with an effective sample size of up to 19,492. SNPs at nine loci reached genome-wide significance: three are newly identified (21q22 near MRPS6-SLC5A3-KCNE2, 6p24 in PHACTR1 and 2q33 in WDR12) and six replicated prior observations (9p21, 1p13 near CELSR2-PSRC1-SORT1, 10q11 near CXCL12, 1q41 in MIA3, 19p13 near LDLR and 1p32 near PCSK9). We tested 554 common copy number polymorphisms (>1% allele frequency) and none met the pre-specified threshold for replication (P < 10(-3)). We identified 8,065 rare CNVs but did not detect a greater CNV burden in cases compared to controls, in genes compared to the genome as a whole, or at any individual locus. SNPs at nine loci were reproducibly associated with myocardial infarction, but tests of common and rare CNVs failed to identify additional associations with myocardial infarction risk.
[show abstract][hide abstract] ABSTRACT: The aim of this study was to assess the correlation between non invasive echo-Doppler parameters of diastolic function and invasively measured end-diastolic left ventricular (LV) filling pressures in patients with normal or depressed LV function.
The patient population was composed of 44 subjects, (34 men and 10 women) 52% with normal ventricular function, who underwent echo-Doppler and hemodynamic evaluation within 24 hours between the two exams.
LV end-diastolic pressure was statistically different (P=0.022) in the 4 subgroups divided on the basis of the mitral flow pattern in the overall population and in the patients with depressed LV function, but not in those with normal LV function. In the overall population LV end-diastolic pressure was significantly correlated with: 1) E/A ratio of mitral flow (r=0.45, P=0.002); 2) mitral E wave peak velocity (r=0.39, P=0.017); 3) isovolumic relaxation time (r=-0.34, P=0.01); 4) left atrial diameter (r=0.33, P=0.037); 5) duration of retrograde A wave of pulmonary venous flow (r=0.33, P=0.03); 6) Pulmonary vein D wave peak velocity (r=0.29, P=0,05). Multivariate analysis showed that the correlation between the echo-Doppler variables and LV end-diastolic pressure was statistically significant only in patients with depressed LV function, but not in those with normal function.
Among the echo-Doppler variables examined, those derived from transmitral flow and pulmonary vein flow show the best correlation with left ventricular end-diastolic pressure; however, the correlation is statistically significant only in patients with depressed LV function. Thus, the echo-Doppler evaluation of LV diastolic function should take into account this limitation and should be based on a multiparametric approach.
[show abstract][hide abstract] ABSTRACT: 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).
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.
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.
This study confirms the feasibility, safety and effectiveness of using SESs to treat ISR, and identifies a risk profile for recurrent ISR and MACE.
Journal of Cardiovascular Medicine 10/2007; 8(9):699-705. · 2.66 Impact Factor
[show abstract][hide abstract] ABSTRACT: We studied plasma erythropoietin (EPO) levels and their relation with CD34(+)VEGFR-2(+) (mature and progenitor endothelial cells) and CD34(+) CD133(+)VEGFR-2(+), or CD34(+) CD117(+)VEGFR-2(+) (early/immature endothelial progenitors) cells in patients with acute myocardial infarction (AMI).
Fifty AMI patients undergoing percutaneous coronary intervention (PCI) within 6 h of symptom onset were enrolled. EPO, measured by ELISA, and cell subsets, by cytofluorimetric analysis, were evaluated before PCI, 24 h and 7 days afterwards. Forty-five healthy subjects (CTRLs) were studied. Plasma EPO levels were higher in AMI patients at admission, 24 h, and 7 days (P = 0.04, P = 0.0001, P = 0.001, respectively) than in CTRLs. No correlation was evidenced between EPO and haemoglobin (Hb) or haematocrit at admission or 24 h after AMI. Differently, both Hb and haematocrit inversely correlated with EPO at day 7 (P = 0.0016, P = 0.029, respectively). Plasma EPO levels correlated with CD34(+)CD133(+)VEGFR-2(+) cells at day 7 (P = 0.03).
AMI patients have increased plasma EPO levels until day 7. In the early phase, plasma EPO levels are Hb-independent; at day 7, an Hb-modulated increase of EPO correlates with the percentage of CD34(+)CD133(+)VEGFR-2(+) cells.
European Heart Journal 09/2007; 28(15):1805-13. · 14.10 Impact Factor
[show abstract][hide abstract] ABSTRACT: The original aim of atherectomy was to reduce restenosis by means of aggressive plaque debulking, and the failure of large randomized trials to show any advantage of atherectomy over balloon angioplasty restricted its wider application. However, single-center registries in which aggressive debulking was performed by experienced operators have reported favorable results in terms of reduced restenosis and improved clinical outcomes when atherectomy was performed before stenting. Plaque debulking reduces the potential for plaque shift and facilitates subsequent high-pressure stent expansion, smoothes the internal vessel surface, scaffolds intimal flaps, and prevents elastic recoil. It has also been demonstrated that atherectomy can play a role in the treatment of complex lesions (ostial left anterior descending coronary artery lesions, left main lesions, and bifurcations), in which plaque shift may compromise the result of the procedure. New-generation devices have shown that atherectomy can be safely and effectively used to treat even relatively small vessels. In the current era of drug-eluting stents characterized by a considerable reduction in restenosis rates, optimal stent geometry and final luminal diameter are still important predictors of restenosis. Given the possible role of plaque shifting at the edges of a stent in causing restenosis, debulking could be added to the local drug effect in complex lesions.
Italian heart journal: official journal of the Italian Federation of Cardiology 07/2005; 6(6):494-7.
[show abstract][hide abstract] ABSTRACT: The aim of this study was to compare the short- (< 30 days) and long-term (> or = 30 days) clinical outcomes of left internal mammary artery bypass grafting (LIMA-LAD) and directional coronary atherectomy plus stent implantation (DCA + stent) in the treatment of isolated proximal left anterior descending coronary (LAD) lesions. One hundred and twenty-six patients underwent LIMA-LAD and 132 consecutive patients underwent DCA + stenting. The primary endpoint was the incidence of short- and long-term major adverse cardiac events (MACE); the secondary endpoints included any periprocedural events and long-term target vessel revascularization (TVR). We found no significant between-treatment difference in the occurrence of short-term MACE, and the long-term MACE rate per 100 person-years was 3.0 in the LIMA-LAD group and 4.6 in the DCA + stent group. After 5-year follow-up, 79% of the patients in the DCA + stent group and 89% of those in the LIMA-LAD group were still MACE-free. The risk of any periprocedural events was six times lower in the DCA + stent group, and the risk of TVR was six times higher. We conclude that both procedures lead to good short- and long-term follow-up results in isolated proximal LAD disease. As fewer periprocedural events and more TVRs occur after DCA + stenting than after LIMA-LAD, they can be considered valuable alternatives to each other.
Catheterization and Cardiovascular Interventions 02/2005; 64(1):45-52. · 2.51 Impact Factor
[show abstract][hide abstract] ABSTRACT: Endothelial progenitor cell (EPC) mobilization has been reported following tissue damage, whereas no data are available regarding the mobilization of hematopoietic progenitor cells (HPCs). We performed the phenotypic and functional analysis of circulating CD34+ progenitor cells in patients with acute myocardial infarction (AMI), assessed from admission up to 60 days, in patients with stable angina pectoris (SA), and in healthy controls (CTRLs). In patients with AMI at admission (T0), the number of circulating CD34+ cells was higher (P < .001) than in CTRLs and became comparable with CTRLs within 60 days. Both the number of CD34+ cells coexpressing CD33, CD38, or CD117 and the number of HPCs was higher (P < .02 for all) in patients with AMI at T0 than in CTRLs, as was the number of hematopoietic colonies (P < .03). Patients with AMI (T0) had a significantly increased number of CD34+ vascular endothelial growth factor receptor 2-positive (VEGFR-2+) cells (P < .002) with respect to CTRLs, including CD34(+) CD133(+)VEGFR-2+ and CD34+ CD117(+)VEGFR-2+ EPCs. The number of endothelial colonies was higher in patients with AMI (T0) than in CTRLs (P < .05). No significant difference was documented between patients with SA and CTRLs. Spontaneous mobilization of both HPCs and EPCs occurs within a few hours from the onset of AMI and is detectable until 2 months.
[show abstract][hide abstract] ABSTRACT: The D allele of the insertion/deletion (I/D) polymorphism of the angiotensin I-converting enzyme (ACE) gene is associated with higher plasma and tissue ACE levels, which enhance the stimulus for neo-intimal hyperplasia. Plaque debulking before stenting reduces the plaque-related determinants of in-stent restenosis and provides an ideal clinical model for studying neointimal hyperplasia. We prospectively studied 113 consecutive patients undergoing elective DCA followed by stent implantation. The presence of I/D in ACE genome DNA was analysed by means of polymerase chain reaction. Follow-up coronary angiography was performed 6-12 months after DCA, and all of the angiograms were quantitatively analysed. The baseline clinical and angiographic characteristics of the patients with a D/D (33%), I/D (52%) and I/I (15%) genotype were well balanced. There were no significant differences in minimal lumen diameter before and after the procedure or at follow-up, and no significant differences in acute gain, late loss or the loss index. Our results indicate that ACE I/D polymorphism does not influence the risk of developing angiographic restenosis in patients undergoing DCA followed by stent implantation.
Thrombosis and Haemostasis 05/2004; 91(4):795-800. · 6.09 Impact Factor
[show abstract][hide abstract] ABSTRACT: The aim of this study was to evaluate the acute and long-term angiographic and clinical results of optimal plaque debulking by means of directional coronary atherectomy (DCA) followed by stent implantation for treatment of left anterior descending (LAD) ostial stenosis. Eighty consecutive patients (66 men; aged 57 +/- 10 years) with angina pectoris, documented anterior myocardial ischemia, and de novo LAD ostial stenosis prospectively underwent DCA and stent deployment. They were evaluated angiographically after 6 months and clinically for up to 30 +/- 29 months. The primary success rate was 98%. The in-hospital complications were 1 death due to in-stent subacute thrombosis 7 days after the procedure, 1 non-Q-wave myocardial infarction, and 1 retrograde left main artery dissection. The angiographic binary restenosis rate was 14.5%, and the loss index was 0.38 +/- 0.35. The target lesion revascularization (TLR) rates at 6, 12, and 24 months were 6.0%, 14.5%, and 16.3%, respectively, and the combined event rates (death, nonfatal myocardial infarction, TLR) at the same times were 8.7%, 17.5%, and 21.2%, respectively. These results indicate that the combined approach of DCA and stent implantation is feasible and safe in patients with LAD ostial lesions, has a high success rate, a low incidence of restenosis, and a good long-term outcome.
The American Journal of Cardiology 12/2002; 90(10):1074-8. · 3.21 Impact Factor