Incidence Of Congestive Heart Failure Research Articles

Association of Holter-Derived Heart Rate Variability Parameters With the Development of Congestive Heart Failure in the Cardiovascular Health Study

ObjectivesThis study sought to determine whether Holter-based parameters of heart rate variability (HRV) are independently associated with incident heart failure among older adults in the CHS (Cardiovascular Health Study) as evidenced by an improvement in the predictive power of the Health Aging and Body Composition Heart Failure (Health ABC) score. BackgroundAbnormal HRV, a marker of autonomic dysfunction, has been associated with multiple adverse cardiovascular outcomes but not the development of congestive heart failure (CHF). MethodsAsymptomatic CHS participants with interpretable 24-h baseline Holter recordings were included (n = 1,401). HRV measures and premature ventricular contraction (PVC) counts were compared between participants with (n = 260) and without (n = 1,141) incident CHF on follow-up. Significantly different parameters between groups were added to the components of the Health ABC score, a validated CHF prediction tool, using stepwise Cox regression. ResultsThe final model included components of the Health ABC score, In PVC counts (adjusted hazard ratio [aHR]: 1.12; 95% confidence interval [CI]: 1.07 to 1.19; p < 0.001) and the following HRV measures: abnormal heart rate turbulence onset (aHR: 1.52; 95% CI: 1.11 to 2.08; p = 0.009), short-term fractal scaling exponent (aHR: 0.27; 95% CI: 0.14 to 0.53; p < 0.001), in very low frequency power (aHR: 1.28; 95% CI: 1.02 to 1.60; p = 0.037), and coefficient of variance of N-N intervals (aHR: 0.94; 95% CI: 0.90 to 0.99; p = 0.009). The C-statistic for the final model was significantly improved over the Health ABC model alone (0.77 vs. 0.73; p = 0.0002). ConclusionsAbnormal HRV parameters were significantly and independently associated with incident CHF in asymptomatic, older adults. When combined with increased PVCs, HRV improved the predictive power of the Health ABC score.

Non-invasive cardiac imaging for evaluation of cardiotoxicity in cancer patients - early detection and follow-up

Cardiotoxicity is an increasingly important clinical entity that occurs as a result of untoward, and incompletely understood, effects on cardiac function. It is primarily caused by the anthracycline agents (doxorubicin, daunorubicin) but has also been observed with monoclonal antibody agents such as trastuzumab and small molecule tyrosine kinase inhibitors. The most feared net result of these agents is left ventricular (LV) dysfunction resulting in symptomatic congestive heart failure (CHF). Other manifestations can include arrhythmias, pericardial constriction, valvulopathy and hypertension. Standard cardiac imaging techniques have largely focused on LV ejection fraction (LVEF) quantifi cation. Contemporary cardiac imaging technologies now exist that are capable of evaluating for and detecting earlier stages of cardiotoxicity, including those which occur prior to changes in LVEF. Therapeutic algorithms have been devised to tailor chemotherapeutic regimens based on these results and have resulted in a dramatically reduced incidence of overt CHF.

Evaluation of the Relationship Between Serum Uric Acid Levels and Cardiovascular Events in Patients With Gout: A Retrospective Analysis Using Electronic Medical Record Data.

The aim of this study was to evaluate relationships between serum uric acid (SUA) and newly emergent acute myocardial infarction (AMI), congestive heart failure (CHF), coronary artery disease (CAD), composite cardiovascular (CV) events (AMI, CHF, CAD), hypertension, hyperlipidemia, and renal disease in gout patients. Retrospective analysis of electronic medical records from Humedica identified adults (≥18 years) with 2 or more International Classification of Diseases, Ninth Revision, Clinical Modification codes for gout 30 days or more apart (first diagnosis = index event) having 1 or more SUA assessment on or after the index date, and at least 6 months preindex and at least 12 months postindex enrollment. Outcomes were measured during 12 months postindex; patients with preindex events were excluded from analysis of those events. The SUA level (0.01-4.00 mg/dL, 4.01-6.00 mg/dL, 6.01-8.00 mg/dL, and ≥8.01 mg/dL) was determined using the closest laboratory assessment before or on the date of the CV event. Tukey-Kramer comparisons were performed for pairs of SUA strata and Cox proportional model estimated hazard ratios. A significantly higher incidence of AMI, CHF, and renal disease was observed for patients with 8.01 mg/dL or greater relative to other SUA levels (P < 0.0001), and a significantly higher incidence of composite CV events (AMI, CHF, and CAD) was observed for hypouricemia (SUA, 0.01-4.00 mg/dL) compared with other SUA levels (P < 0.0001). Cox models confirmed the increased risk associated with SUA 8.01 mg/dL or greater; hazard ratios ranged from 1.16 for hypertension to 2.04 for renal disease. Hyperlipidemia and hypertension were diagnosed concurrently with gout in 24% and 28% of patients, respectively. Hyperuricemia and hypouricemia were associated with an increased risk of CV events.

Association of Blood Pressure Trajectory With Mortality, Incident Cardiovascular Disease, and Heart Failure in the Cardiovascular Health Study.

Common blood pressure (BP) trajectories are not well established in elderly persons, and their association with clinical outcomes is uncertain. We used hierarchical cluster analysis to identify discrete BP trajectories among 4,067 participants in the Cardiovascular Health Study using repeated BP measures from years 0 to 7. We then evaluated associations of each BP trajectory cluster with all-cause mortality, incident cardiovascular disease (CVD, defined as stroke or myocardial infarction) (N = 2,837), and incident congestive heart failure (HF) (N = 3,633) using Cox proportional hazard models. Median age was 77 years at year 7. Over a median 9.3 years of follow-up, there were 2,475 deaths, 659 CVD events, and 1,049 HF events. The cluster analysis identified 3 distinct trajectory groups. Participants in cluster 1 (N = 1,838) had increases in both systolic (SBP) and diastolic (DBP) BPs, whereas persons in cluster 2 (N = 1,109) had little change in SBP but declines in DBP. Persons in cluster 3 (N = 1,120) experienced declines in both SBP and DBP. After multivariable adjustment, clusters 2 and 3 were associated with increased mortality risk relative to cluster 1 (hazard ratio = 1.21, 95% confidence interval: 1.06-1.37 and hazard ratio = 1.20, 95% confidence interval: 1.05-1.36, respectively). Compared to cluster 1, cluster 3 had higher rates of incident CVD but associations were not statistically significant in demographic-adjusted models (hazard ratio = 1.16, 95% confidence interval: 0.96-1.39). Findings were similar when stratified by use of antihypertensive therapy. Among community-dwelling elders, distinct BP trajectories were identified by integrating both SBP and DBP. These clusters were found to have differential associations with outcomes.

Influence of Left Ventricular Stroke Volume on Incident Heart Failure in a Population With Preserved Ejection Fraction (from the Strong Heart Study)

At a given level of left ventricular (LV) systolic function, LV pump performance (assessed by stroke index [SVi]) may differ, depending on LV size. We evaluated whether low SVi may be considered a marker of risk for incident congestive heart failure (HF), independent of LV geometry and systolic function, assessed by ejection fraction (EF) or midwall fractional shortening (MFS), in a large population-based sample with normal EF. Clinical and echocardiographic data from the second Strong Heart Study (SHS) examination, including 2,885 American Indians (59 ± 8years; 63% women) with normal EF (EF ≥51% in men and EF ≥55% in women) and without prevalent HF or significant valve disease, were analyzed. Low SVi was defined as SVi ≤22ml/m2.04. Low SVi was more common among men and associated with lower body mass index, systolic blood pressure, LV mass index, left atrial dimension, EF, and MFS and with higher relative wall thickness. During a mean 12-year follow-up, 209 participants developed HF and 246 had acute myocardial infarction. In Cox regression analysis, low SVi was associated with higher risk of incident HF (hazard ratio 1.38; 95% confidence interval 1.06 to 1.80), independently of age, gender, body mass index, heart rate, hypertension, prevalent cardiovascular disease, left atrial dimension index, LV mass index, LV concentric geometry, EF or MFS, and abnormal wall motion, also accounting for myocardial infarction as a competing risk event. In conclusion, in the SHS, low SVi was associated with higher incident rate of HF, independently of LV geometry and systolic function and other major confounders.

Alcohol Abuse and Cardiac Disease

BackgroundUnderstanding the relationship between alcohol abuse, a common and theoretically modifiable condition, and the most common cause of death in the world, cardiovascular disease, may inform potential prevention strategies. ObjectivesThe study sought to investigate the associations among alcohol abuse and atrial fibrillation (AF), myocardial infarction (MI), and congestive heart failure (CHF). MethodsUsing the Healthcare Cost and Utilization Project database, we performed a longitudinal analysis of California residents ≥21 years of age who received ambulatory surgery, emergency, or inpatient medical care in California between 2005 and 2009. We determined the risk of an alcohol abuse diagnosis on incident AF, MI, and CHF. Patient characteristics modifying the associations and population-attributable risks were determined. ResultsAmong 14,727,591 patients, 268,084 (1.8%) had alcohol abuse. After multivariable adjustment, alcohol abuse was associated with an increased risk of incident AF (hazard ratio [HR]: 2.14; 95% confidence interval [CI]: 2.08 to 2.19; p < 0.0001), MI (HR: 1.45; 95% CI: 1.40 to 1.51; p < 0.0001), and CHF (HR: 2.34; 95% CI: 2.29 to 2.39; p < 0.0001). In interaction analyses, individuals without conventional risk factors for cardiovascular disease exhibited a disproportionately enhanced risk of each outcome. The population-attributable risk of alcohol abuse on each outcome was of similar magnitude to other well-recognized modifiable risk factors. ConclusionsAlcohol abuse increased the risk of AF, MI, and CHF to a similar degree as other well-established risk factors. Those without traditional cardiovascular risk factors are disproportionately prone to these cardiac diseases in the setting of alcohol abuse. Thus, efforts to mitigate alcohol abuse might result in meaningful reductions of cardiovascular disease.

Abstract 12634: The Association of 24-hour Holter-Derived Heart Rate Variability With Incident Heart Failure in the Cardiovascular Health Study

Background: Abnormal heart rate variability (HRV) has been used to predict multiple adverse cardiovascular outcomes but not the development of congestive heart failure (CHF). We hypothesized that the addition of Holter-based HRV parameters to an existing CHF clinical risk model would improve its ability to identify older adults at an increased risk of CHF in the Cardiovascular Health Study (CHS). Methods: The Health ABC Heart Failure (Health ABC) score is a clinically based CHF prediction tool that has been validated in the CHS. Asymptomatic CHS participants with interpretable 24-hour baseline Holter recordings were included (N=1,401). Holter-based HRV measures and premature ventricular contraction (PVC) counts were compared between participants with (N=260) and without (N=1,141) incident CHF on follow up. Significantly different parameters between groups were added to the components of the Health ABC score using stepwise Cox regression. Results: Participants who developed CHF were more likely to be older, male, and have left ventricular hypertrophy (LVH) and coronary artery disease (CAD). They were also more likely to have a higher body mass index, baseline heart rate, systolic blood pressure, fasting glucose and creatinine. The final prediction model included all components of the Health ABC score (age, creatinine, albumin, heart rate, systolic blood pressure, fasting glucose, LVH, smoking and CAD), ln (PVCs+1) (Hazard Ratio [HR]=1.12; 95% CI, 1.06-1.19; p&lt;0.001) and the following HRV measures: abnormal heart rate turbulence onset (HR=1.52; 95% CI, 1.11-2.08; p=0.009), decreased short-term fractal scaling exponent (HR=0.27; 95% CI, 0.14-0.53; p&lt;0.001), increased ln (very low frequency power) (HR=1.27; 95% CI, 1.01-1.60; p=0.039) and decreased coefficient of variance of NN intervals (HR=0.94; 95% CI, 0.90-0.99; p=0.01). The C-statistic for the final model was significantly improved over the Health ABC model alone (0.77 vs. 0.73, p=0.0002). Conclusion: Abnormal HRV parameters were significant and independent predictors of incident CHF in asymptomatic, older adults. When combined with increased PVCs, these measures improved the predictive power of the Health ABC score in identifying CHS participants at an increased risk of developing CHF.

OS 04-09 CARDIORESPIRATORY FITNESS AND RISK FOR DEVELOPING HEART FAILURE IN HYPERTENSIVES

Objective: Hypertension is one of the most common risk factors for congestive heart failure (CHF). Evidence suggests that increased fitness may attenuate the risk for CHF in the general population. However, the association between fitness and CHF incidence in hypertensive patients has not been assessed. Design and Method: A total of 8,725 hypertensive men (mean age 60 ± 10) from Washington DC and Palo Alto Veterans Affairs Medical Centers underwent routine exercise tolerance testing. Peak workload was estimated in metabolic equivalents (METs). We established five fitness categories based on age-stratified quartiles of peak metabolic equivalents (MET) achieved: Least-fit (4.3 ± 1.18 METs; n = 1,643); Low-Fit (5.8 ± 1.10 METs; n = 1,926); Moderately-Fit (7.2 ± 1.2 METs; n = 1,771); Fit (8.4 ± 1.2 METs; n = 1,931) and Highly-Fit (11.2 ± 2.2 METs; n = 1,455). Cox proportional hazard models were applied after adjusting for age, BMI, race, family history of CV disease, CV/antihypertensive medications, and risk factors. P-values < 0.05 using two sided tests were considered statistically significant. Results: During a mean follow-up period of 10.7 ± 6.5 (median 10.4), there were 654 incidences of CHF (7.5%) or 6.7 events per 1000 person-years of follow-up. The association between new onset CHF risk and fitness was inverse and graded. For every 1-MET increase in exercise capacity, the risk was lowered by 16% (HR = 0.84; CI: 0.81–0. 87; p < 0.001). When compared to the individuals in the Least-Fit category, the risk for developing CHF was progressively lower, ranging from 32% (HR = 0.68; CI: 0.55–0.84; p < 0.001) for the next fitness category (Low-Fit) to 70% those in the highest fitness category (HR = 0.30; CI: 0.23–0.41; p < 0.001). Conclusions: Increased cardiorespiratory fitness is associated with lower risk for developing CHF in hypertensive patients.

Pneumoconiosis increases the risk of congestive heart failure: A nationwide population-based cohort study.

The purpose of the study was to determine the relationship between pneumoconiosis and congestive heart failure (CHF).We collected data from the National Health Insurance Research Database in Taiwan. The study sample comprised 8923 patients with pneumoconiosis and 35,692 nonpneumoconiosis controls enrolled from 2000 to 2011. Patients were followed up until the end of 2011 to evaluate the incidence of CHF. The risk of CHF was analyzed using Cox proportional hazard regression models, and the analysis accounted for factors such as sex, age, comorbidities, and air pollutants (μg/m3).The overall incidence of CHF was higher in the pneumoconiosis cohort (15.7 per 1000 person-y) than in the nonpneumoconiosis cohort (11.2 per 1000 person-y), with a crude hazard ratio (HR) of 1.40 (P < 0.001). The HR for CHF was 1.38-fold greater in the pneumoconiosis cohort than in the nonpneumoconiosis cohort (P < 0.001) after the model was adjusted for age, sex, various comorbidities, and air pollutants (μg/m3). The relative risk for CHF in the sex-specific pneumoconiosis cohort compared with the nonpneumoconiosis cohort was significant for men (adjusted HR = 1.40, 95% confidence interval = 1.21–1.62, P < 0.001). The incidence density rates of CHF increased with age; pneumoconiosis patients had a higher relative risk of CHF for all age group.Patients with pneumoconiosis were at higher risk for developing CHF than patients in the nonpneumoconiosis cohort, particularly in cases with coexisting coronary artery disease, hypertension, and chronic obstructive pulmonary disease.

Abstract 301: Aortic Segmental Diameters are Influenced by Both Common and Segment-specific Factors

Background and Objective: Aortic diameter is a critical parameter for the diagnosis of aortic aneurysm. In non-aneurysm patients, a large infrarenal aortic diameter are also a risk for all-cause mortality. Additionally, aortic dimension is associated with several risk factors of coronary artery disease; the measure of subclinical disease; a predictor of incident congestive heart failure; stroke risk; and all-cause and cardiovascular disease mortality. The purpose of this study was to explore the risk factors and potential alternative pathogenic mechanisms of aortic dilatation. Methods and Results: Five hundred and twenty patients with clinically evident arterial disease or cardiovascular risk factors were prospectively recruited. Comprehensive transthoracic M-mode, 2-dimensional, and Doppler echocardiographic studies were performed using commercially and clinical diagnostic ultrasonography technique. The aortic dimensions were assessed at end-diastole at the different levels: (1) the annulus, (2) the mid-point of the sinuses of Valsalva, (3) the sinotubular junction, (4) the ascending aorta at the level of its largest diameter, (5) the transverse arch, (6) the descending aorta posterior to the left atrium, and (7) the abdominal aorta just distal to the origin of the renal arteries. The relationships of aortic dimensions with clinical characteristics were assessed by linear multiple regression analysis. Variables analyzed included common cardiovascular risk factors, co-morbidities, lipid profile, hematological parameters. Age and diastolic blood pressure were positively associated with the diameters of arch, descending, ascending and abdominal aorta. In contrast, female gender and hypertension were negatively associated with the diameters of arch, descending, ascending and abdominal aorta. The presence of coronary arterial disease were positively associated with arch diameter, whereas High-density lipoprotein cholesterol levels were positively associated with the diameters of ascending, descending and abdominal aorta. Effects from other factors varied among aortic segments. Conclusion: Aortic segmental diameters are influenced by both common and segment-specific factors.

Prognosis of Low Normal Left Ventricular Ejection Fraction in an Asymptomatic Population-Based Adult Cohort: The Multiethnic Study of Atherosclerosis

BackgroundReduced left ventricular systolic function predicts worse outcomes. However, the optimal threshold for “normal” left ventricular ejection fraction (LVEF) is uncertain. In general, LVEF ≥ 55% is considered to be “normal” by guidelines, with a low normal designation for LVEF being 50%–55%. We assessed the prognosis of participants with low normal LVEF in the Multiethnic Study of Atherosclerosis. All participants were asymptomatic and had no known clinical cardiovascular disease at baseline. Methods and ResultsA total of 4926 out of 6814 had LVEF assessed with the use of cardiac magnetic resonance imaging (MRI), had no significant valvular disease, did not have myocardial infarction during follow-up, had complete data, and were included in this analysis. A total of 83/4926 (1.7%) had LVEF < 50% (low LVEF) and 101/4926 (2.1%) had low normal LVEF. Cox proportional hazard and cubic spline analyses were used to evaluate the association between LVEF category and 10 years of adjudicated incident congestive heart failure (CHF) and all-cause mortality adjusting for (model 1) age, sex, and race and (model 2) model 1 and diabetes mellitus, smoking, systolic blood pressure (BP), BP medications, body mass index, estimated glomerular filtration rate, low-density lipoprotein, family history of coronary heart disease, educational status, and LV mass. Mean age was 61 ± 10 years, 47% were men, 35% were on BP medications, 9% had diabetes. After 10.2 years of follow-up, 109 (2.2%) had CHF and 427 (8.7%) died. Compared with normal LVEF (≥55%), low normal LVEF and low LVEF were associated with an increased risk for incident CHF during follow-up in our multivariable Cox models: hazard ratios (HRs) 3.64 (95% CI 1.76–7.52) and 9.52 (5.63–17.52), respectively. Unlike low LVEF, low normal LVEF was not associated with increased risk of death compared with normal LVEF in our fully adjusted models: HRs 3.03 (1.94–4.73) and 1.32 (0.72–2.41), respectively. In the adjusted spline analysis HR of LVEF 55% as reference, LVEF had a U-shape association of future CHF risk and LVEF. ConclusionLow normal LVEF is as prevalent as low LVEF in asymptomatic community-dwelling adults. We observed a gradient-response association between the 3 categories of LVEF (low, low normal, and normal) and incident CHF but not for all-cause death.

Risk of Congestive Heart Failure in Early Breast Cancer Patients Undergoing Adjuvant Treatment With Trastuzumab: A Meta-Analysis.

The use of trastuzumab has proven to be a successful strategy in patients with human epidermal growth factor receptor 2 (HER2)-positive breast cancer; however, it is associated with an increased risk of cardiac dysfunction. We performed an up-to-date, comprehensive meta-analysis to clarify the risk of congestive heart failure (CHF) in patients with early breast cancer receiving different durations of adjuvant trastuzumab with the longest-term follow-up. Eligible studies included randomized control trials of HER2-positive early breast cancer patients with or without trastuzumab in adjuvant chemotherapy. Adequate reporting of CHF data were required for inclusion. Statistical analyses were conducted to calculate the overall incidence, relative risk (RR), and 95% confidence interval (CI) by use of a fixed-effects model. Six randomized control trials including 18,111 patients were identified. The overall incidence of high-grade CHF in patients treated with trastuzumab versus placebo was 1.44% (95% CI, 0.79%-2.64%) and the RR was 3.19 (95% CI, 2.03-5.02; p < .00001). In subgroup analysis, the difference in CHF incidence failed to achieve significance. The RR for 8 mg/kg trastuzumab (high dose) was greater than that for 4 mg/kg (low dose) (RR, 6.79, 95% CI, 2.03-22.72, p = .0001; versus RR, 2.64; 95% CI, 1.61-4.32; p = .002). Additionally, higher RRs were observed for patients receiving trastuzumab for 1 year (RR, 3.29; 95% CI, 2.07-5.25) and 2 years (RR, 9.54; 95%CI, 2.19-41.43), but not 9 weeks (RR, 0.50; 95% CI, 0.05-5.49) compared with control groups. No evidence of publication bias was observed. Adjuvant trastuzumab therapy was strongly associated with an increased risk of significant CHF in patients with early breast cancer, particularly in 2-year use. This comprehensive meta-analysis evaluated the risk of congestive heart failure with a usage profile of adjuvant trastuzumab in patients with early breast cancer. Before initiating treatment with trastuzumab, a risk-benefit analysis for individual patients should be critically evaluated, considering that the prognosis is closely related to drug dose and duration of use. Cardiac function should be monitored throughout the treatment period and also during follow-up. Thus, early identification of trastuzumab-related cardiac dysfunction can allow effective medical intervention, elimination of symptoms, recovery of function, and continuation of trastuzumab therapy.

The Clinical Efficacy and Cardiotoxicity of Fixed-Dose Monthly Trastuzumab in HER2-Positive Breast Cancer: A Single Institutional Analysis.

ObjectiveTrastuzumab-containing treatment regimens have been shown to improve survival outcomes in HER2-positive breast cancer (BC). It is much easier to infuse a fixed one-vial dose to every patient on a regular schedule in the general clinical setting. The aims of this study were evaluating the efficacy of a 440 mg fixed-dose of trastuzumab administered on a monthly infusion schedule, and the risk factors for cardiac events.Patients and methodsWe retrospectively reviewed data from 300 HER2-positive BC patients in our institute: 208 were early-stage BC patients undergoing adjuvant trastuzumab treatment, and 92 were metastatic BC patients treated with trastuzumab infusions until disease progression. There were 181 patients receiving regular trastuzumab infusions every 3 weeks (Q3W; 8 mg/kg loading dose followed by 6 mg/kg every 3 weeks), and the other 119 patients were treated monthly with a fixed 440 mg dose (QM; fixed 440 mg every 4 weeks).ResultsThe medians of progression-free survival (PFS) and overall survival (OS) in the adjuvant setting were not reached in both treatment groups. In the metastatic setting, there was no significant difference between groups in PFS or OS. The median time to significant cardiovascular (CV) dysfunction was 4.54 months. The incidence of congestive heart failure requiring medication in our cohort was 3.4%.ConclusionIn our study, we found that fixed-dose monthly trastuzumab was feasible and effective. In addition, the CV risk was not higher with the fixed-dose protocol. This treatment modality could lower the cost and was easier to implement in clinical practice. Larger prospective randomized studies with longer-term follow up are needed to confirm our results.

Bidirectional association between atrial fibrillation and congestive heart failure in the elderly.

The aim of this study was to examine the bidirectional association between atrial fibrillation and congestive heart failure (CHF) in older adults. We studied the association of atrial fibrillation at entry with incident CHF (N = 5281; 85% white, 42% male) and the association of CHF at entry with incident atrial fibrillation (N = 5233; 85% white, 42% male) in the Cardiovascular Health Study (CHS). Baseline atrial fibrillation was identified during the study electrocardiogram and by self-reported history, and incident cases were identified during subsequent study electrocardiograms and hospitalization data. Baseline CHF was identified by self-reported history and adjudication of medical records, and incident cases were identified using hospitalization data. Cox regression was used to compute hazard ratios and 95% confidence intervals (CIs) for the association between atrial fibrillation and incident CHF, and CHF and incident atrial fibrillation, separately. Over a median follow-up of 12.6 years, 534 (10%) participants developed atrial fibrillation. CHF was associated with an increased risk of atrial fibrillation (hazard ratio 2.0, 95% CI 1.4, 3.0). A total of 1692 (32%) participants developed CHF over a median follow-up of 11.7 years and atrial fibrillation was associated with an increased risk of CHF (hazard ratio 1.9, 95% CI 1.5, 2.2). Our results suggest that a bidirectional relationship exists between atrial fibrillation and CHF, with each condition influencing the development of the other.

Abstract P6-11-03: A cost effectiveness analysis of baseline left ventricular function assessment for breast cancer patients undergoing anthracycline chemotherapy

Abstract Background: It is unclear if all breast cancer (BC) patients require baseline left ventricular function (LVEF) assessment prior to anthracycline based chemotherapy (ABC), and the approach is variable in clinical practice. Our objective is to determine the cost effectiveness of obtaining a baseline LVEF assessment prior to (neo) adjuvant ABC in clinical practice. Methods: We performed a retrospective analysis of the Yale Equilibrium Radionuclide Angiography (ERNA) database for 701 breast cancer patients who had a baseline ERNA scan prior to systemic therapy for an initial diagnosis of stages I-IV BC between July 2003 and May 2013. We found that 14 of 701 (2%) patients had a baseline LVEF &amp;lt; 50%. Age, pre-existing cardiac risk factors and coronary artery disease did not predict an abnormal baseline LVEF &amp;lt;50 %. To evaluate the benefit of obtaining a baseline echocardiogram or ERNA before ABC, we considered the screening scenario in which BC patients with a baseline LVEF &amp;lt; 50% on screening echocardiogram are treated with a second (2nd) generation non-ABC and those with baseline LVEF ≥ 50% receive a third (3rd) generation ABC, and compared this with a non-screening scenario with uniform 3rd generation ABC treatment for all patients who do not have a baseline echocardiogram. We used Adjuvant Online to obtain estimates of the disease free (DFS) and overall survival (OS) for a 3rd generation ABC regimen vs a 2nd generation non-ABC regimen for 50 year old patients with a T2N1 hormone receptor positive BC. We implemented these oncologic clinical outcomes (in addition to cardiotoxicity-related clinical outcomes, costs of screening echocardiogram and treatment of congestive heart failure (CHF), quality of life metrics, as reported in the literature) into a simplified decision-analytic cost-effectiveness analysis that accounts for the different disease states and their associated costs and quality of life outcomes. Results: Assuming that 20% of the unscreened patients with a LVEF &amp;lt; 50% will develop CHF if treated with ABC regimen without management of baseline cardiac dysfunction, the base case incremental cost effectiveness ratio (ICER) was determined to be 18,520 $USD/QALY. Sensitivity analysis suggested that the cost-effectiveness of baseline LVEF assessment is primarily driven by the prevalence of patients with LVEF &amp;lt; 50%, the incidence of CHF in this high-risk patient group if treated with ABC regimen, and time to CHF development. While our analysis did not reveal risk factors predictive of low baseline LVEF, our model's dependence on prevalence of LVEF &amp;lt; 50% demonstrates the importance of risk factor stratification. A hypothetical predictive marker which enriches the prevalence of an abnormal baseline LVEF 5-fold to 10% would result in a cost-effectiveness of 10,990 $USD/QALY. The model is less sensitive to the cost of baseline echocardiogram testing. Conclusion: Baseline LVEF assessment was found to be cost-effective under a willingness-to-pay threshold of $50,000/QALY. Our sensitivity analysis suggests that risk factor-guided LVEF baseline LVEF screening may increase the number of high-risk patients in the treatment population, thus further increasing the cost-effectiveness of baseline LVEF assessment. Citation Format: Safonov A, Hatzis C, Stratton J, Gross CP, Russell R, Pusztai L, Abu-Khalaf MM. A cost effectiveness analysis of baseline left ventricular function assessment for breast cancer patients undergoing anthracycline chemotherapy. [abstract]. In: Proceedings of the Thirty-Eighth Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2015 Dec 8-12; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2016;76(4 Suppl):Abstract nr P6-11-03.

New Medications for the Treatment of Diabetes

New Medications for the Treatment of Diabetes

Significance of intraoperative precise management on intracavitary treatment for pulmonary thromboembolism

To compare cardiac adverse events, clinical outcomes and mid-and-long-term effects among massive and sub-massive pulmonary embolism (PE) patients under different periodswho received thrombus fragmentation by pigtail catheter. Two groups of patients who receivedthrombusfragmentation bypigtail catheter in different periods were analyzed retrospectively. Group E: 38 cases received therapy from July 2004 to October 2009 with local anesthesia; Group P: 64 cases with general anesthesia from March 2010 to December 2014. All patients were confirmedPEby CT and angiography. Parts of patients with deep vein thrombosis (DVT) received inferior vena cava filter placement 3 days later. The patients were followed up for 6-24 months after discharge. Cardiac adverse events, clinical outcomes during the thrombusfragmentation process, and mid-and-long-term effects were compared between the two groups. There were no significant differences in preoperative clinical data betweenthe two groups (P>0.05). Compared with group E, clinical warning events were significantly improved in group P (odds ratio(OR): 1.24, 98.3, 1.45, 2.50; P<0.05). Within group P, there were significant differences inarterial oxygen partial pressure (PaO2) [(98.3±8.7)vs(81.3±7.1)], mean pulmonary artery pressure (mPAP) [(25.3±7.9)vs(37.2±7.6)], heart rate (HR) [(94.3±7)vs(122±9)], airway resistance [(16.7±1.6)vs (22.5±2.1)] and mean arterial pressure (MAP) [(53.4±7)vs(42.5±6)] before and after thrombus fragmentationtreatment (P<0.05). The incidence of congestive heart failure and pulmonary arterial hypertension associated with chronic pulmonary thromboembolism (CPEPH) during follow-up were significantly different between group P andgroup E (P<0.05). Thrombus fragmentation by pigtail catheter with intraoperativeprecise management under general anesthesia can reduce cardiac adverse events andimprove the mid-and-long-term effects among PE patients.

Review of current and potential future pharmacological treatments in nonalcoholic steatohepatitis.

Review of current and potential future pharmacological treatments in nonalcoholic steatohepatitis.

The Relationship Between Aortic Root Size and Hypertension: An Unsolved Conundrum.

Thoracic aortic aneurysms rupture and dissection are among the most devastating vascular diseases, being characterized by elevated mortality, despite improvements in diagnostic imaging and surgical techniques.An increased aortic root diameter (ARD) represents the main risk factor for thoracic aortic dissection and rupture and for aortic valve regurgitation.Even though arterial hypertension is commonly regarded as a predisposing condition for the development of thoracic aorta aneurysms, the role of blood pressure (BP) as determinant of aortic root enlargement is still controversial. The use of different methods for indexation of ARD may have in part contributed to the heterogeneous findings obtained in the investigations exploring the relationships between ARD and BP. Indeed, the best methods for ARD indexation, as well as the normal values of aortic root size, are still a matter of debate.Several non-hemodynamic factors influence ARD, including age, gender, and anthropometric variables, such as height, weight and their derivatives body surface area (BSA) and body mass index. Of these factors, anthropometric variables have the greatest impact.Several studies documented an association between ARD enlargement, assessed by echocardiography, and some indices of hypertensive target organ damage such as left ventricular hypertrophy, diastolic dysfunction, and carotid intima-media thickening. Recently, we found that ARD, expressed either as absolute values or normalized for BSA (ARD/BSA) or height (ARD/H), was significantly greater in hypertensive subjects with chronic kidney disease (CKD) when compared to their counterparts with normal renal function. Moreover, at univariate analyses estimated glomerular filtration rate (eGFR) showed significant inverse correlations with ARD not indexed and with ARD/BSA and ARD/H. Taking into account the effect of age, sex, duration of hypertension and other potentially confounding factors, in multiple regression analyses, only the association of GFR with ARD/H and that between GFR and ARD/BSA remained statistically significant. The receiver-operating characteristic curve analysis revealed that an estimated GFR of about 50ml/min/1.73m2 represents the better threshold to distinguish hypertensive patients with dilated aortic root from those with a normal one.Some population-based studies showed that an enlarged ARD might predict an adverse prognosis, even in absence of aneurysmatic alterations.In the Cardiovascular Health Study, a dilated aortic root was independently associated with an increased risk for stroke, cardiovascular and total mortality in both sexes and with incident congestive heart failure only in men. The relationship between ARD and heart failure has been observed also in the Framingham Heart Study. More recently, the PAMELA (Pressioni Arteriose Monitorate E Loro Associazioni) study demonstrated an independent relationship of ARD/H with incident cardiovascular morbidity and mortality.Although the relationship between BP and aortic root size is still a matter of debate, increasing evidence seems to support the notion that aortic root dilatation, even in absence of aneurysmatic alterations, may be regarded as an hypertensive organ damage paralleling other preclinical markers whose unfavourable prognostic significance is firmly established. Future studies are needed to assess whether or not antihypertensive therapy is able to reduce aortic root dimension and the increased risk associated with its enlargement.

Incidence and Management of Proteasome Inhibitor-Related Cardiotoxicity in Multiple Myeloma Patients at Memorial Sloan Kettering Cancer Center

Introduction: Given that the rate of cardiovascular (CV) morbidity increases with age and the median age of patients with multiple myeloma (MM) is 65, CV complications can occur during MM treatment. The proteasome inhibitors (PIs), bortezomib and carfilzomib, may play a role in the development of treatment-related cardiotoxicity as suggested by phase 2 clinical studies and a phase 3 trial (Stewart AK et al. N Engl J Med 2015;372:142-52). Reported treatment-related cardiotoxicity includes hypertension, congestive heart failure (CHF), myocardial infarction, and cardiac arrest. The objectives of this study are to define the incidence of cardiotoxicity in MM patients treated with bortezomib and carfilzomib and to evaluate whether the dose and pre-existing cardiac history affects that incidence.Study design and methods:Using the pharmacy database, we identified all MM patients treated at Memorial Sloan Kettering Cancer Center between 1/2010 to 10/2014 who were treated with bortezomib or carfilzomib in the second-line and relapsed refractory setting. Of note, all patients in the carfilzomib arm received prior bortezomib; thus, MM patients in the carfilzomib arm were more heavily pretreated and the two arms should be compared with caution. Data collected included: baseline demographics, baseline disease status, treatment given including dose and number of cycles, baseline cardiovascular comorbidities and medications, and pre- and post-treatment ejection fraction. Cardiotoxicity recorded was defined as grade 3 or more (requiring intervention) and included: hypertension, CHF, coronary artery disease, pulmonary hypertension, myocardial infarction, stroke, and/or arrhythmias. Descriptive statistics were used to analyze baseline demographics, including median and range for continuous variables and frequency and percentage for categorical variables. Fisher's exact test was used to assess the association between clinical and treatment characteristics and cardiotoxicity.Results: 157 patients were eligible for analysis with 47 in the bortezomib arm and 110 in the carfilzomib arm. The overall incidence of cardiotoxicity across both arms was 17% with an incidence of 9% (n = 4) and 20% (n = 22) in the bortezomib and carfilzomib arms, respectively. The most common events reported were arrhythmias (n = 3) with bortezomib and CHF (n = 12) with carfilzomib. The incidence of CHF and cardiomyopathy was 4% and 19% in the bortezomib and the more heavily pretreated carfilzomib arms, respectively. Baseline cardiac comorbidities were not found to increase the risk of cardiotoxicity while on treatment with carfilzomib (p = 0.815); due to small numbers, we were unable to assess this aspect in the bortezomib arm. Based on a categorization of carfilzomib dose (≤20 mg/m2, 27 mg/m2, or ≥36 mg/m2) starting on cycle 2, there was a significant association between the dose level received and cardiotoxicity (p=0.003); patients treated at dose level ≥36 mg/m2 were most likely to have a cardiac-related event while on therapy. Patients receiving the higher doses were treated on a clinical trial (Lendvai et al. Blood 2014;124:899-906), and they were among the most heavily pretreated. Management of cardiac events with carfilzomib was largely supportive with all patients requiring pharmacological intervention, 64% (n= 14) requiring hospital admission, and 73% (n = 16) requiring treatment delays.Conclusion: Grade 3 or more cardiotoxicity is a potential complication of treatment with PIs. However, there is no increased risk of CV deaths noted in our study. The results show a higher risk of cardiac toxicity in heavily pretreated MM patients receiving higher doses (≥36 mg/m2) of carfilzomib. The number of prior lines of therapy is a major factor when defining CV events in relation to a given therapy. Importantly, both carfilzomib and bortezomib are highly efficacious anti-myeloma drugs; CV risks should be assessed for individual patients and in relation to benefits. DisclosuresLandgren:BMJ Publishing: Honoraria; Medscape: Honoraria; Bristol-Myers Squibb: Honoraria; Celgene: Honoraria; Onyx: Honoraria; International Myeloma Foundation: Research Funding; Onyx: Research Funding; BMJ Publishing: Consultancy; Medscape: Consultancy; Bristol-Myers Squibb: Consultancy; Celgene: Consultancy; Onyx: Consultancy.