Mineralcorticoid Receptor Research Articles

Abstract 14354: Prognostic Impact of Low Serum Chloride Level in Elderly Patients With Heart Failure

Background: Patients with heart failure (HF) are known to be stratified the risk of mortality by serum chloride level. However, since large-scaled studies to date have not included the elderly patients, it is still unclear whether serum chloride level well predicts the prognosis of the elderly patients with HF, whose clinical profiles are different from young adult patients. We aimed to test the hypothesis that hypochloremia gave different prognostic impacts in non-elderly and elderly patients with HF. Methods: This observational study included 1,326 elderly patients ( > 65 year-old) without regular hemodialysis who were hospitalized for worsening of HF and discharged alive. They were divided into two subgroups depending on serum chloride levels at admission (Low-chloride group ( < 97 mEq/L, n=244); Normal-chloride group ( > 98 mEq/L, n=1518)), referred to prior reports. Propensity scores were developed and patients in Normal-chloride group were matched with those in Low-chloride group in a 1:1 ratio. The endpoint of this study was death from any cause. Results: Among 1,326 unmatched patients, Low-chloride group included significantly more male patients, and those with higher BUN, CRP, bilirubin levels, dose of furosemide and atrial fibrillation, and prescriptions of oral anticoagulant, and lower BMI, blood pressure, hemoglobin, prescription of mineral corticoid receptor antagonist, thiazide and statins. Following propensity score matching by diverse baseline parameters, 106 pairs in both groups were included in the matched population. During 413 days of median observational period, 62 patients (28.8%) died. Kaplan-Meier analysis showed that patients in the Low-chloride group had a significantly higher mortality rate (p=0.011, Figure ). Conclusion: In this observational study, baseline hypochloremia was associated with an increased mortality in elderly patients hospitalized with heart failure.

Guideline Directed Medical Therapy at Discharge and Further Uptitration Leading to Reduction in Indication for Prophylactic ICD Implantation during Protected Waiting Period.

Heart failure with reduced ejection fraction (LV-EF < 35%) is diagnosed in app. 11,000,000 patients worldwide. For the treatment of these patients, guideline directed medical therapy has proven to reduce mortality and rehospitalization regardless of the disease’s etiology. It is implemented to treat clinical symptoms by improving the left ventricular ejection fraction. Patients with a transient risk of ventricular tachycardia and sudden cardiac death can be protected by a defibrillator vest. The defibrillator vest is capable to detect and terminate ventricular arrhythmias during Guideline Directed Medical Therapy (GDMT). It is based on the recommendations of the European society of cardiology for 3 months. Afterwards, the WCD wear time could be prolonged, or, in case of persistent low ejection fraction (LV-EF ≤ 35%), an implantable cardioverter defibrillator (ICD) should be implanted, as shown in the WEARIT-II-registry. Our goal was to evaluate the effects of GDMT on LV-recovery and reduction of ICD implantations under protection with a defibrillator vest—depending on the uptitration of GDMT. Methods: 339 consecutive patients between August 2017 and September 2020 with newly diagnosed cardiomyopathy and an EF ≤ 35% were analyzed retrospectively by chart review. All patients were protected by a wearable cardioverter defibrillator (WCD). GDMT as recommended by the ESC started at discharge from hospital. The left ventricular ejection fraction (LV-EF) was determined by transthoracic echocardiography at week 4, 8 and at week 12 (in case of prolonged WCD wear time). Uptitration was performed after 4 and 8 weeks during patient visits. We focused on baseline medication as per GDMT and the dosage increase at week 4, 8 and 12. The aim was the uptitration to the maximum dosage tolerated by the patient. We also compared the LV-EF improvement in the group with and without uptitration of medication dosage. Results: The patient age was, on average, 63.2 years (SD ± 11.9 years). A total of 129 pts (38%) had ICM, 196 (58%) had NICM (incl 66 pts (19%) with DCM and 51 pts (15%) with Myocarditis, 79 pts (24%) with unknown origin) and 14 pts (4%) had other entities (e.g., Tachycardiomyopathy). In total, 21 pts (6%) had an LV-EF of less than 16%, 130 pts (38%) between 16–25% and 183 pts (54%) between 26–35%. GDMT started at discharge from the hospital included treatment with beta blocker for 327 pts (96.5%), ACE-inhibitors/Angiotensin/ARNI for 283 pts (83.5%) and Mineralcorticoid receptor antagonists (MRA) for 334 pts (88.4%). Uptitration was performed in all groups at a rate of 82.3%, 91.1% and 81.0% after 4 weeks and 64.7%, 50.3% and 66.3% after 8 weeks, respectively. After 4 weeks, 25 pts (7.4%) and, after 8 weeks, 171 pts (50.4%) had an EF increase of 5% or more (mean 14.2%). After 4 weeks, 81 patients had an LV-EF more than 35%. A total of 169 pts had a wear time of 12 weeks and an improvement of LVEF of more than 35%. Interestingly, in our study we did not find a significant difference in LV-EF improvement between the group with no uptitration and the group with uptitration. Conclusions: Guideline-directed medical therapy under protection with a WCD from ventricular arrhythmia can reduce the need for implantation of an ICD and can lead to an improvement of ejection fraction. Interestingly, the LV-EF improvement depends on the GDMT at discharge. Current guidelines recommend an initiation of all therapy columns of GDMT (sacubitril/valsartan, ACE-inhibitor/AT1-blocker, mineralcorticoidreceptorblocker, beta blocker) at once and further uptitration to the maximal dosage (ESC Guidelines 2021). A further uptitration of all drugs of GDMT should lead to improvement of LV-EF and consequently to a reduction in ICD implantations.

Where do we stand with acute myocardial infarction patients with severely reduced left ventricular ejection fraction? insights from AMIS Plus Registry

Abstract Background Left ventricular ejection fraction (LVEF) represents one of the strongest predictors of both in-hospital and long-term prognosis in acute myocardial infarction (AMI). Temporal trends data coming from real-word experiences focused on AMI patients with severely reduced LVEF (i.e. &amp;lt;30%) are lacking. Purpose The present study aims at providing a comprehensive picture on temporal trends in AMI patients with severely reduced LVEF, with a particular focus on prevalence, in-hospital management/prognosis and pharmacological therapy at discharge. These data could shed light on the implementation in the clinical arena of guideline-directed therapies in this fragile subgroup of patients and on their effect on real-word short-term prognosis. Methods On a total of 48,543 screened AMI patients included in AMIS Plus Registry between 2005 and 2020, data on LVEF were available for 23,510 patients. Study patients were classified according to LVEF as AMI patients with or without severely reduced LVEF (i.e. patients with LVEF &amp;lt;30% and ≤30%, respectively). Results Overall, 1657 AMI patients (7%) presented with severely reduced LVEF. Prevalence of severe LVEF reduction constantly decreased over the study period (from 11% to 4%, p&amp;lt;0.001; Figure 1). In the subgroup of patients with severely reduced LVEF a significant increase in revascularisation (percutaneous and/or surgical) rate was observed (from 61% to 84%, p&amp;lt;0.001); in-hospital access to advanced short-term mechanical circulatory support (both ECMO and/or Impella) significantly increased from 0% in 2011 to 17% (p=0.05). Rate of cardiogenic shock developed during hospitalization remained stable over time (from 21% to 16%, p=0.7); in-hospital mortality did not significantly decrease and remained well above 20% all over the study period (from 23% to 26%, p=0.65; Figure 2). At discharge, prescription of optimal anti-ischaemic therapy (defined as an association of dual antiplatelet therapy and statine) significantly increased (from 47% to 75%, p&amp;lt;0.001), mainly driven by an increase in dual antiplatelet therapy prescription; however, prescription of optimal cardio-protective therapy (defined as an association of renin-angiotensin-aldosterone-system inhibitors, beta-blocker and mineralcorticoid receptor antagonist) remained low across the study period (from 17% in 2011 to 20%, p=0.96). Conclusion AMI patients with severely reduced ejection fraction still remain a fragile subgroup of patients; in-hospital mortality did not significantly decrease and remained exceedingly high and well above 20% all over the study period; efforts are, therefore, urgently needed to develop therapeutic strategies focused on this subgroup of patients and aiming at improving short-term prognosis. Moreover, access at discharge to optimal cardio-protective therapy remains suboptimal; efforts are needed to improve access to guidelines-directed therapy both at discharge and follow-up in this fragile population. Funding Acknowledgement Type of funding sources: Other. Main funding source(s): Swiss Heart Fundation

Aggressive combined pharmacotherapy for heart failure reduces new onset atrial fibrillation

Abstract Backgrounds Heart failure (HF) is a risk factor for new onset atrial fibrillation (AF), and the new onset AF is associated with a worse prognosis in HF patients. It has been reported that renin-angiotensin system inhibitor (RASi), β-blocker and mineral-corticoid receptor antagonist (MRA) prevent the new onset AF in HF patients. However, the effect of combined pharmacotherapy including angiotensin receptor neprilysin inhibitor (ARNI) and sodium glucose co-transporter 2 inhibitor (SGLT2i) on AF is unknown. We investigated the impact of contemporary regimen of combined pharmacotherapy for HF (RASi/ARNI+β-blocker+MRA+SGLT2i) on new onset AF. Methods and results We retrospectively studied rEF and mrEF patients without AF admitted to our hospital due to decompensated HF between 2015 and 2021 (n=366). Long-term (The mean follow-up was 635±421 days) incidence of new onset AF was investigated with regard to medical therapies. Patients were divided into 2 groups; patients with ≤2 HF drugs (n=181) and patients with ≥3 HF drugs (n=185). Patients with ≤2 HF drugs group were older (77.3 vs 67.0 years old, P&amp;lt;0.001), had a poorer renal function (Cre: 1.66 vs 1.09 mg/dl, P&amp;lt;0.001), and had a higher rate of ischemic heart disease (52 vs 38%, P=0.009), whereas left ventricular systolic function was better (EF: 31.9 vs 27.3%, P&amp;lt;0.001). There were 19 (10.5%) new onsets AF in the ≤2 HF drugs group, whereas only 7 (3.8%) had new onsets AF in the ≥3 HF drugs group (HR 0.36, 95% CI 0.15–0.85, P=0.01). All-cause death and hospitalization for HF were fewer in the ≥3 HF drugs group. A multivariate analysis revealed that ≥3 HF drugs use was an independent negative predictor of new onset AF (HR 0.37, 95% CI 0.15–0.93, P=0.03). Even after a propensity score matching of the clinical variables, the incidence of new onset AF was consistently fewer in the ≥3 HF drugs group (HR 0.36, 95% CI 0.13–0.99, P=0.04). Finally, patients with new onset AF had a higher rate of hospitalization for HF in the studied population (HR 9.68, 95% CI 5.67–16.5, P&amp;lt;0.01). Conclusion Aggressive combined pharmacotherapy for HF may be associated with fewer new onset AF in patients with HF. Funding Acknowledgement Type of funding sources: None.

Refractory Arterial Hypertension: Features of Neurohormonal and Water-salt Imbalanceand Approaches to Antihypertensive Drug Therapy

Refractory arterial hypertension is characterized by a lack of control of target blood pressure, despite the prolonged use &gt;5 antihypertensive drugs with different mechanisms of action, including longacting diuretic chlorthalidone and the mineralcorticoid receptor antagonists (spironolactone or eplerenone). The review presents the results of clinical studies devoted the elucidating peculiarities of the neurohormonal status and water-salt balance in such patients and developing new approaches to antihypertensive drug therapy based on them. According to these studies, individuals with refractory hypertension differ from patients with resistant hypertension with the higher of sympathetic nervous system activity and the absence of an increased of intrathoracic fluid volume, which indirectly indicates a significant decrease in the intravascular fluid volume. In this regard, the review focuses on the data obtained in assessing the clinical efficacy of sympatholytics clonidine and reserpine in patients with resistant and refractory hypertension, as well as renal sodium-glucose co-transporter type 2 inhibitors, which suppress the sympathetic nervous system activity and can be used to overcome refractory hypertension in patients with type 2 diabetes.

Refractory arterial hypertension: hyperactivity of the sympathetic nervous system, kidney and approaches to antihypertensive drug therapy

Improving blood pressure (BP) control and reducing the risk of developing unfavorable cardiovascular and renal outcomes in patients with refractory hypertension (HTN) is an urgent problem of cardiology. According to clinical studies, patients with refractory HTN receiving intensive diuretic therapy with chlorthalidone and a mineralcorticoid receptor antagonist differ from patients with refractory HTN by a higher sympathetic nervous system (SNS) activity. Overactivity of sympathetic nerves may be one of the key pathogenetic factors that is involved in the kidney in the formation of refractory HTN, exerting a direct stimulating effect on the type 3 Na+ / H+ exchanger (NHE3) and type 2 sodium glucose cotransporter (SGLT2), which are involved in BP control by mechanism of pressure natriuresis. The review presents data on the peculiarities of sympathetic regulation of sodium tubular transport and the results of studies devoted the elucidating in the patients with resistant and refractory HTN the clinical efficacy of SGLT2 inhibitors glyflozins, sympatholytic reserpine and brain aminopeptidase A inhibitor firibastat, which suppresses the activity of central structures of SNS.

Choroidal modifications assessed by means of choroidal vascularity index after oral eplerenone treatment in chronic central serous chorioretinopathy.

To investigate choroidal vascularity index (CVI) changes after oral eplerenone treatment in chronic central serous chorioretinopathy (cCSC) using the Spectral-domain (SD)-Optical Coherence Tomography (OCT) with enhanced depth imaging (EDI) mode. Thirty-six eyes of 18 patients suffering from cCSC with monolateral foveal subretinal fluid (FSRF) successfully treated with oral eplerenone treatment and 18 age-matched healthy subjects were enroled in this retrospective study. EDI-OCT images obtained using Heidelberg Spectralis OCT device in patients with cCSC and FSRF (group 1); fellow eye (group 2) or healthy patients (healthy) were exported and then imported into image analysis ImageJ software for subsequent quantitative analysis. The main outcome measures were luminal area (LA) and CVI. A higher value of CVI was detected in group 1 compared to healthy eyes (p = 0.006). LA and CVI significantly reduced during follow up in group 1 and group 2. LA at 120 days was significantly lower compared to all previous time points both in group 1 and group 2 (p < 0.001). Median and [1st -3rd quartile] CVI values were 0.8 [0.7; 1.1] at baseline, 0.8 [0.7; 0.9] at 30 days; 0.7 [0.6; 0.9] at 60 and 90 days and 0.6 [0.5; 0.8] at 120 days in group 1 (p = 0.007) and 0.7 [0.6; 0.9] at baseline, 0.7 [0.7; 0.8] at 30 days; 0.7 [0.6; 0.7] at 60 and 90 days and 0.6 [0.6; 0.7] at 120 days in group 2 (p = 0.018). Choroidal vascularity index reduced in cCSC patients after oral eplerenone treatment during follow up both in eyes with SRF and fellow eyes thus demonstrating the effectiveness of mineral corticoid receptor antagonists in recovering choroidal morphology.

Heart failure medication and its effect on response to cardiac resynchronisation therapy in patients with pacing-induced cardiomyopathy: an UPGRADE post hoc analysis

Abstract Funding Acknowledgements Type of funding sources: Other. Main funding source(s): Austrian National Bank Unlimited scientific grant from the Boston Scientific Investigator Sponsored Research (ISR) Committee Background/Introduction Current heart failure (HF) guidelines recommend optimal medical therapy (OMT) in patients with pacing-induced cardiomyopathy (PICM) prior upgrading to cardiac resynchronisation therapy (CRT). It is unknown, whether previous prescription of heart failure medication reduces the effect of CRT upgrading. Purpose To evaluate the effect of HF medication on CRT response in patients suffering from PICM receiving an upgrade to CRT. Methods The UPGRADE trial was a prospective investigator driven trial evaluating the effect of CRT upgrading in patients with PICM. Key inclusion criteria were symptomatic HF with left ventricular ejection fraction (LVEF) below 40% despite OMT and right ventricular pacing (RVP) above 40%. Device programming had to be adjusted to minimize RVP prior to enrolment. Echocardiographic examinations were performed prior to device implantation and 3-5 months after activation of CRT and were analyzed in blinded fashion. CRT response was defined by a reduction of &amp;gt; 15% in left ventricular end systolic volume (LVESV). Heart failure medication was assessed at implantation of the device. Results Overall, 54 patients were enrolled in the UPGRADE trial between 2014 and 2018. Beta-blockers (BB) were prescribed in 43 (79.6%), mineralcorticoid receptor antagonists (MRA) in 29 (53.7%) and either an angiotensin-converting enzyme (ACE) inhibitor or an angiotensin II receptor blockers (ARB) in 45 (83.3%) of the patients. Therapy with CRT has led to significant improvement in LVEF (mean delta: 12.8 ± 7.8%) and LVESV (delta: 30.7 ± 33.2ml), whereas CRT response was achieved in 30 (55.6%) patients. There was no statistically significant difference in patients with BB intake regarding increase of LVEF (12.4 ± 7.5% vs. 14.6 ± 9.4%, p=0.431), decrease of LVESV (42.8 ± 32.8ml vs. 27.8 ± 33.0ml, p=0.201) or CRT response (22 (53.7%) vs. 8 (80%), p=0.167). Similar results were found regarding ACE inhibitor/ARB [LVEF: 13.1 ± 6.8% vs. 11.5 ± 11.8%, p=0.705; LVESV: 32.6 ± 32.6ml vs. 21.7 ± 36.3ml, p=0.373; CRT response: 26 (61.9%) vs. 4 (44.4%), p=0.460] and MRA intake [LVEF: 13.7 ± 7.3% vs. 11.8 ± 8.4%, p=0.382; LVESV: 34.3 ± 36.8ml vs. 26.7 ± 28.8ml, p=0.423; CRT response: 15 (55.6%) vs. 15 (62.5%), p=0.777]. Conclusion Previous prescription of heart failure medication did not reduce the effect of CRT upgrading in patients suffering from PICM. It remains to be proven, whether similar results may be observed for newer HF agents like sodium-glucose co-transporter 2 inhibitors or angiotensin receptor-neprilysin inhibitors as both were not available in clinical routine at the time of study conduct.

C23 HOW TO IMPROVE ADHERENCE TO ESC HF GUIDELINES THE PONTE (PDTA FOR INTEGRATED FOLLOW–UP TERRITORY HOSPITAL OF THE PATIENT WITH CARDIAC HEART FAILURE) PROJECT

Abstract Background A careful and integrated follow up after hospitalization for heart failure (HF) may represent a feasible strategy to optimize the adherence to ESC guidelines and reduce the occurrence of adverse events (mortality, re–hospitalizations). Methods A strict integration between hospital and local health district proximity office cardiologist through an integrated clinical data sharing software has been implemented in Apulia region, Italy, in order to optimize the management of the HF patient after an hospitalization: the PONTE (PDTA FOR INTEGRATED FOLLOW–UP TERRITORY HOSPITAL OF THE PATIENT WITH CARDIAC HEART FAILURE) (bridge) project. As until December 2021, 1200 patients with HF have been enrolled in the project, both with reduced (HFrEF) and preserved ejection fraction (HFpEF). Adherence to ESC HF guidelines in HFrEF patients before vs after December 2020 was compared. Results In the HFrEF population (56%) the mean age was 63 years, 38% were hypertensive, 15% diabetic, 40% had ischemic heart disease, 42% were previously treated with coronary angioplasty, 56% had an ICD/CRT, 22% had atrial fibrillation. Mean NYHA class was 2.2, mean LVEF 30%, mean NT–proBNP values 4027 pg/mL, mean serum creatinine 1 mg/dL, 91% were taking beta–blockers (BB), 86% mineral corticoid receptor antagonists (MRA), 98% ACE–inhibitors/angiotensin–receptor–antagonists/neprilysin and angiotensin receptor antagonists (ACE/ARB/ARNI), and 13% ARNI. Compared to patients enrolled before 2020, ARNI prescription increased in 2021 (60% vs 13%, p &amp;lt; 0.001); in 30% ARNI were prescribed in hospital before discharge. Furthermore, in 10% of the population (most diabetics), sodium glucose cotransporter type 2 inhibitors (SGLT2i) have been prescribed as indicated by the latest ESC 2021 guidelines. Conclusions The implementation the PONTE project shows an improved adherence to ESC HF guidelines.

Discovery of novel non-steroidal selective glucocorticoid receptor modulators by structure- and IGN-based virtual screening, structural optimization, and biological evaluation

Glucocorticoids (GCs) are the most commonly used anti-inflammatory drugs. However, their excellent therapeutic effects are often accompanied by undesirable side effects. To discover selective glucocorticoid receptor modulators (SGRMs) that preferentially induce transrepression with little or no transactivation activity, a structure-based virtual screening by combining molecular docking and InteractionGraphNet (IGN) rescoring was performed, and compound HP210 was identified. HP210 did not induce the transactivation functions of GR while still acted on the NF-κB mediated tethered transrepression function (IC50 = 2.32 μM), and suppressed the secretion of pro-inflammation cytokines IL-1β and IL-6. Compared with dexamethasone, HP210 showed no cross activities with phylogenetically related mineralcorticoid receptor and progesterone receptor and no significant effect on osteoprotegerin, exhibiting a reduced side-effect profile. Then, guided by the molecular dynamics simulations and binding free energy calculations, compound HP210_b4 with over two-fold higher transrepression activity (IC50 = 0.99 μM) was discovered. This study reported a group of non-steroidal new-scaffold SGRMs, providing valuable clues for the development of novel anti-inflammatory drugs.

Advances in the Treatment Strategies in Hypertension: Present and Future.

Hypertension is the most frequent chronic and non-communicable disease all over the world, with about 1.5 billion affected individuals worldwide. Its impact is currently growing, particularly in low-income countries. Even in high-income countries, hypertension remains largely underdiagnosed and undertreated, with consequent low rates of blood pressure (BP) control. Notwithstanding the large number of clinical observational studies and randomized trials over the past four decades, it is sad to note that in the last few years there has been an impressive paucity of innovative studies. Research focused on BP mechanisms and novel antihypertensive drugs is slowing dramatically. The present review discusses some advances in the management of hypertensive patients, and could play a clinical role in the years to come. First, digital/health technology is expected to be increasingly used, although some crucial points remain (development of non-intrusive and clinically validated devices for ambulatory BP measurement, robust storing systems enabling rapid analysis of accrued data, physician-patient interactions, etc.). Second, several areas should be better outlined with regard to BP diagnosis and treatment targets. Third, from a therapeutic standpoint, existing antihypertensive drugs, which are generally effective and well tolerated, should be better used by exploiting available and novel free and fixed combinations. In particular, spironolactone and other mineral-corticoid receptor antagonists should be used more frequently to improve BP control. In particular, some drugs initially developed for conditions different from hypertension including heart failure and diabetes have demonstrated to lower BP significantly and should therefore be considered. Finally, renal artery denervation is another procedure that has proven effective in the management of hypertension.

Four aces of heart failure therapy: systematic review of established and emerging therapies for heart failure with reduced ejection fraction

Abstract Heart failure with reduced ejection fraction (HFrEF) is a common disease requiring multi-drug therapy. Moreover, it is associated with a poor prognosis, with increasing prevalence in the community. In the last decade, two major drug classes were introduced to the heart failure (HF) specialist's arsenal: angiotensin receptor neprilysin inhibitors (ARNIs) and sodium-glucose-cotransporter 2 inhibitors (SGLT2is). The current paradigm of sequential drug therapy is changing, favoring a multi-drug combination therapy upfront, including four “pillar” classes: beta-blockers, mineralcorticoid receptor antagonists (MRAs), ARNIs, and SGLT-2is. Recent putative placebo analyses of large-scale randomized clinical trials compared a combination of all four drug classes with a standard of care and was in favor of the multi-drug combination revealing a hazard ratio for cardiovascular (CV) death and HF hospitalization of 0.5 and 0.32, respectively. We reviewed the approval landmark trials for the four drug classes and have subincluded a short comment about the implications and impact of each study in clinical practice. Moreover, we present more detailed trials concerning the use of these drugs in different settings (eg, acute phase, in-hospital, and outpatient) and more data about the clinical, biochemical, functional, and echographic remodeling effects of the molecules. The results of the meta-analyses and putative placebo analyses in the literature we reviewed suggest the benefit of offering all the best therapy available upfront. This approach ensures maximal life expectancy gain, especially in younger patients, and cuts the costs of rehospitalizations. Thus, this review underlines the importance of the four-drug approach to HFrEF therapy, as recently stated in the ESC guidelines.

Hyperkalemia as a cause of undertreatment with mineralcorticoid receptor antagonists for patients with newly onset of heart failure with reduced ejection fraction

Abstract Background Despite beneficial effects on mortality and morbidity the use of mineralocorticoid receptor antagonists (MRA) in patients with reduced ejection fraction (&amp;lt;40%) (HFrEF) remains poor. Hyperkalemia is assumed as an important cause, but the reported incidence is low and varies hugely. Thus, available data of magnitude of hyperkalemia in real life settings are insufficient to explain why under-utilization of MRA occurred. Aim To determine the incidence and magnitude of documented hyperkalemia and potential risk of hyperkalemia in patients with HFrEF in a real-world HF population. Methods Patients aged 18–85 years at the time of the baseline, hospitalized for newly onset of HFrEF between 2016–01–01 and 2019–12–31, were identified retrospectively and consecutively from hospital discharge records, by use of international classification of disease (ICD)-10 codes I50.0-I50.9 as principal diagnosis. Potential higher risk of hyperkalemia was based on an overall assessment of current potassium level, presence of diabetes mellitus and eGFR &amp;lt;30 ml/min at patient level. Results In total, 3456 patients with HF were identified, 642 (18.6%) were eligible, hospitalized for newly onset of HFrEF (66.8±12.7 years, 68.4% men and EF 29.4% ±6.8%). After six months 336 (52.3%) did not have MRA of which 279 (83%) never received MRAs and 57 (17%) had MRAs discontinued. Among patients on MRA treatment, 306 (14.4%) needed dose reduction. Occurrence of hypertension, ischemic heart disease, diabetes mellitus and renal dysfunction at baseline did not differ between groups with or without MRA. The incidence and magnitude of documented and potentially higher risk of hyperkalemia were assessed both at baseline and as highest potassium within six months after established diagnosis. Among patients without MRA after six months, at baseline only 3 (0.9%) patients had documented S/P-K ≥6 mmol/L, 7 (2.1%) patients had S/P-K 5.5–5.9 mmol/L and 26 (7.7%) patients had S/P-K 4.8–5.4 mmol/L. Moreover, 12.4% had potentially high risk of hyperkalemia at baseline. During the six-month follow up after initiation of HF therapy, 15 (4.5%) patients had documented hyperkalemia with S/P-K ≥6 mmol/L, 23 (6.8%) patients had S/P-K 5.4–5.9 mmol/L, and 123 (36.6%) patients had S/P-K 4.8–5.4 mmol/L during at least one occasion. Besides, 13.4% had potentially high risk of hyperkalemia. Hyperkalemia occurred frequently (40.4% vs 36.4%) in patients with discontinuation and dose reduction of MRA. Figure 1 presents the distribution of patients with risk of or documented hyperkalemia in the group without MRA. Conclusions Hyperkalemia was the most common cause for both discontinuation and dose reduction of MRA. Hyperkalemia was also increased significantly from baseline and during subsequent up-titration, with 4.6-fold increased risk for borderline hyperkalemia (S/P-K 4.8–5.4). This might explain why physicians refrain from prescribing MRAs to patients with HFrEF. Funding Acknowledgement Type of funding sources: Other. Main funding source(s): Vifor Pharma

PD07-04 ROLE OF UNILATERAL ADRENALECTOMY IN BILATERAL PRIMARY ALDOSTERONISM

You have accessJournal of UrologyAdrenal (PD07)1 Sep 2021PD07-04 ROLE OF UNILATERAL ADRENALECTOMY IN BILATERAL PRIMARY ALDOSTERONISM Yu-Cheng Lu, Kuo-How Huang, Vin-Cent Wu, Kwan-Dun Wu, and Fang-Yu Cha Yu-Cheng LuYu-Cheng Lu More articles by this author , Kuo-How HuangKuo-How Huang More articles by this author , Vin-Cent WuVin-Cent Wu More articles by this author , Kwan-Dun WuKwan-Dun Wu More articles by this author , and Fang-Yu ChaFang-Yu Cha More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000001975.04AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: Mineralcorticoid receptor antagonist was the first-line treatment in bilateral adrenal hyperplasia (BAH) with primary aldosteronism (PA). Some patients were refractory to medical treatment and required second line therapy, such as unilateral adrenalectomy (UA). In this study, we investigated blood pressure and biochemical responses and identified predictive factors in patients with PA after UA. METHODS: From January, 2010 to November, 2018, 102 patients with complete adrenal vein sampling (AVS) as well NP-59 test and confirmatory diagnoses of PA were enrolled. All these patients received UA and followed up for 12 months subsequently. We collected and analyzed all possible correlated parameters that might interfere the clinical and biochemical outcomes. RESULTS: A total of 102 patients were stratified into two groups by AVS and NP-59 results: 20 (19.6%) patients had BAH in Group A and 82 (80.4%) patients had unilateral lesion in Group B. Patients in Group B had better blood pressure control after UA (p<0.001). Both groups had significant improvement in serum aldosterone-renin ratio (ARR), potassium level and reduction of anti-hypertensive drugs. (Group A: p=0.013, p=0.003 and p=0.020 respectively; Group B: p<0.001, p<0.001 and p<0.001 respectively). Patients in Group A had worse clinical outcome with 40% failure rate (p=0.020) but there was no difference in biochemical outcome (p=0.065). Multivariate logistic regression analysis indicated that preoperative ARR (OR: 0.999, p=0.031) could predict biochemical success at 12-month after UA but there were no predictors found for clinical success. CONCLUSIONS: Patients with bilateral PA generally had worse clinical outcome after UA. However, significantly reduced ARR, serum potassium and usage of anti-hypertensive drugs were noted after UA. This study indicated that UA could be beneficial in some patients with bilateral PA and should not be excluded as a treatment option. Source of Funding: No © 2021 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 206Issue Supplement 3September 2021Page: e106-e106 Advertisement Copyright & Permissions© 2021 by American Urological Association Education and Research, Inc.MetricsAuthor Information Yu-Cheng Lu More articles by this author Kuo-How Huang More articles by this author Vin-Cent Wu More articles by this author Kwan-Dun Wu More articles by this author Fang-Yu Cha More articles by this author Expand All Advertisement Loading ...

Myocardial infarction at a young age: risk factors, clinical presentation, features of management in the hospital

Aim: to study the risk factors, clinical peculiarities, diagnosis and treatment of young patients with myocardial infarction (≤ 44 years).Material and methods. The research included 189 patients, who had MI in the period from January 1, 2015 to December 31, 2019 at the age of ≤ 44; 92.1% of patients were men. The average age of all patients was 41,2 (37.3; 43.6).Results. Most frequent risk factors for the development of MI were: smoking — in 77.8%, essential hypertension — in 73.5%, burdened inheritance — in 49.2%, obesity — in 39.7% and pancreatic diabetes — in 10.6% of all cases. ST segment elevation was registered on the electrocardiogram in 87,8% of patients; 4.2% of them had only thrombolytic therapy; thrombolytic therapy was followed by coronarography with the intention of performing percutaneous coronary intervention (PCI) in 30.7% of cases; coronarography with the intention of performing primary PCI was applied to 54.2% of patients. PCI was performed in 76.5% of patients. 12.2% of patients had acute coronary syndrome without ST-segment elevation, and 95.7% of them had coronarography with the intention of performing percutaneous coronary intervention. PCI was performed in 73.9% of patients. Assignment frequency of beta-adrenergic blocking agent prescription was 95,2% (178 out of 187), аngiotensin-convertingenzyme inhibitors and sartans — 95.2% (178 out of 187), statins — 99.5% (188 of 189), dual antiplatelet therapy — 99.5% (188 out of 189), mineral corticoid receptor antagonists with ejection fraction of left ventricle of heart ≤ 40% — 28.6% (2 of 7).Conclusion. The conducted research aims at the discussion of the vital topic of young patients with myocardial infarction management. It focuses on risk factors, clinical and angiographic presentation, and secondary prevention.

THERAPEUTIC EFFECTS OF MINERAL CORTICOID RECEPTOR BLOCKER IN THE COMBINATION ANTIHYPERTENSIVE DRUG THERAPY IN HYPERTENSIVE PATIENTS

Objective: Among the components of renin-angiotensin-aldosterone system, aldosterone is supposed to facilitate the progression of cardiovascular organ injuries not only by promoting renal tubular Na reabsorption but also by causing oxidative stress, inflammation and cardiovascular tissue hypertrophy and fibrosis. Therefore, mineral corticoid receptor blockers (MRB) are expected to exhibit protective effects against cardiovascular organ injuries in hypertensive patients. In the present study, the therapeutic effects of MRB in the combination antihypertensive treatment were examined in hypertensive patients. Design and method: Fifty mg eplerenone (EPL) was added to 24 hypertensive patients under antihypertensive drug therapy who were not achieved the target blood pressure levels. The combination was continued for 3 to 4 months and the effects on blood pressure (BP) and laboratory data including renal function and cardiovascular endocrine system were evaluated. Results: After 3–4 months, office BP was lowered from 148/91 to 135/86 mmHg (p &lt; 0.001/p = 0.002) as well as the home BP (morning 150/86 to 134/81, p = 0.001/p = 0.033; evening 139/80 to 127/74, p = 0.005/p = 0.030). Serum K (4.2 to 4.3mEq/L, p = 0.014) and creatinine (0.82 to 0.87 mg/dL, P &lt; 0.001) were slightly but significantly increased. Serum uric acid was significantly also increased from 5.8 to 6.4 mg/dL (p = 0.015). However, the indices of glucose metabolism and serum lipids were not affected. In addition to the natural increases in plasma renin and aldosterone, plasma B-type natriuretic peptide (BNP: 23 to 17 pg/mL, p = 0.028) and urinary albumin excretion (111 to 70 mg/gCr, p = 0.009) were significantly decreased. Conclusions: In the combination antihypertensive drug therapy, MRB is expected to cardiac and renal injuries and the influences on glucose and lipid metabolisms seem negligible, however, care should be taken for the development of hyperuricemia and renal dysfunction in addition to hyperkalemia.

A CASE OF ACROMEGALY COMPLICATED BY PRIMARY ALDOSTERONISM DIAGNOSED DURING THE COURSE OF HEART FAILURE

Objective: [Case] A 32-year-old male was admitted to the Department of Cardiology of our hospital complaining of weight gain, exertional chest pain, dyspnea, and palpitation. He was pointed out hypertension at the age of 18 and started taking oral antihypertensive drugs at the age of 27. Although his high blood pressure was well-controlled with calcium channel blocker, angiotensin receptor blocker, and alpha-and beta-blocker, he had stopped taking medicines since the age of 30. He was diagnosed as congestive heart failure due to hypertensive heart disease and was transferred to our department for the further examination of suspected secondary hypertension after his heart failure was improved. Design and method: Aldosterone / renin activity ratio (ARR) was &gt;= 200, and primary aldosteronism (PA) was suspected. In consideration of his impaired cardiac function, a captopril challenge test and a rapid ACTH stimulation test were conducted. Since both were positive, the diagnosis of PA was made. Although computed tomography (CT) scans revealed a left adrenal adenoma, adrenal venous sampling showed overproductions of aldosterone from both adrenal glands, and thus he was treated with eplerenone, a mineral corticoid receptor blocker. Results: He was also suspected to have acromegaly because he had protruded chin, thickened lips, enlarged nose, and enlarged hands and feet. Brain magnetic resonance (MR) imaging detected a macroadenoma in the pituitary gland. Endocrinological examinations showed high concentrations of serum GH of 7.78 ng/ml and insulin-like growth factor 1 (IGF-1) of 824 ng/ml (+8.8SD), and 75 g oral glucose tolerance test (OGTT) showed a nadir of GH as 5.22 ng/ml, indicating a failure of suppression of GH. Acromegaly was diagnosed and transsphenoidal sinus pituitary surgery was done after monthly intramuscular injections of octreotide 20 mg four times. Conclusions: [Discussion] We experienced a case of acromegaly complicated by PA diagnosed during the course of heart failure. Both acromegaly and PA may be involved in the development of heart failure, however, the combination of acromegaly and PA is rare. We will discuss Its pathophysiology with a literature review.

Prognostic role of myocardial work in patients with heart failure and reduced ejection fraction treated by sacubitril/valsartan

Abstract Funding Acknowledgements Type of funding sources: None. Background the non-invasive assessment of myocardial work (MW) by pressure-strain loops analysis (PSL) is a relative new tool for the evaluation of myocardial performance. Sacubitril/Valsartan is a treatment for heart failure with reduced ejection fraction (HFrEF) which has a spectacular effect on the reduction of cardiovascular events (MACEs). Purposes of this study were to evaluate 1) the short and medium term effect of Sacubitril/Valsartan treatment on MW parameters; 2) the prognostic value of MW in this specific group of patients. Methods 79 patients with HFrEF (mean age: 66 ± 12 years; LV ejection fraction: 28 ± 9%) were prospectively included in the study and treated with Sacubitril/Valsartan. Echocardiographic examination was performed at baseline, and after 6- and 12-month of therapy with Sacubitril/Valsartan. Results Sacubitril/Valsartan significantly increased myocardial constructive work (CW) (1023 ± 449 vs 1424 ± 484 mmHg%, p &amp;lt; 0.0001) and myocardial work efficiency (WE) [87 (78-90) vs 90 (86-95), p &amp;lt; 0.0001]. During FU (2.6 ± 0.9 years), MACEs occurred in 13 (16%) patients. After correction for LV size, LVEF and WE, global myocardial constructive work (CW) was the only predictor of MACEs [HR 0.99 (0.99-1.00), p = 0.05]. (Table 1). A CW &amp;lt; 910 mmHg (AUC = 0.81, p &amp;lt; 0.0001, Figure 1, left panel) identified patients at particularly increase risk of MACEs [HR 11.09 (1.45-98.94), p = 0.002, log-rank test p &amp;lt; 0.0001] (Figure 2, Right panel). Conclusions in patients with HFrEF who receive a comprehensive background beta-blocker and mineral-corticoid receptor antagonist therapy, Sacubitril/Valsartan induces a significant improvement of myocardial CW and WE. In this population, the estimation of CW before the initiation of Sacubitril/Valsartan therapy allows the prediction of MACEs. Univariable analysis Multivariable analysis HR (95% CI) p-value HR (95% CI) p-value Age, per year 0.99 (0.95-1.04) 0.81 Ischemic cardiomyopathy 1.07 (0.36-3.21) 0.89 LVEDVi*, per ml/m2 1.01 (1.00-1.03) 0.03 LVESVi, per ml/m2 1.01 (1.00-1.03) 0.009 1.01 (0.99-1.02) 0.35 LVEF, per % 0.91 (0.85-0.98) 0.01 1.02 (0.93-1.12) 0.71 CW, per mmHg% 0.99 (0.99-1.00) 0.002 0.99 (0.99-1.00) 0.04 WE, per mmHg% 0.91 (0.86-0.96) 0.001 0.95 (0.88-1.02) 0.16 Predictors of MACEs at univariable and multivariable analysis Abstract Figure 1 A and B

Prognostic role of myocardial work in patients with heart failure and reduced ejection fraction treated by sacubitril/valsartan

The non-invasive assessment of myocardial work (MW) by pressure-strain loops analysis (PSL) is a relative new tool for the evaluation of myocardial performance. Sacubitril/Valsartan is a treatment for heart failure with reduced ejection fraction (HFrEF) which has a spectacular effect on the reduction of cardiovascular events (MACEs). Purposes of this study were to evaluate 1) the short and medium term effect of Sacubitril/Valsartan treatment on MW parameters; 2) the prognostic value of MW in this specific group of patients. 79 patients with HFrEF (mean age: 66 ± 12 years; LV ejection fraction: 28 ± 9%) were prospectively included in the study and treated with Sacubitril/Valsartan. Echocardiographic examination was performed at baseline, and after 6- and 12-month of therapy with Sacubitril/Valsartan. Sacubitril/Valsartan significantly increased myocardial constructive work (CW) (1023 ± 449 vs. 1424 ± 484 mmHg%, P < 0.0001) and myocardial work efficiency (WE) [87 (78–90) vs. 90 (86–95), P < 0.0001]. During FU (2.6 ± 0.9 years), MACEs occurred in 13 (16%) patients. After correction for LV size, LVEF and WE, global myocardial constructive work (CW) was the only predictor of MACEs [HR 0.99 (0.99–1.00), Fig. 1 = 0.05]. ( Table 1 ). A CW < 910 mmHg (AUC = 0.81, P < 0.0001, Fig. 1 A) identified patients at particularly increase risk of MACEs [HR 11.09 (1.45–98.94), P = 0.002, log-rank test P < 0.0001] ( Fig. 1 B). in patients with HFrEF who receive a comprehensive background beta-blocker and mineral-corticoid receptor antagonist therapy, Sacubitril/Valsartan induces a significant improvement of myocardial CW and WE. In this population, the estimation of CW before the initiation of Sacubitril/Valsartan therapy allows the prediction of MACEs.

Sinergy between drugs and devices in the fight against sudden cardiac death and heart failure

The impact of sudden cardiac death (SCD) in heart failure (HF) patients is important and prevention of SCD is a reasonable and clinically justified endpoint if associated with a reduction in all-cause mortality. According to literature, in HF with reduced ejection fraction, only three classes of agents were found effective in reducing SCD and all-cause mortality: beta-blockers, mineralcorticoid receptor antagonists and, more recently, angiotensin-receptor neprilysin-inhibitors. In the PARADIGM trial that tested sacubitril/valsartan vs. enalapril, the 20% relative risk reduction in cardiovascular deaths obtained with sacubitril/valsartan was attributable to reductions in the incidence of both SCD and death due to HF worsening and this effect can be added to the known positive effect of implantable cardioverter-defibrillators in appropriately selected patients. In order to maximize the implementation of all the available treatments, patients with HF should be included in virtuous networks with a dialogue between all the physician involved, with commitment by all these physicians for appropriate decision-making on application of pharmacological and device treatments according to available evidence, as well as commitment for drug titration before and after device implant, taking advantage from remote monitoring, and with the safety of back up device therapy when indicated. There are potential synergistic effects of drug therapy, with all the therapies acting on neuro-hormonal and sympathetic activation, but specifically with sacubitril/valsartan, and device therapy, in particular cardiac resynchronization therapy, with added incremental benefits on positive cardiac remodelling, prevention of HF progression, and prevention of ventricular tachyarrhythmias.