Endoscopic Algorithm for Management of Gastrointestinal Bleeding in Patients With Continuous Flow LVADs: A Prospective Validation Study.

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.

Driveline Infection in Left Ventricular Assist Device Patients: Effect of Standardized Protocols, Pathogen Type, and Treatment Strategy.

Driveline infection (DLI) is common after left ventricular assist device (LVAD). Limited data exist on DLI prevention and management. We investigated the impact of standardized driveline care initiatives, specific pathogens, and chronic antibiotic suppression (CAS) on DLI outcomes. 591 LVAD patients were retrospectively categorized based on driveline care initiatives implemented at our institution (2009-2019). Era (E)1: nonstandardized care; E2: standardized driveline care protocol; E3: addition of marking driveline exit site; E4: addition of "no shower" policy. 87(15%) patients developed DLI at a median (IQR) of 403(520) days. S. aureus and P. aeruginosa were the most common pathogens. 31 (36%) of DLI patients required incision and drainage (I&D) and 5 (5.7%) device exchange. P. aeruginosa significantly increased risk for initial I&D (HR 2.7, 95% CI, 1.1-6.3) and recurrent I&D or death (HR 4.2, 95% CI, 1.4-12.5). Initial I&D was associated with a significant increased risk of death (HR 2.92 (1.33-6.44); P = 0.008) when compared to patients who did not develop DLI. Implementation of standardized driveline care protocol (E2) was associated with increased 2-year freedom from DLI compared to nonstandardized care (HR 0.36, 95% CI, 0.2-0.6, P < 0.01). Additional preventive strategies (E3&E4) showed no further reduction in DLI rates. 57(65%) DLI patients received CAS, 44% of them required escalation to intravenous antibiotics and/or I&D. Presence of P. aeruginosa DLI markedly increased risk for I&D or death. Conditional survival of patients progressing to I&D is diminished. Standardized driveline care protocol was associated with a significant reduction in DLI, while additional preventive strategies require further testing.

Patient-Reported Issues Following Left Ventricular Assist Device Implantation Hospitalization.

The purpose of this study was to explore the information reported by patients via a smartphone application (VAD Care App) used for left ventricular assist device (LVAD) self-care monitoring and reporting post hospital discharge. Specific aims were to examine the type and frequency of issues reported by patients through the app during months 1, 3, and 6 postdischarge. An exploratory-descriptive research design was used with 17 patients (12 males and 5 females) with durable LVADs, mean age of 48.6 ± 16 years. Data generated by the patients' daily smartphone app usage more than 6 months were extracted from the server. Data were coded and clustered according to issues reported by patients via the app and analyzed with descriptive statistics. Three clusters of issues were found: physiologic, behavioral (self-care), and signs and symptoms. LVAD flows and pulsatility indices, hypertension, driveline care, and heart failure symptoms were worse at month 1, and then appeared to improve at months 3-6. However, abnormal levels of the international normalization ratio were common at all assessment points. Further research is needed to understand the mechanism of the reported issues on treatment outcomes, then develop and test interventions to inform evidence-based practice and clinical guidelines for smartphone apps used in LVAD self-care monitoring.

Levels of Trimethylamine N-Oxide Remain Elevated Long Term After Left Ventricular Assist Device and Heart Transplantation and Are Independent From Measures of Inflammation and Gut Dysbiosis.

BACKGROUND: Trimethylamine N-oxide (TMAO)-a gut-derived metabolite-is elevated in heart failure (HF) and linked to poor prognosis. We investigated variations in TMAO in HF, left ventricular assist device (LVAD), and heart transplant (HT) and assessed its relation with inflammation, endotoxemia, oxidative stress, and gut dysbiosis. METHODS: We enrolled 341 patients. TMAO, CRP (C-reactive protein), IL (interleukin)-6, TNF-α (tumor necrosis factor alpha), ET-1 (endothelin-1), adiponectin, lipopolysaccharide, soluble CD14, and isoprostane were measured in 611 blood samples in HF (New York Heart Association class I-IV) and at multiple time points post-LVAD and post-HT. Gut microbiota were assessed via 16S rRNA sequencing among 327 stool samples. Multivariable regression models were used to assess the relationship between TMAO and (1) New York Heart Association class; (2) pre- versus post-LVAD or post-HT; (3) biomarkers of inflammation, endotoxemia, oxidative stress, and microbial diversity. RESULTS: ln-TMAO was lower among HF New York Heart Association class I (1.23 [95% CI, 0.52-1.94] µM) versus either class II, III, or IV (1.99 [95% CI, 1.68-2.30], 1.97 [95% CI, 1.71-2.24], and 2.09 [95% CI, 1.83-2.34] µM, respectively; all P<0.05). In comparison to class II-IV, ln-TMAO was lower 1 month post-LVAD (1.58 [95% CI, 1.32-1.83] µM) and 1 week and 1 month post-HT (0.97 [95% CI, 0.60-1.35] and 1.36 [95% CI, 1.01-1.70] µM). ln-TMAO levels in long-term LVAD (>6 months: 1.99 [95% CI, 1.76-2.22] µM) and HT (>6 months: 1.86 [95% CI, 1.66-2.05] µM) were not different from symptomatic HF. After multivariable adjustments, TMAO was not associated with biomarkers of inflammation, endotoxemia, oxidative stress, or microbial diversity. CONCLUSIONS: TMAO levels are increased in symptomatic HF patients and remain elevated long term after LVAD and HT. TMAO levels were independent from measures of inflammation, endotoxemia, oxidative stress, and gut dysbiosis.

Association of preoperative infections, nasal Staphylococcus aureus colonization and gut microbiota with left ventricular assist device outcomes.

AIMS: Infections are common following left ventricular assist device (LVAD) implantation and predict adverse events. Infections are frequent prior to LVAD implantation although their impact on postoperative outcomes remains unknown. Gut and nasal microbial imbalance may predispose to mucosal colonization with pathogens. Herein, we investigated the predictive role of pre-LVAD infections, and explored the association of nasal Staphylococcus aureus (SA) colonization and gut microbiota, on postoperative outcomes. METHODS AND RESULTS: Overall, 254 LVAD patients were retrospectively categorized based on pre-LVAD infection status: Group 1, bacterial/fungal bloodstream infection (BSI); Group 2, other bacterial/fungal; Group 3, viral; and Group 4, no infection. In a subset of patients, nasal SA colonization (n = 140) and pre-LVAD stool (n = 25) were analysed using 16S rRNA sequencing. A total of 75 (29%) patients had a pre-LVAD infection [Group 1: 22 (29%); Group 2: 41 (55%); Group 3: 12 (16%)]. Pre-LVAD BSIs were independent predictors of 1-year postoperative mortality and infections [Group 1 vs. 4: hazard ratio (HR) 2.70, P = 0.036 vs. HR 1.8, P = 0.046]. In an unadjusted analysis, pre-LVAD infections other than BSIs, INTERMACS profile ≤2, higher serum creatinine, lower serum albumin and nasal SA colonization were also significantly associated with postoperative infections. Patients with early post-LVAD infections exhibited decreased microbial diversity (P < 0.05). CONCLUSIONS: Pre-LVAD infections are common. BSIs independently predict postoperative mortality and infections. Additional studies are needed to confirm our findings that pre-LVAD SA nasal colonization and gut microbial composition can help stratify patients' risk for infectious complications after LVAD implantation.

Left ventricular assist systems and infection-related outcomes: A comprehensive analysis of the MOMENTUM 3 trial.

BACKGROUND: In a randomized controlled trial (MOMENTUM 3), the HeartMate 3 (HM3) fully magnetically levitated centrifugal-flow left ventricular assist device (LVAD) demonstrated superiority over the HeartMate II (HMII) axial-flow LVAD. These findings were driven by hemocompatibility-related outcomes, but infection-related outcomes were not altered by device choice. In this trial-level analysis, we analyzed the clinical patterns of infection-related outcomes over 2 years of support. METHODS: In MOMENTUM 3, 1,020 patients were implanted with either the HM3 (n = 515) or HMII (n = 505) pump. Clinical characteristics and morbidity- and mortality-related outcomes were evaluated to identify predictors associated with major infectious complications, using univariable and multivariable models. RESULTS: The cumulative number of infections at 2 years was 1,213 (634 HM3 and 579 HMII), and major infection occurred in 58% of patients with the HM3 and 56% of patients with the HMII (p = 0.57). Infections of a local nature unrelated to pump components were most common (n = 681/1,213; 56%), followed by driveline-associated infection (n = 329/1,213; 27%), sepsis (n = 194/1,213; 16%), and other events (n = 9/1,213; 0.7%). Bacterial pathogens were implicated in 806 of 1,213 events (66%); significant predictors of infection included sex (women vs men; hazard ratio [HR]: 1.38, p = 0.003), pre-implant use of intra-aortic balloon pump (HR: 1.33, p = 0.02), pre-implant history of cardiac surgery (HR: 1.28, p = 0.01), and body mass index ≥ 30 (HR: 1.40, p < 0.0001). Most deaths in those with infection occurred owing to non-infectious causes. CONCLUSION: Infection is the most common adverse effect in patients implanted with contemporary continuous-flow LVADs, with most such events unrelated to the pump or its peripheral components. Whether chronic mechanical circulatory devices confer an immunomodulatory effect pre-disposing to infection warrants closer scrutiny to understand and ameliorate this morbidity.

Prognostic implications of serial outpatient blood pressure measurements in patients with an axial continuous-flow left ventricular assist device.

BACKGROUND: Elevated blood pressure (BP) has been linked to adverse events during left ventricular assist device support. In this study we investigated the association between outpatient BP and stroke or suspected pump thrombosis among HeartMate II (HMII) recipients. METHODS: We retrospectively studied 220 HMII patients. Serial outpatient BP measurements were averaged. Patients were categorized by: (1) mean arterial pressure (MAP), high (>90 mm Hg) vs intermediate (80 mm Hg ≤ MAP ≤ 90 mm Hg) vs low (<80 mm Hg); (2) systolic BP (SBP), high (≥101 mm Hg, median) vs low; and (3) pulse pressure (PP), high (≥22 mm Hg, median) vs low. To assess visit-to-visit BP variability, patients were divided in quartiles of standard deviation of MAP and SBP. The primary end-point was the composite of stroke or suspected pump thrombosis. RESULTS: The risk for the primary end-point was increased in the high MAP group (adjusted hazard ratio [HR] 2.75, 95% confidence interval [CI] 1.49 to 5.05, vs intermediate MAP; and 6.73, 1.9 to 23.9, vs low MAP). MAP had higher predictive value for the primary end-point compared with SBP (p = 0.05). Patients with high SBP had a higher rate of stroke (HR 2.8, 95% CI 1.09 to 7.17, vs low SBP). The combination of high SBP and low PP was associated with the highest risk for stroke. The lowest quartile of visit-to-visit MAP variability was associated with the highest risk for the primary end-point. CONCLUSIONS: Elevated outpatient BP is associated with increased risk for stroke or suspected pump thrombosis in HMII recipients. Reduced PP and low visit-to-visit BP variability may confer additional risk.

Limited usefulness of endoscopic evaluation in patients with continuous-flow left ventricular assist devices and gastrointestinal bleeding.

BACKGROUND: Gastrointestinal bleeding (GIB) is a frequent cause of re-admission in patients with continuous-flow left ventricular assist devices (CF-LVADs) and is associated with multiple endoscopic procedures and high resource utilization. Our aim was to determine the diagnostic and therapeutic yield of endoscopy and to develop a more cost-effective approach for the management of GIB in CF-LVAD recipients. METHODS: We retrospectively reviewed 428 patients implanted with a CF-LVAD between 2009 and 2016 at the Columbia University Medical Center and identified those hospitalized for GIB. Patients were categorized into upper GIB (UGIB), lower GIB (LGIB) and occult GIB (OGIB), based on clinical presentation. RESULTS: Eighty-seven CF-LVAD patients underwent a total of 164 GIBs, resulting in 239 endoscopies. Index presentation was consistent with UGIB in 30 (34.5%), LGIB in 19 (21.8%) and OGIB in 38 (43.7%) patients. On the first GIB, 147 endoscopies localized a bleeding source in 49 (30%), resulting in 24 (16.3%) endoscopic interventions. Of 45 lesions identified, arteriovenous malformations (AVMs) were the most common (22, 48.9%). A gastric or small bowel source (HR 2.8, p = 0.003) and an endoscopic intervention (HR 1.9, p = 0.04) predicted recurrent GIB. The proposed algorithm may reduce the number of endoscopic procedures by 45% and costs by 35%. CONCLUSIONS: Occult GIB is the most common presentation in CF-LVAD patients and carries the lowest diagnostic and therapeutic yield of endoscopy. Performing an intervention was among the strongest predictors of recurrent GIB. Our proposed algorithm may decrease the number of low-yield procedures and improve resource utilization.

Advanced cardiovascular life support algorithm for the management of the hospitalized unresponsive patient on continuous flow left ventricular assist device support outside the intensive care unit.

Over the past decade, continuous flow left ventricular assist devices (CF-LVADs) have become the mainstay of therapy for end stage heart failure. While the number of patients on support is exponentially growing, at present there are no American Heart Association or European Society of Cardiology Advanced Cardiovascular Life Support guidelines for the management of this unique patient population. We propose an algorithm for the hospitalized unresponsive CF-LVAD patient outside of the intensive care unit setting. Key elements of this algorithm are: creation of a dedicated LVAD code pager and LVAD code team; early assessment and correction of LVAD malfunction; early determination of blood flow using Doppler technique in carotid and femoral arteries; prompt administration of external chest compressions in the absence of Doppler flow; bedside veno-arterial extracorporeal membranous oxygenation support if no response to resuscitation measures; and early consideration for stroke.

Continuous-flow left ventricular assist devices and usefulness of a standardized strategy to reduce drive-line infections.

BACKGROUND: Drive-line infection (DLI) is a common complication of left ventricular assist device (LVAD) support, leading to significant morbidity that jeopardizes the benefits of these devices. It has been reported that DLI incidence is related to drive-line dressing strategies. The aim of this study was to determine whether implementation of a standardized drive-line care kit would reduce the incidence of DLIs. METHODS: DLI data were collected prospectively on all LVAD patients implanted between 2009 and 2013 at Columbia University Medical Center. Drive-line care was altered on June 1, 2011, from a dry sterile dressing without a standard anchoring device to a standardized kit, which included silver gauze dressing and a standard anchoring device. The silver dressing was used until the wound incorporated, with a minimum of 1 month. RESULTS: During the study period, 107 patients were implanted with LVADs before implementation of a standardized kit (Group A) and 159 thereafter (Group B). Median follow-up time (censoring at June 2011) for Group A was 8.73 (IQR 3.51 to 17.47) months and 11.65 (IQR 6.66 to 35.20) months for Group B (p = 0.17). DLI event rate improved from 0.18 to 0.07 event per patient-year, corresponding to a relative risk reduction of 62.5%. In addition, the 1-year freedom from infection was significantly increased in Group B (92.46%) compared with Group A (81.94%) (log rank = 0.036). CONCLUSION: The use of a standardized kit, including silver dressing and a standard anchoring device, leads to decrease in DLI with an absolute risk reduction of 11%. Routine use of these dressing techniques is warranted based on our findings, and may lead to reduction of complications related to infections.

Myocardial Recovery in Patients Receiving Contemporary Left Ventricular Assist Devices: Results From the Interagency Registry for Mechanically Assisted Circulatory Support (INTERMACS).

BACKGROUND: Time course and predictors of myocardial recovery on contemporary left ventricular assist device support are poorly defined because of limited number of recovery patients at any implanting center. This study sought to investigate myocardial recovery using multicenter data from the Interagency Registry for Mechanically Assisted Circulatory Support (INTERMACS). METHODS AND RESULTS: Thirteen thousand four hundred fifty-four adult patients were studied. Device explant rates for myocardial recovery were 0.9% at 1-year, 1.9% at 2-year, and 3.1% at 3-year follow-up. Independent predictors of device explantation for recovery were age <50 years (odds ratio [OR] 2.5), nonischemic etiology (OR 5.4), time since initial diagnosis <2 years (OR 3.4), suboptimal heart failure therapy before implant (OR 2.2), left ventricular end-diastolic diameter <6.5 cm (OR 1.7), pulmonary systolic artery pressure <50 mm Hg (OR 2.0), blood urea nitrogen <30 mg/dL (OR 3.3), and axial-flow device (OR 7.6). Patients with myocarditis (7.7%), postpartum cardiomyopathy (4.4%), and adriamycin-induced cardiomyopathy (4.1%) had highest rates of device explantation for recovery. Use of neurohormonal blockers on left ventricular assist device support was significantly higher in patients who were explanted for recovery. Importantly, 9% of all left ventricular assist device patients who were not explanted for recovery have demonstrated substantial improvement in left ventricular ejection fraction (partial recovery) and had remarkable overlap in clinical characteristic profile compared with patients who were explanted for recovery (complete recovery). Complete and partial recovery rates have declined in parallel with recent changes observed in device indications and technology. CONCLUSIONS: Myocardial recovery is a spectrum of improvement rather than a binary clinical end point. One in every 10 left ventricular assist device patients demonstrates partial or complete myocardial recovery and should be targeted for functional assessment and optimization.

Effect of CYP2C9 and VKORC1 Gene Variants on Warfarin Response in Patients with Continuous-Flow Left Ventricular Assist Devices.

Bleeding and thrombotic complications continue to plague continuous-flow left ventricular assist device (CF-LVAD) therapy in patients with end-stage heart failure. Warfarin genotyping information can be incorporated into decision making for initial dosing as recommended by the Food and Drug Administration; however, clinical utility of this data in the CF-LVAD population has not been well studied. Genotypes testing for CYP2C9 and VCORC1 polymorphisms were determined in 90 CF-LVAD patients. Outcomes studied were the association of CYP2C9 (*1, *2, or *3) and VKORC1 (-1639 G>A) gene variants with time-to-target international normalized ratio (INR), total warfarin dose, maintenance warfarin dose. Continuous-flow left ventricular assist device patients carrying a rare variant in the VKORC1 gene had a significantly lower cumulative warfarin dose until target INR achieved (18.9 vs. 35.0 mg, p = 0.002), days spent until INR target achieved (4.9 vs. 7.0 days, p = 0.021), and discharge warfarin dose (3.2 vs. 5.6 mg, p = 0.001) compared with patients with wild-type genotype. Genotype-guided warfarin dosing may lead to safer anticoagulation and potentially improve outcomes in CF-LVAD patients.