tbuckley/cabot-search huggingface dataset:
Abstract 4137985: Impaired Skeletal Muscle Condition and Stroke Volume Reserve Characterize Poor Exercise Performance in Childhood Cancer Survivors
Authors: Takeshi Tsuda, Kimberly Davidow, Gina DAloisio, Joanne Quillen
Journal: Circulation (2024)

Background: Childhood cancer survivors (CCS) frequently show poor exercise performance, but its pathophysiology and clinical significance are poorly understood. Methods: Poor exercise performers, defined as peak oxygen consumption (VO2)/kg &lt; 80% of predicted maximum VO2/kg, were enrolled, including 40 CCS (20 males, 20 females) and 32 controls (15 males, 17 females) from 79 CCS and 147 age-matched controls, respectively. Peak and submaximal CPET parameters were compared between CCS and controls with poor exercise performance. Submaximal slope parameters represent a trend up to anaerobic threshold (AT). Results: Ages and anthropometric measurements (weight, height, and body mass index) were comparable between CCS and controls in both sexes (Table 1). Both resting and peak heart rate (HR) were significantly higher in CCS than in controls in males. There was no significant difference in peak VO2/kg, peak oxygen pulse (OP)/kg, peak respiratory exchange ratio, or VO2/kg at AT (VAT/kg) between CCS and controls in both sexes. Peak work rate (WR/kg) was significantly lower in CCS compared with that in controls in both sexes, suggesting reduced muscle strength in CCS. Figure 1 demonstrates decreased muscle mass/strength in CCS than in controls. In males, Δ[VO2/kg]/ ΔHR was significantly lower in CCS than in controls, indicating limited stroke volume reserve (SVR) in male CCS. In female, although there was no significant difference in Δ[VO2/kg]/ΔHR between CCS and controls, HR-dependency expressed by ΔHR/Δ[WR/kg] was significantly higher in CCS than in controls, suggesting impaired SVR. ΔVO2/ΔWR, a marker for physical conditioning, was comparable between CCS and controls in both sexes. Conclusions: Poor exercise performance in CCS is characterized mainly by decreased muscle mass/strength and impaired SVR for both sexs. Impaired SVR may be an early sign of subclinical cardiotoxicity. Poor exercise performance in CCS should be improved to prevent future cardiovascular complications.
Abstract 4132498: Hemodynamic and Clinical Outcomes with Balloon-Expandable Valves Versus Self-Expanding Valves in Patients with Small Aortic Annulus Undergoing Transcatheter Aortic Valve Implantation: A Meta-Analysis of Randomized Controlled Trials and Propensity Score Matched Studies
Authors: Mushood Ahmed, Areeba Ahsan, Irra Tariq, Mahnoor Farooq Raja, Asma Mahmood, Shehroze Tabassum, Kamleshun Ramphul, Adeel Ahmad, Asad Rahman, Farhan Shahid, Raheel Ahmed
Journal: Circulation (2024)

Background: Transcatheter aortic valve implantation (TAVI) is thought to be more effective than surgery for patients with small aortic annulus (SAA), however, the comparative efficacy of different transcatheter heart valves (THVs) remains uncertain. The objective of this meta-analysis was to compare the effects of balloon-expandable valves (BEVs) and self-expanding valves (SEVs) on hemodynamic parameters and clinical outcomes in patients with SAA who underwent TAVI. Methods: A thorough literature search was performed across PubMed/MEDLINE, Embase, and the Cochrane Library from their inception until May 2024 to identify eligible randomized controlled trials (RCTs) and propensity-score matched (PSM) studies. Clinical outcomes were evaluated using a random-effects model to pool risk ratios (RRs) with 95% confidence intervals (CIs). Results: The analysis included 8 studies; 2 RCTs and 6 PSM studies, with a total of 2,180 patients with SAA. BEVs were associated with a smaller indexed effective orifice area (MD: -0.18, 95% CI: -0.31 to -0.05) and a higher transvalvular mean pressure gradient (MD: 5.23, 95% CI 3.44 to 7.02) than SEVs. The risk for prosthesis-patient mismatch (PPM) (RR= 1.82, 95% CI: 1.27 to 2.60) and severe PPM (RR= 2.77, 95% CI: 1.93 to 3.98) was significantly higher for patients receiving BEVs than those receiving SEVs. However, no significant difference was observed between BEVs and SEVs regarding the risk of paravalvular leak (RR= 0.98, 95% CI: 0.57 to 1.69) and the permanent pacemaker implantation (RR= 0.78, 95% CI: 0.50 to 1.23). Although patients receiving BEVs showed a slightly lower risk of major bleeding events (RR= 0.69, 95% CI: 0.49 to 0.99), BEVs were associated with a significantly increased risk of 1-year cardiovascular mortality (RR= 1.61, 95% CI: 1.05 to 2.47) compared to those receiving SEVs. However, no significant differences were observed between BEVs and SEVs regarding 30-day all-cause mortality (RR= 1.19, 95% CI: 0.57 to 2.49), 1-year all-cause mortality (RR= 1.17, 95% CI: 0.89 to 1.53), stroke rates (RR= 0.83, 95% CI: 0.52 to 1.31) and any vascular complication (RR= 1.13, 95% CI: 0.72 to 1.75). Conclusion: In patients with SAA, SEVs showed reduced risks of PPM and severe PPM compared to BEVs, along with a larger indexed effective orifice area. Moreover, SEVs were associated with a lower risk of 1-year cardiovascular mortality.
Abstract 4132657: Age-related Differences in Peak Oxygen Uptake in Patients with Multimorbidity Undergoing Cardiac Rehabilitation
Authors: Pauline Gomes, Sophie Miller, Audry Chacin-Suarez, Thomas Olson
Journal: Circulation (2024)

Background: Cardiac rehabilitation (CR) patients demonstrate a high burden of chronic conditions (CC). Both multimorbidity (MM; ≥2 coexisting CC) and aging negatively impact functional capacity, whereas CR improves performance. Age-related difference in cardiorespiratory fitness (CRF, peak oxygen uptake (VO 2 )) in CR patients with MM has not been studied. Hypothesis: We hypothesized improvement in CRF will be attenuated by MM with increasing age in CR patients. Aims: We aimed to identify age-related differences in CRF improvement in CR patients with MM. Methods: Patients ≥18 yrs old who attended ≥1 CR sessions from 1999-2017 and completed cardiopulmonary exercise stress test before and after CR were included. The prevalence of CC was assessed using Rochester Epidemiology Project records-linkage system. Age categories included: Younger (18-49 yrs), Midlife (50-64 yrs) and Older (≥65 yrs). CRF categories included: &lt;0%, 0-8% and &gt;8%. Analysis included Kruskal-Wallis and Chi-squared. Results: Of 622 patients, 75.4% were male. Mean age: 62.9±11.2 yrs; Younger (n=70) age: 42.7±6.8 yrs, 67.1% male; Midlife (n=283) age: 58.3±4.3 yrs, 78.8% male; Older (n=269) age: 73.0±5.2 yrs, 74.0% male. BMI was 29.9±5.4 kg/m 2 (Younger: 30.0±6.7, Midlife: 30.4±5.6, Older: 29.3±4.7; p&lt;.05). Median (Q1, Q3) no. of CR sessions attended was 33(22, 35), with lower attendance in the Younger group: 25(16,34) vs Midlife: 33(20,35) and Older: 34 (29,35), p&lt;.05. Overall, percent change in peak VO 2 was 11.5±21.6% (Younger: 18.8±22.8%, Midlife: 11.6±19.5%, Older: 9.4±23.1%; p&lt;.01). The median number of CC was 7(5,8) with significant differences across groups: Younger: 5(3,7), Midlife: 6(5,8), Older: 7(6,9), p&lt;.01. Number of CC increased with age across all CRF categories (p&lt;.01, Fig. 1). However, there was no difference in number of CC within age groups across categories of CRF, Table 1. Conclusions: Our results suggest that MM increases with age in patients attending CR; however, within a given age group, improvement in CRF does not appear dependent on MM. The impact of age appears to have a greater impact than MM on CRF improvement. Individualized treatment plans should focus on the impact of age-related disparities on CRF improvement among CR patients with MM.
Abstract 4134396: Trends and Disparities in Ischaemic Heart Disease Mortality in the United States: An Analysis of CDC WONDER Database, 1999-2020
Authors: Farman Ali, Faizan Ahmed, Muhammad Abdullah Naveed, Ahila Ali, Bazil Azeem, MUHAMMAD KASHAN, Rabia Iqbal, Syed Muhammad Ishaq, Salman Abdul Basit, Usman Akbar, BADR HARFOUCH
Journal: Circulation (2024)

Backgrounds: Ischemic heart disease (IHD) remains a leading cause of mortality globally and has a high prevalence in the United States, necessitating an understanding of long-term trends to inform interventions. This study examines IHD-related mortality trends among US adults from 1999 to 2020, considering demographic and geographic disparities. Aim: This study aimed to evaluate patterns and geographical variations in mortality associated with IHD among adults in the United States. Methods: Death certificates from the CDC WONDER database spanning from 1999 to 2020 were analyzed to investigate mortality related to IHD among adults aged 35 years and above. Age-adjusted mortality rates (AAMRs) per 100,000 persons and annual percent change (APC) were calculated, stratified by year, sex, race/ethnicity, and geographic region. Results: Ischemic Heart Disease (IHD) caused 12,756,359 deaths among U.S. adults aged 35 and above from 1999 to 2020. Annual trends in age-adjusted mortality rates (AAMRs) showed a decline from 48.7 in 1999 to 28.9 in 2020, with notable fluctuations. Men consistently had higher AAMRs than women. NH Black or African American individuals exhibited the highest AAMRs. Geographically, significant disparities existed among states and regions, with the Northeast having the highest mortality. Nonmetropolitan areas consistently had higher AAMRs compared to metropolitan areas, showing varying trends over the study period. Conclusion: Fluctuations in mortality trends among IHD patients were observed over the study duration, revealing significant disparities across demographic and geographic parameters. Targeted interventions are imperative to alleviate the burden of IHD and mitigate mortality rates in the United States.
Abstract 4135113: Referral to a Heart Failure Clinic Substantially Increases the Use of Angiotensin Receptor Neprilysin Inhibitor (ARNi) and Sodium-glucose cotransporter-2 Inhibitor (SGLT2i) in Heart Failure Patients.
Authors: Gladys Baksh, Omaima Ali, Michele Haydo, Claudia Mae Velasco, Heather Reesor
Journal: Circulation (2024)

Introduction: Addressing access to life-saving therapy is crucial in influencing health outcomes. The stark reality of limited access to pharmacological therapy for heart failure with reduced ejection fraction (HFrEF), particularly novel drugs such as angiotensin receptor neprilysin inhibitors (ARNi) and sodium-glucose cotransporter-2 inhibitors (SGLT2i) for patients with heart failure (HF), underscores the challenges we face. Hypothesis: We analyze the impact of referring patients diagnosed with HF to our HF clinic by evaluating access to the 4 pillars of HFrEF, emphasizing cost-prohibiting pharmacological therapy, and assessing the efficacy of these medications when applied. Methods: This study compared 314 patients who live in counties within and outside the Penn State Health System. The data collected included healthcare insurance coverage, HF etiology, comorbidities, onset, initial and within six months post titration of guideline-directed medical therapy (GDMT) echocardiogram, and medication dose. Results: Among patients referred to our HF clinic, 184 live in counties within, and 130 live outside the Penn State Health System. The average age was 64, 69.4% were male, and a significant number of patients had HFrEF (92.7%). The prevailing comorbidities between the 2 groups were hypertension, hyperlipidemia, and diabetes. Upon completion, there was a significant increase in ARNi (83.1%) and SGLT2i (65.3%) use in both groups. They both (within vs. outside) reached almost similar percentages of triple therapy (77.9% vs. 79.2%; p-value=0.78), except for quadruple therapy (36.4% vs. 44.6%; p-value=0.16) and maximum tolerated dose (83.3% vs. 75%; p-value=0.11). The overall mean ejection fraction (EF) in both groups demonstrated significant improvement from pre-EF (30.5%) to post-EF (45.9%). Conclusion: Despite their location, patients referred to the HF clinic experienced intensified use of cost-prohibiting medications such as ARNi and SGLT2i, compared to the current gap in GDMT use. After optimizing GDMT, both groups had markedly improved EF. These findings suggest that referral to a HF clinic is a promising strategy for addressing the use of life-saving therapy and potentially reducing adverse health outcomes.
Abstract 4134841: A Diagnostic Pitfall: Subclavian Stenosis Mimicking Severe Aortic Stenosis on Echocardiography"
Authors: Shady Ezaldin, MAHMOUD ABDELSALAM, Omar Elsayed, Marciano Lee
Journal: Circulation (2024)

Background: Aortic stenosis (AS) is a common and serious valve disease in the elderly, often diagnosed using echocardiography. However, certain conditions can mimic AS, leading to diagnostic challenges. This case highlights the importance of a comprehensive vascular assessment in patients with atypical symptoms and echocardiographic findings suggestive of severe AS. Case Presentation: An 80-year-old female presented with progressive dizziness and double vision over the past few months. She reported a long-standing history of lower blood pressure in her right arm compared to her left. Her medical history was significant for HER2-positive intraductal breast cancer treated with neoadjuvant chemotherapy. An echocardiogram performed two months prior to presentation, using a Pedoff probe, indicated severe AS with a peak systolic velocity of 5.1 m/sec, a mean systolic gradient of 50 mm Hg, and an aortic valve area of 0.6 cm. Investigations: Given the discrepancy in blood pressure between her arms and the wide open aortic valve on the echo which dosen't corrleate with the doppler numbers, CTA neck and chest was performed, revealing a dense calcific plaque causing severe stenosis at the origin of the left subclavian artery. An angiogram confirmed &gt;75% stenosis of the left subclavian artery, which was treated with angioplasty and stent placement, resulting in &lt;10% residual stenosis. Outcome: Following the intervention, a repeat echocardiogram showed only mild calcification of the aortic valve with a mean gradient of 4 mm Hg, significantly lower than the previous findings. Discussion: This case underscores the potential for subclavian artery stenosis to mimic severe AS on echocardiography, particularly when using the Pedhoff probe. It highlights the need for clinicians to consider vascular anomalies in the differential diagnosis when echocardiographic doppler findings do not correlate with clinical symptoms or with the structural apperance of the valves. Conclusion: Comprehensive assessment and consideration of alternative diagnoses are crucial in patients with suspected severe AS, especially when using Doppler echocardiography. Awareness of the potential for subclavian artery stenosis to cause false-positive echocardiographic findings can prevent unnecessary interventions and guide appropriate management.
Abstract 4135194: Safety and Efficacy of Mechanical Circulatory Support during VT ablation
Authors: Mary Pelling, Michael Debakey, Aparna Sajja, Neal Bhatia, Anand Shah
Journal: Circulation (2024)

Introduction: Ventricular arrythmias are prevalent in patients with advanced heart failure and associated with increased mortality. Outcomes of electrophysiology ablation on patients requiring mechanical circulatory support (MCS) are not well described. We aimed to analyze the safety and efficacy of ventricular tachycardia (VT) ablation in patients requiring MCS at the Emory system. Methods: Patients were identified via retrospective chart review from October 2022 through August 2023. Patients who underwent VT ablation with the support of Impella, left ventricular assist device (LVAD), intra-aortic balloon pump (IABP), and venoarterial extra-corpeal membrane oxygenation (VA ECMO), or any combination of these were included. Results: A total of 7 patients of average age 56 ± 10 years, predominantly male (85.7%), with cardiomyopathy of mean EF 18.6% +/- 8.5 (ischemic 71.4%) underwent MCS supported VT ablation. One patient had 2 separate VT ablation procedures for refractory VT. Of these 8 procedures, 4 utilized a single type of MCS (2 impella, 2 LVAD) while 4 used a second type of MCS in combination with an Impella (2 impella RP, 1 VA ECMO, 1 IABP). Success at time of ablation was present in 75% of cases. Average time of outpatient follow up was 82 ± 31 days. At time of follow up, 50% of patients remained free of VT or with a single VT episode not requiring implantable cardioverter-defibrillator (ICD) shock. One patient had gone on to undergo successful heart transplantation. Procedural complications were noted in one patient, who suffered cardioembolic cerebrovascular accident (CVA) 2 days post-op. Transthoracic echo (TTE) 5 days post-op revealed LV mural thrombus as likely etiology of CVA. Conclusion: While there are no clear guidelines directing the use of MCS during VT ablation, our single academic institution experience suggests safety and feasibility of its use to support select, high risk cases.
Abstract 4133040: Cardiac Favored Transcription of the Exogenous Gene in Mice after A Single Systemic Delivery of AAV9-cBIN1
Authors: Thuy Ha, Jing Li, Pia Balmaceda, Robin Shaw, Tingting Hong
Journal: Circulation (2024)

Introduction: Heart failure (HF) is associated with high mortality and morbidity, and there are limited therapeutic options available to improve cardiac muscle function. Recent studies suggest that the impairment of cardiomyocyte T-tubule microdomains is a key factor in HF pathophysiology. AAV9-cBIN1 gene therapy effectively addresses this impairment. However, the kinetics and biodistribution of AAV9-cBIN1 have not been explored, limiting the knowledge of the transcription efficiency and organ specificity of cBIN1 gene therapy when delivered systemically. Aim: This study aims to elucidate the kinetics and biodistribution of AAV9-cBIN1 in a murine model. Method: Adult male C57BL/6J mice (n=20) were administered a single retro-orbital injection of AAV9-CMV-cBIN1-V5 at a dose (2x10^12 vg/kg) known to effectively transduce the majority of cardiomyocytes. Mice were sacrificed at pre-determined time points: prior to injection (Day 0, n=2) and post-injection at Days 3, 7, 14, 28, 56, and 84 (n=3/group). Tissues were harvested from the heart, lung, liver, kidney, skeletal muscle, and spleen. Genomic DNA was extracted and analyzed using qPCR to determine vector genome (vg) copies. For transcriptional analysis of the AAV9-transduced exogenous gene, mRNA was extracted and converted to cDNA for qRT-PCR quantification of cBin1-V5 , normalized to the housekeeping gene Hprt1 . Results: All mice survived to their designated sacrifice times. Kinetic analysis demonstrated a time-dependent expression of the exogenous cBin1-V5 gene, with peak expression observed at 4 weeks in both the heart and liver, with expression declining in the liver after this peak (Figure 1A). Genomic DNA analysis showed a gradual increase and plateau of viral genome distribution in the heart between 2-4 weeks, while in the liver, distribution peaked sharply between Days 3-7 and then decreased. When correcting the gene transcription of cBin1-V5 (ΔCq of V5/Hprt1 ) for vector DNA vg copies in the tissue, the transcription efficiency in the heart was higher than in the liver (Figure 1B). Outside of the liver and heart, cBin1-V5 mRNA expression was undetectable in all other tissues by Day 56. Conclusion: In adult male mice, a single systemic administration of AAV9-cBIN1 results in robust transduction and higher transcription efficiency in the heart compared to the liver. AAV9-cBIN1 holds promise for targeted gene therapy in cardiac tissues, with minimal off-target expression in other organs.
Abstract 4134483: How succesfully can we presribe the 'four pillars' of medications for patients with heart failure with reduced LV systolic function?
Authors: Robert Bain, Mark Walters, Keeley Wickham, Rachel Jones
Journal: Circulation (2024)

Introduction: European, American and UK guidelines all endorse the prescription of the 'four pillars' of treatment (ACE/ARBs, b-blockers, MRAs and SGLT2 inhibitors) for heart failure with reduced LV systolic function (HFrEF). Many doctors believe that it is difficult to initiate and maintain patients on all these medications. We have studied 162 consecutive patients referred to our service as outpatients from primary care, subsequently diagnosed as having HFrEF, and our ability to establish them on these medications. Methods: Patients referred with potential heart failure (signs, symptoms and raised BNP) were identified as having HFrEF by echocardiography using British Society of Echocardiography (BSE) criteria. Patients attended regular outpatient appointments with a consultant cardiologist and specialist heart failure nurse and were prescribed and uptitrated all appropriate medications with any contraindications and intolerances noted. Results: Table 1 shows the number of patients sucessfully established on maximally tolerated doses of each class of medication. Reasons for not prescibing or discontinuing were: CKD 6, severe aortic stenosis 5, asthma 3, symptomatic bradycardia 5, hypotension 3, type1 diabetes 2, syncope 1, Raynauds 1, patient choice 8 and 6 patients died before all appropriate medications could be initiated. In 10 cases no clinical reason could be identified. It can be seen that a high proportion of patients were successfully established on each individual class of medication and more than two thirds of patients were able to be maintained on all four classes of therapy. Table 2 shows the breakdown of prescribing success according to the severity of LV dysfunction. It can be seen that prescribing success appears to be higher in those with the more severe LV dysfunction. Conclusions: 1. The majority of patients can be established and maintained on appropriate polypharmacy for the treatment of LV systolic dysfunction. 2. The severity of LV systolic dysfunction is not a negative predictor of success in prescribing.
Abstract 4137880: Access to exercise opportunities, physical inactivity and cardiovascular mortality: A nationwide study in the U.S.
Authors: Xiaowen Wang, Yongshi Gu, Ying Wang, Yuqing Qu, Tianling Chen, Philip K. Hopke, Kai Zhang, Yuantao Hao, Wangjian Zhang
Journal: Circulation (2024)

Aims: Despite efforts to promote physical activity, the prevalence of physical inactivity continues to rise. Exercise access influences population activity levels, but county-level variation in physical activity and its link to cardiovascular disease (CVD) mortality is unclear. We explored the associations between access to exercise opportunities, levels of physical inactivity, and CVD mortality across U.S. counties Methods: The County Health Rankings and Roadmaps data and CDC WONDER mortality data were integrated. We compared age-adjusted CVD mortality across county-level quartiles of access to exercise opportunities and physical inactivity. Stratification was performed based on age, sex, race, and urbanization. The rate ratio (RR) for CVD mortality was calculated using generalized linear models. Results: CVD mortality decreased from high to low values of the county-level of physical activity across all demographic subgroups (P&lt;0.001) (Table 1&amp;Figure 1). Access to exercise opportunities was significantly associated with a reduced risk of CVD mortality (RR, 0.93 [0.91–0.95]), which was most pronounced in relation to acute myocardial infarction (AMI) mortality (RR, 0.80 [0.76–0.85]). The county-level physical inactivity was associated with an increased risk of CVD mortality (RR, 1.16 [1.14–1.17]), especially for ischemic heart disease (IHD) mortality (RR, 1.35 [1.31–1.38]) and AMI mortality (RR, 1.32 [1.25–1.38]) (Figure 2). All demographic subgroups demonstrated similar benefits by improving the county-level indicators of physical activity. Conclusion: Counties have the potential to make significant strides in preventing CVD and improving the cardiovascular health of their populations by enhancing access to exercise opportunities and reducing physical inactivity.