Sex-Related Differences in Long-Term Outcomes After Early-Onset Myocardial Infarction.

Importance: There is growing awareness of sex-related differences in cardiovascular risk profiles, but less is known about whether these extend to pre-menopausal females experiencing an early-onset myocardial infarction (MI), who may benefit from the protective effects of estrogen exposure. Methods: A nationwide study involving 125 Italian Coronary Care Units recruited 2,000 patients between 1998 and 2002 hospitalized for a type I myocardial infarction before the age of 45 years (male, n = 1,778 (88.9%). Patients were followed up for a median of 19.9 years (IQR 18.1-22.6). The primary composite endpoint was the occurrence of cardiovascular death, non-fatal myocardial re-infarction or non-fatal stroke, and the secondary endpoint of hospitalization for revascularisation by means of a percutaneous coronary intervention (PCI) or coronary artery bypass surgery (CABG). Results: ST-elevation MI was the most frequent presentation among both men and women (85.1 vs. 87.4%, p = ns), but the men had a greater baseline coronary atherosclerotic burden (median Duke Coronary Artery Disease Index: 48 vs. 23; median Syntax score 9 vs. 7; both p < 0.001). The primary composite endpoint occurred less frequently among women (25.7% vs. 37.0%; adjusted hazard ratio: 0.69, 95% CI 0.52-0.91; p = 0.01) despite being less likely to receive treatment with most secondary prevention medications during follow up. Conclusions: There are significant sex-related differences in baseline risk factors and outcomes among patients with early-onset MI: women present with a lower atherosclerotic disease burden and, although they are less frequently prescribed secondary prevention measures, experience better long-term outcomes. Trial Registration: 4272/98 Ospedale Niguarda, Ca' Granda 03/09/1998.

Long-term outcomes of early-onset myocardial infarction with non-obstructive coronary artery disease (MINOCA).

BACKGROUND: Acute myocardial infarction with non-obstructive coronary artery disease (MINOCA) is frequent in patients experiencing an early-onset MI, but data concerning its long-term prognosis are limited and conflicting. METHODS: The Italian Genetic Study on Early-onset MI enrolled 2000 patients experiencing a first MI before the age of 45 years, and had a median follow-up of 19.9 years. The composite primary endpoint was cardiovascular (CV) death, non-fatal MI, and non-fatal stroke (MACE); the secondary endpoint was rehospitalisation for coronary revascularisation. RESULTS: MINOCA occurred in 317 patients (15.9%) and, during the follow-up, there was no significant difference in MACE rates between them and the patients with obstructive coronary artery disease (MICAD: 27.8% vs 37.5%; adjusted hazard ratio [HR] 0.79, 95% confidence interval [CI] 0.57-1.09;p = 0.15). The CV death rate was lower in the MINOCA group (4.2% vs 8.4%, HR 0.26, 95%CI 0.08-0.86;p = 0.03), whereas the rates of non-fatal reinfarction (17.3% vs 25.4%; HR 0.76, 95%CI 0.52-1.13;p = 0.18), non-fatal ischemic stroke (9.5% vs 3.7%; HR 1.79, 95%CI 0.87-3.70;p = 0.12), and all-cause mortality (14.1% vs 20.7%, HR 0.73, 95%CI 0.43-1.25;p = 0.26) were not significantly different in the two groups. The rate of rehospitalisation for coronary revascularisation was lower among the MINOCA patients (6.7% vs 27.7%; HR 0.27, 95% CI 0.15-0.47;p < 0.001). CONCLUSIONS: MINOCA is frequent and not benign in patients with early-onset MI. Although there is a lower likelihood of CV death,the long-term risk of MACE and overall mortality is not significantly different from that of MICAD patients.

Clinical outcomes of overlapping versus non-overlapping everolimus-eluting absorb bioresorbable vascular scaffolds: An analysis from the multicentre prospective RAI registry (ClinicalTrials.gov identifier: NCT02298413).

OBJECTIVES: To compare clinical outcomes of patients treated with overlapping versus non-overlapping Absorb BVS. BACKGROUND: Limited data are available on the clinical impact of stent overlap with the Absorb BVS bioresorbable stent. METHODS: We compared outcomes of patients receiving overlapping or non-overlapping Absorb BVS in the multicenter prospective RAI Registry. RESULTS: Out of 1,505 consecutive patients treated with Absorb BVS, 1,384 were eligible for this analysis. Of these, 377 (27%) were in the overlap group, and 1,007 (73%) in the non-overlap group. The most frequent overlap configuration was the marker-to-marker type (48%), followed by marker-over-marker (46%) and marker-inside-marker (6%) types. Patients of the overlap group had higher prevalence of multivessel disease and higher SYNTAX score, and required more frequently the use of intravascular imaging. At a median follow-up of 368 days, no difference was observed between overlap and non-overlap groups in terms of a device-related composite endpoint (cardiac death, TV-MI, ID-TLR) (5.8% vs. 4.1%, P = 0.20) or of a patient-related composite endpoint (any death, any MI, any revascularization) (15.4% vs. 12.5%, P = 0.18). Cardiac death (1.0% vs. 1.3%, P = 0.54), MI (4.5% vs. 3.6%, P = 0.51), TVR (4.5% vs. 3.6%, P = 0.51) and stent thrombosis (1.1 vs. 1.5%, P = 1.00) were also comparable between groups. When assessing outcomes of the overlap population according to overlap configurations used, no difference was observed in terms of the device- or patient-related composite endpoints. CONCLUSIONS: Outcomes of patients with or without overlapping BVS were comparable at mid-term follow-up despite higher angiographic complexity of the overlap subset. © 2017 Wiley Periodicals, Inc.

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.

Directional coronary atherectomy plus stent implantation vs. left internal mammary artery bypass grafting for isolated proximal stenosis of the left anterior descending coronary artery.

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.

Different quantitative apoptotic traits in coronary atherosclerotic plaques from patients with stable angina pectoris and acute coronary syndromes.

BACKGROUND: Apoptosis in human atherosclerotic coronary plaques possibly causes plaque destabilization by contributing to the weakening and breaking down of the fibrous cap. We tested the hypothesis that apoptosis is quantitatively increased in unstable atherosclerotic plaques. METHODS AND RESULTS: We analyzed the expression of apoptotic genes such as BAX, CASP1, FAS, FAS L, FOS, MDM2, NFkB2, P53, PCNA, TERT, and XRCC1 in coronary plaques collected with directional coronary atherectomy from 15 patients with stable angina and 15 with acute coronary syndromes without ST elevation (ACS). Total RNA was extracted and cDNA was amplified with a specific set of primers and TaqMan probes. Apoptosis was also revealed by DNA laddering. To clarify the source of mRNAs, we performed in situ reverse transcriptase-polymerase chain reaction coupled with immunocytochemistry and found a substantial overlap between the mRNAs of the above genes and vascular smooth muscle cells. Gene expression analysis showed that the proapoptotic genes (ie, BAX, CASP1, FAS, FAS L, FOS, NFkB2, P53, PCNA) were significantly more expressed (P<0.001) in ACS plaques, whereas the antiapoptotic genes (ie, MDM2, TERT, XRCC1) were more transcribed (P<0.001) in stable angina plaques. Total gDNA gel electrophoresis identified a laddering pattern in the ACS plaques as evidence of end-point apoptosis. Western blotting substantially confirmed the above data. CONCLUSIONS: Our findings support the idea that ACS plaques are committed to apoptosis through an established meshwork of gene activation and inactivation, whereas stable angina plaques retain active cell homeostasis and repair mechanisms.

Angiotensin-converting enzyme insertion/deletion polymorphism and risk of restenosis after directional coronary atherectomy followed by stent implantation.

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.

Activation of the contact system and inflammation after thrombolytic therapy in patients with acute myocardial infarction.

Thrombolytic therapy activates the contact system, and factor XII activation may activate the coagulation cascade and inflammation. It is not known whether an early inflammatory response is induced by thrombolytic therapy in patients with acute myocardial infarction (AMI). We prospectively measured the plasma levels of activated factor XII, cleaved kininogen, prothrombin fragment 1 + 2 (as indexes of the contact phase and coagulation activation), and interleukin-6 and C-reactive protein (CRP) (as indexes of inflammation) in 39 patients hospitalized for AMI within 12 hours of symptom onset: 26 receiving thrombolytic therapy and 13 heparin alone. Blood samples were collected at baseline and after 90 minutes and 24 hours. Patients undergoing thrombolysis had a significant early increase in activated factor XII (from 2.2 ng/ml at baseline to 4.7 ng/ml after 90 minutes; p = 0.0001), cleaved kininogen (from 26% to 37%; p = 0.001), and fragment 1 + 2 (from 1.4 to 2.1 nmol/L; p = 0.0001), whereas the 24-hour levels were similar to baseline levels. The levels of interleukin-6 significantly increased during the first 90 minutes (from 3.9 to 6.3 microg/ml; p = 0.001), and were even higher after 24 hours (11.9 ng/ml, p = 0.0001). CRP levels increased only after 24 hours (p = 0.0001). There were no changes in these parameters in patients receiving heparin alone, except for a 24-hour increase in interleukin-6 and CRP levels. Thus, in patients with AMI receiving thrombolytic therapy, early activation of inflammation parallels the activation of the contact system and the coagulation cascade, which might contribute to microvascular obstruction and reperfusion injury.

Dobutamine-induced ST-segment elevation associated with a biphasic response of wall motion in patients with a recent myocardial infarction is caused by myocardial ischaemia and is abolished by revascularization of the infarct-related artery.

OBJECTIVE: ST-segment elevation is frequently induced by dobutamine in patients with a recent myocardial infarction and may represent dyskinesia of the infarcted region or myocardial viability and ischaemia. Revascularization of the infarct-related artery may abolish myocardial ischaemia, and thus represents a useful tool to verify the significance of this finding. The aim of this study was to assess the relation between ST-segment elevation and wall motion response during dobutamine echo stress test and to evaluate the effect of coronary revascularization with percutaneous coronary angioplasty of the infarct-related artery on stress test results. METHODS AND RESULTS: Twenty-two patients (17 men; mean age 58+/-12 years) with a first acute myocardial infarction (5 anterior (23%) and 17 (77%) inferior) who showed ST-segment elevation during a dobutamine echo stress test performed early (7+/-5 days) after the acute event where included in the analysis. All patients underwent coronary arteriography followed by percutaneous revascularization with coronary angioplasty or atherectomy with or without stenting of the culprit lesion and a second dobutamine echo stress test at a mean of 40+/-20 days after revascularization. The minimal lumen diameter increased from 0.63+/-0.36 to 3+/-0.44 mm and % diameter stenosis decreased from 80+/-11 to 12+/-7 after revascularization. At baseline evaluation there were 62 normal moving segments (34%), 57 (32%) akinetic and 62 (34%) hypokinetic segments within the area at risk. Maximal ST-segment shift changed from a basal mean value of 0.41+/-0.6 to a peak value of 2.15+/-0.9 mm; angina developed in 6/22 patients (22%). A biphasic response to dobutamine indicative of myocardial ischaemia within the infarcted area was observed in 20/22 patients (91%) and in 54/74 (73%) segments showing wall motion abnormalities. After revascularization of the infarct-related artery 78 (43%) segments were considered to be normal, 46 (25%) akinetic and 57 (32%) hypokinetic. Dobutamine-induced ST-segment elevation in 6/22 cases (27%), but the amount of ST-segment shift at peak stress was significantly reduced (from 2.15+/-0.9 to 0.30+/-0.5 mm) and angina was present in 1 patient only (5%) despite a significant increase of double product compared to the pre-revascularization test (from 17,348+/-3536 to 21,005+/-4105, p < 0.003). At echocardiographic analysis, ischaemia involved only 4 segments (2%), 3 of them showing the persistence of a biphasic response to dobutamine. CONCLUSIONS: In patients with a recent myocardial infarction and no baseline dyskinesia dobutamine-induced ST-segment elevation in the infarct-related leads is usually associated with a biphasic response of wall motion within the infarcted region and may be considered an ancillary sign of myocardial ischaemia because it is abolished in the great majority of cases by successful revascularization of the infarct-related artery.

Effectiveness of adjunctive stent implantation following directional coronary atherectomy for treatment of left anterior descending ostial stenosis.

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.

ATPases enzyme activities during ageing in different types of somatic and synaptic plasma membranes from rat frontal cerebral cortex.

The catalytic properties of energy-utilizing ATPases enzyme systems related to ions homeostasis were evaluated in different types of synaptic plasma membranes (SPM) and in somatic plasma membranes (SM) from cerebral cortex of rats aged 5, 10, and 22 months. The following enzymes were evaluated: Na+, K+-ATPase, Ca2+, Mg2+-ATPase, Mg2+-ATPase and the activity of acetylcholine esterase (AChE) was also evaluated. The ATPases located on SM and SPM and synaptic vesicles are involved in the regulation of presynaptic nerve ending homeostasis and postsynaptic activities. Different types of SM and SPM (three types) were obtained by combinations of differential and density gradient ultracentrifugation techniques in sucrose-Ficoll media: the first was obtained by purification of the sediment of mitochondrial supernate and the second after synaptosomal lysis and purification on density gradient. In the cerebral cortex of 5-month-old rats, the catalytic properties of ATPases systems markedly differ according to the different types of SPM and SM, thus indicating that the metabolic role of each ATPase is determined by their subcellular in vivo localization. As regards ageing: (i) ATPase enzyme catalytic activities tend to decrease during ageing in a complex way; (ii) ageing induced specific modifications in individual ATPases according to their subsynaptic localization; and (iii) these effects are probably due to specific biochemical situations that take place at each age, reflecting the bioenergetic state of the cerebral tissue with respect to the energy demand. The cerebral concentration and content of SM proteins were increased by ageing suggesting that many defective noncatalytic proteins may be formed during ageing, as shown by immunoblotting techniques.