Rene A Oliveros

Ischemia-associated intraventricular conduction disturbances during exercise testing as a predictor of proximal left anterior descending coronary artery disease

To determine the incidence and significance of transient intraventricular conduction abnormalities occurring in association with myocardial ischemia during exercise testing, the recordings of 2,200 consecutive exercise tests were reviewed. Ten patients (0.45%) were identified as having both ischemia and intraventricular conduction abnormalities that developed transiently during the exercise test. In all 10 patients both typical angina and electrocardiographic evidence of ischemia developed during exercise. Among the 10 patients, left anterior hemiblock developed in 4, left posterior hemiblock in 2, right bundle branch block (RBBB) in 2, RBBB with left axis deviation in 1, and left anterior hemiblock progressing to complete left bundle branch block (LBBB) in 1. All 10 patients had cardiac catheterization showing significant obstruction of the left anterior descending (LAD) coronary artery at or before the origin of the first septal branch. Eight patients were treated surgically and 2 medically, all with relief of ischemic symptoms. Nine of the 10 had repeat exercise stress testing without angina or electrocardiographic evidence of ischemia and without recurrence of the transient intraventricular conduction disturbance. It is concluded that the development of transient intraventricular conduction abnormalities associated with myocardial ischemia during exercise testing is an uncommon occurrence (0.45%). When such conduction disturbances do develop, the existence of significant disease in the proximal portion of the LAD coronary artery is strongly suggested. With control of myocardial ischemia, the transient conduction disturbances during exercise are ameliorated.

Implementing Cardiovascular Risk Reduction in Patients with Cardiovascular Disease and Diabetes Mellitus

The role of cardiovascular risk reduction in patients with diabetes mellitus is significant as several factors have been found to promote accelerated atherosclerosis in persons with diabetes including hyperglycemia-induced endothelial dysfunction, impaired fibrinolysis, increased platelet aggregation, plaque instability, dysfunctional arterial remodeling, and fibrotic and calcified coronary arteries. Recent attention has focused on identifying a cardiovascular biomarker that would propose a better noninvasive way to detect or visualize subclinical cardiovascular disease and prevent cardiovascular events. This article reviews the use of commonly used cardiovascular risk assessment tools and emerging biomarkers including coronary artery calcium scanning, metabolomics, genomics, and the role of optimal revascularization and risk reduction strategies and their impact on reducing risk in patients with cardiovascular disease and diabetes.

Aortic stiffness: pathophysiology, clinical implications, and approach to treatment.

Aortic stiffness is a hallmark of aging, and classic cardiovascular risk factors play a role in accelerating this process. Current changes in medicine, which focus on preventive care, have led to a growing interest in noninvasive evaluation of aortic stiffness. Aortic stiffness has emerged as a good tool for further risk stratification because it has been linked to increased risk of atherosclerotic heart disease, myocardial infarction, heart failure, and stroke. This has led to the invention and validation of multiple methods to measure aortic stiffness. Pulse wave velocity is emerging as the gold standard for evaluation of aortic stiffness. This review focuses on the pathophysiology involved in aortic stiffness, methods available for evaluation of aortic stiffness, the importance of central pressure as a predictor of future cardiovascular events, and therapies that affect aortic stiffness.

Hypoglycemia From a Cardiologist's Perspective

Hypoglycemia in people with diabetes mellitus (DM) has been potentially linked to cardiovascular morbidity and mortality. Pathophysiologically, hypoglycemia triggers activation of the sympathoadrenal system, leading to an increase in counter‐regulatory hormones and, consequently, increased myocardial workload and oxygen demand. Additionally, hypoglycemia triggers proinflammatory and hematologic changes that provide the substrate for possible myocardial ischemia in the already‐diseased diabetic cardiovascular system. Hypoglycemia creates electrophysiologic alterations causing P‐R–interval shortening, ST‐segment depression, T‐wave flattening, reduction of T‐wave area, and QTc‐interval prolongation. Patients who experience hypoglycemia are at an increased risk of silent ischemia as well as QTc prolongation and consequent arrhythmias. The Action to Control Cardiovascular Risk in Diabetes (ACCORD) trial showed an increase in all‐cause mortality with intensive glycemic control, whereas the Action in Diabetes and Vascular Disease: Preterax and Diamicron Modified Release Controlled Evaluation (ADVANCE) study and Veterans Affairs Diabetes Trial (VADT) showed no benefit with aggressive glycemic control. Women, elderly patients, and those with renal insufficiency are more vulnerable to hypoglycemic events. In fact, hypoglycemia is the most common metabolic complication experienced by older patients with DM in the United States. The concurrent use of medications like β‐blockers warrants caution in DM because they can mask warning signs of hypoglycemia. Here we aim to elucidate the pathophysiology, review the electrocardiographic changes, analyze the current clinical literature, and consider the safety considerations of hypoglycemia as it relates to the cardiovascular system. In conclusion, in the current era of DM and its vascular ramifications, hypoglycemia from a cardiologists perspective deserves due attention.

A Cardiologist’s View of Hypoglycemia

Recent studies have failed to show an improvement in cardiovascular mortality with intensive glycemic control and aggressive glycated hemoglobin (A1c) targets less than 7.0%. Excessive hypoglycemic episodes with intensive glucose-lowering therapy are thought to be a major factor in the failure to show cardiovascular benefit in these trials. In this article, we review the physiology of glucose metabolism, the cardiovascular pathophysiology of hypoglycemia, and the trials with an intensive glucose-lowering strategy that have studied microvascular and macrovascular complications. We also review the current non-insulin drugs available for the treatment of diabetes and their potential hypoglycemic and cardiovascular impacts.

Keeping Your Arteries Young: Vascular Health

quoted saying ‘‘you’re only as old as your arteries.’’ 4 At a pathobiological level, aortic wall stiffness has been associated with processes involving wall matrix, inflammation, and mechanical stress. Increased collagen content and extracellular matrix (arteriosclerosis) is commonly seen in hypertension and aging. In contrast, atherosclerosis relates to endovascular inflammation, increased cellular oxidative stress, and plaque formation; however, both processes can lead to increased vascular stiffness. 5 Patients with increased aortic stiffness have increased aortic pulse wave velocity and reduced arterial compliance. 6 The clinical implication of increased aortic stiffness results in increased afterload on the left ventricle; alteration in coronary perfusion, which affects cardiac diastolic relaxation; and increased myocardial oxygen consumption. Moreover, these surrogates have been tested in multiple trials with important CV outcomes data. Based on the studies so far, it is evident that increased aortic pulse wave velocity is a strong independent predictor of CV risk, regardless of whether it plays a causative role in CV risk or merely serves as a marker of CV disease already present. One example is found in the Strong Heart Study, 7 which evaluated 2405 patients without CV disease at entry with a 5-year follow-up. During this period, 344 patients had CV events that were significantly associated with high central pulse pressure, thus associating high central pulse pressure with increased arterial stiffness. 1 Another study, the Conduit Artery Function Evaluation (CAFE) trial 8 substudy (on behalf of the Anglo-Scandinavian Cardiac Outcomes Trial [ASCOT] Investigators), evaluated the differential impact of BPlowering drugs on central aortic pressure and clinical outcomes. The study enrolled 2073 patients from 5 ASCOT centers after being on treatment for about 1 year. A total of 19,257 patients were enrolled in the ASCOT trial. All patients had hypertension and 3 additional risk factors. They were randomized in a 2 2 factorial design to receive 1 of 2 antihypertensive regimens: amlodipine (5 ⁄10 mg) with or without perindopril (4 ⁄8 mg) or atenolol (50 ⁄100 mg) with or without a diuretic. Despite similar brachial arm systolic BPs in the two treatment arms, there was a significant decrease in both central aortic pulse pressure and central aortic systolic pressure in the angiotensin-converting enzyme (ACE) inhibitor ⁄calcium channel blocker (CCB) arm vs the b-blocker ⁄diuretic arm. This study suggested that ACE inhibitor ⁄CCB treatment was significantly better. In addition, using the Cox proportional hazards modeling, they determined that central aortic pulse pressure was significantly associated with a post hoc‐defined composite outcome of total CV events (unadjusted P<.0001; P<.05 after adjustment for baseline variables). Based on these data, it can be inferred that arterial stiffness and its components do affect CV outcomes. The vascular etiologies of these vessel wall changes require a closer look.

Effect of glitazones on the progression of coronary artery disease in type 2 diabetes patients.

The effect of thiazolidinediones (TZDs) on the progression of atherosclerosis in diabetes patients remains unclear. There has been heightened interest in recent years in this class of diabetes medications due to the non-glycemic lowering effects, such as altering lipids, inflammation and hematologic profiles. There have been several exciting studies over the past few years focused on the mechanism of action of the TZDs with respect to alteration in the cardio-metabolic profile in diabetes patients. New tools such as intravascular ultrasound have been used to follow plaques characteristics over time on a much more sensitive scale than has ever been possible in the past by coronary angiograms. These advances have enabled researchers to follow closely the macrovascular effects of different anti-atherosclerotic medications such as statins and TZDs. This article reviews the pathophysiology of atherosclerosis in diabetes, the role that TZDs play in this process and the imaging trials looking at the progression or regression of atherosclerosis in patients treated with TZDs.

Potential Cardiometabolic Benefits of Renal Artery Denervation in Diabetics

Treatment of hypertension using renal artery sympathetic denervation was first reported as early as 1924, but only recently has the advent of safer, less invasive techniques allowed this treatment modality to emerge as a promising treatment for hypertension. Aside from reductions in blood pressure, the effect of this treatment appears to be more widespread than initially thought. Renal artery sympathetic denervation may globally reduce cardiovascular risk through a variety of mechanisms such as decreased insulin resistance, oxidative stress, and organ hypertrophy, along with improvement in diastolic function and other metabolic parameters. The following is a comprehensive review of current literature on renal artery sympathetic denervation with a focus on potential cardiovascular benefits.

Glucose control and cardiovascular outcomes in clinical trials of sodium glucose co-transporter 2 inhibitor treatments in type 2 diabetes

Currently available medications for the treatment of type 2 diabetes have limitations, and many patients do not achieve glycaemic control. Recently, a new approach has emerged using sodium glucose co-transporter 2 (SGLT2) inhibitors that decrease glucose reabsorption in the kidneys, increasing urinary glucose excretion. These agents offer the potential to improve glycaemic control independently of insulin pathways while avoiding hypoglycaemia. Two drugs of this class, canagliflozin and dapagliflozin, have been approved by the US Food and Drug Administration (FDA); another, empagliflozin, has been filed for regulatory approval and several others are in advanced development. These drugs have been shown to effectively reduce blood glucose, fasting plasma glucose and glycated haemoglobin (HbA1C) levels in phase III clinical trials when used as monotherapy and as add-on therapy to other diabetes medications, including insulin. Another advantage of the SGLT2 inhibitors over existing treatments is the improvement in cardiovascular risk factors, particularly in terms of reductions in blood pressure and body weight. SGLT2 inhibitors have been generally well tolerated. While more long-term safety data are required to elucidate the benefit-risk profile of SGLT2 inhibitors, the rationale for their use in type 2 diabetes therapy is strong.Currently available medications for the treatment of type 2 diabetes have limitations, and many patients do not achieve glycaemic control. Recently, a new approach has emerged using sodium glucose co-transporter 2 (SGLT2) inhibitors that decrease glucose reabsorption in the kidneys, increasing urinary glucose excretion. These agents offer the potential to improve glycaemic control independently of insulin pathways while avoiding hypoglycaemia. Two drugs of this class, canagliflozin and dapagliflozin, have been approved by the US Food and Drug Administration (FDA); another, empagliflozin, has been filed for regulatory approval and several others are in advanced development. These drugs have been shown to effectively reduce blood glucose, fasting plasma glucose and glycated haemoglobin (HbA 1C ) levels in phase III clinical trials when used as monotherapy and as add-on therapy to other diabetes medications, including insulin. Another advantage of the SGLT2 inhibitors over existing treatments is the improvement in cardiovascular risk factors, particularly in terms of reductions in blood pressure and body weight. SGLT2 inhibitors have been generally well tolerated. While more long-term safety data are required to elucidate the benefit–risk profile of SGLT2 inhibitors, the rationale for their use in type 2 diabetes therapy is strong.