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Left ventricular assist devices (LVADs) provide lifesaving therapy for patients with advanced heart failure. The recognition of pump thrombosis, stroke, and nonsurgical bleeding as hemocompatibility-related adverse events (HRAEs) led to pump design improvements and reduced adverse event rates. However, continuous flow can predispose patients to right-sided heart failure (RHF) and aortic insufficiency (AI), especially as patients live longer with their device. Given the hemodynamic contributions to AI and RHF, these comorbidities can be classified as hemodynamic-related events (HDREs). Hemodynamic-driven events are time dependent and often manifest later than HRAEs. This review examines the emerging strategies to mitigate HDREs, with a focus on defining best practices for AI and RHF. As we head into the next generation of LVAD technology, it is important to differentiate HDREs from HRAEs so that we can continue to advance the field and improve the true durability of the pump-patient continuum., Competing Interests: Funding Support and Author Disclosures Dr Grinstein has served as a speaker for Abbott, Medtronic, and CH Biomedical. Mr Borque is an employee of Abbott. Dr Salerno has served as a consultant for Abbott and Medtronic. Dr Pinney has served as a consultant for Abbott, Medtronic, Ancora, CareDx, Procyrion, Transmedics, and Valgen Medtech. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2023 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Competing Interests: Disclosures None.

Background: Invasive hemodynamic variables obtained from right heart catheterization have been used for risk-stratifying patients with advanced heart failure (HF). However, there is a paucity of data on the prognostic value of invasive hemodynamic variables in patients with left ventricular assist devices (LVAD). We hypothesized that cardiac power output (CPO), cardiac power efficiency (CPE), and left ventricular stroke work index (LVSWI) can serve as prognostic markers in patients with LVADs., Methods: Baseline hemodynamic data from patients who had LVAD ramp studies at our institution from 4/2014 to 7/2018 were prospectively collected, from which advanced hemodynamic variables (CPO, CPE, and LVSWI) were retrospectively analyzed. Univariate and multivariable analyses were performed for hemocompatibility-related adverse events (HRAE), HF admissions, and mortality., Results: Ninety-one participants (age 61 ± 11 years, 34% women, 40% Black or African American, and 38% ischemic cardiomyopathy) were analyzed. Low CPE was significantly associated with mortality (HR 2.42, 95% CI 1.02-5.74, p = 0.045) in univariate analysis and Kaplan-Meier analysis (p = 0.04). Low LVSWI was significantly associated with mortality (HR 2.13, 95% CI 1.09-4.17, p = 0.03) in univariate analysis and Kaplan-Meier analysis (p = 0.02). CPO was not associated with mortality. CPO, CPE, and LVSWI were not associated with HRAE or HF admissions., Conclusions: Advanced hemodynamic variables can serve as prognostic indicators for patients with LVADs. Low CPE and LVSWI are prognostic for higher mortality, but no variables were associated with HF admissions or HRAEs., (© 2022 The Authors. Artificial Organs published by International Center for Artificial Organ and Transplantation (ICAOT) and Wiley Periodicals LLC.)

Preoperative cardiopulmonary exercise testing (CPET) is well validated for prognostication before advanced surgical heart failure therapies, but its role in prognostication after LVAD surgery has never been studied. VE/VCO2 slope is an important component of CPET which has direct pathophysiologic links to right ventricular (RV) performance. We hypothesized that VE/VCO 2 slope would prognosticate RV dysfunction after LVAD. All CPET studies from a single institution were collected between September 2009 and February 2019. Patients who ultimately underwent LVAD implantation were selectively analyzed. Peak VO2 and VE/VCO2 slope were measured for all patients. We evaluated their association with hemodynamic, echocardiographic and clinical markers of RV dysfunction as well mortality. Patients were stratified into those with a ventilatory class of III or greater. (VE/VCO2 slope of ≥ 36, n = 43) and those with a VE/VCO2 slope < 36 (n = 27). We compared the mortality between the 2 groups, as well as the hemodynamic, echocardiographic and clinical markers of RV dysfunction. 570 patients underwent CPET testing. 145 patients were ultimately referred to the advanced heart failure program and 70 patients later received LVAD implantation. Patients with VE/VCO2 slope of ≥ 36 had higher mortality (30.2% vs. 7.4%, p = 0.02) than patients with VE/VCO2 slope < 36 (n = 27). They also had a higher incidence of clinically important RVF (Acute severe 9.3% vs. 0%, Severe 32.6% vs 25.9%, p = 0.03). Patients with a VE/VCO2 slope ≥ 36 had a higher CVP than those with a lower VE/VCO2 slope (11.2 ± 6.1 vs. 6.0 ± 4.8 mmHg, p = 0.007), and were more likely to have a RA/PCWP ≥ 0.63 (65% vs. 19%, p = 0.008) and a PAPI ≤ 2 (57% vs. 13%, p = 0.008). In contrast, peak VO2 < 12 ml/kg/min was not associated with postoperative RV dysfunction or mortality. Elevated preoperative VE/VCO2 slope is a predictor of postoperative mortality, and is associated with postoperative clinical and hemodynamic markers of impaired RV performance., (© 2021. The Japanese Society for Artificial Organs.)

Background: Right heart catheterization for invasive hemodynamics has shown only modest correlation with clinical outcomes. We designed a novel hemodynamic variable that incorporates ventricular output and filling pressure. We anticipated that the aortic pulsatility index (API) would correlate with clinical outcomes in patients with heart failure., Methods and Results: We retrospectively analyzed consecutive patients undergoing right heart catheterization with milrinone drug study at our institution (February 2013 to November 2019). The API was calculated as (systolic blood pressure - diastolic blood pressure)/pulmonary capillary wedge pressure. The primary outcome was freedom from advanced therapies, defined as the need for inotropes, temporary mechanical circulatory support, a left ventricular assist device, or orthotopic heart transplantation, or death at 30 days. A total of 224 patient encounters, age 57 years (48-66 years; 34% women; 31% ischemic cardiomyopathy) were included. In univariable analysis, lower baseline API was significantly associated with progression to advanced therapies or death at 30-days (odds ratio 0.43, 95% confidence interval 0.30-0.61; P < .001) compared with those on continued medical management. Receiver operator characteristic analysis specified an optimal cutpoint of 1.45 for API. A Kaplan-Meier analysis indicated an association of API with the primary outcome (79% for API ≥ 1.45 vs 48% for API < 1.45). In multivariable analysis, higher API was strongly associated with freedom from advanced therapies or death (odds ratio 0.38, 95% confidence interval 0.22-0.65, P ≤ .001), even when adjusted for baseline characteristics and routine right heart catheterization measurements., Conclusions: The API is a novel invasive hemodynamic measurement that is associated independently with freedom from advanced therapies or death at 30-day follow-up., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Background: Elevated lactic acid (LA) levels carry a poor prognosis in patients with shock. Data are lacking on the significance of LA levels in patients with acute decompensated heart failure (ADHF)., Hypothesis: This study assessed the relationship between LA levels, hemodynamics and clinical outcomes., Methods: This was a retrospective analysis of registry data of 100 advanced heart failure patients presenting for right heart catheterization (RHC) for concern of ADHF. LA levels (normal ≤2.1 mmol/L) were obtained prior to RHC; no significant changes in therapy were made between LA collection and RHC., Results: Median age was 58 (47.3, 64.8) years; 57% were receiving inotropes prior to RHC. Median pulmonary capillary wedge pressure (PCWP) and cardiac index (CI) were 28 (21, 35) mmHg and 2.0 (1.7, 2.5) L/min/m 2 , respectively. Eighty patients had normal LA prior to RHC. There was no correlation between LA levels and PCWP (R = 0.09, p = .38); 63% of the normal LA group had a PCWP >24 mmHg. There was a moderate inverse correlation between LA and CI (R = - 0.40; p < .001); 58% of the normal LA group had a CI <2.2 L/min/m 2 . Thirty-day survival free of death/hospice, inotrope dependence, progression to heart transplant/left-ventricular assist device implant was comparable between the normal and elevated LA groups (28% vs. 20%; p = .17)., Conclusion: In patients presenting with ADHF, normal LA levels do not exclude the presence of depressed CI (a hemodynamic criteria for cardiogenic shock) and may not offer accurate risk stratification. Invasive hemodynamics should not be delayed based on normal LA levels alone., (© 2021 The Authors. Clinical Cardiology published by Wiley Periodicals LLC.)

Aims: Aortic pulsatility index (API), calculated as (systolic-diastolic blood pressure)/pulmonary capillary wedge pressure (PCWP), is a novel haemodynamic measurement representing both cardiac filling pressures and contractility. We hypothesized that API would better predict clinical outcomes than traditional haemodynamic metrics of cardiac function., Methods and Results: The Evaluation Study of Congestive Heart Failure and Pulmonary Artery Catheterization Effectiveness (ESCAPE) trial individual-level data were used. Routine haemodynamic measurements, including Fick cardiac index (CI), and the advanced haemodynamic metrics of API, cardiac power output (CPO), and pulmonary artery pulsatility index (PAPI) were calculated after final haemodynamic-monitored optimization. The primary outcome was a composite endpoint of death or need for orthotopic heart transplant (OHT) or left ventricular assist device (LVAD) at 6 months. A total of 433 participants were enrolled in the ESCAPE trial of which 145 had final haemodynamic data. Final API measurements predicted the primary outcome, OR 0.47 (95% CI 0.32-0.70, P < 0.001), while CI, CPO, and PAPI did not. Receiver operator characteristic analyses of final advanced haemodynamic measurements indicated API best predicted the primary outcome with a cutoff of 2.9 (sensitivity 76.2%, specificity 55.3%, correctly classified 61.4%, area-under-the-curve 0.71), compared with CPO, CI, and PAPI. Kaplan-Meier analyses indicated API ≥ 2.9 was associated with greater freedom from the primary outcome (83.5%), compared with API < 2.9 (58.4%), P = 0.001. While PAPI was also significantly associated, CI and CPO were not., Conclusions: The novel haemodynamic measurement API better predicted clinical outcomes in the ESCAPE trial when compared with traditional invasive haemodynamic metrics of cardiac function., (© 2021 The Authors. ESC Heart Failure published by John Wiley & Sons Ltd on behalf of European Society of Cardiology.)

Background: The axillary intraaortic balloon pump (IABP) is frequently used in selected patients for circulatory support as a bridge to heart transplantation. The purpose of this study was to investigate the safety and efficacy of axillary intraaortic balloon pump (IABP) support for heart transplant candidates., Methods: The study investigators collected data on 133 patients who underwent axillary IABP support as a bridge to transplantation from July 2009 to April 2019. Of these patients, 94 (70.7%) underwent IABP insertion with surgical axillary grafts, and 39 (29.3%) underwent percutaneous IABP insertion. The outcomes of interest included ambulatory data, IABP-related complications, and successful heart transplantation with this type of support., Results: The overall preoperative ejection fraction was 20.3% ± 8.0%. The median duration of axillary IABP support was 21days, with 131patients (98.5%) mobilizing with the device. Hemodynamic variables significantly improved after the axillary IABP support was placed. Overall, 122 patients (91.7%) were successfully bridged to heart transplantation. Six patients (4.5%) required escalation to further mechanical support. Two patients (1.5%) died while awaiting transplantation. Four patients (3.0%) experienced a stroke during axillary IABP support (3 before transplantation and1 after transplantation). Two of the 3 patients with a stroke diagnosis before transplantation recovered and eventually underwent heart transplantation., Conclusions: With axillary IABP support, most patients were able to ambulate and undergo physical rehabilitation while waiting for heart transplantation. This study demonstrates that axillary IABP results in a high success rate of bridge to transplantation and a low number of complications. Thus, an ambulatory axillary IABP provided efficient and safe support for selected patients as a bridge to heart transplantation., (Copyright © 2021 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.)

Background: Tricuspid regurgitation (TR) is common in advanced heart failure (HF) patients. However, the effect of concomitant tricuspid valve repair or replacement (tricuspid valve intervention [TVI]) with left ventricular assist device (LVAD) implantation is controversial. The aim of this study was to investigate the longitudinal trend of TR after LVAD implantation and the effect of TVI on the TR trend and clinical outcomes., Methods: We retrospectively reviewed patients at our institution who underwent LVAD implantation between April 2014 and August 2018. We evaluated the grade of TR by echocardiography before and after LVAD implantation. Moderate or greater TR was defined as significant., Results: Among 199 consecutive patients, 194 had at least 2 echocardiographic TR assessments before and after LVAD implantation. Of these patients, 108 were included in the TVI-positive (TVI+) group and 86 in the TVI-negative (TVI-) group. In the TVI+ group, the prevalence of significant TR decreased from 52% to about 20% in the first 6 months after implantation (P < .01). Overall survival and HF readmission-free survival were comparable between the TVI+ and TVI- patients. In contrast, patients in both groups who had significant postoperative TR during early follow-up had worse 2-year HF readmission-free survival (36% in patients with significant postoperative TR vs 55% in those without significant postoperative TR; P = .028)., Conclusions: Concomitant TVI with LVAD implantation improved TR in most patients but did not have an impact on clinical outcomes. Significant postoperative TR after LVAD implantation, in patients with and without TVI, was associated with worse HF-free outcomes., (Copyright © 2020 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.)

Background: HeartWare ventricular assist device (HVAD) cannula position is associated with hemodynamics and heart failure readmissions. However, its impact on hemocompatibility-related adverse events (HRAEs) remains uncertain., Methods: HVAD patients were followed for 1 year after index hospitalization, when cannula coronal angle was quantified from chest x-ray film. Invasive right heart catheterization and transthoracic echocardiography were performed. One-year occurrences of each HRAE were compared between those with and without a cannula coronal angle of greater than 65 degrees., Results: Among 63 HVAD patients (median age 60 years, 63% male), 10 (16%) had a cannula coronal angle greater than 65 degrees. The wide-angle group had elevated intracardiac pressures and lower pulmonary artery pulsatility index (P < .05). They also had reduced right ventricular function by echocardiography. Freedom from HRAEs tended to be lower in the wide-angle group (24% vs 62%; P = .11). The rate of gastrointestinal bleeding was significantly higher in the greater than 65 degrees group (0.90 events/year vs 0.40 events/year; P = .013). The rates of stroke and pump thrombosis were statistically comparable irrespective of cannula angle (P > .05)., Conclusions: HVAD cannula coronal angle was associated with reduced right ventricular function and HRAEs. Prospective studies evaluating surgical techniques to ensure optimal device positioning and its effects on HRAEs are warranted., (Copyright © 2020 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.)

Background Decoupling between diastolic pulmonary artery pressure and pulmonary capillary wedge pressure is an index of pulmonary vascular damage. This study assessed the impact of decoupling on right heart function and hemocompatibility-related adverse events. Methods and Results In this prospective study, patients underwent invasive hemodynamic tests following left ventricular assist device implantation. Decoupling was defined as a difference of >5 mm Hg between diastolic pulmonary artery pressure and pulmonary capillary wedge pressure. Among 92 patients with left ventricular assist devices (median age, 61 years; 57% male), 44 patients (48%) had decoupling. Right heart function and size by echocardiographic assessment worsened during a 1-year observational period in the decoupling group as compared with the control group ( P <0.05). The decoupling group had significantly lower 1-year freedom from any hemocompatibility-related adverse events (49% versus 79%; P =0.005), as well as a higher hemocompatibility score (2.14 versus 0.67; P =0.004). The scoring system depicts the severity of hemocompatibility-related adverse events using 4 escalating tiers. Increased tier I scores (1-2 gastrointestinal bleedings or medically managed pump thrombosis; P =0.027) and tier IIIB scores (disabling stroke or hemocompatibility-related adverse event-related death; P =0.041) occurred more frequently in the decoupling group. Conclusions The presence of decoupling between diastolic pulmonary artery pressure and pulmonary capillary wedge pressure was associated with worsening of right heart function and hemocompatibility-related adverse events in patients with left ventricular assist devices.

The purpose of this study is to compare clinical outcomes of left ventricular assist device (LVAD) patients with device thrombosis who underwent device exchange (DE) or medical therapy (MT) alone. Consecutive patients undergoing LVAD implant between July 2008 and December 2017 were included. Device thrombosis was diagnosed with comprehensive assessments including ramp test, laboratory data, device parameters, and clinical presentations. First, MT was initiated in all patients. After MT, DE was considered if device thrombosis was refractory to initial MT, and it caused end-organ impairment and/or hemodynamic instability. Among 319 consecutive LVAD patients, 43 patients (13.5%) were diagnosed with device thrombosis. DE was performed in 28 patients (DE group); device explant was performed in 1 patient. MT was continued in 14 patients (MT group). In-hospital mortality was significantly lower in the DE group than the MT group (3.6% [1/28] vs. 28.6% [4/14], P = .0184). One-year survival was significantly better in the DE group (74.0% vs. 30.1%; log-rank = .001), and freedom from cerebrovascular accident (CVA) at 1 year was greater in the DE group (87.1% vs. 47.7%; log-rank = .004). DE was associated with improved 1-year survival and fewer CVAs. Surgical intervention, if feasible, is recommended for LVAD device thrombosis., (© 2019 International Center for Artificial Organs and Transplantation and Wiley Periodicals, Inc.)

Background: Characterization of right heart catheterization (RHC) waveforms provides diagnostic and clinical information in heart failure patients. We aimed to investigate the implication of RHC waveforms, specifically the y-descent, in patients with left ventricular assist device (LVAD)., Methods and Results: Patients underwent RHC and waveforms were quantified prior to and 6 months after LVAD implantation. The impact of a deep y-descent (>3 mmHg) on echocardiographic measures of right heart function and 1-year hemocompatibility-related adverse event rates were investigated. Eighty-nine patients (median 59 years old, 65 male) underwent RHC. RHC waveform showed unique changes following LVAD implantation, particularly an increase in the steepness of the y-descent. A post-LVAD deep y-descent was associated with reduced right ventricular function and enlarged right heart. Patients with post-LVAD deep y-descent had higher rates of gastrointestinal bleeding (0.866 vs 0.191 events/year) and stroke (0.199 vs 0 events/year) compared with those without (P< .05 for both)., Conclusion: RHC waveforms characterized by deep y-descent on RHC waveform during LVAD support was associated with impaired right ventricular function and worse clinical outcomes., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Tolvaptan is an effective therapy for heart failure patients with symptomatic congestion and hyponatremia. The efficacy of its use in patients with continuous-flow left ventricular assist devices (LVADs) is unknown. The aim of this study was to assess the clinical efficacy and safety of tolvaptan in LVAD patients. We retrospectively reviewed medical records of patients who underwent LVAD implantation between January 2014 and August 2018. Among 217 consecutive LVAD patients, tolvaptan was used in 20 patients. Mean age was 46 ± 14 years old and 14 patients were males. The duration of tolvaptan therapy was 4 (interquartile range 1-8) days. Urine volume significantly increased from 2,623 ± 1,109 ml/day before tolvaptan to 4,308 ± 1,432 ml/day during tolvaptan therapy (p < 0.001). Serum sodium increased from 127 ± 3 to 133 ± 3 mEq/L at the end of tolvaptan therapy (p < 0.001). No patients developed hypernatremia (serum sodium >150 mEq/L). The 90-day overall survival following tolvaptan therapy was 89% in both the tolvaptan group and a propensity score-matched non-tolvaptan group (p = 0.918). Survival free of heart failure readmissions was also comparable between the groups (p = 0.751). In conclusion, short-term use of tolvaptan following LVAD implantation is a safe and effective therapy to augment diuresis and improve hyponatremia.

Increased vascular stiffness is known to be an independent predictor of mortality in patients with heart failure with reduced ejection fraction (HFrEF). The effects of sacubitril-valsartan on vascular structure and function have not been systematically studied in this patient population. We hypothesized that aortic distensibility (AD) and fractional area change (AFAC), as assessed by 2D transthoracic echocardiography (TTE), would improve over time in HFrEF patients on sacubitril-valsartan therapy, due to the vasodilatory properties of the medication. We prospectively studied 30 patients with HFrEF (25 < EF < 40%) on optimal guideline-directed medical therapy who were subsequently started on sacubitril-valsartan. Patients underwent serial 2D TTE imaging at baseline, 3 and 6 months following therapy initiation. Ascending aortic diameters were measured 3 cm above the aortic valve in the parasternal long-axis view and used to calculate AD and AFAC, two markers of vascular compliance. For reference, we also measured AD and AFAC in 30 healthy, age and gender-matched controls at a single time point. Normal controls had significantly higher values of AD and AFAC than HFrEF patients at baseline (AD: 4.0 ± 1.1 vs. 2.2 ± 0.9 cm 2 dyne -1 10 -3 , p < 0.0001 and AFAC: 18.8 ± 3.7% vs. 10.3 ± 4.3%, p < 0.0001). In HFrEF patients on sacubitril-valsartan, both indices of aortic compliance progressively improved towards normal from baseline to 6 months: AD from 2.2 ± 0.9 to 3.6 ± 1.5 cm 2 dyne -1 10 -3 (p < 0.0001) and AFAC from 10.3 ± 4.3 to 13.7 ± 4.1% (p < 0.0001). In conclusion, AD and AFAC are decreased in patients with HFrEF and gradually improve with sacubitril-valsartan treatment. The echocardiographic markers used in this study may become a useful tool to assess the effectiveness of sacubitril-valsartan therapy in HFrEF patients.

Background: Historically, invasive hemodynamic guidance was not superior compared to clinical assessment in patients admitted with acute decompensated heart failure (ADHF). This study assessed the accuracy of clinical assessment vs invasive hemodynamics in patients with ADHF., Methods and Results: We conducted a prospective cohort study of patients admitted with ADHF. Prior to right-heart catheterization (RHC), physicians categorically predicted right atrial pressure, pulmonary capillary wedge pressure, cardiac index and hemodynamic profile (wet/dry, warm/cold) based on physical examination and clinical data evaluation (warm = cardiac index > 2.2 L/min/m 2 ; wet = pulmonary capillary wedge pressure > 18 mmHg). We collected 218 surveys (of 83 cardiology fellows, 55 attending cardiologists, 45 residents, 35 interns) evaluating 97 patients. Of those patients, 46% were receiving inotropes prior to RHC. The positive and negative predictive values of clinical assessment compared to RHC for the cold and wet subgroups were 74.7% and 50.4%. The accuracy of categorical prediction was 43.6% for right atrial pressure, 34.4% for pulmonary capillary wedge pressure and 49.1% for cardiac index, and accuracy did not differ by clinician (P > 0.05 for all). Interprovider agreement was 44.4%. Therapeutic changes following RHC occurred in 71.1% overall (P < 0.001)., Conclusions: Clinical assessment of patients with advanced heart failure presenting with ADHF has low accuracy across all training levels, with exaggerated rates of misrecognition of the most high-risk patients., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Background: Tricuspid regurgitation (TR) is common in patients receiving left ventricular assist device (LVAD) implantation. The current literature is conflicting regarding the effects of concomitant tricuspid valve repair (TVR) at LVAD implantation. We investigated the hemodynamic effects of concomitant TVR at LVAD implantation., Methods: Consecutive clinically stable LVAD outpatients who underwent hemodynamic ramp testings were enrolled in this study, and they were stratified by concomitant TVR. Results of hemodynamic ramp tests were compared between the TVR group and the non-TVR group., Results: Among 65 LVAD patients undergoing ramp tests, 34 patients had received TVR, and 31 had not. There were no significant differences in baseline characteristics between two groups except for higher degree of TR and lower pulmonary artery pulsatility index in the TVR group (P < .05 for both). Following LVAD implantation, the degree of TR improved significantly in the TVR group down to the comparable level with the non-TVR group. During ramp tests, the TVR group had steeper cardiac index slope (0.14 ± 0.12 vs 0.07 ± 0.07 L/min/m 2 /step, P = .002) and higher cardiac index at set LVAD speed (2.99 ± 0.84 vs 2.52 ± 0.42 L/min/m 2 , P = .007)., Conclusions: Concomitant TVR improves cardiac output and its response to LVAD speed change following LVAD implantation. Longitudinal clinical implications of such hemodynamic changes are unknown., (© 2019 Wiley Periodicals, Inc.)

Background Metabolic impairment is common in heart failure patients. Continuous-flow left ventricular assist devices (CF-LVADs) improve hemodynamics and outcomes in patients with advanced heart failure; however, the effect of CF-LVADs on metabolic status is unknown. This study aims to evaluate the changes in metabolic status following CF-LVAD implantation and measure the correlation of metabolic status with outcomes. Methods and Results Prospective data on CF-LVAD patients were obtained. Metabolic evaluation, including hemoglobin A1C, free and total testosterone, thyroid-stimulating hormone (TSH), and free T4, was obtained before and at multiple time points following implantation. Patients with nonelevated thyroid-stimulating hormone and normal hemoglobin A1C and testosterone levels were defined as having normal metabolic status. Baseline characteristics, hemodynamics, and outcomes were collected. One hundred six patients were studied, of which 56 had paired data at baseline and 1- to 3-month follow-up. Before implantation, 75% of patients had insulin resistance, 86% of men and 39% of women had low free testosterone, and 44% of patients had abnormal thyroid function. There was a significant improvement in hemoglobin A1C, free testosterone, and thyroid-stimulating hormone following implantation ( P <0.001 for all). Patients with normal hemoglobin A1C (<5.7%) following implantation had higher 1-year survival free of heart failure readmissions (78% versus 23%; P <0.001). Patients with normal metabolic status following implantation also had higher 1-year survival free of heart failure readmissions (92% versus 54%; P =0.04). Conclusions Metabolic dysfunction is highly prevalent in advanced heart failure patients and improves after CF-LVAD implantation. Normal metabolic status is associated with a significantly higher rate of 1-year survival free of heart failure readmissions.

Aim: Hemocompatibility-related adverse events (HRAE) are a major cause of readmissions in patients with left ventricular assist devices (LVAD). The impact of aortic insufficiency (AI) on HRAE remains uncertain. We aimed to investigate the impact of AI on HRAE., Methods and Results: Patients who underwent LVAD implantation between August 2014 and July 2017 and had echocardiograms 3 months post-LVAD implantation were enrolled. AI severity was assessed by measuring the systolic/diastolic ratio of flow and the rate of diastolic flow acceleration using Doppler echocardiography of the outflow cannula. Regurgitation fraction was derived from these parameters. Significant AI was defined as regurgitation fraction > 30%. Among 105 patients (median age, 56 years; 76% male), 36 patients (34%) had significant AI. Baseline characteristics were statistically not significantly different between those with and without significant AI except for higher rates of ischemic etiology and atrial fibrillation in the significant AI group (P < 0.05 for both). One-year survival free from HRAE was 44% in patients with AI compared to 67% in patients without significant AI (P = 0.018). The average hemocompatibility score, which defines the net burden of HRAE, was higher in the AI group (1.72 vs 0.64; P = 0.009), due mostly to higher tier I (mild HRAE; P = 0.034) and tier IIIB scores (severe HRAE; P = 0.011)., Conclusion: Significant AI, as assessed by Doppler echocardiographic parameters, was associated with HRAE during LVAD support., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Aims: Left ventricular assist device (LVAD) therapy improves the haemodynamics of advanced heart failure patients. However, it is unknown whether haemodynamic optimization improves haemocompatibility-related adverse events (HRAEs). This study aimed to assess HRAEs in patients with optimized haemodynamics., Methods and Results: Eighty-three outpatients [aged 61 (53-67) years, 50 male] underwent a haemodynamic ramp test at 253 (95-652) days after LVAD implantation, and 51 (61%) had optimized haemodynamics (defined as central venous pressure < 12 mmHg, pulmonary artery wedge pressure < 18 mmHg, cardiac index > 2.2 L/min/m 2 ) following LVAD speed adjustment. One-year survival free of any HRAEs (non-surgical bleeding, thromboembolic event, pump thrombosis, or neurological event) was achieved in 75% of the optimized group and in 44% of the non-optimized group (hazard ratio 0.36, 95% confidence interval 0.18-0.73, P = 0.003). The net haemocompatibility score, using four escalating tiers of hierarchal severity to derive a total score for events, was significantly lower in the optimized group than the non-optimized group (1.02 vs. 2.00 points/patient; incidence rate ratio 0.51, 95% confidence interval 0.29-0.90, P = 0.021)., Conclusion: Left ventricular assist device patients in whom haemodynamics can be optimized had greater freedom from HRAEs compared to those without optimized haemodynamics., (© 2018 The Authors. European Journal of Heart Failure © 2018 European Society of Cardiology.)

Background: Left ventricular assist device (LVAD) therapy improves the hemodynamics of advanced heart failure patients. However, it is unknown whether hemodynamic optimization improves clinical outcomes. The aim of this study was to investigate whether hemodynamic optimization reduces hospital readmission rate in LVAD patients., Methods and Results: LVAD patients undergoing an invasive hemodynamic ramp test were prospectively enrolled and followed for 1 year. LVAD speed was optimized using a ramp test, targeting the following goals: central venous pressure <12 mm Hg, pulmonary capillary wedge pressure <18 mm Hg, and cardiac index >2.2 L/(min·m 2 ). The frequency and cause of hospital readmissions were compared between patients who achieved (optimized group) or did not achieve (nonoptimized group) these goals. Eighty-eight outpatients (median 61 years old, 53 male) underwent ramp testing 236 days after LVAD implantation, and 54 (61%) had optimized hemodynamics after LVAD speed adjustment. One-year survival after the ramp study was comparable in both groups (89% versus 88%). The total hospital readmission rate was lower in the optimized group compared with the nonoptimized group (1.15 versus 2.86 events/y, P<0.001). This result was predominantly because of a reduction in the heart failure readmission rate in the optimized group (0.08 versus 0.71 events/y, P=0.016)., Conclusions: LVAD patients, in whom hemodynamics were optimized, had a significantly lower rate of hospital readmissions, primarily because of fewer heart failure admissions. These findings highlight the importance of achieving hemodynamic optimization in LVAD patients.

Background: The NupulseCV intravascular ventricular assist system (iVAS), which consists of a durable pump placed through the subclavian artery, provides extended-duration ambulatory counterpulsation. This study investigated the effect of iVAS on biventricular cardiac function., Methods and Results: We reviewed all heart failure patients who received iVAS implantation as a bridge to transplantation or a bridge to candidacy since April 2016 as part of the iVAS first-in-humans and subsequent feasibility study. We compared data of transthoracic echocardiography performed just before implantation (without iVAS support) and again at 30 days or just before explantation (on iVAS support). Eighteen patients (58.8 ± 7.4 years old and 15 male) received iVAS support for 53 ± 43 days. Fourteen patients were bridged to cardiac replacement therapy after 35 ± 19 days and the remaining 4 patients had been supported for 118 ± 41 days. There were no deaths during iVAS support. At 30 days, there was a significant improvement in left ventricular ejection fraction (16.5% ± 11.9% vs 24.4% ± 12.8%; P = .007) and marked reduction in left atrial size (62.7 ± 35.7 mL/m 2 vs 33.8 ± 17.2 mL/m 2 ; P < .001). Right ventricular fractional area change improved dramatically (25.4% ± 12.9% vs 42.1% ± 12.4%; P < .001). All other right ventricular and right atrial parameters improved significantly as well (size, tricuspid annular plane systolic excursion, and velocity of tricuspid annular systolic motion)., Conclusions: Improvement in biventricular cardiac function was observed after 30 days of iVAS support. Further studies should examine the use of this technology as a bridge to recovery., (Copyright © 2018. Published by Elsevier Inc.)

Background Gastrointestinal bleeding (GIB) is a common complication seen in patients supported with left ventricular assist devices (LVADs) and is related to increased inflammation and angiogenesis. Omega-3 is an unsaturated fatty acid that possesses anti-inflammatory and antiangiogenic properties. This study aims to assess the prophylactic efficacy of treatment with omega-3 on the incidence of GIB in LVAD patients. Methods and Results Among consecutive 166 LVAD patients enrolled in this analysis, 30 patients (49 years old and 26 male) received 4 mg/d of omega-3 therapy for 310±87 days and 136 patients in the control group (58 years old and 98 male) were observed for 302±102 days. One-year GIB-free rate was significantly higher in the omega-3 group as compared with the control group (97% versus 73%; P=0.02). Omega-3 therapy was associated with the occurrence of GIB in both the univariate (hazard ratio, 0.12; 95% CI, 0.02-0.91; P=0.040) and multivariate Cox proportional hazard ratio analyses (hazard ratio, 0.13; 95% CI, 0.02-0.98; P=0.047). The frequency of GIB was significantly lower in the omega-3 group (0.08±0.42 versus 0.37±0.93 events/y; P=0.01), accompanied by significantly lower blood product transfusion and shorter days in the hospital. The frequency of GIB remained lower among the omega-3 group after matching for patient background characteristics (96% versus 73%, P=0.028). Conclusions LVAD patients treated with omega-3 had a significant increase in freedom from GIB. A randomized controlled study is warranted to evaluate the use of omega-3 in LVAD patients.

Background: The assessment of hemodynamics in patients supported with left ventricular assist devices (LVADs) is often challenging. Physical examination maneuvers correlate poorly with true hemodynamics. We assessed the value of novel transthoracic echocardiography (TTE)-derived variables to reliably predict hemodynamics in patients supported with LVAD., Methods and Results: A total of 102 Doppler-TTE images of the LVAD outflow cannula were obtained during simultaneous invasive right heart catheterization (RHC) in 30 patients supported with continuous-flow LVADs (22 HMII, 8 HVAD) either during routine RHC or during invasive ramp testing. Properties of the Doppler signal though the outflow cannula were measured at each ramp stage (RS), including the systolic slope (SS), diastolic slope (DS), and velocity time integral (VTI). Hemodynamic variables were concurrently recorded, including Doppler opening pressure (MAP), heart rate (HR), right atrial pressure, pulmonary artery pressure, pulmonary capillary wedge pressure (PCWP), Fick cardiac output (CO) and systemic vascular resistance (SVR). Univariate and multivariate regression analyses were used to explore the dependence of PCWP, CO, and SVR on DS, SS, VTI, MAP, HR, and RS. Multivariate linear regression analysis revealed significant contributions of DS on PCWP (PCWP pred  = 0.164DS + 4.959; R = 0.68). Receiver operating characteristic (ROC) curve analysis revealed that PCWP pred could predict an elevated PCWP ≥18 mm Hg with a sensitivity (Sn) of 94% and specificity (Sp) of 85% (area under the ROC curve 0.88). CO could be predicted by RS, VTI, and HR (CO pred  = 0.017VTI + 0.016HR + 0.12RS + 2.042; R = 0.61). CO pred could predict CO ≤4.5 L/min with Sn 73% and Sp 79% (AUC 0.81). SVR could be predicted by MAP, VTI, and HR (SVR pred  = 15.44MAP - 5.453VTI - 6.349HR + 856.15; R = 0.84) with Sn 84% and Sp 79% (AUC 0.91) to predict SVR ≥1200 dyn-s/cm 5 ., Conclusions: Doppler-TTE variables derived from the LVAD outflow cannula can reliably predict PCWP, CO, and SVR in patients supported with LVADs and may mitigate the need for invasive testing., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Background: Decoupling between diastolic pulmonary arterial pressure (dPAP) and pulmonary arterial wedge pressure (PAWP) is an index of pulmonary vasculature remodeling and provides prognostic information. Furthermore, decoupling may change during incremental left ventricular assist device (LVAD) speed changes., Methods and Results: In this prospective study, patients underwent an echocardiographic and hemodynamic ramp test after LVAD implantation and were followed for 1 year. The change in decoupling (dPAP - PAWP) between the lowest and highest LVAD speeds during the ramp test was calculated. Survival and heart failure admission rates were assessed by means of Kaplan-Meier analysis. Eighty-seven patients were enrolled in the study: 54 had a Heartmate II LVAD (60.8 ± 9.3 years of age and 34 male) and 33 had an HVAD LVAD (58.6 ± 13.2 years of age and 20 male). Patients who experienced greater changes in decoupling (Δdecoupling >3 mm Hg) had a persistently elevated dPAP at incremental LVAD speed and had worse 1-year heart failure readmission-free survival compared with the group without significant changes in the degree of decoupling (41% vs 75%; P = .001)., Conclusions: An increase in decoupling between dPAP and PAWP at incremental LVAD speed changes was associated with worse prognosis in LVAD patients., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Background: Cardiovascular implantable electronic devices (CIEDs) are common in patients undergoing heart transplantation (HT), and complete removal is not always possible at the time of transplantation., Methods: We retrospectively assessed the frequency of retained CIED leads and clinical consequences in consecutive HT patients from 2013 to 2016. Clinical outcomes included bacteremia, upper-extremity deep venous thrombosis (UEDVT), lead migration, and inability to perform magnetic resonance imaging (MRI)., Results: A total of 138 patients (55 ± 11 years of age, 76% male) were identified; 37 (27%) had retained lead fragments (RLFs) at discharge. Patients with RLFs were older, had longer lead implantation time before HT, and a higher prevalence of dual-coil CIED leads compared with those without RLFs (P < .05 for all). Lead implantation time was identified as an independent predictor for RLFs (P < .05). Patients with RLFs had a higher frequency of DVT compared with the non-RLF group during the 1-year study period (42% vs 21%; P < .04). There was no difference in bacteremia. Fourteen patients (38%) could not undergo clinically indicated MRI., Conclusion: RLFs after HT occur commonly and are associated with a higher rate of UEDVT and limit the use of MRI. Although no significant difference was found in the rates of bacteremia between the groups, this finding might be explained by the overall low incidence. Patients with risk factors for RLFs should be identified before transplantation, and complete lead removal should be considered with a multidisciplinary approach., (Copyright © 2018 Elsevier Inc. All rights reserved.)

We hypothesized that a novel invasive hemodynamic measure reflecting cardiac contractility and filling pressure would predict long-term prognosis. We retrospectively analyzed consecutive patients undergoing right heart catheterization (RHC) with milrinone drug study at our institution between 2/2013-2/2017. In addition to usual RHC measurements aortic pulsatility index (API) was calculated as (systolic blood pressure - diastolic blood pressure)/pulmonary capillary wedge pressure. Univariate and multivariate logistic regression analyses were conducted to determine association with continued medical management (MM) compared to advanced therapies (AT), defined as the combined endpoint of progression to left ventricular assist device, orthotopic heart transplant or need for inotropes, or death at 30 days and 1 year. A total of 120 patients (33% female, average age 57 ± 13 years, 45% ischemic cardiomyopathy) were included in the analysis. Baseline API was higher in patients on MM at 30-days and 1-year post-RHC, OR 2.6 (95% CI 1.6-4.5,p<0.001), OR 3.1 (95% CI 1.7-5.6,p<0.001), respectively, compared to those that progressed to AT or death. In univariate analysis a 1-point increase in API was associated with increased odds of MM compared to progression to AT or death, OR 2.6 (95% CI 1.6-4.5, p <0.001), OR 3.1 (95% CI 1.7-5.6, p <0.001) at 30-day and 1-year follow-up, respectively. In multivariate analysis API was strongly associated with continued MM and freedom from AT or death when adjusted for Fick cardiac index and pulmonary artery pulsatility index at 30-days and 1-year, respectively, OR 2.4 (95% CI 1.3-4.3, p =0.004), OR 3.2 (95% CI 1.5-6.6, p =0.002). Change in API after milrinone infusion was not significantly associated with MM at 30-day or 1-year follow-up. API is a novel invasive hemodynamic measurement that better predicts freedom from AT or death at 30-day and 1-year follow-up when compared to traditional RHC measurements. [ABSTRACT FROM AUTHOR]

A 69-year-old man with no past medical history was admitted with acute-onset heart failure with rapid progression to cardiogenic shock requiring veno-arterial extracorporeal membrane oxygenation. He underwent urgent heart transplantation (HT) within one week of listing. He received immunosuppression with methylprednisolone, mycophenolate, and tacrolimus. Retrospective crossmatch was negative. The explanted heart showed diffuse giant cell myocarditis (GCM) (Figures A-C) One week after transplant he had normal biventricular filling pressures with preserved cardiac output and a Grade 0 endomyocardial biopsy (EMB). During his second post-operative week, he developed paroxysmal atrial fibrillation, for which flecainide 50 mg twice daily was initiated. Two weeks post-transplant he had normal hemodynamics, but three of four EMB samples showed multinucleated giant cells (Figure D). Cardiac magnetic resonance (CMR) imaging was done at the time of diagnosis and was notable for non-specific diffuse late gadolinium enhancement throughout the left ventricular myocardium which "could be related to recent history of heart transplant or a diffuse infiltrative process." He was treated with a three-day course of IV methylprednisolone, one gram daily, followed by an oral steroid taper. Mycophenolate was increased from 1000 mg to 1500 mg twice daily. Tacrolimus goal remained at 10-12 [units]. EMB three- and four-weeks post-transplant did not show any evidence of GCM. Serial surveillance EMB have not shown any further recurrence of GCM throughout the first post-transplant year. Additionally, repeat CMR one- and six-months after initial imaging showed resolution of all abnormalities. Prednisone 5 mg daily will be continued indefinitely due to his GCM history. A 69-year-old man with GCM requiring urgent HT was noted to have recurrence of GCM two weeks after transplant. Following a three-day steroid pulse, the patient did not have any further recurrence of GCM during the first transplant year. [ABSTRACT FROM AUTHOR]

The addition of inotropic support is a common practice utilized to improve renal function and stimulate diuresis in heart failure patients. Here we assessed whether improvement in estimated glomerular filtration rate (eGFR) correlated with hemodynamic responsiveness to milrinone bolus. All heart failure patients who underwent milrinone loading at the time of right heart catheterization between February 2013 and November 2019 at a single academic institution were included in this analysis. Baseline hemodynamics were collected, and following a 50mcg/kg bolus of milrinone over 10 minutes, repeat invasive hemodynamics were measured. Renal function was assessed up to 4 weeks prior to RHC, at time of RHC and 7 +/-3 days post-RHC via measurement of a basic metabolic panel. Renal function response was defined as improvement of eGFR to a numerically lower stage of chronic kidney disease (CKD). The cohort of patients with and without renal improvement were compared to one another with respect to percent change in Right Atrial Pressure (RAP), Fick Cardiac Index (CI), Pulmonary Artery Pressure Index (PAPI), Systemic Vascular Resistance (SVR), Pulmonary Vascular Resistance (PVR), Aortic Pulsatility Index (API), and mean Pulmonary Artery Pressure (mPAP) after milrinone dosing. A total of 210 patients, median age 57 years (IQR 47-66 years); 33% women; 30% ischemic cardiomyopathy, 6% CKD Stage 1, 31% CKD Stage 2, 50% CKD Stage 3, 10% CKD Stage 4, and 3% CKD Stage 5 were included. When comparing patients with no response or worsening kidney function to patients with improved kidney function there were no significant differences in percent change in RAP, Fick CI, PAPI, SVR, PVR and mPAP after milrinone dosing (p=0.89, 0.71, 0.99, 0.44, 0.66, 0.72, 0.05 respectively) regardless of baseline kidney function. There were no significant associations between hemodynamic response to milrinone bolus and short-term change in renal function. Hemodynamic responsiveness to milrinone does not correlate with improved renal function. [ABSTRACT FROM AUTHOR]

Hemocompatibility-related adverse events (HRAE) are thought to be largely driven by the pump-patient interaction. We hypothesized that patients with left ventricular assist devices (LVADs) with low left ventricular stroke work index (LVSWI), and thus less native contribution to total flow, would have more adverse clinical outcomes. Hemodynamic data was prospectively collected from LVAD patients who had undergone a right heart catheterization with ramp study at our institution between April 2014 and July 2018. LVSWI was calculated as 0.0136 * ((cardiac index/heart rate) * 1000) * (mean arterial pressure - pulmonary capillary wedge pressure). We used a previously identified cutoff point of 31.73 for LVSWI to separate patients into low and high LVSWI groups. Univariate and multivariate logistic regression analyses were performed to determine the association between LVSWI and HRAE, heart failure (HF) readmission, and mortality. A total of 93 patients were included in this analysis - average age 61 +/- 11 years, 34% women, 40% Black, and 38% ischemic cardiomyopathy. Low LVSWI was not significantly associated with HRAE (HR 1.65, 95% CI 0.93-2.91, p = 0.081) in univariate analysis, but was statistically significant (HR 1.81, 95% CI 1.02-3.22, p = 0.042) when adjusted for LVAD type (HeartWare HVAD, Heartmate II, and Heartmate 3). Low LVSWI was significantly associated with HF readmission (HR 3.02, 95% CI 1.46-6.24, p = 0.0029) and mortality (HR 2.97, 95% CI 1.29-6.85, p = 0.011), even when adjusted for LVAD type (HR 3.15, 95% CI 1.52-6.54, p = 0.0021 and HR 3.13, 95% CI 1.36-7.21, p = 0.0074, respectively). Low LVSWI in LVAD patients is associated with poor prognosis and worse clinical outcomes such as increased HF readmission and mortality. [ABSTRACT FROM AUTHOR]

LVAD speed optimization via invasive ramp studies have been shown to reduce LVAD related morbidity. Many LVAD implanting centers use non-invasive echocardiographic (TTE) ramp studies for optimization and use mitral (MR) and aortic insufficiency (AI) severity as surrogates for unloading and optimization. We examined the prognostic value of residual MR and AI after invasive hemodynamic optimization. Patients underwent simultaneous TTE and hemodynamic LVAD ramp study with hemodynamic and TTE measurements at each incremental speed increase. The device was set at a speed that demonstrated an optimized hemodynamic profile with target CVP <12mmHg, PCWP <18mmHg, and cardiac index> 2.2L/min/m2. MR and AR severity at the optimized speed was quantified by TTE and the impact of residual regurgitant lesions on heart failure (HF) readmission-free survival and hemocompatibility related adverse events (HRAE) free survival and overall survival at 3 years was determined. After hemodynamic optmization, mean PCWP was 13.7mmHg, CI was 2.73L/min/m2 and RAP was 9.4mmHg for the entire cohort. 24 patients had residual mild/moderate or greater AI and 27 patients had mild or greater MR after optimization. Freedom from HRAE was higher in those without residual AI (45% vs 24%, p =0.05) at 3 years with no difference in overall survival or HF admission (Figure Top). Patients without residual MR had higher 3 year survival compared to those with residual MR (75% vs 51%, p =0.03). There was a trend toward higher HRAE and HF readmission rates in those with residual MR (Figure Bottom). Residual AI and MR after LVAD hemodynamic speed optimization has negative consequences with regard to HRAE and HF readmission-free survival and overall mortality at 3 years. Additional speed optimization may be needed in this cohort to mitigate morbidity and mortality. [ABSTRACT FROM AUTHOR]