The Hemodynamic Effects of Aortic Regurgitation in Patients Supported by a HeartMate 3 Left Ventricular Assist Device.

BACKGROUND: Aortic regurgitation (AR) is a common complication following left ventricular assist device (LVAD) implantation. We evaluated the hemodynamic implications of AR in patients with HeartMate 3 (HM3) LVAD at baseline and in response to speed changes. METHODS AND RESULTS: Clinically stable outpatients supported by HM3 who underwent a routine hemodynamic ramp test were retrospectively enrolled in this analysis. Patients were stratified based on the presence of at least mild AR at baseline speed. Hemodynamic and echocardiographic parameters were compared between the AR and non-AR groups. Sixty-two patients were identified. At the baseline LVAD speed, 29 patients (47%) had AR, while 33 patients (53%) did not. Patients with AR were older and supported on HM3 for a longer duration. At baseline speed, all hemodynamic parameters were similar between the groups including central venous pressure, pulmonary capillary wedge pressure, pulmonary arterial pressures, cardiac output and index, and pulmonary artery pulsatility index (p > 0.05 for all). During the subacute assessment, AR worsened in some, but not all, patients, with increases in LVAD speed. There were no significant differences in 1-year mortality or hospitalization rates between the groups, however, at 1-year, ≥ moderate AR and right ventricular failure (RVF) were detected in higher rates among the AR group compared to the non-AR group (45% vs. 0%; p < 0.01, and 75% vs. 36.8%; p = 0.02, respectively). CONCLUSIONS: In a cohort of stable outpatients supported with HM3 who underwent a routine hemodynamic ramp test, the presence of mild or greater AR did not impact the ability of HM3 LVADs to effectively unload the left ventricle during early subacute assessment. Although the presence of AR did not affect mortality and hospitalization rates, it resulted in higher rates of late hemodynamic-related events in the form of progressive AR and RVF.

CAV Trajectories Among Patients With No or Mild CAV at 10 Years Posttransplant.

Cardiac allograft vasculopathy (CAV) is a major cause of morbidity and mortality following heart transplantation (HT). Prior studies identified distinct CAV trajectories in the early post-HT period with unique predictors, but the evolution of CAV in later periods is not well-described. This study assessed the prevalence of late CAV progression and associated risk factors in HT recipients with ISHLT CAV 0/1 at 10 years post-HT. Consecutive adult patients who underwent HT from January 2000 to December 2008 were evaluated and grouped by CAV trajectories into progressors (developed ISHLT CAV 2/3) or nonprogressors (remained ISHLT CAV 0/1). A total of 130 patients were included with a median age at angiography of 61.7 years and a median follow-up time of 4.8 years. 8.5% progressed to CAV 2/3, while the remaining 91.5% were nonprogressors. Progression was not associated with death or retransplantation (27.3% [progressor] vs. 21.0% [nonprogressor], p = 0.70). These data may inform shared decision-making about late CAV screening.

Pre-operative pectoralis muscle area index is associated with biomarkers of inflammation and endotoxemia and predicts clinical outcomes after left ventricular assist device implantation: A cohort study.

BACKGROUND: Pre-left ventricular assist device (LVAD) pectoralis muscle assessment, an estimate of sarcopenia, has been associated with postoperative mortality and gastrointestinal bleeding, though its association with inflammation, endotoxemia, length-of-stay (LOS), and readmissions remains underexplored. METHODS: This was a single-center cohort study of LVAD patients implanted 1/2015-10/2018. Preoperative pectoralis muscle area was measured on chest computed tomography (CT), adjusted for height squared to derive pectoralis muscle area index (PMI). Those with PMI in the lowest quintile were defined as low-PMI cohort; all others constituted the reference cohort. Biomarkers of inflammation (interleukin-6, adiponectin, tumor necrosis factor-α [TNFα]) and endotoxemia (soluble (s)CD14) were measured in a subset of patients. RESULTS: Of the 254 LVAD patients, 95 had a preoperative chest CT (median days pre-LVAD: 7 [IQR 3-13]), of whom 19 (20.0%) were in the low-PMI cohort and the remainder were in the reference cohort. Compared with the reference cohort, the low-PMI cohort had higher levels of sCD14 (2594 vs. 1850 ng/mL; p = 0.04) and TNFα (2.9 vs. 1.9 pg/mL; p = 0.03). In adjusted analyses, the low-PMI cohort had longer LOS (incidence rate ratio 1.56 [95% confidence interval 1.16-2.10], p = 0.004) and higher risk of 90-day and 1-year readmissions (subhazard ratio 5.48 [1.88-16.0], p = 0.002; hazard ratio 1.73 [1.02-2.94]; p = 0.04, respectively). CONCLUSIONS: Pre-LVAD PMI is associated with inflammation, endotoxemia, and increased LOS and readmissions.

Unplanned hospital readmissions following HeartMate 3 implantation: Readmission rates, causes, and impact on survival.

BACKGROUND: Hospital readmissions following left ventricular assist device (LVAD) remain a frequent comorbidity, associated with decreased quality of life and increased resources utilization. This study sought to determine causes, predictors, and impact on survival of hospitalizations during HeartMate 3 (HM3) support. METHODS: All patients implanted with HM3 between November 2014 to December 2019 at Columbia University Irving Medical Center were consecutively enrolled in the study. Demographics and clinical characteristics from the index admission and the first outpatient visit were collected and used to estimate 1-year and 900-day readmission-free survival and overall survival. Multivariable analysis was performed for subsequent readmissions. RESULTS: Of 182 patients who received a HM3 LVAD, 167 (92%) were discharged after index admission and experienced 407 unplanned readmissions over the median follow up of 727 (interquartile range (IQR): 410.5, 1124.5) days. One-year and 900-day mean cumulative number of all-cause unplanned readmissions was 0.43 (95%CI, 0.36, 0.51) and 1.13 (95%CI, 0.99, 1.29). The most frequent causes of rehospitalizations included major infections (29.3%), bleeding (13.2%), device-related (12.5%), volume overload (7.1%), and other (28%). One-year and 900-day survival free from all-cause readmission was 38% (95%CI, 31-46%) and 16.6% (95%CI, 10.3-24.4%). One-year and 900-day freedom from 2, 3, and ≥4 readmissions were 60.7%, 74%, 74.5% and 26.2%, 33.3%, 41.3%. One-year and 900-day survival were unaffected by the number of readmissions and remained >90%. Male sex, ischemic etiology, diabetes, lower serum creatinine, longer duration of index hospitalization, and a history of readmission between discharge and the first outpatient visit were associated with subsequent readmissions. CONCLUSIONS: Unplanned hospital readmissions after HM3 are common, with infections and bleeding accounting for the majority of readmissions. Irrespective of the number of readmissions, one-year survival remained unaffected.

Anti-factor Xa and activated partial thromboplastin time strategies for unfractionated heparin dosing after HeartMate 3 left ventricular assist device implantation.

BACKGROUND: No clear guidelines exist for perioperative anticoagulation management after durable left ventricular assist device insertion. In this study, we sought to compare outcomes between anti-factor Xa (FXa) and activated partial thromboplastin time (aPTT) in monitoring unfractionated heparin (UFH) dosing after HeartMate 3 (HM3) insertion. METHODS: This is a single-center retrospective review of patients who received UFH after HM3 insertion between 01/2020-12/2022. Post-operative UFH dose was titrated by aPTT goal 45-60 sec (n = 53) or FXa goal 0.1-0.2 U/mL (n = 59). Baseline differences between cohorts were balanced by inverse probability treatment weighting. RESULTS: At baseline, unadjusted FXa patients were more likely to be white (47.5% vs. 35.8%, p < 0.001), INTERMACS 1-2 (69.5% vs. 47.2%, p = 0.013), have history of coronary artery disease (66.1% vs. 43.4%, p = 0.026), and lower eGFR (54.1 vs. 63.7 mL/min/1.73 m2, p = 0.029) compared to the aPTT group. After adjusting for several bleeding/thrombosis risk factors, 97.5% of FXa and 91.0% of aPTT patients reached therapeutic levels with comparable UFH duration and maximum dose. Moreover, in-hospital mortality (2.5% vs. 3.1%, p = 0.842), major bleeding events (4.2% vs. 9.2%, p = 0.360), and thromboembolic events (21.8% vs. 10.1%, p = 0.151) remained without significant differences between FXa and aPTT cohorts. There was a high degree of variability in FXa (r2 = 0.20) and aPTT (r2 = 0.22) values for any given UFH dose. CONCLUSIONS: No differences in frequency of bleeding or thromboembolic events were observed in this study between FXa versus aPTT cohorts after HM3 implantation. More longitudinal studies are warranted to determine whether or not one assay is superior to the other.

The Difference Between Cystatin C- and Creatinine-Based Estimated GFR in Heart Failure With Reduced Ejection Fraction: Insights From PARADIGM-HF.

RATIONALE & OBJECTIVE: The clinical implications of the discrepancy between cystatin C (cysC)- and serum creatinine (Scr)-estimated glomerular filtration rate (eGFR) in patients with heart failure (HF) and reduced ejection fraction (HFrEF) are unknown. STUDY DESIGN: Post-hoc analysis of randomized trial data. SETTING & PARTICIPANTS: 1,970 patients with HFrEF enrolled in PARADIGM-HF with available baseline cysC and Scr measurements. EXPOSURE: Intraindividual differences between eGFR based on cysC (eGFRcysC) and Scr (eGFRScr; eGFRdiffcysC-Scr). OUTCOMES: Clinical outcomes included the PARADIGM-HF primary end point (composite of cardiovascular [CV] mortality or HF hospitalization), CV mortality, all-cause mortality, and worsening kidney function. We also examined poor health-related quality of life (HRQoL), frailty, and worsening HF (WHF), defined as HF hospitalization, emergency department visit, or outpatient intensification of therapy between baseline and 8-month follow-up. ANALYTICAL APPROACH: Fine-Gray subdistribution hazard models and Cox proportional hazards models were used to regress clinical outcomes on baseline eGFRdiffcysC-Scr. Logistic regression was used to investigate the association of baseline eGFRdiffcysC-Scr with poor HRQoL and frailty. Linear regression models were used to assess the association of WHF with eGFRcysC, eGFRScr, and eGFRdiffcysC-Scr at 8-month follow-up. RESULTS: Baseline eGFRdiffcysC-Scr was higher than +10 and lower than-10mL/min/1.73m2 in 13.0% and 35.7% of patients, respectively. More negative values of eGFRdiffcysC-Scr were associated with worse outcomes ([sub]hazard ratio per standard deviation: PARADIGM-HF primary end point, 1.18; P=0.008; CV mortality, 1.34; P=0.001; all-cause mortality, 1.39; P<0.001; worsening kidney function, 1.31; P=0.05). For a 1-standard-deviation decrease in eGFRdiffcysC-Scr, the prevalences of poor HRQoL and frailty increased by 29% and 17%, respectively (P≤0.008). WHF was associated with a more pronounced decrease in eGFRcysC than in eGFRScr, resulting in a change in 8-month eGFRdiffcysC-Scr of-4.67mL/min/1.73m2 (P<0.001). LIMITATIONS: Lack of gold-standard assessment of kidney function. CONCLUSIONS: In patients with HFrEF, discrepancies between eGFRcysC and eGFRScr are common and are associated with clinical outcomes, HRQoL, and frailty. The decline in kidney function associated with WHF is more marked when assessed with eGFRcysC than with eGFRScr. PLAIN-LANGUAGE SUMMARY: Kidney function assessment traditionally relies on serum creatinine (Scr) to establish an estimated glomerular filtration rate (eGFR). However, this has been challenged with the introduction of an alternative marker, cystatin C (cysC). Muscle mass and nutritional status have differential effects on eGFR based on cysC (eGFRcysC) and Scr (eGFRScr). Among ambulatory patients with heart failure enrolled in PARADIGM-HF, we investigated the clinical significance of the difference between eGFRcysC and eGFRScr. More negative values (ie, eGFRScr>eGFRcysC) were associated with worse clinical outcomes (including mortality), poor quality of life, and frailty. In patients with progressive heart failure, which is characterized by muscle loss and poor nutritional status, the decline in kidney function was more pronounced when eGFR was estimated using cysC rather than Scr.

The impact of pre-existing hematologic disorders on morbidity and mortality following heart transplantation: Focus on early graft dysfunction.

BACKGROUND: Heart transplantation (HT) is the gold standard therapy for advanced heart failure, providing excellent long-term outcomes. However, postoperative outcomes are limited by bleeding, infections, and primary graft dysfunction (PGD) that contribute to early mortality after HT. HT candidates with pre-existing hematologic disorders, bleeding, and clotting, may represent a higher risk population. We assessed the short- and long-term outcomes of patients with pre-existing hematologic disorders undergoing HT. METHODS AND RESULTS: Medical records of all adult patients who received HT from January 2010 to December 2019 at our institution were retrospectively reviewed. Hematologic disorders were identified via chart review and adjudicated by a board-certified hematologist. Inverse probability weighting and multivariable models were used to adjust for potential pretransplant confounders. Four hundred and ninety HT recipients were included, of whom 29 (5.9%) had a hematologic disorder. Hematologic disorders were associated with severe PGD requiring mechanical circulatory support (aOR 3.15 [1.01-9.86]; p = .049), postoperative infections (aOR 2.93 [1.38-6.23]; p = .01), and 3-year acute cellular rejection (ACR) (≥1R/1B) (aSHR 2.06 [1.09-3.87]; p = .03). There was no difference in in-hospital mortality (aOR 1.23 [.20-7.58], p = .82) or 3-year mortality (aHR 1.58 [.49-5.12], p = .44). CONCLUSIONS: Patients with hematologic disorders undergoing HT are at increased risk of severe PGD, postoperative infections, and ACR, while in-hospital and 3-year mortality remain unaffected.

The utilization of molecular microscope in management of heart transplant recipients in the era of noninvasive monitoring.

INTRODUCTION: Monitoring for graft rejection is a fundamental tenet of post-transplant follow-up. In heart transplantation (HT) in particular, rejection has been traditionally assessed with endomyocardial biopsy (EMB). EMB has potential complications and noted limitations, including interobserver variability in interpretation. Additional tests, such as basic cardiac biomarkers, cardiac imaging, gene expression profiling (GEP) scores, donor-derived cell-free DNA (dd-cfDNA) and the novel molecular microscope diagnostic system (MMDx) have become critical tools in rejection surveillance beyond standard EMB. METHODS: This paper describes an illustrative case followed by a review of MMDx within the context of other noninvasive screening modalities for rejection. CONCLUSIONS: We suggest MMDx be used to assist with early detection of rejection in cases of discordance between EMB and other noninvasive studies.

Predictors of 1-year outcome after cardiac re-transplantation: Machine learning analysis.

BACKGROUND: As cardiac re-transplantation is associated with inferior outcomes compared with primary transplantation, allocating scarce resources to appropriate re-transplant candidates is important. The aim of this study is to elucidate the factors associated with 1-year mortality in cardiac re-transplantation using the random forests algorithm for survival analysis. METHODS: We retrospectively reviewed the United Network for Organ Sharing registry and identified all adult (> 17 years old) recipients who underwent cardiac re-transplantation between January 2000 and March 2020. The random forest algorithm on Cox modeling was used to calculate the variable importance (VIMP) of independent variables for contributing to 1-year mortality. RESULTS: A total of 1294 patients underwent cardiac re-transplantation. Of these, 137 patients were re-transplanted within 1 year of their first transplant, while 1157 patients were re-transplanted more than 1 year after their first transplant. One-year mortality was significantly higher for patients receiving early transplantation compared with those receiving late transplantation (Early 40.6% vs. Late 13.6%, log-rank P < .001). Machine learning analysis showed that total bilirubin (> 2 mg/dl) (VIMP, 2.99%) was an independent predictor of 1-year mortality after early re-transplant. High BMI (> 30.0 kg/m2 ) (VIMP, 1.43%) and ventilator dependence (VIMP, 1.47%) were independent predictors of 1-year mortality for the late re-transplantation group. CONCLUSION: Machine learning showed that optimal 1-year survival following cardiac re-transplantation was significantly related to liver function in early re-transplantation, and to obesity and preoperative ventilator dependence in late re-transplantation.

Deep vein thrombosis and pulmonary embolism after heart transplantation.

INTRODUCTION: Venous thromboembolism (VTE), such as deep vein thrombosis (DVT) and pulmonary embolism (PE), is an important and serious postoperative complication after heart transplantation. We sought to characterize in-hospital VTE after heart transplantation and its association with clinical outcomes. METHOD: Adult (≧18 years) patients undergoing heart transplantation from 2015 to 2019 at our center were retrospectively reviewed. Post-transplant VTE was defined as newly diagnosed venous system thrombus by imaging studies. RESULTS: There were 254 patients. The cohort's median age was 55 years. A total of 61 patients were diagnosed with VTE, including one with right atrial thrombus, 54 with upper extremity DVT in which one patient subsequently developed PE, four with lower extremity DVT, and two with upper and lower extremity DVT. The cumulative incidence of VTE was 42% at 60-days of post heart transplant. Patients with VTE had longer hospital stay (P < .001), higher in-hospital mortality (P = .010), and worse 5-year survival (P = .009). On the multivariable Cox analysis, history of DVT/PE and intubation for more than 3 days were associated with an increased risk of in hospital VTE. CONCLUSION: The incidence of VTE in heart transplant recipients is high. Post-transplant surveillance, and appropriate preventive measures and treatment strategies after diagnosis are warranted.

Right Ventricular Pressure-Volume Analysis During Left Ventricular Assist Device Speed Optimization Studies: Insights Into Interventricular Interactions and Right Ventricular Failure.

BACKGROUND: Interventricular interaction, which refers to the impact of left ventricular (LV) function on right ventricular (RV) function and vice versa, has been implicated in the pathogenesis of RV failure in LV assist device (LVAD) recipients. We sought to understand more about interventricular interaction by quantifying changes in the RV systolic and diastolic function with varying LVAD speeds. METHODS AND RESULTS: Four patients (ages 22-69 years, 75% male, and 25% with ischemic cardiomyopathy) underwent a protocolized hemodynamic ramp test within 12 months of LVAD implantation where RV pressure-volume loops were recorded with a conductance catheter. The end-systolic PV relationship and end-diastolic PV relationship were compared using the V20 and V10 indices (volumes at which end-systolic PV relationship and end-diastolic PV relationship reach a pressure of 20 and 10 mm Hg, respectively). The ∆V20 and ∆V10 refer to the change in V20 and V10 from the minimum to maximum LVAD speeds. RV PV loops demonstrated variable changes in systolic and diastolic function with increasing LVAD speed. The end-systolic PV relationship changed in 1 patient (patient 2, ∆V20 = 23.5 mL), reflecting a decrease in systolic function with increased speed, and was unchanged in 3 patients (average ∆V20 = 7.4 mL). The end-diastolic PV relationship changed with increasing speed in 3 of 4 patients (average ∆V10 = 12.5 mL), indicating an increase in ventricular compliance, and remained unchanged in one participant (patient 1; ∆V10 = 4.0 mL). CONCLUSIONS: Interventricular interaction can improve RV compliance and impair systolic function, but the overall effect on RV performance in this pilot investigation is heterogeneous. Further research is required to understand which patient characteristics and hemodynamic parameters influence the net impact of interventricular interaction.

Extracorporeal photopheresis and its role in heart transplant rejection: prophylaxis and treatment.

Heart transplantation is the gold standard therapeutic option for select patients with end-stage heart failure. Unfortunately, successful long-term outcomes of heart transplantation can be hindered by immune-mediated rejection of the cardiac allograft, specifically acute cellular rejection, antibody-mediated rejection, and cardiac allograft vasculopathy. Extracorporeal photopheresis is a cellular immunotherapy that involves the collection and treatment of white blood cells contained in the buffy coat with a photoactive psoralen compound, 8-methoxy psoralen, and subsequent irradiation with ultraviolet A light. This process is thought to cause DNA and RNA crosslinking, ultimately leading to cell destruction. The true mechanism of therapeutic action remains unknown. In the last three decades, extracorporeal photopheresis has shown promising results and is indicated for a variety of conditions. The American Society for Apheresis currently recommends the use of extracorporeal photopheresis for the treatment of cutaneous T-cell lymphoma, scleroderma, psoriasis, pemphigus vulgaris, atopic dermatitis, graft-versus-host disease, Crohn's disease, nephrogenic systemic fibrosis, and solid organ rejection in heart, lung, and liver transplantation. In this review, we aim to explore the proposed effects of extracorporeal photopheresis and to summarize published data on its use as a prophylactic and therapy in heart transplant rejection.

United network for organ sharing outcomes after heart transplantation for al compared to ATTR cardiac amyloidosis.

Light-chain (AL) cardiac amyloidosis (CA) has a worse prognosis than transthyretin (ATTR) CA. In this single-center study, we compared post-heart transplant (OHT, orthotopic heart transplantation) survival for AL and ATTR amyloidosis, hypothesizing that these differences would persist post-OHT. Thirty-nine patients with CA (AL, n = 18; ATTR, n = 21) and 1023 non-amyloidosis subjects undergoing OHT were included. Cox proportional hazards modeling was used to evaluate the impact of amyloid subtype and era (early era: from 2001 to 2007; late era: from 2008 to 2018) on survival post-OHT. Survival for non-amyloid patients was greater than ATTR (P = .034) and AL (P < .001) patients in the early era. One, 3-, and 5-year survival rates were higher for ATTR patients than AL patients in the early era (100% vs 75%, 67% vs 50%, and 67% vs 33%, respectively, for ATTR and AL patients). Survival in the non-amyloid cohort was 87% at 1 year, 81% at 3 years, and 76% at 5 years post-OHT. In the late era, AL and ATTR patients had unadjusted 1-year, 3-year, and 5-year survival rates of 100%, which was comparable to non-amyloid patients (90% vs 84% vs 81%). Overall, these findings demonstrate that in the current era, differences in post-OHT survival for AL compared to ATTR are diminishing; OHT outcomes for selected patients with CA do not differ from non-amyloidosis patients.

Predictors of survival following trans-catheter aortic valve closure for left ventricular assist device associated aortic insufficiency.

OBJECTIVE: This study sought to assess the long-term clinical benefits and predictors of survival of trans-catheter aortic valve closure in left ventricular assist device (LVAD) patients. BACKGROUND: LVADs have been shown to increase survival and quality of life in patients with end-stage heart failure. However, severe aortic insufficiency (AI) can develop in up to 50% of patients at 12 months resulting in significant morbidity and mortality. Trans-catheter treatment of LVAD associated AI has emerged as a potential alternative to surgical treatment. METHODS: We conducted a retrospective analysis of all patients undergoing trans-catheter aortic valve closure using an Amplatzer Multi-Fenestrated Septal Occluder "Cribriform" device to assess potential clinical and procedural factors associated with survival. Student's t-tests were used to compare baseline patient demographics and procedural characteristics, as well as patient outcomes immediately post procedure and at 6 months. A P-value of less than 0.05 was considered statistically significant. RESULTS: A total of 10 patients (70% male, median age 59 years) were included. Technical success was accomplished in 100% of patients with a 6 month survival rate of 30% (3/10). Compared with survivors, non-survivors had a higher rate of pre-procedural clinical co-morbidities, an increased likelihood of right ventricular failure, and received larger occluder devices. CONCLUSIONS: Trans-catheter aortic valve closure successfully treats late severe AI in LVAD patients, however, the presence or development of right heart failure portends a worse prognosis. Further studies are needed to investigate the factors involved in the development of right ventricular failure, and potential treatment, in patients undergoing trans-catheter aortic valve closure.

Left Ventricular Decompression During Speed Optimization Ramps in Patients Supported by Continuous-Flow Left Ventricular Assist Devices: Device-Specific Performance Characteristics and Impact on Diagnostic Algorithms.

BACKGROUND: Echocardiographic ramp tests have been widely used to help guide speed adjustments and for identification of potential device malfunctions in patients with axial continuous-flow left ventricular assist devices (LVADs) (Heartmate II LVAD [HMII]). Recently, the use of centrifugal-flow LVADs (Heartware LVAD [HVAD]) has been on the rise. The purpose of this study was to evaluate the utility of ramp tests for assessing ventricular decompression in HVAD patients. METHODS AND RESULTS: In this prospective study, ramp tests were performed before index hospitalization discharge or at the time of device malfunction. Vital signs, device parameters (including flow), and echocardiographic parameters (including left ventricular end-diastolic dimension [LVEDD], frequency of aortic valve [AV] opening, and valvular insufficiency) were recorded in increments of 100 rpm, from 2,300 rpm to 3,200 rpm. Twenty-six ramp tests were performed, 19 for speed optimization and 7 for device malfunction assessment. The average speed after the speed optimization ramp tests was 2,534.74 ± 156.32 RPM, and the AV closed at a mean speed of 2,751.77 ± 227.16 rpm, with 1 patient's valve remaining open at the maximum speed. The reduction in LVEDD for each speed increase was significantly different when the AV was open or closed, at -0.09 cm/increment and -0.15 cm/increment, respectively (P = .013), which is significantly different than previously established HMII LVEDD slopes. There were also significant changes in overall device flow (P = .001), upper flow (P = .031), and lower flow (P = .003) after AV closure. The power slope did not change significantly after the AV closed (P = .656). Five of the 19 tests were stopped before completion owing to suction events, but all tests reached ≥3,000 rpm. CONCLUSIONS: The parameter slopes for the HMII cannot be directly applied to ramp studies in HVAD patients. Overall, the LVEDD slope is drastically smaller in magnitude than the previously reported HMII findings, and speed adjustments were not based on the degree of left ventricular unloading. Therefore, the slope of the LVEDD-rpm relationship is not likely to be helpful in evaluating HVAD function.

Advances in the pathophysiology and treatment of heart failure with preserved ejection fraction.

PURPOSE OF REVIEW: With the failure of multiple trials to identify a successful therapy for heart failure with preserved ejection fraction (HFpEF), attention has shifted to defining specific phenotypes within the HFpEF spectrum in an effort to develop a targeted approach to treatment. Here we summarize the most recent studies investigating the pathophysiology and clinical features of HFpEF, and discuss recent clinical trials in the context of developing treatments that look toward the underlying cause of this disorder. RECENT FINDINGS: Advances in basic science and clinical research have further characterized HFpEF, identifying multiple pathophysiological mechanisms that ultimately lead to exercise intolerance and volume overload. The success of small studies focused on specific subsets of the HFpEF population has promoted the concept that there may not be one treatment strategy that can universally be applied to HFpEF. SUMMARY: HFpEF is associated with significant morbidity and mortality and accounts for approximately half of patients with chronic heart failure. HFpEF is a complex disease, encompassing a diverse cohort of patients and marked by the presence of multiple etiological mechanisms. The failure to develop successful therapies for the management of HFpEF may be because of inadequate standardization of the HFpEF diagnosis, overly broad inclusion criteria and inadequate differentiation of disease subtypes. Given the heterogeneity among patients with HFpEF, much of the current research is focused on understanding of pathophysiology and identifying disease phenotypes that may respond to a targeted treatment approach. Several newer approaches, including neprilysin inhibition and device therapy, offer promise for a new era of HFpEF treatment.

Evolution of Mechanical Circulatory Support for advanced heart failure.

This comprehensive review highlights the significant advancements in Left Ventricular Assist Device (LVAD) therapy, emphasizing its evolution from the early pulsatile flow systems to the cutting-edge continuous-flow devices, particularly the HeartMate 3 (HM3) LVAD. These advancements have notably improved survival rates, reduced complications, and enhanced the quality of life (QoL) for patients with advanced heart failure. The dual role of LVADs, as a bridge-to-transplantation and destination therapy is discussed, highlighting the changing trends and policies in their application. The marked reduction in hemocompatibility-related adverse events (HRAE) with the HM3 LVAD, compared to previous models signifies ongoing progress in the field. Challenges such as managing major infections are discussed, including innovative solutions like energy transfer systems aimed at eliminating external drivelines. It explores various LVAD-associated complications, including HRAE, infections, hemodynamic-related adverse events, and cardiac arrhythmias, and underscores emerging strategies for predicting post-implantation outcomes, fostering a more individualized patient care approach. Tools such as the HM3 risk score are introduced for predicting survival based on pre-implant factors, along with advanced imaging techniques for improved complication prediction. Additionally, the review highlights potential new technologies and therapies in LVAD management, such as hemodynamic ramp tests for optimal speed adjustment and advanced remote monitoring systems. The goal is to automate LVAD speed adjustments based on real-time hemodynamic measurements, indicating a shift towards more effective, patient-centered therapy. The review concludes optimistically that ongoing research and potential future innovations hold the promise of revolutionizing heart failure management, paving the way for more effective and personalized treatment modalities.

Acute right ventricular geometric change predicts outcomes in HeartMate 3 patients.

BACKGROUND: The physiological response of the right ventricle (RV) following left ventricular assist device (LVAD) implantation is difficult to predict. We aimed to investigate RV geometric and functional changes after LVAD insertion and their effects on clinical outcomes. METHODS: We retrospectively reviewed 188 patients who underwent HeartMate 3 implantation at our center between November 2014 and September 2021. The RV end-diastolic diameter (RVEDD) and RV end-diastolic area (RVEDA) were measured on preoperative and predischarge transthoracic echocardiography. The nonadapted group included patients with increased RVEDD and RVEDA at discharge. The composite outcome was defined as death or readmission due to worsening right heart failure. RESULTS: There were 82 patients (44%) who had a nonadapted and 106 patients (56%) who had an adapted RV. Preoperatively, the nonadapted group had smaller RVEDD (46 vs 49 mm, p < 0.001) and RVEDA (27 vs 31 cm2, p < 0.001). At discharge, the nonadapted group had larger RVEDD (51 vs 43 mm, p < 0.001) and RVEDA (33 vs 27 cm2, p < 0.001). Kaplan-Meier analysis demonstrated worse 3-year survival (77% vs 91%, p = 0.006) and freedom from composite outcome (58% vs 85%, p < 0.001) in the nonadapted group. A multivariable Cox proportional hazards model showed that nonadaption (hazard ratio [HR] 3.09, 95% confidence interval [CI] 1.29-7.40, p = 0.01) and age (HR 3.73, 95% CI 1.42-9.77, p = 0.007) were independent predictors of composite outcome. CONCLUSIONS: Acute RV dimensional changes after LVAD insertion may represent intrinsic RV function and may be a useful prognostic marker.

"Durable left ventricular assist devices as a bridge to transplantation in The Old and The New World".

Heart transplantation remains the gold standard treatment for end-stage heart failure patients without contraindications. However, limited donor availability and long wait times have created a need for left ventricular assist devices (LVAD) to be used as a bridge to transplantation in appropriately selected patients. Improvements in LVAD technology have resulted in improved short- and long-term outcomes, further supporting the use of these devices for a bridge-to-transplant (BTT) indication. LVAD utilization as BTT exhibits notable disparities worldwide, mainly due to variations in organ availability, allocation policies, and financial constraints. Although Europe has experienced a consistent increase in the use of LVAD for this purpose, the United Network for Organ Sharing 2018 policy amendment resulted in a significant reduction in the number of LVADs used for BTT in the US. To overcome this issue, modifications in the US allocation policy to consider factors such as days on device support, age, and type of complications may be necessary to potentially increase implantation rates.The authors provide an overview comparing the current state of heart transplantation in the US and Europe, with a particular focus on how distinct allocation policies and organ availability impact medical practices. Additionally, the review will examine critical aspects ranging from patient selection and pre-implantation optimization to post-transplant outcomes.

Myocardial Recovery With HeartMate 3 Left Ventricular Assist Device: An Attainable Goal That Needs Better Precision.

Despite advances in our understanding of myocardial recovery among left ventricular assist device (LVAD) patients, with 10-30% of patients achieving substantial myocardial improvement, the rates of LVAD support cessation remain extremely low (1-2%). These numbers are in stark contrast to clinical trial data where successful LVAD cessation is reported in up to 47% of patients. The majority of LVAD programs lack structured recovery programs and targeted protocols, likely underscoring the heterogeneity that exists among LVAD patients with myocardial recovery. This perspective summarizes the current medical and surgical challenges with respect to 1) identifying the appropriate candidates for LVAD cessation; 2) methods to wean LVAD support; 3) reviewing surgical techniques for cessation of current generation HeartMate 3 LVAD; and 4) approaching shared decision making for LVAD cessation between patients and providers given the uncertainties that remain in the field.