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Aldosterone antagonist

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https://www.readbyqxmd.com/read/29664406/racial-differences-in-characteristics-and-outcomes-of-patients-with-heart-failure-and-preserved-ejection-fraction-in-the-treatment-of-preserved-cardiac-function-heart-failure-trial
#1
Eldrin F Lewis, Brian Claggett, Amil M Shah, Jiankang Liu, Sanjiv J Shah, Inder Anand, Eileen O'Meara, Nancy K Sweitzer, Jean L Rouleau, James C Fang, Akshay S Desai, Tamrat M Retta, Scott D Solomon, John F Heitner, Thomas D Stamos, Robin Boineau, Bertram Pitt, Marc A Pfeffer
BACKGROUND: Black patients have been shown to have different baseline characteristics and outcomes compared with nonblack patients in cohort studies. However, few studies have focused on heart failure (HF) with preserved ejection fraction (HFpEF) patients. We aimed to determine the difference in cardiovascular outcomes in black and nonblack patients with HFpEF and to determine the relative efficacy and safety of spironolactone in black and nonblack patients. METHODS AND RESULTS: Patients with HFpEF, randomized to spironolactone versus placebo in the TOPCAT trial (Treatment of Preserved Cardiac Function Heart Failure With an Aldosterone Antagonist) in North and South America, were grouped according to self-described black and nonblack race...
March 2018: Circulation. Heart Failure
https://www.readbyqxmd.com/read/29660263/characteristics-and-long-term-prognosis-of-patients-with-heart-failure-and-mid-range-ejection-fraction-compared-with-reduced-and-preserved-ejection-fraction-a-systematic-review-and-meta-analysis
#2
Josephine Lauritsen, Finn Gustafsson, Jawdat Abdulla
AIMS: This study aimed to assess by a meta-analysis the clinical characteristics, all-cause and cardiovascular mortality, and hospitalization of patients with heart failure (HF) with mid-range ejection fraction (HFmrEF) compared with HF with reduced ejection fraction (HFrEF) and HF with preserved ejection fraction (HFpEF). METHODS AND RESULTS: Data from 12 eligible observational studies including 109 257 patients were pooled. HFmrEF patients were significantly different and occupied a mid-position between HFrEF and HFpEF: mean age 73...
April 16, 2018: ESC Heart Failure
https://www.readbyqxmd.com/read/29606640/timing-of-postdischarge-follow-up-and-medication-adherence-among-patients-with-heart-failure
#3
Leslie L Chang, Haolin Xu, Adam D DeVore, Roland A Matsouaka, Clyde W Yancy, Gregg C Fonarow, Larry A Allen, Adrian F Hernandez
BACKGROUND: Medication adherence improves outcomes for patients with heart failure, but adherence rates remain low. We examined the association between earlier postdischarge follow-up and medication adherence. METHODS AND RESULTS: We performed a retrospective cohort study of patients ≥65 years who were hospitalized for heart failure, covered by Medicare Part D, and discharged alive from April 2006 to October 2012 using the Get With The Guidelines-Heart Failure Registry linked to Medicare claims...
April 1, 2018: Journal of the American Heart Association
https://www.readbyqxmd.com/read/29601411/antihypertensive-drug-use-in-resistant-and-nonresistant-hypertension-and-in-controlled-and-uncontrolled-resistant-hypertension
#4
Alejandro de la Sierra, Pedro Armario, Anna Oliveras, José R Banegas, Manuel Gorostidi, Ernest Vinyoles, Juan J de la Cruz, Julián Segura, Luis M Ruilope
BACKGROUND AND AIM: Treatment-resistant hypertension (TRH) is associated with particular clinical features, nonadherence, and suboptimal treatment. We assessed possible associations of antihypertensive drug classes, specific agents inside each class, and types of combinations, with the presence of non-TRH vs. TRH, and with controlled vs. uncontrolled TRH. METHODS: Comparisons were done in 14 264 patients treated with three drugs (non-TRH: 2988; TRH: 11 276) and in 6974 treated with at least four drugs (controlled TRH: 1383; uncontrolled TRH: 5591)...
March 29, 2018: Journal of Hypertension
https://www.readbyqxmd.com/read/29570216/cardiac-resynchronization-therapy-a-comparative-analysis-of-mortality-in-african-americans-and-caucasians
#5
John M Fontaine, Sona M Franklin, Gilbert Essilfie, Lilian E Ahiable
BACKGROUND: Cardiac resynchronization therapy (CRT) is recommended in patients with heart failure, reduced left ventricular ejection fraction and a prolonged QRS duration. African-Americans are underrepresented in clinical trials and CRT is underutilized, consequently, the benefits and outcomes of CRT are not well-defined. METHODS: We evaluated 294 patients, determined survival using Kaplan-Meier analysis, and used Cox proportional hazards regression model to determine predictors of mortality...
March 23, 2018: Pacing and Clinical Electrophysiology: PACE
https://www.readbyqxmd.com/read/29561839/ccr2-antagonism-leads-to-marked-reduction-in-proteinuria-and-glomerular-injury-in-murine-models-of-focal-segmental-glomerulosclerosis-fsgs
#6
Zhenhua Miao, Linda S Ertl, Dale Newland, Bin Zhao, Yu Wang, Xiaoping Zang, James J Campbell, Xiaoli Liu, Ton Dang, Shichang Miao, Antoni Krasinski, Sreenivas Punna, Yibin Zeng, Jeffrey McMahon, Penglie Zhang, Israel F Charo, Thomas J Schall, Rajinder Singh
Focal segmental glomerulosclerosis (FSGS) comprises a group of uncommon disorders that present with marked proteinuria, nephrotic syndrome, progressive renal failure and characteristic glomerular lesions on histopathology. The current standard of care for patients with FSGS include immunosuppressive drugs such as glucocorticoids followed by calcineurin inhibitors, if needed for intolerance or inadequate response to glucocorticoids. Renin-angiotensin-aldosterone (RAAS) blockers are also used to control proteinuria, an important signature of FSGS...
2018: PloS One
https://www.readbyqxmd.com/read/29556787/dysregulation-of-the-renin-angiotensin-system-and-the-vasopressinergic-system-interactions-in-cardiovascular-disorders
#7
REVIEW
Ewa Szczepanska-Sadowska, Katarzyna Czarzasta, Agnieszka Cudnoch-Jedrzejewska
PURPOSE OF REVIEW: In many instances, the renin-angiotensin system (RAS) and the vasopressinergic system (VPS) are jointly activated by the same stimuli and engaged in the regulation of the same processes. RECENT FINDINGS: Angiotensin II (Ang II) and arginine vasopressin (AVP), which are the main active compounds of the RAS and the VPS, interact at several levels. Firstly, Ang II, acting on AT1 receptors (AT1R), plays a significant role in the release of AVP from vasopressinergic neurons and AVP, stimulating V1a receptors (V1aR), regulates the release of renin in the kidney...
March 19, 2018: Current Hypertension Reports
https://www.readbyqxmd.com/read/29532764/entresto-a-new-panacea-for-heart-failure
#8
Peter H Khalil, Ghazal Kabbach, Debabrata Mukherjee, Sarmad Said
Heart Failure (HF) is one of the main health care burdens in the United States and in the world. Many drugs are approved and used in practice for management of this condition; including beta blockers, diuretics, aldosterone antagonists, angiotensin converting enzyme inhibitors (ACEI's), and angiotensin receptor blockers (ARBs). Recently, the Food and Drug Administration (FDA) approved a drug with brand name Entresto (Sacubitril/Valsartan or LCZ696), an angiotensin receptor neprilysin inhibitor for the use in Heart Failure with Reduced Ejection Fraction (HFrEF) patients instead of ACEI's and ARBs...
March 13, 2018: Cardiovascular & Hematological Agents in Medicinal Chemistry
https://www.readbyqxmd.com/read/29525327/obesity-related-heart-failure-with-a-preserved-ejection-fraction-the-mechanistic-rationale-for-combining-inhibitors-of-aldosterone-neprilysin-and-sodium-glucose-cotransporter-2
#9
REVIEW
Milton Packer, Dalane W Kitzman
Obesity-related heart failure with a preserved ejection fraction (HFpEF) is an important phenotype prevalent in the community, especially in people with metabolic disorders (e.g., dyslipidemia, diabetes). These individuals exhibit a marked expansion of plasma volume, but ventricular distensibility is limited, most likely as a result of cardiac microvascular rarefaction acting in concert with myocardial and pericardial fibrosis. Consequently, the increase in plasma volume causes a disproportionate increase in cardiac filling pressures, leading to heart failure, even though systolic ejection is not impaired...
March 7, 2018: JACC. Heart Failure
https://www.readbyqxmd.com/read/29506889/targeted-treatment-of-primary-aldosteronism-the-consensus-of-taiwan-society-of-aldosteronism
#10
Kuo-How Huang, Chih-Chin Yu, Ya-Hui Hu, Chin-Chen Chang, Chieh-Kai Chan, Shih-Cheng Liao, Yao-Chou Tsai, Shih-Chieh Jeff Chueh, Vin-Cent Wu, Yen-Hung Lin
BACKGROUND/PURPOSE: Even with the increasing recognition of primary aldosteronism (PA) as a cause of refractory hypertension and an issue of public health, the consensus of its optimal surgical or medical treatment in Taiwan has not been reached. Our objective was to develop a clinical practice guideline that is feasible for real-world management of PA patients in Taiwan. METHODS: The Taiwan Society of Aldosteronism (TSA) Task Force recognized the above-mentioned issues and reached this Taiwan PA consensus at its inaugural meeting, in order to provide updated information of internationally acceptable standards, and also to incorporate our local disease characteristics and constraints into PA management...
March 2, 2018: Journal of the Formosan Medical Association, Taiwan Yi Zhi
https://www.readbyqxmd.com/read/29501806/sudden-death-in-heart-failure-with-preserved-ejection-fraction-a-competing-risks-analysis-from-the-topcat-trial
#11
Muthiah Vaduganathan, Brian L Claggett, Neal A Chatterjee, Inder S Anand, Nancy K Sweitzer, James C Fang, Eileen O'Meara, Sanjiv J Shah, Sheila M Hegde, Akshay S Desai, Eldrin F Lewis, Jean Rouleau, Bertram Pitt, Marc A Pfeffer, Scott D Solomon
BACKGROUND: Sudden death (SD) may be an important mode of death in heart failure with preserved ejection fraction (HFpEF). OBJECTIVES: To investigate rates and predictors of SD or aborted cardiac arrest (ACA) in HFpEF. METHODS: We studied 1,767 patients with HFpEF (EF≥45%) enrolled in the Americas region of the TOPCAT trial. We identified independent predictors of composite SD/ACA with step-wise backward selection using competing risks regression analysis accounting for non-sudden causes of death...
March 4, 2018: JACC. Heart Failure
https://www.readbyqxmd.com/read/29496021/post-myocardial-infarction-heart-failure
#12
REVIEW
M Cecilia Bahit, Ajar Kochar, Christopher B Granger
Heart failure (HF) complicating myocardial infarction (MI) is common and may be present at admission or develop during the hospitalization. Among patients with MI, there is a strong relationship between degree of HF and mortality. The optimal management of the patient with HF complicating MI varies according to time since the onset of infarction. Medical therapy for HF after MI includes early (within 24 h) initiation of angiotensin-converting enzyme inhibitors and early (within 7 days) use of aldosterone antagonists...
March 2018: JACC. Heart Failure
https://www.readbyqxmd.com/read/29486908/update-of-pathophysiology-and-management-of-diabetic-kidney-disease
#13
REVIEW
Yi-Chih Lin, Yu-Hsing Chang, Shao-Yu Yang, Kwan-Dun Wu, Tzong-Shinn Chu
Diabetic kidney disease (DKD) is a major cause of morbidity and mortality in patients with diabetes mellitus and the leading cause of end-stage renal disease in the world. The most characteristic marker of DKD is albuminuria, which is associated with renal disease progression and cardiovascular events. Renal hemodynamics changes, oxidative stress, inflammation, hypoxia and overactive renin-angiotensin-aldosterone system (RAAS) are involved in the pathogenesis of DKD, and renal fibrosis plays the key role. Intensified multifactorial interventions, including RAAS blockades, blood pressure and glucose control, and quitting smoking, help to prevent DKD development and progression...
February 24, 2018: Journal of the Formosan Medical Association, Taiwan Yi Zhi
https://www.readbyqxmd.com/read/29482507/consequences-of-continuing-renin-angiotensin-aldosterone-system-antagonists-in-the-preoperative-period-a-systematic-review-and-meta-analysis
#14
Qiong Ling, Yu Gu, Jiaxin Chen, Yansheng Chen, Yongyong Shi, Gaofeng Zhao, Qianqian Zhu
BACKGROUND: Patients who use angiotensin-converting enzyme inhibitors (ACEIs)/angiotensin II receptor blockers (ARBs) are prone to developing side effects like hypotension and even refractory hypotension during anesthesia use, and whether ACEIs/ARBs should be continued or discontinued in such patients remains debatable. The present systematic review and meta-analysis was conducted to clarify the consequences of continuing or withholding these drugs, especially with regards to the incidence of intraoperative hypotension, in patients who continue to use ACEIs/ARBs on the day of their scheduled surgery...
February 26, 2018: BMC Anesthesiology
https://www.readbyqxmd.com/read/29475874/diastolic-blood-pressure-and-adverse-outcomes-in-the-topcat-treatment-of-preserved-cardiac-function-heart-failure-with-an-aldosterone-antagonist-trial
#15
Pratik B Sandesara, Wesley T O'Neal, Heval M Kelli, Matthew Topel, Ayman Samman-Tahhan, Laurence S Sperling
BACKGROUND: Although diastolic blood pressure (DBP) is independently associated with an increased risk of adverse cardiovascular outcomes in the general population, it is unclear if a similar relationship exists in patients with heart failure with preserved ejection fraction. METHODS AND RESULTS: This analysis included 1703 (mean age, 72±10 years; 50% men; 78% white) patients with heart failure with preserved ejection fraction enrolled in the TOPCAT (Treatment of Preserved Cardiac Function Heart Failure With an Aldosterone Antagonist) Trial from the Americas who were treated for hypertension...
February 23, 2018: Journal of the American Heart Association
https://www.readbyqxmd.com/read/29474466/preclinical-pharmacology-of-azd9977-a-novel-mineralocorticoid-receptor-modulator-separating-organ-protection-from-effects-on-electrolyte-excretion
#16
Krister Bamberg, Ulrika Johansson, Karl Edman, Lena William-Olsson, Susanna Myhre, Anders Gunnarsson, Stefan Geschwindner, Anna Aagaard, Anna Björnson Granqvist, Frédéric Jaisser, Yufeng Huang, Kenneth L Granberg, Rasmus Jansson-Löfmark, Judith Hartleib-Geschwindner
Excess mineralocorticoid receptor (MR) activation promotes target organ dysfunction, vascular injury and fibrosis. MR antagonists like eplerenone are used for treating heart failure, but their use is limited due to the compound class-inherent hyperkalemia risk. Here we present evidence that AZD9977, a first-in-class MR modulator shows cardio-renal protection despite a mechanism-based reduced liability to cause hyperkalemia. AZD9977 in vitro potency and binding mode to MR were characterized using reporter gene, binding, cofactor recruitment assays and X-ray crystallopgraphy...
2018: PloS One
https://www.readbyqxmd.com/read/29472988/mineralocorticoid-hypertension-and-hypokalaemia-induced-by-posaconazole
#17
Charlotte Boughton, David Taylor, Lea Ghataore, Norman Taylor, Benjamin C Whitelaw
We describe severe hypokalaemia and hypertension due to a mineralocorticoid effect in a patient with myelodysplastic syndrome taking posaconazole as antifungal prophylaxis. Two distinct mechanisms due to posaconazole are identified: inhibition of 11β hydroxylase leading to the accumulation of the mineralocorticoid hormone 11-deoxycorticosterone (DOC) and secondly, inhibition of 11β hydroxysteroid dehydrogenase type 2 (11βHSD2), as demonstrated by an elevated serum cortisol-to-cortisone ratio. The effects were ameliorated by spironolactone...
2018: Endocrinology, Diabetes & Metabolism Case Reports
https://www.readbyqxmd.com/read/29467196/specific-activation-of-the-alternative-cardiac-promoter-of-cacna1c-by-the-mineralocorticoid-receptor
#18
Thassio R Mesquita, Gaëlle Auguste, Débora Falcón, Gema Ruiz-Hurtado, Rogelio Salazar-Enciso, Jessica Sabourin, Florence Lefebvre, Say Viengchareun, Hussein Kobeissy, Patrick Lechène, Valérie Nicolas, Amaya Fernandez-Celis, Susana Gómez, Sandra Lauton Santos, Eric Morel, Angelica Rueda, Natalia López-Andrés, Ana Maria Gómez, Marc Lombès, Jean-Pierre Benitah
RATIONALE: The MR (mineralocorticoid receptor) antagonists belong to the current therapeutic armamentarium for the management of cardiovascular diseases, but the mechanisms conferring their beneficial effects are poorly understood. Part of the cardiovascular effects of MR is because of the regulation of L-type Cav 1.2 Ca2+ channel expression, which is generated by tissue-specific alternative promoters as a long cardiac or short vascular N-terminal transcripts. OBJECTIVE: To analyze the molecular mechanisms by which aldosterone, through MR, modulates Cav 1...
March 30, 2018: Circulation Research
https://www.readbyqxmd.com/read/29462546/role-of-the-renin-angiotensin-system-in-hepatic-fibrosis-and-portal-hypertension
#19
Kwang Yong Shim, Young Woo Eom, Moon Young Kim, Seong Hee Kang, Soon Koo Baik
The renin-angiotensin system (RAS) is an important regulator of cirrhosis and portal hypertension. As hepatic fibrosis progresses, levels of the RAS components angiotensin (Ang) II, Ang-(1-7), angiotensin-converting enzyme (ACE), and Ang II type 1 receptor (AT1R) are increased. The primary effector Ang II regulates vasoconstriction, sodium homoeostasis, fibrosis, cell proliferation, and inflammation in various diseases, including liver cirrhosis, through the ACE/Ang II/AT1R axis in the classical RAS. The ACE2/Ang-(1-7)/Mas receptor and ACE2/Ang-(1-9)/AT2R axes make up the alternative RAS and promote vasodilation, antigrowth, proapoptotic, and anti-inflammatory effects; thus, countering the effects of the classical RAS axis to reduce hepatic fibrogenesis and portal hypertension...
February 21, 2018: Korean Journal of Internal Medicine
https://www.readbyqxmd.com/read/29460366/ejection-fraction-as-a-statistical-index-of-left-ventricular-systolic-function-the-first-full-allometric-scrutiny-of-its-appropriateness-and-accuracy
#20
Lorenzo Lolli, Alan M Batterham, Greg Atkinson
Left ventricular ejection fraction (EF) is a ratio that is deemed to accurately normalize stroke volume (SV) to end-diastolic volume (EDV). Ratios are now well-recognized for not normalizing the numerator, in this case SV, consistently for the denominator, EDV. We aimed to provide the first allometric-based scrutiny of the conventional assumptions that underpin the EF ratio. We allometrically modelled untransformed SV and EDV measurements from 112 preclinical heart failure patients in the Multi-Ethnic Study of Atherosclerosis (MESA), and 864 chronic heart failure patients in the Treatment of Preserved Cardiac Function Heart Failure with an Aldosterone Antagonist (TOPCAT) study...
February 20, 2018: Clinical Physiology and Functional Imaging
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