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Item Congestive heart failure clinics and telemedicine: The key to reducing hospital readmissions in the United States(VM Media Group, 2022) Ramgobin, Devyani; Vo, Maique; Golarmari, Reshma; Jain, Rahul; Jain, Rohit; Medicine, School of MedicineThe United States healthcare system currently faces an economic challenge related to frequent hospital readmission rates. As such, hospitals have begun implementing strategies to reduce readmission rates for specific medical conditions such as congestive heart failure, which had a 30-day readmission rate of 23.2% in 2014. Patient education and frequent monitoring of symptoms have since allowed patients to work together with doctors and nurses to take charge of their healthcare management. Due to heart failure clinics and the rise of telemedicine and telemonitoring, heart failure readmission rates have since decreased.Item Evaluating Depressive Symptoms, BDNF Val66Met, and APOE-ε4 as Moderators of Response to Computerized Cognitive Training in Heart Failure(Elsevier, 2023) Pressler, Susan J.; Jung, Miyeon; Giordani, Bruno; Titler, Marita G.; Gradus-Pizlo, Irmina; Reid Lake, Kittie; Wierenga, Kelly L.; Clark, David G.; Perkins, Susan M.; Smith, Dean G.; Mocci, Evelina; Dorsey, Susan G.; School of NursingBackground: Depressive symptoms, brain-derived neurotrophic factor (BDNF) Val66Met, and apolipoprotein (APOE)-ε4 may moderate response to computerized cognitive training (CCT) interventions among patients with heart failure (HF). Objectives: The purpose of this study was to examine moderators of intervention response to CCT over 8 months among patients with HF enrolled in a 3-arm randomized controlled trial. Outcomes were memory, serum BDNF, working memory, instrumental activities of daily living (IADLs), and health-related quality of life (HRQL). Methods: 256 patients with HF were randomized to CCT, computerized crossword puzzles active control, and usual care control groups for 8 weeks. Data were collected at enrollment, baseline, 10 weeks, and 4 and 8 months. Mixed effects models were computed to evaluate moderators. Results: As previously reported, there were no statistically significant group by time effects in outcomes among the 3 groups over 8 months. Tests of moderation indicated that depressive symptoms and presence of BDNF Val66Met and APOE-ε4 were not statistically significant moderators of intervention response in outcomes of delayed recall memory, serum BDNF, working memory, IADLs, and HRQL. In post hoc analysis evaluating baseline global cognitive function, gender, age, and HF severity as moderators, no significant effects were found. HF severity was imbalanced among groups (P = .049) which may have influenced results. Conclusions: Studies are needed to elucidate biological mechanisms of cognitive dysfunction in HF and test novel interventions to improve memory, serum BDNF, working memory, IADLs and HRQL. Patients may need to be stratified or randomized by HF severity within intervention trials.Item Genome-Wide Association Study for Anthracycline-Induced Congestive Heart Failure(American Association for Cancer Research, 2017-01-01) Schneider, Bryan P.; Shen, Fei; Gardner, Laura; Radovich, Milan; Li, Lang; Miller, Kathy D.; Jiang, Guanglong; Lai, Dongbing; O’Neill, Anne; Sparano, Joseph A.; Davidson, Nancy E.; Cameron, David; Gradus-Pizlo, Irmina; Mastouri, Ronald A.; Suter, Thomas M.; Foroud, Tatiana; Sledge, George W., Jr.; Medicine, School of MedicinePURPOSE: Anthracycline-induced congestive heart failure (CHF) is a rare but serious toxicity associated with this commonly employed anticancer therapy. The ability to predict which patients might be at increased risk prior to exposure would be valuable to optimally counsel risk-to-benefit ratio for each patient. Herein, we present a genome-wide approach for biomarker discovery with two validation cohorts to predict CHF from adult patients planning to receive anthracycline. EXPERIMENTAL DESIGN: We performed a genome-wide association study in 3,431 patients from the randomized phase III adjuvant breast cancer trial E5103 to identify single nucleotide polymorphism (SNP) genotypes associated with an increased risk of anthracycline-induced CHF. We further attempted candidate validation in two independent phase III adjuvant trials, E1199 and BEATRICE. RESULTS: When evaluating for cardiologist-adjudicated CHF, 11 SNPs had a P value <10-5, of which nine independent chromosomal regions were associated with increased risk. Validation of the top two SNPs in E1199 revealed one SNP rs28714259 that demonstrated a borderline increased CHF risk (P = 0.04, OR = 1.9). rs28714259 was subsequently tested in BEATRICE and was significantly associated with a decreased left ventricular ejection fraction (P = 0.018, OR = 4.2). CONCLUSIONS: rs28714259 represents a validated SNP that is associated with anthracycline-induced CHF in three independent, phase III adjuvant breast cancer clinical trials.Item Pilot trial of paclitaxel-trastuzumab adjuvant therapy for early stage breast cancer: a trial of the ECOG-ACRIN cancer research group (E2198)(SpringerNature, 2015-12-22) Schneider, Bryan P.; O’Neill, Anne; Shen, Fei; Sledge, George W.; Thor, Ann D.; Kahanic, Stephen P.; Zander, Paul J.; Davidson, Nancy E.; Department of Medicine, IU School of MedicineBACKGROUND: Blockade of human epidermal growth factor receptor type 2 (HER2) has dramatically improved outcome for patients with HER2-positive breast cancer. Trastuzumab, an anti-HER2 monoclonal antibody, has previously demonstrated improvement in overall survival (OS) in patients with metastatic and early stage HER2-positive breast cancer. However, trastuzumab can cause congestive heart failure (CHF) with an increased frequency for patients who have also received an anthracycline. The current trial was designed to evaluate the impact of the duration of trastuzumab on CHF. METHODS: E2198 included 227 eligible women with histologically confirmed stage II or IIIA HER2-positive breast cancer. The patients were randomised to receive 12 weeks of paclitaxel and trastuzumab followed by four cycles of doxorubicin and cyclophosphamide (abbreviated Arm) or the aforementioned treatment with additional 1 year of trastuzumab (conventional Arm). The primary end point was to evaluate the safety of this variable duration of trastuzumab therapy, particularly cardiac toxicity defined as CHF or left ventricular ejection fraction decrease >10%. Secondary end points included disease-free survival (DFS) and OS. RESULTS: Compared with 12-week treatment with trastuzumab, 1 year of trastuzumab-based therapy did not increase the frequency or severity of cardiac toxicity: three patients on the abbreviated Arm and four on the conventional Arm experienced CHF. The 5-year DFS was 76% and 73% for the abbreviated and conventional Arms, respectively, with a hazard ratio (HR) of 1.3 (95% CI: 0.8-2.1; P=0.3). There was also no statistically significance difference in OS (HR, 1.4; P=0.3). CONCLUSIONS: Compared with 12 weeks of treatment, 1 year of treatment with trastuzumab did not significantly increase the risk of cardiac toxicity. Although not powered for efficacy comparisons, the longer duration of trastuzumab therapy did not demonstrate a signal for marked superiority.Item Precision cardio-oncology: understanding the cardiotoxicity of cancer therapy(Nature Research, 2017-09-12) Han, Xinqiang; Zhou, Yun; Liu, Wendi; Medicine, School of MedicineCurrent oncologic treatments have brought a strong reduction in mortality in cancer patients. However, the cancer therapy-related cardiovascular complications, in particular chemo-therapy and radiation therapy-induced cardiotoxicities are a major cause of morbidity and mortality in people living with or surviving cancer. The simple fact is that all antineoplastic agents and radiation therapy target tumor cells but also result in collateral damage to other tissues including the cardiovascular system. The commonly used anthracycline chemotherapy agents can induce cardiomyopathy and congestive heart failure. Targeted therapies with human epidermal growth factor antibodies, tyrosine kinase inhibitors or vascular endothelial growth factor antibodies, and the antimetabolites also have shown to induce cardiomyopathy and myocardial ischemia. Cardiac arrhythmias and hypertension have been well described with the use of tyrosine kinase inhibitors and antimicrotubule agents. Pericarditis can happen with the use of cyclophosphamide or cytarabine. Mediastinal radiation can cause constrictive pericarditis, myocardial fibrosis, valvular lesions, and coronary artery disease. Despite significant progresses in the understanding of the molecular and pathophysiologic mechanisms behind the cardiovascular toxicity of cancer therapy, there is still lack of evidence-based approach for the monitoring and management of patients. This review will focus mainly on the recent advances in the molecular mechanisms of cardiotoxicity related to common cancer therapies while introducing the concept of cardio-oncology service. Applying the general principles of multi-disciplinary approaches toward the diagnosis, prevention, monitoring, and treatment of cancer therapy-induced cardiomyopathy and heart failure will also be discussed.Item Predictors of emergency medical services use by adults with heart failure; 2009-2017(Elsevier, 2020-09) Pressler, Susan J.; Jung, Miyeon; Lee, Christopher S.; Arkins, Thomas P.; O'Donnell, Daniel; Cook, Ryan; Bakoyannis, Giorgos; Newhouse, Robin; Gradus-Pizlo, Irmina; Pang, Peter S.; Emergency Medicine, School of MedicineBACKGROUND: Heart failure (HF) necessitates frequent transport by emergency medical services (EMS), but few studies have been conducted to evaluate predictors of EMS use and of multiple EMS transports that are amenable to intervention. OBJECTIVES: To characterize prehospital clinical status of community-dwelling adults with reported HF who used EMS across 8 years and to evaluate predictors of EMS use and multiple EMS transports. METHODS: Data were from a database in a large Midwestern county. Descriptive statistics, logistic and negative binomial regression were used for analysis. RESULTS: EMS transports were evaluated for 6582 adults with 16,905 transports. The most common chief complaints were respiratory problems, feeling sick, and chest pain. Shortness of breath, chest pain, level of consciousness, age, gender, race, and hospital site predicted multiple transports. CONCLUSIONS: Clinicians need to educate patients with HF about ways to manage shortness of breath and chest pain and when to activate EMS.Item Six-Minute Walk Test as a Predictive Measure of Exercise Capacity in Adults with Type 2 Diabetes(Wolters Kluwer, 2018-07) Nolen-Doerr, Eric; Crick, Kent; Saha, Chandan; de Groot, Mary; Pillay, Yegan; Shubrook, Jay H.; Donley, David; Hornsby, W. Guyton; Biostatistics, School of Public HealthObjective: The 6 Minute Walk Test (6MWT) is a measure that is routinely used to assess a response to treatment for cardiopulmonary diseases such as pulmonary fibrosis and congestive heart failure. The measure has never been verified as a valid measure of exercise capacity in the highly prevalent patient population of type 2 diabetes (T2DM). This study investigated the correlation between the 6MWT and graded exercise testing (GXT) in an effort to validate the 6MWT as a quality tool for assessing exercise capacity in adults with T2DM. Research Design and Method: This is a secondary data analysis of Program ACTIVE II, a randomized controlled trial designed to assess the effectiveness of two behavioral interventions on depression and glycemic outcomes in adults with T2DM. The correlation of 6MWT and predicted VO2 max (PVO2M) using GXT was examined in a subsample of participants at the time of study enrollment and at post-intervention. Results: PVO2M showed a significant correlation with 6MWT distance both at baseline (r=0.57, p=0.014) and post-intervention (r = 0.66, p = 0.037). The regression analysis of baseline data revealed that 6MWT distance alone explained 45% (F = 13.03, p = .0024) of the variability in PVO2M. When combined with the SF-12 physical health component score (PCS), 6MWT explained 66% (F = 13.62, p < .001) of the variance in PVO2M. After adjusting for PCS, 6MWT distance explained an additional 30% variability in PVO2M. Conclusions: Findings from this study indicate that the 6MWT and predicted exercise capacity are significantly correlated. The 6MWT can be used to estimate exercise capacity in adults with T2DM.Item Sleep-disordered breathing is associated with depletion of circulating endothelial progenitor cells and elevation in pulmonary arterial pressure in patients with decompensated systolic heart failure(SciencePress, 2015-07) Zhang, Han; Feng, Liu; Wan, Qi-Lin; Hong, Yan; Li, Yan-Ming; Cheng, Guan-Chang; Han, Xin-Qiang; Department of Medicine, IU School of MedicineBACKGROUND: Sleep-disordered breathing (SDB) is known to occur frequently in and may predict worsening progression of patients with congestive heart failure (CHF). SDB is also known to play an important role in the development of idiopathic pulmonary arterial hypertension (PAH) via inducing endothelial dysfunction and vascular remodeling, a pathological process that can be significantly influenced by factors such as osteoprotegerin (OPG) and endothelial progenitor cells (EPCs). The objective of this study is to determine if CHF with SDB is associated with changes in OPG, EPCs, and PAH. METHODS: EPCs were isolated, cultured, and quantified from CHF patients with SDB (n = 52), or without SDB (n = 68). OPG and N-terminal pro-brain natriuretic peptide (NT-proBNP) from each group was analyzed and correlated with EPCs and the mean pulmonary artery pressure (mPAP) measured by right heart catheterization. RESULTS: A significant decrease in circulating EPCs (29.30 ± 9.01 vs. 45.17 ± 10.51 EPCs/× 200 field; P < 0.05) was found in CHF patients with SDB compared to those without SDB. Both OPG (789.83 ± 89.38 vs. 551.29 ± 42.12 pg/mL; P < 0.05) and NT-proBNP (5946.50 ± 1434.50 vs. 3028.60 ± 811.90 ng/mL; P < 0.05) were also significantly elevated in SDB CHF patients who also had significantly elevated mPAP (50.2 ± 9.5 vs. 36.4 ± 4.1 mm Hg; P < 0.05). EPC numbers correlated inversely with the episodes of apnea and hypopnea per hour (RDI, r = -0.45, P = 0.037) and blood level of OPG (r = -0.53, P = 0.011). Although NT-proBNP was also increased significantly in patients with SDB, it had no correlation with either EPCs or RDI. CONCLUSIONS: SDB due to hypoxemia from decompensated CHF is associated with (1) OPG elevation, (2) EPC depletion, and (3) mPAP elevation. The inverse relationship of circulating OPG with EPCs suggests a likely mechanism for hypoxemia and OPG in the development of pulmonary vascular dysfunction via depleting EPCs, thus worsening prognosis of CHF.