Heart Failure Sample Clauses

Heart Failure. Fatal and serious heart failure or left ventricular dysfunction occurred in 5% of Iclusig-treated patients (22/449). Eight percent of patients (35/449) experienced any grade of heart failure or left ventricular dysfunction. Monitor patients for signs or symptoms consistent with heart failure and treat as clinically indicated, including interruption of Iclusig. Consider discontinuation of Iclusig in patients who develop serious heart failure. Hepatotoxicity: Iclusig can cause hepatotoxicity, including liver failure and death. Fulminant hepatic failure leading to death occurred in an Iclusig-treated patient within one week of starting Iclusig. Two additional fatal cases of acute liver failure also occurred. The fatal cases occurred in patients with blast phase CML (BP-CML) or Philadelphia chromosome positive acute lymphoblastic leukemia (Ph+ ALL). Severe hepatotoxicity occurred in all disease cohorts. Iclusig treatment may result in elevation in ALT, AST, or both. Monitor liver function tests at baseline, then at least monthly or as clinically indicated. Interrupt, reduce or discontinue Iclusig as clinically indicated. Hypertension: Treatment-emergent hypertension (defined as systolic BP≥140 mm Hg or diastolic BP≥90 mm Hg on at least one occasion) occurred in 67% of patients (300/449). Eight patients treated with Iclusig (2%) experienced treatment-emergent symptomatic hypertension as a serious adverse reaction, including one patient (<1%) with hypertensive crisis. Patients may require urgent clinical intervention for hypertension associated with confusion, headache, chest pain, or shortness of breath. In 131 patients with Stage 1 hypertension at baseline, 61% (80/131) developed Stage 2 hypertension. Monitor and manage blood pressure elevations during Iclusig use and treat hypertension to normalize blood pressure. Interrupt, dose reduce, or stop Iclusig if hypertension is not medically controlled. Pancreatitis: Clinical pancreatitis occurred in 6% (28/449) of patients (5% Grade 3) treated with Iclusig. Pancreatitis resulted in discontinuation or treatment interruption in 6% of patients (25/449). The incidence of treatment-emergent lipase elevation was 41%. Check serum lipase every 2 weeks for the first 2 months and then monthly thereafter or as clinically indicated. Consider additional serum lipase monitoring in patients with a history of pancreatitis or alcohol abuse. Dose interruption or reduction may be required. In cases where lipase elevations are accomp...

Heart Failure. Heart failure (HF) is a life-threatening chronic disease that prevents the heart from pumping sufficient levels of blood around the body. HF affects approximately 64 million people worldwide. HF remains as fatal as some of the most common cancers in both men (prostate and bladder cancers) and women (breast cancer). 5 Chronic HF is the leading cause of hospitalisation for those over the age of 65 and represents a significant clinical and economic burden. 6 AstraZeneca's ambition is to be the leading company in HF, expanding from Forxiga today in heart failure with reduced ejection fraction (HFrEF), to the full HF spectrum including cardiomyopathies. AstraZeneca is investing in multiple investigational therapies with diverse mechanisms of action to address the spectrum of patient need in this area. Cardiomyopathy due to ATTR is caused by aging or genetic mutations resulting in misfolded TTR protein and accumulation as amyloid fibrils in the cardiac myocardium. In patients with ATTR-CM, both the mutant and wild type TTR protein builds up as fibrils in tissues, including the heart. The presence of TTR fibrils interferes with the normal functions of these tissues. As the TTR protein fibrils enlarge, more tissue damage occurs and the disease worsens, resulting in poor quality of life and eventually death. Worldwide, there are an estimated 300,000-500,000 patients with ATTR-CM3,4; however, many of those patients remain undiagnosed. NI006 is an investigational human monoclonal antibody that specifically targets misfolded transthyretin and is designed to directly address the pathology of ATTR-CM by enabling removal of amyloid fibril deposits in the heart. ▇▇▇▇▇▇▇, AstraZeneca Rare Disease, is the group within AstraZeneca focused on rare diseases, created following the 2021 acquisition of Alexion Pharmaceuticals, Inc. As a leader in rare diseases for nearly 30 years, Alexion is focused on serving patients and families affected by rare diseases and devastating conditions through the discovery, development and commercialisation of life-changing medicines. Alexion focuses its research efforts on novel molecules and targets in the complement cascade and its development efforts on haematology, nephrology, neurology, metabolic disorders, cardiology and ophthalmology. Headquartered in Boston, Massachusetts, ▇▇▇▇▇▇▇ has offices around the globe and serves patients in more than 50 countries.

Heart Failure. Compensated hypertrophy is often seen to undergo a transition to heart failure [135]. Thus, although neurohumoral stimuli are accumulating to stimulate the heart to higher achievements, the heart is not able to do so leading to increased filling pressures and venous congestion. The failing heart has undergone many changes, the most prominent being changes in the calcium handling proteins [136]. The changing geometry, architecture and properties of the chamber are generally indicated as (adverse) chamber remodeling, in severe cases associated with atrioventricular valve insufficiency, dyssynchronous contractions of the chamber’s wall segments, and rhythm disturbances. An important mediator of ventricular remodeling is the neurohumoral activation of the heart by the sympathetic nervous system and the renin-angiotensin-aldosteron system (RAAS). Full recognition of their deleterious influences on the heart has led to the foundation of the cornerstones of heart failure therapy: β-blockers and ACE- inhibitors (or angiotensin receptor type 1-blockers). In the myocardial tissue the ECM undergoes a series of changes due to (i) myocardial collagen accumulation, (ii) collagen fibril disruption, (iii) altered arrangement and reduced cross-linking between collagen fibers, and (iv) synthesis of proteins that are not present in the healthy myocardium. To the latter group of proteins belong tenascin-C [137], thrombospondin-2 [138], matrix Gla protein [139], and osteopontin [139]. The volume percentage of ECM in failing myocardial tissue is usually increased, which is often accompanied by increased serum levels of aminoterminal propeptide of type I procollagen (PINP) and aminoterminal propeptide of type III procollagen (PIIINP), two propeptides that are liberated from the tissue upon collagen type I and type III synthesis. At the same time serum levels of carboxyterminal cross-linked telopeptide of type I collagen (ICTP) are low, representing a low rate of collagen degradation [17]. These changes in ECM composition are ascribed to the myocardial fibroblasts that are stimulated by high plasma levels of catecholamines, angiotensin-II and aldosteron. High levels of collagen degrading enzymes, such as collagenases, may lead to increases in LV dimensions and subsequent cardiomyocyte slippage that may contribute to progressive LV remodelling [22]. In an animal model of hypertensive heart disease, increased expression of collagenases coincided with the transition from hypertrophy...