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Survival after implant of a left ventricular assist device (LVAD) continues to improve for patients with end-stage heart failure. Meanwhile, more patients are implanted with a destination therapy, rather than bridge-to-transplant, indication, meaning the population of patients living long-term on LVADs will continue to grow. Non-LVAD healthcare providers will encounter such patients in their scope of practice, and familiarity and comfort with the physiology and operation of these devices and common problems is essential. This review article describes the history, development, and operation of the modern LVAD. Common LVAD-related complications such as bleeding, infection, stroke, and right heart failure are reviewed and an approach to the patient with an LVAD is suggested. Nominal operating parameters and device response to various physiologic conditions, including hypo- and hypervolemia, hypertension, and device failure, are reviewed.

Early right heart failure (ERHF) remains a common complication after continuous-flow left ventricular assist device (cf-LVAD) and has been associated with increased mortality. The specific criteria used to define ERHF remain somewhat arbitrary. Correlating the degree of ERHF with outcomes after LVAD could inform a more clinically relevant definition. We identified 196 patients who underwent first durable cf-LVAD between 2008 and 2015 at a single center. Postimplant ERHF was graded as absent, mild (requiring inotropic support for 14-20 days), moderate (inotropes for ≥ 21 days), or severe (requiring unplanned RVAD at any time during the index hospitalization). ERHF was associated with clinical outcomes including 1 year survival and New York Heart Association (NYHA) class and 6 minute walk distance (6MWD) at 3 and 6 months. Survival was assessed using the Kaplan-Meier method with log-rank testing and multivariate Cox proportional-hazards modeling. Compared to patients without ERHF, those with mild ERHF had similar 1 year survival (hazard ratio [HR] 0.69, 95% confidence interval [CI]: 0.26-1.80, p = 0.45), while mortality was substantially increased in patients with moderate (HR 2.65, 95% CI: 1.27-5.54, p = 0.009) and severe ERHF (HR 8.16, 95% CI: 3.97-16.76, p < 0.0001). The severity of ERHF was associated with 6MWD at both 3 months (p = 0.001) and 6 months (p = 0.013). The relationship between ERHF and postimplant survival and functional status persisted in multivariate modeling. A simple, modified grading system for ERHF severity is strongly associated with 1 year survival and functional capacity after cf-LVAD. These results argue against using a binary definition for ERHF and suggest the need to modify definition of ERHF severity.

The PAINESD score predicts the risk of periprocedural acute hemodynamic decompensation (AHD) and postprocedural mortality in patients undergoing catheter ablation (CA) of scar-related ventricular tachycardia (VT). The role of prophylactic placement of percutaneous left ventricular assist devices (pLVADs) in high-risk patients is unknown.The purpose of this study was to evaluate the outcomes of prophylactic use of pLVAD in high-risk patients undergoing CA of scar-related VT.We included 75 patients undergoing CA of scar-related VT in whom a prophylactic pLVAD was implanted because of perceived high risk. The control population was a propensity-matched group of 75 patients who did not undergo prophylactic pLVAD placement. The PAINESD score was used for propensity matching.The median PAINESD score was 13 (41% with score ≥15) in the prophylactic pLVAD group and 12 (40% with score ≥15) in the control group. Periprocedural AHD occurred in 5 patients (7%) in the prophylactic pLVAD group and in 17 patients (23%) in the control group (P.01). The 12-month cumulative incidence of VT was 40% in the prophylactic pLVAD group vs 41% in the control group (P = .97), while the 12-month incidence of death/transplant was 33% vs 66%, respectively (P.01). In multivariable analysis, left ventricular ejection fraction (HR 0.97, 95% CI 0.95-0.99, P = .03), chronic kidney disease (HR 2.24, 95% CI 1.35-3.72, P.01), VT recurrence (HR 2.33, 95% CI 1.31-4.14, P.01), and prophylactic pLVAD (HR 0.28, 95% CI 0.16-0.49, P .01) were all independently associated with death/transplant.Prophylactic pLVAD placement in high-risk patients undergoing CA of scar-related VT is associated with a reduced risk of AHD and death/transplant during follow-up without affecting VT-free survival.

Pre-exposure prophylaxis (PrEP) with tenofovir disoproxil fumarate (TDF)/emtricitabine is 99% effective in preventing HIV when taken daily. Young men/transgender women of color who have sex with men are the most at risk to become infected with HIV, with the lowest PrEP adherence. We investigated the association of depression, anxiety, and history of childhood trauma with PrEP adherence. PrEP adherence was measured by urine TDF testing. Patients were evaluated for depression (Patient Health Questionnaire-9 [PHQ-9]), anxiety (Generalized Anxiety Disorder-7 [GAD-7]), and history of childhood trauma (Adverse Childhood Experiences [ACEs]). Urine TDF levels were compared across scores on each screening tool using a Student’s t-test. A p-value of ≤ 0.05 was considered significant. Thirty-one subjects (mean age: 21.7 years, SD: 2.8) were enrolled between 3/2015 and 7/2016. Lower PrEP adherence was associated with a GAD-7 score diagnostic for generalized anxiety (80.7% versus 92.7%, p = 0.04) and a high ACE score (4+) (84.5% versus 95.7%, p = 0.05). A PHQ-9 score diagnostic for major depression was not associated with PrEP adherence. The presence of generalized anxiety and a history of childhood trauma, but not major depression, were associated with decreased PrEP adherence. The benefits of mental health interventions and trauma-informed care in PrEP programs should be considered in larger studies to potentially increase adherence.

Introduction: Inflammatory markers, such as C-reaction protein (CRP), have been shown to be highly associated with cardiovascular disease. However, it is unclear if baseline levels of cardiovascular fitness in young, healthy persons are related to inflammatory biomarkers who have not yet manifested cardiovascular disease. Methods: Data was compiled from the National Health and Nutrition Examination Survey (NHANES). Cardiovascular fitness level (low, moderate, high) was categorized by estimated VO2 max (with age/sex adjustment cut points). Associations with CRP-based cardiovascular risk were analyzed using ANOVA/Kruskal-Wallis and Chi-squared. Ordered logistic regression was employed to identify predictors of increasing CRP-based cardiovascular risk. To account for the complex survey design, all analyses were conducted using appropriate estimated weights following NHANES analytic guidelines. Results: 2,201 participants from 1999-2004 from ages 12-49 completed cardiovascular fitness testing and had full laboratory analysis. A sensitivity analysis was performed grouping participants into CRP-based cardiovascular risk categories (low 3 mg/L) based on the 2003 AHA/CDC Scientific Statement. Increase in cardiovascular fitness category was associated with decrease in CRP-based cardiovascular risk (OR 0.83, 95% CI 0.75 to 0.91, p Conclusions: In a sample representative of the United States civilian non-institutionalized population, lower levels of cardiovascular fitness were associated with increased inflammatory biomarkers related to cardiovascular risk, even with adjustment for fitness-related covariates. Further studies will help us to understand the therapeutic role on VO2 max and cardiovascular fitness improvement in reducing atherosclerosis-related inflammation.

Pulmonary arterial compliance (PAC), invasively assessed by the ratio of stroke volume to pulmonary arterial (PA) pulse pressure, is a sensitive marker of right ventricular (RV)-PA coupling that differs across the spectrum of pulmonary hypertension (PH) and is predictive of outcomes. We assessed whether the echocardiographically derived ratio of RV outflow tract velocity time integral to PA systolic pressure (RVOT-VTI/PASP) (a) correlates with invasive PAC, (b) discriminates heart failure with preserved ejection-associated PH (HFpEF-PH) from pulmonary arterial hypertension (PAH), and (c) is associated with functional capacity. We performed a retrospective cohort study of patients with PAH (n = 70) and HFpEF-PH (n = 86), which was further dichotomized by diastolic pressure gradient (DPG) into isolated post-capillary PH (DPG

Background Right ventricular (RV) adaptation to afterload is crucial for patients undergoing continuous-flow left ventricular assist device (cf-LVAD) implantation. We hypothesized that stratifying patients by RV pulsatile load, using pulmonary arterial compliance (PAC), and RV response to load, using the ratio of central venous to pulmonary capillary wedge pressure (CVP:PCWP), would identify patients at high risk for early right heart failure (RHF) and 6-month mortality after cf-LVAD. Methods During the period from January 2008 to June 2014, we identified 151 patients at our center with complete hemodynamics prior to cf-LVAD. Pulsatile load was estimated using PAC indexed to body surface area (BSA), according to the formula: indexed PAC (PACi) = [SV / (PA systolic – PA diastolic )] / BSA, where SV is stroke volume and PA is pulmonary artery. Patients were divided into 4 hemodynamic groups by PACi and CVP:PCWP. RHF was defined as the need for unplanned RVAD, inotropic support ≥14 days or death due to RHF within 14 days. Risk factors for RHF and 6-month mortality were examined using logistic regression and Cox proportional hazards modeling. Results Sixty-one patients (40.4%) developed RHF and 34 patients (22.5%) died within 6 months. Patients with RHF had lower PACi (0.92 vs 1.17 ml/mm Hg/m 2 , p=0.008) and higher CVP:PCWP (0.48 vs 0.37, p=0.001). Higher PACi was associated with reduced risk of RHF (adjusted odds ratio [adj-OR] 0.61, 95% confidence interval [CI] 0.39 to 0.94, p=0.025) and low PACi with increased risk of 6-month mortality (adjusted hazard ratio [adj-HR] 3.18, 95% CI 1.40 to 7.25, p=0.006). Compared to patients with low load (high PACi) and adequate right heart response to load (low CVP:PCWP), patients with low PACi and high CVP:PCWP had an increased risk of RHF (OR 4.74, 95% CI 1.23 to 18.24, p=0.02) and 6-month mortality (HR 8.68, 95% CI 2.79 to 26.99, p Conclusions A hemodynamic profile combining RV pulsatile load and response to load identifies patients at high risk for RHF and 6-month mortality after cf-LVAD.

Osborn waves, or J waves, initially described by John Osborn in 1953 in hypothermic dog experiments, are highly sensitive and specific for hypothermia. Initially thought to be secondary to a hypothermia-induced “injury current,” they have more recently been attributed to a voltage differential between epicardial and endocardial potassium (Ito) currents. While the exact conditions required to induce such waves have been debated, numerous clinical scenarios of environmental and iatrogenic hypothermia have been described. Below, we report a novel case of hypothermia—that of neurosarcoidosis-induced central hypothermia with resultant Osborn waves and other associated findings found on electrocardiogram (ECG).

INTRODUCTION Balance impairment contributes to gait dysfunction, falls, and reduced quality of life in adults with Charcot-Marie-Tooth disease (CMT) but has been minimally examined in pediatric CMT. METHODS The CMT Pediatric Scale (CMTPedS) was administered to 520 children with CMT. Associations between balance function (Bruininks-Oseretsky Test of Motor Proficiency [BOT-2]) and sensorimotor and gait impairments were investigated. RESULTS Daily trips/falls were reported by 42.3% of participants. Balance (BOT-2) varied by CMT subtype, was impaired in 42% of 4-year-olds, and declined with age (P < 0.001). Vibration (P < 0.001), pinprick (P < 0.004), ankle dorsiflexion strength (P < 0.001), and foot alignment (P < 0.004) were associated with BOT-2 balance (adjusted R2 = 0.28). The visual dependence of balance increased with age. DISCUSSION Balance impairment occurs from a young age in children with CMT. Balance intervention studies are required in pediatric CMT and should consider the degree of sensorimotor impairment, foot malalignment, and visual dependence. Muscle Nerve, 2019.

Background Pulmonary arterial compliance (PAC), a marker of right ventricular (RV) afterload, represented as the ratio of stroke volume (SV) to pulmonary artery pulse pressure (PP), has been shown to be prognostic in heart failure populations. Prior work has shown that the ratio of right ventricular outflow tract pulsed-wave Doppler velocity time integral (RVOT-VTI; an echo-derived estimate of RV SV) and PA systolic pressure (PASP), correlates well with PAC obtained from invasive hemodynamics in patients with heart failure with preserved ejection fraction (HFpEF). We sought to explore this relationship in patients with heart failure with reduced ejection fraction (HFrEF) in a pre-left ventricular assist device (LVAD) cohort. Methods From a cohort of 196 patients with HFrEF awaiting LVAD implant at the Hospital of the University of Pennsylvania from 1/2008 to 2/2015, 72 patients underwent quantitative analysis of pre-implant echocardiogram by an independent reviewer (median days between echo and invasive hemodynamics were 3 [IQR 1-7]). We examined the relationship between RVOT-VTI/PASP with invasive PAC (calculated as SV/PP) using Pearson's rank coefficient and multivariate linear regression analysis. Results There were 42 patients (58%) with sufficient study quality to generate RVOT-VTI/PASP. The median RVOT-VTI/PASP was 0.16 cm/mmHg (IQR 0.11-0.23) and the median PAC was 1.61 ml/ mmHg (IQR 1.36-2.37). There was a modest but significant correlation between RVOT-VTI/PASP and PAC (r2 = 0.47; p=0.002) (Figure). In multivariate linear regression modeling, the relationship between RVOT-VTI/PASP and PAC was maintained (beta-coef 5.5, p=0.015) after adjusting for PCWP (beta-coef -0.016, p=0.5) and PVR (beta-coef -0.24, p=0.03). Conclusions In this small HFrEF cohort, RVOT-VTI/PASP, a proposed non-invasive metric of RV afterload that can be readily obtained on routine echocardiography, correlates with invasive PAC. Additional larger studies among patients with HFrEF are needed to determine if this relationship is maintained and is robust enough for the non-invasive estimation of PAC.

Background Pulmonary hypertension (PH) in the setting of left heart disease (PH-LHD) is the most common cause of PH in the general population, with a prevalence of up to 80% and is associated with high morbidity and mortality. We have previously demonstrated the utility of right ventricular outflow tract (RVOT) Doppler notching as a composite marker of pulmonary vascular disease (PVD) in patients with PH-associated with heart failure with preserved ejection fraction (HFpEF). Our study examines the ability of RVOT Doppler notching to predict survival in patients with PH-HFpEF. Methods We retrospectively evaluated consecutive patients referred to the Penn PH program between January 2007 and March 2013 diagnosed with PH-HFpEF. Patients were included who had right heart catheterization with mean pulmonary artery pressure ≥ 25mmHg and pulmonary artery wedge pressure > 15 mmHg. All patients underwent echocardiographic and hemodynamic assessment as indicated clinically. Statistical analysis included student's t-test and chi-squared to assess continuous and categorical variables, respectively, along with use of Cox regression and the Kaplan-Meier estimator to evaluate survival. Results Of 86 patients, 53 had notching and 33 did not. Baseline characteristics were similar across both groups. Patients with notching had higher diastolic pulmonary gradient (8.2±6.4 vs 1.4±4.3, p Conclusions In PH-HFpEF, RVOT Doppler notching is a composite marker of PVD and is a strong predictor of long-term survival. Further work is needed to validate this marker in larger cohorts.

Introduction: Right ventricular failure (RVF) is a common complication after continuous-flow left ventricular assist device (cf-LVAD) and carries an increased risk of mortality. There is a spectrum of early RVF and the optimal definition is controversial, hindering efforts to identify relevant risk factors. Correlating the severity of RVF with outcome after LVAD could inform clinical criteria for this important syndrome. Hypothesis: Increasing severity of RVF will be associated with worse one-year survival. Methods: We identified 196 patients undergoing isolated durable cf-LVAD since 2005 at our center. Post-implant RVF was graded as absent, mild (requiring inotropes for 14-20 days), moderate (requiring inotropes for ≥ 21 days), or severe (requiring unplanned RVAD at any time during the index hospitalization). One-year survival, censored at the time of heart transplant or VAD explant for recovery, was examined using Kaplan-Meier plots, the log-rank test, and Cox proportional-hazard modeling. Results: Seventy-three patients (37.2%) developed RVF: 35 (17.9%) mild, 24 (12.2%) moderate, and 14 (7.1%) severe. The median follow-up time was 266 days (IQR: 81-761), and 51 patients (26%) died within one year. Compared to patients without RVF, those with mild RVF had similar one-year survival (HR 0.69, 95%CI:0.26-1.80, p=0.45) while the risk of death was substantially increased in patients with moderate (HR 2.65, 95%CI:1.27-5.54, p=0.009) and severe RVF (HR 8.16, 95%CI:3.97-16.76, p Conclusions: A simple grading system for the severity of early RVF is strongly associated with one-year survival after cf-LVAD, supporting the notion that there is a spectrum of post-implant RVF. If confirmed in other cohorts, targeting risk-prediction and risk-mitigation strategies for moderate and severe RVF could improve post-LVAD survival.

Background: Pulmonary hypertension (PH) due to heart failure with preserved ejection fraction (HFpEF) is a leading cause of PH. Within this population, the diastolic pressure gradient (DPG) distinguishes those with combined post- and pre-capillary PH (DPG ≥7 mm Hg; CpcPH), and isolated post