How hyperglycemia promotes atherosclerosis: molecular mechanisms

Both type I and type II diabetes are powerful and independent risk factors for coronary artery disease (CAD), stroke, and peripheral arterial disease. Atherosclerosis accounts for virtually 80% of all deaths among diabetic patients. Prolonged exposure to hyperglycemia is now recognized a major factor in the pathogenesis of atherosclerosis in diabetes. Hyperglycemia induces a large number of alterations at the cellular level of vascular tissue that potentially accelerate the atherosclerotic process. Animal and human studies have elucidated three major mechanisms that encompass most of the pathological alterations observed in the diabetic vasculature: 1) Nonenzymatic glycosylation of proteins and lipids which can interfere with their normal function by disrupting molecular conformation, alter enzymatic activity, reduce degradative capacity, and interfere with receptor recognition. In addition, glycosylated proteins interact with a specific receptor present on all cells relevant to the atherosclerotic process, including monocyte-derived macrophages, endothelial cells, and smooth muscle cells. The interaction of glycosylated proteins with their receptor results in the induction of oxidative stress and proinflammatory responses 2) oxidative stress 3) protein kinase C (PKC) activation with subsequent alteration in growth factor expression. Importantly, these mechanisms may be interrelated. For example, hyperglycemia-induced oxidative stress promotes both the formation of advanced glycosylation end products and PKC activation

Morphine in the Setting of Acute Heart Failure: Do the Risks Outweigh the Benefits?

The use of opioids in acute pulmonary oedema is considered standard therapy by many physicians. The immediate relieving effect of morphine on the key symptomatic discomfort associated with acute heart failure, dyspnoea, facilitated the categorisation of morphine as a beneficial treatment in this setting. During the last decade, several retrospective studies raised concerns regarding the safety and efficacy of morphine in the setting of acute heart failure. In this article, the physiological effects of morphine on the cardiovascular and respiratory systems are summarised, as well as the potential clinical benefits and risks associated with morphine therapy. Finally, the reported clinical outcomes and adverse event profiles from recent observational studies are discussed, as well as future perspectives and potential alternatives to morphine in the setting of acute heart failure

Revascularization for coronary artery disease in diabetes mellitus: Angioplasty, stents and coronary artery bypass grafting

Author Manuscript: 2011 April 14Patients with diabetes mellitus (DM) are prone to a diffuse and rapidly progressive form of atherosclerosis, which increases their likelihood of requiring revascularization. However, the unique pathophysiology of atherosclerosis in patients with DM modifies the response to arterial injury, with profound clinical consequences for patients undergoing percutaneous coronary intervention (PCI). Multiple studies have shown that DM is a strong risk factor for restenosis following successful balloon angioplasty or coronary stenting, with greater need for repeat revascularization and inferior clinical outcomes. Early data suggest that drug eluting stents reduce restenosis rates and the need for repeat revascularization irrespective of the diabetic state and with no significant reduction in hard clinical endpoints such as myocardial infarction and mortality. For many patients with 1- or 2-vessel coronary artery disease, there is little prognostic benefit from any intervention over optimal medical therapy. PCI with drug-eluting or bare metal stents is appropriate for patients who remain symptomatic with medical therapy. However, selection of the optimal myocardial revascularization strategy for patients with DM and multivessel coronary artery disease is crucial. Randomized trials comparing multivessel PCI with balloon angioplasty or bare metal stents to coronary artery bypass grafting (CABG) consistently demonstrated the superiority of CABG in patients with treated DM. In the setting of diabetes CABG had greater survival, fewer recurrent infarctions or need for re-intervention. Limited data suggests that CABG is superior to multivessel PCI even when drug-eluting stents are used. Several ongoing randomized trials are evaluating the long-term comparative efficacy of PCI with drug-eluting stents and CABG in patients with DM. Only further study will continue to unravel the mechanisms at play and optimal therapy in the face of the profoundly virulent atherosclerotic potential that accompanies diabetes mellitus.National Institutes of Health (U.S.) (GM 49039

Surviving Cancer without a Broken Heart

Chemotherapy-associated myocardial toxicity is increasingly recognized with the expanding armamentarium of novel chemotherapeutic agents. The onset of cardiotoxicity during cancer therapy represents a major concern and often involves clinical uncertainties and complex therapeutic decisions, reflecting a compromise between potential benefits and harm. Furthermore, the improved cancer survival has led to cardiovascular complications becoming clinically relevant, potentially contributing to premature morbidity and mortality among cancer survivors. Specific higher-risk populations of cancer patients can benefit from prevention and screening measures during the course of cancer therapies. The pathobiology of chemotherapy-induced myocardial dysfunction is complex, and the individual patient risk for heart failure entails a multifactorial interaction between the selected chemotherapeutic regimen, traditional cardiovascular risk factors, and individual susceptibility. Treatment with several specific chemotherapeutic agents, including anthracyclines, proteasome inhibitors, epidermal growth factor receptor inhibitors, vascular endothelial growth factor inhibitors, and immune checkpoint inhibitors imparts increased risk for cardiotoxicity that results from specific therapy-related mechanisms. We review the pathophysiology, risk factors, and imaging considerations as well as patient surveillance, prevention, and treatment approaches to mitigate cardiotoxicity prior, during, and after chemotherapy. The complexity of decision-making in these patients requires viable discussion and partnership between cardiologists and oncologists aiming together to eradicate cancer while preventing cardiotoxic sequelae

Role of CABG in the management of obstructive coronary arterial disease in patients with diabetes mellitus

Multiple studies have shown that diabetes mellitus (DM) can affect the efficacy of revascularization therapies and subsequent clinical outcomes. Selection of the appropriate myocardial revascularization strategy is critically important in the setting of multivessel coronary disease. Optimal medical therapy is an appropriate first-line strategy in patients with DM and mild symptoms. When medical therapy does not adequately control symptoms, revascularization with either PCI or CABG may be used. In patients with treated DM, moderate to severe symptoms and complex multivessel coronary disease, coronary artery bypass graft surgery provides better survival, fewer recurrent infarctions and greater freedom from re-intervention. Decisions regarding revascularization in patients with DM must take into account multiple factors and as such require a multidisciplinary team approach (‘heart team’).National Institutes of Health (U.S.) (R01 GM-49039

Coronary Artery Disease and Diabetes Mellitus

Coronary artery disease (CAD) is a major determinant of the long-term prognosis among patients with diabetes mellitus (DM). DM is associated with a 2 to 4-fold increased mortality risk from heart disease. Furthermore, in patients with DM there is an increased mortality after MI, and worse overall prognosis with CAD. Near-normal glycemic control for a median of 3.5 to 5 years does not reduce cardiovascular events. Thus, the general goal of HbA1c <7% appears reasonable for the majority of patients. Iatrogenic hypoglycemia is the limiting factor in the glycemic management of diabetes, and is an independent cause of excess morbidity and mortality. Statins are effective in reducing major coronary events, stroke, and the need for coronary revascularization

Supplementary Material for: Biventricular Rupture with Extracardiac Left-to-Right Shunt Complicating Acute Myocardial Infarction

<b><i>Background:</i></b> Simultaneous rupture of the left and right ventricles is an extremely rare mechanical complication of acute myocardial infarction (MI). When associated with the formation of a false aneurysm, an extracardiac left-to-right shunt may occur. <b><i>Methods:</i></b> We summarized all published data describing this unique condition. We searched the PubMed and Google Scholar databases for case reports in peer-reviewed journals from 1 January 1980 to 1 May 2015. We identified 16 articles describing 17 cases. <b><i>Results:</i></b> In all but 1 case, biventricular wall rupture (BVWR) resulted from an inferior MI. The clinical presentations of BVWR were variable and included cardiogenic shock, congestive heart failure and an absence of any cardiac symptoms. In most cases, there was a hemodynamically significant left-to-right shunt, with pulmonary to systemic blood flow (Qp/Qs) >2. Diagnostic difficulties were reported in most cases, and some patients were initially misdiagnosed as having ventricular septal rupture (VSR). Surgical closure of the defect was successful in most cases, and some asymptomatic patients were managed conservatively. <b><i>Conclusion:</i></b> BVWR with an intact interventricular septum and extracardiac left-to-right shunt is a rare mechanical complication of acute MI, often misdiagnosed as VSR. It has a variable clinical course, probably related to the magnitude of the shunt