Letter by Fragasso et al regarding article by Tuunanen et al, Free fatty acid depletion acutely decreases cardiac work and efficiency in cardiomyopathic heart failure

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Transient cardiac left ventricular diastolic dysfunction following strenuous exercise

The long term clinical significance of exercise-induced \u201ccardiac fatigue\u201d has not been clearly addressed. The aim of this study was to assess the effects of repetitive competitive high altitude running on left ventricular performance. Eleven athletes were studied before and after two high altitude races in two consecutive years. On both occasions 12-lead elettrocardiography (ECG) as well as Doppler echocardiography were performed 24 hours before, shortly after (within 30 min) and 24 hours after the end of the race. Measurements included ejection fraction, early (E) and late (A) transmitral inflow velocities, their ratio (E/A) and percent atrial contribution (AC). Similar studies were performed in 11 age- and sex-matched control subjects at baseline and following a maximal exercise test. Ejection fraction remained stable in both. Conversely, Doppler E/A ratio significantly decreased in atletes early after the race from 1.9\ub10.1 to 1.3\ub10.1 (p<0.05) for the first race and from 1.7\ub10.1 to 1.4\ub10.1 (p<0.05) for the second race. The decrease was mainly due to a reduction in E (p<0.05), since A was not modified. AC increased from 20%\ub13% to 28%\ub15% (p<0.05) and from 21%\ub13% to 26%\ub16% (p<0.05), respectively. All parameters returned to baseline at a 24-hour control. Compared to controls, all athletes had significantly higher resting E and A velocities and lower E/A ratio and AC to ventricular filling shortly after exercising. All parameters returned to baseline at the 24-hour controls. These findings are consistent with previous studies reporting transient cardiac fatigue following strenuous exercise. However, the functional effects of these changes do not seem to interfere with cardiac function and athletic performance in both the short term and medium-long term

A high carbohydrate meal yields a lower ischemic threshold than a high fat meal in patients with stable coronary disease

Objective: To assess the ischemic threshold and stress-induced left ventricular dysfunction after high fat (HFM) and high carbohydrate (HCM) meals in patients with stable coronary disease. Methods: Twelve patients (68 +/- 7 years) underwent stress (treadmill exercise testing) echocardiography after fasting (8 h), after HFM and HCM (2 h). Time to 1 mm ST-segment depression (time to 1 mm) and stress wall motion score index (WMSI) were evaluated. Before eating and just before exercise testing glucose, insulin, triglycerides, total cholesterol and FFA levels were measured. Results: Results are expressed as medians (Q1-Q3). HFM did not affect exercise variables compared to fasting, whereas HCM reduced the ischemic threshold [time to 1 mm from 376 (343-493) to 297 (180-420) s, p = 0.003]. Compared to fasting [1.47 (1.31-1.66)], stress WMSI was higher after HCM [1.56 (1.44-1.69)] (p = 0.04) but not after HFM [1.56 (1.30-1.63)]. Glycemia and insulinemia were significantly higher after HCM, compared to fasting and HFM. Conclusions: In patients with coronary disease, exercise testing after a high carbohydrate meal results in a lower ischemic threshold and greater ischemia magnitude. Conversely, compared to fasting, a high fat meal does not induce additional detrimental effects. Hyperglycemia and hyperinsulinemia were the only metabolic determinants identified as potential metabolic mechanisms of this phenomenon

Drug-eluting stent implantation in coronary trifurcation lesions

BACKGROUND: There is no specific study evaluating the outcome of DES implantation in trifurcation lesions. OBJECTIVE: To evaluate the mid-term clinical and angiographic outcome of drug-eluting stent (DES) implantation in trifurcation lesions. METHODS: All complications and major adverse cardiac events, including cardiac death, Q-wave myocardial infarction (MI), target lesion revascularization (TLR), and target vessel revascularization (TVR) were recorded in-hospital and during clinical follow up. RESULTS: A total of 15 consecutive patients undergoing percutaneous coronary intervention with DES in de novo trifurcation lesions were identified. Lesions were located as follows: 13 (86.7%) at the distal left main coronary artery (LMCA) comprising the left anterior descending artery (LAD), the left circumflex artery (LCX) and an intermediate branch; 1 between the LAD, diagonal, and septal branches; and 1 between the LCX, obtuse marginal and posterior lateral branches. Stenting was performed in all 3 branches in 8 patients, in 2 branches in 6 patients, and in 1 branch in 1 patient. The mean follow-up period was 19.0 +/- 8.3 months. TLR occurred in 3 patients (20%) with LMCA lesions. TVR occurred in 6 patients (40%). Of those, 3 were due to TLR, while the other 3 for progression of nontarget lesions. No deaths, Q-wave MIs or stent thromboses were recorded. CONCLUSION: Most trifurcation lesions were found in the distal LMCA. DES implantation in trifurcation lesions can be performed with a low incidence of death, Q-wave MI or stent thrombosis

Effects of metabolic modulation by trimetazidine on left ventricular function and phosphocreatine/adenosine triphosphate ratio in patients with heart failure

Aims: The addition of trimetazidine to standard treatment has been shown to improve left ventricular (LV) function in patients with heart failure. The aim of this study is to non-invasively assess, by means of in vivo (31)P-magnetic resonance spectroscopy ((31)P-MRS), the effects of trimetazidine on LV cardiac phosphocreatine and adenosine triphosphate (PCr/ATP) ratio in patients with heart failure. Methods and results: Twelve heart failure patients were randomized in a double-blind, cross-over study to placebo or trimetazidine (20 mg t.i.d.) for two periods of 90 days. At the end of each period, all patients underwent exercise testing, 2D echocardiography, and MRS. New York Heart Association (NYHA) class, ejection fraction (EF), maximal rate-pressure product, and metabolic equivalent system (METS) were evaluated. Relative concentrations of PCr and ATP were determined by cardiac (31)P-MRS. On trimetazidine, NYHA class decreased from 3.04 (plus or minus) 0.26 to 2.45 (plus or minus) 0.52 (P= 0.005), whereas EF (34 (plus or minus) 10 vs. 39 (plus or minus) 10%, P= 0.03) and METS (from 7.44 (plus or minus) 1.84 to 8.78 (plus or minus) 2.72, P= 0.03) increased. The mean cardiac PCr/ATP ratio was 1.35 (plus or minus) 0.33 with placebo, but was increased by 33% to 1.80 (plus or minus) 0.50 (P= 0.03) with trimetazidine. Conclusion: Trimetazidine improves functional class and LV function in patients with heart failure. These effects are associated to the observed trimetazidine-induced increase in the PCr/ATP ratio, indicating preservation of the myocardial high-energy phosphate levels. (copyright) The European Society of Cardiology 2006. All rights reserved

The anti-ischemic effect of trimetazidine in patients with postprandial myocardial ischemia is unrelated to meal composition

Background: Previous studies provide evidence for a significant reduction of coronary flow reserve after ingestion of meals of different compositions. A possible role of hyperinsulinemia and increased free fatty acid levels, which are deleterious during acute myocardial ischemia and reperfusion, has been hypothesized. We assessed in patients with stable coronary disease the effects of high-fat meals (HFMs) and high-carbohydrate meals (HCMs) on ischemic threshold and stress left ventricular function on placebo and after partial fatty acid inhibition by trimetazidine (TMZ). Methods: Ten patients (9 men, age 68 (plus or minus) 7 years) were allocated to placebo and TMZ (40 mg TID), both administered in the 24 hours preceding testing, according to a randomized double-blind study design. All patients underwent stress (treadmill exercise testing according to the Bruce protocol) echocardiography after fasting (8 hours) and after an HFM and HCM (2 hours) either on placebo or on TMZ. Time to 1-mm ST-segment depression (time to 1 mm) and stress wall motion score index (WMSI) were evaluated. Results: An HFM did not affect exercise variables compared with fasting, whereas an HCM resulted in a reduction of the ischemic threshold (time to 1 mm from 402 (plus or minus) 141 to 292 (plus or minus) 123 seconds, P= .025). Compared with placebo, TMZ improved time to 1 mm after fasting, HFM, and HCM (432 (plus or minus) 153 vs 402 (plus or minus) 141, 439 (plus or minus) 118 vs 380 (plus or minus) 107, 377 (plus or minus) 123 vs 292 (plus or minus) 123, F(1,9)= 26.91, P= .0006). Compared with placebo, on TMZ, stress WMSI decreased from 1.55 (plus or minus) 0.25 to 1.29 (plus or minus) 0.14 after fasting, from 1.57 (plus or minus) 0.10 to 1.39 (plus or minus) 0.28 after HFM, and from 1.64 (plus or minus) 0.21 to 1.39 (plus or minus) 0.21 after HCM (F(1,9)= 37.04, P= .0002). Interestingly, stress WMSI on TMZ was never different from rest WMSI on placebo. Conclusions: In patients with coronary disease, exercise testing after an HCM results in more severe myocardial ischemia compared with that after an HFM. The observed beneficial effects of the partial fatty acid inhibitor TMZ seem to be unrelated to meal composition and are possibly caused by the better glucose use induced by the drug. (copyright) 2006 Mosby, Inc. All rights reserved

Insulin resistance and endothelial function are improved after folate and vitamin B12 therapy in patients with metabolic syndrome : relationship between homocysteine levels and hyperinsulinemia

OBJECTIVE: The purpose of this study was (a) to study whether a folate and vitamin B12 treatment, aimed at decreasing homocysteine levels, might ameliorate insulin resistance and endothelial dysfunction in patients with metabolic syndrome according to the National Cholesterol Education Program-Adult Treatment Panel-III criteria and (b) to evaluate whether, under these metabolic conditions, there is a relationship between hyperhomocysteinemia and insulin resistance. DESIGN AND METHODS: A double-blind, parallel, identical placebo-drug, randomized study was performed for 2 months in 50 patients. Patients were randomly allocated to two groups. In group 1, patients were treated with diet plus placebo for 2 months. In group 2, patients were treated with diet plus placebo for 1 month, followed by diet plus folic acid (5 mg/day) plus vitamin B12 (500 microg/day) for another month. RESULTS: In group 2, folate treatment significantly decreased homocysteine levels by 27.8% (12.2+/-1.2 vs 8.8+/-0.7 micromol/l; P<0.01). A significant decrement was observed for insulin levels (19.9+/-1.7 vs 14.8+/-1.6 microU/ml; P<0.01) accompanied by a 27% reduction in the homeostasis model assessment levels. A positive relationship was found between the decrement of homocysteine and insulin levels (r=0.60; P<0.002). In parallel, endothelial dysfunction significantly improved in the treated group, since post-ischemic maximal hyperemic vasodilation increased by 29.8% and cGMP by 13.6% while asymmetrical dimethylarginine levels decreased by 21.7%. On the contrary, in group 1 patients, treated with placebo, no changes were shown in any of the variables. CONCLUSIONS: Folate and vitamin B12 treatment improved insulin resistance and endothelial dysfunction, along with decreasing homocysteine levels, in patients with metabolic syndrome, suggesting that folic acid has several beneficial effects on cardiovascular disease risk factors

SICI-GISE Position paper on the use of the magnesium bioresorbable scaffold Magmaris in clinical practice

Bioresorbable scaffolds have emerged as a potential breakthrough for the treatment of coronary artery lesions. The need for drug release and plaque scaffolding is temporary, and leaving a permanent stent once the process of plaque recoil and vessel healing has ended might be superfluous or even deleterious exposing the patient to the risk of very late thrombosis, eliminating vessel reactivity, impairing non-invasive imaging and precluding possible future surgical revascularization. This long-term potential limitation of permanent bare metal stents might be overcome by using a resorbable scaffold. The metallic and antithrombotic properties makes the resorbable magnesium scaffold an appealing technology for the treatment of coronary artery lesions. Notwithstanding this, its mechanical properties substantially differ from those of conventional bare metal stents, and previous experience using polymer-based scaffolds has shown that a standardized implantation technique and optimal patient and lesion selection are key factors for a successful implantation. A panel of expert cardiologists gathered to find a consensus on the best practices for Magmaris implantation in a selected patient population and to discuss the rationale for new potential future indications