Evaluating the metabolic approach to treatment of diabetic coronary patients

Diabetic patients with coronary artery disease have an altered myocardial metabolism of glucose and free fatty acids (FFA) and accelerated and diffuse atherogenesis with involvement of peripheral coronary segments that causes chronic hypoperfusion and hibernation. Therefore, in coronary diabetic patients the ischaemic metabolic changes that occur as a consequence of the mismatch between blood supply and cardiac metabolic requirements are heightened by the diabetic metabolic alterations. Important metabolic alterations in diabetic patients are the decreased utilization of glucose and the increase in muscular and myocardial FFA uptake and oxidation. These metabolic changes are responsible for the increased susceptibility of the diabetic heart to myocardial ischaemia and to a greater decrease of myocardial performance for a given amount of ischaemia compared to non diabetic hearts. A therapeutic approach aimed at an improvement of cardiac metabolism through manipulations of the utilization of metabolic substrates should result in an improvement of myocardial ischaemia and of left ventricular function. The inhibition of FFA oxidation improves cardiac metabolism at rest, increases the cardiac resistance to ischaemia and therefore reduces the decline of left ventricular function due to chronic hypoperfusion and repetitive episodes of myocardial ischaemia in patients with and without diabetes. Modulation of myocardial FFA metabolism should be the key target for metabolic interventions in diabetic patients with coronary artery disease

Diabetes mellitus and ischemic heart disease. the role of ion channels

Diabetes mellitus is one the strongest risk factors for cardiovascular disease and, in particular, for ischemic heart disease (IHD). The pathophysiology of myocardial ischemia in diabetic patients is complex and not fully understood: some diabetic patients have mainly coronary stenosis obstructing blood flow to the myocardium; others present with coronary microvascular disease with an absence of plaques in the epicardial vessels. Ion channels acting in the cross-talk between the myocardial energy state and coronary blood flow may play a role in the pathophysiology of IHD in diabetic patients. In particular, some genetic variants for ATP-dependent potassium channels seem to be involved in the determinism of IH

Heart rate modulation in stable coronary artery disease without clinical heart failure: What we have already learned from SIGNIFY?

An elevated heart rate is a marker of cardiovascular risk in patients with stable coronary artery disease. Ivabradine selectively inhibits the “f” current in the sinus node and reduces heart rate without any modifications of blood pressure, myocardial contractility and arteriolar resistance. However the addition of ivabradine to standard therapy to reduce heart rate did not improve outcomes in the recent SIGNIFY trial. Moreover, a significant interaction between the effect of ivabradine among subgroups with and without angina was detected, with a worse outcome in patients in CCS class >II at baseline. The explanation for this surprising finding despite a significant reduction in angina and myocardial revascularization procedures is uncertain. A J-curve for heart rate was not demonstrated. We speculate a significant interference on adverse events (mainly atrial fibrillation and consequently acute coronary syndromes) and on the outcome of unfavorable interactions between ivabradine and diltiazem, verapamil and strong inhibitors of CYP3A4 (4.6% of the total population). Indeed, when these patients are excluded from subgroup analysis, the harmful effect of Ivabradine among patients with severe angina disappears. In conclusion, heart rate is a marker of risk but is not a risk factor and/or a target of therapy in patients with stable coronary artery disease and preserved ventricular systolic function. Standard doses of ivabradine are indicated for treatment of angina as an alternative or in addition to beta-blockers, but should not be administered in association with CYP3A4 inhibitors or heart rate-lowering calcium-channel blockers

Telemonitoring for the Management of Patients with Heart Failure

Advances in technology now make it possible to manage heart failure (HF) from a remote to a telemonitoring approach using either noninvasive solutions or implantable devices. Nowadays, it is possible to monitor at-home parameters that can be recorded, stored and remotely transmitted to physicians, allowing them to make decisions for therapeutic modification, hospitalization or access to the emergency room. Standalone systems are available that are equipped with self-intelligence and are able to acquire and elaborate data that can inform the remote physician of impending decompensation before it results in additional complications. The development of miniature implantable devices, which could measure haemodynamic variables and transmit them to a monitor outside the body, offers the possibility for the physician to obtain more frequent evaluations of HF patients and the opportunity to take these data into account in management decisions. At present, several telemonitoring devices are available, but the only Food and Drug Administration-approved system is the cardio-microelectromechanical system, which is an implantable pulmonary arterial pressure (PAP) monitoring device that allows a direct monitoring of the PAP via a sensor implanted in the pulmonary artery. This information is then uploaded to a web-based interface from which healthcare providers can track the results and manage patients. At present, the challenge point for telemedicine management of HF is to find the more relevant biological parameter to monitor the clinical status

Heart Rate Control in Non-Paroxysmal Atrial Fibrillation. A New Indication for Ivabradine?

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Glyco-metabolic Effects of Ranolazine: A truly Multifaceted Drug?

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The combination of nutraceutical and simvastatin enhances the effect of simvastatin alone in normalising lipid profile without side effects in patients with ischemic heart disease

Abstract Background hyperlipidemia is one of the most important cardiovascular risk factors. Statins at high doses are commonly prescribed to lower LDL-cholesterol, but are often poorly tolerated. In particular, muscle pain and increase of creatine phosphokinase are frequent side effects. The purpose of this study was to assess whether the addition of a nutraceutical to simvastatin may result in the achievement of the therapeutic target (LDL-cholesterol less than 70mg/dL) without side effects in patients with ischemic heart disease. Methods Sixty-four patients with ischemic heart disease treated with simvastatin 20mg who had not achieved the therapeutic target were enrolled. Patients were randomised 1:1. Patients of group A (n=32) were given simvastatin 40mg per day and patients of group B (n=32) were given simvastatin 20mg plus 2 tablets of a nutraceutical composed of bergamot, phytosterols, artichoke, vitamin C. Results After 3months, patients in both groups showed a significant reduction from baseline in total cholesterol, LDL-c and tryglicerides. However, in group A, 4 patients reported myalgia (9,7%) with an increase in creatine phosphokinase; whereas no adverse events occurred in group B. Conclusions The association of a nutraceutical and simvastatin 20mg may be a valid therapeutic option for the treatment of hyperlipidemia in patients with ischemic heart disease intolerant to statin at high doses, in the absence of side effects. Further studies are needed to clarify the mechanisms of action of nutraceuticals

Additive effects of nutraceuticals to non-pharmacologic intervention to improve lipid profile in the real world clinical practice in European countries — The PIN (Portugal Italy Nutraceutical) Study

PEARL trial. Patientswere randomly assigned to atorvastatin (20 mg day, N= 50) or rosuvastatin (10 mg day, N= 50) for 30 days. After another 1-week wash-out period to avoid any carryover effect, cross-over was performed, and patients were switched to the other drug which was continued for 30 days. Platelet reactivity (expressed as P2Y(12) reaction units (PRU) by the point-of-care VerifyNow assay [Accumetrics, San Diego, California]) was measured before and at the end of each 30-day treatment period. High platelet reactivity after clopidogrel was defined as a PRU value N 208. Results: After the 30-day treatment with atorvastatin, platelet reactivity did not significantly change as compared with baseline, pre-treatment evaluation (119 ± 66 vs 136 ± 59 PRU, NS), with 2 patients only showing a PRU N 208. Similarly, after 30-day treatment with rosuvastatin, platelet reactivity was unchanged as compared with baseline (135 ± 46 vs 128 ± 62 PRU, NS), with PRU N 208 occurring in 3 patients. Conclusion: Atorvastatin does not negatively affect DAPT as compared with rosuvastatin when is given to stable CAD patients with baseline normal platelet reactivity while on DAPT. (ClinicalTrials.gov Identifier: NCT01567774)

Testosterone Therapy in Women With Chronic Heart Failure A Pilot Double-Blind, Randomized, Placebo-Controlled Study

ObjectivesThe primary objective of this study was to assess the effect of a 6-month testosterone supplementation therapy on functional capacity and insulin resistance in female patients with chronic heart failure (CHF).BackgroundPatients with CHF show decreased exercise capacity and insulin sensitivity. Testosterone supplementation improves these variables in men with CHF. No study has evaluated the effects of testosterone supplementation on female patients with CHF.MethodsThirty-six elderly female patients with stable CHF, (ejection fraction 32.9 ± 6) were randomly assigned (2:1 ratio) to receive testosterone transdermal patch (T group, n = 24) or placebo (P group, n = 12), both on top of optimal medical therapy. At baseline and after 6 months, patients underwent 6-min walking test (6MWT), cardiopulmonary exercise test, echocardiogram, quadriceps maximal isometric voluntary contraction, dynamic quadriceps isokinetic strength (peak torque), and insulin resistance assessment by homeostasis model.ResultsDistance walked at 6MWT as well as peak oxygen consumption significantly improved in the T group, whereas they were unchanged in the P group (p < 0.05 for all comparisons). The homeostasis model was significantly reduced in the T group in comparison with the P group (−16.5% vs. +5%, respectively; p < 0.05). Maximal voluntary contraction and peak torque increased significantly in the T group but did not change in the P group. Increase in distance walked at 6MWT was related to the increase in free testosterone levels (r = 0.593, p = 0.01). No significant changes in echocardiographic parameters were observed in either group. No side effects requiring discontinuation of T were detected.ConclusionsTestosterone supplementation improves functional capacity, insulin resistance, and muscle strength in women with advanced CHF. Testosterone seems to be an effective and safe therapy for elderly women with CHF