Luca Altamura

Ethanol Abolishes Ischemic Preconditioning in Humans

OBJECTIVES This study sought to assess the effect of acute alcohol intake on ischemic preconditioning (IPC) in humans using the clinical model of 2 sequential balloon inflations during a percutaneous coronary intervention (PCI). BACKGROUND Ischemic preconditioning is the most potent form of endogenous myocardial protection from irreversible ischemic injury. Experimental observations suggest that acute ethanol administration might abolish IPC. METHODS We studied 30 consecutive patients (22 men, mean age 65 years) undergoing elective coronary angioplasty who were randomized to receive an oral dose of 40 g ethylic alcohol (administered as 149 ml of Gordons Gin) or 149 ml of water 30 min before PCI. Intracoronary electrocardiogram was continuously monitored to assess the greatest ST-segment elevation or depression from baseline. RESULTS In placebo-treated patients, the change of ST-segment shift during the second inflation was significantly smaller than that during the first inflation (19.3 +/- 9.1 vs. 15.7 +/- 8.7, p = 0.005). In contrast, in gin-treated patients, the change of ST-segment shift during the second inflation was significantly greater than that during the first inflation (18.7 +/- 7.2 vs. 22 +/- 10, p = 0.03). The group-inflation interaction for ST-segment changes was highly significant (p < 0.001). CONCLUSIONS This randomized, prospective study in humans shows that administration of a moderate dose of ethanol abolishes IPC occurring during sequential episodes of myocardial ischemia and is associated with worsening ischemia. Based on our study, intake of moderate to high doses of alcoholic beverages should be avoided in patients at high risk of acute myocardial infarction.

Effect of Atorvastatin (80 mg) Initiated at the Time of Coronary Artery Stent Implantation on C-Reactive Protein and Six-Month Clinical Events

and Hall, 1991:467–471. 8. Strandberg TE, Vanhanen H, Tikkanen MJ. Associations between change in C-reactive protein and serum lipids during statin treatment. Ann Intern Med 2000;32:579–583. 9. Albert MA, Danielson E, Rifai N, Ridker PM. Effect of statin therapy on C-reactive protein levels. The Pravastatin Inflammation/CRP Evaluation (PRINCE): a randomized trial and cohort study. JAMA 2001;286:64–70. 10. Ridker PM, Rifai N, Clearfield M, Downs JR, Weis SE, Miles JS. Measurement of C-reactive protein for targeting of statin therapy in the primary prevention of acute coronary events. N Engl J Med 2001;344:1959 – 1965. 11. Claxton AJ, Cramer J, Pierce C. A systematic review of the associations between dose regimens and medication compliance. Clin Ther 2001;23:1296–1310. 12. Horne R. Compliance, adherence and concordance, In: Taylor K. Harding G, eds. Pharmacy Practice. London: Taylor and Francis, 2001:165–184. 13. Ryan AA. Medication compliance and older people: a review of the literature. Int J Nursing. Studies 1999;36:153–162.

Twenty year follow-up after successful percutaneous balloon mitral valvuloplasty in a large contemporary series of patients with mitral stenosis

BACKGROUND Percutaneous balloon mitral valvuloplasty (PMV) is currently considered the standard of care for suitable patients with rheumatic mitral stenosis. We sought to assess very long-term outcome after PMV. METHODS Between 1991 and 2010, 482 consecutive patients underwent successful PMV in a single center. Procedural success was defined as post-procedural valve area ≥ 1.5 cm(2) and regurgitation moderate or less, without in-hospital major adverse cardiac and cerebro-vascular events. The primary endpoint was 20-year incidence of major adverse cardiac events (MACE), including cardiovascular death and need for mitral surgery or repeat PMV. RESULTS Long-term follow-up (mean 11.6 ± 4.9 years; range 0.5 to 20) was completed in 441 (91.5%) patients. The incidence of the primary endpoint was 41.9% (95% confidence interval [CI]: 37.3 to 46.7%). The rate of cardiovascular death, need for mitral surgery or repeat PMV was 9.1% (95% CI: 6.6 to 12.1), 27% (95% CI: 22.9 to 31.4), and 5.9% (95% CI: 3.9 to 8.5), respectively. Cumulative MACE-free survival at 20 years was 35.9 ± 4.7%. At multivariate analysis, male gender (hazard ratio [HR]: 1.99; 95% CI: 1.4-2.8, p < 0.001), echocardiographic score > 8 (HR: 2.19; 95% CI: 1.6-2.9, p < 0.001), atrial fibrillation (HR: 1.54; 95% CI: 1.2-2.1, p = 0.003) and valve area ≤ 1.75 cm(2) after PMV (HR: 3.1; 95% CI: 2.3-4.2, p < 0.001) were identified as independent predictors of the primary endpoint. CONCLUSIONS Up to 20 years after successful PMV, a sizeable proportion of patients still exhibit a good clinical result.

A comparison of coronary artery stenting with angioplasty for isolated stenosis of the proximal left anterior descending coronary artery: five year clinical follow up

Background: Stent implantation for isolated stenosis of the proximal left anterior descending coronary artery (LAD) with preserved left ventricular function has been found to have a better clinical and angiographic outcome at one year than balloon angioplasty (PTCA). Objective: To establish whether those results are maintained at five year follow up. Methods: Patients were followed at least every six months. For those who died during follow up, data were obtained from medical records. Main outcome measures: Freedom from death, non-fatal myocardial infarction, cerebrovascular accident, and repeated target lesion revascularisation. Secondary end points were revascularisation in a remote region and freedom from angina. Results: Follow up was complete in all patients. At five years, the primary end point was reached more often by patients randomised to stent implantation than to PTCA (80% v 53%; odds ratio (OR) 0.29 (95% confidence interval (CI) 0.13 to 0.69); p  =  0.0034). In the PTCA group, 35% of patients underwent target lesion revascularisation v 15% in the stent group (OR 0.33, 95% CI 0.13 to 0.80; p  =  0.014). There was a trend towards increased mortality in the PTCA group than in the stent group (17% v 7%; OR 0.36, 95% CI 0.10 to 1.21; p  =  0.098). No significant differences were found between PTCA and stent groups for non-fatal myocardial infarction (8% v 5%; OR 0.58, 95% CI 0.13 to 2.54; p  =  0.46) or cerebrovascular accident (2% v 0%). Conclusions: In patients with isolated stenosis of the proximal LAD, a five year clinical follow up confirmed a better outcome in those treated with stenting than with PTCA.

Persistent enhanced platelet activation in patients with acute myocardial infarction and coronary microvascular obstruction: clinical implications

About 30% of patients with acute ST-segment elevation myocardial infarction (STEMI) undergoing recanalisation of the infarct-related coronary artery do not achieve valid myocardial reperfusion (no-reflow phenomenon or coronary microvascular obstruction [MVO]). The mechanisms of MVO are incompletely understood. In this study we investigated the role platelet activation in the pathogenesis of coronary MVO in STEMI patients. We enrolled 48 STEMI patients (age 56.2 ± 11 years; 31 men), treated by primary percutaneous coronary intervention (PCI) followed by double anti-platelet treatment, and 20 control patients with stable coronary artery disease (CAD) on single anti-platelet treatment (age 57.5 ± 6 years, 12 men). STEMI patients were divided into two groups: 35 patients with complete myocardial reperfusion (MR) and 13 patients with coronary MVO despite successful PCI. Platelet activation was assessed on admission and at one-month follow-up by measuring platelet receptor expression and monocyte-platelet aggregates (MPAs). Platelet receptor expression, platelet receptor conformational change for fibrinogen binding availability and MPA formation were increased in STEMI patients with MVO compared to both STEMI patients with MR and stable CAD patients, both on admission and at one-month follow-up (p<0.05 for all).Among STEMI patients, platelet activation is greater in those who display coronary MVO, compared to those with MR, after successful PCI, both on admission and one month after STEMI, suggesting that enhanced platelet activation might be involved in the pathogenesis of MVO. The persistence of enhanced platelet activation despite double classical anti-platelet therapy suggests that new anti-platelet strategies should be considered in patients with coronary MVO.

Long-term outcome of provisional side-branch T-stenting for the treatment of unprotected distal left main coronary artery disease.

Percutaneous coronary intervention (PCI) on distal left main (LM) remains an independent predictor of poor outcome. The strategy of implanting one stent on the main branch (MB), with provisional stenting on the side‐branch (SB) only when required (provisional T‐stenting), has become the default approach to most bifurcation lesions. This prospective registry sought to investigate the long‐term safety and efficacy of provisional SB T‐stenting for the treatment of unprotected distal LM disease in patients undergoing PCI. From January 2006 to May 2009, 107 consecutive patients affected by unprotected distal LM disease underwent PCI at our center with the intent to use a provisional SB‐stenting technique. We evaluated the rate of major adverse cardiac events (MACE) at long‐term follow‐up (up to 12–41 months). Procedural success was obtained in 98% of patients. A final kissing balloon inflation was performed in 95% and intravascular ultrasound in 83% of patients. Additional stenting on the SB after provisional stenting on MB was required in 29% of lesions. Long‐term follow‐up (3.5 years; 25–75th percentile and 1.1–4.5 years) was completed in 97% of patients. The cumulative incidence of MACE was 32.7%: all‐cause death was 15.8%, nonfatal myocardial infarction 8.4%, and target vessel revascularization 21.5%. At multivariable analysis, age (hazard ratio, 2.08; 95% confidence interval: 2.01–3.32, P = 0.03), European System for Cardiac Operative Risk Evaluation (HR 1.20, 95% CI: 1.04–1.33, P = 0.02), and diabetes mellitus (HR 3.48, 95% CI: 1.12–6.87, P = 0.01) were identified as independent predictors of MACE. In patients with unprotected distal LM disease undergoing PCI, a provisional strategy of stenting the MB only is associated with good long‐term clinical outcomes.

One-Year Outcome From an All-Comers Population of Patients With ST-Segment Elevation Myocardial Infarction Treated With Biolimus-Eluting Stent With Biodegradable Polymer

To evaluate the performance of biolimus‐eluting stent (BES) in patients with ST‐elevation myocardial infarction (STEMI) undergoing percutaneous coronary intervention (PCI) in a real world clinical scenario.