Marco Zimarino

Stent implantation versus balloon angioplasty in chronic coronary occlusions : Results from the GISSOC Trial

OBJECTIVES In this multicenter, randomized trial we evaluated whether stent implantation after successful recanalization of a chronic coronary occlusion reduced the incidence of restenosis. BACKGROUND Percutaneous transluminal coronary angioplasty (PTCA) in chronic total occlusions is associated with a higher rate of angiographic restenosis and reocclusion than PTCA in subtotal stenoses. Preliminary reports have suggested a decreased restenosis rate after stent implantation in coronary total occlusions. METHODS We randomly assigned 110 patients with recanalized total occlusion to Palmaz-Schatz stent implantation, followed by 1 month of anticoagulant therapy versus no other treatment. The primary end point was the minimal lumen diameter (MLD) of the treated segment at follow-up, as determined by quantitative angiography at a core laboratory. RESULTS Repeat coronary angiography was performed 9 months after the procedure in 88% of patients. The MLD (mean +/- SD) at follow-up was 1.74 +/- 0.88 mm in patients assigned to stent implantation and 0.85 +/- .75 mm in patients assigned to PTCA (p < 0.001). Stent implantation was associated with a lower incidence of restenosis (defined as diameter stenosis > or =50% at follow-up) (32% vs. 68%, p < 0.001) and reocclusion (8% vs. 34%, p = 0.003) than balloon PTCA. Likewise, stent-treated patients had less recurrent ischemia (14% vs. 46%, p = 0.002) and target lesion revascularization (5.3% vs. 22%, p = 0.038), but experienced a longer hospital stay. CONCLUSIONS Palmaz-Schatz stent implantation after successful balloon PTCA of chronic total occlusions improves the midterm angiographic and clinical outcome and could be the preferred treatment option in selected patients with occluded vessels.

Awake Systolic Blood Pressure Variability Correlates With Target-Organ Damage in Hypertensive Subjects

Growing evidence associates blood pressure (BP) variability with cardiovascular events in hypertensive patients. Here we tested the existence of a relationship between awake BP variability and target-organ damage in subjects referred for suspected hypertension. Systolic and diastolic BP variability were assessed as the standard deviation of the mean out of 24-hour, awake and asleep BP recordings in 180 untreated subjects, referred for suspected hypertension. Measurements were done at 15-minute intervals during daytime and 30-minute intervals during nighttime. Left ventricular mass index (by echo), intima-media thickness (by carotid ultrasonography), and microalbuminuria were assessed as indices of cardiac, vascular and renal damage, respectively. Intima-media thickness and left ventricular mass index progressively increased across tertiles of awake systolic BP variability (P for trend=0.001 and 0.003, respectively). Conversely, microalbuminuria was similar in the 3 tertiles (P=NS). Multivariable analysis identified age (P=0.0001), awake systolic BP (P=0.001), awake systolic BP variability (P=0.015) and diastolic BP load (P=0.01) as independent predictors of intima-media thickness; age (P=0.0001), male sex (P=0.012), awake systolic (P=0.0001) and diastolic BP (P=0.035), and awake systolic BP variability (P=0.028) as independent predictors of left ventricular mass index; awake systolic BP variability (P=0.01) and diastolic BP load (P=0.01) as independent predictors of microalbuminuria. Therefore, awake systolic BP variability by non-invasive ambulatory BP monitoring correlates with sub-clinical target-organ damage, independent of mean BP levels. Such relationship, found in subjects referred for recently suspected hypertension, likely appears early in the natural history of hypertension.

Multiple arterial conduits without cardiopulmonary bypass: early angiographic results

BACKGROUND Lack of angiographic results and technical difficulty in grafting the vessels in the lateral and posterior walls have reduced interest in myocardial revascularization without cardiopulmonary bypass (CPB). We describe our experience to demonstrate the feasibility of coronary surgical intervention without CPB in multivessel disease. METHODS From May 21, 1997, through February 1998, 227 patients underwent revascularization with two or more arterial conduits as the first operation: 122 without CPB (group A) and 105 with CPB (group B). Group A included a greater number of high-risk patients. RESULTS Mean +/- SD anastomoses per patient were 2.5 +/- 0.6 in group A and 2.8 +/- 0.8 in group B (p = NS). No patient died in group A, whereas 1 patient (0.9%) died in group B. The postoperative complication rate was low in both groups, but intensive care unit and in-hospital stays were shorter in group A than in group B (14.1 +/- 7.1 versus 27.3 +/- 36 hours, p < 0.001, and 4.1 +/- 1.6 versus 5.4 +/- 2.4 days, p < 0.001, respectively [group A versus group B]). Sixty-seven patients in Group A (54.9%) underwent postoperative angiography 33 +/- 35 days after operation. The patency rate was 98.9% (98.2% for the marginal branches). CONCLUSIONS Arterial revascularization of the coronary arteries without CPB is feasible, with results similar to those obtained with CPB. The two techniques, in our opinion, are complementary, not antagonistic.

Low-Density Lipoprotein Level Reduction by the 3-Hydroxy-3-Methylglutaryl Coenzyme-A Inhibitor Simvastatin Is Accompanied by a Related Reduction of F2-Isoprostane Formation in Hypercholesterolemic Subjects No Further Effect of Vitamin E

Background—Both statins and vitamin E, by reducing the rate of lipid peroxidation, may interfere with oxidative stress, but the impact of their combination is unknown. Methods and Results—We randomized 43 hypercholesterolemic patients (21 men, 22 women, age 63±11 years) to either simvastatin, to achieve >20% reduction of total cholesterol, or simvastatin plus 600 mg/d vitamin E for 2 months. Patients were then crossed over to the alternative treatment. Lipid parameters documented patients’ compliance to simvastatin, whereas plasma levels of vitamin E documented compliance and absorption of vitamin E. We assessed urinary excretion of the isoprostane 8-iso-prostaglandin F2&agr; (8-iso-PGF2&agr;) as an in vivo index of oxidative stress at baseline and after each month of therapy. 8-Iso-PGF2&agr; was significantly reduced by simvastatin, from 361±148 pg/mg creatinine (mean±SD) at baseline to 239±124 pg/mg creatinine after 1 month. The addition of vitamin E did not reduce such levels any further (256±125 after 1 month). Linear regression analysis showed a weak inverse relationship of 8-iso-PGF2&agr; with vitamin E levels but a much stronger relationship with LDL cholesterol (R2=0.162;P <0.001). Conclusions—In hypercholesterolemic patients, LDL cholesterol is a major correlate of oxidative stress. Concomitant with LDL cholesterol reduction, simvastatin causes a drastic reduction of oxidative stress to a level that is not further reduced by the addition of vitamin E. Results of clinical trials with vitamin E may have been hampered by inadequate knowledge of the background level of lipid peroxidation, which is a major determinant of vitamin E bioactivity.

Celecoxib, ibuprofen, and the antiplatelet effect of aspirin in patients with osteoarthritis and ischemic heart disease.

We performed a placebo‐controlled, randomized study to address whether celecoxib or ibuprofen undermines the functional range of inhibition of platelet cyclooxygenase (COX)–1 activity by aspirin in patients with osteoarthritis and stable ischemic heart disease.

Cardiovascular morbidity and mortality related to orthostatic hypotension: a meta-analysis of prospective observational studies

BACKGROUND Whether orthostatic hypotension (OH) is a risk factor for cardiovascular morbidity and death is uncertain. Currently available evidence derives from non-homogeneous and partly ambiguous studies. OBJECTIVE We aimed at assessing the relationship between OH and death or major adverse cardiac and cerebrovascular events (MACCEs) by integrating results of previous studies. METHODS We performed a meta-analysis of prospective observational studies reporting on the association between prevalent OH, mortality, and incident MACCE, published from 1966 through 2013. Mantel-Haenszel pooled estimates of relative risk (RR) and 95% confidence intervals (CIs) for all-cause death were assessed as the primary endpoint at the longest follow-up; incident coronary heart disease (CHD), heart failure (HF), and stroke were assessed as secondary endpoints. We also performed post hoc subgroup analyses stratified by age and a meta-regression analysis. RESULTS We identified a total of 13 studies, including an overall population of 121 913 patients, with a median follow-up of 6 years. Compared with the absence of OH, the occurrence of OH was associated with a significantly increased risk of all-cause death (RR 1.50; 95% CI 1.24-1.81), incident CHD (RR 1.41; 95% CI 1.22-1.63), HF (RR 2.25; 95% CI 1.52-3.33), and stroke (RR 1.64; 95% CI 1.13-2.37). When analysed according to age, pooled estimates of RR (95% CI) for all-cause death were 1.78 (1.25-2.52) for patients <65 years old, and 1.26 (0.99-1.62) in the older subgroup. CONCLUSION Orthostatic hypotension is associated with a significantly increased risk of all-cause death, incident CHD, HF, and stroke.

ESC working group position paper on myocardial infarction with non-obstructive coronary arteries

The management of acute myocardial infarction (AMI)1 has evolved over the past century and particularly in the past 50 years. Important milestones include the development of the electrocardiogram, coronary care units, coronary angiography, reperfusion therapies, and troponin assays. These innovations are the foundation of contemporary AMI management strategies that include a diagnosis centred on elevated troponin values associated with corroborative clinical evidence,1 early use of coronary angiography, and reperfusion therapies.2–4 Pivotal in the evolution of these contemporary strategies were the early AMI coronary angiography studies undertaken by DeWood et al. These pioneering studies demonstrated that, in patients presenting with ST elevation myocardial infarction (STEMI), almost 90% had an occluded coronary artery provided that angiography was undertaken within 4 h of chest pain onset.5 In contrast, in AMI patients who did not present with ST elevation (non-ST elevation myocardial infarction or NSTEMI), only 26% had an occluded coronary artery when angiography was performed within 24 h of symptom onset.6 In both of these landmark studies,5,6 >90% of the acute MI patients had angiographic evidence of obstructive coronary artery disease (CAD), underscoring the importance of the atherosclerotic process in the pathogenesis of AMI. Although DeWoods studies underscore the importance of obstructive CAD in AMI, it is fascinating that ∼10% had no significant CAD on coronary angiography. This is confirmed in several large AMI registries7–9 where 1–13% of AMIs occurred in the absence of obstructive CAD thereby eliciting an important set of questions—what is the mechanism of the myocardial damage in these patients? Do these patients differ from those with obstructive CAD? Should they be …

Coronary stent implantation is superior to balloon angioplasty for chronic coronary occlusions: six-year clinical follow-up of the GISSOC trial.

OBJECTIVES We investigated whether the benefits of stent implantation over balloon percutaneous transluminal coronary angioplasty (PTCA) for treatment of chronic total coronary occlusions (CTO) are maintained in the long term. BACKGROUND Several randomized trials have shown that in CTO, stent implantation confers clinical and angiographic mid-term outcomes superior to those observed after PTCA. However, limited information on the long-term results of either technique is available. METHODS Six-year clinical follow-up of patients enrolled in the Gruppo Italiano di Studio sullo Stent nelle Occlusioni Coronariche (GISSOC) trial was performed by direct visit or telephone interview. Major adverse cardiac events (MACE), defined as cardiac death, myocardial infarction, target lesion revascularization (TLR), and anginal status, were recorded. RESULTS Freedom from MACE at six years was 76.1% in the stent group, compared with 60.4% in the PTCA group (p = 0.0555). This difference was due mainly to TLR-free survival rates (85.1% vs. 65.5% for the stent and PTCA groups, respectively; p = 0.0165). Eleven patients underwent TLR after the nine-month follow-up visit (stent group: n = 5; PTCA group: n = 6); however, in most cases, restenosis of the study occlusion was evident at nine-month angiography. CONCLUSIONS This study represents the longest reported clinical follow-up of patients after percutaneous recanalization of CTO and demonstrates that the superiority of stent implantation over balloon PTCA is maintained in the long term. Stent and PTCA results appear to remain stable after nine-month angiographic follow-up. Stent implantation in CTO that can be recanalized percutaneously is therefore a valuable long-term therapeutic option.

Late Thrombosis After Double Versus Single Drug-Eluting Stent in the Treatment of Coronary Bifurcations A Meta-Analysis of Randomized and Observational Studies

OBJECTIVES This study sought to hypothesize that the higher risk of myocardial infarction (MI) documented after a routine double drug-eluting stent (DES) strategy (DDS) compared with a single DES strategy (SDS) with provisional stenting in percutaneous coronary interventions (PCI) of bifurcation lesions is driven by an increased rate of DES thrombosis. BACKGROUND The results of currently available randomized, controlled trials (RCTs) were inconclusive in the choice between SDS and DDS. Meta-analyses have shown an increased risk of MI in the DDS group, without identifying the underlying mechanism(s). METHODS We performed a meta-analysis of 12 major (>100 patients) studies of bifurcation DES PCI: 5 RCTs and 7 nonrandomized observational studies, for a total of 6,961 patients. Random-effects models were used to calculate summary risk ratios (RRs). As a primary endpoint, we assessed the RRs and 95% confidence intervals (CIs) of definite DES thrombosis; death, MI, and target vessel revascularization (TVR) were evaluated as secondary endpoints. RESULTS Compared with SDS, DDS had an increased risk of DES thrombosis (RR: 2.31; 95% CI: 1.33 to 4.03) and MI (RR: 1.86; 95% CI: 1.34 to 2.60). Mortality (RR: 1.18; 95% CI: 0.85 to 1.65) and TVR (RR: 1.02; 95% CI: 0.80 to 1.30) were similar. The RRs of MI and DES thrombosis were associated (p = 0.040). CONCLUSIONS In PCI of coronary bifurcations, SDS should be the preferred approach, as DDS is associated with an increased risk of MI, likely driven by DES thrombosis.

Complete myocardial revascularization: between myth and reality

Myocardial revascularization in patients with multi-vessel coronary artery disease may be accomplished, by percutaneous interventions or surgery, either on all diseased lesions or directed to selectively targeted coronary segments. The extent of planned revascularization is often a major determinant of treatment strategy. Revascularization of all diseased coronary segments-complete myocardial revascularization-has a potential long-term benefit, but is more complex and may increase in-hospital untoward events. Revascularization may otherwise be incomplete, either because of the operators inability to treat all diseased coronary segments or by choice of deciding to selectively revascularize only large areas of myocardium at risk. Although incomplete revascularization may negatively affect long-term outcomes, it may be, when wisely chosen, the preferred treatment strategy in selected patient categories because of its lower immediate risks. The patients clinical status, ventricular function, and the presence of co-morbidities may orient clinical decisions in favour of incomplete revascularization.