Titration Of Medical Therapy Research Articles

THU518 Ectopic Cushing Syndrome In A Case Of Ewing Sarcoma

Abstract Disclosure: M. Fasen: None. S.E. Mayson: None. Background: Ewing sarcoma (ES) is a rare and aggressive neoplasm occurring in bone and soft tissue in children to young adults. It is part of a spectrum of neoplastic diseases known as the ES family of tumors that display varying degrees of neuroendocrine features. Ectopic Cushing’s syndrome (ECS) is also a rare but severe condition associated with unregulated ACTH or CRH secretion by neuroendocrine tumors (NETs) that can cause severe hypercortisolism. The most common tumors associated with ECS include small cell lung carcinoma, bronchial carcinoid and medullary carcinoma of the thyroid gland. Sarcomas causing ECS are extremely rare with only a handful of cases reported in the literature, mostly in children. Herein we detail what we believe to be the first reported case of ECS occurring in an adult male patient with ES. Clinical Case: A 23-year-old man with ES metastatic to pancreas, liver and bone was admitted to the hospital with acute on chronic back pain and lower extremity weakness, and subsequently diagnosed with cord compression and neutropenia from chemotherapy. New onset hypertension and refractory hypokalemia were observed prompting endocrinology consultation. Physical examination revealed facial fullness, central obesity and wide violaceous striae on his abdomen and axillae. Biochemical evaluation demonstrated blood glucose consistently over 300 mg/dL, serum potassium 2.5 mmol/L, renin 0.9 ng/ml/hr (0.2-1.6 ng/ml/hr), aldosterone renin ratio < 3.3, morning cortisol 73 ug/dL (4-22 ug/dL), and ACTH 1020 pg/mL (72-63 pg/mL). A 1 mg overnight dexamethasone suppression test yielded a serum cortisol of 90 ug/dL and 24-hour urine free cortisol was 6388 ug/d (<60 ug/d). MRI brain demonstrated a normal pituitary gland, and FDG PET-CT showed new areas of uptake in bone concerning for metastatic progression and new bilateral adrenal enlargement without nodularity. High dose dexamethasone suppression testing was deferred in the context of rapid neuropsychiatric deterioration characterized by somnolence and psychosis. The decision was made to treat immediately with spironolactone and ketoconazole, as well as insulin for hyperglycemia management. His mental status, blood pressure, serum potassium, glucose and cortisol improved following the initiation and titration of medical therapy. He was discharged home with addition of metyrapone and hospice support. Two months later the patient succumbed to his illness. Conclusion: The severity of hypercortisolism is a negative predictor of survival and prompt control should be the main therapeutic goal along with prevention of cortisol-induced complications in patients with ECS. ACTH and CRH immunostaining of the patient’s ES histopathology slides is pending. Presentation: Thursday, June 15, 2023

Diagnostic and Therapeutic Strategies for Stable Coronary Artery Disease Following the ISCHEMIA Trial.

Until recently, coronary revascularization with coronary artery bypass grafting or percutaneous coronary intervention has been regarded as the standard choice for stable coronary artery disease (CAD), particularly for patients with a significant burden of ischemia. However, in conjunction with remarkable advances in adjunctive medical therapy and a deeper understanding of its long-term prognosis from recent large-scale clinical trials, including ISCHEMIA (International Study of Comparative Health Effectiveness With Medical and Invasive Approaches), the approach to stable CAD has changed drastically. Although the updated evidence from recent randomized clinical trials will likely modify the recommendations for future clinical practice guidelines, there are still unresolved and unmet issues in Asia, where prevalence and practice patterns are markedly different from those in Western countries. Herein, the authors discuss perspectives on: 1) assessing the diagnostic probability of patients with stable CAD; 2) application of noninvasive imaging tests; 3) initiation and titration of medical therapy; and 4) evolution of revascularization procedures in the modern era.

Titration of medical therapy and clinical outcomes among patients with heart failure with reduced ejection fraction: Findings from the HF-ACTION trial

Clinical guidelines recommend titration of angiotensin converting enzyme inhibitors (ACEi) and beta-blockers among patients with heart failure with reduced ejection fraction (HFrEF) to maximally tolerated doses. Patient characteristics associated with dose titration and clinical outcomes subsequent to dose titration remain poorly characterized. Among 1999 ambulatory patients with chronic HFrEF in the HF-ACTION trial, use and dosing of ACEi and evidence-based beta-blockers were examined at baseline and 6-month follow-up. Multivariable logistic regression models were used to assess factors associated with dose escalation (medication initation or dosing increase) or dose de-escalation (medication discontinuation or dosing decrease). Cox proportional hazard regression models were used to examine associations between dose trajectory group (stable target, stable sub-target, dose escalation, and dose de-escalation) and subsequent mortality and hospitalization outcomes. For both ACEi and beta-blockers, hospitalization for heart failure in the 6 months prior to enrollment (odds ratio [OR] 2.32 [95% confidence interval 1.58-3.42]) for ACEi; 1.42 [1.05-1.9] for beta-blockers) and higher systolic blood pressure (OR 1.01 [1.00-1.03] per 1 mmHg increase for ACEi; 1.01 [1.00-1.02] for beta-blockers) were associated with dose escalation. Hospitalization 6 months prior to enrollment for any cause (including HF or non-HF causes) was associated with dose de-escalation (OR 1.60 [1.14-2.25] for ACEi; 1.67 [1.20-2.33] for beta-blockers). After adjustment for patient characteristics, compared with stable target dosing, dose de-escalation of either medication was associated with greater all-cause mortality (adjusted hazard ratio [aHR] 1.64 [1.11-2.42] for ACEi; 1.62 [1.04-2.53] for beta-blockers). Compared with stable target dosing, both dose de-escalation (aHR 1.98 [1.36-2.87]) and stable sub-target dosing (aHR 1.49 [1.18-1.87]) of beta-blockers were associated with greater cardiovascular mortality or hospitalization for heart failure. Among outpatients with chronic HFrEF, patient characteristics including recent hospitalization status and blood pressure were associated with odds of subsequent escalation and de-escalation of ACEi and beta-blocker therapy. Compared with patients receiving guildeline-recommended target doses, dose de-escalation of either medication and sub-target dosing of beta-blockers were associated with greater morbidity and mortality over long-term follow-up.

The Future of Exercise-Based Cardiac Rehabilitation for Patients With Heart Failure.

Cardiac rehabilitation (CR) is a comprehensive program that includes exercise training, titration of medical therapy, lifestyle modification, educational support, and psychosocial assessment. All these components are safe and beneficial resulting in significant improvements in quality of life, functional capacity, mortality, and hospital readmission. Current guidelines support its use in a broad spectrum of cardiac disease. This review focuses on exercise-based CR for heart failure (HF) patients in whom CR is a recommended treatment. Exercise should be prescribed according to a personalized approach, optimizing, and tailoring the rehabilitative program to the patient's characteristics. Specific CR programs are dedicated to older patients, those with HF and preserved ejection fraction, and recipients of cardiac implantable electronic devices or left ventricular assistance device. Telemedicine may increase CR participation and overcome some of the barriers that limit its utilization.

Patient factors associated with titration of medical therapy in patients with heart failure with reduced ejection fraction: data from the QUALIFY international registry.

AimsFailure to prescribe key medicines at evidence‐based doses is associated with increased mortality and hospitalization for patients with Heart Failure with reduced Ejection Fraction (HFrEF). We assessed titration patterns of guideline‐recommended HFrEF medicines internationally and explored associations with patient characteristics in the global, prospective, observational, longitudinal registry.Methods and resultsData were collected from September 2013 through December 2014, with 7095 patients from 36 countries [>18 years, previous HF hospitalization within 1–15 months, left ventricular ejection fraction (LVEF) ≤ 40%] enrolled, with dosage data at baseline and up to 18 months from 4368 patients. In 4368 patients (mean age 63 ± 17 years, 75% male) ≥ 100% target doses at baseline: 30.6% (ACEIs), 2.9% (ARBs), 13.9% (BBs), 53.8% (MRAs), 26.2% (ivabradine). At final follow‐up, ≥100% target doses achieved in more patients for ACEI (34.8%), BB (18.0%), and ivabradine (30.5%) but unchanged for ARBs (3.2%) and MRAs (53.7%). Adjusting for baseline dosage, uptitration during follow‐up was more likely with younger age, higher systolic blood pressure, and in absence of chronic kidney disease or diabetes for ACEIs/ARBs; younger age, higher body mass index, higher heart rate, lower LVEF, and absence of coronary artery disease for BBs. For ivabradine, uptitration was more likely with higher resting heart rate.ConclusionsThe international QUALIFY Registry suggests that few patients with HFrEF achieve target doses of disease‐modifying medication, especially older patients and those with co‐morbidity. Quality improvement initiatives are urgently required.

Evaluation of procalcitonin in a fluorescent immunoassay AFIAS-6 analyzer

Biomarkers have become an integral part of practicing medicine, especially in heart failure. The natriuretic peptides are commonly used in the evaluation of heart failure, but their role extends beyond diagnosis and includes risk stratification and management of heart failure patients. Newer biomarkers have arrived and are becoming part of routine care of heart failure patients. Both ST2 and high-sensitivity troponin have significant prognostic value for mortality, but also may assist in the titration of medical therapy. Procalcitonin can help guide appropriate antibiotic use in patients with heart failure. The ability to appropriately use and interpret these biomarkers is imperative to the care of heart failure patients, especially as these newer biomarkers become widely used.

Early Discharge in Low-Risk Patients Hospitalized for Acute Coronary Syndromes: Feasibility, Safety and Reasons for Prolonged Length of Stay.

IntroductionLength of hospital stay (LHS) is an indicator of clinical effectiveness. Early hospital discharge (≤72 hours) is recommended in patients with acute coronary syndromes (ACS) at low risk of complications, but reasons for prolonged LHS poorly reported.MethodsWe collected data of ACS patients hospitalized at the Geneva University Hospitals from 1st July 2013 to 30th June 2015 and used the Zwolle index score to identify patients at low risk (≤ 3 points). We assessed the proportion of eligible patients who were successfully discharged within 72 hours and the reasons for prolonged LHS. Outcomes were defined as adherence to recommended therapies, major adverse events at 30 days and patients' satisfaction using a Likert-scale patient-reported questionnaire.ResultsAmong 370 patients with ACS, 255 (68.9%) were at low-risk of complications but only 128 (50.2%)were eligible for early discharge, because of other clinical reasons for prolonged LHS (e.g. staged coronary revascularization, cardiac monitoring) in 127 patients (49.8%). Of the latter, only 45 (35.2%) benefitted from an early discharge. Reasons for delay in discharge in the remaining 83 patients (51.2%) were mainly due to delays in additional investigations, titration of medical therapy, admission or discharge during weekends. In the early discharge group, at 30 days, only one patient (2.2%) had an adverse event (minor bleeding), 97% of patients were satisfied by the medical care.ConclusionEarly discharge was successfully achieved in one third of eligible ACS patients at low risk of complications and appeared sufficiently safe while being overall appreciated by the patients.

WORSENING RENAL FUNCTION DURING AGGRESSIVE HEART FAILURE MANAGEMENT IS NOT ASSOCIATED WITH POOR OUTCOMES: RESULTS FROM THE PRO-BNP OUTPATIENT TAILORED CHRONIC HEART FAILURE THERAPY (PROTECT) STUDY

Worsening renal function (WRF) has been linked to poor outcomes in patients with heart failure (HF). When WRF develops during aggressive titration of medical therapy, it commonly leads to less aggressive care. It remains unclear if biomarker guided HF management causes more WRF. 151 patients

Echocardiographic Indices Do Not Reliably Track Changes in Left-Sided Filling Pressure in Healthy Subjects or Patients With Heart Failure With Preserved Ejection Fraction

In select patient populations, Doppler echocardiographic indices may be used to estimate left-sided filling pressures. It is not known, however, whether changes in these indices track changes in left-sided filling pressures within individual healthy subjects or patients with heart failure with preserved ejection fraction (HFpEF). This knowledge is important because it would support, or refute, the serial use of these indices to estimate changes in filling pressures associated with the titration of medical therapy in patients with heart failure. Forty-seven volunteers were enrolled: 11 highly screened elderly outpatients with a clear diagnosis of HFpEF, 24 healthy elderly subjects, and 12 healthy young subjects. Each patient underwent right heart catheterization with simultaneous transthoracic echo. Pulmonary capillary wedge pressure (PCWP) and key echo indices (E/e' and E/Vp) were measured at two baselines and during 4 preload altering maneuvers: lower body negative pressure -15 mm Hg; lower body negative pressure -30 mm Hg; rapid saline infusion of 10 to 15 mL/kg; and rapid saline infusion of 20 to 30 mL/kg. A random coefficient mixed model regression of PCWP versus E/e' and PCWP versus E/Vp was performed for (1) a composite of all data points and (2) a composite of all data points within each of the 3 groups. Linear regression analysis was performed for individual subjects. With this protocol, PCWP was manipulated from 0.8 to 28.8 mm Hg. For E/e', the composite random effects mixed model regression was PCWP=0.58×E/e'+7.02 (P<0.001), confirming the weak but significant relationship between these 2 variables. Individual subject linear regression slopes (range, -6.76 to 11.03) and r(2) (0.00 to 0.94) were highly variable and often very different than those derived for the composite and group regressions. For E/Vp, the composite random coefficient mixed model regression was PCWP=1.95×E/Vp+7.48 (P=0.005); once again, individual subject linear regression slopes (range, -16.42 to 25.39) and r(2) (range, 0.02 to 0.94) were highly variable and often very different than those derived for the composite and group regressions. Within individual subjects the noninvasive indices E/e' and E/Vp do not reliably track changes in left-sided filling pressures as these pressures vary, precluding the use of these techniques in research studies with healthy volunteers or the titration of medical therapy in patients with HFpEF.