Health Literacy in Patients Considering a Left Ventricular Assist Device: Findings From the DECIDE-LVAD Trial.

OBJECTIVE: To assess the interaction of health literacy and a shared intervention concerning decision quality in patients considering the destination therapy of left ventricular assist device (DT LVAD) implantation. BACKGROUND: Evidence is limited for the use of decision aids by patients with low health literacy and with life-threatening illnesses. METHODS: We performed a secondary analysis of the DECIDE-LVAD Trial, a randomized, stepped-wedge trial conducted from 2015-2017 in the United States. The intervention was the integration of a formal shared decision-making intervention. The main outcome was decision quality as measured by LVAD knowledge and values-treatment concordance. Two components of health literacy were measured by the Rapid Estimate of Adult Literacy in Medicine and Subjective Numeracy Scale instruments. RESULTS: Of the 228 patients studied, 44% (n = 101) received the formal shared decision-making intervention, and half had low health literacy. Knowledge of LVAD improved for patients with low literacy in the intervention group compared to the control group: the difference in increased knowledge score was 10.6%; P = 0.04. Values-treatment concordance improved significantly for patients with low literacy in the intervention group compared to the control group: the median improvement in values-treatment correlation coefficient was 0.43; P = 0.03. These benefits were not significant in those with adequate literacy (n = 171). Patients with low numeracy (n = 94) did not show significant improvements in either measure of decision quality, and patients with adequate numeracy (n = 134) showed improvement in LVAD knowledge but not in values-treatment concordance. CONCLUSIONS: Patients considering DT LVAD implantation with low literacy showed improvement in decision quality after the integration of a shared decision-making intervention.

Association of COVID-19 Vaccination With Risk of COVID-19 Infection, Hospitalization, and Death in Heart Transplant Recipients.

Importance: Orthotopic heart transplant (OHT) recipients are at increased risk for morbidity and mortality after SARS-CoV-2 infection. Although antibody response to COVID-19 vaccination is lower in solid organ transplant recipients, there has been no study assessing the safety and effectiveness of COVID-19 vaccination in OHT recipients. Objective: To assess the safety and effectiveness of COVID-19 vaccination and associations with SARS-CoV-2 infection and clinical outcomes in a large population of adult OHT recipients. Design, Setting, and Participants: This case-control study examined data from a US heart transplant program at a single center for all adult recipients of OHT who were followed up from January 15, 2021, through January 31, 2022. Main Outcomes and Measures: The primary outcome was number of SARS-CoV-2 infections and related hospitalizations, intensive care unit (ICU) admissions, and deaths between vaccinated vs unvaccinated adult recipients of OHT. Results: A total of 436 patients who received OHT were included in the study, of which 106 patients were infected with COVID-19. The mean (SD) age was 54 (17) years; 303 (69.5%) were men and 133 (30.5%) were women. There were 366 patients in the vaccinated cohort with 72 COVID-19 infections (19.7%), 15 hospitalizations (4.1%), 4 ICU admissions (1.1%), and 3 deaths (0.8%). There were 70 patients in the unvaccinated cohort with 34 COVID-19 infections (48.6%), 10 hospitalizations (14.3%), 3 ICU admissions (4.3%), and 3 deaths (4.3%). COVID-19 vaccination was associated with a lower risk of COVID-19 infection (risk ratio [RR], 0.41; 95% CI, 0.30-0.56), hospitalization (RR, 0.29; 95% CI, 0.14-0.61), and death (RR, 0.19; 95% CI, 0.05-0.82). Among the 366 vaccinated OHT recipients, there was no echocardiographic evidence of graft dysfunction, clinically significant rejection, or allosensitization at 6 months after they received the COVID-19 vaccine. Conclusions and Relevance: Patients with OHT who are infected with SARS-CoV-2 are at greater risk of severe infection and death compared with immunocompetent individuals. COVID-19 vaccination was associated with fewer COVID-19 infections, hospitalizations, and deaths, with no heart transplant-specific adverse events. COVID-19 vaccination for all OHT recipients is of paramount importance.

Right Heart Failure While on Left Ventricular Assist Device Support Is Associated with Primary Graft Dysfunction.

Primary graft dysfunction (PGD) is a potentially devastating complication of heart transplantation. Understanding the risk factors for PGD in the modern era of heart transplantation is of vital importance. This study investigated the relationship between post-left ventricular assist device (LVAD) right heart failure (RHF) and transplant outcomes. Patients with durable, continuous-flow LVADs who were transplanted between 2010 and 2016 at Barnes-Jewish Hospital were included in the study. Data collection was performed through retrospective chart review. The primary outcome was the incidence of PGD stratified by pretransplant incidence of RHF while on LVAD support. Among the 141 patients included in the study, 41 developed RHF. In the RHF cohort, 18 patients developed PGD as compared to 14 patients in the group without RHF (44% vs. 14%; p < 0.001). Mortality was significantly higher in the RHF group at 30 days (20% vs. 1%; p < 0.001) and 1 year (22% vs. 6%; p = 0.013). In a multivariable logistic regression model adjusted for confounding variables, RHF was associated with a nearly fourfold increased risk of PGD (odds ratio, 3.91; p = 0.003). The results of this study show that patients supported with LVADs who develop early severe RHF or late RHF are at increased risk of PGD and death following cardiac transplantation.

Expected vs Actual Outcomes of Elective Initiation of Inotropic Therapy During Heart Failure Hospitalization.

OBJECTIVE: To describe the intent and early outcomes of elective inotrope use during heart failure hospitalization. PATIENTS AND METHODS: A prospective multisite design was used to collect data for hemodynamically stable patients started electively on inotrope therapy between January 1 and August 31, 2018. We prospectively recorded data when intravenous inotropic therapy was initiated, including survey of the attending cardiologists regarding expectations for the clinical course. Patients were followed up for events through hospital discharge and an additional survey was administered at the end of hospitalization. RESULTS: For the 92 patients enrolled, average age was 60 years and ejection fraction was 24%±12%. At the time of inotrope initiation, attending heart failure cardiologists predicted that 50% (n=46) of the patients had a "high or very high" likelihood of becoming dependent on intravenous inotropic therapy and 58% (n=53) had a "high" likelihood of death, transplant, or durable ventricular assist device placement within the next 6 months. Provider predictions regarding death/hospice or need for continued home infusions were accurate only 51% (47 of 92) of the time. Only half the patients (n=47) had goals-of-care conversations before inotrope treatment initiation. CONCLUSION: More than half the patients (51 of 92) electively started on inotrope treatment without present or imminent cardiogenic shock ultimately required home inotrope therapy, died during admission, or were discharged with hospice. Heart failure clinicians could not reliably identify those patients at the time of inotrope therapy initiation and goals-of-care discussions were not frequently performed.

Heartland virus infection in a heart transplant recipient from the Heartland.

Tick-borne infections represent a significant health risk each year in the United States. Immunocompromised patients are typically at risk of more severe disease manifestations than their immunocompetent counterparts. Here we report a case of a newly emerging phlebovirus, Heartland virus, in a heart transplant recipient.

The Combination of Tricuspid Annular Plane Systolic Excursion and HeartMate Risk Score Predicts Right Ventricular Failure After Left Ventricular Assist Device Implantation.

Right ventricular (RV) failure is difficult to predict and is a major determinant of poor outcomes after left ventricular assist device (LVAD) implantation. We evaluated the associations of the following variables with severe RV failure in LVAD patients: tricuspid annular plane systolic excursion (TAPSE), pulmonary artery pulsatility index (PAPi), simplified RV contraction pressure index (sRVCPI), and HeartMate Risk Score (HMRS). We performed a retrospective case-control study on 216 patients who underwent continuous-flow LVAD implantation between 2008 and 2014. The primary analysis assessed the ability of HMRS, PAPi, sRVCPI, and TAPSE to predict severe RV failure. A secondary analysis evaluated the incremental benefit of combining predictive variables. Seventy-four patients developed severe RV failure (24%). Compared with the control group, the severe RV failure group had lower TAPSE (1.30 vs. 1.55; p < 0.001), lower PAPi (1.77 vs. 2.47; p = 0.001), lower sRVCPI (42.71 vs. 57.82; p < 0.001), and higher HMRS (2.12 vs. 1.65; p < 0.001). All four variables had similar receiver operating characteristic curves with modest area under the receiver operating characteristic curve (0.63-0.67, all p values < 0.001). In the evaluation of combined predictive variables, the combination of TAPSE with HMRS was found to be best for predicting severe RV failure. In summary, patients at risk for severe RV failure after LVAD implantation were successfully identified using TAPSE, PAPi, sRCPI, and HMRS. The combination of TAPSE and HMRS-incidentally, the least invasive and most readily available variables-proved to be superior to RV-centric metrics for predicting severe RV failure. The predictive and clinical use of these two variables should be tested prospectively.

A Case Series of Acute Myocardial Infarction in Left Ventricular Assist Device-Supported Patients.

Acute myocardial infarction (AMI) is an underrecognized phenomenon in patients with continuous-flow left ventricular assist devices (CF-LVAD). Previously, there has been an optimistic expectation of a benign clinical course; however, AMI in LVAD-supported patients can result in profound consequences and management remains controversial. We describe a case series of AMI in four CF-LVAD patients, each with a different presentation, clinical course, treatment, and outcome. The clinical variability and mixed outcomes of these patients highlights the unique challenges in diagnosis and management of AMI in this population, particularly the uncertain role of percutaneous intervention (PCI), and underscores the potentially poor prognosis of this entity. Several key points emerge from this review. First, LVAD-supported patients frequently have underlying abnormalities on the electrocardiogram (ECG) that obscure the diagnosis of AMI. Second, clinicians should have a high degree of suspicion for AMI in the presence of suggestive clinical features, elevated cardiac biomarkers, or new-onset ventricular arrhythmias. Third, the decision to proceed with PCI requires careful evaluation of the risk of hemorrhage, and strong consideration should be given to the use of bleeding avoidance strategies during and after PCI.

Relationship Between Anticoagulation Intensity and Thrombotic or Bleeding Outcomes Among Outpatients With Continuous-Flow Left Ventricular Assist Devices.

BACKGROUND: We evaluated thrombotic and bleeding outcomes in patients with continuous-flow left ventricular assist devices (CF-LVADs), stratified by anticoagulation intensity. Previous studies of outpatients with CF-LVADs have suggested that target international normalized ratio (INR) values <2.5 (range, 2-3) may be used. However, recent studies reported an increase in pump thrombosis among CF-LVADs, especially within the first 6 months of implant. METHODS AND RESULTS: We retrospectively reviewed 249 outpatients at our center who received a CF-LVAD between January 2005 and August 2013. Using Poisson models, we analyzed their 10 927 INRs to determine INR-specific rates of thrombotic (ischemic stroke and suspected pump thrombosis) and hemorrhagic (gastrointestinal bleeding and hemorrhagic stroke) events occurring outside of the hospital. In multivariate analyses, we adjusted for age, sex, atrial fibrillation, coronary disease, and LVAD type as time-dependent Cox proportional hazard models. During a mean follow-up of 17.6±13.6 months, thrombotic events occurred in 46 outpatients. The highest event rate (0.40 thrombotic events per patient-year) was in the INR range of <1.5, but INR values of 1.5 to 1.99 also had high rates (0.16 thrombotic events per patient-year). INR was inversely associated with thrombotic events (hazard ratio, 0.40; 95% confidence interval, 0.22-0.72; P=0.002). The optimal INR based on weighted mortality of thrombotic and bleeding events was 2.6. CONCLUSIONS: INR is inversely related to thrombotic events occurring outside of the hospital among patients supported with CF-LVADs. INR values <2.0 increase the rate of thrombotic events occurring outside of the hospital among patients supported with CF-LVADs.

Pre-Operative Right Ventricular Dysfunction Is Associated With Gastrointestinal Bleeding in Patients Supported With Continuous-Flow Left Ventricular Assist Devices.

OBJECTIVES: This study sought to determine whether severe right ventricular (RV) dysfunction in the pre-operative setting is associated with an increased risk of gastrointestinal bleeding (GIB) post-left ventricular assist device (LVAD). BACKGROUND: GIB is a significant complication in patients supported with continuous-flow LVADs. The impact of RV dysfunction on the risk of GIB has not been investigated. METHODS: We retrospectively identified 212 patients who survived index hospitalization after implantation of HeartMate II (Thoratec Corp., Pleasanton, California) or Heartware HVAD (HeartWare Corp., Framingham, Massachusetts) from June 2009 to April 2013. Patients with severe RV dysfunction on pre-LVAD echocardiogram (n = 37) were compared to patients without severe RV dysfunction (n = 175). The primary outcome was freedom from GIB. RESULTS: The majority of patients were male (79%) with a median INTERMACS (Interagency Registry for Mechanically Assisted Circulatory Support) profile of 2 at LVAD implantation. There were no significant differences between cohorts with respect to demographics, comorbidities, device type, international normalization ratio, or aspirin strategy. During follow-up, 81 patients had GIB events: 23 of 37 (62%) in the severe RV dysfunction group versus 58 of 175 (33%) in the control group (p = 0.001). After adjustment for age and ischemic cardiomyopathy, severe RV dysfunction was associated with increased risk of GIB (hazard ratio: 1.799, 95% confidence interval: 1.089 to 2.973, p = 0.022). CONCLUSIONS: In this single-center sample of patients supported with continuous-flow LVADs, severe RV dysfunction on pre-LVAD echocardiogram was associated with an increased risk of GIB. Further studies are needed to investigate possible mechanisms by which RV dysfunction increases the risk of GIB and to identify patient populations who may benefit from alterations in antithrombotic strategies.

Clinical outcomes with use of erythropoiesis stimulating agents in patients with the HeartMate II left ventricular assist device.

OBJECTIVES: This study evaluated clinical outcomes associated with erythropoiesis stimulating agent (ESA) use in left ventricular assist devices (LVAD)-supported patients. BACKGROUND: Use of ESAs in patients with LVADs may minimize blood transfusions and decrease allosensitization. ESAs increase thrombotic events, which is concerning because LVADs are sensitive to pump thrombosis (PT). METHODS: We retrospectively reviewed 221 patients at our center who received a HeartMate II (Thoratec Corp., Pleasanton, California) LVAD between January 1, 2009 and June 6, 2013. Patients were divided into those who received ESAs during index admission (n = 121) and those who did not (n = 100). Suspected PT was defined as evidence of thrombus in the LVAD or severe hemolysis (lactate dehydrogenase >1,000 mg/dl or plasma-free hemoglobin >40 mg/dl). Outcomes were compared between cohorts using inverse probability-weighted analyses. RESULTS: During a mean follow-up of 14.2 ± 11.9 months, suspected PT occurred in 37 patients (ESA 23%, no ESA 12%; p =0.03). The ESA cohort received ESAs 13.9 ± 60.9 days after LVAD implantation. At 180 days, event-free rates for suspected PT were ESA 78.6% versus no ESA 94.5% (p < 0.001). ESA use had higher rates of suspected PT (hazard ratio [HR]: 2.35; 95% confidence interval [CI]: 1.38 to 4.00; p = 0.002). For every 100-unit increase in cumulative ESA dosage, the hazard of suspected PT increased by 10% (HR: 1.10; 95% CI: 1.04 to 1.16; p < 0.001). After inverse probability weighting, ESA use was associated with a significantly higher rate of all-cause mortality (HR: 1.62; 95% CI: 1.12 to 2.33; p = 0.01). CONCLUSIONS: ESA use in LVAD patients is associated with higher rates of suspected PT.

Systolic blood pressure on discharge after left ventricular assist device insertion is associated with subsequent stroke.

BACKGROUND: Stroke is a significant complication in patients supported with continuous-flow left ventricular assist devices (CF-LVAD) and hypertension is a significant risk factor for stroke, but the association between blood pressure and stroke in LVAD patients is not well characterized. METHODS: We identified 275 consecutive patients who survived implant hospitalization between January 2005 and April 2013. Patients were grouped according to systolic blood pressure (SBP) as above a median and below a median of 100 mm Hg by their averaged systolic blood pressure during the 48 hours before discharge from implantation hospitalization. The groups were compared for the primary outcome of time to stroke. RESULTS: The above-median SBP group had mean SBP of 110 mm Hg and the below-median SBP group had mean SBP of 95 mm Hg. There were no significant between-group differences in body mass index, smoking, vascular disease, hypertension, atrial fibrillation, or prior stroke. During a mean follow-up of 16 months, stroke occurred in 16% of the above-median SBP group vs in 7% of the below-median SBP group (hazard ratio, 2.38; 95% confidence interval, 1.11-5.11), with a similar proportion of hemorrhagic and ischemic strokes in each group. In Cox proportional hazard models adjusting for age, diabetes, or prior stroke, the hazard ratio remained statistically significant. SBP as a continuous variable predictor of stroke had an area under the curve of 0.64 in a receiver operating characteristic curve analysis. CONCLUSIONS: In this large, CF-LVAD cohort, elevated SBP was independently associated with a greater risk of subsequent stroke. These results identify management of hypertension as a potential modifiable risk factor for reducing the incidence of stroke in patients supported by CF-LVAD.

Ethambutol toxicity exacerbating the phenotype of CMT2A2.

INTRODUCTION: CMT2A2 is associated with mutations in the mitofusin 2 gene, which encodes a protein involved in mitochondrial fusion. Ethambutol is an antimycobacterial agent associated with toxic optic neuropathies. Ethambutol-induced optic neuropathy occurs in patients with mutations in a related fusion gene, OPA1, which is responsible for autosomal dominant optic atrophy. METHODS: We describe a patient with CMT2A2 (MFN2 mutation: T669G, F223L) who developed accelerated weakness, vocal cord paralysis, and optic atrophy after receiving ethambutol. RESULTS: Deterioration began within months of initiating ethambutol therapy. After discontinuation of ethambutol, neurologic deterioration stabilized with subsequent improvement in visual fields. CONCLUSIONS: CMT2A2 is part of a group of genetic disorders which share an association with the process of mitochondrial fusion. This case shows that patients with CMT2A2, and possibly other mitochondrial fusion defects, may be uniquely susceptible to ethambutol-induced neurotoxicity. This has implications regarding the underlying pathophysiology of mitochondrial fusion defects.