Publications by authors named "Liviu Klein"

74 Publications

Use of Ballistocardiography to Monitor Cardiovascular Hemodynamics in Preeclampsia.

Womens Health Rep (New Rochelle) 2021 20;2(1):97-105. Epub 2021 Apr 20.

Division of Cardiology, Department of Internal Medicine, University of California San Francisco, San Francisco, California, USA.

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 ballistocardiogram (BCG) can be used to assess cardiovascular hemodynamics noninvasively in women with preeclampsia. 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. In normotensive controls, the J-amp × HR was significantly lower early postpartum (E-PP) compared with the second trimester (T2;  = 0.016) and third trimester (T3;  = 0.001). Women with preeclampsia had a significantly lower J-amp × HR compared with normotensive controls during the first trimester (T1;  = 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. 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.
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http://dx.doi.org/10.1089/whr.2020.0127DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8080913PMC
April 2021

Two-Year Follow Up of the LATERAL Clinical Trial: A Focus on Adverse Events.

Circ Heart Fail 2021 Apr 19;14(4):e006912. Epub 2021 Apr 19.

Department of Thoracic and CV Surgery, Loyola University Medical Center, Maywood, IL (E.C.M.).

Background: The 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.

Methods: AEs 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.

Results: During 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.

Conclusions: Two-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.
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http://dx.doi.org/10.1161/CIRCHEARTFAILURE.120.006912DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8059760PMC
April 2021

Effect of preload reducing therapy on right ventricular size and function in patients with arrhythmogenic right ventricular cardiomyopathy.

Heart Rhythm 2021 Mar 17. Epub 2021 Mar 17.

Department of Cardiology, University of California San Francisco, San Francisco, California.

Background: Arrhythmogenic right ventricular cardiomyopathy (ARVC) is an important cause of sudden cardiac death in young people and athletes. To date, no treatment has proven to slow the progression of the disease. Preload reducing agents such as nitrates and diuretics have shown promising results in preventing training-induced development of ARVC in a murine model.

Objective: The purpose of this study was to describe our experience with preload reducing therapy in patients with ARVC and symptomatic right ventricular (RV) dysfunction.

Methods: We performed retrospective chart review of prospectively collected registry data and included 20 patients with definite ARVC who had serial echocardiographic measurements and an implantable cardioverter-defibrillator. Six of the 20 patients with RV end-diastolic area (RVEDA) above median (>25 cm) and New York Heart Association functional class II-IV symptoms were successfully treated with long-term isosorbide dinitrate 5-40 mg tid (at maximum tolerated dose) and hydrochlorothiazide-spironolactone 25-25 mg daily. The main outcomes of interest were RVEDA, RV fractional area change (FAC), and RV outflow tract measurements. Generalized estimating equations with repeated measures were used to identify the association between preload reducing agents and echocardiographic structural progression.

Results: Patients who received preload reducing agents (n = 6) were older and had larger RVs with lower FAC at baseline. However, treatment with preload reducing agents was associated with less RVEDA enlargement during mean 3.3 (range 1-6.7) years of treatment in multivariate analysis (% change in RVEDA associated with treatment -7.71; 95% confidence interval -13.29 to -2.13; P = .007).

Conclusion: Preload reducing agents show promising results in slowing RV enlargement in patients with ARVC and show possible disease-modifying potential.
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http://dx.doi.org/10.1016/j.hrthm.2021.03.018DOI Listing
March 2021

When the At-Risk Do Not Develop Heart Failure: Understanding Positive Deviance Among Postmenopausal African American and Hispanic Women.

J Card Fail 2021 Feb 22;27(2):217-223. Epub 2020 Nov 22.

Division of General Medicine and Clinical Epidemiology, University of North Carolina, Chapel Hill, North Carolina.

Background: African 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 Results: Using 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) in unadjusted analyses; however, no psychosocial factors were associated with heart failure hospitalization in fully adjusted analyses.

Conclusions: Among postmenopausal African American and Hispanic women, a significant proportion remained free from heart failure hospitalization despite having the highest genetic risk profile and 1 or more traditional risk factors. No observed psychosocial factors were associated with incident heart failure hospitalization in high-risk African Americans and Hispanics. Additional investigation is needed to understand protective factors among high-risk African American and Hispanic women.
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http://dx.doi.org/10.1016/j.cardfail.2020.11.009DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7880886PMC
February 2021

Association of Sedentary Time and Incident Heart Failure Hospitalization in Postmenopausal Women.

Circ Heart Fail 2020 12 24;13(12):e007508. Epub 2020 Nov 24.

Brown University Warren Alpert School of Medicine, and School of Public Health, Providence, RI (C.A.N., C.B.E.).

Background: The 2018 US Physical Activity Guidelines recommend reducing sedentary behavior (SB) for cardiovascular health. SB's role in heart failure (HF) is unclear.

Methods: We 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.

Results: Controlling 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 <0.001) and sitting time (1.00 [referent], 1.14 [1.01-1.28], 1.54 [1.34-1.78], trend <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 <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 <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.

Conclusions: SB was associated with increased risk of incident HF hospitalization in postmenopausal women. Targeted efforts to reduce SB could enhance HF prevention in later life.
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http://dx.doi.org/10.1161/CIRCHEARTFAILURE.120.007508DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7738397PMC
December 2020

Cardiac Function Monitoring for Patients Undergoing Cancer Treatments Using Wearable Seismocardiography: A Proof-of-Concept Study.

Annu Int Conf IEEE Eng Med Biol Soc 2020 07;2020:4075-4078

Advances in cancer therapeutics have dramatically improved the survival rate and quality of life in patients affected by various cancers, but have been accompanied by treatment-related cardiotoxicity, e.g. left ventricular (LV) dysfunction and/or overt heart failure (HF). Cardiologists thus need to assess cancer treatment-related cardiotoxic risks and have close followups for cancer survivors and patients undergoing cancer treatments using serial echocardiography exams and cardiovascular biomarkers testing. Unfortunately, the cost-prohibitive nature of echocardiography has made these routine follow-ups difficult and not accessible to the growing number of cancer survivors and patients undergoing cancer treatments. There is thus a need to develop a wearable system that can yield similar information at a minimal cost and can be used for remote monitoring of these patients. In this proof-of-concept study, we have investigated the use of wearable seismocardiography (SCG) to monitor LV function non-invasively for patients undergoing cancer treatment. A total of 12 subjects (six with normal LV relaxation, five with impaired relaxation and one with pseudo-normal relaxation) underwent routine echocardiography followed by a standard six-minute walk test. Wearable SCG and electrocardiogram signals were collected during the six-minute walk test and, later, the signal features were compared between subjects with normal and impaired LV relaxation. Pre-ejection period (PEP) from SCG decreased significantly (p < 0.05) during exercise for the subjects with impaired relaxation compared to the subjects with normal relaxation, and changes in PEP/LV ejection time (LVET) were also significantly different between these two groups (p < 0.05). These results suggest that wearable SCG may enable monitoring of patients undergoing cancer treatments by assessing cardiotoxicity.
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http://dx.doi.org/10.1109/EMBC44109.2020.9176074DOI Listing
July 2020

Outcome of patients on heart transplant list treated with a continuous-flow left ventricular assist device: Insights from the TRans-Atlantic registry on VAd and TrAnsplant (TRAViATA).

Int J Cardiol 2021 02 18;324:122-130. Epub 2020 Sep 18.

University Hospital, Leuven, Belgium.

Background: Geographic variations in management and outcomes of individuals supported by continuous-flow left ventricular assist devices (CF-LVAD) between the United States (US) and Europe (EU) is largely unknown.

Methods: We created a retrospective, multinational registry of 524 patients who received a CF-LVAD (either HVAD or Heartmate II) between January 2008 and April 2017. Follow up spanned from date of CF-LVAD implant to post-HTx period with a median follow up of 44.8 months.

Results: The cohort included 299 (57.1%) EU and 225 (42.9%) US patients. Although the US cohort was significantly older with a higher prevalence of comorbidities, survival was similar between the cohorts (US 63.1%, EU 68.4% at 5 years, unadjusted log-rank test p = 0.43).Multivariate analyses suggested that older age, higher body mass index, elevated creatinine, use of temporary mechanical circulatory support prior CF-LVAD, and implantation of HVAD were associated with increased mortality. Among CF-LVAD patients undergoing HTx, the median time on CF-LVAD support was shorter in the US, meanwhile US donors were younger. Finally, the pattern of adverse events (stroke, gastrointestinal bleedings, late right ventricular failure, and driveline infection) during support differed significantly between US and EU.

Conclusions: Although waitlisted patients in the US on CF-LVAD have higher risk comorbid conditions, the overall outcome is similar in US and EU. Geographic variations with regards to donor characteristics, duration of CF-LVAD support prior to transplant, and adverse events on support can explain the disparity in the utilization of mechanical bridge to transplant strategy between US and EU.
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http://dx.doi.org/10.1016/j.ijcard.2020.09.026DOI Listing
February 2021

Wearable Patch-Based Estimation of Oxygen Uptake and Assessment of Clinical Status during Cardiopulmonary Exercise Testing in Patients With Heart Failure.

J Card Fail 2020 Nov 27;26(11):948-958. Epub 2020 May 27.

Department of ECE, Georgia Institute of Technology, Atlanta, Georgia.

Background: To estimate oxygen uptake (VO) 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 VO. However, CPX requires specialized equipment, as well as trained professionals to conduct the study.

Methods And Results: We 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 VO 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 VO from the wearable features yielded a moderate correlation (R of 0.64) with a root mean square error of 2.51 ± 1.12 mL · kg · min on the training-testing set, whereas R and root mean square error on the validation set were 0.76 and 2.28 ± 0.93 mL · kg · min, 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.

Conclusions: Wearable SCG and ECG can assess CPX VO and thereby classify clinical status for patients with HF. These methods may provide value in the risk stratification of patients with HF by tracking cardiopulmonary parameters and clinical status outside of specialized settings, potentially allowing for more frequent assessments to be performed during longitudinal monitoring and treatment.
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http://dx.doi.org/10.1016/j.cardfail.2020.05.014DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7704799PMC
November 2020

Detecting Suspected Pump Thrombosis in Left Ventricular Assist Devices via Acoustic Analysis.

IEEE J Biomed Health Inform 2020 07 13;24(7):1899-1906. Epub 2020 Jan 13.

Objective: Left 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.

Methods: 13 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.

Results: Accuracy, 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.

Significance: We 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.
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http://dx.doi.org/10.1109/JBHI.2020.2966178DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7380556PMC
July 2020

Heart-lung transplantation: A viable option for connective tissue diseases.

Clin Transplant 2020 02 9;34(2):e13776. Epub 2020 Jan 9.

Division of Cardiology, Department of Medicine, University of California San Francisco, San Francisco, California.

Background: While lung transplantation (LTx) has been effective for connective tissue disease (CTD) patients with pulmonary involvement, outcomes for heart-lung transplantation (HLTx) are less defined. The aim of this study is to evaluate HLTx in CTD patients utilizing the UNOS database.

Methods: HLTx patients with CTD (HLTx-CTD) were compared to both LTx patients with CTD (LTx-CTD) and HLTx patients with all other indications (HLTx-OI) from 1999 to 2018. Primary outcome was 1- and 5-year graft survival. Secondary outcomes included freedom from first-year rejection and outcomes prior to transplant discharge.

Results: 1143/29 323 adults received first-time HLTx or LTx for CTD. Seventeen were HLTx-CTD (3.3% of total HLTx) and 1126 were LTx-CTD (3.9% of total LTx). There were 492 HLTx-OI. Transplant hemodynamic values including cardiac output, pulmonary capillary wedge pressure, and calculated pulmonary vascular resistance were significantly worse for HLTx-CTD vs LTx-CTD (4.2 vs 5.4 L/min, P = .005; 14 vs 10 mm Hg, P = .009; 439 vs 267 dynes, P = .007, respectively). Cardiac status 1 was more common for HLTx-CTD vs HLTx-OI (94% vs 56%, P < .001). HLTx-CTD 1 and 5-year graft survival was similar compared to LTx-CTD and HLTx-OI.

Conclusion: HLTx-CTD is a valid option for carefully selected patients with CTD cardiac and pulmonary involvement with similar morbidity and mortality compared to LTx-CTD and HLTx-OI.
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http://dx.doi.org/10.1111/ctr.13776DOI Listing
February 2020

Improving risk prediction in heart failure using machine learning.

Eur J Heart Fail 2020 01 12;22(1):139-147. Epub 2019 Nov 12.

Division of Cardiology, Department of Medicine, UC San Diego, La Jolla, CA, USA.

Background: Predicting mortality is important in patients with heart failure (HF). However, current strategies for predicting risk are only modestly successful, likely because they are derived from statistical analysis methods that fail to capture prognostic information in large data sets containing multi-dimensional interactions.

Methods And Results: We used a machine learning algorithm to capture correlations between patient characteristics and mortality. A model was built by training a boosted decision tree algorithm to relate a subset of the patient data with a very high or very low mortality risk in a cohort of 5822 hospitalized and ambulatory patients with HF. From this model we derived a risk score that accurately discriminated between low and high-risk of death by identifying eight variables (diastolic blood pressure, creatinine, blood urea nitrogen, haemoglobin, white blood cell count, platelets, albumin, and red blood cell distribution width). This risk score had an area under the curve (AUC) of 0.88 and was predictive across the full spectrum of risk. External validation in two separate HF populations gave AUCs of 0.84 and 0.81, which were superior to those obtained with two available risk scores in these same populations.

Conclusions: Using machine learning and readily available variables, we generated and validated a mortality risk score in patients with HF that was more accurate than other risk scores to which it was compared. These results support the use of this machine learning approach for the evaluation of patients with HF and in other settings where predicting risk has been challenging.
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http://dx.doi.org/10.1002/ejhf.1628DOI Listing
January 2020

Long-Term Corticosteroid-Sparing Immunosuppression for Cardiac Sarcoidosis.

J Am Heart Assoc 2019 09 6;8(18):e010952. Epub 2019 Sep 6.

Division of Cardiology Department of Medicine University of California, San Francisco San Francisco CA.

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.
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http://dx.doi.org/10.1161/JAHA.118.010952DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6818011PMC
September 2019

Menopausal Hormone Therapy and Risks of First Hospitalized Heart Failure and its Subtypes During the Intervention and Extended Postintervention Follow-up of the Women's Health Initiative Randomized Trials.

J Card Fail 2020 Jan 17;26(1):2-12. Epub 2019 Sep 17.

Division of Preventive Medicine, Brigham and Women's Hospital, Harvard Medical School and Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, MA.

Background: We assessed whether postmenopausal hormone therapy (HT) was associated with incident heart failure (HF) and its subtypes and examined whether there was a modifying effect of age on the associations.

Methods And Results: Postmenopausal women aged 50-79 enrolled in the Women's Health Initiative HT trials were analyzed. The 16,486 women with a uterus were randomized to receive conjugated equine estrogens (CEE 0.625 mg/day) plus medroxyprogesterone acetate (MPA 2.5 mg/day) or placebo, and 10,739 women with prior hysterectomy were randomized to receive CEE (0.625 mg/day) alone or placebo. Incident HF was defined as the first HF hospitalization. HF with reduced ejection fraction (HFrEF) or preserved EF (HFpEF) was defined as EF < 50% or ≥ 50%. During the intervention phase, median follow-up was 5.6 years in the CEE-plus-MPA trial and 7.2 years in the CEE-alone trial. During the cumulative follow-up of 18.9 years, women randomized to HT vs placebo in the 2 combined trials had incidence rates of 3.90 vs 3.89 per 1000 person-years for total HF; 1.25 vs 1.40 per 1000 person-years for HFrEF, and 1.88 vs 1.79 per 1000 person-years for HFpEF, respectively. There were no significant effects of HT on the risk of total incident HF or its subtypes in either trial, and age at randomization did not significantly modify the results.

Conclusions: Postmenopausal HT did not alter the risk of hospitalization for HF or its subtypes during the intervention or cumulative 18.9 years of follow-up, and results did not vary significantly by age at randomization.

Trial Registration: clinicaltrials.gov Identifier: NCT0000611 https://clinicaltrials.gov/ct2/show/NCT00000611?cond=women%27s±health±initiative&rank=5.
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http://dx.doi.org/10.1016/j.cardfail.2019.09.006DOI Listing
January 2020

Internal Jugular Vein as Alternative Access for Implantation of a Wireless Pulmonary Artery Pressure Sensor.

Circ Heart Fail 2019 08 1;12(8):e006060. Epub 2019 Aug 1.

Heart and Vascular Center, University of California San Francisco (A.S.H., L.K.).

Background: A wireless pulmonary artery pressure sensor (CardioMEMS) is approved for implantation via the femoral vein. The internal jugular vein (IJ) is an attractive alternative access route commonly used in pulmonary artery catheterization.

Methods And Results: Retrospective chart review was performed for all sensor implants from 10 providers at 4 centers from September 2016 to June 2018. To compare procedural outcomes and discharge efficiency between groups, multivariate analyses incorporating potential confounders were performed. Seventy-three (28%) patients had femoral access, and 189 (72%) had IJ access; demographics were similar between the groups. Complications, including one case of hematoma and 4 cases of mild hemoptysis, and 30-day mortality (2%-3%) did not differ between groups. Provider preference for IJ access substantially increased over time, with IJ accounting for 90% of cases in 2018. After risk-adjustment, IJ cases had 20% (5%-33%) shorter fluoroscopy time (=0.01) and 24% (7%-38%) lower contrast volume (=0.008). Compared with outpatient femoral cases, outpatient IJ cases had 62% (52%-69%) faster needle-to-door time and were 34 times (6-235) more likely to have same-day discharge (<0.001 for both).

Conclusions: IJ access for CardioMEMS implant is a safe alternative associated with superior procedural and discharge outcomes. Implanters at 4 high-volume centers adopted IJ access as the preferred implant approach.
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http://dx.doi.org/10.1161/CIRCHEARTFAILURE.119.006060DOI Listing
August 2019

Classification of Decompensated Heart Failure From Clinical and Home Ballistocardiography.

IEEE Trans Biomed Eng 2020 05 15;67(5):1303-1313. Epub 2019 Aug 15.

Objective: To 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.

Methods: 1) 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.

Results: The best AUC score for the task of classification obtained was 0.78 using slight variant of the leave one subject out validation method.

Conclusion: This work demonstrates that high quality BCG signals can be collected in a home environment and used to detect the clinical state of HF patients.

Significance: In 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.
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http://dx.doi.org/10.1109/TBME.2019.2935619DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7271768PMC
May 2020

Atrial arrhythmias in patients with arrhythmogenic right ventricular cardiomyopathy: Prevalence, echocardiographic predictors, and treatment.

J Cardiovasc Electrophysiol 2019 10 24;30(10):1801-1810. Epub 2019 Jul 24.

Division of Cardiology, Department of Medicine, University of California San Francisco, San Francisco, California.

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.
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http://dx.doi.org/10.1111/jce.14069DOI Listing
October 2019

Noninvasive estimation of pulmonary vascular resistance improves portopulmonary hypertension screening in liver transplant candidates.

Clin Transplant 2019 07 5;33(7):e13585. Epub 2019 Jun 5.

Department of Medicine, University of California San Francisco, San Francisco, California.

Despite limitations in sensitivity and specificity, estimation of the pulmonary artery systolic pressure (ePASP) on echocardiography is used for portopulmonary hypertension (PoPH) screening in liver transplant (LT) candidates. We proposed that alternative echocardiographic models, such as estimated pulmonary vascular resistance (ePVR), may provide improved testing characteristics in PoPH screening. In a retrospective analysis of 100 LT candidates, we found that the formula ePVR = ePASP/VTI  + 3 if MSN (VTI  = right ventricular outflow tract time velocity integral; MSN = mid-systolic notching of the VTI Doppler signal) significantly improves accuracy of PoPH screening compared to ePASP. We determined the optimal ePVR cutoff for PoPH screening to be 2.76 Wood units, as this cutoff provided 100% sensitivity and 73% specificity in screening for clinically significant PoPH. Comparatively, ePASP at a cutoff of 40 mm Hg provided 91% sensitivity and 48% specificity. We devised a new screening algorithm based on the use of ePVR at intermediate ePASP values (35-54 mm Hg), and we confirmed the testing characteristics of this algorithm in a separate validation cohort of 50 LT candidates. In screening LT candidates for PoPH, the ePASP lacks accuracy, leading to unnecessary RHCs and undiagnosed cases of PoPH. A screening algorithm which incorporates the ePVR may be more reliable.
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http://dx.doi.org/10.1111/ctr.13585DOI Listing
July 2019

Pregnancy complications and premature cardiovascular events among 1.6 million California pregnancies.

Open Heart 2019;6(1):e000927. Epub 2019 Feb 27.

Department of Medicine, University of California San Francisco, San Francisco, California, USA.

Background: Cardiovascular complications of pregnancy present an opportunity to assess risk for subsequent cardiovascular disease. We sought to determine whether peripartum cardiomyopathy and hypertensive disorder of pregnancy subtypes predict future myocardial infarction, heart failure or stroke independent of one another and of other risks such as gestational diabetes, preterm birth and intrauterine growth restriction.

Methods And Results: The California Healthcare Cost and Utilization Project database was used to identify all hospitalised pregnancies from 2005 to 2009, with follow-up through 2011, for a retrospective cohort study. Pregnancies, exposures, covariates and outcomes were defined by International Classification of Diseases, Ninth Revision codes. Among 1.6 million pregnancies (mean age 28 years; median follow-up time to event excluding censoring 2.7 years), 558 cases of peripartum cardiomyopathy, 123 603 hypertensive disorders of pregnancy, 107 636 cases of gestational diabetes, 116 768 preterm births and 23 504 cases of intrauterine growth restriction were observed. Using multivariable Cox proportional hazards models, peripartum cardiomyopathy was independently associated with a 39.2-fold increase in heart failure (95% CI 30.0 to 51.9), resulting in ~1 additional hospitalisation per 1000 person-years. There was a 13.0-fold increase in myocardial infarction (95% CI 4.1 to 40.9) and a 7.7-fold increase in stroke (95% CI 2.4 to 24.0). Hypertensive disorders of pregnancy were associated with 1.4-fold (95% CI 1.0 to 2.0) to 7.6-fold (95% CI 5.4 to 10.7) higher risk of myocardial infarction, heart failure and stroke, resulting in a maximum of ~1 additional event per 1000 person-years. Gestational diabetes, preterm birth and intrauterine growth restriction had more modest associations.

Conclusion: These findings support close monitoring of women with cardiovascular pregnancy complications for prevention of early cardiovascular events and study of mechanisms underlying their development.
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http://dx.doi.org/10.1136/openhrt-2018-000927DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6443129PMC
February 2021

Evaluation of a lateral thoracotomy implant approach for a centrifugal-flow left ventricular assist device: The LATERAL clinical trial.

J Heart Lung Transplant 2019 04;38(4):344-351

Division of Cardiothoracic Surgery, St. Paul's Hospital, University of British Columbia, Vancouver, British Columbia, Canada.

Background: The HeartWare centrifugal-flow ventricular assist device system (HVAD) is a viable option for treatment of advanced heart failure. There is a growing trend toward the use of less invasive techniques in cardiac surgery, and the thoracotomy technique for HVAD implantation may provide benefits not available with conventional approaches.

Methods: The LATERAL trial is a multicenter, prospective, non-randomized, single-arm trial that utilized data from 144 patients enrolled in the Interagency Registry for Mechanically Assisted Circulatory Support (INTERMACS) database at 26 centers in the United States and Canada. The primary composite end-point was success at 180 days defined as alive on the originally implanted device and free from disabling stroke (modified Rankin Scale score >3), transplanted or explanted for recovery. The key secondary end-point was mean length of initial hospital stay.

Results: The primary end-point was successfully achieved in 88.1% of patients and was significantly greater than the pre-defined performance goal of 77.5% set from historical sternotomy data (p = 0.0012). The key secondary end-point-mean length of initial hospital stay -was 18 days and was significantly shorter than the pre-defined performance goal of 26.1 days obtained from historical sternotomy data (p < 0.0001). The adverse event profile further demonstrated the safety of the thoracotomy approach. The overall patient survival was good, and bleeding requiring reoperation was significantly less frequent than that observed in previous studies using the sternotomy approach.

Conclusions: This prospective clinical trial provides validation that implantation of the HVAD system via the thoracotomy approach used in the LATERAL study represents a safe and effective alternative to median sternotomy in selected patients intended for a bridge-to-transplant indication.
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http://dx.doi.org/10.1016/j.healun.2019.02.002DOI Listing
April 2019

Feasibility and utility of intraoperative epicardial scar characterization during left ventricular assist device implantation.

J Cardiovasc Electrophysiol 2019 02 21;30(2):183-192. Epub 2018 Dec 21.

Department of Medicine, Section of Cardiology, Center for Arrhythmia Care, University of Chicago Medicine, Chicago, Illinois.

Introduction: Ventricular arrhythmias (VA) after left ventricular assist device (LVAD) placement are associated with increased morbidity and mortality. We sought to assess epicardial voltage characteristics at the time of LVAD implantation and investigate relationships between scar burden and postimplant VA.

Methods And Results: Consecutive patients underwent open chest epicardial electroanatomic mapping immediately before LVAD implantation. Areas of low voltage and sites with local abnormal potentials were identified. Patients were followed prospectively for postimplant VA and clinical outcomes. Between 2015 and 2017, 36 patients underwent high-density intraoperative epicardial voltage mapping; 15 had complete maps suitable for analysis. Mapping required a median of 11.8 (interquartile range [IQR], 8.5-12.7) minutes, with a median of 2650 (IQR, 2139-3191) points sampled per patient. Over a median follow-up of 311 (IQR, 168-469) postoperative days, four patients (27%) experienced sustained VA. Patients with postimplant VA were more likely to have had preimplant implantable cardioverter defibrillator shocks (100% vs 27%; P = 0.03), ventricular tachycardia storm (75% vs 9%; P = 0.03), and lower ejection fraction (13.5 vs 19.0%, P = 0.05). Patients with postimplant VA also had a significantly higher burden of epicardial low bipolar voltage points: 55.4% vs 24.9% of points were less than 0.5 mV (P = 0.01), and 88.9% vs 63.7% of points less than 1.5 mV (P = 0.004).

Conclusions: Intraoperative high-density epicardial mapping during LVAD implantation is safe and efficient, facilitating characterization of a potentially arrhythmogenic substrate. An increased burden of the epicardial scar may be associated with a higher incidence of postimplant VA. The role of empiric intraoperative epicardial ablation to mitigate risk of postimplant VA requires further study.
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http://dx.doi.org/10.1111/jce.13803DOI Listing
February 2019

Physical Activity and Incidence of Heart Failure in Postmenopausal Women.

JACC Heart Fail 2018 12 5;6(12):983-995. Epub 2018 Sep 5.

Department of Family Medicine, Warren Alpert Medical School of Brown University, Providence, Rhode Island; Department of Epidemiology, Brown University School of Public Health, Center for Primary Care and Prevention, Memorial Hospital of Rhode Island, Providence, Rhode Island.

Objectives: This 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).

Background: The role of physical activity in HF risk among older women is unclear, particularly for incidence of HFpEF or HFrEF.

Methods: Women 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.

Results: After 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.

Conclusions: Higher levels of recreational physical activity, including walking, are associated with significantly reduced HF risk in community-dwelling older women.
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http://dx.doi.org/10.1016/j.jchf.2018.06.020DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6275092PMC
December 2018

Risk Factor Burden, Heart Failure, and Survival in Women of Different Ethnic Groups: Insights From the Women's Health Initiative.

Circ Heart Fail 2018 05;11(5):e004642

Division of Cardiology, University of California San Francisco (L.K.).

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 (<0.0001, interaction of race/ethnicity and RF number =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 (<0.0001) but differed by racial/ethnic group (interaction =0.001). The number of RFs was not associated with the risk of death after developing HF in any group (=0.25; interaction =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.
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http://dx.doi.org/10.1161/CIRCHEARTFAILURE.117.004642DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5935135PMC
May 2018

Sex and Race Differences in Lifetime Risk of Heart Failure With Preserved Ejection Fraction and Heart Failure With Reduced Ejection Fraction.

Circulation 2018 04 19;137(17):1814-1823. Epub 2018 Jan 19.

Division of Cardiology (A.P., W.O., C.A., J.D.B.)

Background: Lifetime 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.

Methods: Participant-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.

Results: We 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.

Conclusions: Lifetime 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 improve population-level HF prevention and control.
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http://dx.doi.org/10.1161/CIRCULATIONAHA.117.031622DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6417883PMC
April 2018

Novel Wearable Seismocardiography and Machine Learning Algorithms Can Assess Clinical Status of Heart Failure Patients.

Circ Heart Fail 2018 01;11(1):e004313

From the School of Electrical and Computer Engineering, Georgia Institute of Technology, Atlanta (O.T.I., M.B.P., A.Q.J., A.D., A.O.B.); Division of Cardiology (S.D., T.D.M., L.K.) and Department of Bioengineering and Therapeutic Sciences (S.R.), University of California, San Francisco; and Department of Anesthesiology and Department of Biomedical Engineering, Northwestern University, Chicago, IL (M.E., J.A.H.).

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]; <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]; <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.
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http://dx.doi.org/10.1161/CIRCHEARTFAILURE.117.004313DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5769154PMC
January 2018

(Re)Discovering the Neurohormonal and Hemodynamic Duality of Heart Failure.

Authors:
Liviu Klein

J Am Coll Cardiol 2017 10;70(15):1887-1889

Division of Cardiology, University of California San Francisco, San Francisco, California. Electronic address:

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http://dx.doi.org/10.1016/j.jacc.2017.08.058DOI Listing
October 2017

Reproductive Factors and Incidence of Heart Failure Hospitalization in the Women's Health Initiative.

J Am Coll Cardiol 2017 May;69(20):2517-2526

Division of Cardiology, University of California, San Francisco, San Francisco, California. Electronic address:

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.
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http://dx.doi.org/10.1016/j.jacc.2017.03.557DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5602586PMC
May 2017

Relationship Between Physical Activity, Body Mass Index, and Risk of Heart Failure.

J Am Coll Cardiol 2017 Mar;69(9):1129-1142

Division of Cardiology, UTSW Medical Center, Dallas, Texas; Department of Clinical Sciences, UTSW Medical Center, Dallas, Texas. Electronic address:

Background: Lower 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).

Objectives: This study sought to quantify dose-response associations between LTPA, BMI, and the risk of different HF subtypes.

Methods: Individual-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.

Results: The 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/m) was associated with a greater increase in risk of HFpEF than HFrEF.

Conclusions: Our study findings show strong, dose-dependent associations between LTPA levels, BMI, and risk of overall HF. Among HF subtypes, higher LTPA levels and lower BMI were more consistently associated with lower risk of HFpEF compared with HFrEF.
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http://dx.doi.org/10.1016/j.jacc.2016.11.081DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5848099PMC
March 2017

The cost-effectiveness of real-time pulmonary artery pressure monitoring in heart failure patients: a European perspective.

Eur J Heart Fail 2017 05 7;19(5):661-669. Epub 2017 Feb 7.

Health Economics and Decision Science, School of Health and Related Research, The University of Sheffield, Sheffield, UK.

Aims: Heart 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 Results: A 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).

Conclusion: The 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.
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http://dx.doi.org/10.1002/ejhf.747DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5434803PMC
May 2017

Disseminated Acanthamoeba infection in a heart transplant recipient treated successfully with a miltefosine-containing regimen: Case report and review of the literature.

Transpl Infect Dis 2017 Apr 6;19(2). Epub 2017 Mar 6.

Division of Infectious Diseases, UCSF, San Francisco, CA, USA.

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.
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http://dx.doi.org/10.1111/tid.12661DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5510642PMC
April 2017

Partial LVAD restores ventricular outputs and normalizes LV but not RV stress distributions in the acutely failing heart in silico.

Int J Artif Organs 2016 Oct 14;39(8):421-430. Epub 2016 Sep 14.

 Department of Surgery, University of California at San Francisco, San Francisco - USA.

Purpose: Heart failure is a worldwide epidemic that is unlikely to change as the population ages and life expectancy increases. We sought to detail significant recent improvements to the Dassault Systèmes Living Heart Model (LHM) and use the LHM to compute left ventricular (LV) and right ventricular (RV) myofiber stress distributions under the following 4 conditions: (1) normal cardiac function; (2) acute left heart failure (ALHF); (3) ALHF treated using an LV assist device (LVAD) flow rate of 2 L/min; and (4) ALHF treated using an LVAD flow rate of 4.5 L/min.

Methods And Results: Incorporating improved systolic myocardial material properties in the LHM resulted in its ability to simulate the Frank-Starling law of the heart. We decreased myocardial contractility in the LV myocardium so that LV ejection fraction decreased from 56% to 28%. This caused mean LV end diastolic (ED) stress to increase to 508% of normal, mean LV end systolic (ES) stress to increase to 113% of normal, mean RV ED stress to decrease to 94% of normal and RV ES to increase to 570% of normal. When ALHF in the model was treated with an LVAD flow rate of 4.5 L/min, most stress results normalized. Mean LV ED stress became 85% of normal, mean LV ES stress became 109% of normal and mean RV ED stress became 95% of normal. However, mean RV ES stress improved less dramatically (to 342% of normal values).

Conclusions: These simulations strongly suggest that an LVAD is effective in normalizing LV stresses but not RV stresses that become elevated as a result of ALHF.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5067236PMC
http://dx.doi.org/10.5301/ijao.5000520DOI Listing
October 2016