Optimal Medical Therapy Research Articles

Abstract 4135741: Perioperative and Long-term Impact of Contemporary Optimal Guideline-Directed Medical Therapy in Patients with Reduced Ejection Fraction Undergoing Aortic Valve Surgery for Pure Severe Chronic Aortic Regurgitation

Background: Although recent studies have showed improved outcomes, aortic valve replacement (AVR) for chronic aortic regurgitation (AR) in the presence of reduced left ventricular ejection fraction (LVEF) is associated with a higher surgical risk. Contemporary long-term outcome remains poorly investigated. Methods: Between January 2004 and August 2019, we identified 122 patients who underwent AVR for pure chronic severe AR with LVEF less than 50%. Patients with severe reduced LVEF (<35%, n=37) were compared with those with mild to moderate reduced LVEF (35% to 50%, n=85). Results: Preoperative and intraoperative characteristics were similar in both groups. Operative mortality for the entire cohort was 1,6% (n=2) and similar across the LVEF spectrum. Postoperative intra-aortic balloon pump has been used in 2/37 patients with LVEF < 35% compared to 0/85 patients with LVEF 35-50% (p = 0.09). Patients with severely reduced LVEF had a longer length of stay (10.1±5.5 vs 7.8±3.5 days, p=0,02) while the rate of stroke, atrial fibrillation, acute renal failure, and pulmonary infection were similar between groups. Postoperatively, optimal medical therapy was achieved in most patients and more than a quarter of patients with LVEF < 35% benefited from cardiac resynchronization therapy. At the latest follow-up, mean LVEF was 42±12% in the severe reduced LVEF (vs. baseline 28±6%, p<0.001) and 51±9% in the mild to moderate reduced LVEF group (vs. baseline 45±4%, p<0.001). Freedom from cardiovascular (CV) death at ten years was 87.2% in the severe reduced LVEF group and 94.7% in patients with mild to moderate reduced LVEF (p=0.10). Freedom from heart failure (HF) hospitalization at ten years was higher in the mild to moderate reduced LVEF group (96.3%) than in the severely reduced LVEF group (88.3%) (p=0.009). Conclusion: In this contemporary cohort of patients undergoing AVR for chronic severe AR, patients with severely reduced EF treated with optimal guideline-directed medical therapy had a similar operative mortality and freedom from CV death than patients with mild to moderate reduced LVEF. Favorable left ventricular remodeling was observed in both groups at 1 year follow-up. Hospitalization for HF was low with less than 15% in both groups at 10 years follow-up; although rehospitalisation occurred more frequently in severe reduced LVEF group.

Abstract 4138477: Small Vessels, Big Challenges: Clinical and Demographic Correlates of Failure to Respond to Optimal Medical Therapy in Patients with Microvascular Angina

Background: Microvascular angina (MVA), resulting from coronary microvascular dysfunction, affects 40-50% of patients with exertional chest pain or dyspnea and a normal coronary angiogram. This condition significantly impairs quality of life and elevates the risk of major cardiac events, including myocardial infarction, stroke and death. MVA is classified as 'structural' (coronary flow reserve [CFR] <2.5&index of microcirculatory resistance [IMR] >25) or 'functional' (CFR <2.5&IMR <25). Current treatments are empirical, necessitating further investigation. Methods: This single-centre, retrospective study conducted in South Wales from 2019-24 examined MVA cases confirmed via national electronic health records. The Canadian Cardiovascular Society (CCS) angina grade was assessed at diagnosis and post optimal medical therapy (OMT) during clinic visits. Ordinal logistic regression was used to identify independent correlates of higher CCS grade, considering baseline LDL, age, diffuse epicardial disease, sex, hypertension, kidney function, smoking status and HbA1c levels as covariates. Results: Among 64 identified MVA cases (median age 69 yrs, IQR 61.3-77.8; 68.8% male), 81.3% had structural MVA, 6.3% functional MVA and 12.5% mixed disease. Coronary vessel testing was performed on 1, 2 or 3 vessels in 29.7% (n=19), 53.1% (n=34; 21 positive [+ve] in 2 vessels, 13 +ve in 1 vessel) and 17.2% (n=11; 5 +ve in 3 vessels, 5 +ve in 2 vessels, 1 +ve in 1 vessel) of cases, respectively. The LAD was most commonly affected vessel (82.8%). At diagnosis, 79.7% had CCS grade III or higher (Fig 1). Post OMT, 45.3% achieved CCS grade 0-I, 31.8% CCS grade II and 15.6% remained at CCS grade III (refractory angina). Medications included ranolazine (84.4%), beta-blockers (70.3%) and calcium channel blockers (28.1%). Ordinal logistic regression analysis (X 2 =0.27, p=0.033) identified baseline LDL (95% CI [0.16, 1.26]; p=0.011), age (95% CI [-0.12, -0.001]; p=0.045), diffuse epicardial disease (95% CI [0.016, 2.13]; p=0.047) and male sex (95% CI [0.066, 2.36]; p=0.038) as independent correlates of higher CCS grade, signifying poor response to OMT. Conclusion: MVA manifests regionally, underscoring the need for multi-territory testing. Although tailored OMT proved effective for many, 15.6% of patients continued to experience refractory symptoms (CCS grade III). This highlights the necessity for alternative therapeutic strategies to improve patient outcomes in this challenging condition.

Abstract 4137925: Long-term Outcome of Initial Thoracic Endovascular Repair or Medical Therapy in Acute Uncomplicated Type B Aortic Dissection: Real-world Data from a Nationwide Claims-Database in Japan.

Introduction: Thoracic endovascular aortic repair (TEVAR) has emerged as a promising treatment option for patients with type B aortic dissection (TBAD). However, there is a lack of evidence regarding the long-term morbidity of initial TEVAR compared to optimal medical therapy (OMT) in acute uncomplicated TBAD (uTBAD). Objective: To evaluate real-world data(RWD) on the long-term outcome of Japanese patients with acute uTBAD using a nationwide claims database. Methods: This retrospective cohort study utilizes JMDC, a nationwide claims database under Japan's universal healthcare system. We included patients who were initially hospitalized with a diagnosis of acute TBAD. We defined acute uTBAD by excluding those who died within one month, suffered aortic rupture, traumatic thoracic aortic injury, underwent open-chest surgery, experienced stroke or paralysis, or had less than six months of history in the JMDC. Patients who underwent TEVAR within three months of the index hospitalization (TEVAR group) were compared with those who received optimal medical therapy (OMT group). Propensity score (PS) matching was performed based on age, sex, and year of hospitalization. Using the Kaplan-Meier method, we calculated the cumulative rate of all-cause mortality and aorta-related events. Results: Of 18,445 patients diagnosed with aortic disease between January 2005 and December 2020, 641 were included in the study (OMT group: n=580, TEVAR group: n=61). After PS-matching, demographics of the groups (OMT_PSM: n=183 vs. TEVAR_PSM: n=61) were female (12.6% vs. 13.1%), median age (54 years [IQR, 48-60] vs. 54 years [IQR, 50-61]) and follow-up time (18 months [8-32] vs. 19 months [9-32]), respectively. Kaplan-Meier curves for the aortic-related events (Figure1, 2) are shown as long-term outcomes. Conclusions: This study successfully demonstrated that the estimated 5-year aortic-related event rate in acute uTBAD patients undergoing OMT is approximately 20%, demonstrating the relevance of the RWD source. However, the number of death events in the TEVAR and OMT groups was not sufficient to provide statistical power. Therefore, further studies are warranted to evaluate the long-term prognosis of initial TEVAR for uTBAD.

Abstract 4131737: Atherosclerotic Cardiovascular Disease Risk Management in a Primary Care Residency Clinic

The 2018 AHA/ACC Multisociety Guideline on the Management of Blood Cholesterol recommends to target an LDL-C <70mg/dL in very high risk ASCVD patients. If the patient is on maximally tolerated statin therapy and LDL-C remained >70mg/dL, addition of ezetimibe was recommended. If LDL continued to be elevated, the addition of PCSK9 inhibitor was discussed. In 2019, the European Atherosclerosis Society recommended lowering the target LDL-C goal to <55mg/dL in patients with very high ASCVD risk. This is based on prior studies demonstrating dose-dependent reduction in ASCVD with LDL-C reduction. The purpose of this study is to identify individuals at very high ASCVD risk and determine if they are on optimal medical therapy to achieve LDL <55mg/dL with the intention to improve atheroscloertic cardiovascular risk management in primary care residency clinics. A review of electronic medical records from a primary care residency clinic was performed. Patients with hyperlipidemia and prior ASCVD event were identified. Additional data including lipid panel and current medical management were collected. Patients were stratified into very high risk and not very high risk groups according to AHA classification and analyzed. A total of 1,727 patients were found to have hyperlipidemia and a prior ASCVD event. The not very high risk group had an average age of 51 years with 54% (n=40) females and 45.9% (n=34) males. The very high risk group contained 95.7% (n=1,653) patients. The average age in the very high risk group was 68 years with 53.2% (n=879) of patients being female and 46.8% (n=774) being males. Of those patients, 73.6% (n=1,216) had an LDL ≥ 55 mg/dL. In these patients, 563 were on high intensity statin, 163 on moderate intensity statin and 15 on low intensity statin. There were 475 patients not on any statin. Of those on statin therapy, 66 were on ezetimibe alone and 10 were on both ezetimibe and PCSK9 inhibitors. Over 95% of patients with a prior ASCVD event were identified as being very high risk. Our data demonstrates that 3 in 4 patients were not on optimal medical therapy based on a stricter LDL goal. There was poor escalation of medical therapy as not all patients were on high intensity statin and only 10% of patients were on ezetimibe while even fewer patients were on additional PCSK9 inhibitor therapy. This study highlights the importance of risk stratification and vigilance in optimizing medical therapy.

Abstract 4132291: Assessing the Efficacy of Preventive Percutaneous Coronary Intervention vs Optimal Medical Therapy for the Treatment of Vulnerable Plaque: A Meta-analysis

Introduction: Rupture and thrombosis of lipid-rich atherosclerotic plaques (vulnerable plaques) contributes to majority of acute coronary syndrome (ACS). Current guidelines recommend optimal medical therapy (OMT) for stabilization of vulnerable plaques. Recent evidence of preventive percutaneous intervention (PCI) as a targeted treatment shows improvement in outcomes in these patients. Hypothesis/Goals/Aims: We aim to evaluate the efficacy of preventive percutaneous coronary intervention (PCI) compared to optimal medical therapy (OMT) for treatment of non-vulnerable plaque within five years of follow up from available selected randomized controlled trials (RCTs). Methods: PubMed, Cochrane, OVID, and NIH Clinical Trials were searched for RCTs evaluating preventive PCI compared to standard of care medical therapy. All trials reported primary common endpoints as death from cardiac cause and myocardial infarction (MI). Secondary outcomes included all-cause mortality, any revascularization, hospitalization for unstable and progressive angina, and composite death (any cause, MI, or any revascularization). Sub analyses for secondary outcomes were included if measured by RCT. A fixed effect model with Mantel-Haenszel statistical method was used to calculate risk ratios, Z scores, and a 95% confidence interval. Results: Ten RCTs (n=15955 patients) were included. Preventive PCI of vulnerable plaques revealed a significant benefit in lowering incidence of MI (RR: 0.86 [0.77, 0.86], p=0.01) and death from cardiac cause (RR: 0.73 [0.62, 0.86], p=0.004). Similarly, patients undergoing preventive PCI had a lower incidence of hospitalization for unstable or progressive angina (RR: 0.75 [0.62, 0.91], p<0.0001) and composite death (RR: 0.55 [0.46, 0.67], p<0.001). No difference was noted in all-cause mortality. Incidence of revascularization had a significant benefit with OMT therapy compared to preventive PCI (RR: 1.84 [1.75, 1.94], p<0.0001). Conclusion: Preventive PCI in vulnerable plaque demonstrates cardiovascular benefit as a result from lower incidence of MI, death from cardiac cause, composite death and fewer hospitalization for unstable or progressive angina.

Abstract 4137306: Percutaneous Coronary Intervention Versus Optimal Medical Therapy for Vulnerable Atherosclerotic Coronary Plaques: A Pilot Meta-Analysis of Randomized Controlled Trials

Background: Vulnerable coronary plaques are identified as thin-capped fibroatheromas with substantial plaque and a lipid-enriched necrotic core. These plaques are often non-flow-limiting on assessment; however, they have been associated with future adverse clinical outcomes, such as unstable angina, myocardial infarction, and sudden cardiac death. Current guidelines do not recommend revascularization of such coronary plaques; however, percutaneous coronary intervention (PCI) can theoretically slow atherosclerotic progression and potentially reduce future adverse events. Methods: Major electronic databases were searched for randomized controlled trials (RCTs) that compared PCI to optimal medical therapy (OMT) for vulnerable coronary plaques. The outcomes were pooled using a random-effects model, and the results were expressed as risk ratios (RR) with corresponding 95% confidence intervals (CI). Results: 3 RCTs with 1811 patients (909: PCI and 902: OMT) were included. PCI demonstrated a statistically insignificant trend towards a decreased risk of all-cause mortality [RR: 0.40; 95% CI: 0.13, 1.27; p=0.12], cardiovascular mortality [RR: 0.17; 95% CI: 0.02, 1.38; p=0.10], myocardial infarction [RR: 0.78; 95% CI: 0.35, 1.72; p=0.53], target vessel-related myocardial infarction [RR: 0.68; 95% CI: 0.04, 11.27; p=0.79], ischemia-driven target vessel revascularization [RR: 0.22; 95% CI: 0.04, 1.22; p=0.08], and major adverse cardiovascular events [RR: 0.41; 95% CI: 0.14, 1.18; p=0.10] compared to OMT. Conclusion: This study concluded that PCI was comparable to OMT in patients with vulnerable atherosclerotic coronary plaques. Further large-scale RCTs with longer follow-up durations are required to confirm these findings.

Abstract 4144585: Association of renal function with mortality and heart failure hospitalization rates after Transcatheter Mitral Valve Edge to Edge Repair

Background: Transcatheter edge to edge repair (TEER) is an established treatment for patients with symptomatic severe functional MR on optimal medical therapy or severe symptomatic primary MR and high surgical risk. Renal dysfunction is associated with adverse outcomes but the threshold at which risks rise are uncertain. Aim To determine the association of estimated glomerular filtration rate (eGFR) with adverse outcomes in patients undergoing TEER for severe symptomatic mitral regurgitation (MR) in Ontario, Canada. Methods: This was a population-based retrospective cohort study using linked administrative datasets of patients who underwent TEER in Ontario, Canada, between 2011 and 2023. The key exposure was eGFR, which was modeled using restricted cubic splines. Outcomes were 1-year mortality, cardiovascular mortality (CV) and heart failure hospitalization (HF). Cause-specific hazards regression was used to model the association between eGFR and outcomes, utilizing eGFR 30ml/min/1.73m2 as the reference value. Results: We studied 2076 patients, of whom 294 (14.2%) had eGFR <30ml/min/1.73m2 and 841 (40.5%) had eGFR 30-60ml/min/1.73m2. The incidence at one year was 16.8% for all-cause mortality, 11% for CV mortality and 14.2% for HF hospitalizations. The Figure illustrates that the predicted incidence of adverse outcomes increases with lower eGFR, with subtle differences in patterns of change in risk at lower eGFR levels such that all-cause mortality and CV mortality begin to rise rapidly at eGFR values ≤30ml/min/1.73m2, while HF hospitalization increases linearly at eGFR ≤50ml/min/1.73m2. Conclusions: There was a progressive increase in all-cause, CV mortality and HF hospitalization after TEER for patients with lower eGFR, particularly those with values <30 ml/min/1.73m2. This data can inform patient discussions and guide post-procedural follow-up.

Abstract 4125729: Elevated Pre-Procedural Serum Natriuretic Peptide Levels Are Associated with All-Cause Mortality in Patients Undergoing Transcatheter Edge-to-Edge Mitral Valve Repair: A Systematic Review and Meta-Analysis

Background: Transcatheter edge-to-edge mitral valve repair (TEER) is an established procedure in patients with severe mitral regurgitation (MR) and elevated surgical risk on optimal medical therapy. However, there remains considerable mortality in this patient population. Some studies have shown that serum brain natriuretic peptide (BNP) and N-terminal pro b-type natriuretic peptide (NT-proBNP) predict all-cause mortality after TEER, whereas other studies have shown mortality to be independent of these markers. To address this gap in knowledge, we sought to examine the existing literature to determine whether there is an association between pre-procedural serum natriuretic peptides and mortality after TEER. Hypothesis: Among patients undergoing TEER, elevated pre-procedural BNP and NT-proBNP are associated with increased all-cause mortality. Methods: Databases including MEDLINE, Embase, and Cochrane Library were searched from inception through September 2023 for studies assessing pre-procedural serum natriuretic peptide levels and mortality among patients undergoing TEER. Pooled hazard ratios (HR) and standardized mean differences (SMD) were calculated using a random-effects model estimated by restricted maximum likelihood with the Hartung-Knapp modification. Results: A total of 30 studies comprising 10259 patients undergoing TEER met inclusion criteria. 25 studies measured NT-proBNP and 5 studies measured BNP. Elevated pre-procedural NT-proBNP (>5000 or >10000 pg/mL) was associated with increased all-cause mortality in both adjusted (HR = 2.94; 95% CI = 1.75 - 4.95; I2 = 46.8%) and unadjusted (HR = 5.16; 95% CI = 1.85 - 14.40; I2 = 0.0%) analyses (Figures 1 and 2). Pre-procedural BNP and NT-proBNP were also significantly lower among survivors at 12 months compared to non-survivors (SMD = 0.82; 95% CI = 0.37 - 1.27; I2 = 78.3%) (Figure 3). This association was demonstrated in patients with primary or secondary MR. Conclusions: Pre-procedural BNP and NT-proBNP levels are significant predictors of all-cause mortality in patients undergoing TEER for primary or secondary MR. This supports the inclusion of BNP or NT-proBNP in pre-procedural assessments to help inform patient discussions and guide post-procedural follow-up and monitoring.

Abstract 4119680: First-in-Man Treatment of Heart Failure by Repeated Intravenous Infusions of a Cardiovascular Cell-Derived Extracellular Vesicle-Enriched Secretome

Background: Most of the effects of intramyocardially transplanted stem cells can be duplicated by the sole administration of their secretome but this approach has not yet been tested in heart failure (HF). Methods: The SECRET-HF phase I trial (NCT05774509) was designed according to a Bayesian optimal interval scheme to assess the effects of repeated intravenous infusions of a cellular secretome in 12 patients with a non-ischemic dilated cardiomyopathy. The main inclusion criteria are severe symptoms (NYHA Class III despite an optimal guideline-directed medical therapy), a reduced left ventricular (LV) ejection fraction (EF ≤40%) and ineligibility for a heart transplant. The Investigational Medicinal Product was derived from human induced pluripotent stem cells reprogrammed from a healthy donor and differentiated in cardiovascular progenitor cells (CPC). Following CPC culture in a dedicated "vesiculation" medium, the conditioned media were collected, filtered, enriched for extracellular vesicles, concentrated by tangential flow filtration and scaled out into glass vials stored at -80°C. Quality controls were implemented throughout the whole process which was conducted according to current Good Manufacturing Practices. Results: Three patients, out of the 4 of the initial low-dose cohort, have now been treated. All had been previously fitted with an automatic internal cardioverter defibrillator (AICD). The secretome was delivered intravenously 3 times, 3 weeks apart, at a dose of 20 x10 9 particles/kg for each infusion. By November, 2024, the follow-up will be 16, 9, 6 and 2 months for each of them (mean: 8 months). So far, none of the treated patients has experienced a dose-limiting toxicity; in particular, there have been no post-treatments ventricular arrhythmia detected by the AICD, no allo-immunization and no inflammation based on the enumeration of lymphocyte subpopulations by flow cytometry. At 6 months, the first patient improved to NYHA Class II with a decrease in echographic LVEDV and LVESV (from 108 mL/m 2 to 87 mL/m 2 and from 80 mL/m 2 to 60 mL/m 2 , respectively) and a concomitant increase in LVEF from 25% to 32%. At 1 month post-treatment, the second patient also reports a symptomatic improvement (NYHA Class II) with an increase in EF from 21% to 28%. Conclusions: This initial experience supports the safety of repeated intravenous administrations of a cardiovascular cellular secretome as a potential noninvasive and user-friendly treatment of severe HF.

Abstract 4135127: Traveling more than a 20-mile radius to a Heart Failure Center can affect the quality of Heart Failure Care.

Introduction: We recognized the profound importance of access to care among patients with heart failure (HF). The geographical location of HF centers may significantly impact health outcomes, especially for those with limited transportation. This social determinant of health (SDOH) aspect is critical in bridging the gap in achieving HF care. Hypothesis/Methods: This was a single-center observational study conducted at a tertiary heart failure center in central Pennsylvania. We assessed the impact of travel distance by comparing patients who travel within a 20-mile radius to those who travel beyond a 20-mile radius. A total of 322 patients were referred to the HF clinic and enrolled in a guideline-directed medical therapy (GDMT) optimization program. Data collected included distance to Hershey Medical Center (HMC), health insurance coverage, HF etiology, onset, and echocardiogram. The distance was calculated based on the patient’s zip code. Results: Among patients enrolled in the HF-GDMT program, 194 travel within 20 miles, and 128 travel beyond a 20-mile radius to HMC. The mean travel distance to HMC was 9.1 miles (within) and 40.9 miles beyond 20 miles. The majority of patients were 81.3% white, 67% male, and the average age was 64. Most patients had heart failure with reduced ejection fraction (HFrEF) at 92.9%, 63% nonischemic, and 57.5% new onset. The comorbidities in both groups were similar, including hypertension, hyperlipidemia, and coronary artery disease (CAD). When comparing both groups, those who traveled beyond the 20-mile radius to HMC had more chronic HF at 55.5% vs. 34% in patients who traveled within the 20-mile radius. Upon enrollment, most patients were on suboptimal doses of either 1 or 2 of the four pillars of GDMT for HFrEF. Conclusions: The findings of this study revealed that patients with HF who travel beyond a 20-mile radius to HMC are more likely to have chronic HF, suggesting a delay in seeking care. A delay in referral may affect the timely initiation of appropriate GDMT and will likely lead to worse health outcomes. This underscores the urgent need for interventions to address barriers like transportation to improve HF care, offering a potential avenue for better patient outcomes.

Abstract 4133830: Uncovering the Gaps: Analyzing Prescribing Patterns of Combination Therapy with SGLT2-inhibitors and GLP-1 Receptor Agonists in Established Atherosclerotic Cardiovascular Disease (ASCVD) and Type 2 Diabetes (T2DM)

Introduction: Combination therapy with SGLT2 inhibitors (SGLT2i) and GLP-1 receptor agonists (GLP1RA) reduces major cardiovascular events (MACE) and improves HbA1c, blood pressure, weight, and renal disease progression. The European Society of Cardiology recommends this therapy for ASCVD and T2DM, independent of HbA1c. This study evaluates prescribing patterns in the Internal Medicine Residency Clinics for patients with ASCVD and T2DM. Aims: To investigate demographic and social determinants of health (SDOH) influencing the prescription of combination therapy versus no therapy in an outpatient population and identify factors affecting prescribing patterns and guideline adherence. Methods: We reviewed 828 electronic records of T2DM and ASCVD patients from March 2024. Patients were grouped into combination therapy (SGLT2i and GLP1RA) and no therapy groups. Data on demographics (Table 1) and SDOH (Table 2) were analyzed. Patients on monotherapy or those who did not complete the SDOH questionnaire were excluded. Descriptive statistics were used to summarize demographics. Welch’s t-test compared continuous variables, and chi-square or Fisher’s exact tests compared categorical variables. Analyses were done with SAS 9.4 with significance at 0.05. Results: Age significantly differed between groups (t = 4.56, p < .05), with older patients less likely to receive therapy. Sex was also significant (p < .05); more females were in the no therapy group. No significant association was found between SDOH and combination therapy (p > .05). Conclusion: Over 90% of patients with T2DM and ASCVD were not on optimal medical therapy to reduce MACE, with nearly half on no medications. This highlights the need for increased awareness and targeted interventions to improve outcomes. Future research will explore insurance status and physician awareness to address prescription discrepancies. Limitations: Patients with a GFR <30 are precluded from SGLT2i usage but were not excluded from this study.

Abstract 4135525: Bridging the Gap: How a Specialized Heart Failure Program Improves Guideline-Directed Medical Therapy Optimization for Rural Patients

Background: Previous research has shown that patients with heart failure with reduced ejection fraction (HFrEF) living in rural areas have suboptimal utilization of guideline-directed medical therapy (GDMT). Considering the associated increased mortality risk, this highlights the need for novel approaches to improve GDMT optimization for rural patients. The aim of this study was to evaluate how rural residence influences outcomes in a multidisciplinary, telehealth-based HF-GDMT optimization program implemented at our institution. Methods: We studied 322 patients who participated in a HF-GDMT optimization program led by a HF nurse practitioner and clinical pharmacist at Penn State Hershey Medical Center. We categorized residence at the time of enrollment using the Rural-Urban Commuting Area (RUCA) classification system. Differences in patient characteristics and program outcomes between the two groups were analyzed. P < 0.05 indicated statistical significance. Results: Among the 322 patients enrolled, 56 (17.4%) resided in rural areas and 266 (82.6%) in urban areas. Rural patients were younger (mean age 61.1 vs. 65.1; p=0.04) and the two groups differed significantly in racial demographics (p=0.006). The rural group had a higher proportion of patients with chronic HF (55.4% vs. 39.8%; p=0.038) and fewer patients with a recent HF hospitalization (30.4% vs. 49.2%; p=0.012). As far as outcomes, program completion rates were similar between rural and urban patients (83.9% vs. 83.1%; p=1). Those who received target doses of the four GDMT drug classes versus the maximum tolerated dose were also similar between the rural and urban groups (21.4% vs. 15.8%; p=0.32). Conclusions: Patients from rural areas were more likely to present with chronic HF and less likely to have recent HF hospitalizations compared to their urban counterparts, suggesting potential disparities in access to HF care. Despite these differences, program outcomes, measured by completion rates and GDMT medication titration, were comparable between the two groups. Our findings emphasize the crucial role of specialized HF programs in advancing GDMT use for rural patients, which may ultimately improve HF outcomes and bridge the healthcare gap.

Effects of Implementing a Heart Failure Order Set to Optimize Guideline-Directed Medical Therapy and Diuresis in Patients with Acute Heart Failure.

Background: Utilization of guideline-directed medical therapy in patients hospitalized for acute heart failure is suboptimal during the hospitalization and after discharge. An inpatient heart failure order set may be a convenient and useful intervention to improve heart failure therapy in the inpatient setting. Methods: This is a retrospective study that assessed the use of an inpatient heart failure order set on pharmacologic therapy in patients hospitalized for acute heart failure from May to August 2022. Patients with heart failure with an ejection fraction less than 50% were included in the analysis. The co-primary endpoints were maintenance or optimization of guideline-directed medical therapy during the hospitalization. Results: Maintenance of guideline-directed medical therapy was significantly greater when providers used the heart failure order set (OR 2.35, 95% CI 1.03-5.33, P = .041). Optimization of guideline-directed medical therapy was also statistically greater with use of the order set (OR 11.31, 95% CI 4.37-29.31, P < .001). Conclusions: An inpatient heart failure order set may be an effective strategy to improve heart failure pharmacotherapy in patients hospitalized with acute heart failure.

Clip It or Let It: The Efficacy of Mitral Valve Transcatheter Edge-to-Edge Repair Versus Conservative Treatment in Reducing Mortality Among Patients With Ischemic Mitral Regurgitation

BACKGROUND: Despite revascularization and optimal medial therapy (OMT) residual ischemic mitral regurgitation (IMR) continues in a self-aggravating vicious cycle to affect prognosis and survival adversely. Mitral valve surgery in combination with coronary artery bypass graft remains a subject of debate due to the absence of a net overall benefit. Mitral valve transcatheter edge-to-edge repair (M-TEER) has been gaining grounds as a viable option from observational studies, but results from randomized controlled trials (RCTs) have yielded mixed results. Thus, this study was conducted to determine whether the current collective data support the efficacy of M-TEER with OMT versus OMT alone in patients with clinically significant IMR. METHODS: A literature search from PubMed/MEDLINE, Cochrane Review Central, Clinical Trials Registry, ResearchGate, Mendeley, and Google Scholar for relevant RCTs and observational studies was conducted and reviewed independently by three reviewers. Published and unpublished studies indexed from inception until 2023 were included. The pooled estimates for the primary outcome of all-cause mortality and secondary outcomes of cardiac mortality and heart failure hospitalizations were measured using R Studio statistical software (R Foundation forStatistical Computing, Vienna, Austria). RESULTS: Seven eligible studies (five observational and two RCTs) allocated 1610 IMR patients to M-TEER + OMT (n = 942) or OMT alone (n = 668). The effect estimate using random-effects model demonstrated M-TEER with OMT to significantly reduce 1-year (odds ratio [OR], 0.67; 95% confidence interval [CI], 0.52–0.86; P = 0.002) and 2-year (OR, 0.50; 95% CI, 0.38–0.67; P &lt; 0.00001) all-cause mortality. Cardiac mortality (OR, 0.58; 95% CI, 0.27–1.23; P = 0.15) and heart failure hospitalization (OR, 0.45; 95% CI, 0.18–1.13; P = 0.09) did not reach statistical significance between the treatment arms. CONCLUSION: In patients with IMR, M-TEER on top of OMT was able to afford a 2-year allcause mortality advantage. KEYWORDS: ischemic mitral regurgitation, mitral valve transcatheter edge-to-edge repair, optimal medical therapy

Social Determinants of Health and Disparities in Guideline-Directed Medical Therapy Optimization for Heart Failure.

Fewer than 20% of eligible patients with heart failure with reduced ejection fraction receive all 4 pillars of guideline-directed medical therapy. Understanding disparities by race, ethnicity, sex, and adverse social determinants of health is necessary to equitably optimize quadruple therapy. Utilizing the American Heart Association's Get With The Guidelines-Heart Failure registry, we examined associations between race and ethnicity, sex, and adverse social determinants of health (insurance type and documented social need [any barrier to accessing health care]) with quadruple therapy optimization (QTO) in patients with heart failure with reduced ejection fraction hospitalized between July 1, 2021, and September 30, 2023, with complete medication data at discharge. We calculated adjusted mean differences (AMDs) in the discharge QTO score (range, 0%-100%) reflecting the proportion of eligible use of renin-angiotensin system inhibitors, β-blockers, mineralocorticoid receptor antagonists, and sodium-glucose cotransporter-2 inhibitors and compared across demographic and adverse social determinants of health groups. Among 82 637 patients (median age, 66 years; 32.5% female; 57.0% non-Hispanic White; 76.4% prior heart failure with reduced ejection fraction), the overall mean QTO score was 56.2% (SD, 25.5). After adjustment, compared with non-Hispanic White individuals, Black (AMD, 2.56 percentage points [95% CI, 2.16-2.96]) and Hispanic individuals (AMD, 0.71 percentage points [95% CI, 0.11-1.31]) had higher QTO scores. Females had higher QTO scores than males (AMD, 1.94 percentage points [95% CI, 1.58-2.31]). Patients with no insurance (AMD, -4.90 percentage points [-5.62 to -4.17]), Medicaid (AMD, -0.45 percentage points [-0.89 to -0.01]), and Medicare (AMD, -1.64 percentage points [-2.10 to -1.18]) had lower QTO scores versus private insurance. Those with an identified social need (n=24 651) had lower QTO scores than those without (AMD, -3.40 percentage points [95% CI, -4.10 to -2.71]). Disparities in QTO were most evident for patients with no insurance, Medicaid, Medicare, or potentially an identified social need. Future efforts should focus on reducing gaps to improve equitable guideline-directed medical therapy use.

Cognitive Behavioral Therapy for Paroxysmal Atrial Fibrillation: Heart Rate Variability, Physical Activity, and Sleep

BackgroundCognitive behavioral therapy for symptom preoccupation in paroxysmal atrial fibrillation (AF-CBT) significantly improved AF-specific quality of life in a recent trial. To what extent this may this may be associated with changes in physiological parameters is yet to be determined. ObjectivesThe purpose of this study was to assess the effects of AF-CBT on heart rate variability (HRV), physical activity, and sleep. MethodsPatients with symptomatic paroxysmal AF on optimal medical therapy (mean ± standard deviation 65.4 ± 8.3 years, 58% females, 61% on beta-blockers) were randomized to a 10-week online AF-CBT (n = 65) or AF education (n = 62). AF-CBT was therapist-led and focused on social and physical avoidance. A 5-day Patch-Holter with an integrated accelerometer was applied at baseline, post-treatment, and at 3-month follow-up to assess AF burden, HRV, physical activity, and sleep duration. Subjective assessments were made by the International Physical Activity (IPAQ) and Insomnia Severity Index questionnaires. ResultsAt baseline, participants walked on average 8040 ± 2600 steps/day and slept 8.0 ± 1.1 hours. Objective and subjective physical activity and sleep duration remained unchanged after treatment, with no significant difference between the groups. The Insomnia Severity Index score went from subclinical insomnia (12.2 ± 6.7) to near normal values (8.1 ± 5.6), a significant change compared to controls (P = 0.032). No changes were found in AF burden or HRV indices at rest during the day or at night. ConclusionsIn this select cohort, AF-CBT decreased insomnia severity but had no impact on HRV or physical activity. Thus, AF-CBT may operate through psychological and behavioral factors that are not targeted by current medical and lifestyle interventions.

Coronary Sinus Narrowing for TreatingRefractory Angina: REDUCER-I Multicenter "Real-World" Observational Study Primary Endpoint Analysis.

Patients with refractory angina are often ineligible for revascularization and have poor quality of life despite optimal medical therapy. The coronary sinus (CS) Reducer (Shockwave Medical Inc) was safe and effective in the treatment of refractory angina in the COSIRA (Coronary Sinus Reducer for Treatment of Refractory Angina) randomized sham-controlled trial. This study sought to perform the primary endpoint analysis of the complete REDUCER-I (An Observational Study of the Neovasc Reducer System) study cohort. REDUCER-I is a nonrandomized, "real-world" study of patients with refractory angina treated with the CS Reducer conducted at 25 centers from 9 European countries. The primary effectiveness endpoint was an improvement in Canadian Cardiovascular Society (CCS) class at 6months. The primary safety endpoints were major adverse cardiac events and device- or procedure-related serious adverse events through 30days. Study follow-up is planned through 5 years with some interim 3-year analyses included here. From 2016 to 2023, 400 patients were enrolled, including 78.0% (312/400) male patients, 54.3% (216/398) with previous myocardial infarction, 73.6% (293/398) with previous revascularization, and 72.0% (280/389) CCS class III/IV. Major adverse cardiac event and serious adverse event rates were 1.6% (95%CI: 0.7-3.6) and 1.1% (4/371), respectively, with no deaths within 30days. At 6months, 69.8% (240/344) of patients improved by≥1 CCS class. Six-minute walk distances improved by 34.1 ± 85.8m at 6months (P< 0.0001). Interim 3-year results showed CCS class and Seattle Angina Questionnaire quality of life improvements were sustained (P< 0.0001). The complete primary endpoint analysis of the REDUCER-I study shows patients with refractoryangina were safely and effectively treated with the CS Reducer. Improvements in angina and quality of lifeappear sustained through 3 years.

A retrospective analysis on optimal medical therapy for patients with symptomatic lower extremity peripheral artery disease: a French observational study

ObjectivePatients with symptomatic lower extremity artery disease (LEAD) should have an optimal management in terms of lipid goal [i.e. controlled LDL-cholesterol (LDLc)] and medical treatment (triple therapy with an antiplatelet agent, a statin and an angiotensin-converting enzyme inhibitor or a angiotensin-receptor antagonist). Prevalence of LEAD patients with a LDLc < 0.55 g/l is unknown. Aims of this study were to: (i) describe the prevalence of patients with a LDLc < 0.55 g/l, (ii) describe the prevalence of patients with an optimal medical treatment; (iii) compare this management between patients with a vascular surgery history and those without a vascular surgery history; and (iv) evaluate the number of patients eligible for new lipid-lowering therapies according to FOURIER and REDUCE-IT criteria.MethodsIn this single-center retrospective study, prevalence is expressed as numbers and percentages. Comparison of the number of well managed patients between LEAD patients with a vascular surgery history and those without was performed. Number of patients who would be eligible for FOURIER and REDUCE-IT studies were calculated.ResultsAmong the LEAD patients included in the analysis (n = 225), only 12.4% (n = 28) had a LDLc < 0.55 g/L. The prevalence of patients who received the optimal medical treatment was 50.7% (n = 114). There was no statistical difference in the prevalence of patients with and without vascular surgery history achieving the LDLc goal (n = 9 (10.6%) vs. n = 19 (13.6%); p = not significant). Ninety-three patients (46.0%) would be eligible for EVOLOCUMAB treatment according to the Fourier study design whereas 17 patients (8.4%) would be eligible for treatment with ICOSAPENT ETHYL according to the REDUCE-IT study design.ConclusionA majority of LEAD patients did not reach the LDLc goals. LEAD patients with a vascular surgery history did not experience a better management whereas they had a more consistent follow-up.

Diversity of Staphylococcus aureus enterotoxin genes and its potential impact on severity of mastitis in dairy cows.

Staphylococcus aureus enterotoxins (SEs) can lead to food poisoning and appear to play a pivotal role in the development and severity of mastitis. This study aimed to evaluate whether the presence and diversity of S. aureus Enterotoxin genes mastitis-causing are associated with the development and severity of mastitis in dairy cows. Comparative analysis of S. aureus isolates from cows with clinical and subclinical mastitis (103 isolates each, CM and SM respectively) was conducted, examining the occurrence of enterotoxins (sea-see, seg-sez, sel26, sel27, sel01 and se02). Clinical isolates exhibited greater diversity, with 14 genes compared to four in subclinical isolates, and higher gene frequency (100% vs. 86.4%). Among the classical SEs, only sec (1%) and sed (4.9%) were detected in clinical isolates, suggesting a potential insignificance in the development of mastitis. Conversely, the selw and selx genes were among the most prevalent in both clinical and subclinical mastitis isolates. While their role in human food poisoning has not been definitively established, they appear to influence mastitis development. Statistical analysis revealed significant differences in clinical isolates carrying seg, seh, sei, seo, seul1, seul2, selw, and selx genes compared to subclinical isolates, suggesting their potential involvement in the severity of mastitis. Determining the frequency of SE gene and its role in mastitis establishment and in clinical mastitis severity, as well as understanding how enterotoxins contribute to pathogenicity in clinical and subclinical mastitis, is crucial for guiding optimal medical therapy for animals and establishing effective veterinary treatments to mitigate economic losses in the dairy industry.

Percutaneous revascularization in late-presenting STEMI with absence of viability: effects on left ventricular remodeling and scar

Abstract Introduction In patients with ST-elevation myocardial infarction (STEMI), percutaneous coronary intervention (PCI) should be conducted within 12 hours of symptom onset. The potential benefits attributable to late reperfusion in STEMI fall under the "open artery hypothesis" where the stunned peri-infarction zone after revascularization would restore blood supply and contractility. Purpose To estimate the differences on the LV ejection fraction (LVEF), indexed LV end-systolic volume (iLVESV) and scar in patients with STEMI without viabilitity randomized to optimal medical therapy (OMT) alone or OMT and a late percutaneous coronary intervention (PCI) performed between 24 hours and 30 days after the event. Methods Patients with non-reperfused STEMI were evaluated from September 2021 to June 2022 at a tertiary cardiology hospital. The patients underwent Cardiac Magnetic Resonance (CMR) to assess myocardial viability and were classified as non-viable if they had only 1 wall segment with less than fifty percent thickness of the affected wall with late gadolinium enhancement. The patients were randomized to PCI or OMT alone. CMR was repeated at 6 months to evaluate LVEF, iLVESV and fibrosis. This summary presents a planned partial analysis of the 6-month results (N=51). Descriptive statistics analysis included central and dispersion estimators, or absolute and relative frequencies. To explore the differences between groups and time, Mann-Whitney and Wilcoxon tests were run, and results were given as point-estimates and confidence intervals at 95% (95% CI). A significance level of 5% was adopted for inferential analysis. Results 51 patients (60±11 years, 71% male) were included in the analysis. Of this total, 24 were randomized to PCI + OMT, and 27 to isolated OMT. The groups showed balanced distribution regarding clinical characteristics and initial CMR parameters (LVEF, iLVESV, and fibrosis). The difference in LVEF at the end of 6 months between the OMT and PCI groups was 2.07%, favoring the OMT group; however, this difference was not significant (p= 0.677, 95% CI: -5 to 10). Between the groups, the difference at the end of 6 months in iLVESV was -6.82 ml/m², also without statistical significance (p= 0.858, 95% CI: -19 to 11). There was a significant reduction in the amount of fibrosis in both PCI group with -14.68g (p= 0.011) and in the OMT group with -12.57g (p= 0.009). Detailed results are presented in Table 1. Conclusion Despite a significant reduction in fibrosis in both groups, there was no superiority observed in late PCI compared to isolated OMT in reducing reverse remodeling and fibrosis in patients with non-viable STEMI when compared to isolated OMT.Remodeling changes.