Relationship of ejection fraction and natriuretic peptide trajectories in heart failure with baseline reduced and mid-range ejection fraction.

BACKGROUND: The prognostic importance of trajectories of neurohormones relative to left ventricular function over time in heart failure with reduced and mid-range EF (HFrEF and HFmrEF) is poorly defined. OBJECTIVE: To evaluate left ventricular ejection fraction (LVEF) and B-type natriuretic peptide (BNP) trajectories in HFrEF and HFmrEF. METHODS: Analyses of LVEF and BNP trajectories after incident HF admissions presenting with abnormal LV systolic function were performed using 3 methods: a Cox proportional hazards model with time-varying covariates, a dual longitudinal-survival model with shared random effects, and an unsupervised analysis to capture 3 discrete trajectories for each parameter. RESULTS: Among 1,158 patients (68.9 ± 13.0 years, 53.3% female), both time-varying LVEF measurements (P=.001) and log-transformed BNP measurements (p-values=2 × 10-16) were independently associated with survival during 6 years after covariate adjustment. In the dual longitudinal/survival model, both LVEF and BNP trajectories again were independently associated with survival (P<.0001 in each model); however, LVEF was more dynamic than BNP (P <.0001 for time covariate in LVEF longitudinal model versus P=.88 for the time covariate in BNP longitudinal model). In the unsupervised analysis, 3 discrete LVEF trajectories (dividing the cohort into approximately thirds) and 3 discrete BNP trajectories were identified. Discrete LVEF and BNP trajectories had independent prognostic value in Kaplan-Meier analyses (P<.0001), and substantial membership variability across BNP and LVEF trajectories was noted. CONCLUSION: Although LVEF trajectories have greater temporal variation, BNP trajectories provide additive prognostication and an even stronger association with survival times in heart failure patients with abnormal LV systolic function.

Pulmonary Artery Proportional Pulse Pressure (PAPP) Index Identifies Patients With Improved Survival From the CardioMEMS Implantable Pulmonary Artery Pressure Monitor.

BACKGROUND: Pulmonary artery proportional pulse pressure (PAPP) was recently shown to have prognostic value in heart failure (HF) with reduced ejection fraction (HFrEF) and pulmonary hypertension. We tested the hypothesis that PAPP would be predictive of adverse outcomes in patients with implantable pulmonary artery pressure monitor (CardioMEMS™ HF System, St. Jude Medical [now Abbott], Atlanta, GA, USA). METHODS: Survival analysis with Cox proportional hazards regression was used to evaluate all-cause deaths and HF hospitalisation (HFH) in CHAMPION trial1 patients who received treatment with the CardioMEMS device based on the PAPP. RESULTS: Among 550 randomised patients, 274 had PAPP ≤ the median value of 0.583 while 276 had PAPP>0.583. Patients with PAPP≤0.583 (versus PAPP>0.583) had an increased risk of HFH (HR 1.40, 95% CI 1.16-1.68, p=0.0004) and experienced a significant 46% reduction in annualised risk of death with CardioMEMS treatment (HR 0.54, 95% CI 0.31-0.92) during 2-3 years of follow-up. This survival benefit was attributable to the treatment benefit in patients with HFrEF and PAPP≤0.583 (HR 0.50, 95% CI 0.28-0.90, p<0.05). Patients with PAPP>0.583 or HF with preserved EF (HFpEF) had no significant survival benefit with treatment (p>0.05). CONCLUSION: Lower PAPP in HFrEF patients with CardioMEMS constitutes a higher mortality risk status. More studies are needed to understand clinical applications of PAPP in implantable pulmonary artery pressure monitors.

Nuclear cardio-oncology: From its foundation to its future.

Cardio-oncology is a growing field focused on the prevention and treatment of cardiovascular disease in oncologic patients. While a major focus of chemotherapy-related cardiac dysfunction has been on left ventricular ejection fraction, oncologic treatment can lead to cardiovascular pathology in a variety of ways. The use of multimodality imaging is essential to the care of these patients, with nuclear cardiology playing an important role. We will review nuclear cardiology's history, its current role, and its promising future in cardio-oncology and the management of these patients.

Tyrosine kinase inhibitor toxicity manifesting as comorbid Moyamoya syndrome and obstructive coronary artery disease: A case report and review of the literature.

Tyrosine kinase inhibitors (TKIs) have assumed an increasingly vital role in treating various hematologic and oncologic malignancies. However, adverse effects with respect to vascular disease have been reported following administration of this class of medications. Here, we present a case report of TKI toxicity, manifesting as comorbid Moyamoya syndrome and obstructive coronary artery disease leading to a type 1 non-ST-elevation myocardial infarction. This patient eventually required percutaneous coronary intervention with drug-eluting stent placement in the right coronary artery. Given the expanding indications of TKI therapy, this case highlights a growing population subset which may require coronary and/or peripheral interventions to treat sequela from otherwise life-prolonging treatment.

Right atrial to left atrial volume index ratio is associated with increased mortality in patients with pulmonary hypertension.

BACKGROUND: Pulmonary hypertension (PH) is characterized by increased pulmonary vascular resistance leading to right heart failure. Elevated right atrial (RA) pressure reflects right ventricular (RV) pressure overload and is an established risk factor for mortality in PH. We hypothesized that PH patients with an increased ratio of RA to LA volume index (RAVI/LAVI), would have increased mortality. METHODS: We evaluated the association of RAVI/LAVI with mortality in 124 patients seen at a single academic center's PH clinic after adjusting for the REVEAL risk score, an established risk score in PH. LA and RA volume indices were measured in the four-and two-chamber views by two independent researchers. Multivariable logistic regression was used to model the independent association of RAVI/LAVI with survival. RESULTS: Among 124 patients (mean age 62 ± 12.7 years, 68.6% female), each unit increase in RAVI/LAVI was associated with a nearly twofold increase in mortality (OR: 1.91, 95% CI: 1.20-3.04). In a multivariable logistic regression, each unit increase in RAVI/LAVI was associated with a nearly twofold increase in mortality (OR: 1.73, 95% CI: 1.003-2.998). Furthermore, RAVI/LAVI in the highest quartile (>1.42) was significantly associated with elevated right atrial pressure (RAP) to pulmonary artery wedge pressure ratio (RAP/PAWP) (0.76 ± 0.41, P = 0.02) compared with the lowest quartile (<0.77), suggesting an interaction between invasive hemodynamic data, atrial structural changes, and mortality in PH. CONCLUSIONS: Increased RAVI/LAVI in PH is associated with decreased survival and accounts for atrial structural remodeling related to invasive hemodynamics. These findings support further study of this index in predicting outcomes in PH.

Pelvic synovial sarcoma of unknown primary origin: case report and literature review.

A case report of a 26-year-old woman with pelvic pain for one-month duration is presented. The physical exam was unremarkable, but a right pelvic mass was found on ultrasound. Computed tomography (CT) of the abdomen/pelvis confirmed a heterogeneous 6 x 4.4 cm mass within the right pelvis adjacent to the superior-lateral aspect of the uterus. Laparoscopy was performed, and the mass was found to be friable and necrotic. The origin of the mass was not able to be determined due to the collapse of the mass upon instrumentation. Histology revealed spindle cells. Further studies, including immunochemical staining, revealed a synovial sarcoma. Patient underwent laparotomy for staging and in hopes of obtaining clear tumor margins. Surgery revealed subsequent tumors involving the mesentery of the small intestine and the peritoneal wall. Biopsies taken at surgery did not reveal the primary origin of the original pelvic tumor.

New insights into myocardial glucose metabolism: surviving under stress.

PURPOSE OF REVIEW: Myocardial glucose uptake and metabolism are essential for maintaining myocardial energetics under circumstances of stress, such as myocardial ischemia or hypertrophy. We will discuss new information as to the mechanisms of altered glucose uptake as a consequence of impaired insulin action as well as emerging alternative cellular signaling mechanisms that lead to increased noninsulin dependent glucose uptake and metabolism. We will also review provocative clinical data that demonstrate the limitations of tight glycemic control as a mechanism to confer myocardial protection in patients with type 2 diabetes and discuss potential mechanistic explanations for the paradoxical results. RECENT FINDINGS: New studies have shed important light on the distal mechanisms involved in insulin-mediated Glut 4 translocation. There are also important new insights into the role of AMP kinase and hypoxia-induced factor-1alpha in mediating myocardial glucose uptake while conferring cardioprotection. SUMMARY: The importance of understanding the link between glucose uptake and cardioprotection is underscored by recent clinical trials that have failed to demonstrate a benefit between tight glycemic control and reduced cardiovascular events. These data underscore the need for additional agents that affect both outcomes.

Glucagon-like peptide-1 and myocardial protection: more than glycemic control.

Pharmacologic intervention for the failing heart has traditionally targeted neurohormonal activation and ventricular remodeling associated with cardiac dysfunction. Despite the multitude of agents available for the treatment of heart failure, it remains a highly prevalent clinical syndrome with substantial morbidity and mortality, necessitating alternative strategies of targeted management. One such area of interest is the ability to modulate myocardial glucose uptake and its impact on cardioprotection. Glucose-insulin-potassium (GIK) infusions have been studied for decades, with conflicting results regarding benefit in acute myocardial infarction. Based on the same concepts, glucagon-like peptide-1-[7-36] amide (GLP-1) has recently been demonstrated to be a more effective alternative in left ventricular (LV) systolic dysfunction. This paper provides a review on the current evidence supporting the use of GLP-1 in both animal models and humans with ischemic and nonischemic cardiomyopathy.

Intra-incisional liposomal bupivacaine and its impact on postcesarean analgesia: a retrospective study.

PURPOSE: The efficacy of long-acting intraincisional bupivacaine in reducing postoperative opioid use among women who have undergone a cesarean is currently unknown. MATERIALS AND METHODS: This was a retrospective case-control study with a 1:1 allocation. We identified 40 patients in each group, for a total of 80. The treatment group was administered 266 mg of liposomal bupivacaine after completion of the cesarean and was compared to historical controls. Data regarding anesthesia administered, opioid consumption, nonsteroidal anti-inflammatory use, acetaminophen use, type of cesarean, reason for cesarean, and length of postoperative stay were recorded. RESULTS: The treatment group used 41.51 mg of morphine equivalents, while the control group consumed 69.90 mg (p < .001); multivariate analysis demonstrated a mean difference of 26.52 mg (95%CI 12.76-40.28). Univariate analysis demonstrated mean difference in intravenous (IV) ketorolac (40.77 mg, p < .001) and IV acetaminophen (1333.33 mg, p < .001) was different and greater in the treatment group; this was controlled for in the multivariate model. There was no difference in oral and IV ibuprofen or oral acetaminophen use between groups. There were no differences between the type of anesthesia, length of stay, reason for cesarean, and classical sections between groups. CONCLUSIONS: Incisional administration of liposomal bupivacaine may be an effective adjunct in reducing opioid use postoperatively and may be a useful adjunct within an enhanced recovery program.

Effecting the sixth core competency: a project-based curriculum.

OBJECTIVE: In agreement with the Accreditation Council for Graduate Medical Education guidelines, a systems-based practice (SBP) curriculum was implemented to provide a hands-on, team-based experience, while providing an opportunity to contribute to quality improvement, and to develop a method to assess residents' understanding of SBP. STUDY DESIGN: During departmental conferences, issues affecting our health care operations were identified. Seven teams were formed and the actionable items were investigated. The salient issues and potential solutions were presented to the department. RESULTS: This project resulted in the development of tools designed to assess competency in SBP, communication skills, and professionalism. Completion of a pre- and posttest and annual oral examination questions revealed a significant improvement in the comprehension of SBP. CONCLUSION: This project served as an effective educational forum for the competencies of SBP, communication skills, and professionalism. This initiative also offered improvement of patient care and/or educating peer providers, thereby fulfilling the goal of SBP in the process of education.

Glucagon-like peptide-1 increases myocardial glucose uptake via p38alpha MAP kinase-mediated, nitric oxide-dependent mechanisms in conscious dogs with dilated cardiomyopathy.

BACKGROUND: We have shown that glucagon-like peptide-1 (GLP-1[7-36] amide) stimulates myocardial glucose uptake in dilated cardiomyopathy (DCM) independent of an insulinotropic effect. The cellular mechanisms of GLP-1-induced myocardial glucose uptake are unknown. METHODS AND RESULTS: Myocardial substrates and glucoregulatory hormones were measured in conscious, chronically instrumented dogs at control (n=6), DCM (n=9) and DCM after treatment with a 48-hour infusion of GLP-1 (7-36) amide (n=9) or vehicle (n=6). GLP-1 receptors and cellular pathways implicated in myocardial glucose uptake were measured in sarcolemmal membranes harvested from the 4 groups. GLP-1 stimulated myocardial glucose uptake (DCM: 20+/-7 nmol/min/g; DCM+GLP-1: 61+/-12 nmol/min/g; P=0.001) independent of increased plasma insulin levels. The GLP-1 receptors were upregulated in the sarcolemmal membranes (control: 98+/-2 density units; DCM: 256+/-58 density units; P=0.046) and were expressed in their activated (65 kDa) form in DCM. The GLP-1-induced increases in myocardial glucose uptake did not involve adenylyl cyclase or Akt activation but was associated with marked increases in p38alpha MAP kinase activity (DCM+vehicle: 97+/-22 pmol ATP/mg/min; DCM+GLP-1: 170+/-36 pmol ATP/mg/min; P=0.051), induction of nitric oxide synthase 2 (DCM+vehicle: 151+/-13 density units; DCM+GLP-1: 306+/-12 density units; P=0.001), and GLUT-1 translocation (DCM+vehicle: 21+/-3% membrane bound; DCM+GLP-1: 39+/-3% membrane bound; P=0.005). The effects of GLP-1 on myocardial glucose uptake were blocked by pretreatment with the p38alpha MAP kinase inhibitor or the nonspecific nitric oxide synthase inhibitor nitro-l-arginine. CONCLUSIONS: GLP-1 stimulates myocardial glucose uptake through a non-Akt-1-dependent mechanism by activating cellular pathways that have been identified in mediating chronic hibernation and the late phase of ischemic preconditioning.