Mineralocorticoid Receptor Antagonists Research Articles

Rates of Sudden Death After Myocardial Infarction-Insights From the VALIANT and PARADISE-MI Trials.

Sudden death is a leading cause of death after acute myocardial infarction (AMI). The Prospective ARNi vs ACE Inhibitor Trial to Determine Superiority in Reducing Heart Failure Events After MI (PARADISE-MI) and Valsartan in Acute Myocardial Infarction (VALIANT) trials enrolled patients with pulmonary congestion and/or left ventricular dysfunction after AMI. Whether the prognosis in such patients has changed over time has not been examined. To compare the rate of sudden death/resuscitated cardiac arrest (RCA) after AMI in the PARADISE-MI and VALIANT trials. This was a secondary analysis of multicenter randomized clinical trials enrolling patients after AMI. In the primary analysis, the VALIANT cohort was restricted to patients with "PARADISE-MI-like" characteristics (eg, at least 1 augmenting risk factor and no history of heart failure). The baseline characteristics of people in both trials were compared. The VALIANT trial enrolled from December 1998 to June 2001, and the PARADISE-MI trial enrolled between December 2016, and March 2020. The median follow-up in the VALIANT and PARADISE-MI trials was 24.7 and 22 months, respectively. People with AMI, complicated by pulmonary congestion and/or left ventricular dysfunction, were included in the analysis. Sudden death after AMI. A total of 5661 patients were included in the PARADISE-MI cohort (mean [SD] age, 63.7 [11.5] years; 4298 male [75.9%]), 9617 were included in the VALIANT (PARADISE-MI-like) cohort (mean [SD] age, 66.1 [11.5] years; 6504 male [67.6%]), and 14 703 patients were included in the VALIANT (total) cohort (mean [SD] age, 64.8 [11.8] years; 10 133 male [68.9%]). In the PARADISE-MI-like cohort of the VALIANT trial, 707 of 9617 participants (7.4%) experienced sudden death/RCA. A total of 148 of 5661 people (2.6%) in the PARADISE-MI trial experienced sudden death/RCA. Sudden death rates were highest in the first month after infarction in both trials: 19.3 (95% CI, 16.4-22.6) per 100 person-years in the VALIANT trial and 9.5 (95% CI, 7.0-12.7) per 100 person-years in the PARADISE-MI trial, and these rates declined steadily thereafter. Compared with the VALIANT cohort, people in the PARADISE-MI trial were more often treated with percutaneous coronary intervention for their qualifying AMI and received a β-blocker, statin, and mineralocorticoid receptor antagonist more frequently. After AMI, the risk of sudden death/RCA was highest in the first month, declining rapidly thereafter. Results revealed that compared with counterparts from 20 years ago, the rate of sudden death/RCA in patients with a reduced left ventricular ejection fraction and/or pulmonary congestion was 2- to 3-fold lower in people receiving contemporary management. Interventions to further protect people in the highest risk first month after infarction are needed. ClinicalTrials.gov Identifier: NCT02924727.

Women have a higher risk of hospital admission associated with hyponatremia than men while using diuretics

BackgroundHyponatremia is a common electrolyte disturbance and known adverse drug reaction of diuretics. Women tend to be more susceptible for diuretic associated hyponatremia. The aim of this study was to find more evidence whether women have a higher risk of diuretic associated hyponatremia than men measured at hospital admission for specific diuretic groups and whether there is a sex difference in risk of severity of hyponatremia.MethodsAll patients using a diuretic and admitted for any reason to Tergooi MC and Haga Teaching hospital in the Netherlands between the 1st of January 2017 and the 31st of December 2021, with recorded sodium levels at admission were included in this study. Cases were defined as patients with a sodium level <135 mmol/L, while control patients had a sodium level ≥135 mmol/L at admission. Logistic regression analysis was used to calculate odds ratios (OR) with 95% CIs for women versus men and adjusted for potential confounding covariables (age, body mass index, potassium serum level, systolic and diastolic blood pressure, estimated glomerular filtration rate, number of diuretics, comedications and comorbidities). Stratified analyses were conducted for specific diuretic groups (thiazides, loop diuretics and aldosterone antagonists), and adjusted for dose. Furthermore, stratified analyses were performed by severity of hyponatremia (severe: <125 mmol/L), mild: 125–134 mmol/L).ResultsA total of 2,506 patients (50.0% women) were included, of which 516 had hyponatremia at admission (20.6%, 56.2% women). Women had a statistically significantly higher risk for hyponatremia at admission than men (OR 1.37; 95% CI 1.12–1.66) and after adjustment for potential risk factors (ORadj 1.55; 95% CI 1.22–1.98). Stratified analyses showed increased odds ratios for thiazides (ORadj 1.35; 95% CI 1.00–1.83) and loop diuretics (ORadj 1.62; 95% CI 1.19–2.19) among women. Use of aldosterone antagonists was also increased but not statistically significant (ORadj 1.15; 95% CI 0.73–1.81). Women had a statistically higher risk to develop mild and severe hyponatremia than men (ORadj 1.36; 95% CI 1.10–1.68 and ORadj 1.96; 95%CI 1.04–3.68, respectively).ConclusionWomen have a higher risk of a hospital admission associated with hyponatremia while using diuretics than men. Further research is necessary to provide sex-specific recommendations.

Mineralocorticoid receptor (MR) antagonist eplerenone and MR modulator balcinrenone prevent renal extracellular matrix remodeling and inflammation via the MR/proteoglycan/TLR4 pathway.

Excessive activation of the mineralocorticoid receptor (MR) is implicated in cardiovascular and renal disease. Decreasing MR activation with MR antagonists (MRA) is effective to slow chronic kidney disease (CKD) progression and its cardiovascular comorbidities in animal models and patients. The present study evaluates the effects of the MR modulator balcinrenone and the MRA eplerenone on kidney damage in a metabolic CKD mouse model combining nephron reduction and a 60% high fat diet. Balcinrenone and eplerenone prevented the progression of renal damages, extracellular matrix remodeling and inflammation to a similar extent. We identified a novel mechanism linking MR activation to the renal proteoglycan deposition and inflammation via the TLR4 pathway activation. Balcinrenone and eplerenone similarly blunted this pathway activation.

Impact of guideline directed medical therapy on myocardial function in adults with congenital heart disease

BackgroundGuideline-directed heart failure therapy with angiotensin receptor blocker/neprilysin inhibitor (ARNi) and sodium-glucose transporter inhibitors (SGLT2i) has been incrementally beneficial in improving outcomes in heart failure patients. ObjectiveEvaluate the feasibility and efficacy of guideline-directed medical therapy (GDMT) in adults congenital heart disease (ACHD) patients. MethodsIn a retrospective cohort study, 46 ACHD patients with either New York Heart Association (NYHA) Class II symptoms or systemic ejection fraction (EF) <45%, optimized on a combination of beta-blocker (BB), ARNi, mineralocorticoid receptor antagonist (MRA) and SGLT2i were evaluated. ResultsForty-six patients with a mean age 42.6 ± 12.1 years prescribed GDMT were identified. Twenty-eight (61%) were male, 20 (43%) had a systemic right ventricle (RV) and 9 (20%) had single-ventricle physiology. Over the optimization period, 20 (43%) were sustained on ARNi and 42 (91%) on SGLT2i in addition to treatment with BB and MRA. Over a period of 45 weeks, echocardiography parameters for left ventricle (LV) ejection fraction (EF) (+7.5%, p = 0.006), systemic ventricle (SV) velocity time integral (VTI) (+1.9 cm, p = 0.012) and LV global longitudinal strain (GLS) (−2.5%, p = 0.005) improved when 3–4 medications were used versus 1–2 medications alone. The use of either ARNi or SGLT2i (+8.1%, p = 0.017) or in combination (+7.0%, p = 0.043) increased LVEF compared to the use of neither medication. ConclusionCombination GDMT is beneficial in improving myocardial characteristics in ACHD patients with systemic RV and LV.

Effect of Reduced Dose Spironolactone in Heart Failure With Reduced Ejection Fraction Patients Intolerant of Full Dose Mineralocorticoid Receptor Antagonists

Effect of Reduced Dose Spironolactone in Heart Failure With Reduced Ejection Fraction Patients Intolerant of Full Dose Mineralocorticoid Receptor Antagonists

Who Can Receive Clinical Benefit from Mid-Term Vericiguat Add-on Therapy Among Patients with Systolic Heart Failure Receiving Quadruple Medical Therapy?

Vericiguat, a soluble guanylate cyclase stimulator known for augmenting cyclic guanosine monophosphate production, has garnered substantial clinical attention in patients with systolic heart failure. Despite its proven efficacy, discerning the specific subset of individuals who can enjoy clinical advantages from vericiguat therapy in contemporary real-world clinical practice, particularly among the individuals undergoing "quadruple medical therapy" comprising administration of a beta-blocker, angiotensin receptor neprilysin inhibitor, mineralocorticoid receptor antagonist, and sodium-glucose co-transporter 2 inhibitor, remains an unresolved query. This study involved patients undergoing 3-month vericiguat therapy alongside complete quadruple medical therapy in a contemporary real-world clinical practice. Baseline characteristics associated with the primary outcome, defined as a reduction in serum NT pro-B-type natriuretic peptide (BNP) levels over the 3-month therapeutic duration, were scrutinized. A cohort of 24 patients (median age: 66 years; 20 males) were included. All participants diligently adhered to the 3-month vericiguat therapy in conjunction with the quadruple medical regimen. A higher baseline systolic blood pressure emerged as an independent factor linked to the primary outcome, yielding an adjusted odds ratio of 1.31 (95% confidence interval: 1.03-1.65, P = 0.026) at a threshold of 105 mmHg. This threshold notably stratified the trajectories of serum NT pro-BNP levels during the 3-month vericiguat therapy. In conclusion, preservation of baseline systolic blood pressure emerged as a pivotal determinant for reaping the clinical benefits from mid-term vericiguat therapy among patients with systolic heart failure receiving quadruple medical therapy.

Steroidomics-Based Screening for Primary Aldosteronism: Impact of antihypertensive Drugs.

Diagnosis of primary aldosteronism (PA) is complicated by the need to withdraw antihypertensive medications that interfere with test results, particularly renin. This study examined whether machine learning-based steroid-probability scores offer a renin measurement-independent approach for testing less prone to interference than the aldosterone-to-renin ratio (ARR). This prospective multicenter cohort study involved the use of plasma steroidomics and the ARR in 839 patients tested for PA, including 190 with and 578 without PA (71 indeterminate). Receiver operating characteristic curves for steroid-probability scores and the ARR were examined with and without interfering medications. Impacts of individual medications on plasma aldosterone, 18-oxocortisol, 18-hydroxycortisol, steroid-probability scores, renin, and ARRs were examined by multivariable and paired analyses in patients with and without PA. Receiver operating characteristic curves indicated a significant impact of interfering antihypertensive medications on the diagnostic performance of the ARR and minimal impact on steroid-probability scores. Mineralocorticoid receptor antagonists increased plasma aldosterone, 18-oxocortisol, and 18-hydroxycortisol in patients without PA and resulted in false-positive test results for steroid-probability scores and false-negative results for the ARR. Diuretics increased aldosterone, 18-oxocortisol, and steroid-probability scores in patients without PA, whereas angiotensin-converting enzyme inhibitors decreased aldosterone, steroid-probability scores, and ARRs. Beta-adrenoceptor blockers, dihydropyridine calcium channel blockers, and angiotensin receptor blockers had negligible impact on mineralocorticoids and steroid-probability scores. Among antihypertensive drugs that impact plasma aldosterone, 18-oxocortisol, and 18-hydroxycortisol, mineralocorticoid receptor antagonists stood out as a cause of false-positive results for derived steroid-probability scores. Other antihypertensives have minimal or no impact, an advantage for use of steroid-probability scores over the ARR when those medications cannot be withdrawn. URL: https://drks.de/; Unique identifier: DRKS00017084.

A new perspective on proteinuria and drug therapy for diabetic kidney disease

Diabetic kidney disease (DKD) is one of the leading causes of end-stage renal disease worldwide and significantly increases the risk of premature death due to cardiovascular diseases. Elevated urinary albumin levels are an important clinical feature of DKD. Effective control of albuminuria not only delays glomerular filtration rate decline but also markedly reduces cardiovascular disease risk and all-cause mortality. New drugs for treating DKD proteinuria, including sodium-glucose cotransporter two inhibitors, mineralocorticoid receptor antagonists, and endothelin receptor antagonists, have shown significant efficacy. Auxiliary treatment with proprietary Chinese medicine has also yielded promising results; however, it also faces a broader scope for development. The mechanisms by which these drugs treat albuminuria in patients with DKD should be described more thoroughly. The positive effects of combination therapy with two or more drugs in reducing albuminuria and protecting the kidneys warrant further investigation. Therefore, this review explores the pathophysiological mechanism of albuminuria in patients with DKD, the value of clinical diagnosis and prognosis, new progress and mechanisms of treatment, and multidrug therapy in patients who have type 2 diabetic kidney disease, providing a new perspective on the clinical diagnosis and treatment of DKD.

Pilot trial of an electronic decision support to improve care for emergency department patients with acute heart failure.

Emergency department (ED) providers play an important role in the management of patients with acute heart failure (AHF). We present findings from a pilot study of an electronic decision support that includes personalized risk estimates using the STRIDE-HF risk tool and tailored recommendations for initiating guideline directed medical therapy (GDMT) among appropriate patients. Among ED patients treated for AHF who were discharged from the ED or the ED-based observation unit in two EDs from 1 January 2023 to 31 July 2023, we assess prescriptions to the four classes of GDMT at two intervals: (1) ED arrival and (2) ED discharge. Specifically, we report active prescriptions for beta-blockers (BBs), renin-angiotensin receptor system inhibitors (RASis), sodium-glucose transport protein 2 inhibitors (SGLT2is) and mineralocorticoid receptor antagonists (MRA) among patients with reduced ejection fraction (HFrEF) and mildly reduced (HFmrEF). Second, we describe rates of 30-day serious adverse events (SAE) (death, cardiopulmonary resuscitation, balloon-pump insertion, intubation, new dialysis, myocardial infarction or coronary revascularization) among patients predicted to be very low risk by STRIDE-HF and discharged home. Among 234 discharged patients, 55% were female and 76% were non-White. We found 51 (21.8%), 21 (9.0%) and 126 (53.8%) had HFrEF, HFmEF and HFpEF, respectively, while 36 (15.4%) were missing EF, and 51 (22%) were very low risk, 82 (35%) were low risk, 60 (26%) were medium risk and 41 (18%) were high risk. Among HFrEF patients, 68.6%, 66.7%, 25.5% and 19.6% were on a RASi, BB, SGLT2i and MRA, respectively, at ED arrival, while 42.9%, 66.7%, 14.3% and 4.8% of HFmrEF patients were on a RASi, BB, SGLT2i and MRA, respectively. Among patients with HFpEF, only 6 (4.8%) were on an SGLT2i at ED arrival. The most prescribed new medication at ED discharge was an SGLT2i, with a nearly 10% increase in the proportion of patients with an active prescription for SGLT2i at ED discharge among HFrEF and HFmEF patients. We observed no 30-day SAE among the 51 patients predicted to be very low risk and discharged home. Ongoing treatment with GDMT at ED arrival was sub-optimal. Initiation among appropriate patients at discharge may be feasible and safe.

The combination of valsartan and spironolactone mitigated mitral regurgitation induced cardiac dysfunction in a novel rat model.

Despite its high prevalence, effective treatment for degenerative mitral regurgitation (MR) remains elusive. Although the mineralocorticoid-receptor antagonist spironolactone, in conjunction with renin-angiotensin system (RAS) inhibitors, has been shown to reduce mortality in patients with heart failure with reduced ejection fraction (HFrEF), its efficacy in managing degenerative MR is uncertain. In this study, we aimed to compare the effectiveness of valsartan (a renin-angiotensin system inhibitor), spironolactone, and combination therapy in mitigating MR-induced myocardial dysfunction. Using a mini-invasive model of degenerative MR, we administered valsartan (31 mg/kg/day), spironolactone (80 mg/kg/day), or a combination of both to rats over a 4-week period. Serial echocardiography and pressure-volume loops were utilized to assess cardiac function and hemodynamics. Rats with degenerative MR treated with valsartan or spironolactone alone did not show significant improvement in myocardial dysfunction. In contrast, combination therapy resulted in significant improvement. Similarly, the pressure-volume relationship was significantly improved in rats treated with the combination therapy compared to that in rats treated with a single therapy. Mechanistically, combination therapy effectively suppressed circulating and cardiac expression of aldosterone- and apoptosis-associated proteins. Overall, combination treatment with valsartan and spironolactone significantly attenuated the degenerative MR-induced myocardial stress and dysfunction, suggesting a potential therapeutic avenue for managing degenerative MR-induced HF.

Use of heart failure medical therapy before and after a cancer diagnosis: A longitudinal study.

We aim to evaluate change in the use of prognostic guideline-directed medical therapies (GDMTs) for heart failure (HF) before and after a cancer diagnosis as well as the matched non-cancer controls, including renin-angiotensin-system inhibitors (RASIs), beta-blockers, and mineralocorticoid receptor antagonists (MRAs). We conducted a longitudinal study in patients with HF in the UK Clinical Practice Research Datalink between 2005 and 2021. We selected patients with probable HF with reduced ejection fraction (HFrEF) based on diagnostic and prescription records. We described the longitudinal trends in the use and dosing of GDMTs before and after receiving an incident cancer diagnosis. HF patients with cancer were matched with a 1:1 ratio to HF patients without cancer to investigate the association between cancer diagnosis and treatment adherence, persistence, initiation, and dose titration as odds ratios (ORs) with 95% confidence intervals (CIs) using multivariable logistic regression models. Of 8504 eligible HFrEF patients with incident cancer, 4890 were matched to controls without cancer. The mean age was 75.7 (±8.4) years and 73.9% were male. In the 12months following a cancer diagnosis, patients experienced reductions in the use and dosing of GDMT. Compared with the non-cancer controls, patients with cancer had higher risks for poor adherence for all three medication classes (RASIs: OR=1.51, 95% CI=1.35-1.68; beta-blockers: OR=1.22, 95% CI=1.08-1.37; MRAs: OR=1.31, 95% CI=1.08-1.59) and poor persistence (RASIs: OR=2.04, 95% CI=1.75-2.37; beta-blockers: OR=1.35, 95% CI=1.12-1.63; MRAs: OR=1.49, 95% CI=1.16-1.93), and higher risks for dose down-titration for RASIs (OR=1.69, 95% CI=1.40-2.04) and beta-blockers (OR=1.31, 95% CI=1.05-1.62). Cancer diagnosis was not associated with treatment initiation or dose up-titration. Event rates for HF hospitalization and mortality were higher in patients with poor adherence or persistence to GDMTs. Following a cancer diagnosis, patients with HFrEF were more likely to have reduced use of GDMTs for HF.

Effectiveness and Safety of Spironolactone in the Treatment of IgA Nephropathy: A Retrospective Self-Controlled Study.

It's crucial to utilize combination therapy for IgAN patients to reduce proteinuria and maintain stable kidney function. We demonstrate the safety and efficacy of low-dose spironolactone in management of IgAN patients. Adult IgAN patients treated with spironolactone were evaluated. Patients were separated into two categories according to whether 24h-proteinuria was reduced by more than 20% after two-months of spironolactone treatment compared to baseline levels. 88 patients were analyzed and 24h-proteinuria decreased from 0.93g to 0.70 g (p＜0.001) after two-months of treatment with spironolactone, accompanied by a slight decrease in EPI-eGFR from 75.7 to 73.9 mL/min/1.73 m2 (p = 0.033). Intriguingly, 47 patients in effective MRA group showed less endocapillary hypercellularity (p = 0.040). In ineffective group, 18 patients discontinued MRA treatment because of 24h-proteinuria increased from 0.83 g to 1.04 g, while the other 23 patients were continued with spironolactone and proteinuria decreased to 0.57 g in the sixth month (p = 0.001). Furthermore, 12 patients with persistent high proteinuria during prednisone therapy, were added with spironolactone. 24-proteinuria were dropped from 0.95 g to 0.73 g at the second month, and to 0.50 g at the sixth month. In our study, we confirmed spironolactone's efficacy in reducing urine protein excretion in IgA nephropathy patients within two months of treatment. However, response varied among patients, with those showing endocapillary proliferation (E1) in renal biopsies having poor spironolactone responsiveness. Administering mineralocorticoid receptor antagonists (MRAs) to patients with eGFR over 30 ml/min did not result in hyperkalemia, indicating the treatment's safety. Key Words：IgA Nephrology, Proteinuria, Spironolactone, Renal function.

Assessing agreement between population-level administrative pharmaceutical databases and patient-reported medication dispensation in cardiac rehabilitation patients

BackgroundPharmacoepidemiology has emerged as a crucial field in evaluating the use and effects of medications in large populations to ensure their safe and effective use. This study aimed to assess the agreement of cardiac medication use between a provincial medication database, the Pharmaceutical Information Network (PIN), and reconciled medication data from confirmation through patient interviews for patients referred to cardiac rehabilitation. MethodsThe study included data from patients referred to the TotalCardiology Rehabilitation CR program, and medication data was available in both TotalCardiology Rehabilitation charts and PIN. The accuracy of medication data obtained from patient interviews was compared to that obtained from PIN with proportions and kappa statistics to evaluate the reliability of PIN data in assessing medication use. ResultsPatient-reported usage was higher for statins (41.6 %) vs. 38.4 %), ACE/ARB, beta-blockers (75.7 %) vs. 73.7 %), DOAC (3.5 %) vs. 2.6 %), and ADP-receptor antagonists (71.0 %) vs. 68.1 %) than if PIN was used. Patient-reported usage data was lower for Ezetimibe (4.7 vs. 4.8 %), Aldosterone antagonists (5.4 %) vs. 5.5 %), digoxin (0.9 %) vs. 1.0 %), calcium channel blockers (19.2 vs. 19.9 %) and warfarin (7.2 %) vs. 8.1 %). The results indicated that the differences between the two sources were very small, with an average agreement of 95.3 % and a kappa of 0.70. ConclusionThe studyʼs results, which show a high level of agreement between PIN and patient self-reporting, affirm the reliability of PIN data as a source for obtaining an accurate assessment of medication use. This finding is crucial in the context of pharmacoepidemiology research, where the accuracy of data is paramount. Further research to explore the complementary use of both data sources will be valuable.

Differences in the approach to guideline‐directed medical therapy in patients with heart failure with reduced ejection fraction: A survey of cardiologists, internists, and pharmacists

AbstractIntroductionGuideline‐directed medical therapy (GDMT) has significantly improved outcomes in patients with heart failure with reduced ejection fraction. However, GDMT prescribing remains suboptimal. The purpose of this study was to survey cardiologists, internists, and pharmacists on their approach to GDMT prescribing.MethodsA survey containing 20 clinical vignettes of patients with heart failure with reduced ejection fraction was answered by 127 cardiologists, 68 internists, and 89 pharmacists. Each vignette presented options for adjusting GDMT. Responses were dichotomized to the answer of interest. A mixed‐effect model was used to calculate the odds of changing GDMT between pharmacists and physicians.ResultsPharmacists were more likely to make changes to GDMT compared with internists (92.1 vs. 82%; odds ratio [OR] 3.02 [1.50–6.06]; p = 0.002). In medically naïve patients, pharmacists were more likely to initiate beta‐blockers than internists (45.4 vs. 32.0%; OR 2.19 [1.00–4.79], p = 0.049). Pharmacists were more likely than both internists and cardiologists to initiate mineralocorticoid receptor antagonists (34.4 vs. 11.5%; OR 4.95 [2.41–10.18]; p &lt; 0.001 and 34.4 vs. 13.9%; OR 3.95 [2.16–7.21]; p &lt; 0.001). Pharmacists were more likely than both internists and cardiologists to titrate beta‐blockers (30.9 vs. 16.4%; OR 3.15 [1.92–5.19]; p &lt; 0.001 and 30.9 vs. 22.0%; OR 1.88 [0.18–2.87]; p = 0.0030). Pharmacists were more likely than internists to titrate angiotensin receptor‐neprilysin inhibitors (61.8 vs. 34.1%; OR 3.54 [1.50–8.39]; p = 0.004).ConclusionsThe survey results show pharmacists were more likely to make any adjustments to GDMT than internists and cardiologists. Pharmacists prefer adding spironolactone and titrating beta‐blockers compared with cardiologists and internists. Compared with only internists, pharmacists were more likely to initiate beta‐blockers and titrate the dose of angiotensin receptor‐neprilysin inhibitor.

High-intensity care for GDMT titration.

Heart failure (HF) is a systemic disease associated with a high risk of morbidity, mortality, increased risk of hospitalizations, and low quality of life. Therefore, effective, systemic treatment strategies are necessary to mitigate these risks. In this manuscript, we emphasize the concept of high-intensity care to optimize guideline-directed medical therapy (GDMT) in HF patients. The document highlights the importance of achieving optimal recommended doses of GDMT medications, including beta-blockers, renin-angiotensin-aldosterone inhibitors, mineralocorticoid receptor antagonists, and sodium-glucose cotransporter inhibitors to improve patient outcomes, achieve effective, sustainable decongestion, and improve patient quality of life. The document also discusses potential obstacles to GDMT optimization, such as clinical inertia, physiological limitations, comorbidities, non-adherence, and frailty. Lastly, it also attempts to provide possible future scenarios of high-intensive care that could improve patient outcomes.

Potential Role of Mineralocorticoid Receptor Antagonists in Nondiabetic Chronic Kidney Disease and Glomerular Disease.

Glomerular disease is a leading cause of chronic kidney disease (CKD) and end-stage kidney disease. Although diabetic kidney disease is the most common cause of glomerular disease, non-diabetic causes include malignancy, systemic autoimmune conditions, drug effects, or genetic conditions. Nondiabetic glomerular diseases are rare diseases, with a paucity of high-quality clinical trials in this area. Furthermore, late referral can result in poor patient outcomes. This manuscript reviews the current management of nondiabetic glomerular disease and explores the latest developments in drug treatment in this area. Current treatment of nondiabetic glomerular disease aims to manage complications (edema, hypertension, proteinuria, hyperlipidemia, hypercoagulability, and thrombosis) as well as target the underlying cause of glomerular disease. Treatment options include renin-angiotensin-aldosterone system inhibitors, statins/non-statin alternatives, loop diuretics, anticoagulation agents, immunosuppressives, and lifestyle and dietary modifications. Effective treatment of nondiabetic glomerular disease is limited by heterogeneity and a lack of understanding of the disease pathogenesis. Sodium-glucose cotransporter-2 inhibitors and nonsteroidal mineralocorticoid receptor antagonists (ns-MRAs, such as finerenone), with their broad anti-inflammatory and antifibrotic effects, have emerged as valuable therapeutic options for a range of cardiorenal conditions, including CKD. ns-MRAs are an evolving drug class of particular interest for the future treatment of nondiabetic glomerular disease, and there is evidence that these agents may improve kidney prognosis in various subgroups of patients with CKD. The benefits offered by ns-MRAs may present an opportunity to reduce the progression of CKD from a spectrum of glomerular disease. Several novel ns-MRA are in clinical development for both diabetic and nondiabetic CKD.

Myocardial injury and clinical outcome in octogenarians after non-ST-elevation myocardial infarction.

The aim of this study was to analyze age-associated myocardial injury and clinical outcome after non-ST-elevation myocardial infarction (NSTEMI). This prospective, multicenter study consists of 440 patients with NSTEMI enrolled at 7 centers. All patients were treated with primary percutaneous coronary intervention and underwent cardiac magnetic resonance (CMR) imaging 1-10 days after study inclusion. CMR parameters of myocardial injury and clinical outcome were evaluated by creating 2 subgroups: <80 years vs. ≥80 years. The clinical endpoint was the 1-year incidence of major adverse cardiac events (MACE) consisting of death, re-infarction and new congestive heart failure. Elderly patients ≥80 years accounted for 13.9% of the study population and showed a divergent cardiovascular risk profile compared to the subgroup of patients <80 years. CMR imaging did not reveal significant differences regarding infarct size, microvascular obstruction, left ventricular ejection fraction or multidimensional strain analysis between the study groups. At 1-year follow-up, MACE rate was significantly increased in patients ≥80 years compared to patients aged <80 years (19.7% vs. 9.6%; p = 0.019). In a multiple stepwise logistic regression model, the number of diseased vessels, aldosterone antagonist use and left ventricular global longitudinal strain were identified as independent predictors for MACE in all patients, while there was no independent predictive value of age regarding 1-year clinical outcome. This prospective, multicenter analysis shows that structural and functional myocardial damage is similar in younger and older patients with NSTEMI. Furthermore, in this heterogeneous but also clinically representative cohort with reduced sample size, age was not independently associated with 1-year clinical outcome, despite an increased event rate in patients ≥80 years.

New Therapeutics for Heart Failure Worsening: Focus on Vericiguat.

Heart failure (HF) is a syndrome characterized by signs and symptoms resulting from structural or functional cardiac abnormalities, confirmed by elevated natriuretic peptides or evidence of congestion. HF patients are classified according to left ventricular ejection fraction (LVEF). Worsening HF (WHF) is associated with increased short- and long-term mortality, re-hospitalization, and healthcare costs. The standard treatment of HF includes angiotensin-converting enzyme inhibitors, angiotensin receptor-neprilysin inhibitors, mineralocorticoid-receptor antagonists, beta-blockers, and sodium-glucose-co-transporter 2 inhibitors. To manage systolic HF by reducing mortality and hospitalizations in patients experiencing WHF, treatment with vericiguat, a direct stimulator of soluble guanylate cyclase (sGC), is indicated. This drug acts by stimulating sGC enzymes, part of the nitric oxide (NO)-sGC-cyclic guanosine monophosphate (cGMP) signaling pathway, regulating the cardiovascular system by catalyzing cGMP synthesis in response to NO. cGMP acts as a second messenger, triggering various cellular effects. Deficiencies in cGMP production, often due to low NO availability, are implicated in cardiovascular diseases. Vericiguat stimulates sGC directly, bypassing the need for a functional NO-sGC-cGMP axis, thus preventing myocardial and vascular dysfunction associated with decreased sGC activity in heart failure. Approved by the FDA in 2021, vericiguat administration should be considered, in addition to the four pillars of reduced EF (HFrEF) therapy, in symptomatic patients with LVEF < 45% following a worsening event. Cardiac rehabilitation represents an ideal setting where there is more time to implement therapy with vericiguat and incorporate a greater number of medications for the management of these patients. This review covers vericiguat's metabolism, molecular mechanisms, and drug-drug interactions.

Optimizing Guideline-Directed Medical Therapy During Hospitalization Improves Prognosis in Patients With Worsening Heart Failure Requiring Readmissions.

We previously demonstrated that higher simple guideline-directed medical therapy (GDMT) scores (comprising renin-angiotensin system inhibitors, β-blockers, mineralocorticoid antagonists, and sodium-glucose cotransporter 2 inhibitors) at discharge were correlated with improved prognosis in heart failure (HF) patients. HF readmissions are linked to adverse outcomes, emphasizing the need for enhanced optimization of GDMT.Methods and Results: Using the simple GDMT score, we evaluated the effect of revising and modifying in-hospital GDMT on the prognosis of patients with HF readmissions. In this retrospective analysis of 2,100 HF patients, we concentrated on 1,222 patients with HF with reduced ejection/moderately reduced ejection fraction, excluding patients with HF with preserved ejection fraction, on dialysis, or who died in hospital. A higher current GDMT score was associated with better HF prognosis. Of the 1,222 patients in the study, we analyzed 372 cases of rehospitalization, calculating the simple GDMT scores at admission and discharge. Patients were divided into groups according to score improvement. Multivariate analysis showed a significant association between improved in-hospital simple GDMT score and the composite outcome (HF readmission+all-cause mortality; hazard ratio 0.459; 95% confidence interval 0.257-0.820; P=0.008). Even after propensity score matching to adjust for background, among rehospitalized patients, those with an improved in-hospital simple GDMT score had a better prognosis. Our results highlight the potential of robust interventions and score elevation during hospitalization leading to improved outcomes.

Safety and Tolerability of Initiating Sacubitril-Valsartan With Spironolactone During Hospitalization for Acute Decompensated Heart Failure.

Background: Initiation of sacubitril-valsartan and mineralocorticoid receptor antagonists (MRA) during hospitalization for acute decompensated heart failure (ADHF) may be an ideal time to optimize guideline-directed medical therapy. However, there is limited research assessing the safety of combining these agents in the hospital. Methods: This was a multi-center, retrospective, propensity-score matched cohort study performed at 7 acute-care hospitals within a large health care system. All adult patients admitted with ADHF between January 1, 2019 to December 31, 2021 who received sacubitril-valsartan with MRA (MRA group) or without MRA (non-MRA group) and had a left ventricular ejection fraction (LVEF) < 40% were included in the study. Results: 220 patients were screened during the study time frame with 179 meeting inclusion criteria. Following propensity-score matching, 50 patients in the MRA group were matched to 50 patients in the non-MRA group. The overall incidence of adverse drug reactions (ADRs) was 24% in the non-MRA group compared to 20% in the MRA group (P = .629). There was a significantly greater incidence of hyperkalemia in the MRA group (0% vs 10%; P = .022). None of the patients in the non-MRA group were readmitted within 30 days due to an ADR compared to 6% in the MRA group (P = .079). Conclusion: The addition of spironolactone to sacubitril-valsartan in the hospital setting following stabilization of ADHF did not lead to a significantly greater incidence of overall ADRs, but patients were more likely to develop hyperkalemia and there was a numerically higher incidence of 30-day readmissions due to ADRs.