Lessons Learned from the ISCHEMIA Trial for the Management of Patients with Stable Ischemic Heart Disease.

The recent landmark International Study of Comparative Health Effectiveness With Medical and Invasive Approaches (ISCHEMIA) trial was undertaken to assess whether stable angina patients with moderate to severe baseline ischemia would benefit from an invasive approach with revascularization versus a conservative approach of intensive lifestyle intervention and pharmacologic secondary prevention. This trial addressed the hypothesis that treating ischemia with an invasive approach would reduce major adverse cardiac events more than a noninvasive pharmacologic and lifestyle approach. ISCHEMIA is discussed in detail, along with current implications for contemporary management of this very common cardiac disorder afflicting millions of patients worldwide.

Enhanced prostatic Esr1+ luminal epithelial cells in the absence of SRD5A2.

Steroid 5α reductase 2 (SRD5A2) converts testosterone to dihydrotestosterone and is crucial for prostatic development. 5α reductase inhibitors (5ARI) reduce prostate size in benign prostate hyperplasia (BPH) and ameliorate lower urinary tract symptoms secondary to BPH. However, the mechanisms of 5ARI functioning are still not fully understood. Here, we used a Srd5a2-/- mouse model and employed single-cell RNA sequencing to explore the impact of SRD5A2 absence on prostate cellular heterogeneity. Significant alterations in luminal epithelial cell (LE) populations were observed, alongside an increased proportion and proliferative phenotype of estrogen receptor 1 (ESR1)+ LE2 cells, following an SRD5A2-independent ESR1 differentiation trajectory. LE2 cells exhibited enhanced estrogen response gene signatures, suggesting an alternative pathway for prostate growth when SRD5A2 is absent. Human prostate biopsy analysis revealed an inverse correlation between the expressions of SRD5A2 and LE2 markers (ESR1/PKCα), and an inverse correlation between SRD5A2 and the clinical efficiency of 5ARI. These findings provide insights into 5ARI resistance mechanisms and potential alternative therapies for BPH-related lower urinary tract symptoms. © 2024 The Pathological Society of Great Britain and Ireland.

Therapy duration and improvement of ventricular function in de novo heart failure: the Heart Failure Optimization study.

BACKGROUND AND AIMS: In patients with de novo heart failure with reduced ejection fraction (HFrEF), improvement of left ventricular ejection fraction (LVEF) is expected to occur when started on guideline-recommended medical therapy. However, improvement may not be completed within 90 days. METHODS: Patients with HFrEF and LVEF ≤ 35% prescribed a wearable cardioverter-defibrillator between 2017 and 2022 from 68 sites were enrolled, starting with a registry phase for 3 months and followed by a study phase up to 1 year. The primary endpoints were LVEF improvement > 35% between Days 90 and 180 following guideline-recommended medical therapy initiation and the percentage of target dose reached at Days 90 and 180. RESULTS: A total of 598 patients with de novo HFrEF [59 years (interquartile range 51-68), 27% female] entered the study phase. During the first 180 days, a significant increase in dosage of beta-blockers, renin-angiotensin system inhibitors, and mineralocorticoid receptor antagonists was observed (P < .001). At Day 90, 46% [95% confidence interval (CI) 41%-50%] of study phase patients had LVEF improvement > 35%; 46% (95% CI 40%-52%) of those with persistently low LVEF at Day 90 had LVEF improvement > 35% by Day 180, increasing the total rate of improvement > 35% to 68% (95% CI 63%-72%). In 392 patients followed for 360 days, improvement > 35% was observed in 77% (95% CI 72%-81%) of the patients. Until Day 90, sustained ventricular tachyarrhythmias were observed in 24 wearable cardioverter-defibrillator carriers (1.8%). After 90 days, no sustained ventricular tachyarrhythmia occurred in wearable cardioverter-defibrillator carriers. CONCLUSIONS: Continuous optimization of guideline-recommended medical therapy for at least 180 days in HFrEF is associated with additional LVEF improvement > 35%, allowing for better decision-making regarding preventive implantable cardioverter-defibrillator therapy.

Medical Therapy Before, During and After Hospitalization in Medicare Beneficiaries With Heart Failure and Diabetes: Get With The Guidelines - Heart Failure Registry.

BACKGROUND: Patients hospitalized with heart failure (HF) and diabetes mellitus (DM) are at risk for worsening clinical status. Little is known about the frequency of therapeutic changes during hospitalization. We characterized the use of medical therapies before, during and after hospitalization in patients with HF and DM. METHODS: We identified Medicare beneficiaries in Get With The Guidelines-Heart Failure (GWTG-HF) hospitalized between July 2014 and September 2019 with Part D prescription coverage. We evaluated trends in the use of 7 classes of antihyperglycemic therapies (metformin, sulfonylureas, GLP-1RA, SGLT2-inhibitors, DPP-4 inhibitors, thiazolidinediones, and insulins) and 4 classes of HF therapies (evidence-based ß-blockers, ACEi or ARB, MRA, and ARNI). Medication fills were assessed at 6 and 3 months before hospitalization, at hospital discharge and at 3 months post-discharge. RESULTS: Among 35,165 Medicare beneficiaries, the median age was 77 years, 54% were women, and 76% were white; 11,660 (33%) had HFrEF (LVEF ≤ 40%), 3700 (11%) had HFmrEF (LVEF 41%-49%), and 19,805 (56%) had HFpEF (LVEF ≥ 50%). Overall, insulin was the most commonly prescribed antihyperglycemic after HF hospitalization (n = 12,919, 37%), followed by metformin (n = 7460, 21%) and sulfonylureas (n = 7030, 20%). GLP-1RA (n = 700, 2.0%) and SGLT2i (n = 287, 1.0%) use was low and did not improve over time. In patients with HFrEF, evidence-based beta-blocker, RASi, MRA, and ARNI fills during the 6 months preceding HF hospitalization were 63%, 62%, 19%, and 4%, respectively. Fills initially declined prior to hospitalization, but then rose from 3 months before hospitalization to discharge (beta-blocker: 56%-82%; RASi: 51%-57%, MRA: 15%-28%, ARNI: 3%-6%, triple therapy: 8%-20%; P < 0.01 for all). Prescription rates 3 months after hospitalization were similar to those at hospital discharge. CONCLUSIONS: In-hospital optimization of medical therapy in patients with HF and DM is common in participating hospitals of a large US quality improvement registry.

Improving Guideline-Directed Medical Therapy for Patients With Heart Failure With Reduced Ejection Fraction: A Review of Implementation Strategies.

Despite recent advances in the use of guideline-directed medical therapy (GDMT) for patients with heart failure with reduced ejection fraction (HFrEF), achievement of target GDMT use and up-titration to goal dosages continue to be modest. In recent years, a number of interventional approaches to improve the usage of GDMT have been published, but many are limited by single-center experiences with small sample sizes. However, strategies including the use of multidisciplinary teams, dedicated GDMT titration algorithms and clinician audits with feedback have shown promise. There remains a critical need for large, rigorous trials to assess the utility of differing interventions to improve the use and titration of GDMT in HFrEF. Here, we review existing literature in GDMT implementation for those with HFrEF and discuss future directions and considerations in the field.

Safety Indicators in Patients Receiving High-intensity Care After Hospital Admission for Acute Heart Failure: The STRONG-HF Trial.

BACKGROUND: Safety, Tolerability and Efficacy of Rapid Optimization, Helped by NT-proBNP Testing, of Heart Failure Therapies (STRONG-HF) demonstrated the safety and efficacy of rapid up-titration of guideline-directed medical therapy (GDMT) with high-intensity care (HIC) compared with usual care in patients hospitalized for acute heart failure (HF). In the HIC group, the following safety indicators were used to guide up-titration: estimated glomerular filtration rate of <30 mL/min/1.73 m2, serum potassium of >5.0 mmol/L, systolic blood pressure (SBP) of <95 mmHg, heart rate of <55 bpm, and N-terminal pro-B-type natriuretic peptide concentration of >10% higher than predischarge values. METHODS AND RESULTS: We examined the impact of protocol-specified safety indicators on achieved dose of GDMT and clinical outcomes. Three hundred thirteen of the 542 patients in the HIC arm (57.7%) met ≥1 safety indicator at any follow-up visit 1-6 weeks after discharge. As compared with those without, patients meeting ≥1 safety indicator had more severe HF symptoms, lower SBP, and higher heart rate at baseline and achieved a lower average percentage of GDMT optimal doses (mean difference vs the HIC arm patients not reaching any safety indicator, -11.0% [95% confidence interval [CI] -13.6 to -8.4%], P < .001). The primary end point of 180-day all-cause death or HF readmission occurred in 15.0% of patients with any safety indicator vs 14.2% of those without (adjusted hazard ratio 0.84, 95% CI 0.48-1.46, P = .540). None of each of the safety indicators, considered alone, was significantly associated with the primary end point, but an SBP of <95 mm Hg was associated with a trend toward increased 180-day all-cause mortality (adjusted hazard ratio 2.68, 95% CI 0.94-7.64, P = .065) and estimated glomerular filtration rate decreased to <30 mL/min/1.73 m2 with more HF readmissions (adjusted hazard ratio 3.60, 95% CI 1.22-10.60, P = .0203). The occurrence of a safety indicator was associated with a smaller 90-day improvement in the EURO-QoL 5-Dimension visual analog scale (adjusted mean difference -3.32 points, 95% CI -5.97 to -0.66, P = .015). CONCLUSIONS: Among patients with acute HF enrolled in STRONG-HF in the HIC arm, the occurrence of any safety indicator was associated with the administration of slightly lower GDMT doses and less improvement in quality of life, but with no significant increase in the primary outcome of 180-day HF readmission or death when appropriately addressed according to the study protocol.

Sodium-Glucose Cotransporter 2 Inhibitors and Mycotic Genital or Urinary Tract Infections in Heart Failure.

Sodium-glucose cotransporter 2 inhibitors (SGLT2is) improve clinical outcomes in persons with heart failure (HF). This class of agents has been consistently associated with an increased risk of mycotic genital infections (MGIs), and in some, but not all trials, urinary tract infections (UTIs). Other medications widely used for cardiac conditions do not cause MGIs and UTIs, so cardiologists and their supporting teams will be encountering clinical questions that they previously did not have to address. This review provides clinicians with practical recommendations about SGLT2i use in individuals with HF as related to the associated MGI and possible UTI risks. Overall, given the benefit of SGLT2is in clinical outcomes, the threshold for not initiating or discontinuing SGLT2is due to concerns for MGIs or UTIs should be high for persons with HF. Likewise, when SGLT2is are discontinued for such concerns, the threshold for reinitiation should be low.

Safety and Efficacy of SGLT2 Inhibitors for Amyloid Light-Chain Cardiomyopathy.

BACKGROUND: Sodium-glucose cotransporter-2 inhibitors (SGLT2is) have demonstrated benefit in patients with heart failure, but minimal data exist concerning the use of these medications in amyloid light-chain cardiomyopathy (AL-CM). We performed a retrospective study to assess the safety and efficacy of SGLT2is in AL-CM. METHODS: We queried our institutional registry and identified 27 patients with AL-CM who received SGLT2is. The safety analysis included all 27 patients and assessed SGLT2i-associated adverse events, hospitalizations and deaths. To decrease confounding, the efficacy analysis included only a subset of patients with stable disease (on stable anti-plasma cell therapy for ≥ 2 months prior to baseline and had achieved at least a hematologic Very Good Partial Response) and compared disease-marker changes in these patients (n = 17) with those of a contemporaneous untreated control cohort from our registry (n = 21). RESULTS: The mean age of the overall population was 68.6 (standard deviation 9.4) years. Of the patients, 7 (14.6%) had diabetes, and 19 (39.6%) had chronic kidney disease. In the safety analysis, the median follow-up time was 10.9 (interquartile range 7.2) months. Two (7.4%) patients discontinued SGLT2is due to hypovolemia and genital irritation, and 6 (22.2%) additional patients temporarily held SGLT2is due to an adverse event that is commonly related to volume depletion. There were 13 hospitalizations, all considered unrelated to SGLT2i use, and no deaths occurred. In the efficacy analysis, SGLT2i-treated patients had more severe disease at baseline than controls, demonstrating significantly higher median troponin-T and loop diuretic dosage (P < 0.05). Compared with controls, SGLT2i treatment was associated with significantly greater reductions in loop diuretic dosage (P < 0.001) and NTproBNP levels (P = 0.033) across 3-, 6- and 12-month follow-up timepoints. SGLT2i treatment was also associated with a significantly greater reduction in mean arterial pressure at 12 months (P = 0.031) but not at other timepoints. No significant differences were observed in changes in weight, eGFR, troponin-T, proteinuria, or albumin levels. CONCLUSIONS: In this small-scale retrospective study, we demonstrate that SGLT2is are well tolerated by most patients with AL-CM, but volume depletion symptoms may limit continuous use. SGLT2is may aid management of congestion in AL-CM, as evidenced by reduced diuretic dosage and NTproBNP levels without adverse renal effects. Larger long-term studies are needed to build on our findings.

Assessment and management of heart failure in patients with chronic kidney disease.

Heart failure (HF) and chronic kidney disease (CKD) are two pathological conditions with a high prevalence in the general population. When they coexist in the same patient, a strict interplay between them is observed, such that patients affected require a clinical multidisciplinary and personalized management. The diagnosis of HF and CKD relies on signs and symptoms of the patient but several additional tools, such as blood-based biomarkers and imaging techniques, are needed to clarify and discriminate the main characteristics of these diseases. Improved survival due to new recommended drugs in HF has increasingly challenged physicians to manage patients with multiple diseases, especially in case of CKD. However, the safe administration of these drugs in patients with HF and CKD is often challenging. Knowing up to which values ​​of creatinine or renal clearance each drug can be administered is fundamental. With this review we sought to give an insight on this sizable and complex topic, in order to get clearer ideas and a more precise reference about the diagnostic assessment and therapeutic management of HF and CKD.

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.

Real-world use of medical therapy in moderate asymptomatic carotid stenosis.

OBJECTIVE: Despite level 1 evidence demonstrating the benefit of carotid endarterectomy for the prevention of stroke in patients with severe asymptomatic carotid stenosis (ACS), there has been a trend toward recommending optimal medical therapy (OMT) alone. This recommendation has been promulgated based on the observation that modern advances in OMT reduce the overall stroke risk in the general population, but the success of this treatment strategy is dependent on patient and provider adherence. In current practice, patients with moderate ACS are nearly all treated with OMT alone. The objective of this study was to evaluate adherence to OMT in a cohort of patients with moderate ACS undergoing treatment with OMT alone. METHODS: Consecutive carotid duplex ultrasound examinations were reviewed for the years 2019 and 2020. Those with moderate (50%-69%) ACS based on Society for Vascular Surgery guidelines were included in the study. Patients were assessed for OMT at the time of the index duplex, the first follow-up visit, and at each subsequent follow-up visit until the end of the study. OMT was defined as abstinence from smoking, aspirin or other antiplatelet use, and statin or other lipid-lowering therapy. Patients were stratified based on their ability to achieve OMT, and each component was evaluated to identify shortfalls in therapy. RESULTS: A total of 323 duplex ultrasound examinations with moderate ACS in 255 patients were identified. Of the 255 patients, 143 (56.1%) were on OMT at the time of the first duplex; that number increased to 163 (63.9%) by the first follow-up visit and 175 (68.6%) by the completion of the study. There were 112 (43.9%) patients who were not on OMT at the time of the index duplex, 43 (38.4%) of whom achieved OMT over a median follow-up time of 2.7 years. By the end of follow-up, 86 (76.8%) were taking aspirin or another antiplatelet medication, 93 (83.0%) were on statin or other lipid-lowering therapy, and 74 (66.1%) were abstinent from smoking. Pre-duplex smoking was independently associated with failure to achieve OMT (hazard ratio: 0.452, P = .017). CONCLUSIONS: Among patients with moderate ACS who were not previously on OMT, the rate of OMT achievement is poor. Although advances in lipid management through statin therapy have been praised for their role in improving the effectiveness of OMT, smoking cessation represents an important target for improving uptake and as a result effectiveness of OMT.

Efficacy of revascularization in CTO patients based on hibernating myocardium therapy.

BACKGROUND: The effectiveness of percutaneous coronary intervention (PCI) for chronic total occlusion (CTO) is still uncertain, especially for patients with ischemic left ventricular dysfunction. This study aimed to assess hibernating myocardium (HM), as determined by single-photon emission computed tomography (SPECT) and 18F-FDG positron emission tomography (PET), and to compare the benefits of PCI and optimal medical therapy (OMT). METHODS: A retrospective study collected data from 332 patients with CTO and ischemic left ventricular dysfunction. The study compared patients who underwent PCI or OMT via propensity score matching (PSM) analysis which was performed with a 1:2 matching protocol using the nearest neighbour matching algorithm. The primary endpoint of the study was the occurrence of major adverse cardiac events (MACE), defined as a composite of cardiac death, readmission for worsening heart failure (WHF), revascularization and myocardial infarction (MI). RESULTS: After PSM, there were a total of 246 individuals in the PCI and OMT groups. Following Cox regression, hibernating myocardium/total perfusion defect (HM/TPD) was identified as an independent risk factor (hazard ratio (HR): 1.03, 95% confidence interval (CI): 1.008-1.052, p = .007). The cut-off value of HM/TPD was 38%. The results of the subgroup analysis suggest that for patients with HM/TPD >38%, the OMT group had a greater risk of MACE (p = .035). A sensitivity analysis restricting patients with single-vessel CTO lesions, HM/TPD remained an independent predictor (HR 1.025, 95% CI 1.008-1.043, p = .005). CONCLUSION: HM/TPD is an independent predictor of MACE, and for patients with HM/TPD > 38%, CTO-PCI had a lower risk of MACE compared with OMT. However, further validation is still needed through large-scale studies.

Percutaneous coronary revascularization versus medical therapy in chronic coronary syndromes: An updated meta-analysis of randomized controlled trials.

INTRODUCTION: Coronary artery disease (CAD) is a main cause of morbidity and mortality. The effectiveness of coronary revascularization in chronic coronary syndromes (CCS) is still debated. Our recent study showed the superiority of coronary revascularization over optimal medical therapy (OMT) in reducing cardiovascular (CV) mortality and myocardial infarction (MI). The recent publication of the ORBITA-2 trial suggested superiority of percutaneous coronary revascularization (PCI) in reducing angina and improving quality of life. Therefore, we aimed to provide an updated meta-analysis evaluating the impact of PCI on both clinical outcomes and angina in CCS. METHODS: Relevant studies were screened in PubMed/Medline until 08/01/2024. Randomized controlled trials (RCTs) comparing PCI to OMT in CCS were selected. The primary outcome was CV death. Secondary outcomes were MI, all-cause mortality, stroke, major bleeding and angina severity. RESULTS: Nineteen RCTs involving 8616 patients were included. Median follow-up duration was 3.3 years. Revascularization significantly reduced CV death (4.2% vs. 5.5%; OR = .77; 95% CI .62-.96, p = .02). Subgroup analyses favoured revascularization in patients without chronic total occlusions (CTOs) (p = .052) and those aged <65 years (p = .02). Finally, a follow-up duration beyond 3 years showed increased benefit of coronary revascularization (p = .04). Secondary outcomes analyses showed no significant differences, except for a lower angina severity in the revascularization group according to the Seattle Angina Questionnaire (SAQ) (p = .04) and to the Canadian Cardiovascular Society (CCS) classification (p = .005). CONCLUSIONS: PCI compared to OMT significantly reduces CV mortality and angina severity, improving quality of life in CCS patients. This benefit was larger without CTOs, in patients aged <65 years and with follow-up duration beyond 3 years.

Compliance with Guideline-Directed Medical Therapy and Early Implantable Cardioverter-Defibrillator Activation in Heart Failure: A Retrospective Study.

Background: This study was conducted to evaluate compliance with guideline-directed optimal medical therapy (OMT) and its association with early implantable cardioverter-defibrillator (ICD) activation in patients with heart failure and reduced ejection fraction (HFrEF). Methods: Retrospective data from 307 patients who underwent ICD implantation for primary prevention from 2011 to 2017 were collected and analyzed. Results: Among the study participants, only 23.8% received the maximum tolerated dose of OMT prior to ICD implantation, with 59.0% receiving all three OMT medication groups. No significant difference in OMT compliance was found between patients with ischemic cardiomyopathy (ICM) and those with non-ischemic dilated cardiomyopathy (DCM). However, DCM patients received ICDs more frequently at the time of diagnosis than ICM patients (13.8% vs. 0.7%). Early ICD activation (within 3 months) occurred in only one patient who had not received appropriate OMT, representing 0.7% of all ICM patients. Furthermore, early activation was also infrequent in patients who received OMT (2.9% of ICM patients and 2.6% of DCM patients). Echocardiography follow-up data revealed that 20.4% of ICM patients and 29.8% of DCM patients who did not receive OMT before ICD implantation showed improvement in the left ventricular ejection fraction (EF) to 35% or more. Conclusions: This study found suboptimal compliance with OMT prior to ICD implantation in HFrEF patients. The results showed that early ICD activation was rare in all patient groups, especially those who did not receive the prescribed 3 months of OMT. More research is needed to investigate longer waiting periods for the evaluation of potential EF improvement, and to better evaluate the eligibility of HFrEF patients for ICD. The current findings have potential implications for clinical practice and patient outcomes.

The long-term effect of bariatric/metabolic surgery versus pharmacologic therapy in type 2 diabetes mellitus patients: A systematic review and meta-analysis.

Metabolic/bariatric surgery as a treatment for obesity and related diseases, such as type 2 diabetes mellitus (T2DM), has been increasingly recognised in recent years. However, compared with conventional pharmacologic therapy, the long-term effect (≥ 5 years) of metabolic surgery in T2DM patients is still unclear. This study aimed to evaluate the diabetes remission rate, incidence of diabetic microvascular complications, incidence of macrovascular complications, and mortality in T2DM patients who received metabolic surgery versus pharmacologic therapy more than 5 years after the surgery. Searching the database, including PubMed, Embase, Web of Science, and Cochrane Library from the inception to recent (2024), for randomised clinical trials (RCTs) or cohort studies comparing T2DM patients treated with metabolic surgery versus pharmacologic therapy reporting on the outcomes of the diabetes remission rate, diabetic microvascular complications, macrovascular complications, or mortality over 5 years or more. A total of 15 articles with a total of 85,473 patients with T2DM were eligible for review and meta-analysis in this study. There is a significant long-term increase in diabetes remission for metabolic surgery compared with conventional medical therapy in the overall pooled estimation and RCT studies or cohort studies separately (overall: OR = 4.58, 95% CI: 1.89-11.07, P < 0.001). Significant long-term decreases were found in the pooled results of microvascular complications incidence (HR = 0.57, 95% CI: 0.41-0.78, P < 0.001), macrovascular complications incidence (HR = 0.59, 95% CI: 0.50-0.70, P < 0.001) and mortality (HR = 0.53, 95% CI: 0.53-0.79, P = 0.0018). Metabolic surgery showed more significant long-term effects than pharmacologic therapy on diabetes remission, macrovascular complications, microvascular complications incidence, and all-cause mortality in patients with T2DM using currently available evidence. More high-quality evidence is needed to validate the long-term effects of metabolic surgery versus conventional treatment in diabetes management.

The 'Prostate Embolisation AS first-line therapY compAred to meDication in treatment naïVe men with prostAte eNlargement, a randomised ControllEd trial' (P-EASY ADVANCE): a randomised controlled trial of prostate embolisation vs medication for BPH.

OBJECTIVE: To compare prostate artery embolisation (PAE) to the combination of tamsulosin and dutasteride therapy as a potential first-line therapy for obstructive benign prostatic hyperplasia (BPH) in treatment-naïve patients in the 'Prostate Embolisation AS first-line therapY compAred to meDication in treatment naïVe men with prostAte eNlargement, a randomised ControllEd trial' (P-EASY ADVANCE). PATIENTS AND METHODS: A total of 39 men with enlarged prostates, moderate-severe lower urinary tract symptoms (LUTS) and obstructed/equivocal urodynamic studies (UDS), and who had no prior treatment for BPH, were randomised to receive either combined medical therapy with tamsulosin and dutasteride (medication) or PAE. Follow-up UDS, International Prostate Symptom Score (IPSS), uroflowmetry and ultrasound were performed at short- to medium-term intervals following interventions and compared to baseline. RESULTS: The medication and PAE treatment groups had similar baseline characteristics, including prostate volumes (87.8 and 85.4 mL respectively), maximum urinary flow rate (Qmax; 6.5 and 6.6 mL/s, respectively), IPSS (19.5 and 21, respectively) and obstructed UDS (79% and 74%, respectively). Both interventions improved voiding and bladder outflow obstruction from baseline, with more patients unobstructed after PAE (63%) compared to medication (28%) (P = 0.03). PAE patients had significantly greater reductions in prostate size (P < 0.001), incomplete emptying (P = 0.002), total IPSS (P = 0.032), Qmax (P = 0.006) and quality of life (P = 0.001). Altered ejaculation, erectile dysfunction and nausea were more common in the medication group. CONCLUSION: Prostate artery embolisation was more effective than combined medical therapy at reducing urinary obstruction, decreasing prostate volume and improving LUTS in patients with BPH who had not previously been treated. This is the first randomised control study to compare PAE and combined medical therapy in exclusively treatment-naïve patients and raises the potential of PAE as an alternative early treatment option for BPH. Further randomised comparative trials are planned to further validate the role of PAE in mitigating obstructive BPH.

Assessment of multimodal treatment options in recurrent and persistent acromegaly: a systematic review and meta-analysis.

PURPOSE: In patients with acromegaly, secondary treatment options in cases of hormonal non-remission or tumor progression include repeat transsphenoidal surgery (TSS), radiation-based treatment (RT), or medical therapy (MT). In this study, we aim to evaluate the clinical effectiveness of various second-line treatment options for acromegaly. METHODS: Using the PRISMA guideline, a systematic review was performed by searching MEDLINE (PubMed), Web of Science, Scopus, and Cochrane electronic bibliographic databases from conception to the end of 2022. Outcomes of interest included hormonal remission rate, complications, and mortality associated with each treatment modality for refractory acromegaly. RESULTS: A total of 79 studies including 3,208 refractory acromegaly patients (44.90% males) were analyzed, with a mean patient age of 43.89 years. There was a statistically significant difference between various therapeutic modalities in terms of remission rate, with MT offering the highest remission rate (62.55%), followed by RT (50.15%) and TSS (37.39%). Subgroup analysis of radiotherapeutic and medical modalities did not show a significant difference in remission rate between different kinds of sub-modalities in each treatment approach. Recurrence following secondary treatment was not different in patients treated with reoperation TSS compared to other modalities. CONCLUSIONS: The management of persistent and recurrent acromegaly optimally requires a multimodal approach. In different scenarios of refractory acromegaly based on previous treatment, secondary treatments may vary in terms of remission rate and complications. Medical agents provide considerable effectiveness as a second-line therapy for recurrent or persistent disease. In selected cases, however, reoperation still provides an opportunity for cure or freedom from medications. The findings of this study may help clinicians to prioritize varying options involved in this multifaceted decision-making process.

Management of ventricular tachycardias: insights on centre settings, procedural workflow, endpoints, and implementation of guidelines-results from an EHRA survey.

Ventricular tachycardia (VT), and its occurrence, is still one of the main reasons for sudden cardiac death and, therefore, for increased mortality and morbidity foremost in patients with structural heart [Kahle A-K, Jungen C, Alken F-A, Scherschel K, Willems S, Pürerfellner H et al. Management of ventricular tachycardia in patients with ischaemic cardiomyopathy: contemporary armamentarium. Europace 2022;24:538-51]. Catheter ablation has become a safe and effective treatment option in patients with recurrent VT [Cronin EM, Bogun FM, Maury P, Peichl P, Chen M, Namboodiri N et al. 2019 HRS/EHRA/APHRS/LAHRS expert consensus statement on catheter ablation of ventricular arrhythmias. Heart Rhythm 2020;17:e2-154]. Previous and current guidelines provide guidance on indication for VT ablation and risk assessment and evaluation of underlying disease. However, no uniform recommendation is provided regarding procedural strategies, timing of ablation, and centre setting. Therefore, these specifics seem to differ largely, and recent data are sparse. This physician-based European Heart Rhythm Association survey aims to deliver insights on not only infrastructural settings but also procedural specifics, applied technologies, ablation strategies, and procedural endpoints. Therefore, these findings might deliver a real-world scenario of VT management and potentially are of guidance for other centres.

Medical Therapy and Clinical Outcomes in Cardiac Sarcoidosis Patients With Systolic Heart Failure.

BACKGROUND: Cardiac sarcoidosis (CS) may result in systolic heart failure (heart failure with reduced ejection fraction [HFrEF]), but its response to guideline-directed medical therapy (GDMT) remains uncertain. METHODS AND RESULTS: We investigated 881 patients evaluated for CS to identify those with diagnosed CS, left ventricular ejection fraction (LVEF) ≤40% at diagnosis, and follow-up echocardiogram within 11-24 months. Demographics, LVEF, GDMT as quantified by Kansas City Medical Optimization (KCMO) score, and immunosuppressive treatment were recorded. The primary outcome was a composite of event-free survival (unplanned heart failure hospitalization, left ventricular assist device [LVAD]/heart transplant, or death). Seventy-nine (9%) CS patients met the inclusion criteria (35% female, median age 57 years, mean LVEF 30.9%, median New York Heart Association class II [46%], mean number of GDMT agents 1.7, and mean KCMO score 31.8). Most (87%) were treated with immunosuppressive treatment. At follow-up (median 16 months), the mean number of GDMT agents increased to 2.2 (P=0.02), and the mean KCMO score to 70.1 (P<0.001). Mean LVEF improved to 39.9% (excluding LVAD/transplant; P<0.001) and the change in LVEF was correlated with follow-up KCMO score (P<0.001). The primary outcome occurred in 13 (16%) patients and differed by KCMO score (log-rank P<0.001), but not by immunosuppressive treatment (log-rank P=0.36). CONCLUSIONS: GDMT optimization is associated with better cardiac remodeling and clinical outcomes in CS patients with HFrEF.

Guideline-Directed Medical Therapy for Elderly Patients With Acute Myocardial Infarction Who Undergo Percutaneous Coronary Intervention　- Insights From a Retrospective Observational Study.

BACKGROUND: The efficacy of guideline-directed medical therapy (GDMT) in the elderly remains unclear. This study evaluated the impact of GDMT (aspirin or a P2Y12inhibitor, angiotensin-converting enzyme inhibitor or angiotensin receptor blocker, ß-blocker, and statin) at discharge on long-term mortality in elderly patients with acute myocardial infarction (AMI) who had undergone percutaneous coronary intervention (PCI). METHODS AND RESULTS: Of 2,547 consecutive patients with AMI undergoing PCI in 2009-2020, we retrospectively analyzed 573 patients aged ≥80 years. The median follow-up period was 1,140 days. GDMT was prescribed to 192 (33.5%) patients at discharge. Compared with patients without GDMT, those with GDMT were younger and had higher rates of ST-segment elevation myocardial infarction and left anterior descending artery culprit lesion, higher peak creatine phosphokinase concentration, and lower left ventricular ejection fraction (LVEF). After adjusting for confounders, GDMT was independently associated with a lower cardiovascular death rate (hazard ratio [HR] 0.35; 95% confidence interval [CI] 0.16-0.81), but not with all-cause mortality (HR 0.77; 95% CI 0.50-1.18). In the subgroup analysis, the favorable impact of GDMT on cardiovascular death was significant in patients aged 80-89 years, with LVEF <50%, or with an estimated glomerular filtration rate ≥30 mL/min/1.73 m2. CONCLUSIONS: GDMT in patients with AMI aged ≥80 years undergoing PCI was associated with a lower cardiovascular death rate but not all-cause mortality.