Thinking outside the box: Use of the pressure wire to assess intracranial large artery stenoses.

A novel study investigating the utility of the 0.014″ diameter pressure wire to assess the hemodynamic significance of intermediate intracranial stenosis. Technical aspects of pressure wire positioning across intracranial arteries are described. Further research is required to clarify the assessment of pressure gradients in the cerebral circulation and to define the optimal threshold for intervention.

Cardiac Manifestations of Congenital Generalized Lipodystrophy.

IN BRIEF Congenital lipodystrophy is a rare genetic disorder characterized by a near-complete absence of fat cells, hypoleptinemia leading to a voracious appetite, and marked insulin resistance. This article focuses on the known cardiovascular manifestations of patients with congenital lipodystrophy, including cardiomyopathy, cardiac arrhythmias, and accelerated atherosclerosis arising from a markedly deranged metabolic milieu. Future research that targets leptin deficiency (metreleptin) and apoC3 mRNA (antisense oligonucleotide) could open a window for potential pharmacological treatment of this challenging disorder.

Imaging of vulnerable plaques using near-infrared spectroscopy for risk stratification of atherosclerosis.

Although the prevalent approach in cardiology is largely "stenosis-centric," it has been long known that most acute coronary events are caused by apparently angiographically nonsignificant stenosis. This has led to a gradual paradigm shift from detection of significant stenosis to detection of lesion instability. A number of imaging modalities have been developed that help in this quest; however, none have been as promising as near-infrared spectroscopy used for detection of coronary plaque characteristics. In this article we discuss the various invasive imaging tools available to the interventional cardiologist, with special emphasis on near-infrared spectroscopy as a key emerging imaging technology.

Differential cardiovascular profiles of sodium-glucose cotransporter 2 inhibitors: critical evaluation of empagliflozin.

One of the most feared repercussions of type 2 diabetes mellitus is the risk of adverse cardiovascular outcomes. The current antidiabetic agents on the market have had difficulty in showing cardiovascular outcome improvement. The EMPA-REG OUTCOME trial studied the sodium-glucose cotransporter 2 inhibitor empagliflozin in type 2 diabetic patients at high risk of cardiovascular events. The trial results revealed a decrease in the composite primary end points of death from cardiovascular causes, nonfatal myocardial infarction, and nonfatal stroke in those taking empagliflozin vs placebo. Those taking the medication also had a significant decrease in death from any cause, death from cardiovascular cause, and hospitalization for heart failure. The EMPA-REG trial is paradigm shifting because it demonstrates a clear mortality benefit to cardiovascular outcomes with a low side-effect profile, in contrast to prior outcome studies of hypoglycemic agents. Further studies are required to better clarify the long-term safety and efficacy of this promising class of diabetic drugs.

Myocardial tissue caveolae.

Caveolae and their coat proteins, caveolins (Cav), are cave-like invaginations found in the plasma membrane of a variety of cells. These unique vesicles and their coat proteins, Cavs, have diverse effects on endothelial function, nitric oxide synthesis regulation, signal transduction, cholesterol metabolism, and apoptosis. Animal studies in Cav knockout mice demonstrate the vital role of these structural proteins on endothelial and vascular function. Genetic studies have proposed that beside neoplasia, Cavs may play a role in the development of atherosclerosis, cardiomyopathy, long QT syndrome, pulmonary fibrosis, and muscular dystrophy. The role of Cav expression in atherosclerotic disease is poorly understood and remains controversial. Interestingly, there is emerging evidence between low Cav-1 levels and the vulnerable plaque, which could potentially identify Cav-1 as a novel plaque biomarker. Cavs, through intricate biochemical pathways involving endothelial nitric oxide synthase and mitogen-activated protein kinase, are known to affect the cardiovascular system at multiple levels. In the present review, we aim to highlight the nature and types of caveolae, caveolar signaling mechanisms and regulation, and the pathophysiology of Cavs as it pertains to the cardiovascular system. Ongoing research is needed to clarify the diagnostic and prognostic role of these novel proteins and to determine how the effects of Cavs can translate into clinical medicine.

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 Veteran's 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 ß-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 cardiologist's perspective deserves due attention.

Acute coronary syndrome in patients with diabetes mellitus: perspectives of an interventional cardiologist.

Diabetes mellitus (DM) is well known to be a coronary artery disease risk equivalent but the cellular mechanism is not completely understood. Recently, virtual histology intravascular ultrasound has demonstrated that patients with DM tend to have a higher occurrence of vulnerable plaques as compared with patients without DM. Insulin-sensitizing agents, such as metformin, have been shown to have limited cardioprotective effects, whereas thiazolidinediones, such as rosiglitazone, have been reported to have possible deleterious effects on cardiovascular mortality in a meta-analysis; however, limited data exist. In contrast, pioglitazone has been reported to have a significant benefit in patients with type 2 DM with acute coronary syndrome (ACS). Animal and human studies have demonstrated the myocardial protective effects of incretins and hold promise in reducing the incidence of major adverse cardiac events in patients with DM. Moreover, in addition to aspirin, the early use of potent antiplatelet agents, such as prasugrel and intravenous glycoprotein IIb-IIIa inhibitors, in patients with DM presenting with ACS is crucial for reducing cardiovascular events in most patients. Thus, patients with DM deserve special attention in global risk factor reduction and development of newer therapeutic agents to improve glycemic control while minimizing or reducing cardiovascular events. This article focuses on ACS in patients with DM, the pathophysiology of "vulnerable blood" in patients with DM, and newer treatment strategies to improve outcomes in this high-risk patient population.