Use Of Aldosterone Antagonists Research Articles

Wearable cardioverter defibrillator after ICD-system explantation: data from a multicenter registry

Abstract Background Data on the use of wearable cardioverter defibrillator (WCD) among patients after cardiac implantable electronic device explantation of 1- to 3-chamber Implantable Cardioverter-defibrillator system (ICD) are sparse. Subsequently several guidelines give a different recommendation regarding WCD indication in this cohort. Objectives We aimed to study the baseline characteristics and outcome of patients treated with WCD after ICD explantation. The primary outcome is appropriate WCD shock. Methods 1104 patients were included in a multicenter registry from seven European centers. Among this cohort 109 patients received a WCD to bridge the time after ICD-system explantation until reimplantation due to a persistent ICD-indication. The mean follow-up time of the whole cohort was 824±773 days. Cardiovascular history and non-cardiovascular morbidities were evaluated. In addition, the presence of ventricular tachyarrhythmias and/or WCD shocks was evaluated in the explantation group. Furthermore, after ICD-reimplantation the rate of rehospitalization for ventricular tachyarrhythmias, atrial fibrillation, stroke and congestive heart failure was followed. Results In the explantation group patients were older (65±14 versus 59±15; p<0.001) and were hospitalized longer (21±15 days versus 14±12 days; p<0.001). The index LVEF differed significantly (35.7±14.1% versus 29.3±11.5%; p<0.001). The LVEF value did not differ significantly over short-term follow-up (35.7±14.2% versus 37.9±11.9%; p=0.204). Wear days among patients after ICD-system explantation were 61±46 days. An appropriate WCD shock was documented in 7.3% after ICD-system explantation during WCD use. Up to 80.6% of patients after ICD-system explantation received a reimplantation. The rate of rehospitalization due to ventricular tachyarrhythmias was 7.3%, due to heart failure 6.8% and due to atrial fibrillation 4.1%. After ICD-implantation the rate of appropriate shocks was 12/89 (13.4%). In the multivariable regression analysis myocarditis and ICD-system explantation were positive predictors for the risk of ventricular tachyarrhythmias, but nevertheless an improved left ventricular ejection fraction (LVEF) and use of aldosterone antagonists were negative predictors for the risk of ventricular tachyarrhythmias. Conclusions Cccurrence of malignant arrythmia after ICD-system explantation is high and the use of WCD among these patients could be beneficial in preventing sudden cardiac death.

S-15-2: COMMUNITY-BASED APPROACHES TO PREVENTION AND MANAGEMENT OF HYPERTENSION

There are multiple level factors that contribute to hypertension prevalence and control across various racial/ethnic populations. Hypertension rates in non-Hispanic Black (African American) adults in the USA are among the highest globally, impacted by the social determinants of health. Clinical approaches include team-based care, encouraging self-measured blood pressure, and strengthening community-clinical linkages. Prevention of new-onset hypertension and complications has been clearly demonstrated with community-level NaCl substitution in China and Peru. In the USA, Black population treatment approaches as community interventions include early initiatives from the Association of Black Cardiologists and the Healthy Heart Community Prevention Project (HHCPP) in New Orleans. The HHCPP was one of the early adopters of using barbers and hair stylists as hypertension control centers, working with faith-based institutions, and doing community education and outreach. Evidence-based approaches, now proven to be effective, include the faith-based treatment program for hypertension in New York, NY and a very successful in cluster-randomized trial demonstrating hypertension control in Black barbershops in Los Angeles, CA. The positive components of the Los Angeles barbershop intervention include trusted site of blood pressure intervention, physician-pharmacist collaboration, and effective anti-hypertensive medication including initial two drug protocol with amlodipine and a long-acting RAS blocker, and the appropriate use of aldosterone antagonists. Ongoing research include a small pilot study, simple text messaging and social support in New Orleans for medication adherence which will be reported at the AHA 2022 scientific sessions, and a large church-based health intervention study addressing primary prevention, including hypertension in New Orleans among 42 selected African American churches using community health workers in a combination of exercise weight-loss programs, self-monitoring blood pressure, glucose, and physical activity, and group education centers. In the USA, the American Heart Association in conjunction with the US Department of Health and Human services have initiated a national hypertension control initiative. Overarching strategies include patient and public education, community outreach and integration, and healthcare organization including provider and clinician training, as well as management evaluation of the project. This national program will engage community partners with federal health centers. In conclusion, hypertension can be controlled with evidence-based medicines, not only in clinical settings, but also with interventions in the community environment. Therapeutic lifestyle and evidence-based pharmacotherapy along with self-monitored blood pressure can lead to blood pressure control, especially in racial/ethnic populations.

Abstract 15707: Age Does Not Modify the Impact of Natriuretic Peptide-Guided Therapy on Clinical Outcomes or Serial Natriuretic Peptide Levels

Introduction: Older age is independently associated with greater NT-proBNP levels. As such, the aim of this study was to establish the influence of age on serial NT-proBNP levels over time and the impact of age on response to natriuretic peptide-guided therapy (NPGT) versus usual care for heart failure with reduced ejection fraction (HFrEF). Hypothesis: Age will modify the effect of NPGT on serial NT-proBNP in patients with HFrEF. Methods: Using data from GUIDE-IT, the impact of age on the association of NPGT with serial NT-proBNP and long-term outcomes was assessed. Time-to-event analyses and generalized linear mixed modeling were used to evaluate the effect of age, by quartile, on long-term outcomes and serial NT-proBNP by randomized treatment (NPGT vs. usual care), respectively. Results: In this cohort (N=893), the median age was 63 [range 21-90, IQR 53-71] years and was 32% female and 36% black race. Age was modestly correlated with NT-proBNP (Spearman rho 0.34, p<0.001). At baseline, older age was associated with lower doses of ACEI/ARB (p-trend 0.019) and aldosterone antagonist use (p-trend<0.001), but not beta-blocker use (p=0.06). Older age was associated with a greater risk of all-cause death (log-rank, p<0.001) but not associated with a greater risk of combined CV death or HF hospitalization (log-rank, P=0.56). Although older age was associated with greater NT-proBNP levels over time (Q4 vs. Q1 beta 2.1 x pg/mL/days, p<0.001), it did not modify the association of NPGT on serial NT-proBNP ( Figure, Q4, Q3, and Q2 vs. Q1 by treatment arm, p-interaction>0.09 for all). Age also did not modify the impact of NPGT on either mortality or the composite, CV death or HF hospitalization (P-interaction>0.05 for both). Conclusions: Older age was associated with greater NT-proBNP levels. However, age did not modify the association of NPGT on clinical outcomes or serial NT-proBNP. These data do not support the hypothesis that age modifies the NT-proBNP response to HFrEF treatments.

LVAD OPTIMIZE Clinic Improves Medication Use and Reduces Hospitalizations Post-Implant

Purpose Guidance on use of GDMT following left ventricular assist device (LVAD) remains scant despite studies showing optimal use may reduce morbidity and mortality. We aimed to evaluate the impact of an LVAD OPTIMIZE clinic on medication utilization and outcomes. Methods A multidisciplinary clinic composed of advanced practice providers, pharmacists, nutritionists, and nurses was developed and enrolled patients after discharge from LVAD implantation. Candidates for enrollment were those who could make the scheduled visits. Our OPTIMIZE clinic consisted of a total of 6 visits each two weeks apart and included medication optimization as well as nutrition and pharmacy counseling. Patients who survived to discharge and were not enrolled in the OPTIMIZE clinic were utilized as controls and their variables were collected approximately 3-4 months post-implant. T-test, Chi square, and negative binomial regression were utilized to compare variables and outcomes between groups. Results From January 2019 and March 2021, 26 patients completed OPTIMIZE clinic. Our control group consisted of 43 LVAD patients. Enrolled patients had an average age of 55.3 (±12.8) years, 11 (42.3%) were female, 24 (92.3%) were HeartMate 3 and 2 (7.8%) were HeartWare, and were enrolled an average of 38 (±16) days post-implant. At the end of OPTIMIZE, there was a 150% increase in beta blocker use (8 vs 20), 140% increase in ARNi use (5 vs 12), 17% increase in aldosterone antagonist use (18 vs 21), 41% reduction in loop diuretic use (17 vs 10), and 7 patients were started on SGLT2i (0 at baseline). Comparison of medication use, lab values, and hospitalizations at the end of LVAD OPTIMIZE clinic compared to controls at similar time points is shown in Table 1. Conclusion A multidisciplinary LVAD OPTIMIZE clinic can help improve medication utilization post-implant and is associated with lower rates of hospitalization and less renal dysfunction. Further studies are needed to help clarify optimal GDMT utilization and timing of initiation in this population. Guidance on use of GDMT following left ventricular assist device (LVAD) remains scant despite studies showing optimal use may reduce morbidity and mortality. We aimed to evaluate the impact of an LVAD OPTIMIZE clinic on medication utilization and outcomes. A multidisciplinary clinic composed of advanced practice providers, pharmacists, nutritionists, and nurses was developed and enrolled patients after discharge from LVAD implantation. Candidates for enrollment were those who could make the scheduled visits. Our OPTIMIZE clinic consisted of a total of 6 visits each two weeks apart and included medication optimization as well as nutrition and pharmacy counseling. Patients who survived to discharge and were not enrolled in the OPTIMIZE clinic were utilized as controls and their variables were collected approximately 3-4 months post-implant. T-test, Chi square, and negative binomial regression were utilized to compare variables and outcomes between groups. From January 2019 and March 2021, 26 patients completed OPTIMIZE clinic. Our control group consisted of 43 LVAD patients. Enrolled patients had an average age of 55.3 (±12.8) years, 11 (42.3%) were female, 24 (92.3%) were HeartMate 3 and 2 (7.8%) were HeartWare, and were enrolled an average of 38 (±16) days post-implant. At the end of OPTIMIZE, there was a 150% increase in beta blocker use (8 vs 20), 140% increase in ARNi use (5 vs 12), 17% increase in aldosterone antagonist use (18 vs 21), 41% reduction in loop diuretic use (17 vs 10), and 7 patients were started on SGLT2i (0 at baseline). Comparison of medication use, lab values, and hospitalizations at the end of LVAD OPTIMIZE clinic compared to controls at similar time points is shown in Table 1. A multidisciplinary LVAD OPTIMIZE clinic can help improve medication utilization post-implant and is associated with lower rates of hospitalization and less renal dysfunction. Further studies are needed to help clarify optimal GDMT utilization and timing of initiation in this population.

S1794 Refractory Hypokalemia in the Setting of Ogilvie Syndrome

Introduction: Ogilvie Syndrome often results from a disruption of the parasympathetic nervous system due to electrolyte abnormalities. This case study examines a unique presentation of Ogilvie Syndrome involving secretory diarrhea with increased fecal potassium losses resulting in refractory hypokalemia. This case explores the use of cholinesterase inhibitors, aldosterone antagonists and potassium sparing diuretics in the management of such cases of colonic pseudo-obstruction. Case Description/Methods: An 83 year-old male presented with encephalopathy and abdominal pain. Physical examination was notable for significant abdominal distention. Labs demonstrated severe hypokalemia. CT abdomen revealed massive colonic distention with cecal diameter at 10 cm. Neither CT nor contrast enema study showed signs of mechanical obstruction. Initial management was focused on replacing potassium prior to considering other pharmacologic therapy. Despite aggressive replacement, the hypokalemia persisted. Further workup of the hypokalemia was consistent with non-renal losses. Stool studies were consistent with fecal potassium losses. A potassium-sparing diuretic and aldosterone antagonist were used to increase potassium levels, but with ongoing diarrhea, hypokalemia continued to recur. The patient was subsequently treated with neostigmine with swift resolution of the pseudo-obstruction. Once the diarrhea resolved, the patient was able to maintain his response to hypokalemia therapy. Discussion: Ogilvie syndrome is a functional obstruction thought to be due to disturbance in the parasympathetic system that has been associated with electrolyte abnormalities and is usually treated with conservative management including electrolyte replacement and physical therapy. Colonic pseudo-obstruction is often associated with secretory diarrhea and hypokalemia. In some patients, most commonly, end stage renal patients, an overexpression of potassium cotransporters helps eliminate potassium when kidneys are unable. This has been thought to contribute to hypersecretion of potassium with diarrhea. Our patient had severe hypokalemia despite aggressive electrolyte replacement with high fecal potassium losses. As aldosterone increases urinary excretion of potassium in the urine, antagonists are used to treat hypokalemia. While it is not yet the standard of care, it is important to recognize that potassium-sparing aldosterone antagonists can improve and aid in the management of this type of Ogilvie Syndrome.

Диуретики в современной нефрологии

В работе рассмотрена проблема использования петлевых диуретиков у пациентов с хронической болезнью почек, которая сочетается с кардиоваскулярными рисками, а именно: сердечной недостаточностью, артериальной гипертензией, отечным синдромом, в том числе на фоне сахарного диабета. Представлены три терапевтических интервала торасемида и ксипамида, который можно добавлять к торасемиду для усиления диуретического эффекта. Приведены схемы их назначения и дозировки торасемида. На конкретных клинических примерах определены причины и клинические ситуации задержки жидкости при болезнях почек, освещена роль задержки жидкости в формировании кардиоваскулярных осложнений. Дана сравнительная характеристика эффективности различных доз торасемида, которые чаще всего используются в современной нефрологии. Рассмотрены практика и особенности их назначения в отдельных нефрологических ситуациях, последовательность и комплексность в формировании терапевтического эффекта в зависимости от гидратации пациента, данных биоимпеданса и диагноза. Проанализирован терапевтический подход согласно современным руководствам по сердечной недостаточности. Подчеркнута необходимость подбора дозы торасемида для достижения адекватного диуреза. Обращается внимание на возможность непрерывного назначения торасемида у пациентов, имеющих высокие значения натрийуретического пептида. В других клинических ситуациях использования торасемида требовалось прерывистое его назначение по причине формирования резистентности к его применению. Подчеркнута необходимость поддержания нормонатриемии у пациентов, длительно получающих диуретики. Указаны частые побочные действия диуретиков, возможность их избегания и коррекции. Представлены показатели, которые требуют контроля при назначении диуретиков. В конце статьи даны практические рекомендации для врачей, которые позволят обоснованно назначать петлевые диуретики, в частности торасемид. Акцентировано внимание на широком диапазоне дозирования торасемида в зависимости от клинической ситуации и расчетной скорости клубочковой фильтрации пациента с хронической болезнью почек и сопутствующими клиническими состояниями. Рекомендовано преимущественное применение торасемида, ксипамида, антагонистов альдостерона.

Incidence and impact of acute cardiorenal syndrome

Abstract Funding Acknowledgements Type of funding sources: None. Background Acute (or type 1) cardio-renal syndrome (ACRS) is defined as the acute kidney injury in patients hospitalized for acute heart failure (HF), which often is associated to a complex and complicated clinical course. In addition, renal failure is a strong predictor of long-term adverse events in patients with acute heart failure (HF). Purpose To investigate the impact of ACRS, what factors are related to its occurrence, and how it affects the outcome of patients hospitalized with acute HF. Methods We studied consecutive patients hospitalized with acute HF from January 2019 to December 2020. Renal function as well as other biomarkers were recorded and monitored during hospitalization, and correlated with various clinical characteristics, risk factors and patient outcome. Results The sample consists of 612 patients, mean age 77 ± 12 years, 63% men with average duration of hospitalization 6 ± 4 days. A total of 37 deaths (6%) were observed. ACRS was found in 141 patients (23%) and independent prognostic factors for its occurrence were ischemic cardiomyopathy, age, prolonged hospitalization, use of aldosterone antagonists and high CRP upon admission. The incidence of ACRS during hospitalization was an independent prognostic factor of death (r = 0.15, p = 0.02) and anemia (r = 0.24, p = 0.04), while the outcome of death was more common in patients with ACRS - but without statistical significance - compared to patients without ACRS. Conclusion Deterioration of renal function in acute HF is associated with anemia and death. Factors such as ischemic cardiomyopathy, age, length of hospital stay seem to play a role in the onset of ACRS and should be taken into account in these patients, to prevent negative outcomes.

Prognostic value of BNP in STEMI patients

Abstract Funding Acknowledgements Type of funding sources: None. OnBehalf Portuguese Registry of Acute Coronary Syndromes (ProACS) Introduction Brain natriuretic peptide (BNP) is a highly sensitive and specific biomarker on the extension of myocardial infarction, strongly related to short and long-term prognosis in patients with ST elevation myocardial infarction (STEMI). Objective To evaluate diagnostic and prognostic value of BNP levels in a Portuguese cohort of STEMI patients. Material and methods Retrospective analysis of patients admitted with STEMI included in the Portuguese Registry of Acute Coronary Syndromes between 2010-19. Patients were divided in three groups regarding BNP: Group 1 if BNP <100 pg/ml; Group 2 100 ≤ BNP < 400 pg/ml and Group 3 ≥400 pg/ml. Independent predictors of a composite of all-cause mortality and rehospitalization for cardiovascular causes were assessed by multivariate logistic regression. Results 1650 patients were included, mean age 64 ± 13 years, 75.4% male. 39.0% (n = 643) integrated group 1, 39.5% (n = 652) group 2 and 21.5% (n = 355) group 3. Group 3 patients were significantly older (58 ± 11 vs 66 ± 13 vs 72 ± 12 years, p < 0.001), had more classic cardiovascular risk factors, except for smoker status, and more previous history of cardiovascular disease, chronic kidney disease, chronic obstructive pulmonary disease and cancer. Anterior STEMI was the most frequent location (51.1%), however group 3 patients presented with lower systolic blood pressure (136 ± 30 vs 140 ± 31 vs 131 ± 28 mmHg, p < 0.001) and higher heart rate (76 ± 17 vs 77 ± 19 vs 84 ± 26 bpm, p < 0.001) and KK class (KK class > I 5.6 vs 9.5 vs 28.5%, p < 0.001). They also presented higher levels of creatinine (1 ± 0.5 vs 1.2 ± 0.9 vs 1.5 ± 1 mg/dl, p < 0.001) and the lowest levels of hemoglobin (13.5 ± 1.6 vs 12.6 ± 1.9 vs 11.7 ± 2.1 g/dl, p < 0.001). Mean ejection fraction (EF) was lower in group 3 (58 ± 11 vs 53 ± 12 vs 44 ± 13%, p < 0.001). Multivessel disease was more common in group 3 (34.8 vs 44.8 vs 51.3%, p < 0.001), where a higher percentage was proposed to medical therapy (2.8 vs 3.5 vs 8.5%, p < 0.001). In the patients proposed to revascularization, although not statistically significant, there was a trend towards surgical revascularization or hybrid approach. In-hospital complications were more frequent in group 3, especially heart failure (HF) (18.9% mean vs 45.4%, p < 0.001), and mortality was seven times superior in group 3 versus group 1 (1.2% vs. 8.5%, p < 0.001). The composite endpoint of 1-year mortality and cardiovascular rehospitalization occurred in 12%. After propensity score application, the 1-year endpoint total mortality rate and cardiovascular readmission was 20.3%, and higher BNP was associated with higher rates (p < 0.001). Predictor factors for the composite endpoint, evaluated through Cox multivariate regression were previous HF, multivessel disease, EF < 30% and the use of nitrates and aldosterone antagonists. The use of aspirin was a protector factor. Conclusion BNP levels during index hospitalization were a powerful prognostic biomarker for all-cause mortality MACE in patients admitted with STEMI.

Development and external validation of prediction models to predict implantable cardioverter-defibrillator efficacy in primary prevention of sudden cardiac death.

AimsThis study was performed to develop and externally validate prediction models for appropriate implantable cardioverter-defibrillator (ICD) shock and mortality to identify subgroups with insufficient benefit from ICD implantation. Methods and resultsWe recruited patients scheduled for primary prevention ICD implantation and reduced left ventricular function. Bootstrapping-based Cox proportional hazards and Fine and Gray competing risk models with likely candidate predictors were developed for all-cause mortality and appropriate ICD shock, respectively. Between 2014 and 2018, we included 1441 consecutive patients in the development and 1450 patients in the validation cohort. During a median follow-up of 2.4 (IQR 2.1–2.8) years, 109 (7.6%) patients received appropriate ICD shock and 193 (13.4%) died in the development cohort. During a median follow-up of 2.7 (IQR 2.0–3.4) years, 105 (7.2%) received appropriate ICD shock and 223 (15.4%) died in the validation cohort. Selected predictors of appropriate ICD shock were gender, NSVT, ACE/ARB use, atrial fibrillation history, Aldosterone-antagonist use, Digoxin use, eGFR, (N)OAC use, and peripheral vascular disease. Selected predictors of all-cause mortality were age, diuretic use, sodium, NT-pro-BNP, and ACE/ARB use. C-statistic was 0.61 and 0.60 at respectively internal and external validation for appropriate ICD shock and 0.74 at both internal and external validation for mortality.ConclusionAlthough this cohort study was specifically designed to develop prediction models, risk stratification still remains challenging and no large group with insufficient benefit of ICD implantation was found. However, the prediction models have some clinical utility as we present several scenarios where ICD implantation might be postponed.

Association between levosimendan, postoperative AKI, and mortality in cardiac surgery: Insights from the LEVO-CTS trial

We aimed to evaluate the association between levosimendan treatment and acute kidney injury (AKI) as well as assess the clinical sequelae of AKI in cardiac surgery patients with depressed left ventricular function (ejection fraction <35%). Patients in the LEVO-CTS trial undergoing on-pump coronary artery bypass grafting (CABG), valve, or CABG/valve surgery were stratified by occurrence and severity of postoperative AKI using the AKIN classification. The association between levosimendan infusion and AKI was modeled using multivariable regression. Among 854 LEVO-CTS patients, 231 (27.0%) experienced postoperative AKI, including 182 (21.3%) with stage 1, 35 (4.1%) with stage 2, and 14 (1.6%) with stage 3 AKI. The rate of AKI was similar between patients receiving levosimendan or placebo. The odds of 30-day mortality significantly increased by AKI stage compared to those without AKI (stage 1: adjusted odds ratio [aOR] 2.0, 95% confidence interval [CI] 0.8-4.9; stage 2: aOR 9.1, 95% CI 3.2-25.7; stage 3: aOR 12.4, 95% CI 3.0-50.4). No association was observed between levosimendan, AKI stage, and odds of 30-day mortality (interaction P = .69). Factors independently associated with AKI included increasing age, body mass index, diabetes, and increasing baseline systolic blood pressure. Increasing baseline eGFR and aldosterone antagonist use were associated with a lower risk of AKI. Postoperative AKI is common among high-risk patients undergoing cardiac surgery and associated with significantly increased risk of 30-day death or dialysis. Levosimendan was not associated with the risk of AKI.

Clinical Representativeness of the PARADIGM-HF Study in an Outpatient Cohort of Patients with Heart Failure, Including Chagas Disease, Treated According to Guideline-directed Medical Therapy: Prospective Study, in a Single Center in Brazil

Background: In the PARADIGM-HF trial there was a 20% reduction in hospitalization and cardiovascular mortality in patients with heart failure (HF) and treated according to guideline-directed medical therapy. Eligibility for the use of sacubitril/valsartan in the real world has varied between 12% and 76%. There are no studies on the national scene on this eligibility.&#x0D; Aims: To investigate the clinical eligibility of the PARADIGM-HF trial in patients with HF in the outpatient clinic of a university institution, which also includes Chagas disease, and to compare the profile of the two populations.&#x0D; Study Design: This is a single center, prospective, observational study.&#x0D; Place and Duration of Study: Department of Internal Medicine, Faculty of Medicine, Hospital das Clínicas, Federal University of Minas Gerais, Brazil, duration 6 consecutive months.&#x0D; Methods and Results: We included 136 consecutive outpatients with HF, 53 women, and mean age of 54.2 years, underwent clinical and laboratory evaluation. The main etiologies of HF were ischemic, Chagas disease and idiopathic. The means of baseline variables were 117.2 mmHg for systolic blood pressure, 78.4 bpm for heart rate, 1.8 for dyspnea functional class, 0.39 for ejection fraction (EF) and 74.2 mL/min for creatinine clearance. The exclusion criteria considered in the PARADIGM-HF trial and present in this study were systolic blood pressure less than 95 mmHg in 15.4% and creatinine clearance less than 30 mL/min in 5.1% of patients. 22.1% had mid-range EF and 55.9% had reduced EF. Comparing this cohort of patients with the population of the PARADIGM-HF trial, age, systolic blood pressure, proportion of male patients, ischemic etiology, hypertension, patients with atrial fibrillation, use of angiotensin-converting enzyme inhibitor, furosemide and beta-blocker were lower in this study (p ≤ 0.01, chi-square and Student's t tests). The proportion of diabetic patients, use of angiotensin receptor blocker, aldosterone antagonist and digoxin were similar between groups as well as proportion of patients with cardiac resynchronization therapy.&#x0D; Conclusions: Up to 44% of patients in this study did not meet the main randomized trial criteria. Chagas disease was one of the main etiologies. Furthermore, systolic blood pressure, proportion of hypertensive patients was lower, which may have influenced the underutilization of some medications.

Association Between Medication Use and Bullous Pemphigoid

The association between the use of medications and the development of bullous pemphigoid (BP) is unclear. To assess the associations between previous exposure to certain medications and BP. For this systematic review and meta-analysis, PubMed, the Cochrane Central Register of Controlled Trials, and Embase were searched for relevant studies from inception to February 20, 2020. Case-control or cohort studies and randomized clinical trials that examined the odds or risk of BP in patients with previous medication use were included. No geographic or language limitations were imposed. The Meta-analysis of Observational Studies in Epidemiology (MOOSE) guideline was followed. The Newcastle-Ottawa Scale was used to evaluate the risk of bias of included observational studies; Cochrane Collaboration's tool was used for randomized clinical trials. Aggregate data were used to conduct a random-effects model meta-analysis if the included studies were sufficiently homogenous. Subgroup analyses were performed for use of various medications of the same category. Odds ratio (OR), hazard ratio, and risk ratio of bullous pemphigoid in association with medication use. This meta-analysis included 13 case-control studies, 1 cohort study, and 1 randomized clinical trial with a total of 285 884 participants. The meta-analysis of case-control studies showed a significant association of BP with previous use of aldosterone antagonists (pooled OR, 1.75; 95% CI, 1.28-2.40), dipeptidyl peptidase 4 inhibitors (pooled OR, 1.92; 95% CI, 1.55-2.38), anticholinergics (pooled OR, 3.12; 95% CI, 1.54-6.33), and dopaminergic medications (pooled OR, 2.03; 95% CI, 1.34-3.05). One cohort study found an increased risk of BP among patients receiving dipeptidyl peptidase 4 inhibitors (hazard ratio, 2.38; 95% CI, 1.16-4.88; P = .02). One trial found a higher occurrence of BP in patients with diabetes receiving linagliptin (0.2% in diabetes group vs 0% in the placebo group). The findings of this systematic review and meta-analysis suggest that aldosterone antagonists, dipeptidyl peptidase 4 inhibitors, anticholinergics, and dopaminergic medications are associated with BP. These medications should be judiciously prescribed, particularly in high-risk patients who are elderly and have disabling neurologic disorders.

P1584 Characteristics of a new subgroup in chronic heart failure: heart failure with mid-range ejection fraction (HFmrEF)

Abstract Introduction Classification of patients with heart failure is based on left ventricular ejection fraction (LVEF). Until recently, two types of patients had been distinguished based on LVEF: those with reduced ejection fraction (HFrEF) and those with HF with preserved ejection fraction (HFpEF). The ESC guidelines of 2016 introduced a third separate subgroup for patients with a LVEF in the range of 40-50%: Heart failure with mid-range ejection fraction (HFmrEF). Purpose The goal of this study is to characterize and compare this subgroup (HFmrEF) to the other two subgroups (HFpEF and HFrEF). Secondly, mortality rates were studied and compared, depending on LVEF classification and global longitudinal strain (GLS). Methods All patients with Chronic Heart Failure (CHF) seen at the heart failure clinic, during a 1-year period were enrolled in this retrospective study. As an inclusion criterion in our study population, we only allowed patients with chronic heart failure, who were treated at least once with diuretics or a cardiac resynchronization therapy for heart failure. After gathering data of the HF population, the 3 subgroups (HFrEF, HFpEF and HFmrEF) were compared on the basis of different parameters like comorbidities, lab results, medication, ECG and echocardiography. Results HFmrEF significantly differed from HFpEF concerning the following parameters: higher prevalence of male gender and ischemic aetiology, lower prevalence of valvular and hypertensive aetiology, more dilated left ventricles and higher usage of ACE inhibitors and betablockers. HFmrEF was similar to HFpEF concerning older age, high prevalence of tachyarrhythmia, low use of device therapy and aldosterone antagonists. The survival rate after 853 days was 81,6% in HFrEF, 76,3% in HFmrEF and 81,1% in HFpEF (p = 0,634). When looking at the whole patient population, the Kaplan Meier estimation was significant (p &amp;lt; 0,001) with a survival rate after 853 days of 33,3% for the group with lower absolute values than 6,3% for GLS and 85% for group with higher absolute strain values. Conclusion Patients with HFmrEF didn’t really differentiate as one class apart from HFrEF or HFpEF, but some characteristics were similar to HFrEF, and some others to HFpEF. Finally some characteristics of HFmrEF were more in a grey zone with none of the characteristics of both HFrEF nor HFpEF. The all cause survival rate in 853 days among the 3 LVEF based groups, were quite similar. While the Kaplan Meier estimation indicated a lot higher mortality when GLS&amp;gt;-6,3% compared to GLS &amp;lt;-6,3%. Classifying chronic HF patients is probably more complex than simply stratifying patients by LVEF cut-off values. One must not forget to take comorbidities and aetiology in mind while managing heart failure. Abstract P1584 Figure. Aetiology in LVEF based groups

Development of hypotension in patients newly diagnosed with heart failure in UK general practice: retrospective cohort and nested case–control analyses

ObjectivesHypotension is of particular relevance for patients with heart failure (HF), since almost all HF drugs cause lowering of blood pressure (BP) and it is associated with a poor prognosis....

Aldosterone impairs coronary adenosine-mediated vasodilation via reduced functional expression of Ca2+-activated K+ channels

Elevated plasma aldosterone (Aldo) levels are associated with greater risk of cardiac ischemic events and cardiovascular mortality. Adenosine-mediated coronary vasodilation is a critical cardioprotective mechanism during ischemia; however, whether this response is impaired by increased Aldo is unclear. We hypothesized that chronic Aldo impairs coronary adenosine-mediated vasodilation via downregulation of vascular K+ channels. Male C57BL/6J mice were treated with vehicle (Con) or subpressor Aldo for 4 wk. Coronary artery function, assessed by wire myography, revealed Aldo-induced reductions in vasodilation to adenosine and the endothelium-dependent vasodilator acetylcholine but not to the nitric oxide donor sodium nitroprusside. Coronary vasoconstriction to endothelin-1 and the thromboxane A2 mimetic U-46619 was unchanged by Aldo. Additional mechanistic studies revealed impaired adenosine A2A, not A2B, receptor-dependent vasodilation by Aldo with a tendency for Aldo-induced reduction of coronary A2A gene expression. Adenylate cyclase inhibition attenuated coronary adenosine dilation but did not eliminate group differences, and adenosine-stimulated vascular cAMP production was similar between Con and Aldo mice. Similarly, blockade of inward rectifier K+ channels reduced but did not eliminate group differences in adenosine dilation whereas group differences were eliminated by blockade of Ca2+-activated K+ (KCa) channels that blunted and abrogated adenosine and A2A-dependent dilation, respectively. Gene expression of several coronary KCa channels was reduced by Aldo. Together, these data demonstrate Aldo-induced impairment of adenosine-mediated coronary vasodilation involving blunted A2A-KCa-dependent vasodilation, independent of blood pressure, providing important insights into the link between plasma Aldo and cardiac mortality and rationale for aldosterone antagonist use to preserve coronary microvascular function.NEW & NOTEWORTHY Increased plasma aldosterone levels are associated with worsened cardiac outcomes in diverse patient groups by unclear mechanisms. We identified that, in male mice, elevated aldosterone impairs coronary adenosine-mediated vasodilation, an important cardioprotective mechanism. This aldosterone-induced impairment involves reduced adenosine A2A, not A2B, receptor-dependent vasodilation associated with downregulation of coronary KCa channels and does not involve altered adenylate cyclase/cAMP signaling. Importantly, this effect of aldosterone occurred independent of changes in coronary vasoconstrictor responsiveness and blood pressure.

Aldosterone Antagonists Reduce the Risk of Cardiovascular Mortality in Dialysis Patients: A Meta-Analysis.

Background and Purpose. Cardiovascular disease is the major cause of death in dialysis patients. Although aldosterone antagonists were considered a treatment for severe heart failure patients to reduce cardiac mortality, whether treating patients undergoing maintenance dialysis with aldosterone antagonists could reduce the risk of cardiocerebrovascular (CCV) remains unclear. We aim to systematically assess the efficacy and tolerability of the addition of aldosterone antagonists to conventional therapy in patients undergoing maintenance dialysis. Materials and Methods. We searched PubMed, EMBASE, the Cochrane Library, the Chinese Biomedical Literature Database (CBM), and the China National Knowledge Infrastructure (CNKI) for relevant articles. The primary endpoint of interest was CCV mortality. The secondary endpoints were all-cause mortality, left ventricular mass index (LVMI), and left ventricular ejection fraction (LVEF). Publication bias was evaluated using funnel plots and Egger's test. The meta-analysis was performed using Review Manager software version 5.3. Results. This analysis included 10 randomized controlled trials (RCTs) with 1172 total chronic dialysis patients. The use of aldosterone antagonists in the dialysis population resulted in a marked reduction in CCV mortality (RR 0.42, 95% CI 0.26-0.65, P=0.0002) and all-cause mortality (RR0.46, 95%CI 0.32-0.66, P<0.0001). The LVEF was improved by treatment with aldosterone antagonists (WMD 6.35%, P<0.00001). Moreover, aldosterone antagonists decreased the LVMI (WMD -8.69 g/m2, P=0.0006), whereas aldosterone antagonists increased the occurrence of hyperkalemia (RR1.70, 95%CI 1-2.88, P=0.05) and gynecomastia (RR 8.01, 95% CI 2.44- 26.27, P=0.0006). Conclusions. Addition of aldosterone antagonists to conventional treatment in chronic dialysis patients may reduce CCV mortality, improve cardiac function, and simultaneously decrease LVMI.

Long-term and clinical profile of heart failure with recovered ejection fraction in a non-tertiary hospital

IntroductionHeart failure (HF) with recovered ejection fraction (EF) is emerging as a different HF subtype. There is little information about his clinical profile in hospitals that are not a reference. MethodsWe analyzed characteristics and prognosis in patients with recovered HF followed prospectively in the HF Unit of a non-tertiary hospital. ResultsA total of 431 patients with HF with reduced EF were followed (median 50 months, 79.3% males, mean age 70.3±12.2years). Of the patients, 26.9% (N 116) recovered EF, mainly in the first year of follow-up (76.7%). Compared with patients that did not recovered EF in the follow-up, they were younger, rate of ischemic origin of cardiomyopathy was less frequent and presented less comorbidity. Mortality was lower in patients with recovered HF (survival median of 85.2±2.1 vs. 74.2±1.9 months [log-rank χ2 11.5, p=0.001], hazard ratio 0.37, 95% confidence interval [CI]: 0.21–0.67, p=0.002). Etiology of deaths was not mainly secondary to HF. Younger age of 68 years (odds ratio [OR] 0–98, 95% CI: 0.96–0.99; p=0.025), ischemic origin (OR 1.12, 95% CI: 1.01–1.21; p=0.003) and use of aldosterone antagonists (OR 1.89, 95% CI: 1.09–3.26; p=0.023) were the variables independently associated to normalization of EF. ConclusionHF with recovered EF is a frequent phenomenon. It has a more favorable clinical course, prognosis and basal characteristics than HF with persistent reduced EF. Further studies are needed to identify natural history and optimal medications for HF-recovered patients.

Características y evolución de la insuficiencia cardiaca con función sistólica recuperada en un hospital no terciario

IntroductionHeart failure (HF) with recovered ejection fraction (EF) is emerging as a different HF subtype. There is little information about his clinical profile in hospitals that are not a reference. MethodsWe analysed characteristics and prognosis in patients with recovered HF followed prospectively in the HF Unit of a non-tertiary hospital. ResultsA total of 431 patients with HF with reduced EF were followed (median 50 months, 79.3% males, mean age 70.3±12.2years). Of the patients, 26.9% (N 116) recovered EF, mainly in the first year of follow-up (76.7%). Compared with patients that did not recovered EF in the follow-up, they were younger, rate of ischemic origin of cardiomyopathy was less frequent and presented less comorbidity. Mortality was lower in patients with recovered HF (survival median of 85.2±2.1 vs. 74.2±1.9 months [log-rank χ2 11.5, P=0.001], hazard ratio 0.37, 95% confidence interval [CI]: 0.21-0.67, P=0.002). Aetiology of deaths was not mainly secondary to HF. Younger age of 68 years (odds ratio [OR] 0-98, 95% CI: 0.96-0,99; P=0.025), ischemic origin (OR 1.12, 95% CI: 1.01-1.21; P=0.003) and use of aldosterone antagonists (OR 1.89, 95% CI: 1.09-3.26; P=0.023) were the variables independently associated to normalisation of EF. ConclusionHF with recovered EF is a frequent phenomenon. It has a more favourable clinical course, prognosis and basal characteristics than HF with persistent reduced EF. Further studies are needed to identify natural history and optimal medications for HF-recovered patients.

Risk Factors and Outcomes of Rapid Correction of Severe Hyponatremia.

Rapid correction of severe hyponatremia can result in serious neurologic complications, including osmotic demyelination. Few data exist on incidence and risk factors of rapid correction or osmotic demyelination. In a retrospective cohort of 1490 patients admitted with serum sodium <120 mEq/L to seven hospitals in the Geisinger Health System from 2001 to 2017, we examined the incidence and risk factors of rapid correction and osmotic demyelination. Rapid correction was defined as serum sodium increase of >8 mEq/L at 24 hours. Osmotic demyelination was determined by manual chart review of all available brain magnetic resonance imaging reports. Mean age was 66 years old (SD=15), 55% were women, and 67% had prior hyponatremia (last outpatient sodium <135 mEq/L). Median change in serum sodium at 24 hours was 6.8 mEq/L (interquartile range, 3.4-10.2), and 606 patients (41%) had rapid correction at 24 hours. Younger age, being a woman, schizophrenia, lower Charlson comorbidity index, lower presentation serum sodium, and urine sodium <30 mEq/L were associated with greater risk of rapid correction. Prior hyponatremia, outpatient aldosterone antagonist use, and treatment at an academic center were associated with lower risk of rapid correction. A total of 295 (20%) patients underwent brain magnetic resonance imaging on or after admission, with nine (0.6%) patients showing radiologic evidence of osmotic demyelination. Eight (0.5%) patients had incident osmotic demyelination, of whom five (63%) had beer potomania, five (63%) had hypokalemia, and seven (88%) had sodium increase >8 mEq/L over a 24-hour period before magnetic resonance imaging. Five patients with osmotic demyelination had apparent neurologic recovery. Among patients presenting with severe hyponatremia, rapid correction occurred in 41%; nearly all patients with incident osmotic demyelination had a documented episode of rapid correction. This article contains a podcast at https://www.asn-online.org/media/podcast/CJASN/2018_06_05_CJASNPodcast_18_7_G.mp3.

Diagnosis and management of resistant hypertension: state of the art.

Resistant hypertension is defined as a lack of ambulatory blood pressure response to optimized medical treatment after exclusion of secondary hypertension in patients who are fully adherent to antihypertensive therapy. Patients with resistant hypertension are at high risk of complications, particularly cardiovascular events, and optimization of medical treatment remains the cornerstone of their management. Such optimization should be based on simple algorithms and include the use of aldosterone antagonists. The available data from clinical trials do not support the use of device-based approaches such as renal denervation, baroreflex activation therapy or arteriovenous anastomosis for the treatment of resistant hypertension in the majority of patients. Therefore, device treatment remains a last-resort for patients with truly resistant hypertension in the context of clinical research in highly skilled tertiary referral centres. Future research should focus on improving understanding of the intrinsic (physiological and psychological factors) and extrinsic (environmental stressors) mechanisms that contribute to a lack of response to blood-pressure-lowering drugs in adherent patients. The use of biomarkers to identify patients with early target organ damage and new technologies, such as renal nerve stimulation, to predict blood pressure responses to renal denervation could aid the selection of patients who might benefit from device therapies.