Son V. Pham

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.

2017 update on pain management in patients with chronic kidney disease

Abstract The prevalence of pain has been reported to be >60–70% among patients with advanced and end-stage kidney disease. Although the underlying etiologies of pain may vary, pain per se has been linked to lower quality of life and depression. The latter is of great concern given its known association with reduced survival among patients with end-stage kidney disease. We herein discuss and update the management of pain in patients with chronic kidney disease with and without requirement for renal replacement therapy with the focus on optimizing pain control while minimizing therapy-induced complications.

Correction of hyponatremia and osmotic demyelinating syndrome: have we neglected to think intracellularly?

BackgroundOsmotic demyelination syndrome (ODS) is a complication generally associated with overly rapid correction of hyponatremia. Traditionally, nephrologists have been trained to focus solely on limiting the correction rate. However, there is accumulating evidence to suggest that the prevention of ODS is beyond achieving slow correction rates.MethodsWe (1) reviewed the literature for glial intracellular protective alterations during hyperosmolar stress, a state presumed equivalent to the rapid correction of hyponatremia, and (2) analyzed all available hyponatremia-associated ODS cases from PubMed for possible contributing factors including correction rates and concurrent metabolic disturbances involving hypokalemia, hypophosphatemia, hypomagnesemia, and/or hypoglycemia.ResultsIn response to acute hyperosmolar stress, glial cells undergo immediate extracellular free water shift, followed by active intracellular Na+, K+ and amino acid uptake, and eventual idiogenic osmoles synthesis. At minimum, protective mechanisms require K+, Mg2+, phosphate, amino acids, and glucose. There were 158 cases of hyponatremia-associated ODS where both correction rates and other metabolic factors were documented. Compared with the rapid correction group (>0.5xa0mmol/L/h), the slow correction group (≤0.5xa0mmol/L/h) had a greater number of cases with concurrent hypokalemia (49.4 vs. 33.3xa0%, pxa0=xa00.04), and a greater number of cases with any concurrent metabolic derangements (55.8 vs. 38.3xa0%, pxa0=xa00.03).ConclusionGlial cell minimizes volume changes and injury in response to hyperosmolar stress via mobilization and/or utilization of various electrolytes and metabolic factors. The prevention of ODS likely requires both minimization of correction rate and optimization of intracellular response during the correction phase when a sufficient supply of various factors is necessary.

Play of Chance Versus Concerns Regarding Dipeptidyl Peptidase-4 Inhibitors: Heart Failure and Diabetes

The delicate balance of disease management versus off-target effects of treatment continues to be a vital concern to both patients and physicians. This article offers a brief overview of heart failure in diabetes and comments on the recent outcome trials of dipeptidyl peptidase-4 (DPP-4) inhibitors, with a closer look at a few pathobiological concerns.nnThe importance of safe antidiabetic treatments becomes apparent when one considers the increasing obesity and diabetes pandemics. Approximately 150,000 patients with moderate-high cardiovascular (CV) risk factor profiles are currently enrolled in trials of antidiabetic agents. Establishing the CV safety of newer antidiabetic agents, especially with respect to heart failure, remains crucial.nnHeart failure syndrome is a symptom complex composed of worsening shortness of breath, orthopnea, paroxysmal nocturnal dyspnea, fatigue, and the well-known manifestation of ankle edema. The syndrome is characterized by physical findings of fluid retention (dependent edema), a third heart sound, rales sounds, and distension of the neck veins. In addition, heart failure is associated with chronic inflammation and a prothrombotic state. Endothelial dysfunction and proteomic and neurohormonal activation occur many months before development of the syndrome complex.1,2nnNewer areas of basic science research have identified potential prognostic indicators in chronic heart failure (miR126 and miR508-5p) that might be used as novel markers leading to earlier diagnosis and treatment of heart failure.3,4 Heart failure has several etiologies ranging from mechanical and electrical dysfunction to structural and valvular abnormities. Moreover, the consequences of heart failure are multi-systemic and adversely affect the liver, kidneys, bone marrow, and muscle.nnRecent data from the Olmstead County population study5 showed that patients with diabetes had equal amounts of systolic and diastolic dysfunction. Patients with diabetes frequently have preserved left-ventricular function (a normal ejection fraction) but with a poorly compliant left ventricle that is …

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.

EMPA-REG OUTCOME: The Cardiologist's Point of View

Cardiologists could view empagliflozin as a cardiovascular drug that also has a beneficial effect on reducing hyperglycemia in patients with type 2 diabetes mellitus (T2DM). The effects of empagliflozin in lowering the risk of cardiovascular death and hospitalization for heart failure in T2DM patients with high cardiovascular risk during the recent Empagliflozin Cardiovascular Outcome Event Trial in Type 2 Diabetes Mellitus Patients-Removing Excess Glucose (EMPA-REG OUTCOME) trial may be explained principally in terms of changes to cardiovascular physiology; namely, by the potential ability of empagliflozin to reduce cardiac workload and myocardial oxygen consumption by lowering blood pressure, improving aortic compliance, and improving ventricular arterial coupling. These concepts and hypotheses are discussed in this report.

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.

Does dipeptidyl peptidase IV inhibitor increase the risk of heart failure? A cardiologist's paradox

Diabetes patients have a higher burden of cardiovascular disease compared with the general population. In addition, type 2 diabetes portends a very high risk for major adverse cardiovascular events. The SAVOR trial showed that patients with documented type 2 diabetes and a previous history of, or risk factors for, cardiovascular disease had a 1-year cardiovascular event rate of 2–3%. Whereas in the EXAMINE trial, type 2 diabetes patients with acute coronary syndrome had a 1-year event rate between 6 and 7% after revascularization. Both of these prospective trials used new dipeptidyl peptidase IV (DPP-4) inhibitors as the treatment modality. Clinically, this class of compounds is extremely well tolerated by patients. The new DPP-4 inhibitors were promising from previous meta-analyses at reducing cardiovascular outcomes. In this article, we review literature on the cardiovascular outcomes with oral hypoglycemic agents, focusing on the two recent, large prospective trials on DDP-4 inhibitors. It is important to recognize that these trials enrolled different patients. The SAVOR trial had type 2 diabetes patients (>40 years old) with established cardiovascular disease or multiple cardiovascular risk factors, whereas EXAMINE trial had type 2 diabetes patients (>18 years old) 15–90 days postrevascularization for acute coronary syndrome. The primary cardiovascular endpoint was a composite of cardiovascular death, nonfatal myocardial infarction, or nonfatal stroke. Neither trial showed a significant cardiovascular benefit. However, neither trial showed increased cardiovascular mortality. Cardiovasc Endocrinol 3:111–116

Myocardial considerations in type 2 diabetes: 2018: 2型糖尿病患者的心肌问题:2018年

Heart failure (HF) continues to be one of the biggest public health problems in the 21st century, affecting 5.7 million adults in the US and accounting for one in nine deaths. Half of those developing HF die within 5 years of diagnosis. The cost associated with HF (i.e. for healthcare services, medications, and missed days of work) is estimated to be US

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

30 billion dollars per year. The leading causes of HF continue to be coronary heart disease (the most common), hypertension, and diabetes. In recent years, increasing numbers of patients with diabetes developing shortness of breath have been found to have left ventricular (LV) diastolic dysfunction. This is found in approximately 28% of asymptomatic and 81% of symptomatic patients with HF and is referred to as HF with preserved ejection fraction (HFpEF). Currently, there is no good treatment for HFpEF, with a number of failed trials. Moreover, recent landmark HF trials had only a low prevalence of diabetes patients (see Fig. 1). Bursi et al. prospectively evaluated 556 patients from Olmsted County (MN, USA) using echocardiograms, finding that 44% of patients in that community had isolated LV diastolic dysfunction. At 6 months, mortality was 16% for both preserved and reduced ejection fraction (EF; ageand sex-adjusted hazard ratio 0.85; 95% confidence interval [CI] 0.61–1.19; P = 0.33 for preserved vs reduced EF). In summary, HF is found and well recognized in diabetes patients. It is also frequently reported as diastolic dysfunction with normal EF, commonly found in hypertensive patients with diabetes. In a recently published HF position paper, in current type 2 diabetes mellitus (T2DM) trials the prevalence of HF is approximately 20% (Fig. 2). Moreover, the prevalence of T2DM in HF trials is approximately 35%. There have been numerous HF trials completed, but only three major trials found a significant increase in adjusted allcause and cardiovascular mortality (Table 1).