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BackgroundA better understanding is needed of the burdens and benefits of left ventricular assist device (LVAD) implantation on patients' physical, mental, and social well-being. The purpose of this report was to evaluate the validity of Patient-Reported Outcomes Measurement Information System (PROMIS) measures for LVAD patients and to estimate clinically important score differences likely to have implications for patient treatment or care.MethodsAdults from 12 sites across all US geographic regions completed PROMIS measures ≥3 months post-LVAD implantation. Other patient-reported outcomes (eg, Kansas City Cardiomyopathy Questionnaire-12 item), clinician ratings, performance tests, and clinical adverse events were used as validity indicators. Criterion and construct validity and clinically important differences were estimated with Pearson correlations, ANOVA methods, and Cohen d effect sizes.ResultsParticipants' (n=648) mean age was 58 years, and the majority were men (78%), non-Hispanic White people (68%), with dilated cardiomyopathy (55%), long-term implantation strategy (57%), and New York Heart Association classes I and II (54%). Most correlations between validity indicators and PROMIS measures were medium to large (≥0.3; p<0.01). Most validity analyses demonstrated medium-to-large effect sizes (≥0.5) and clinically important differences in mean PROMIS scores (up to 14.8 points). Ranges of minimally important differences for 4 PROMIS measures were as follows: fatigue (3-5 points), physical function (2-3), ability to participate in social roles and activities (3), and satisfaction with social roles and activities (3-5).ConclusionsThe findings provide convincing evidence for the relevance and validity of PROMIS physical, mental, and social health measures in patients from early-to-late post-LVAD implantation. Findings may inform shared decision-making when patients consider treatment options. Patients with an LVAD, their caregivers, and their clinicians should

AimsIn heart failure (HF) with preserved ejection fraction (HFpEF), excessive redistribution of blood volume into the central circulation leads to elevations of intracardiac pressures with exercise limitations. Splanchnic ablation for volume management (SAVM) has been proposed as a therapeutic intervention. Here we present preliminary safety and efficacy data from the initial roll-in cohort of the REBALANCE-HF trial.Methods and resultsThe open-label (roll-in) arm of REBALANCE-HF will enrol up to 30 patients, followed by the randomized, sham-controlled portion of the trial (up to 80 additional patients). Patients with HF, left ventricular ejection fraction (LVEF) ≥50%, and invasive peak exercise pulmonary capillary wedge pressure (PCWP) ≥25 mmHg underwent SAVM. Baseline and follow-up assessments included resting and exercise PCWP, New York Heart Association (NYHA) class, Kansas City Cardiomyopathy Questionnaire (KCCQ), 6-min walk test, and N-terminal pro-B-type natriuretic peptide (NT-proBNP). Efficacy and safety were assessed at 1 and 3 months. Here we report on the first 18 patients with HFpEF that have been enrolled into the roll-in, open-label arm of the study across nine centres; 14 (78%) female; 16 (89%) in NYHA class III; and median (interquartile range) age 75.2 (68.4-81) years, LVEF 61.0 (56.0-63.2)%, and average (standard deviation) 20 W exercise PCWP 36.4 (±8.6) mmHg. All 18 patients were successfully treated. Three non-serious moderate device/procedure-related adverse events were reported. At 1-month, the mean PCWP at 20 W exercise decreased from 36.4 (±8.6) to 28.9 (±7.8) mmHg (p < 0.01), NYHA class improved by at least one class in 33% of patients (p = 0.02) and KCCQ score improved by 22.1 points (95% confidence interval 9.4-34.2) (p < 0.01).ConclusionThe preliminary open-label results from the multicentre REBALANCE-HF roll-in cohort support the safety and efficacy of SAVM in HFpEF. The findings require confirmation in the ongoing r

OBJECTIVE: Tracking changes in hemodynamic congestion and the consequent proactive readjustment of treatment has shown efficacy in reducing hospitalizations for patients with heart failure (HF). However, the cost-prohibitive nature of these invasive sensing systems precludes their usage in the large patient population affected by HF. The objective of this research is to estimate the changes in pulmonary artery mean pressure (PAM) and pulmonary capillary wedge pressure (PCWP) following vasodilator infusion during right heart catheterization (RHC), using changes in simultaneously recorded wearable seismocardiogram (SCG) signals captured with a small wearable patch. METHODS: A total of 20 patients with HF (20% women, median age 55 (interquartile range (IQR), 44-64) years, ejection fraction 24 (IQR, 16-43)) were fitted with a wearable sensing patch and underwent RHC with vasodilator challenge. We divided the dataset randomly into a training-testing set (n = 15) and a separate validation set (n = 5). We developed globalized (population) regression models to estimate changes in PAM and PCWP from the changes in simultaneously recorded SCG. RESULTS: The regression model estimated both pressures with good accuracies: root-mean-square-error (RMSE) of 2.5 mmHg and R2 of 0.83 for estimating changes in PAM, and RMSE of 1.9 mmHg and R2 of 0.93 for estimating changes in PCWP for the training-testing set, and RMSE of 2.7 mmHg and R2 of 0.81 for estimating changes in PAM, and RMSE of 2.9 mmHg and R2 of 0.95 for estimating changes in PCWP for the validation set respectively. CONCLUSION: Changes in wearable SCG signals may be used to track acute changes in intracardiac hemodynamics in patients with HF. SIGNIFICANCE: This method holds promise in tracking longitudinal changes in hemodynamic congestion in hemodynamically-guided remote home monitoring and treatment for patients with HF.

AIMS: Prognostic enrichment strategies can make trials more efficient, although potentially at the cost of diminishing external validity. Whether using a risk score to identify a population at increased mortality risk could improve trial efficiency is uncertain. We aimed to assess whether Machine learning Assessment of RisK and EaRly mortality in Heart Failure (MARKER-HF), a previously validated risk score, could improve clinical trial efficiency. METHODS AND RESULTS: Mortality rates and association of MARKER-HF with all-cause death by 1 year were evaluated in four community-based heart failure (HF) and five HF clinical trial cohorts. Sample size required to assess effects of an investigational therapy on mortality was calculated assuming varying underlying MARKER-HF risk and proposed treatment effect profiles. Patients from community-based HF cohorts (n = 11 297) had higher observed mortality and MARKER-HF scores than did clinical trial patients (n = 13 165) with HF with either reduced ejection fraction (HFrEF) or preserved ejection fraction (HFpEF). MARKER-HF score was strongly associated with risk of 1-year mortality both in the community (hazard ratio [HR] 1.48, 95% confidence interval [CI] 1.44-1.52) and clinical trial cohorts with HFrEF (HR 1.41, 95% CI 1.30-1.54), and HFpEF (HR 1.74, 95% CI 1.53-1.98), per 0.1 increase in MARKER-HF. Using MARKER-HF to identify patients for a hypothetical clinical trial assessing mortality reduction with an intervention, enabled a reduction in sample size required to show benefit. CONCLUSION: Using a reliable predictor of mortality such as MARKER-HF to enrich clinical trial populations provides a potential strategy to improve efficiency by requiring a smaller sample size to demonstrate a clinical benefit.

BackgroundThe LATERAL trial validated the safety and efficacy of the thoracotomy approach for implantation of the HeartWare HVAD System, leading to Food and Drug Administration approval. We sought to analyze 24-month adverse event (AE) rates, including a temporal analysis of the risk profile, associated with the thoracotomy approach for the HVAD system.MethodsAEs from the LATERAL trial were evaluated over 2 years postimplant. Data was obtained from the Interagency Registry for Mechanically Assisted Circulatory Support database for 144 enrolled United States and Canadian patients. Temporal AE profiles were expressed as events per patient year.ResultsDuring 162.5 patient years of support, there were 25 driveline infections (0.15 events per patient year), 50 gastrointestinal bleeds (0.31 events per patient year), and 21 strokes (0.13 events per patient year). Longitudinal AE analysis at follow-up intervals of <30 and 30 to 180 days, and 6 to 12 and 12 to 24 months revealed the highest AE rate at <30 days, with a decrease in total AEs within the first 6 months. After 6 months, most AE rates either stabilized or decreased through 2 years, including a 95% overall freedom from disabling stroke.ConclusionsTwo-year follow-up of the LATERAL trial revealed a favorable morbidity profile in patients supported with the HVAD system, as AE rates were more likely to occur in the first 30 days postimplant, and overall AE rates were significantly reduced after 6 months. Importantly, 2-year freedom from disabling stroke was 95%. These data further support the improving AE profile of patients on long-term HVAD support. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT02268942.

Objective: Pregnancy requires a complex physiological adaptation of the maternal cardiovascular system, which is disrupted in women with pregnancies complicated by preeclampsia, putting them at higher risk of future cardiovascular events. The measurement of body movements in response to cardiac ejection via ballistocardiogram (BCG) can be used to assess cardiovascular hemodynamics noninvasively in women with preeclampsia. Methods: Using a previously validated, modified weighing scale for assessment of cardiovascular hemodynamics through measurement of BCG and electrocardiogram (ECG) signals, we collected serial measurements throughout pregnancy and postpartum and analyzed data in 30 women with preeclampsia and 23 normotensive controls. Using BCG and ECG signals, we extracted measures of cardiac output, J-wave amplitude × heart rate (J-amp × HR). Mixed-effect models with repeated measures were used to compare J-amp × HRs between groups at different time points in pregnancy and postpartum. Results: In normotensive controls, the J-amp × HR was significantly lower early postpartum (E-PP) compared with the second trimester (T2; p = 0.016) and third trimester (T3; p = 0.001). Women with preeclampsia had a significantly lower J-amp × HR compared with normotensive controls during the first trimester (T1; p = 0.026). In the preeclampsia group, there was a trend toward an increase in J-amp × HR from T1 to T2 and then a drop in J-amp × HR at T3 and further drop at E-PP. Conclusions: We observe cardiac hemodynamic changes consistent with those reported using well-validated tools. In pregnancies complicated by preeclampsia, the maximal force of contraction is lower, suggesting lower cardiac output and a trend in hemodynamics consistent with the hyperdynamic disease model of preeclampsia.

BackgroundAfrican American and Hispanic postmenopausal women have the highest risk for heart failure compared with other races, but heart failure prevalence is lower than expected in some national cohorts. It is unknown whether psychosocial factors are associated with lower risk of incident heart failure hospitalization among high-risk postmenopausal minority women.Methods and resultsUsing the Women's Health Initiative Study, African American and US Hispanic women were classified as high-risk for incident heart failure hospitalization with 1 or more traditional heart failure risk factors and the highest tertile heart failure genetic risk scores. Positive psychosocial factors (optimism, social support, religion) and negative psychosocial factors (living alone, social strain, depressive symptoms) were measured using validated survey instruments at baseline. Adjusted subdistribution hazard ratios of developing heart failure hospitalization were determined with death as a competing risk. Positive deviance indicated not developing incident heart failure hospitalization with 1 or more risk factors and the highest tertile for genetic risk. Among 7986 African American women (mean follow-up of 16 years), 27.0% demonstrated positive deviance. Among high-risk African American women, optimism was associated with modestly reduced risk of heart failure hospitalization (subdistribution hazard ratio 0.94, 95% confidence interval 0.91-0.99), and social strain was associated with modestly increased risk of heart failure hospitalization (subdistribution hazard ratio 1.07, 95% confidence interval 1.02-1.12) in the initial models; however, no psychosocial factors were associated with heart failure hospitalization in fully adjusted analyses. Among 3341 Hispanic women, 25.1% demonstrated positive deviance. Among high-risk Hispanic women, living alone was associated with increased risk of heart failure hospitalization (subdistribution hazard ratio 1.97, 95% confidence interval 1.06-3.63) i

BackgroundAfrican American and Hispanic postmenopausal women have the highest risk for heart failure compared with other races, but heart failure prevalence is lower than expected in some national cohorts. It is unknown whether psychosocial factors are associated with lower risk of incident heart failure hospitalization among high-risk postmenopausal minority women.Methods and resultsUsing the Women's Health Initiative Study, African American and US Hispanic women were classified as high-risk for incident heart failure hospitalization with 1 or more traditional heart failure risk factors and the highest tertile heart failure genetic risk scores. Positive psychosocial factors (optimism, social support, religion) and negative psychosocial factors (living alone, social strain, depressive symptoms) were measured using validated survey instruments at baseline. Adjusted subdistribution hazard ratios of developing heart failure hospitalization were determined with death as a competing risk. Positive deviance indicated not developing incident heart failure hospitalization with 1 or more risk factors and the highest tertile for genetic risk. Among 7986 African American women (mean follow-up of 16 years), 27.0% demonstrated positive deviance. Among high-risk African American women, optimism was associated with modestly reduced risk of heart failure hospitalization (subdistribution hazard ratio 0.94, 95% confidence interval 0.91-0.99), and social strain was associated with modestly increased risk of heart failure hospitalization (subdistribution hazard ratio 1.07, 95% confidence interval 1.02-1.12) in the initial models; however, no psychosocial factors were associated with heart failure hospitalization in fully adjusted analyses. Among 3341 Hispanic women, 25.1% demonstrated positive deviance. Among high-risk Hispanic women, living alone was associated with increased risk of heart failure hospitalization (subdistribution hazard ratio 1.97, 95% confidence interval 1.06-3.63) i

Background: There is conflicting observational data on the survival benefit cardiac implantable electronic devices (CIED) in patients with LVADs. Methods: Patients in whom an LVAD was implanted between January 2008 and April 2017 in the multinational Trans-Atlantic Registry on VAD and Transplant (TRAViATA) registry were separated into four groups based on the presence of CIED prior to LVAD implantation: none (n = 146), implantable cardiac defibrillator (ICD) (n = 239), cardiac resynchronization without defibrillator (CRT-P) (n = 28), and CRT with defibrillator (CRT-D) (n = 111). Results: A total of 524 patients (age 52 years ±12, 84.4% male) were followed for 354 (interquartile range: 166–701) days. After multivariable adjustment, there were no differences in survival across the groups. In comparison to no device, only CRT-D was associated with late right ventricular failure (RVF) (hazard ratio 2.85, 95% confidence interval [CI] 1.42–5.72, p = 0.003). There was no difference in risk of early RVF across the groups or risk of ICD shocks between those with ICD and CRT-D. Conclusion: In a multinational registry of patients with LVADs, there were no differences in survival with respect to CIED subtype. However, patients with a pre-existing CRT-D had a higher likelihood of late RVF suggesting significant lon

Objective: Pregnancy requires a complex physiological adaptation of the maternal cardiovascular system, which is disrupted in women with pregnancies complicated by preeclampsia, putting them at higher risk of future cardiovascular events. The measurement of body movements in response to cardiac ejection via ballistocardiogram (BCG) can be used to assess cardiovascular hemodynamics noninvasively in women with preeclampsia. Methods: Using a previously validated, modified weighing scale for assessment of cardiovascular hemodynamics through measurement of BCG and electrocardiogram (ECG) signals, we collected serial measurements throughout pregnancy and postpartum and analyzed data in 30 women with preeclampsia and 23 normotensive controls. Using BCG and ECG signals, we extracted measures of cardiac output, J-wave amplitude × heart rate (J-amp × HR). Mixed-effect models with repeated measures were used to compare J-amp × HRs between groups at different time points in pregnancy and postpartum. Results: In normotensive controls, the J-amp × HR was significantly lower early postpartum (E-PP) compared with the second trimester (T2; p = 0.016) and third trimester (T3; p = 0.001). Women with preeclampsia had a significantly lower J-amp × HR compared with normotensive controls during the first trimester (T1; p = 0.026). In the preeclampsia group, there was a trend toward an increase in J-amp × HR from T1 to T2 and then a drop in J-amp × HR at T3 and further drop at E-PP. Conclusions: We observe cardiac hemodynamic changes consistent with those reported using well-validated tools. In pregnancies complicated by preeclampsia, the maximal force of contraction is lower, suggesting lower cardiac output and a trend in hemodynamics consistent with the hyperdynamic disease model of preeclampsia.

BackgroundAfrican American and Hispanic postmenopausal women have the highest risk for heart failure compared with other races, but heart failure prevalence is lower than expected in some national cohorts. It is unknown whether psychosocial factors are associated with lower risk of incident heart failure hospitalization among high-risk postmenopausal minority women.Methods and resultsUsing the Women's Health Initiative Study, African American and US Hispanic women were classified as high-risk for incident heart failure hospitalization with 1 or more traditional heart failure risk factors and the highest tertile heart failure genetic risk scores. Positive psychosocial factors (optimism, social support, religion) and negative psychosocial factors (living alone, social strain, depressive symptoms) were measured using validated survey instruments at baseline. Adjusted subdistribution hazard ratios of developing heart failure hospitalization were determined with death as a competing risk. Positive deviance indicated not developing incident heart failure hospitalization with 1 or more risk factors and the highest tertile for genetic risk. Among 7986 African American women (mean follow-up of 16 years), 27.0% demonstrated positive deviance. Among high-risk African American women, optimism was associated with modestly reduced risk of heart failure hospitalization (subdistribution hazard ratio 0.94, 95% confidence interval 0.91-0.99), and social strain was associated with modestly increased risk of heart failure hospitalization (subdistribution hazard ratio 1.07, 95% confidence interval 1.02-1.12) in the initial models; however, no psychosocial factors were associated with heart failure hospitalization in fully adjusted analyses. Among 3341 Hispanic women, 25.1% demonstrated positive deviance. Among high-risk Hispanic women, living alone was associated with increased risk of heart failure hospitalization (subdistribution hazard ratio 1.97, 95% confidence interval 1.06-3.63) i

BackgroundThe LATERAL trial validated the safety and efficacy of the thoracotomy approach for implantation of the HeartWare HVAD System, leading to Food and Drug Administration approval. We sought to analyze 24-month adverse event (AE) rates, including a temporal analysis of the risk profile, associated with the thoracotomy approach for the HVAD system.MethodsAEs from the LATERAL trial were evaluated over 2 years postimplant. Data was obtained from the Interagency Registry for Mechanically Assisted Circulatory Support database for 144 enrolled United States and Canadian patients. Temporal AE profiles were expressed as events per patient year.ResultsDuring 162.5 patient years of support, there were 25 driveline infections (0.15 events per patient year), 50 gastrointestinal bleeds (0.31 events per patient year), and 21 strokes (0.13 events per patient year). Longitudinal AE analysis at follow-up intervals of <30 and 30 to 180 days, and 6 to 12 and 12 to 24 months revealed the highest AE rate at <30 days, with a decrease in total AEs within the first 6 months. After 6 months, most AE rates either stabilized or decreased through 2 years, including a 95% overall freedom from disabling stroke.ConclusionsTwo-year follow-up of the LATERAL trial revealed a favorable morbidity profile in patients supported with the HVAD system, as AE rates were more likely to occur in the first 30 days postimplant, and overall AE rates were significantly reduced after 6 months. Importantly, 2-year freedom from disabling stroke was 95%. These data further support the improving AE profile of patients on long-term HVAD support. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT02268942.

BackgroundHeart failure (HF) is a leading cause of cardiac morbidity among women, whose risk factors differ from those in men. We used machine-learning approaches to develop risk- prediction models for incident HF in a cohort of postmenopausal women from the Women's Health Initiative (WHI).MethodsWe used 2 machine-learning methods-Least Absolute Shrinkage and Selection Operator (LASSO) and Classification and Regression Trees (CART)-to perform variable selection on 1227 baseline WHI variables for the primary outcome of incident HF. These variables were then used to construct separate Cox proportional hazard models, and we compared these results, using receiver-operating characteristic (ROC) curve analysis, against a comparator model built using variables from the Atherosclerosis Risk in Communities (ARIC) HF prediction model. We analyzed 43,709 women who had 2222 incident HF events; median follow-up was 14.3 years.ResultsLASSO selected 10 predictors, and CART selected 11 predictors. The highest correlation between selected variables was 0.46. In addition to selecting well-established predictors such as age, myocardial infarction, and smoking, novel predictors included physical function, number of pregnancies, number of previous live births and age at menopause. In ROC analysis, the CART-derived model had the highest C-statistic of 0.83 (95% confidence interval [CI], 0.81-0.85), followed by LASSO 0.82 (95% CI, 0.81-0.84) and ARIC 0.73 (95% CI, 0.70-0.76).ConclusionsMachine-learning approaches can be used to develop HF risk-prediction models that can have better discrimination compared with an established HF risk model and may provide a basis for investigating novel HF predictors.

BACKGROUND: Prior studies of structural and electrocardiographic changes in arrhythmogenic right ventricular (RV) cardiomyopathy and their role in predicting ventricular arrhythmias (ventricular tachycardia) have shown conflicting results. METHODS: We reviewed 405 ECGs, 315 transthoracic echocardiographies, and 441 implantable cardioverter defibrillator interrogations in 64 arrhythmogenic RV cardiomyopathy patients (56% men, mean age [SD], 44.2 [14.6] years) over a mean follow-up of 10 (range, 2.3-19) years. Generalized estimating equations were used to identify the association between ECG abnormalities, clinical variables, and transthoracic echocardiographic measurements (>mild degree of tricuspid regurgitation, RV outflow tract diameter in parasternal long axis and short axis, RV end-diastolic area, fractional area change). RESULTS: There was a 4.65 (95% CI, 0.51%-8.8%) increase in RV end-diastolic area, a 3.75 (95% CI, 1.17%-6.34%) decrease in fractional area change, and 1.9 (95% CI, 1.3-2.8) higher odds (odds ratio) of RV wall motion abnormality with every 5-year increase in age after patients' first transthoracic echocardiography. >Mild tricuspid regurgitation was an independent predictor of RV enlargement and dysfunction (hazard ratio of >10% drop in fractional area change from baseline [95% CI], 3.51 [1.77-6.95] and hazard ratio of >10% increase in RV end-diastolic area from baseline [95% CI], 4.90 [2.52-9.52]). Patients with implantable cardioverter defibrillator were more likely to develop >mild tricuspid regurgitation and larger structural and functional disease progression. More pronounced increase in RV end-diastolic area was translated into higher rates of any ventricular tachycardia. Inferior T-wave inversions and sum of R waves (mm) in V1 to V3 were predictors of RV enlargement and dysfunction with the former also predicting risk of any ventricular tachycardia. CONCLUSIONS: Arrhythmogenic RV cardiomyopathy is a progressive disease. Tric

ObjectiveLeft ventricular assist devices (LVADs) fail in up to 10% of patients due to the development of pump thrombosis. Remote monitoring of patients with LVADs can enable early detection and, subsequently, treatment and prevention of pump thrombosis. We assessed whether acoustical signals measured on the chest of patients with LVADs, combined with machine learning algorithms, can be used for detecting pump thrombosis.Methods13 centrifugal pump (HVAD) recipients were enrolled in the study. When hospitalized for suspected pump thrombosis, clinical data and acoustical recordings were obtained at admission, prior to and after administration of thrombolytic therapy, and every 24 hours until laboratory and pump parameters normalized. First, we selected the most important features among our feature set using LDH-based correlation analysis. Then using these features, we trained a logistic regression model and determined our decision threshold to differentiate between thrombosis and non-thrombosis episodes.ResultsAccuracy, sensitivity and precision were calculated to be 88.9%, 90.9% and 83.3%, respectively. When tested on the post-thrombolysis data, our algorithm suggested possible pump abnormalities that were not identified by the reference pump power or biomarker abnormalities.SignificanceWe showed that the acoustical signatures of LVADs can be an index of mechanical deterioration and, when combined with machine learning algorithms, provide clinical decision support regarding the presence of pump thrombosis.

ObjectiveTo improve home monitoring of heart failure patients so as to reduce emergency room visits and hospital readmissions. We aim to do this by analyzing the ballistocardiogram (BCG) to evaluate the clinical state of the patient.Methods1) High quality BCG signals were collected at home from HF patients after discharge. 2) The BCG recordings were preprocessed to exclude outliers and artifacts. 3) Parameters of the BCG that contain information about the cardiovascular system were extracted. These features were used for the task of classification of the BCG recording based on the status of HF.ResultsThe best AUC score for the task of classification obtained was 0.78 using slight variant of the leave one subject out validation method.ConclusionThis work demonstrates that high quality BCG signals can be collected in a home environment and used to detect the clinical state of HF patients.SignificanceIn future work, a clinician/caregiver can be introduced into the system so that appropriate interventions can be performed based on the clinical state monitored at home.

BackgroundTo estimate oxygen uptake (VO2) from cardiopulmonary exercise testing (CPX) using simultaneously recorded seismocardiogram (SCG) and electrocardiogram (ECG) signals captured with a small wearable patch. CPX is an important risk stratification tool for patients with heart failure (HF) owing to the prognostic value of the features derived from the gas exchange variables such as VO2. However, CPX requires specialized equipment, as well as trained professionals to conduct the study.Methods and resultsWe have conducted a total of 68 CPX tests on 59 patients with HF with reduced ejection fraction (31% women, mean age 55 ± 13 years, ejection fraction 0.27 ± 0.11, 79% stage C). The patients were fitted with a wearable sensing patch and underwent treadmill CPX. We divided the dataset into a training-testing set (n = 44) and a separate validation set (n = 24). We developed globalized (population) regression models to estimate VO2 from the SCG and ECG signals measured continuously with the patch. We further classified the patients as stage D or C using the SCG and ECG features to assess the ability to detect clinical state from the wearable patch measurements alone. We developed the regression and classification model with cross-validation on the training-testing set and validated the models on the validation set. The regression model to estimate VO2 from the wearable features yielded a moderate correlation (R2 of 0.64) with a root mean square error of 2.51 ± 1.12 mL · kg-1 · min-1 on the training-testing set, whereas R2 and root mean square error on the validation set were 0.76 and 2.28 ± 0.93 mL · kg-1 · min-1, respectively. Furthermore, the classification of clinical state yielded accuracy, sensitivity, specificity, and an area under the receiver operating characteristic curve values of 0.84, 0.91, 0.64, and 0.74, respectively, for the training-testing set, and 0.83, 0.86, 0.67, and 0.92, respectively, for the validation set.ConclusionsWearable SCG and E

BackgroundThe 2018 US Physical Activity Guidelines recommend reducing sedentary behavior (SB) for cardiovascular health. SB's role in heart failure (HF) is unclear.MethodsWe studied 80 982 women in the Women's Health Initiative Observational Study, aged 50 to 79 years, who were without known HF and reported ability to walk ≥1 block unassisted at baseline. Mean follow-up was 9 years for physician-adjudicated incident HF hospitalization (1402 cases). SB was assessed repeatedly by questionnaire. Time-varying total SB was categorized according to awake time spent sitting or lying down (≤6.5, 6.6-9.5, >9.5 h/d); sitting time (≤4.5, 4.6-8.5, >8.5 h/d) was also evaluated. Hazard ratios and 95% CI were estimated using Cox regression.ResultsControlling for age, race/ethnicity, education, income, smoking, alcohol, menopausal hormone therapy, and hysterectomy status, higher HF risk was observed across incremental tertiles of time-varying total SB (hazard ratios [95% CI], 1.00 [referent], 1.15 [1.01-1.31], 1.42 [1.25-1.61], trend P<0.001) and sitting time (1.00 [referent], 1.14 [1.01-1.28], 1.54 [1.34-1.78], trend P<0.001). The inverse trends remained significant after further controlling for comorbidities including time-varying myocardial infarction and coronary revascularization (hazard ratios: SB, 1.00, 1.11, 1.27; sitting, 1.00, 1.09, 1.37, trend P<0.001 each) and for baseline physical activity (hazard ratios: SB 1.00, 1.10, 1.24; sitting 1.00, 1.08, 1.33, trend P<0.001 each). Associations with SB exposures were not different according to categories of baseline age, race/ethnicity, body mass index, physical activity, physical functioning, diabetes, hypertension, or coronary heart disease.ConclusionsSB was associated with increased risk of incident HF hospitalization in postmenopausal women. Targeted efforts to reduce SB could enhance HF prevention in later life.

Background Long-term corticosteroid therapy is the standard of care for treatment of cardiac sarcoidosis (CS). The efficacy of long-term corticosteroid-sparing immunosuppression in CS is unknown. The goal of this study was to assess the efficacy of methotrexate with or without adalimumab for long-term disease suppression in CS, and to assess recurrence and adverse event rates after immunosuppression discontinuation. Methods and Results Retrospective chart review identified treatment-naive CS patients at a single academic medical center who received corticosteroid-sparing maintenance therapy. Demographics, cardiac uptake of 18-fluorodeoxyglucose, and adverse cardiac events were compared before and during treatment and between those with persistent or interrupted immunosuppression. Twenty-eight CS patients were followed for a mean 4.1 (SD 1.5) years. Twenty-five patients received 4 to 8 weeks of high-dose prednisone (>30 mg/day), followed by taper and maintenance therapy with methotrexate±low-dose prednisone (low-dose prednisone, <10 mg/day). Adalimumab was added in 19 patients with persistently active CS or in those with intolerance to methotrexate. Methotrexate±low-dose prednisone resulted in initial reduction (88%) or elimination (60%) of 18-fluorodeoxyglucose uptake, and patients receiving adalimumab-containing regimens experienced improved (84%) or resolved (63%) 18-fluorodeoxyglucose uptake. Radiologic relapse occurred in 8 of 9 patients after immunosuppression cessation, 4 patients on methotrexate-containing regimens, and in no patients on adalimumab-containing regimens. Conclusions Corticosteroid-sparing regimens containing methotrexate with or without adalimumab is an effective maintenance therapy in patients after an initial response is confirmed. Disease recurrence in patients on and off immunosuppression support need for ongoing radiologic surveillance regardless of immunosuppression regimen.

Background Long-term corticosteroid therapy is the standard of care for treatment of cardiac sarcoidosis (CS). The efficacy of long-term corticosteroid-sparing immunosuppression in CS is unknown. The goal of this study was to assess the efficacy of methotrexate with or without adalimumab for long-term disease suppression in CS, and to assess recurrence and adverse event rates after immunosuppression discontinuation. Methods and Results Retrospective chart review identified treatment-naive CS patients at a single academic medical center who received corticosteroid-sparing maintenance therapy. Demographics, cardiac uptake of 18-fluorodeoxyglucose, and adverse cardiac events were compared before and during treatment and between those with persistent or interrupted immunosuppression. Twenty-eight CS patients were followed for a mean 4.1 (SD 1.5) years. Twenty-five patients received 4 to 8 weeks of high-dose prednisone (>30 mg/day), followed by taper and maintenance therapy with methotrexate±low-dose prednisone (low-dose prednisone, <10 mg/day). Adalimumab was added in 19 patients with persistently active CS or in those with intolerance to methotrexate. Methotrexate±low-dose prednisone resulted in initial reduction (88%) or elimination (60%) of 18-fluorodeoxyglucose uptake, and patients receiving adalimumab-containing regimens experienced improved (84%) or resolved (63%) 18-fluorodeoxyglucose uptake. Radiologic relapse occurred in 8 of 9 patients after immunosuppression cessation, 4 patients on methotrexate-containing regimens, and in no patients on adalimumab-containing regimens. Conclusions Corticosteroid-sparing regimens containing methotrexate with or without adalimumab is an effective maintenance therapy in patients after an initial response is confirmed. Disease recurrence in patients on and off immunosuppression support need for ongoing radiologic surveillance regardless of immunosuppression regimen.

Introduction The clinical role of atrial arrhythmias (AA) in arrhythmogenic right ventricular cardiomyopathy (ARVC) and the echocardiographic variables that predict them are not well defined. We describe the prevalence, types, echocardiographic predictors, and management of AA in patients with ARVC. Methods We retrospectively evaluated medical records of 117 patients with definite ARVC (2010 Task Force Criteria) from two tertiary care centers. We identified those patients with sustained AA (>30 seconds), including atrial fibrillation (AF), atrial flutter (AFL), and atrial tachycardia (AT). We collected demographic, genetic, and clinical data. The median follow‐up was 3.4 years (interquartile range = 2.0‐5.7). Results Total 26 patients (22%) had one or more types of AA: AF (n = 19), AFL (n = 9), and AT (n = 8). We performed genetic testing on 84 patients with ARVC (71.8%). Two patients with AA (8%) had peripheral emboli, and one patient (4%) suffered inappropriate implantable cardioverter‐defibrillator shock. We performed catheter ablation of AA in eight patients (31%), with no procedural complications. Right atrial area and left atrial volume index were independently associated with increased odds of AA; odds ratio (OR), 1.1 (95% confidence interval [CI]:1.02‐1.16) (P = .01) and OR, 1.1 (95% CI:1.03‐1.15) (P = .003), respectively. An increase in tricuspid annular plane peak systolic excursion was independently associated with reduced odds; OR, 0.3 (95% CI: 0.1‐0.94) (P = .003). Conclusions Atrial arrhythmias (AA) are common in patients with arrhythmogenic right ventricular cardiomyopathy (ARVC). Inappropriate shocks and systemic emboli may be associated with AA. Atrial size and right ventricular dysfunction may help identify patients with ARVC at increased odds of AA.

BACKGROUND:The higher risk of heart failure (HF) in African-American and Hispanic women compared with white women is related to the higher burden of risk factors (RFs) in minorities. However, it is unclear if there are differences in the association between the number of RFs for HF and the risk of development of HF and death within racial/ethnic groups. METHODS AND RESULTS:In the WHI (Women's Health Initiative; 1993-2010), African-American (n=11 996), white (n=18 479), and Hispanic (n=5096) women with 1, 2, or 3+ baseline RFs were compared with women with 0 RF within their respective racial/ethnic groups to assess risk of developing HF or all-cause mortality before and after HF, using survival analyses. After adjusting for age, socioeconomic status, and hormone therapy, the subdistribution hazard ratio (95% confidence interval) of developing HF increased as number of RFs increased (P<0.0001, interaction of race/ethnicity and RF number P=0.18)-African-Americans 1 RF: 1.80 (1.01-3.20), 2 RFs: 3.19 (1.84-5.54), 3+ RFs: 7.31 (4.26-12.56); Whites 1 RF: 1.27 (1.04-1.54), 2 RFs: 1.95 (1.60-2.36), 3+ RFs: 4.07 (3.36-4.93); Hispanics 1 RF: 1.72 (0.68-4.34), 2 RFs: 3.87 (1.60-9.37), 3+ RFs: 8.80 (3.62-21.42). Risk of death before developing HF increased with subsequent RFs (P<0.0001) but differed by racial/ethnic group (interaction P=0.001). The number of RFs was not associated with the risk of death after developing HF in any group (P=0.25; interaction P=0.48). CONCLUSIONS:Among diverse racial/ethnic groups, an increase in the number of baseline RFs was associated with higher risk of HF and death before HF but was not associated with death after HF. Early RF prevention may reduce the burden of HF across multiple racial/ethnic groups.

ObjectivesThis study prospectively examined physical activity levels and the incidence of heart failure (HF) in 137,303 women, ages 50 to 79 years, and examined a subset of 35,272 women who, it was determined, had HF with preserved ejection fraction (HFpEF) and HF with reduced EF (HFrEF).BackgroundThe role of physical activity in HF risk among older women is unclear, particularly for incidence of HFpEF or HFrEF.MethodsWomen were free of HF and reported ability to walk at least 1 block without assistance at baseline. Recreational physical activity was self-reported. The study documented 2,523 cases of total HF, and 451 and 734 cases of HFrEF and HFpEF, respectively, during a mean 14-year follow-up.ResultsAfter controlling for age, race, education, income, smoking, alcohol, hormone therapy, and hysterectomy status, compared with women who reported no physical activity (reference group), inverse associations were observed across incremental tertiles of total physical activity for overall HF (hazard ratio [HR]: Tertile 1 = 0.89, Tertile 2 = 0.74, Tertile 3 = 0.65; trend p < 0.001), HFpEF (HR: 0.93, 0.70, 0.68; p < 0.001), and HFrEF (HR: 0.81, 0.59, 0.68; p = 0.01). Additional controlling for potential mediating factors included attenuated time-varying coronary heart disease (CHD) (nonfatal myocardial infarction, coronary revascularization) diagnosis but did not eliminate the inverse associations. Walking, the most common form of physical activity in older women, was also inversely associated with HF risks (overall: 1.00, 0.98, 0.93, 0.72; p < 0.001; HFpEF: 1.00, 0.98, 0.87, 0.67; p < 0.001; HFrEF: 1.00, 0.75, 0.78, 0.67; p = 0.01). Associations between total physical activity and HF were consistent across subgroups, defined by age, body mass index, diabetes, hypertension, physical function, and CHD diagnosis. Analysis of physical activity as a time-varying exposure yielded findings comparable to those of baseline physical activity.ConclusionsHigher levels of

BackgroundThe higher risk of heart failure (HF) in African-American and Hispanic women compared with white women is related to the higher burden of risk factors (RFs) in minorities. However, it is unclear if there are differences in the association between the number of RFs for HF and the risk of development of HF and death within racial/ethnic groups.Methods and resultsIn the WHI (Women's Health Initiative; 1993-2010), African-American (n=11 996), white (n=18 479), and Hispanic (n=5096) women with 1, 2, or 3+ baseline RFs were compared with women with 0 RF within their respective racial/ethnic groups to assess risk of developing HF or all-cause mortality before and after HF, using survival analyses. After adjusting for age, socioeconomic status, and hormone therapy, the subdistribution hazard ratio (95% confidence interval) of developing HF increased as number of RFs increased (P<0.0001, interaction of race/ethnicity and RF number P=0.18)-African-Americans 1 RF: 1.80 (1.01-3.20), 2 RFs: 3.19 (1.84-5.54), 3+ RFs: 7.31 (4.26-12.56); Whites 1 RF: 1.27 (1.04-1.54), 2 RFs: 1.95 (1.60-2.36), 3+ RFs: 4.07 (3.36-4.93); Hispanics 1 RF: 1.72 (0.68-4.34), 2 RFs: 3.87 (1.60-9.37), 3+ RFs: 8.80 (3.62-21.42). Risk of death before developing HF increased with subsequent RFs (P<0.0001) but differed by racial/ethnic group (interaction P=0.001). The number of RFs was not associated with the risk of death after developing HF in any group (P=0.25; interaction P=0.48).ConclusionsAmong diverse racial/ethnic groups, an increase in the number of baseline RFs was associated with higher risk of HF and death before HF but was not associated with death after HF. Early RF prevention may reduce the burden of HF across multiple racial/ethnic groups.

BackgroundThe higher risk of heart failure (HF) in African-American and Hispanic women compared with white women is related to the higher burden of risk factors (RFs) in minorities. However, it is unclear if there are differences in the association between the number of RFs for HF and the risk of development of HF and death within racial/ethnic groups.Methods and resultsIn the WHI (Women's Health Initiative; 1993-2010), African-American (n=11 996), white (n=18 479), and Hispanic (n=5096) women with 1, 2, or 3+ baseline RFs were compared with women with 0 RF within their respective racial/ethnic groups to assess risk of developing HF or all-cause mortality before and after HF, using survival analyses. After adjusting for age, socioeconomic status, and hormone therapy, the subdistribution hazard ratio (95% confidence interval) of developing HF increased as number of RFs increased (P<0.0001, interaction of race/ethnicity and RF number P=0.18)-African-Americans 1 RF: 1.80 (1.01-3.20), 2 RFs: 3.19 (1.84-5.54), 3+ RFs: 7.31 (4.26-12.56); Whites 1 RF: 1.27 (1.04-1.54), 2 RFs: 1.95 (1.60-2.36), 3+ RFs: 4.07 (3.36-4.93); Hispanics 1 RF: 1.72 (0.68-4.34), 2 RFs: 3.87 (1.60-9.37), 3+ RFs: 8.80 (3.62-21.42). Risk of death before developing HF increased with subsequent RFs (P<0.0001) but differed by racial/ethnic group (interaction P=0.001). The number of RFs was not associated with the risk of death after developing HF in any group (P=0.25; interaction P=0.48).ConclusionsAmong diverse racial/ethnic groups, an increase in the number of baseline RFs was associated with higher risk of HF and death before HF but was not associated with death after HF. Early RF prevention may reduce the burden of HF across multiple racial/ethnic groups.

ObjectivesThis study prospectively examined physical activity levels and the incidence of heart failure (HF) in 137,303 women, ages 50 to 79 years, and examined a subset of 35,272 women who, it was determined, had HF with preserved ejection fraction (HFpEF) and HF with reduced EF (HFrEF).BackgroundThe role of physical activity in HF risk among older women is unclear, particularly for incidence of HFpEF or HFrEF.MethodsWomen were free of HF and reported ability to walk at least 1 block without assistance at baseline. Recreational physical activity was self-reported. The study documented 2,523 cases of total HF, and 451 and 734 cases of HFrEF and HFpEF, respectively, during a mean 14-year follow-up.ResultsAfter controlling for age, race, education, income, smoking, alcohol, hormone therapy, and hysterectomy status, compared with women who reported no physical activity (reference group), inverse associations were observed across incremental tertiles of total physical activity for overall HF (hazard ratio [HR]: Tertile 1 = 0.89, Tertile 2 = 0.74, Tertile 3 = 0.65; trend p < 0.001), HFpEF (HR: 0.93, 0.70, 0.68; p < 0.001), and HFrEF (HR: 0.81, 0.59, 0.68; p = 0.01). Additional controlling for potential mediating factors included attenuated time-varying coronary heart disease (CHD) (nonfatal myocardial infarction, coronary revascularization) diagnosis but did not eliminate the inverse associations. Walking, the most common form of physical activity in older women, was also inversely associated with HF risks (overall: 1.00, 0.98, 0.93, 0.72; p < 0.001; HFpEF: 1.00, 0.98, 0.87, 0.67; p < 0.001; HFrEF: 1.00, 0.75, 0.78, 0.67; p = 0.01). Associations between total physical activity and HF were consistent across subgroups, defined by age, body mass index, diabetes, hypertension, physical function, and CHD diagnosis. Analysis of physical activity as a time-varying exposure yielded findings comparable to those of baseline physical a

BackgroundLifetime risk of heart failure has been estimated to range from 20% to 46% in diverse sex and race groups. However, lifetime risk estimates for the 2 HF phenotypes, HF with preserved ejection fraction (HFpEF) and HF with reduced ejection fraction (HFrEF), are not known.MethodsParticipant-level data from 2 large prospective cohort studies, the CHS (Cardiovascular Health Study) and MESA (Multiethnic Study of Atherosclerosis), were pooled, excluding individuals with prevalent HF at baseline. Remaining lifetime risk estimates for HFpEF (EF ≥45%) and HFrEF (EF <45%) were determined at different index ages with the use of a modified Kaplan-Meier method with mortality and the other HF subtype as competing risks.ResultsWe included 12 417 participants >45 years of age (22.2% blacks, 44.8% men) who were followed up for median duration of 11.6 years with 2178 overall incident HF events with 561 HFrEF events and 726 HFpEF events. At the index age of 45 years, the lifetime risk for any HF through 90 years of age was higher in men than women (27.4% versus 23.8%). Among HF subtypes, the lifetime risk for HFrEF was higher in men than women (10.6% versus 5.8%). In contrast, the lifetime risk for HFpEF was similar in men and women. In race-stratified analyses, lifetime risk for overall HF was higher in nonblacks than blacks (25.9% versus 22.4%). Among HF subtypes, the lifetime risk for HFpEF was higher in nonblacks than blacks (11.2% versus 7.7%), whereas that for HFrEF was similar across the 2 groups. Among participants with antecedent myocardial infarction before HF diagnosis, the remaining lifetime risks for HFpEF and HFrEF were up to 2.5-fold and 4-fold higher, respectively, compared with those without antecedent myocardial infarction.ConclusionsLifetime risks for HFpEF and HFrEF vary by sex, race, and history of antecedent myocardial infarction. These insights into the distribution of HF risk and its subtypes could inform the development of targeted strategies to

BACKGROUND:Remote monitoring of patients with heart failure (HF) using wearable devices can allow patient-specific adjustments to treatments and thereby potentially reduce hospitalizations. We aimed to assess HF state using wearable measurements of electrical and mechanical aspects of cardiac function in the context of exercise. METHODS AND RESULTS:Patients with compensated (outpatient) and decompensated (hospitalized) HF were fitted with a wearable ECG and seismocardiogram sensing patch. Patients stood at rest for an initial recording, performed a 6-minute walk test, and then stood at rest for 5 minutes of recovery. The protocol was performed at the time of outpatient visit or at 2 time points (admission and discharge) during an HF hospitalization. To assess patient state, we devised a method based on comparing the similarity of the structure of seismocardiogram signals after exercise compared with rest using graph mining (graph similarity score). We found that graph similarity score can assess HF patient state and correlates to clinical improvement in 45 patients (13 decompensated, 32 compensated). A significant difference was found between the groups in the graph similarity score metric (44.4±4.9 [decompensated HF] versus 35.2±10.5 [compensated HF]; P<0.001). In the 6 decompensated patients with longitudinal data, we found a significant change in graph similarity score from admission (decompensated) to discharge (compensated; 44±4.1 [admitted] versus 35±3.9 [discharged]; P<0.05). CONCLUSIONS:Wearable technologies recording cardiac function and machine learning algorithms can assess compensated and decompensated HF states by analyzing cardiac response to submaximal exercise. These techniques can be tested in the future to track the clinical status of outpatients with HF and their response to pharmacological interventions.

BackgroundIn the current era, where advanced heart failure (AHF) has become an American Board of Internal Medicine-certified subspecialty, new data are needed to benchmark and value levels of clinical effort performed by AHF specialists (AHFMDs).Methods and resultsA 36-question survey was sent to 728 AHFMDs, members of the Heart Failure Society of America, and 224 (31%) responded. Overall, 56% worked in academic medical centers (AMCs) and were younger (48 ± 9 y vs 52 ± 10 y; P < .01) and were represented by a higher proportion of women (34% vs 21%, P < .01) compared with non-AMCs. The percentage of time in clinical care was lower in AMCs (64 ± 19% vs 78 ± 18%; P = .002), with similar concentration on evaluation and management services (79 ± 18% in AMCs vs 72 ± 18 % in non-AMCs; P = NS). The majority of nonclinical time was spent in program administration (10% in both AMCs and non-AMCs) and education/research (15% in AMC vs 5% in non-AMCs). Although 69% of respondents were compensated by work-relative value units (wRVUs), only a small percentage knew their target or the amount of RVUs generated. The mean annual wRVUs generated were lower in AMCs compared to non-AMCs (5,452 ± 1,961 vs 9,071 ± 3,484; P < .001). The annual compensation in AMCs was lower than in non-AMCs (45% vs 10% <$250,000 and 17% vs 61% >$350,000; P < .001) and the satisfaction with compensation was higher in non-AMCs.ConclusionsAHFMDs' compensation is largely dependent by practice type (AMC vs non-AMC) and clinical productivity as measured by wRVUs. These data provide an opportunity for benchmarking work effort and compensation for AHFMDs, allowing distinction from segments of cardiologists with greater opportunity to accrue procedural wRVUs. They also show several differences between AMCs and non-AMCs that should be considered when formulating work assignment and compensation for AHFMDs.

BackgroundIn the current era, where advanced heart failure (AHF) has become an American Board of Internal Medicine-certified subspecialty, new data are needed to benchmark and value levels of clinical effort performed by AHF specialists (AHFMDs).Methods and resultsA 36-question survey was sent to 728 AHFMDs, members of the Heart Failure Society of America, and 224 (31%) responded. Overall, 56% worked in academic medical centers (AMCs) and were younger (48 ± 9 y vs 52 ± 10 y; P < .01) and were represented by a higher proportion of women (34% vs 21%, P < .01) compared with non-AMCs. The percentage of time in clinical care was lower in AMCs (64 ± 19% vs 78 ± 18%; P = .002), with similar concentration on evaluation and management services (79 ± 18% in AMCs vs 72 ± 18 % in non-AMCs; P = NS). The majority of nonclinical time was spent in program administration (10% in both AMCs and non-AMCs) and education/research (15% in AMC vs 5% in non-AMCs). Although 69% of respondents were compensated by work-relative value units (wRVUs), only a small percentage knew their target or the amount of RVUs generated. The mean annual wRVUs generated were lower in AMCs compared to non-AMCs (5,452 ± 1,961 vs 9,071 ± 3,484; P < .001). The annual compensation in AMCs was lower than in non-AMCs (45% vs 10% <$250,000 and 17% vs 61% >$350,000; P < .001) and the satisfaction with compensation was higher in non-AMCs.ConclusionsAHFMDs' compensation is largely dependent by practice type (AMC vs non-AMC) and clinical productivity as measured by wRVUs. These data provide an opportunity for benchmarking work effort and compensation for AHFMDs, allowing distinction from segments of cardiologists with greater opportunity to accrue procedural wRVUs. They also show several differences between AMCs and non-AMCs that should be considered when formulating work assignment and compensation for AHFMDs.

Sudden cardiac deaths account for 350,000 to 380,000 deaths in the United States annually. Implantable cardioverter-defibrillators have improved sudden death outcomes in patients with heart failure, but only a minority of patients with defibrillators receives appropriate therapy for ventricular arrhythmias. The risk prediction for sudden death and selection of patients for defibrillators is based largely on left ventricular ejection fraction and heart failure symptoms because there are no other risk stratification tools that can determine the individual patients who will derive the greatest benefit. There are several other pharmacologic strategies designed to prevent sudden death in patients with heart failure.

Sudden cardiac deaths account for 350,000 to 380,000 deaths in the United States annually. Implantable cardioverter-defibrillators have improved sudden death outcomes in patients with heart failure, but only a minority of patients with defibrillators receives appropriate therapy for ventricular arrhythmias. The risk prediction for sudden death and selection of patients for defibrillators is based largely on left ventricular ejection fraction and heart failure symptoms because there are no other risk stratification tools that can determine the individual patients who will derive the greatest benefit. There are several other pharmacologic strategies designed to prevent sudden death in patients with heart failure.

AimsHeart failure (HF) treatment guided by physicians with access to real-time pressure measurement from a wireless implantable pulmonary artery pressure (PAP) sensor (CardioMEMS), has previously been shown to reduce HF-related hospital admissions in the CHAMPION trial. However, uncertainty remains regarding the value of CardioMEMS in European health systems where healthcare costs are significantly lower than in the USA.Methods and resultsA Markov model was developed to estimate the cost-effectiveness of PAP-guided treatment of HF using the CardioMEMS™ HF system compared with usual care. Cost-effectiveness was measured as the incremental cost per quality-adjusted life year (QALY) gained. In the base case analysis over a time horizon of 10 years, PAP-guided HF therapy increased cost compared with usual care by £10 916 (€14 030). QALYs per patient for usual care and PAP-guided patients were 2.57 and 3.14, respectively, reflecting an increase of 0.57 QALYs with PAP-guided treatment. The resultant incremental cost-effectiveness ratio (ICER) is £19 274 (€24 772) per QALY gained. The base case analysis did not include staff time, due to a lack of data concerning this variable. Running the model with estimated staff time included resulted in an increased ICER of between £22 342 and £25 464 per QALY gained (€28 709-32 721).ConclusionThe analysis indicates that integrating wireless PAP monitoring into the management of UK HF patients is likely to be a cost-effective addition to the HF treatment pathway for appropriate patients.

AimsHeart failure (HF) treatment guided by physicians with access to real-time pressure measurement from a wireless implantable pulmonary artery pressure (PAP) sensor (CardioMEMS), has previously been shown to reduce HF-related hospital admissions in the CHAMPION trial. However, uncertainty remains regarding the value of CardioMEMS in European health systems where healthcare costs are significantly lower than in the USA.Methods and resultsA Markov model was developed to estimate the cost-effectiveness of PAP-guided treatment of HF using the CardioMEMS™ HF system compared with usual care. Cost-effectiveness was measured as the incremental cost per quality-adjusted life year (QALY) gained. In the base case analysis over a time horizon of 10 years, PAP-guided HF therapy increased cost compared with usual care by £10 916 (€14 030). QALYs per patient for usual care and PAP-guided patients were 2.57 and 3.14, respectively, reflecting an increase of 0.57 QALYs with PAP-guided treatment. The resultant incremental cost-effectiveness ratio (ICER) is £19 274 (€24 772) per QALY gained. The base case analysis did not include staff time, due to a lack of data concerning this variable. Running the model with estimated staff time included resulted in an increased ICER of between £22 342 and £25 464 per QALY gained (€28 709-32 721).ConclusionThe analysis indicates that integrating wireless PAP monitoring into the management of UK HF patients is likely to be a cost-effective addition to the HF treatment pathway for appropriate patients.

Disseminated acanthamoebiasis is a rare, often fatal, infection most commonly affecting immunocompromised patients. We report a case involving sinuses, skin, and bone in a 60-year-old woman 5 months after heart transplantation. She improved with a combination of flucytosine, fluconazole, miltefosine, and decreased immunosuppression. To our knowledge, this is the first case of successfully treated disseminated acanthamoebiasis in a heart transplant recipient and only the second successful use of miltefosine for this infection among solid organ transplant recipients. Acanthamoeba infection should be considered in transplant recipients with evidence of skin, central nervous system, and sinus infections that are unresponsive to antibiotics. Miltefosine may represent an effective component of a multidrug therapeutic regimen for the treatment of this amoebic infection.

BackgroundLower leisure-time physical activity (LTPA) and higher body mass index (BMI) are independently associated with risk of heart failure (HF). However, it is unclear if this relationship is consistent for both heart failure with preserved ejection fraction (HFpEF) and heart failure with reduced ejection fraction (HFrEF).ObjectivesThis study sought to quantify dose-response associations between LTPA, BMI, and the risk of different HF subtypes.MethodsIndividual-level data from 3 cohort studies (WHI [Women's Health Initiative], MESA [Multi-Ethnic Study of Atherosclerosis], and CHS [Cardiovascular Health Study]) were pooled and participants were stratified into guideline-recommended categories of LTPA and BMI. Associations between LTPA, BMI, and risk of overall HF, HFpEF (ejection fraction ≥45%), and HFrEF (ejection fraction <45%) were assessed by using multivariable adjusted Cox models and restricted cubic splines.ResultsThe study included 51,451 participants with 3,180 HF events (1,252 HFpEF, 914 HFrEF, and 1,014 unclassified HF). In the adjusted analysis, there was a dose-dependent association between higher LTPA levels, lower BMI, and overall HF risk. Among HF subtypes, LTPA in any dose range was not associated with HFrEF risk. In contrast, lower levels of LTPA (<500 MET-min/week) were not associated with HFpEF risk, and dose-dependent associations with lower HFpEF risk were observed at higher levels. Compared with no LTPA, higher than twice the guideline-recommended minimum LTPA levels (>1,000 MET-min/week) were associated with an 19% lower risk of HFpEF (hazard ratio: 0.81; 95% confidence interval: 0.68 to 0.97). The dose-response relationship for BMI with HFpEF risk was also more consistent than with HFrEF risk, such that increasing BMI above the normal range (≥25 kg/m2) was associated with a greater increase in risk of HFpEF than HFrEF.ConclusionsOur study findings show strong, dose-dependent associations between LTPA levels, BMI, a

BACKGROUND:Reproductive factors reflective of endogenous sex hormone exposure might have an effect on cardiac remodeling and the development of heart failure (HF). OBJECTIVES:This study examined the association between key reproductive factors and the incidence of HF. METHODS:Women from a cohort of the Women's Health Initiative were systematically evaluated for the incidence of HF hospitalization from study enrollment through 2014. Reproductive factors (number of live births, age at first pregnancy, and total reproductive duration [time from menarche to menopause]) were self-reported at study baseline in 1993 to 1998. We employed Cox proportional hazards regression analysis in age- and multivariable-adjusted models. RESULTS:Among 28,516 women, with an average age of 62.7 ± 7.1 years at baseline, 1,494 (5.2%) had an adjudicated incident HF hospitalization during an average follow-up of 13.1 years. After adjusting for covariates, total reproductive duration in years was inversely associated with incident HF: hazard ratios (HRs) of 0.99 per year (95% confidence interval [CI]: 0.98 to 0.99 per year) and 0.95 per 5 years (95% CI: 0.91 to 0.99 per 5 years). Conversely, early age at first pregnancy and nulliparity were significantly associated with incident HF in age-adjusted models, but not after multivariable adjustment. Notably, nulliparity was associated with incident HF with preserved ejection fraction in the fully adjusted model (HR: 2.75; 95% CI: 1.16 to 6.52). CONCLUSIONS:In post-menopausal women, shorter total reproductive duration was associated with higher risk of incident HF, and nulliparity was associated with higher risk for incident HF with preserved ejection fraction. Whether exposure to endogenous sex hormones underlies this relationship should be investigated in future studies.

We present a low power multi-modal patch designed for measuring activity, altitude (based on high-resolution barometric pressure), a single-lead electrocardiogram, and a tri-axial seismocardiogram (SCG). Enabled by a novel embedded systems design methodology, this patch offers a powerful means of monitoring the physiology for both patients with chronic cardiovascular diseases, and the general population interested in personal health and fitness measures. Specifically, to the best of our knowledge, this patch represents the first demonstration of combined activity, environmental context, and hemodynamics monitoring, all on the same hardware, capable of operating for longer than 48 hours at a time with continuous recording. The three-channels of SCG and one-lead ECG are all sampled at 500 Hz with high signal-to-noise ratio, the pressure sensor is sampled at 10 Hz, and all signals are stored to a microSD card with an average current consumption of less than 2 mA from a 3.7 V coin cell (LIR2450) battery. In addition to electronic characterization, proof-of-concept exercise recovery studies were performed with this patch, suggesting the ability to discriminate between hemodynamic and electrophysiology response to light, moderate, and heavy exercise.

Heart failure is an important and growing public health problem in women. Risk factors for incident hospitalized heart failure with preserved ejection fraction (HFpEF) compared with heart failure with reduced ejection fraction (HFrEF) in women and differences by race/ethnicity are not well characterized. We prospectively evaluated the risk factors for incident hospitalized HFpEF and HFrEF in a multiracial cohort of 42 170 postmenopausal women followed up for a mean of 13.2 years. Cox regression models with time-dependent covariate adjustment were used to define risk factors for HFpEF and HFrEF. Differences by race/ethnicity about incidence rates, baseline risk factors, and their population-attributable risk percentage were analyzed. Risk factors for both HFpEF and HFrEF were as follows: older age, white race, diabetes mellitus, cigarette smoking, and hypertension. Obesity, history of coronary heart disease (other than myocardial infarction), anemia, atrial fibrillation, and more than one comorbidity were associated with HFpEF but not with HFrEF. History of myocardial infarction was associated with HFrEF but not with HFpEF. Obesity was found to be a more potent risk factor for African American women compared with white women for HFpEF (P for interaction=0.007). For HFpEF, the population-attributable risk percentage was greatest for hypertension (40.9%) followed by obesity (25.8%), with the highest population-attributable risk percentage found in African Americans for these risk factors. In this multiracial cohort of postmenopausal women, obesity stands out as a significant risk factor for HFpEF, with the strongest association in African American women. URL: http://www.clinicaltrials.gov. Unique identifier: NCT00000611.

Ballistocardiography, the measurement of the reaction forces of the body to cardiac ejection of blood, is one of the few techniques available for unobtrusively assessing the mechanical aspects of cardiovascular health outside clinical settings. Recently, multiple experimental studies involving healthy subjects and subjects with various cardiovascular diseases have demonstrated that the ballistocardiogram (BCG) signal can be used to trend cardiac output, contractility, and beat-by-beat ventricular function for arrhythmias. The majority of these studies has been performed with "fixed" BCG instrumentation-such as weighing scales or chairs-rather than wearable measurements. Enabling wearable, and thus continuous, recording of BCG signals would greatly expand the capabilities of the technique; however, BCG signals measured using wearable devices are morphologically dissimilar to measurements from "fixed" instruments, precluding the analysis and interpretation techniques from one domain to be applied to the other. In particular, the time intervals between the electrocardiogram (ECG) and BCG-namely, the R-J interval, a surrogate for measuring contractility changes-are significantly different for the accelerometer compared to a "fixed" BCG measurement. This paper addresses this need for quantitatively normalizing wearable BCG measurement to "fixed" measurements with a systematic experimental approach. With these methods, the same analysis and interpretation techniques developed over the past decade for "fixed" BCG measurement can be successfully translated to wearable measurements.

BackgroundVitamin D supplementation may be an inexpensive intervention to reduce heart failure (HF) incidence. However, there are insufficient data to support this hypothesis. This study evaluates whether vitamin D plus calcium (CaD) supplementation is associated with lower rates of HF in postmenopausal women and whether the effects differ between those at high versus low risk for HF.Methods and resultsAnalyses were restricted to 35 983 (of original 36 282) women aged 50 to 79 years old in the Women's Health Initiative randomized trial of CaD supplementation who were randomized 1:1 in a double-blinded fashion to receive 1000 mg/d of calcium plus 400 IU/d of vitamin D3 or placebo. Overall, 744 adjudicated incident HF cases (intervention, 363; control, 381) occurred during a median follow-up of 7.1 (interquartile range, 1.6) years. CaD supplementation, compared with placebo, was not associated with reduced HF risk in the overall population, hazard ratio, 0.95; P=0.46. However, CaD supplementation had differential effects (P interaction=0.005) in subgroups stratified by baseline risk status of HF defined by the presence (high risk=17 449) or absence (low risk=18 534) of pre-existing HF precursors including coronary heart diseases, diabetes mellitus, or hypertension: 37% (hazard ratio, 0.63 [95% confidence interval, 0.46-0.87]) lower risk of HF in the low-risk versus hazard ratio, 1.06; P=0.51, in the high-risk subgroups.ConclusionsCaD supplementation did not significantly reduce HF incidence in the overall cohort, however, it was beneficial among postmenopausal women without major HF precursors while of little value in high-risk subgroups. Additional studies are warranted to confirm these findings and investigate the underlying mechanism.Clinical trial registration urlhttp://www.clinicaltrials.gov. Unique identifier: NCT00000611.

Ballistocardiography, the measurement of the reaction forces of the body to cardiac ejection of blood, is one of the few techniques available for unobtrusively assessing the mechanical aspects of cardiovascular health outside clinical settings. Recently, multiple experimental studies involving healthy subjects and subjects with various cardiovascular diseases have demonstrated that the ballistocardiogram (BCG) signal can be used to trend cardiac output, contractility, and beat-by-beat ventricular function for arrhythmias. The majority of these studies has been performed with "fixed" BCG instrumentation-such as weighing scales or chairs-rather than wearable measurements. Enabling wearable, and thus continuous, recording of BCG signals would greatly expand the capabilities of the technique; however, BCG signals measured using wearable devices are morphologically dissimilar to measurements from "fixed" instruments, precluding the analysis and interpretation techniques from one domain to be applied to the other. In particular, the time intervals between the electrocardiogram (ECG) and BCG-namely, the R-J interval, a surrogate for measuring contractility changes-are significantly different for the accelerometer compared to a "fixed" BCG measurement. This paper addresses this need for quantitatively normalizing wearable BCG measurement to "fixed" measurements with a systematic experimental approach. With these methods, the same analysis and interpretation techniques developed over the past decade for "fixed" BCG measurement can be successfully translated to wearable measurements.

BackgroundVitamin D supplementation may be an inexpensive intervention to reduce heart failure (HF) incidence. However, there are insufficient data to support this hypothesis. This study evaluates whether vitamin D plus calcium (CaD) supplementation is associated with lower rates of HF in postmenopausal women and whether the effects differ between those at high versus low risk for HF.Methods and resultsAnalyses were restricted to 35 983 (of original 36 282) women aged 50 to 79 years old in the Women's Health Initiative randomized trial of CaD supplementation who were randomized 1:1 in a double-blinded fashion to receive 1000 mg/d of calcium plus 400 IU/d of vitamin D3 or placebo. Overall, 744 adjudicated incident HF cases (intervention, 363; control, 381) occurred during a median follow-up of 7.1 (interquartile range, 1.6) years. CaD supplementation, compared with placebo, was not associated with reduced HF risk in the overall population, hazard ratio, 0.95; P=0.46. However, CaD supplementation had differential effects (P interaction=0.005) in subgroups stratified by baseline risk status of HF defined by the presence (high risk=17 449) or absence (low risk=18 534) of pre-existing HF precursors including coronary heart diseases, diabetes mellitus, or hypertension: 37% (hazard ratio, 0.63 [95% confidence interval, 0.46-0.87]) lower risk of HF in the low-risk versus hazard ratio, 1.06; P=0.51, in the high-risk subgroups.ConclusionsCaD supplementation did not significantly reduce HF incidence in the overall cohort, however, it was beneficial among postmenopausal women without major HF precursors while of little value in high-risk subgroups. Additional studies are warranted to confirm these findings and investigate the underlying mechanism.Clinical trial registration urlhttp://www.clinicaltrials.gov. Unique identifier: NCT00000611.