Evaluation of cardiomyopathy in acute myeloid leukemia patients treated with anthracyclines.

BACKGROUND: Acute myeloid leukemia patients receive anthracycline-containing induction chemotherapy. Anthracyclines cause cardiotoxicity; however, there is a paucity of data reflecting the risk of cardiotoxicity in the acute myeloid leukemia population, and risk factors for development of reduced left ventricular ejection fraction are not well established in this population. METHODS: A retrospective cohort study of adult acute myeloid leukemia patients receiving anthracycline-containing induction chemotherapy between March 2011 and August 2017 was performed. Baseline and all additional cardiac monitoring within one year of induction were collected. Home medications and new medication initiation were determined via the electronic health record and new outpatient prescriptions. RESULTS: Of 97 evaluable patients, 25 (25.8%) developed reduced left ventricular ejection fraction and 18 (18.6%) experienced clinical heart failure within one year of induction. The median difference from baseline to lowest left ventricular ejection fraction was -5.0 percentage points, with a range of +10.0 to -52.5. The median time to onset of reduced left ventricular ejection fraction was 27 days, at a median cumulative anthracycline dose of 270 mg/m2. No patient-specific or medication-specific factors were significantly associated with the risk of developing reduced left ventricular ejection fraction. Of 14 patients started on medical management for reduced left ventricular ejection fraction, 10 (71%) responded to therapy. CONCLUSIONS: In this retrospective analysis, we observed that acute myeloid leukemia patients experienced reduced left ventricular ejection fraction more quickly and at lower doses than previously reported in the solid tumor population. Reduced left ventricular ejection fraction was at least partially reversible in most patients started on medical management. Although no factors were significantly associated with decreased cardiomyopathy risk, future assessment of cardioprotective medications may be warranted.

Comparative Analysis of Established Risk Scores and Novel Hemodynamic Metrics in Predicting Right Ventricular Failure in Left Ventricular Assist Device Patients.

BACKGROUND: Right ventricular failure (RVF) portends poor outcomes after left ventricular assist device (LVAD) implantation. Although numerous RVF predictive models have been developed, there are few independent comparative analyses of these risk models. METHODS AND RESULTS: RVF was defined as use of inotropes for >14 days, inhaled pulmonary vasodilators for >48 hours or unplanned right ventricular mechanical support postoperatively during the index hospitalization. Risk models were evaluated for the primary outcome of RVF by means of logistic regression and receiver operating characteristic curves. Among 93 LVAD patients with complete data from 2011 to 2016, the Michigan RVF score (C = 0.74 [95% CI 0.61-0.87]; P = .0004) was the only risk model to demonstrate significant discrimination for RVF, compared with newer risk scores (Utah, Pitt, EuroMACS). Among individual hemodynamic/echocardiographic metrics, preoperative right ventricular dysfunction (C = 0.72 [95% CI 0.58-0.85]; P = .0022) also demonstrated significant discrimination of RVF. The Michigan RVF score was also the best predictor of in-hospital mortality (C = 0.67 [95% CI 0.52-0.83]; P = .0319) and 3-year survival (Kaplan-Meier log-rank 0.0135). CONCLUSIONS: In external validation analysis, the more established Michigan RVF score-which emphasizes preoperative hemodynamic instability and target end-organ dysfunction-performed best, albeit modestly, in predicting RVF and demonstrated association with in-hospital and long-term mortality.

Clinical Impact of Changes in Hemodynamic Indices of Contractile Function During Treatment of Acute Decompensated Heart Failure.

BACKGROUND: The objective of this work was to determine the impact of improving right ventricular versus left ventricular stroke work indexes (RVSWI vs LVSWI) during therapy for acute decompensated heart failure (ADHF). METHODS AND RESULTS: Cox proportional hazards regression and logistic regression were used to analyze key factors associated with outcomes in 175 patients (mean age 56.7 ± 13.6 years, 29.1% female) with hemodynamic data from the Evaluation Study of Congestive Heart Failure and Pulmonary Artery Catheterization Effectiveness trial. In this cohort, 28.6% and 69.7%, respectively, experienced the outcomes of death, transplantation, or ventricular assist device implantatation (DVADTX) and DVADTX or HF rehospitalization (DVADTXHF) during 6 months of follow-up. Increasing RVSWI (ΔRVSWI) from baseline to discharge was associated with a decrease in DVADTXHF (hazard ratio [HR] 0.923, 95% confidence interval [CI] 0.871-0.979) per 0.1 mm Hg⋅L⋅m-2 increase); however, increasing LVSWI (ΔLVSWI) had only a nonsignificant association with decreased DVADTXHF (P = .11) In a multivariable model, patients with ΔRVSWI ≤1.07 mm Hg⋅L⋅m-2 and ΔLVSWI ≤4.57 mm Hg⋅L⋅m-2 had a >2-fold risk of DVADTXHF (HR 2.05, 95% CI 1.23-3.41; P = .006). CONCLUSION: Compared with left ventricular stroke work, increasing right ventricular stroke work during treatment of ADHF was associated with better outcomes. The results promise to inform optimal hemodynamic targets for ADHF.

Diastolic pulmonary gradient predicts outcomes in group 1 pulmonary hypertension (analysis of the NIH primary pulmonary hypertension registry).

BACKGROUND: Diastolic pulmonary gradient (DPG), calculated as the difference between pulmonary artery diastolic pressure and mean pulmonary capillary wedge pressure ≥ 7 mmHg is associated with pulmonary vascular disease and portends poor prognosis in heart failure (HF). The prognostic relevance of DPG in group 1 pulmonary hypertension (PH) is uncertain. METHODS: Using the Pulmonary Hypertension Connection (PHC) risk equation for 225 patients in the NIH-PPH, the 5-year probability of death was calculated, which was then compared with DPG using a Cox proportional hazards model. Kaplan-Meier survival curves were determined for two cohorts using the median DPG of 30 mmHg as cutoff, and significance was tested using the log-rank test. RESULTS: The mean age was 38.1 ± 16.0 years old, 63% female, and 72% were "white". The mean DPG was 31.6 mmHg ± 13.8 mm Hg and only 1.8% had a DPG <7 mm Hg. Increasing DPG was significantly associated with increased 5-year mortality even after adjustment for the PHC risk equation (HR 1.29 per 10 mm Hg increase). When DPG was dichotomized based on the median of 30 mm Hg, the HR for DPG >30 mm Hg with respect to 5-year mortality was 2.03. After adjustment for pulmonary artery systolic pressure (PASP), increasing DPG remained significantly associated with decreased 5 years survival (HR 1.99 for DPG > 30 mm Hg). CONCLUSIONS: DPG is independently associated with survival in group 1 PH patients even after adjustment for the PHC risk equation or PASP. Patients with increased DPG had a 2-fold increased risk of mortality. The use of DPG for guiding treatment and prognosis in group 1 PH should be further investigated.

Decreased Pulmonary Arterial Proportional Pulse Pressure After Pulmonary Artery Catheter Optimization for Advanced Heart Failure Is Associated With Adverse Clinical Outcomes.

BACKGROUND: This study evaluated the novel index pulmonary arterial proportional pulse pressure (PAPP) in the Evaluation Study of Congestive Heart Failure and Pulmonary Artery Catheterization Effectiveness (ESCAPE) trial. METHODS AND RESULTS: Multivariable Cox proportional hazards and logistical regression were used to model 6-month death; death, transplantation, or left ventricular assist device (DTLVAD); and DTLVAD or heart failure rehospitalization (DTLVADHF) with respect to PAPP. Among 175 patients with final hemodynamic data, 15.5% and 33.9%, respectively, died in optimal PAPP (PAPP >0.50) and nonoptimal PAPP (PAPP ≤0.50) groups (P = .008), and PAPP was independently associated with death, DTLVAD, and DTLVADHF (P < .01 for all outcomes). The hypothesized logistic regression model with pulmonary capillary wedge pressure, creatinine, and nonoptimal PAPP had an area under the curve of 0.818 (P < .0001) for death. Furthermore, PAPP as a continuous variable was the most powerful predictor of DTLVADHF (hazard ratio 0.793 per 0.1 increase in PAPP [95% confidence interval 0.659-0.955], chi square 8.80; P = .01) in the Cox model, with no other clinical, laboratory, or hemodynamic parameters significant after adjustment for PAPP. CONCLUSIONS: PAPP, a novel parameter for right-sided proportional pulse pressure, is an independent and powerful predictor of adverse clinical outcomes in advanced HF. Increased PAPP promises to be a useful therapeutic target in patients with pulmonary arterial pressure assessment.

Management of hyperglycemia with the administration of intravenous exenatide to patients in the cardiac intensive care unit.

OBJECTIVE: To evaluate the feasibility, effectiveness, and safety of intravenous exenatide to control hyperglycemia in the cardiac intensive care unit (CICU). METHODS: A prospective, single-center, open-label, nonrandomized pilot study. Forty patients admitted to the CICU with glucose levels of 140 to 400 mg/dL received intravenous exenatide as a bolus followed by a fixed dose infusion for up to 48 hours. Exenatide effectiveness was benchmarked to two historical insulin infusion cohorts, one (INT) with a target glucose of 90 to 119 mg/dL (n = 84) and the other (MOD) with a target of 100 to 140 mg/dL (n = 71). RESULTS: Median admission glucose values were 185.5 mg/dL (161.0, 215.5), 259.0 mg/dL (206.0, 343.0), and 189.5 mg/dL (163.5, 245.0) in the exenatide, MOD, and INT groups, respectively (P<.001). Steady state glucose values were similar between the exenatide (132.0 mg/dL [110.0, 157.0]) and the MOD groups (127.0 mg/dL [105.0, 161.0], P = .15), but lower in the INT group (105.0 mg/dL [92.0, 128.0], P<.001 for exenatide versus INT). Median (IQR) time to steady state was 2.0 hours (1.5, 5.0) in the exenatide group compared to 12.0 hours (7.0, 15.0) in the MOD group (P<.001) and 3.0 hours (1.0, 5.0) in the INT group (P = .80 for exenatide versus INT). Exenatide was discontinued in 3 patients after failure to achieve glycemic control. No episodes of severe hypoglycemia (<50 mg/dL) occurred in patients who received exenatide. Nausea was reported by 16 patients and vomiting by 2 patients. CONCLUSION: Intravenous exenatide is effective in lowering glucose levels in CICU patients, but its use may be limited by nausea.

Evidence-based diuretic therapy for improving cardiovascular prognosis in systemic hypertension.

Diuretics are among the most commonly prescribed cardiovascular (CV) medications. The strength of evidence supporting the effectiveness of diuretics in lowering blood pressure and for preventing major adverse CV events in patients with hypertension varies considerably among diuretic classes and even among agents within the same class. Unfortunately, common prescribing habits among American physicians, including specialists in CV diseases, are not in line with the existing evidence regarding diuretic therapy for improving CV prognosis. In conclusion, although hydrochlorothiazide is the standard diuretic used for hypertension, the outcomes data suggest that chlorthalidone, indapamide, and possibly even the aldosterone receptor blockers (spironolactone and eplerenone) may be superior agents.

Strategies for optimizing glycemic control and cardiovascular prognosis in patients with type 2 diabetes mellitus.

Type 2 diabetes mellitus (DM) is a major cardiovascular (CV) risk factor and, as such, is considered a coronary artery disease risk equivalent. Although glycemic control is associated with decreased CV events epidemiologically, many prospective clinical trials have failed to conclusively demonstrate that aggressive glycemic control improves the CV prognosis of patients with type 2 DM, especially those with long-standing DM. Many therapies for type 2 DM with widely divergent mechanisms of action are available. Some of these drugs, in addition to their glucose-lowering actions, have properties that may reduce or increase CV events. Agents that lower both insulin resistance and postprandial hyperglycemia while at the same time avoiding hypoglycemia may be beneficial for CV health. This article reviews the evidence regarding the use of these agents and appropriate glycemic control targets for improving the adverse CV prognosis associated with type 2 DM. We conducted a systematic review of English articles using MEDLINE and the Cochrane Controlled Trials Register (1970-2010) using the following search terms: cardiovascular disease, randomized trials, hypoglycemia, and insulin resistance.

Review article: eplerenone: an underused medication?

In this article, we review the evidence supporting the use of eplerenone for improving cardiovascular prognosis. Activation of the renin-angiotensin-aldosterone system plays a major role in the pathogenesis of heart disease, and blockage of this system has been shown to improve prognosis in several cardiovascular conditions. The 2 marketed aldosterone antagonists, spironolactone and eplerenone, improve prognosis in patients with left ventricular (LV) dysfunction and are effective antihypertensive medications. In addition, a potential role for aldosterone antagonists in the treatment of patients with heart failure and preserved LV function has been suggested and is currently being evaluated in clinical trials. In patients with myocardial infarction having LV dysfunction and evidence of heart failure, eplerenone improves cardiovascular outcomes and attenuates myocardial remodeling. In addition, eplerenone is effective for the treatment of hypertension, where it regresses both LV hypertrophy and proteinuria (2 powerful markers of increased cardiovascular risk). In contrast to spironolactone, eplerenone essentially lacks the sexual side effects that sometimes limit the use of spironolactone. Hyperkalemia is the main potential side effect of eplerenone, especially when used in combination with other medications that can cause hyperkalemia. Adequate patient selection and monitoring are therefore of utmost importance when using this medication. In conclusion, eplerenone is a medication that offers the cardiovascular therapeutic and prognostic benefits of aldosterone antagonism but with fewer side effects compared to spironolactone.

Neckties for physicians: Yes? No? Maybe?

Nosocomial infections, especially those involving resistant microorganisms, represent one of the challenging problems of modern medicine. Health care providers play an important role in the transmission of these infections. White coats and neckties are among the culprits implicated as vectors for transmission of infections by health care providers. Both pathogenic and non-pathogenic bacteria commonly colonize neckties and avoiding neckties is a simple measure that may prove helpful in our fight against nosocomial infections.

Dietary strategies for the prevention & treatment of metabolic syndrome.

Obesity and the metabolic syndrome are epidemic health problems that are the root of many of the chronic diseases in our society. The increase in obesity in western societies can be largely attributed to changes in diet associated with modern civilization. Dietary strategies to reduce postprandial glucose and triglyceride spikes, and to increase the intake of dietary antioxidants, potassium, and omega-3 fatty acids will be helpful for improving health and reducing metabolic syndrome and obesity.

Dobutamine-induced chest pain does not predict ischemic findings on myocardial perfusion imaging.

BACKGROUND: Chest pain occurs frequently during dobutamine stress testing and is commonly attributed to ischemia. However, the pathophysiologic significance of dobutamine-induced chest pain is uncertain. The purpose of this study is to explore the correlation between dobutamine-induced chest pain and evidence of ischemia on myocardial perfusion imaging (MPI). METHODS AND RESULTS: This study included 1608 patients who underwent dobutamine stress MPI at the Mid America Heart Institute (Kansas City, Mo) and were analyzed retrospectively. Patients were divided into those with chest pain during dobutamine infusion versus those without it. Multivariate and chi(2) analyses were conducted to explore the relationship between chest pain and ischemic changes on MPI. Of 1608 patients, 208 (13%) had chest pain with dobutamine whereas 1400 (87%) did not. MPI ischemia was seen in 47% of patients with chest pain and 43% without chest pain (P = .28). Chest pain was not any more predictive of ischemia when analyzed separately by gender (P = .31). Multivariate analysis did not identify chest pain as a predictor of ischemia (P = .19). Significant predictors of scintigraphic ischemic changes were age (P = .001), gender (P < .0001), smoking (P = .0149), and known coronary artery disease (P < .0001). CONCLUSION: This large retrospective study suggests that chest pain during dobutamine stress testing is not a predictor of ischemia when analyzed against reversible perfusion defects on SPECT MPI.