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• Results indicate that peripheral venous and tissue congestion are mediators of heart failure pathophysiology via induction of inflammation, oxidative stress, neurohormonal and endothelial activation, and suppression of endogenous defense mechanisms. • Treatment of congestion may have a critical role not only in symptom relief, but also in forestalling disease progression. • These results may also justify future testing of new adjuvant therapies (eg, short-term anti-inflammatory and anti-oxidant treatments) in patients with acute heart failure. Venous congestion (VC) is a hallmark of symptomatic heart failure (HF) requiring hospitalization; however, its role in the pathogenesis of HF progression remains unclear. We investigated whether peripheral VC exacerbates inflammation, oxidative stress and neurohormonal and endothelial cell (EC) activation in patients with HF with reduced ejection fraction (HFrEF). Two matched groups of patients with HFrEF and with no peripheral VC vs without recent HF hospitalization were studied. We modeled peripheral VC by inflating a cuff around the dominant arm, targeting ∼ 30 mmHg increase in venous pressure (venous stress test [VST]). Blood and ECs were sampled before and after 90 minutes of VST. We studied 44 patients (age 53 ± 12 years, 32% female). Circulating endothelin-1, tumor necrosis factor-α, interleukin-6, isoprostane, angiotensin II (ang-2), angiopoietin-2, vascular cell adhesion molecule-1, and CD146 significantly increased after the VST. Enhanced endothelin-1 and angiopoietin-2 responses to the VST were present in patients with vs without recent hospitalization and were prospectively associated with incident HF-related events; 6698 messenger ribonucleic acid (mRNA probe sets were differentially expressed in ECs after VST. Experimental VC exacerbates inflammation, oxidative stress, neurohormonal and EC activation and promotes unfavorable transcriptome remodeling in ECs of patients with HFrEF. A distinct biological sensitivity to VC appears to be associated with high risk for HF progression. [Display omitted] [ABSTRACT FROM AUTHOR]

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. 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). 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. The Hemodynamic Effects of Aortic Regurgitation in Patients Supported with HM3. [Display omitted] [ABSTRACT FROM AUTHOR]

De novo aortic insufficiency (AI) is a common adverse event after continuous-flow left ventricular assist device (LVAD) placement and is associated with morbidity and mortality. This study aims to compare the development of de novo AI between HeartMate 3 (Abbott) and HeartMate II LVAD recipients. A retrospective review was conducted of clinical characteristics and serial echocardiograms (1 month, 6 months, and 1 year postimplantation) of HeartMate 3 patients implanted between November 2014 and March 2019 and of HeartMate II patients implanted between April 2004 and December 2015 at Columbia University Irving Medical Center. One hundred twenty-two patients were excluded from analysis for a history of aortic valve surgery, concomitant aortic valve surgery with LVAD implant, or more than trace preoperative AI left untreated. De novo AI was defined as development of more than mild AI after LVAD implant. Included in the study were 121 HeartMate 3 patients and 270 HeartMate II patients. After accounting for competing risks of death and transplantation, there was no significant difference in the development of de novo AI by 1 year postimplantation between HeartMate II and HeartMate 3 patients (P =.68). There was no significant difference in severity of AI developed up to 1 year post-implantation between HeartMate II and HeartMate 3 patients. Development of de novo AI is comparable between HeartMate 3 and HeartMate II patients. There is no significant difference in severity of AI between HeartMate II and HeartMate 3 patients. [ABSTRACT FROM AUTHOR]

The intra-aortic balloon pump (IABP) is widely implanted as temporary mechanical circulatory support for cardiogenic shock (CS). However, its use is declining following the results of the IABP-SHOCK II trial, which failed to show a clinical benefit of the IABP in acute coronary syndrome (ACS)-related CS. Acute-on-chronic heart failure has become an increasingly recognized, distinct cause of CS (HF-CS). The pathophysiology of HF-CS differs from that of ACS-CS because it typically represents the progression from a state of congestion (with relatively preserved cardiac output) to a low-output state with hypoperfusion. The IABP is a volume-displacement pump that promotes forward flow from a high-capacitance reservoir to low-capacitance vessels, improving peripheral perfusion and decreasing left ventricular afterload in the setting of high filling pressures. The IABP can improve ventricular-vascular coupling and, therefore, myocardial energetics. Additionally, many patients with HF-CS are candidates for cardiac replacement therapies (left ventricular assist device or heart transplantation) and, therefore, may benefit from a bridge strategy that stabilizes the hemodynamics and end-organ function in preparation for more durable therapies. Notably, the new United Network for Organ Sharing donor heart allocation system has recently prioritized patients on IABP support. This review describes the role of IABP in the treatment of HF-CS. It also briefly discusses new strategies for vascular access as well as fully implantable versions for longer duration of support. [ABSTRACT FROM AUTHOR]

Among left ventricular assist device patients, the most commonly infected component is the drive line, which can be managed with antibiotics and local debridement. Infection of intrathoracic device components is less common but more difficult to manage. Herein we describe the incidence of deep device infection (DDI) at our center as well as management and outcomes. We retrospectively reviewed 658 patients who underwent implantable left ventricular assist device insertion with HeartMate 2 (Abbott) or HeartMate 3 (Abbott) devices between January 2004 and June 2021. DDI was defined according to radiographic and clinical criteria. Cumulative incidence was calculated using a Fine-Gray subdistribution model; survival analysis was performed using the method of Kaplan and Meier. There were 32 (4.8%) DDIs during this study period. Drive line infection and re-exploration for bleeding were associated with development of DDI. Cumulative incidence of DDI increased over time, affecting 11% (7%-18%) at 5 years. The dominant microbes involved in DDI were Pseudomonas aeruginosa (19%) and methicillin-resistant Staphylococcus aureus (13%). Nineteen patients (59%) with device infection underwent device exchange, 6 (19%) underwent initial transplant, and 7 (22%) were treated solely with debridement and antibiotics. Of those who underwent device exchange, 12 (63%) developed reinfection of their new device and 6 underwent subsequent heart transplant. Patients who underwent transplantation for management of device infection had improved 5-year survival (80% vs 11%; P =.01) but 3 patients (25%) developed deep sternal wound infection after transplant. DDI is a rare but challenging complication in this destination era. Heart transplantation is the preferred management strategy for eligible patients but infectious complication is common. [Display omitted] [ABSTRACT FROM AUTHOR]

Background: There is a paucity of data on depression, anxiety and post-traumatic stress disorder after left ventricular assist device (LVAD) implantation. We designed an observational study to integrate these with functional capacity and health-related quality of life (HR-QOL) in surviving LVAD patients.Methods and Results: Consenting patients between 1 month and 9 years after LVAD implantation (n = 121) were screened for functional capacity (World Health Organization Disability Assessment Schedule 2.0 [WHODAS 2.0)]); HR-QOL (European Quality of Life [EQ-5D] and Visual Assessment Scales [EQ-VAS]), depression (Patient Health Questionnaire [PHQ-9], anxiety (Generalized Anxiety Disorder Scale [GAD-7]) and post-traumatic stress disorder (Impact of Event Scale Revised [IES-R]). Of the 94% of patients who consented, 34.7% reported impaired functional capacity (WHODAS 2.0 score of ≥25%), 23.1%-34.7% HR-QOL problems (domain EQ-5D of ≥3), 10.7% "poor health" (EQ-VAS of ≤40), 14.9% depression (PHQ-9 of >14), 11.7% suicidal ideation and 17.5% anxiety (GAD-7 of >10). Among these patients, 23.5% had a positive screen for post-traumatic stress disorder (IES-R of ≥24). An EQ-VAS of 80 or greater predicted good functional capacity (P < .001).Conclusions: One-third of discharged LVAD patients reported impaired function, HR-QOL, and psychological issues. A standardized evaluation before and after LVAD implantation could facilitate psychologic prehabilitation, inform decision-making, and identify indications for mental health intervention. [ABSTRACT FROM AUTHOR]

Background: Heart failure predisposes to intracardiac thrombus (ICT) formation. There are limited data on the prevalence and impact of preexisting ICT on postoperative outcomes in left ventricular assist device patients. We examined the risk for stroke and death in this patient population.Methods and Results: We retrospectively studied patients who were implanted with HeartMate (HM) II or HM3 between February 2009 and March 2019. Preoperative transthoracic echocardiograms, intraoperative transesophageal echocardiograms and operative reports were reviewed to identify ICT. There were 525 patients with a left ventricular assist device (median age 60.6 years, 81.8% male, 372 HMII and 151 HM3) included in this analysis. An ICT was identified in 44 patients (8.4%). During the follow-up, 43 patients experienced a stroke and 55 died. After multivariable adjustment, presence of ICT increased the risk for the composite of stroke or death at 6-month (hazard ratio [HR] 1.82, 95% confidence interval [CI] 1.00-3.33, P = .049). Patients with ICT were also at higher risk for stroke (HR 2.45, 95% CI 1.14-5.28, P = .021) and death (HR 2.36, 95% CI 1.17-4.79 P = .016) at 6 months of follow-up.Conclusions: The presence of ICT is an independent predictor of stroke and death at 6 months after left ventricular assist device implantation. Additional studies are needed to help risk stratify and optimize the perioperative management of this patient population. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Background: In the general population, increased aortic stiffness is associated with an increased risk of cardiovascular events. Previous studies have demonstrated an increase in aortic stiffness in patients with a continuous flow left ventricular assist device (CF-LVAD). However, the association between aortic stiffness and common adverse events is unknown.Methods and Results: Forty patients with a HeartMate II (HMII) (51 $ 11 years; 20% female; 25% ischemic) implanted between January 2011 and September 2017 were included. Two-dimensional transthoracic echocardiograms of the ascending aorta, obtained before HMII placement and early after heart transplant, were analyzed to calculate the aortic stiffness index (AO-SI). The study cohort was divided into patients who had an increased vs decreased AO-SI after LVAD support. A composite outcome of gastrointestinal bleeding, stroke, and pump thrombosis was defined as the primary end point and compared between the groups. While median AO-SI increased significantly after HMII support (AO-SI 4.4-6.5, P = .012), 16 patients had a lower AO-SI. Patients with increased (n = 24) AO-SI had a significantly higher rate of the composite end point (58% vs 12%, odds ratio 9.8, P < .01). Similarly, those with increased AO-SI tended to be on LVAD support for a longer duration, had higher LVAD speed and reduced use of angiotensin-converting enzyme inhibitors or angiotensin II receptor blockers.Conclusions: Increased aortic stiffness in patients with a HMII is associated with a significantly higher rates of adverse events. Further studies are warranted to determine the causality between aortic stiffness and adverse events, as well as the effect of neurohormonal modulation on the conduit vasculature in patients with a CF-LVAD. [ABSTRACT FROM AUTHOR]

Vasoplegia is a frequent complication of left ventricular assist device (LVAD) implantation. We investigated the effectiveness of methylene blue (MB) for vasoplegia in LVAD recipients. Twenty-seven patients received MB for vasoplegia after LVAD implantation and met study criteria between March 2015 and May 2018. Propensity score inverse probability weighting identified 41 controls who did not receive MB for post-LVAD vasoplegia. Clinical outcomes were compared between control and MB groups and between patients who received doses during (n = 15) and after surgery (n = 12). Hemodynamics and vasopressor requirements were analyzed using analysis of covariance. Median total MB dose was 1.9 mg/kg (interquartile range, 1.2-2.2 mg/kg). Methylene blue recipients experienced a transient initial decline in norepinephrine requirement from 141 ng/kg per min (95% confidence interval [CI], 81-201 ng/kg per min) to 117 ng/kg per min (95% CI, 58-176 ng/kg per min; P =.022) and a delayed decline in vasopressin from 4.8 U/h (95% CI, 3.8-5.8 U/h) to 4.0 U/h (95% CI, 2.8-5.1 U/h) (P =.004). In-hospital mortality, postoperative complications, and end-organ dysfunction did not differ from those of controls. There were no observed differences in mean arterial pressure, vasopressor requirements, or outcomes between patients who received doses during or after surgery. Weighted overall mortality in the entire study cohort was 8.8%. Although MB may affect vasopressor requirements, clinical outcomes in vasoplegia after LVAD implantation did not improve and were not affected by the timing of administration. [ABSTRACT FROM AUTHOR]

Although extremely high pulmonary vascular resistance (PVR) is a relative contraindication for heart transplantation (HTx), recent data with continuous-flow left ventricular assist devices (LVADs) indicate HTx outcomes may be different when high PVR is managed with an LVAD. This study clarifies the contemporary association between PVR at HTx and posttransplant survival in LVAD vs non-LVAD cohorts. We reviewed the United Network for Organ Sharing registry for adults who received a transplant from 2008 to 2015. In those with continuous-flow LVADs and those with no VADs at HTx, (non-VAD), we grouped patients by low PVR (PVR <3), intermediate PVR (PVR 3 to <6), and high PVR (PVR ≥6) groups. Adjusted hazard ratios (aHRs) for death after HTx were calculated by Cox regression. The non-LVAD cohort included 6270 patients (4385 in low, 1643 in intermediate, and 242 in high PVR), and the LVAD cohort included 4111 patients (3227 in low, 798 in intermediate, and 86 in high PVR). The high PVR LVAD group had the worst survival, which was not significant, likely to low power (P =.300). The aHR for death in non-LVAD was 1.047 (95% confidence interval, 1.010-1.088) and in LVAD was 1.063 (95% confidence interval, 1.010-1.119). Cubic spline analysis demonstrated nonlinear associations between PVR and the aHR, especially in the LVAD cohort. There was no significant evidence to conclude the effect of pretransplant PVR on posttransplant survival is higher in LVAD vs non-LVAD patients, based on analysis of the United Network for Organ Sharing database. However, further investigations are indicated to clarify HTx candidacy in those with extremely high PVR even after LVAD. [ABSTRACT FROM AUTHOR]

• Our algorithm for LVAD GIB was associated with a 68% increase in the diagnostic yield and a 113% increase in the therapeutic yield of endoscopy. • Implementation of our endoscopic algorithm decreased length of stay by 4 days and cost by 18%. • There was no observed increase in re-bleeding rates after algorithm implementation. Gastrointestinal bleeding (GIB) is a common complication of left ventricular assist device (LVAD) therapy accounting for frequent hospitalizations and high resource utilization. We previously developed an endoscopic algorithm emphasizing upfront evaluation of the small bowel and minimizing low-yield procedures in LVAD recipients with GIB. We compared the diagnostic and therapeutic yield of endoscopy, health-care costs, and re-bleeding rates between conventional GIB management and our algorithm using chi-square, Fisher's exact test, Wilcoxon-Mann-Whitney, and Kaplan-Meier analysis. We identified 33 LVAD patients with GIB. Presentation was consistent with upper GIB in 20 (61%), lower GIB in 5 (15%), and occult GIB in 8 (24%) patients. Forty-one endoscopies localized a source in 23 (56%), resulting in 14 (34%) interventions. Algorithm implementation compared with our conventional cohort was associated with a 68% increase in endoscopic diagnostic yield (P <.01), a 113% increase in therapeutic yield (P =.01), a 27% reduction in the number of procedures per patient (P <.01), a 33% decrease in length of stay (P <.01), and an 18% reduction in estimated costs (P <.01). The same median number of red blood cell transfusions were used in the 2 cohorts, with no increase in re-bleeding events in the algorithm cohort (33.3%) compared with our conventional cohort (43.7%). Our endoscopic management algorithm for GIB in LVAD patients proved effective in reducing low-yield procedures, improving the diagnostic and therapeutic yield of endoscopy, and decreasing health-care resource utilization and costs, while not increasing the risk of a re-bleeding event. Image, graphical abstract [ABSTRACT FROM AUTHOR]

Background: Left ventricular assist device (LVAD) therapy has revolutionized the treatment options for patients with advanced heart failure. Patient selection is essential for obtaining successful results. However, few data exist concerning the outcomes of patients evaluated for LVAD therapy but subsequently rejected or deferred.Methods and Results: This is a retrospective review of all patients referred for LVAD therapy at our institution between January 2009 and December 2016. Baseline demographics and Interagency Registry for Mechanically Assisted Circulatory Support profiles were collected, and reasons for rejection or deferral for LVAD placement were investigated. A total of 669 patients were referred for LVAD therapy, and 228 patients (34%) were turned down. The yearly acceptance rate ranged between 57% and 75%. The average age of the turned-down cohort was 60.8 ± 12.5 years; 83% were men. Reasons for rejection included: patient being too sick (34%); psychosocial concerns (25%); patient declined (16%); decision was deferred for medical optimization (15%); or patient being too well (10%). The percentage of patients who were rejected due to psychosocial concerns has increased over time (P = 0.02), whereas the rate of deferral for medical optimization has remained stable (P = 0.10). One-year survival after initial LVAD consultation was 42% in those who were too sick, 64% in those with psychosocial concerns, 68% in patients who declined, 86% in those deferred for medical optimization; and 100% in those too well (P < 0.01).Conclusions: One-year survival is reduced among patients who were initially turned down for LVAD therapy, except for those in whom this decision was deferred for medical optimization or because the patient was too well. Psychosocial concerns have become a significant barrier to LVAD therapy. [ABSTRACT FROM AUTHOR]

Bleeding and thrombotic morbidity is common and impacts outcomes following heart transplantation (HT). HT candidates with pre-existing primary bleeding and clotting disorders ("hematology cohort-HC") may represent a higher risk population. We aim to assess the short- and long-term outcomes of patients with preexisting bleeding or clotting disorders undergoing HT. : We hypothesize that HC will have higher rates of post-operative bleeding (requiring recurrent operative procedures), thrombotic complications, primary graft failure, and longer length of stay (LOS), as well as increased mortality, when compared to those without such hematologic conditions undergoing HT. Patients who received HT from January 2010 to December 2019 were retrospectively reviewed, excluding re-transplantation and multi-organ recipients. HC was identified via chart review and adjudicated by a dedicated hematologist. Basic demographics and outcome variables were abstracted. Inverse probability weighting and multivariable logistic, negative binomial, and Cox proportional hazards models were used to adjust for potential pretransplant confounders. 494 HT patients were eligible for inclusion, of whom 29 were included in the HC (Table 1). HC consisted of heparin-induced thrombocytopenia (4 patients), immune thrombocytopenia purpura (4), possible antiphospholipid antibody syndrome (2), thrombocytosis (2), antithrombin III deficiency (1), Factor V Leiden (1), polycythemia vera (1), clinically relevant hypercoagulable state not otherwise specified (14). HC was associated with severe primary graft failure requiring ECMO (aOR 3.50 [1.31-9.33]; p =0.01) and longer post-transplant LOS (adjusted mean LOS 30.0 days for HC vs. 25.2 for control, p =0.04). There was no difference in mortality between the two groups, both in-hospital (aHR 0.83 [0.06-12.0], p =0.89) and at 5-year follow up (aHR 1.42 [0.53-3.84], p =0.49). HT in patients with primary bleeding or clotting disorders is associated with increased risk of severe primary graft failure and longer LOS. Larger prospective studies are needed to assess the impact on mortality and determine the degree to which pre-existing hematologic conditions directly lead to post-transplant adverse outcomes. [ABSTRACT FROM AUTHOR]

The use of short-term mechanical circulatory support (ST-MCS) has increased for refractory cardiogenic shock. However, there are scant data about bridge-to-recovery patients. We retrospectively reviewed 502 patients with cardiogenic shock who received venoarterial extracorporeal membrane oxygenation or a temporary surgical ventricular assist device as ST-MCS between 2010 and 2016. There were 178 patients (35.5%) who survived through device explantation. Of these, 149 patients (29.7%) survived to discharge and were included for analysis. The primary outcome was midterm survival without undergoing heart replacement therapy. In our bridge-to-recovery cohort, 101 patients (67.8%) were men, and the median age was 59 years (interquartile range, 51 to 67 years). Etiology of cardiogenic shock included postcardiotomy shock in 35.6% of patients (n = 53), allograft failure in 26.8% (n = 40), acute myocardial infarction (AMI) in 24.2% (n = 36), and other acute decompensated heart failure in 14.4% (n = 20). There were 24 major events (16.1%) recorded, including 21 patients who died and 3 patients who received heart replacement therapy during median follow-up of 306 days (interquartile range, 58.25 to 916.75 days). Overall freedom from event at 3 years was 74.2%. In subgroup analysis, AMI patients had a significantly worse freedom-from-event rate at 40.4% (p < 0.001). By univariate Cox analysis, AMI etiology (p = 0.003), length of ST-MCS (p = 0.06), blood urea nitrogen (p = 0.012), and left ventricular ejection fraction (p = 0.005) at discharge were predictors for adverse events. The overall midterm outcome of patients explanted from ST-MCS is favorable except for AMI patients. [ABSTRACT FROM AUTHOR]

Background: Early right ventricular (RV) failure after left ventricular assist device (LVAD) implantation increases morbidity and mortality. Percutaneous right ventricular assist device (pRVAD) support is an alternative to more invasive surgical RVAD (sRVAD).Methods and Results: We retrospectively reviewed patients receiving isolated pRVAD or sRVAD after durable LVAD at our center in the years 2007-2018. Hemodynamic parameters before and after implantation and survival outcomes were compared among groups. Nineteen patients received pRVAD and 21 sRVAD. Hemodynamic parameters improved immediately with the use of pRVAD; central venous pressure decreased (from 15.9 ± 2.4 to 12.3 ± 3.2 mm Hg; P<.001) and cardiac index increased (from 2.4 ± 0.5 to 3.5 ± 0.8 L·min-1·m-2; P<.001). These were sustained after device removal and were similar to those with the use of sRVAD. Patients with pRVAD required fewer blood transfusions and mechanically ventilated days than those with sRVAD. Among survivors, intensive care unit and hospital days were fewer with the use of pRVAD: 21 (16-27) versus 34 (27-46) ICU days (P = .01); 43.5 (30-66) versus 91 (62-111) hospital days (P = .03). There was no significant difference in 30-day mortality with the use of pRVAD compared with sRVAD (21.1% vs 42.9%; P = .14), but there was a trend toward a higher rate of discharge free from hemodialysis (73.7% vs 47.6%; P = .09).Conclusions: Novel pRVAD systems for RV failure provide hemodynamic benefits similar to sRVAD, are associated with less morbidity, and should be considered as an alternative to sRVAD. [ABSTRACT FROM AUTHOR]

Background Blood type O heart transplant recipients wait longer than non-O recipients and frequently require bridging left ventricular assist devices (LVADs). However, rarely has the effect of this disparity been shown in a large registry. This study used Markov simulation to clarify the outcome difference between O and non-O candidates and how allocation change could affect survival. Methods We reviewed the United Network for Organ Sharing registry for adults listed for heart transplantation from 2008 to 2015. Cumulative incidences of death or transplant and survival after listing were compared between O and non-O using propensity matching. A four-state Markov model—waiting without LVAD, waiting with LVAD, transplantation, and death—was created to simulate survival after listing. Sensitivity analysis was performed to see how the percentage of O hearts in non-O recipients would affect survivals. Results A total of 8,187 O and non-O candidates were included after matching. The cumulative incidence of transplantation was lower in O (p < 0.001), and death after listing was significantly higher (p < 0.001). During a median follow-up of 2.1 years, 69.6% of non-O candidates were transplanted, compared with 54.9% of O candidates (p < 0.001). Despite this disparity, 19% of non-O recipients received O hearts. Our simulated survival demonstrated that decreasing the O heart percentage in non-O recipients from the current 19% to 5% would provide similar survival in O and non-O after listing. Conclusions Under the current strategy, there are death and transplant rate differences between O and non-O candidates. Our simulation-based allocation strategy might aid in mitigating this discrepancy across blood types. [ABSTRACT FROM AUTHOR]

Here we have evaluated tick host specificity with two different methodological approaches considering Amblyomma tigrinum and Amblyomma triste immatures as targets. Firstly, the Std* index was applied, which considers host phylogenetic relationships weighted by the prevalence of the parasite; followed by generalized linear models to explore associations between different host species and burdens and prevalence of larvae and nymphs, independently. The Std* index showed that A. tigrinum larvae and nymphs infest host species belonging to different orders and classes, respectively; while A. triste immatures fed on hosts that belong to different tribes, showing that both tick species have low specificity and thus, a generalist behavior. When analyzing prevalence and burdens, we found that both tick species infest some hosts more heavily compared with the rest. Even though immature stages of A. triste and A. tigrinum are generalists, the level of infestation within the range of usual hosts of these two species is uneven. This shows that a generalist behavior may result in dissimilar levels of infestation across a range of usual hosts. [ABSTRACT FROM AUTHOR]

Background Hospital readmissions have an adverse effect on the quality of life in patients with end-stage heart failure. We examined the temporal pattern, predictors, and outcomes of readmission in continuous flow left ventricular assist device–supported patients. Methods We retrospectively reviewed inpatient data of 350 consecutive patients who received a continuous-flow left ventricular assist device at our center between May 2004 and December 2014. A total time–restricted model was used to estimate hazard ratios for readmission, and the Nelson nonparametric method was used to estimate mean cumulative function for each cause of readmission. Results The mean age was 57 ± 13 years, 82.6% received a HeartMate II (Abbott Laboratories, Chicago, IL), and 26.3% were destination therapy. The 30-day readmission rate was 21.7%, and 264 readmissions (41.1%) occurred within the first 6 months of support. The leading cause of readmission was bleeding (0.74 mean cumulative events per person), followed by infection (0.7), device failure (0.52), arrhythmia (0.3), and right heart failure (0.28) at 3 years. The number of readmissions did not have an adverse effect on survival (hazard ratio, 1.03; 95% confidence interval, 0.92 to 1.17; p = 0.58). Increase in each body mass index unit was associated with 1.029 times the rate of overall readmission ( p = 0.041). Patients with a body mass index of 30 kg/m 2 or higher had increased readmissions for device failure ( p = 0.008) and right heart failure ( p = 0.03). Conclusions Readmission burden is highest during the first few months of continuous-flow left ventricular assist device support, but survival is not affected. Patients with an elevated body mass index are at increased risk for readmissions for device failure and right heart failure. [ABSTRACT FROM AUTHOR]

Objective Venous-arterial extracorporeal membrane oxygenation (VA-ECMO) is a well-established therapy for refractory cardiopulmonary failure. Femoral cannulation offers a quick and effective means of providing circulatory support but is not without complication. Inflammation or lymphatic disruption at the site of cannulation can cause the formation of lymphoceles, leading to the patient's discomfort and possibly necessitating intervention. The purpose of this study was to evaluate the incidence of in-hospital lymphocele formation in VA-ECMO patients and to identify predictors for their development. Methods We conducted a single-center retrospective review of 192 patients who underwent femoral VA-ECMO insertion and subsequent decannulation from March 2007 to August 2016 for cardiogenic shock. Baseline demographics, risk factors, and cannulation strategies were examined. Groin lymphocele formation was assessed as the primary outcome. Results Median age was 58 years (interquartile range, 48-67 years) with a median duration of support of 4 days (interquartile range, 2-6 days). Lymphocele formation was identified in 31 patients (16%). Patients who developed lymphoceles were more likely to have post-heart transplantation primary graft dysfunction (PGD) as an indication for ECMO support compared with those who did not (54.2% vs 8%; P < .001). ECMO duration was similar between groups, but lymphocele patients were more likely to have undergone femoral cutdown procedures (68% vs 42%; P = .010). Compared with those PGD patients who did not develop lymphoceles, PGD lymphocele patients had higher rates of diabetes mellitus preoperatively (62% vs 8%; P = .006). Thirteen (42%) patients required surgical incision and drainage, and 4 of these patients (31%) required repeated surgical intervention. Conclusions Lymphocele formation is relatively common after femoral VA-ECMO. There was a significantly higher incidence of lymphocele formation in diabetic patients requiring support for PGD after heart transplantation. [ABSTRACT FROM AUTHOR]

Background Optimal anticoagulation strategy remains uncertain in patients with heparin-induced thrombocytopenia (HIT) and undergoing left ventricular assist device (LVAD) implantation. We describe our protocol of abciximab and heparin in these patients. Methods Our protocol is to administer abciximab, 0.25 mg/kg loading dose, followed by continuous infusion of 0.125 μg · kg −1 · min −1 throughout cardiopulmonary bypass. Full-dose heparin is then given with subsequent additional doses to maintain an activated clotting time of 400 seconds or longer. The abciximab infusion is stopped 15 minutes after heparin reversal with protamine, and platelets are transfused. Results Six patients underwent LVAD implantation with this protocol in our program. HIT was confirmed in 4 patients was suspected in 2, which was negative after the operation. One patient received a HeartMate XVE (Thoratec Corp, Pleasanton, CA) and the others received HeartMate II (Thoratec Corp). There were no thromboembolic complications. One patient required chest reexploration for bleeding and temporary right VAD support. Postoperative anticoagulation with argatroban was restarted on median postoperative day 3 (range, days 1 to 6) and warfarin was started on day 5 (range, days 3 to 12). Median postoperative intensive care unit stay was 9 days (range, 5 to 76 days), and hospital stay was 22 days (range, 18 to 132 days). After the initial LVAD implantation, 1 patient required HeartMate XVE LVAD exchange to HeartMate II and subsequent heart transplant, both of which were performed with the abciximab/heparin protocol. A HeartMate II device was explanted in another patient after myocardial recovery. The remaining 4 patients are alive on device support. Conclusions This is the first report of a novel abciximab/heparin protocol for LVAD implantation in patients with HIT. The preliminary results suggest the feasibility and safety of this protocol. [ABSTRACT FROM AUTHOR]

Background Few studies have evaluated the long-term effects of continuous blood flow with reduced pulsatility on end-organ function. Methods Between May 2004 and December 2015, 469 patients underwent continuous-flow left ventricular assist device (LVAD) implantation at our center. Our study included 59 (13%) patients who were supported with an LVAD for a minimum of 3 years. We evaluated postoperative renal function and hepatic function at 1 and 6 months, and 1, 2, and 3 years after implantation in those 59 patients. Results The patients’ mean age was 63 ± 13 years, 81% were male, 53% had an ischemic cause of heart failure, and 68% underwent LVAD implantation as destination therapy. All laboratory determinations showed significant improvements at 1 month after the procedure. Hepatic values remained in a normal range for up to 3 years, although renal function improvement was predominantly transient. One month after implantation, the mean estimated glomerular filtration rate (eGFR) was improved from 58.2 ± 27.9 to 77.7 ± 33.5 mL/min/1.73 m 2 . However, 46 (78%) patients showed a gradual decline in eGFR to only 1.7% above the preoperative value after 3 years ( p = 0.67 vs baseline). The risk factors for impaired renal function after long-term support were age 60 years or older, ischemic cause, and late right heart failure. Conclusions Continuous-flow LVAD improves renal and hepatic functions in patients with advanced heart failure. However, in most, the initial improvement in renal function is largely transient and returns to baseline after a prolonged support period. [ABSTRACT FROM AUTHOR]

Primary graft dysfunction and very early graft rejection are rare complications of orthotopic heart transplantation (OHT). Surveillance for graft rejection OHT relays on endomyocardial biopsies (EMB) at regular intervals. The histopathological information combined with clinical and hemodynamic assessment is key in the management of HT recipients. The reliability of first-week EMB is uncertain, due to the proximity to the procedure, which may predispose to inaccuracies related to a higher incidence of ischemic and inflammatory changes and may confer a high false-positive rate. We set out to assess the utility of the first-week EMB in correctly diagnosing clinically significant rejection, graft dysfunction, and short- and long-term adverse events. Using the institution OHT registry, we included consecutive patients who underwent OHT between the years 2010 and 2019. Patient demographic, baseline characteristics, immunosuppression regimen, and EMB pathology results were collected. A biopsy that was taken <10 days from transplant was included in this analysis. Acute cellular rejection (ACR) was considered positive if greater than grade 1R. We identified patients with a positive first biopsy result and correlated the biopsy result with clinical and invasive hemodynamic evidence for rejection. We included 472 patients who underwent OHT. Of them. 17 patients (3.6%) had a positive first EMB of equal to or greater than 2R within a median period of 7 days (IQR 6,8). 15 patients had normal graft function and hemodynamics and only 2 patients (0.4%) had graft dysfunction. All patients were treated for ACR with pulse steroids and showed ≤ Grade 1R/1A in subsequent EMB (week 2). 30 days, 6 months, and 1-year overall survival was 100%. The rate of rejection in the first 10 days is extremely low. Furthermore, graft dysfunction or hemodynamic instability is rare. The overall outcome of this cohort was excellent. This questions the relevance of EMB in that time period. HT physicians should be mindful of the effect of ischemic injury and non-rejection-related transient inflammation on the pre-test probability of early rejection. Those findings call to question the utility of EMB in the first 10 days. [ABSTRACT FROM AUTHOR]

Summary: Recent advances in microbiome research have informed the potential role of the gut microbiota in the regulation of metabolic, cardiovascular, and renal systems, and, when altered, in the pathogenesis of various cardiometabolic disorders, including chronic kidney disease (CKD). The improved understanding of gut dysbiosis in cardiometabolic pathologies in turn has led to a vigorous quest for developing therapeutic strategies. These therapeutic strategies aim to investigate whether interventions targeting gut dysbiosis can shift the microbiota toward eubiosis and if these shifts, in turn, translate into improvements in (or prevention of) CKD and its related complications, such as premature cardiovascular disease. Existing evidence suggests that multiple interventions (eg, plant-based diets; prebiotic, probiotic, and synbiotic supplementation; constipation treatment; fecal microbiota transplantation; and intestinal dialysis) might result in favorable modulation of the gut microbiota in patients with CKD, and thereby potentially contribute to improving clinical outcomes in these patients. In this review, we summarize the current understanding of the characteristics and roles of the gut microbiota in CKD and discuss the potential of emerging gut microbiota–targeted interventions in the management of CKD. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Objectives To facilitate venoarterial extracorporeal membrane oxygenation (ECMO) insertion for cardiogenic shock, we recently adopted a strategy of using a 15F arterial cannula in all patients, rather than 1 designed to maximize flow. We aimed to compare the clinical outcomes of these 2 strategies. Methods In this retrospective study, 101 consecutive patients supported with ECMO via femoral cannulation between March 2007 and March 2013 were divided into 2 groups: Group L (17F-24F arterial cannula to accommodate full flow [ie, cardiac index of 2.5 L/m 2 /min]; n = 51) and Group S (15F arterial cannula; n = 50). The primary outcomes of interest were patients' overall status at 24 hours of support and cannulation-related adverse events. Results There were no significant differences in patient demographics, etiology of cardiogenic shock, or severity of illness before ECMO initiation between the 2 groups. Group L had significantly higher ECMO flow than Group S (flow index at 24 hours: 2.2 ± 0.7 vs 1.7 ± 0.3 L/m 2 /min; P < .001). However, there was no significant difference in use of vasoactive medication/hemodynamic parameters/laboratory parameters. Group L had higher incidence of cannulation-related adverse events (35% vs 22% in Group S [ P = .14]), particularly in cannulation site bleeding (28% vs 10% [ P = .03]). Thirty-day survival was 55% in Group L versus 52% in Group S ( P = .77). Bleeding complication occurred in 53% in Group L versus 32% in Group S ( P = .03). Conclusions Compared with the use of larger cannulas, ECMO with a 15F arterial cannula appears to provide comparable clinical support with reduced bleeding complications. [ABSTRACT FROM AUTHOR]

In this study we analyzed seasonal trends of immature stages of Ixodes loricatus parasitizing Akodon azarae (Sigmodontinae) in a locality of the Paraná Delta, Buenos Aires, Argentina. The data encompassed two consecutive years and the analysis included the control of potential confounders using Generalized Linear Mixed Models (GLMM) with a negative binomial response. Larvae had within-year differences in abundance, but the peak months differed drastically between both sampling years, indicating that there was no consistent seasonal pattern. Regarding nymphs, a seasonal pattern was first apparent, but it vanished completely when potential confounders were considered, strongly suggesting that the association with season was spurious and caused by the confounders. Our results showed that the occurrence of immature I. loricatus in its hosts does not follow a distinct seasonal pattern, and highlight the usefulness of controlling for confounding and statistically assessing consistency between years when establishing tick seasonality. [ABSTRACT FROM AUTHOR]

In the present study, we report the first in vitro isolation and infection intensity of Rickettsia parkeri in Amblyomma triste ticks from Argentina. No genetic differences in the molecular targets evaluated were found between R. parkeri isolates from Argentina and those R. parkeri isolates reported in Uruguay and Brazil, both obtained from A. triste . Only a minor difference was observed when compared to R. parkeri isolated from Amblyomma maculatum from United States. Moreover, the prevalence of infection by R. parkeri in ticks collected from the vegetation in the Paraná Delta was high (20.4%). Interestingly, the distribution of R. parkeri infection intensity observed in A. triste ticks was distinctly bimodal, with approximately 60% of the infected ticks presenting high rickettsial loads (3.8 × 10 5 –4.5 × 10 7 ompA copies/tick) and the remainder with low rickettsial levels (5.6 × 10 1 –6.5 × 10 3 ompA copies/tick). This bimodality in R. parkeri infection intensity in ticks could determine differences in the severity of the disease, but also be important for the infection dynamics of this pathogen. Further research exploring the distribution of rickettsial infection levels in ticks, as well as its determinants and implications, is warranted. [ABSTRACT FROM AUTHOR]

Abstract: Background: The venous endothelium is a key regulator of central blood volume, organ perfusion, and hemostasis in heart failure (HF). We previously reported activation of the inflammatory/oxidative program in venous endothelial cells collected from decompensated HF patients. The underlying causes are unknown. We tested the hypothesis that the pro-inflammatory state of HF and vascular strain associated with congestion can activate the endothelial inflammatory/oxidative and hemostatic programs. Methods and Results: We studied 6 normal (NL) dogs (left ventricular ejection fraction [LVEF] >50%, central venous pressure [CVP] = 8 ± 2 mm Hg) and 6 dogs with HF (LVEF ∼30%, CVP 8 ± 2 mm Hg) produced by intracoronary microembolizations. Normal dogs were studied at baseline and 1 hour after fluid load to a target CVP ≥20 mm Hg. Endothelial cells were scraped from jugular veins; mRNA expression was analyzed by reverse transcription polymerase chain reaction. The endothelial inflammatory/oxidative and hemostatic programs were significantly activated in HF dogs compared with NL. In NL dogs, fluid load significantly activated the endothelial inflammatory/oxidative and hemostatic programs, and, concurrently, caused a significant increase in plasma neurohumoral indices to levels that approached those of HF dogs. Conclusions: The pro-inflammatory state of HF and vascular strain associated with congestion can both activate venous endothelial cells in dogs in a manner consistent with that seen in HF patients. [Copyright &y& Elsevier]

Abstract: Background: The effects of chronic inhibition of 5′-phosphodiesterase with sildenafil on functional capacity, ventilatory efficiency, oxygen uptake, pulmonary hypertension, and endothelial function in chronic heart failure (CHF) are unknown. Methods: We conducted a randomized, double-blind, placebo-controlled trial to assess the acute (1 hour after 50 mg by mouth) and chronic (4 weeks after 50 mg 3 times per day by mouth) effects of sildenafil in outpatients with CHF. The outcomes were cardiopulmonary exercise test parameters (chronic effect), echocardiographic-derived pulmonary artery systolic pressure, and plethysmography-derived forearm blood flow (acute and chronic effects). Results: Nineteen patients with CHF (48 ± 12 years) with an ejection fraction of 28% ± 6% were studied. Patients who received sildenafil (n = 11) showed improved maximal oxygen uptake, ventilatory efficiency, and oxygen uptake kinetics. Sildenafil decreased pulmonary artery systolic pressure levels at 60 minutes and at 4 weeks compared with changes after placebo (P = .004 for group and time interaction). Improvement in ventilatory efficiency was positively associated with reductions in pulmonary artery systolic pressure. Patients allocated to placebo demonstrated a trend toward decreased forearm blood flow after reactive hyperemia, whereas this remained unchanged in patients allocated to sildenafil. Conclusions: Sildenafil administration for 4 weeks in stable outpatients with CHF improves functional capacity, ventilatory efficiency, oxygen uptake kinetics, and pulmonary hypertension. These effects may be mediated in part by improvements in endothelial function. [Copyright &y& Elsevier]

Abstract: Background: Oxidative stress is an important pathophysiologic feature in chronic heart failure (CHF) and may in part result from the inability to counteract acute surges of circulating oxidant products. Oxidized low-density lipoprotein (oxLDL) is an emerging prognostic marker in CHF. Accordingly, we investigated the effect of exercise-induced oxidative stress on circulating levels of oxLDL and its association with clinical outcomes in CHF. Methods and Results: Plasma levels of oxLDL and low-density lipoprotein cholesterol (LDL-c) were measured at rest and after maximal exercise in 48 subjects with CHF and 12 healthy controls. Subjects with CHF had a higher baseline oxLDL (77.7 ± 3.2 U/L vs 57.9 ± 5.0 U/L, P = .01) and a higher baseline oxLDL/LDL-c ratio (0.87 ± 0.04 vs 0.49 ± 0.04, P ≤ .001). Exercise induced an increase in oxLDL in subjects with CHF (77.7 ± 3.2 U/L to 85.3 ± 3.0 U/L, P ≤ .001) but not in controls (57.9 ± 5.0 to 61.4 ± 5.5, P = .17). In 39 subjects for whom follow-up data were available, an increase in oxLDL of more than 11.0 U/L was associated with an increased risk to meet a combined end point of death and need for ventricular assist device or heart transplant during a 19-month follow-up period (hazard ratio 8.6; 95% confidence interval 1.0–73.8, P = .05); this remained significant when adjusted for peak oxygen consumption, left ventricular ejection fraction, New York Heart Association class, sex, and age (hazard ratio 46.6, 95% confidence interval 1.5–1438.1, P = .02). Conclusion: Plasma oxLDL and the oxLDL/LDL-c ratio are elevated in subjects with CHF. Whether assessment of oxLDL during maximal exercise allows early identification of subjects at highest risk for adverse outcomes should be systematically investigated. [Copyright &y& Elsevier]

Abstract: Background: Tailored atrioventricular delay (AVd) and interventricular delay (VVd) combination improves hemodynamics in patients treated with cardiac resynchronization therapy (CRT). Whether tailored AVd-VVd combination changes over time is not known. Methods and Results: Twenty-two patients (18 M, aged 69.9 ± 12.5 years, New York Heart Association class III, QRS ≥ 130 ms, ejection fraction 29.6 ± 8.8%) were implanted with a biventricular device with programmable VVd. Myocardial performance index (MPI) was evaluated during pacing at different VVds and AVds at baseline and after 6 and 12 months. The optimal AVd-VVd combination was identified by the minimum MPI. After optimization, the appropriate AVd-VVd combination was programmed in each patient. MPI at 6-month follow-up after optimization was significantly higher compared with baseline (.79 ± .21 vs. .59 ± .15, P < .05). Re-optimization of AVd-VVd combination was required after 6 months in 21 of 22 (95%) patients. Re-optimization significantly reduced MPI compared with the value prior to re-optimization (.56 ± .15 vs. .79 ± .21, P < .05). The MPI remained unchanged at 12-month compared with 6-month follow-up (.59 ± .19 vs. .56 ±.15, P = NS). Clinical symptoms and reverse left ventricular remodeling were sustained at 6-month and 12-month follow-up. Conclusion: Optimal AVd and VVd combination changes over time in patients with heart failure. Sustained improvement in clinical symptoms and reverse left ventricular remodeling after CRT are not temporally associated with improvement in MPI. [Copyright &y& Elsevier]

There is renewed interest in the utility of the intra-aortic balloon pump (IABP) for short-term and durable support in patients with chronic systolic heart failure (HF) who present with acute decompensation and cardiogenic shock (CS). However, the clinical characteristics of IABP-responders and non-responders remain incompletely defined. We sought to identify predictors of early IABP response to guide optimal use of IABP therapy in this population. We retrospectively analyzed the records of chronic systolic HF patients who presented at our institution between 2011-2018 with acute decompensated HF with hemodynamic evidence of CS and underwent IABP placement. IABP-responder was defined as having an immediate increase in cardiac output (CO) and an immediate decrease in mean pulmonary artery pressure (MPAP) above the median values of the cohort. Logistic regression was used to identify predictors of hemodynamic response. During the study period, 218 chronic systolic HF patients underwent IABP insertion for acute decompensation with CS. The mean age was 59.4 ±13.4 years, 79.8% were men, and 38.5% had ischemic cardiomyopathy (ICM). The average hemodynamic response to IABP in the whole cohort was a CO increase of 0.57 ±0.85L/min and a MPAP reduction of 5.1 ±7.6mmHg; IABP-responders had a CO increase of 1.21 ±0.87L/min and a MPAP reduction of 12.1 ±5.9mmHg (figure). Univariable predictors of IABP-response were ICM, presence of severe mitral regurgitation, baseline heart rate, elevated MPAP, and elevated systemic vascular resistance (SVR). Following multivariable logistic regression, independent predictors of IABP-response were elevated baseline SVR (OR 2.05, 95% CI 1.01 - 4.17; p=0.047) and elevated MPAP (OR 2.47, 95% CI 1.23 - 5.00; p=0.01). MPAP reduction decreased the odds of death or need for escalation to another short-term circulatory support device while CO increase did not [OR 0.52 (0.28 - 0.97; p=0.04) vs. 0.83 (0.45 - 1.54; p=0.56)]. A subset of chronic systolic HF patients had a robust hemodynamic response to IABP insertion with CO augmentation and MPAP reduction. Elevated baseline SVR and MPAP are predictors of robust response following device insertion. These parameters may be used to identify patients who may respond favorably to IABP counterpulsation therapy. [ABSTRACT FROM AUTHOR]

Accuracy of serum creatinine (sCr) in the estimation of renal function among heart transplant (HT) pts may be limited by changes in muscle mass. Cystatin C (CysC) is independent from muscle mass and provides an alternative measure of estimated glomerular filtration rate (eGFR). We hypothesized that: i) sCr would overestimate renal function due to muscle wasting; and ii) this would cause overdosing of valganciclovir (VGC) and, thereby, leukopenia. Herein, we aimed to: i) compare post-HT changes in CysC- and sCr-based eGFR; and ii) explore whether the use of CysC in lieu of sCr carries the potential to reduce the rate of VGC-induced leukopenia. Pts transplanted between 6/2016 and 4/2019 had serial measurements of CysC and sCr pre- and post-HT. eGFR was assessed using CKD-EPI-CysC (eGFR CysC) and MDRD (eGFR sCr). Linear mixed models were used to regress post-HT changes in eGFR CysC , eGFR sCr and sCr/CysC ratio (a validated marker of muscle mass). In a subgroup of patients receiving VGC, eGFR was assessed as a time-varying covariate at 1-, 3-, and 6-months post-HT. The primary endpoint was rate of VGC-induced leukopenia within 1-month of renal function assessment. Appropriateness of VGC dosing for renal impairment was assessed using, in addition to eGFR CysC and eGFR sCr, creatinine clearance (CrCl) as per manufacturer's recommendation. A total of 309 samples were collected in 83 pts. eGFR CysC was markedly lower than eGFR sCr early post-HT (Figure A). While eGFR sCr declined long-term, eGFR CysC showed an opposite trend with a gradual improvement. The decline in eGFR sCr mirrored the rise in sCr/CysC ratio, suggesting that increase in muscle mass may contribute to this decline. Among 57 pts who were on VGC at 1-, 3-, and 6-months post-HT, 117 samples were available. Based on sCr-based equations (eGFR sCr and CrCl), VGC was appropriately dosed in the majority of samples (72% and 64%, respectively). However, based on eGFR CysC , VGC was inappropriately dosed in 54 (46%) samples: 11 (9%) underdosed, 43 (37%) overdosed (Figure B). Among 31 episodes of VGC-induced leukopenia within 1-month of sampling, 15 (48%) occurred in samples with VGC overdosed by eGFR CysC. In adjusted models, higher CysC but not sCr was associated with increased risk for leukopenia (OR: CysC: 1.47, 95%CI 1.04-2.06; sCr: 1.19, 95%CI 0.79-1.79). eGFR CysC and eGFR sCr markedly differ early post-HT with critical implications in the dosing of VGC. The use of CysC in lieu of sCr may prevent VGC overdosing and reduce the rate of leukopenia in HT pts. [ABSTRACT FROM AUTHOR]

The aim of this study was to assess the presence of Rickettsia in soft ticks (Acari: Argasidae) collected from insectivorous bats (Chiroptera) in Santa Fe province, Argentina. First, a subset of ticks were mounted in Hoyer's medium to be determined by morphological characters and then confirmed by sequencing the mitochondrial 16S rRNA gene. Also ticks were processed by PCR assays using primers CS-78 and CS-323, which amplify a fragment of the Rickettsia spp. gltA gene. Positive ticks were subjected to a second PCR round with primers Rr190.70p and Rr190.701n of the spotted fever group rickettsiae ompA gene. A phylogenetic analysis was performed with Maximum-likelihood method, and the best fitting substitution models were determined with the Akaike Information Criterion. Five bats of the species Eptesicus diminutus Osgood, 1915, Eptesicus furinalis (d'Orbigny and Gervais, 1847), Eptesicus spp. (Vespertilionidae), and Molossops temminckii Burmeister, 1854 (Molossidae) were parasitized with Ornithodoros hasei (Schulze, 1935) larvae. One E. diminutus ticks' tested positive to " Candidatus Rickettsia wissemanii", a spotted fever group rickettsiae. The association O. hasei –" Ca. R. wissemanii" detected in this study represents the first evidence of a Rickettsia in Ornithodoros ticks in Argentina and the third report of this association in America. Also, this finding constitutes the first record of " Ca. R. wissemanii" in Argentina. Finally, we found for the first time the insectivorous bats E. diminutus and E. furinalis parasitized with O. hasei larvae. These findings add two new hosts and a new location, the southernmost recorded to date, for O. hasei. [ABSTRACT FROM AUTHOR]

Background: Gastrointestinal bleeding (GIB) is a common complication of left ventricular assist device (LVAD) therapy accounting for frequent hospitalizations and high resource utilization.Methods: We previously developed an endoscopic algorithm emphasizing upfront evaluation of the small bowel and minimizing low-yield procedures in LVAD recipients with GIB. We compared the diagnostic and therapeutic yield of endoscopy, health-care costs, and re-bleeding rates between conventional GIB management and our algorithm using chi-square, Fisher's exact test, Wilcoxon-Mann-Whitney, and Kaplan-Meier analysis.Results: We identified 33 LVAD patients with GIB. Presentation was consistent with upper GIB in 20 (61%), lower GIB in 5 (15%), and occult GIB in 8 (24%) patients. Forty-one endoscopies localized a source in 23 (56%), resulting in 14 (34%) interventions. Algorithm implementation compared with our conventional cohort was associated with a 68% increase in endoscopic diagnostic yield (P< .01), a 113% increase in therapeutic yield (P= .01), a 27% reduction in the number of procedures per patient (P < .01), a 33% decrease in length of stay (P < .01), and an 18% reduction in estimated costs (P < .01). The same median number of red blood cell transfusions were used in the 2 cohorts, with no increase in re-bleeding events in the algorithm cohort (33.3%) compared with our conventional cohort (43.7%).Conclusions: Our endoscopic management algorithm for GIB in LVAD patients proved effective in reducing low-yield procedures, improving the diagnostic and therapeutic yield of endoscopy, and decreasing health-care resource utilization and costs, while not increasing the risk of a re-bleeding event. [ABSTRACT FROM AUTHOR]

Outcomes have improved in patients bridged to heart transplant on contemporary continuous-flow ventricular assist devices over the past decade. We evaluated mechanical circulatory support as a means to bridge patients to cardiac retransplantation. We retrospectively reviewed 464 patients who underwent cardiac retransplant from the United Network for Organ Sharing database between January 2006 and November 2016. Pre- and post-transplant data were compared between patients bridged to retransplant with mechanical circulatory support (n = 81) and those without mechanical circulatory support (n = 383). The mean ages for the patients in the mechanical circulatory support and nonmechanical circulatory support cohorts were 41.2 ± 16 years and 42.1 ± 15.7 years, respectively (P =.64). Patients bridged with mechanical circulatory support were placed on extracorporeal membrane oxygenation (n = 29, 35.8%), a total artificial heart (n = 13, 16.0%), or a temporary or durable ventricular assist device (n = 39, 48.1%). Twelve patients (14.8%) were placed on a second device before retransplant. Thirty-nine percent of the mechanical circulatory support group were indicated for listing because of primary graft dysfunction or acute rejection versus 6% of the nonmechanical circulatory support group (P <.01). Likewise, 30% of patients in the mechanical circulatory support group were listed for cardiac allograft vasculopathy compared with 59% of the nonmechanical circulatory support group (P <.01). Thirty-day mortality was significantly higher in the mechanical circulatory support group (17.8% vs 4.8%, P <.01). However, patients who were bridged with a ventricular assist device or total artificial heart had comparable midterm outcomes to the nonmechanical circulatory support group. Patients who require mechanical circulatory support bridge to retransplantation belong to a high-risk cohort. Comparable midterm outcomes to the nonmechanical circulatory support cohort were demonstrated when patients' conditions allow for bridge with a ventricular assist device or total artificial heart. Bridging to retransplantation with extracorporeal membrane oxygenation remains a relative contraindication. [ABSTRACT FROM AUTHOR]

Background The use of percutaneous mechanical circulatory support (MCS) in the treatment of cardiogenic shock has increased. However, limitations in flow capability, ventricular unloading effect, durability, and mobility remain. We reviewed our single-center experience with continuous-flow external ventricular assist devices (VADs) to determine the role of temporary VADs for cardiogenic shock in the contemporary MCS era. Methods We retrospectively reviewed 252 patients who underwent continuous-flow external VAD insertion between January 2007 and December 2016. To investigate the change in indications, device configurations, and outcomes, we divided the cohort into 2 groups—2007 to 2011 (Era 1; n = 127) and 2012 to 2016 (Era 2; n = 125)—and compared early and late outcomes. Results Indications and device configurations changed significantly over time. The use of preoperative percutaneous MCS (53% vs 23%; P < .01) and use of minimally invasive VAD configurations (23% vs 6.7%; P < .01) were greater in Era 2 compared with Era 1. The rate of bridge to the next destinations, including myocardial recovery, transplantation, and durable VAD, was similar in the 2 groups. In-hospital mortality was significantly better in Era 2 (50% vs 37%; P = .04). Overall survival at 1 year was 57% in Era 2 versus 43% in Era 1 ( P = .04). Conclusions Better outcomes in the recent era could be associated with the changes in practice patterns using continuous-flow external VAD in patients with refractory cardiogenic shock. [ABSTRACT FROM AUTHOR]

Objective The role of short-term mechanical circulatory support has increased in patients with refractory cardiogenic shock. However, limited data exist on the outcomes of a bridge to a durable left ventricular assist device strategy using short-term mechanical circulatory support. Methods We retrospectively reviewed 382 patients who underwent continuous-flow left ventricular assist device insertion between 2004 and 2014. Of these, 45 (12%) were bridged with short-term mechanical circulatory support devices for refractory cardiogenic shock. We analyzed early and midterm outcomes in this bridged cohort. Multivariate Cox proportional hazards modeling was performed to evaluate the predictor of overall death in the entire cohort. Results The mean age of the bridged cohort was 53 ± 10 years, and 87% were male. The types of initial support included percutaneous devices in 24 patients (53%) and external continuous-flow ventricular assist device in 21 patients (47%). The median duration of short-term mechanical circulatory support was 14.0 (interquartile range, 7.5-29.5) days. The short-term mechanical circulatory support significantly improved end-organ function and hemodynamics. After conversion to durable left ventricular assist device insertion, in-hospital mortality was 18%. The incidence of right ventricular assist device use was high at 27%. The overall survival was 70% and 62% at 1 and 2 years, respectively. Cox multivariate hazard analysis in the entire cohort demonstrated that the use of a postoperative right ventricular assist device was a significant predictor of overall death (hazard ratio, 4.04; P < .001; 95% confidence interval, 1.97-7.94), but the use of a short-term mechanical circulatory support was not ( P = .937). Conclusions Short-term mechanical circulatory support can optimize patients in refractory cardiogenic shock and serve as a bridge to implantation of a durable left ventricular assist device. However, the early mortality rate after durable left ventricular assist device implantation is high because of unrecognized right ventricular failure. [ABSTRACT FROM AUTHOR]

Objectives Severe right ventricular failure often is considered a contraindication for left ventricular assist device (LVAD) therapy and necessitates use of biventricular assist devices (BiVADs). Available options for BiVADs are limited, and comparative outcomes are largely unknown. Methods Heart transplant candidates who were registered on the United Network for Organ Sharing waitlist and underwent long-term contemporary LVAD (n = 3195) or BiVAD (n = 408) implantation, from January 2010 through June 2014, were retrospectively analyzed. We evaluated clinical characteristics and outcomes of patients requiring a BiVAD, as well as regional differences in utilization of this technology. Results Patients requiring a BiVAD were younger (48.9 vs 53.3 years), had a higher proportion of nonischemic disease (69.1% vs 58.2%), a higher bilirubin level (0.9 vs 0.7 mg/dL), and a lower 6-month survival rate (68.1% vs 92.7%) after device implantation (all P < .05). Postimplantation and posttransplantation survival was comparable for commonly used BiVAD configurations, including total artificial heart, continuous flow BiVAD, a continuous-flow LVAD coupled with a right-sided device, and pulsatile flow. Significant variation was found in regional utilization of these devices, regardless of differences in transplantation waitlist times. A large body surface area was an independent predictor of mortality on a BiVAD (hazard ratio = 2.12, P = .017). Conclusions Outcomes of patients requiring a BiVAD remain poor in the contemporary device era, regardless of the configuration used. Among other clinical factors, body surface area should be incorporated into decision making for device selection in these patients. [ABSTRACT FROM AUTHOR]

Objective Patients evaluated for a continuous-flow left ventricular assist device frequently present with severe right ventricular dysfunction with tricuspid regurgitation. Long-term outcomes of concurrent tricuspid valve procedures in continuous-flow left ventricular assist device implantation are unclear. Methods From May 2004 to December 2013, 336 patients received continuous-flow left ventricular assist devices. Among these, 8 patients with prior tricuspid valve procedures were excluded. At continuous-flow left ventricular assist device implantation, 76 patients underwent tricuspid valve procedures (group A), including 68 repairs and 8 replacements. The remaining 252 patients did not receive concurrent tricuspid valve procedures (group B). Results Preoperatively, group A had higher central venous pressure/pulmonary capillary wedge pressure ( P = .032), total bilirubin ( P = .009), and percentage of moderate or greater tricuspid regurgitation (98.7% vs 18.8%; P < .001). In group A, cardiopulmonary bypass time (136 ± 52.0 minutes vs 83.9 ± 38.8 minutes; P < .001), intraoperative platelet use (13.6 ± 6.70 units vs 11.7 ± 5.92 units; P = .042), and bleeding requiring reoperation (27.5% vs 16.7%; P = .046) were significantly increased. In-hospital mortality was similar (10.5% vs 6.4%; P = .22). On-device 2-year survival was 73.9% in group A and 74.2% in group B ( P = .24). At 2 years, mean cumulative readmissions for right heart failure was 0.21 in group A and 0.27 in group B ( P = .95). A generalized linear mixed-effects model showed that tricuspid valve procedures are protective for developing future significant tricuspid regurgitation (odds ratio, 0.38; 95% confidence interval, 0.19-0.76; P = .006). Conclusions Concomitant tricuspid valve procedures at continuous-flow left ventricular assist device implantation can be performed safely and are protective against worsening tricuspid regurgitation during the first 2 years of support. [ABSTRACT FROM AUTHOR]

Objectives Aortic insufficiency (AI) after continuous-flow left ventricular assist device implantation can affect patient outcomes. Central aortic valve closure (CAVC) is a strategy commonly practiced; however, its efficacy has not been extensively investigated. Methods From March 2004 to May 2014, a total of 340 patients received a continuous-flow left ventricular assist device (89; 26.2%) as destination therapy (DT). Outcomes were compared between patients with CAVC (n = 57 [16.8%]; group A) versus without repair (n = 283 [83.2%]; group B). Results Patients in group A were older, were more likely to be having DT, had a greater cardiopulmonary bypass and aortic crossclamp time, and more often received intraoperative transfusions than did patients in group B. Twenty-three (40.4%) patients in group A had significant pre-existing AI, defined as >mild AI, whereas none did in group B. Kaplan-Meier analysis revealed that freedom from significant AI was 66.7% and 59.9% at 2 years ( P = .77) in groups A and B, respectively. In the DT cohort, freedom from significant AI was 78.1% and 41.8% at 2 years ( P = .077). A generalized mixed-effects model demonstrated a 57% and 69% decrease in the odds of significant AI progression among repaired patients in the entire and DT cohort, respectively, after adjusting for time effect and degree of baseline pre-existing AI. Conclusions Despite pre-existing AI, the prevalence of significant AI in patients with CAVC was comparable to the AI in those without pre-existing AI/CAVC. The efficacy of this technique was more evident in DT patients. Thus, CAVC may be an effective and durable strategy, especially in patients who require lengthy device support. [ABSTRACT FROM AUTHOR]

Objectives Pulmonary hypertension is often considered a contraindication to orthotopic heart transplantation. Left ventricular assist device support may improve pulmonary hypertension by unloading the left ventricle, making patients eligible for transplantation. We sought to investigate the effect of continuous-flow left ventricular assist device support on pulmonary hypertension and compare post-transplantation outcomes in patients with preexisting pulmonary hypertension. Methods Between March 2004 and December 2013, 256 potential orthotopic heart transplantation candidates underwent continuous-flow left ventricular assist device implantation at Columbia University. Preimplantation right heart catheterization data were available for 227 patients. Patients were divided into 2 groups on the basis of preimplantation pulmonary vascular resistance: low (<5 Wood units) (n = 182) and high (≥5 Wood units) (n = 45). Postimplantation and post-transplantation outcomes were compared between the groups. Results Pulmonary vascular resistance in the high resistance group decreased significantly during left ventricular assist device support ( P < .001). Post-transplantation in-hospital mortality was significantly higher in patients with high vascular resistance ( P < .05). However, 3-year survival after transplantation was similar between groups (85.0% and 79.0% for low and high vascular resistance, respectively; P = .45). Conclusions Continuous-flow left ventricular assist device therapy reduced pulmonary vascular resistance. Subsequent orthotopic heart transplantation in patients with significantly elevated pulmonary vascular resistance resulted in higher in-hospital mortality but similar 3-year survival. [ABSTRACT FROM AUTHOR]