Sexual Quality of Life in Left Ventricular Assist Device Patients and Their Partners.

BACKGROUND: Living with a left ventricular assist device (LVAD) comes with potentially burdensome aspects posed by, for example, battery packs and device drivelines. We aim to describe the impact of living with a durable LVAD on sexual quality of life (QOL), depression, and anxiety in patients and their partners. METHODS AND RESULTS: In this single-center, prospective, observational study, patients ≥4 months after LVAD implantation and their partners completed the Sexual Activities in Left Ventricular Assist Device Patients or Partners questionnaire to assess their sexual QOL, the 8-item Patient Health Questionnaire (PHQ-8) to assess symptoms of depression and the 7-item Generalized Anxiety Disorder (GAD-7) to assess symptoms of anxiety. Sixty patients and 60 partners completed the questionnaires 2.3 ± 1.9 years after implantation. Eighty-seven percent of the patients and 13% of partners were male. The mean age of patients was 57.4 ± 13.3 years, with 90% living with their partner. Ten percent of patients and 18% of partners had a current diagnosis of a psychological condition, most frequently depression and/or anxiety. Overall, 49% of participants indicated the LVAD influenced their sexual activity (patients 53% vs partners 45%; P = .33). Disturbances from the driveline were the most common problem indicated. Twenty-four percent of participants had scored in the mild to moderate depression range on the PHQ-8 and 28% scored in the mild to severe anxiety range on the GAD-7. The median total GAD-7 (1 [interquartile range (IQR) 0-4.25] vs 2.5 [IQR 0-5]; P = .06) were comparable between patients and partners; whereas patients had a higher total PHQ-8 score (3 [IQR 0-5.25] vs 1 [IQR 0-3.25]; P = .02). A preference to receive information regarding sexuality while on LVAD support was indicated by 54% of participants and did not differ between patients and partners (P > .99). Written resources were the most commonly preferred source of information. CONCLUSIONS: LVADs severely affect the sexual QOL for patients and their partners. The presence of a driveline is a major cause for concern. Patients prefer receiving written information on how to improve their sexual QOL.

Early elevated donor-derived cell-free DNA levels in heart transplant recipients following precision-controlled cardiac transport system or ice-cooled organ transport.

BACKGROUND: Recent innovations in temperature-controlled cardiac transportation allow for static hypothermic preservation of transplant organs during transportation. We assessed differences in donor-derived cell-free DNA (dd-cfDNA) using the SherpaPak cardiac transport system (SCTS) and traditional ice transportation. METHODS: Single-organ heart transplant recipients between January 2020 and January 2022 were included if they had dd-cfDNA measures ≤6 weeks post-transplant along with the baseline biopsy at 6 weeks as part of the surveillance protocol and no biopsy-confirmed rejection ≤90 days. Elevated dd-cfDNA ≥.20% were compared between groups using logistic regression including a subject effect. RESULTS: Of 65 hearts transplanted, 30 were transported with SCTS and 35 on ice. Recipient characteristics were similar between groups. Donors in the SCTS group were older (34 vs. 40 years, p = .04) with a longer total ischemic time (171 vs. 212 min, p = .002). Recipients in the SCTS group had a greater risk of elevated dd-cfDNA unadjusted and adjusted for donor age, and prolonged ischemic times > 3.5 h (Unadjusted odds ratio: 4.9, 95%-CI: 1.08-22.5, p = .039 and Adjusted odds ratio: 5.5, 95%-CI: 1.03-29.6, p = .046). Primary graft dysfunction rates and 1-year mortality were comparable between groups. CONCLUSION: Elevated dd-cfDNA in patients procured with SCTS may indicate that graft injury was not negated relative to ice transport. However, there were no clinical differences noted in short or long-term outcomes including mortality despite a longer ischemic time in the SCTS group.

Observed elevated donor-derived cell free DNA in orthotopic heart transplant recipients without clinical evidence of rejection.

Donor-derived cell free DNA (dd-cfDNA) has rapidly become part of rejection surveillance following orthotopic heart transplantation. However, some patients show elevated dd-cfDNA without clinical evidence of rejection. With the aim to provide a clinical description of this subpopulation, we retrospectively analyzed 35 cardiac transplant recipients at our center who experienced elevated (≥.20%) dd-cfDNA in the absence of clinical rejection, out of a total 106 recipients who had dd-cfDNA results available during the first year. The median time to first elevated dd-cfDNA level was 46 days, and the highest dd-cfDNA recorded within 1 year was .31% [inter-quartile range, .23-.45]. Twenty-two (63%) patients experienced infections (cytomegalovirus (CMV) or other), and 16 (46%) presented with de novo donor-specific antibodies. Cluster analysis revealed four distinct groups characterized by (a) subclinical rejection with 50% CMV (n = 16), (b) non-CMV infections and the longest time to first elevated dd-cfDNA (187 days) (n = 8), (c) right ventricular dysfunction (n = 6), and (d) women who showed the youngest median age (45 years) and highest median dd-cfDNA (.50%) (n = 5). Continued prospective analysis is needed to determine if these observations warrant changes in patient management to optimize the utilization of this vital non-invasive graft surveillance tool.

De novo tacrolimus extended-release tablets (LCPT) versus twice-daily tacrolimus in adult heart transplantation: Results of a single-center non-inferiority matched control trial.

Extended-release tacrolimus for prophylaxis of allograft rejection in orthotopic heart transplant (OHT) recipients is currently not FDA-approved. One such extended-release formulation of tacrolimus known as LCPT allows once-daily dosing and improves bioavailability compared to immediate-release tacrolimus (IR-tacrolimus). We compared the efficacy and safety of LCPT to IR-tacrolimus applied de novo in adult OHT recipients. Twenty-five prospective recipients on LCPT at our center from 2017 to 2019 were matched 1:2 with historical control recipients treated with IR-tacrolimus based on age, gender, and baseline creatinine. The primary composite outcome of death, acute cellular rejection, and/or new graft dysfunction within 1 year was compared using non-inferiority analysis. LCPT demonstrated non-inferiority to IR-tacrolimus, with a primary outcome risk reduction of 20% (90% CI: -40%, -.5%; non-inferiority P = .001). Tacrolimus trough levels peaked at 2-3 months and were higher in LCPT (median 14.5 vs. 12.7 ng/ml; P = .03) with similar dose levels (LCPT vs. IR-tacrolimus: .08 vs. .09 mg/kg/day; P = .33). Cardiovascular-related readmissions were reduced by 62% (P = .046) in LCPT patients. The complication rate per transplant admission and all-cause readmission rate did not differ significantly. These results suggest that LCPT is non-inferior in efficacy to IR-tacrolimus with a similar safety profile and improved bioavailability in OHT.

Health-Related Quality of Life in Patients With a Left Ventricular Assist Device (QOLVAD) Questionnaire: Initial Psychometrics of a New Instrument.

BACKGROUND: Patients with a left ventricular assist device are a unique and growing population who deserve their own valid, reliable instrument for health-related quality of life. OBJECTIVE: We developed and tested the Health-Related Quality of Life with a Left Ventricular Assist Device (QOLVAD) questionnaire. METHODS: In a prospective, descriptive study, patients from 7 sites completed the QOLVAD and comparator questionnaires. Construct validity was tested using confirmatory factor analysis. Convergent validity was tested using correlations of QOLVAD scores to well-established measures of subjective health status, depression, anxiety, and meaning/faith. Reliability and test-retest reliability were quantified. RESULTS: Patients (n = 213) were 58.7 ± 13.9 years old; 81.0% were male, 73.7% were White, and 48.0% had bridge to transplant. Questionnaires were completed at a median time of 44 weeks post ventricular assist device. The 5 QOLVAD domains had acceptable construct validity (root mean square error of approximation = 0.064, comparative and Tucker-Lewis fit indices > 0.90, weighted root mean square residual = 0.95). The total score and domain-specific scores were significantly correlated with the instruments to which they were compared. Internal consistency reliability was acceptable for all subscales (α = .79-.83) except the cognitive domain (α = .66). Unidimensional reliability for the total score was acceptable (α = .93), as was factor determinacy for multidimensional reliability (0.95). Total test-retest reliability was 0.875 (P < .001). CONCLUSION: Our analysis provided initial support for validity and reliability of the QOLVAD for total score, physical, emotional, social, and meaning/spiritual domains. The QOLVAD has potential in research and clinical settings to guide decision making and referrals; further studies are needed.

Outpatient COVID-19 surveillance testing in orthotopic heart transplant recipients.

COVID-19 case fatality rate in the United States is currently reported at 4.8% based on the confirmed cases of COVID-19. However, there are conflicting reports of estimated deaths in the post-cardiac transplantation patient population associated with COVID-19. METHODS: Observational, retrospective analysis of a large cohort of post Orthotopic Heart Transplantation (OHT) patients in a high volume heart transplantation program in Dallas, Texas underwent outpatient COVID-19 screening and testing for both SARS-CoV-2 nasopharyngeal RT-PCR and anti-SARS-CoV2 IgG serology as a result of a clinic protocol to facilitate re-opening of face-to-face outpatient clinical visits. RESULTS: The full outpatient cohort tested at time of their clinic visit tested negative for COVID-19 by nasopharyngeal RT-PCR. Only 2 patients tested seropositive for anti-SARS-COV2 IgG. Five positive inpatient cases were also identified and all, but one recovered. CONCLUSION: A COVID-19 surveillance protocol can be easily instituted in this high-risk population and facilitate safe transplant clinic operation. As the cases and prevalence increase across the United States, further strategies will need to be developed to determine the best course of action to help manage this select population while minimizing their exposure to the ongoing pandemic.

Durable left ventricular assist device implantation in extremely obese heart failure patients.

Left ventricular assist devices (LVADs) have improved clinical outcomes and quality of life for those with end-stage heart failure. However, the costs and risks associated with these devices necessitate appropriate patient selection. LVAD candidates are becoming increasingly more obese and there are conflicting reports regarding obesity's effect on outcomes. Hence, we sought to evaluate the impact of extreme obesity on clinical outcomes after LVAD placement. Consecutive LVAD implantation patients at our center from June 2008 to May 2016 were studied retrospectively. We compared patients with a body mass index (BMI) ≥40 kg/m2 (extremely obese) to those with BMI < 40 kg/m2 with respect to patient characteristics and surgical outcomes, including survival. 252 patients were included in this analysis, 30 (11.9%) of whom met the definition of extreme obesity. We found that patients with extreme obesity were significantly younger (47[33, 57] vs. 60[52, 67] years, P < 0.001) with fewer prior sternotomies (16.7% vs. 36.0%, P = 0.04). They had higher rates of pump thrombosis (30% vs. 9.0%, P = 0.003) and stage 2/3 acute kidney injury (46.7% vs. 27.0%, P = 0.003), but there were no differences in 30-day or 1-year survival, even after adjusting for age and clinical factors. Extreme obesity does not appear to place LVAD implantation patients at a higher risk for mortality compared to those who are not extremely obese; however, extreme obesity was associated with an increased risk of pump thrombosis, suggesting that these patients may require additional care to reduce the need for urgent device exchange.

Repeat Cardiac Transplant Indicated by Severe Cardiac Allograft Vasculopathy in a Patient With Danon Disease.

Danon disease is a rare, X-linked dominant, lysosomal storage disorder, presenting with cardiomyopathy mostly in adolescent men. Male patients face a high mortality rate and rarely live to the age of 25 years unless they receive a heart transplant. Because they generally undergo heart transplantation at a young age, many patients ultimately face both short- and long-term complications. We present a 32-year-old man diagnosed with Danon disease; a nonsense mutation in the LAMP-2 gene. Progressive heart failure symptoms resulted in initial heart transplant at age 27 years. He subsequently developed severe cardiac allograft vasculopathy that led to graft failure requiring a redo orthotopic heart transplant. This is one of only two reported Danon disease cases described to date surviving repeat orthotopic heart transplants. We present this case to highlight the importance of heart transplantation in the management of Danon disease, to emphasize the risk of cardiac allograft vasculopathy post-transplant, and to discuss management strategies.

Three-year outcomes of de novo tacrolimus extended-release tablets (LCPT) compared to twice-daily tacrolimus in adult heart transplantation.

BACKGROUND: Extended-release tacrolimus for prophylaxis of allograft rejection in heart transplant (HT) recipients is currently not FDA-approved. One such extended-release formulation of tacrolimus known as LCPT allows once-daily dosing and improves bioavailability compared to immediate-release (IR-) tacrolimus. We compared long-term efficacy and safety of LCPT to IR-tacrolimus applied de novo in adult OHT recipients. METHODS: 25 prospective recipients on LCPT at our center from 2017 to 2019 were matched 1:2 with historical control recipients treated with IR-tacrolimus based on age, gender, and baseline creatinine. The primary composite outcome of death, acute cellular rejection, and/or new graft dysfunction within 3 years following transplant was compared between groups using non-inferiority analysis. RESULTS: LCPT demonstrated non-inferiority to IR-tacrolimus, with a primary outcome risk reduction of 16% (90%CI, -37%, -1%, non-inferiority p = 0.002) up to 3 years following heart transplant. Up to 3-years post-transplant, 14 patients remained on once-daily LCPT and 10 patients were switched to IR-tacrolimus due to lack of insurance coverage. There were no significant differences in the rate of chronic kidney disease requiring dialysis, cytomegalovirus requiring treatment, cardiac allograft vasculopathy, and malignancy within 3 years following transplant. CONCLUSION: LCPT is non-inferior in efficacy to IR-tacrolimus in heart transplantation with a similar safety profile. Narrowly-constrained FDA labels specific to kidney transplant remain a barrier to consistent access to many immunosuppressant medications for recipients of non-kidney solid organs. We recommend the FDA consider developing facile pathways for expanding the approved label of extended-release tacrolimus formulations to heart transplant recipients.

Heart transplant Recipients' perspectives on invasive versus Non-invasive graft failure surveillance Methods.

BACKGROUND: Heart transplant recipients must regularly be assessed for graft rejection; however, endomyocardial biopsy (EMB), can be stressful, painful, and inconvenient. AlloMap® is the only commercially available non-invasive test for graft rejection. Current guidelines include AlloMap® testing in low-risk patients OBJECTIVES: To examine the patients' perspective, this study compared patients' experiences of AlloMap® and EMB surveillance at our center. METHODS: We enrolled consecutive heart transplant recipients who were to undergo routine EMB and AlloMap® testing (on different visits) to quantify their anxiety on the GAD-7 scale and their pain level on the Polyclinic Pain Scale. We assessed paired differences of anxiety and pain within patients according to surveillance method. RESULTS: We studied 43 participants (median age 60.5[54, 66] years; 35(81%) men; 27(63%) Caucasian). The median GAD-7 scores were 1[0, 4] and 2[0, 5] prior to EMB and AlloMap®, respectively (paired difference: 0[-1, 1],P = 0.323). The median pain scores were 1[0, 1] and 0[0, 0] for EMB and AlloMap®, respectively. Patients experienced less pain with AlloMap® testing compared to EMB (EMB-AlloMap;1[0, 1],P = 0.006). Seven (16%) participants experienced a total of 9 adverse events (pain, bruising, bleeding, swelling) from EMB vs 2(5%) participants who experienced a total of 3 adverse events (pain, bruising) from AlloMap®(P = 0.059). CONCLUSION: Heart transplant recipients had less pain and fewer adverse events while undergoing graft rejection surveillance with AlloMap® testing compared to EMB. An additional benefit of AlloMap® testing is that it may be performed at home and reduce these high-risk patients' infectious exposures.

The Utility of Home Sleep Apnea Testing in the Advanced Heart Failure Populations.

Untreated sleep disorders form a risk of coronary artery disease, hypertension, obesity, and diabetes mellitus. Access to polysomnography is limited, especially during the COVID-19 pandemic, with home sleep apnea testing (HSAT) being a potentially viable alternative. We describe an HSAT protocol in patients with advanced heart failure (HF). In a single-center, observational analysis between 2019 and 2021 in patients with advanced HF and heart transplant (HT), 135 screened positive on the STOP-Bang sleep survey and underwent a validated HSAT (WatchPAT, ZOLL-Itamar). HSAT was successful in 123 patients (97.6%), of whom 112 (91.1%; 84 HF and 28 HT) tested positive for sleep apnea. A total of 91% of sleep apnea cases were obstructive, and 63% were moderate to severe. Multivariable linear regression showed that the apnea hypopnea index was 34% lower in the HT group than in the HF group (p = 0.046) after adjusting for gender, and that this effect persisted in White patients but not among African-Americans. Patient characteristics were similar between groups, with coronary artery disease, diabetes mellitus, and hypertension as the most prevalent co-morbidities. In conclusion, sleep apnea remains prevalent in patients with HF with a high co-morbidity burden. HSAT is a feasible and effective tool for screening and diagnosis in this population.

The Effect of Obstructive Sleep Apnea on 3-Year Outcomes in Patients Who Underwent Orthotopic Heart Transplantation.

Despite the well-known association between obstructive sleep apnea (OSA) and cardiovascular disease, there is a paucity of data regarding OSA in orthotopic heart transplant (OHT) recipients and its effect on clinical outcomes. Hence, we sought to determine the association between OSA, as detected by polysomnography, and late graft dysfunction (LGD) after OHT. In this retrospective review of consecutive OHT recipients from 2012 to 2014 at our center, we examined LGD, i.e., graft failure >1 year after OHT, through competing risks analysis. Due to small sample size and event counts, as well as preliminary testing which revealed statistically similar demographics and outcomes, we pooled patients who had treated OSA with those who had no OSA. Of 146 patients, 29 (20%) had untreated OSA, i.e., OSA without use of continuous positive airway pressure therapy, at the time of transplantation. Patients with untreated OSA were significantly older, heavier, and more likely to have baseline hypertension than those with treated/no OSA. Although there were no differences between groups in regard to short-term complications of acute kidney injury, cardiac allograft vasculopathy, or primary graft dysfunction, there were significant differences in the occurrence of LGD. Those with untreated OSA were at 3 times the risk of developing LGD than those with treated/no OSA (hazard ratio 3.2; 95% confidence interval 1.3 to 7.9; p = 0.01). Because OSA is a common co-morbidity of OHT patients and because patients with untreated OSA have an elevated risk of LGD, screening for and treating OSA should occur during the OHT selection period.

Patient activation with respect to advanced heart failure therapy in patients over age 65 years.

BACKGROUND: Clinical and ethical issues persist in determining candidacy for advanced heart failure (HF) therapies in elderly patients. Selection takes many factors into account, including "activation" (engagement and ability to self-manage). OBJECTIVE: To investigate effects of age, activation, and depression/anxiety on selection and 6-month survival of participants considered for therapy. METHODS: Consecutive people referred for advanced HF therapy completed the Patient Activation Measure and Hospital Anxiety and Depression Scale. We analyzed data from participants by age (≥65 vs. <65 years), stratified by approval for therapy. RESULTS: Among 168 referred, 109 were approved, with no difference in activation between age groups (88% highly activated). Similarly, activation was not associated with age among those not approved. Activation was related to anxiety in older, approved participants, but not to depression. CONCLUSIONS: Concerns regarding reduced self-management in the elderly may not be valid. Age alone should not disqualify a candidate for advanced HF therapy.

Gene expression profiling scores in dual organ transplant patients are similar to those in heart-only recipients.

BACKGROUND: Serial gene expression profiling (GEP) may reduce the need for endomyocardial biopsies for detecting acute cellular rejection (ACR) after transplantation, but its performance in dual organ transplant recipients is currently unknown. METHODS: We analyzed 18 months of follow-up in a national cohort of 27 dual organ recipients (18 heart-kidney, 8 heart-liver, 1 heart-lung) matched to 54 heart-only recipients for gender, age, and time to first GEP (AlloMap®) test. ACR, antibody-mediated rejection (AMR), cytomegalovirus infections, biopsies, and longitudinal GEP scores were evaluated. RESULTS: During the first 90 days post-transplant, the mean GEP score for dual organ recipients was 25.2 ±â€¯9.1, vs. 23.5 ±â€¯7.7 for heart-only recipients (P = 0.48), with final GEP scores being 29.1 ±â€¯6.1 and 32.3 ±â€¯3.4, respectively (P = 0.34). GEP scores increased over time (P < 0.001) at a similar rate (P = 0.33) for both groups. One heart-only recipient had treated ACR (GEP score = 17). Fourteen subjects had cytomegalovirus infection, 8 of whom were dual-organ. During follow-up, mean GEP score among patients with cytomegalovirus infection was 32.3, compared to 26.7 (p < 0.001) in patients without cytomegalovirus. Only 4 (2%) of 233 biopsies were positive for mild AMR; all occurring in 2 heart-only recipients (GEP scores = 18-33). CONCLUSIONS: This largest cohort to date suggests that dual organ transplantation alone should not be reason to omit GEP testing from post-transplant medical management, as the two groups' scores did not differ significantly. Confirming that GEP scores increase over time for heart-only and dual organ recipients and in the presence of cytomegalovirus infection, our work shows promise for the use of serial GEP testing in dual organ recipients.

Use of a percutaneous temporary circulatory support device as a bridge to decision during acute decompensation of advanced heart failure.

BACKGROUND: Prognosis is poor for patients with decompensated advanced heart failure (HF) refractory to medical therapy. Evaluating candidacy for durable mechanical circulatory support (MCS), cardiac transplantation, or palliative care is complex, and time is often needed to stabilize the patient hemodynamically. The Impella 5.0 (Abiomed, Danvers, MA) is a minimally invasive axial-flow catheter capable of providing full temporary hemodynamic support. We report a multicenter series on the use of this device for bridge to decision (BTD) in decompensated advanced HF patients. METHODS: In a retrospective evaluation at 3 centers of patients with advanced HF who acutely decompensated and received the Impella 5.0 for BTD, we analyzed demographics, procedural characteristics, in-hospital and intermediate-term outcomes, and in-hospital complications. RESULTS: There were 58 patients who met inclusion criteria from 2010 to 2015. All were inotrope dependent. The mean ejection fraction was 13%, and median age was 59 years (interquartile range, 48-64 years). Mean duration of support was 7 days (range, 0-22 days). Thirty-nine patients survived to next therapy (67%), with most receiving durable MCS (n = 20) or heart transplantation (n = 15). In-hospital complications included bleeding (n = 9) and hemolysis (n = 4). Of patients who survived to the next therapy, 1-year survival was 65% for those who received durable MCS, 87% for those who received a transplant, and 75% for those who were stabilized and weaned. CONCLUSIONS: The Impella 5.0 may provide a BTD strategy for patients with advanced HF and acute hemodynamic instability. Prospective studies are needed to evaluate the safety and effectiveness of this device in this patient population.

Probability of Accurate Heart Failure Diagnosis and the Implications for Hospital Readmissions.

Heart failure (HF) is a complex syndrome with inherent diagnostic challenges. We studied the scope of possibly inaccurately documented HF in a large health care system among patients assigned a primary diagnosis of HF at discharge. Through a retrospective record review and a classification schema developed from published guidelines, we assessed the probability of the documented HF diagnosis being accurate and determined factors associated with HF-related and non-HF-related hospital readmissions. An arbitration committee of 3 experts reviewed a subset of records to corroborate the results. We assigned a low probability of accurate diagnosis to 133 (19%) of the 712 patients. A subset of patients were also reviewed by an expert panel, which concluded that 13% to 35% of patients probably did not have HF (inter-rater agreement, kappa = 0.35). Low-probability HF was predictive of being readmitted more frequently for non-HF causes (p = 0.018), as well as documented arrhythmias (p = 0.023), and age >60 years (p = 0.006). Documented sleep apnea (p = 0.035), percutaneous coronary intervention (p = 0.006), non-white race (p = 0.047), and B-type natriuretic peptide >400 pg/ml (p = 0.007) were determined to be predictive of HF readmissions in this cohort. In conclusion, approximately 1 in 5 patients documented to have HF were found to have a low probability of actually having it. Moreover, the determination of low-probability HF was twice as likely to result in readmission for non-HF causes and, thus, should be considered a determinant for all-cause readmissions in this population.