Multicenter study of universal prophylaxis versus pre-emptive therapy for patients at intermediate risk (R+) for CMV following heart transplantation.

INTRODUCTION: Heart transplant (HT) recipients with prior exposure to cytomegalovirus (CMV R+) are considered intermediate risk for CMV-related complications. Consensus guidelines allow for either universal prophylaxis (UP) or preemptive therapy (PET) (serial CMV testing) approaches to CMV prevention in such patients. Whether an optimal approach to mitigate CMV related risks exists in this setting remains uncertain. We therefore assessed the utility of PET as compared to UP in CMV R+ HT recipients. METHODS: Retrospective analysis of all CMV R+ HT recipients from 6 U.S. centers between 2010 and 2018 was performed. The primary outcome was the development of CMV DNAemia or end-organ disease resulting in the initiation/escalation of anti-CMV therapy. The secondary outcome was CMV-related hospitalization. Additional outcomes included incidence of acute cellular rejection (ACR) ≥ grade 2R, death, cardiac allograft vasculopathy (CAV), and leukopenia. RESULTS: Of 563 CMV R+ HT recipients, 344 (61.1%) received UP. PET was associated with increased risk for the primary (adjusted HR 3.95, 95% CI: 2.65-5.88, p < .001) and secondary (adjusted HR 3.19, 95% CI: 1.47-6.94, p = .004) outcomes, and with increased ACR ≥ grade 2R (PET 59.4% vs. UP 34.4%, p < .001). Incidence of detectable CAV was similar at 1 year (PET 8.2% vs. UP 9.5%, p = .698). UP was associated with increased incidence of leukopenia within 6 months post-HT (PET 34.7% vs. UP 43.6%, p = .036). CONCLUSION: The use of a PET CMV prophylaxis strategy in intermediate risk HT recipients associated with increased risk of CMV infection and CMV-related hospitalization, and may associate with worse post-HT graft outcomes.

Influence of physiological and psychological factors on cognitive dysfunction in heart failure patients.

AIM: Our study aimed to examine factors that contribute to cognitive dysfunction in patients with heart failure (HF). BACKGROUND: Although a majority of patients with HF have mild to moderate cognitive impairment, little is known about factors that influence progressive cognitive decline in this population. METHODS: We examined the influence of physiological factors (NYHA functional class II - IV, ejection fraction, co-morbidity burden, polypharmacy), psychosocial factors (anxiety, depression, evaluation for advanced therapy), and associated toxicities (anticholinergic drug burden), on cognitive dysfunction. Data were analyzed using mean (SE) for continuous variables and frequency and percent for categorical variables. Differences between NYHA functional classification (Class II vs. Class III/IV) were examined using Chi Square. Linear regression models were used to assess associations among model variables. RESULTS: Of the 113 participants with HF, Class III-IV HF were more cognitively impaired than those with NYHA Class II (p < 0.0001), had higher anxiety (p = 0.002), and depression (p = 0.003), and lower EF (p = 0.041). A majority of participants had a moderate anticholinergic drug burden, and NYHA Class III/IV participants had significantly higher medication counts than Class II participants (p = 0.034). Regression analysis found that NYHA Class III/IV, anxiety, depression and evaluation for advanced therapy significantly influenced cognitive dysfunction. CONCLUSIONS: Findings support a high prevalence of cognitive dysfunction, anxiety, and depression in NYHA class II-IV with a greater level of cognitive dysfunction in class III/IV patients.

Report from the 2018 consensus conference on immunomodulating agents in thoracic transplantation: Access, formulations, generics, therapeutic drug monitoring, and special populations.

In 2009, the International Society for Heart and Lung Transplantation recognized the importance and challenges surrounding generic drug immunosuppression. As experience with generics has expanded and comfort has increased, substantial issues have arisen since that time with other aspects of immunomodulation that have not been addressed, such as access to medicines, alternative immunosuppression formulations, additional generics, implications on therapeutic drug monitoring, and implications for special populations such as pediatrics and older adults. The aim of this consensus document is to address critically each of these concerns, expand on the challenges and barriers, and provide therapeutic considerations for practitioners who manage patients who need to undergo or have undergone cardiothoracic transplantation.

Elevated AT1R Antibody and Morbidity in Patients Bridged to Heart Transplant Using Continuous Flow Left Ventricular Assist Devices.

BACKGROUND: We studied longitudinal levels of angiotensin-II type 1 receptor antibody (AT1R-Ab) and their effects on adverse events (death, treated rejection and cardiac allograft vasculopathy) in patients who were bridged to heart transplant using a continuous flow left ventricular assist device (LVAD). METHODS AND RESULTS: Sera of 77 patients bridged to heart transplant (from 2009 to 2017) were tested for AT1R-Ab and CRP before and after LVAD. Elevated AT1R-Ab was defined as >10.0 U/mL. The median follow-up after transplant was 3.6 years (interquartile range, 2.2-5.6 years). After LVAD, AT1R-Ab levels increased from baseline and remained elevated until transplant. Freedom from adverse events at 5 years was lower in those with elevated AT1R-Ab levels at time of transplant. In an adjusted, multivariable Cox analysis, an AT1R-Ab level of >10 U/mL was associated with developing the primary end point (adjusted hazard ratio 3.4, 95% confidence interval 1.2-9.2, P = .017). Although C-reactive protein levels were high before and after LVAD placement, C-reactive protein did not correlate with AT1R-Ab. CONCLUSIONS: In LVAD patients bridged to heart transplant, an increased AT1R-Ab level at time of transplant was associated with poor outcomes after heart transplant. Post-LVAD AT1R-Ab elevations were not correlated with serum markers of systemic inflammation. Larger studies are needed to examine the pathologic role of AT1R-Ab in heart transplant.

Heart failure symptom clusters and quality of life.

BACKGROUND: Heart failure (HF) is a progressive symptomatic illness with reports suggesting that patients experience multiple symptoms. Symptom clusters constitute symptoms that co-occur, are related, and influence outcomes. OBJECTIVES: The specific aims of this study were to (1) examine prevalent symptoms experienced by persons with HF, (2) identify symptoms forming clusters, and (3) evaluate the impact of HF symptom clusters on quality of life (QOL). METHODS: 117 participants (62% male; 50% black; age = 56) were recruited. Prevalent symptoms were evaluated; principle components analysis (PCA) was used to extract symptom clusters; regression analysis was used to evaluate factors influencing QOL, defined as life satisfaction. RESULTS: Three symptom clusters-sickness behavior, discomforts of illness, and GI distress-were extracted. Sickness behavior significantly influenced QOL (ß = -0.603 p = 0.0001), explaining 40% of the variance (F = 75.12; R2 = 0.404; p = 0.0001). CONCLUSIONS: The Sickness Behavior cluster had a negative impact on QOL and suggests that incorporating an evaluation of these symptoms may facilitate identification and treatment of symptoms having an additive and detrimental influence on QOL. Studies to examine the stability of the clusters are warranted.

Pregnancy-related allograft rejection following heart transplant.

Current recommendations do not discourage pregnancy in stable, orthotopic heart transplant (OHT) recipients who are more than 1 year posttransplant, although a highly specialized level of care with a multidisciplinary team is recommended. These patients may incur significant risk to themselves, their allograft, and/or their fetuses. Recognition and treatment of posttransplant complications in pregnancy also may be difficult. Although the risk of recurrent pregnancies in patients with peripartum cardiomyopathy (PPCM) is well defined, the risk of pregnancy after a PPCM patient has undergone OHT is unknown. A case of severe allograft rejection in a woman with a history of PPCM who became pregnant nearly 3 years after OHT is presented and her subsequent management is described. The data available on pregnancy after transplant are based on case reports, registry data, and reviews. The decision to become pregnant should be preceded by an extensive discussion including the patient, her partner, her obstetrician, and the transplant team, reviewing potential risks to her health as well as to her allograft and the fetus. Providers should be clear that many questions pertaining to pregnancy after transplant remain unanswered, and the patient should be comfortable going forward in this situation.

Surveillance Endomyocardial Biopsy in the Modern Era Produces Low Diagnostic Yield for Cardiac Allograft Rejection.

BACKGROUND: The changing epidemiology of cardiac allograft rejection has prompted many to question the yield of surveillance endomyocardial biopsy (EMB) in heart transplantation (HT) patients. We sought to determine the yield of EMB in the modern era. METHODS: We evaluated 2597 EMBs in 182 consecutive HT patients who survived to their first EMB. The EMBs were categorized as asymptomatic or clinically driven and were compared based on era of antiproliferative therapy use at our center (early azathioprine era: 1990-2000 vs modern mycophenolate era: 2000-2011). RESULTS: In the modern era, patients had a higher prevalence of risk factors for developing rejection (≥ International Society of Heart and Lung Transplantation grade 2R); however, the frequency of rejection was decreased at all times (0-6 months: 60.2% vs 21.5%, P < 0.001, 6-12 months: 26.8% vs 1.8%, P < 0.001, 12-36 months: 32.3% vs 10.5%, P = 0.006). The yield of asymptomatic EMB decreased in the modern era between 0 and 6 months (10.9% vs 3.12%), 6 to 12 months (17% vs 0%), and years 2 to 3 (6.1% vs 1.5%). In the early era, the odds ratio of rejection during asymptomatic EMB compared to a clinically driven EMB was 0.47 (95% confidence interval, 0.31-0.71) and was decreased in the modern era (0.17 [0.07-0.42], P = 0.04). The probability of detecting rejection on asymptomatic EMB was significantly reduced in the modern era, even after adjustment for tacrolimus and induction therapy (1% vs 8%, P < 0.001). CONCLUSIONS: The clinical yield of surveillance EMB has decreased in the modern era. The EMB in asymptomatic patients longer than 6 months after HT warrants further scrutiny.

Heart failure symptom clusters and functional status - a cross-sectional study.

AIM: To identify symptom clusters in individuals with heart failure and evaluate the relationship of the identified clusters to functional status. BACKGROUND: Heart Failure is a global health problem affecting approximately 1-2% of the adult population in developed countries worldwide. Individuals with heart failure may experience as many as nine symptoms and may limit activities that worsen their symptoms or adjust the way they engage in activities. DESIGN: Cross-sectional. METHODS: A convenience sample of individuals (n = 117) with a confirmed diagnosis of heart failure was recruited from an academic medical centre during 2011-2012. Prevalent heart failure symptoms and functional status outcomes (functional limitations and mobility) were evaluated. Factor analysis using the principal components method was used to extract symptom clusters. Regression analysis using a backwards stepwise model-building approach was used to examine the effects of the symptom clusters, age and co-morbidity on functional limitations and mobility. RESULTS: Three symptom clusters, sickness behaviour, discomforts of illness and gastrointestinal distress were extracted. When sickness behaviours and discomforts of illness were both present, functional limitations were more sensitive to sickness behaviours. Sickness behaviour and co-morbidity were related to limited mobility. CONCLUSIONS: Individuals with heart failure may be helped to improve their functional status by managing sickness behaviour and discomforts of illness symptoms. Identification of symptom clusters may lead to the development of interventions focusing on a cluster of heart failure symptoms.

Psychosocial assessment of candidates and risk classification of patients considered for durable mechanical circulatory support.

BACKGROUND: The psychosocial assessment of candidates for transplantation (PACT), developed to assess candidates for heart transplant, has not been routinely used to assess left ventricular assist device (LVAD) candidacy. We examined the efficacy of the PACT to assess psychosocial outcomes in LVAD patients. METHODS: We reviewed patients who received LVAD implants between June 2006 and April 2011 and retrospectively applied the PACT. We determined the accuracy of identifying social success with the PACT and revised domains to reflect criteria influencing social success for LVAD patients. RESULTS: Forty-eight patients (72% men, 44% non-white, 50.4 years old) were divided into high-scoring and low-scoring groups. Nine patients with low PACT scores were falsely categorized as high-risk, whereas 4 with high scores had poor social outcomes. The score had a high positive-predictive value (0.86) but low negative-predictive value (0.31). The PACT was revised (modified [m]PACT) to measure indicators, such as social support and understanding of care requirements, identified to more closely affect LVAD outcome. The mPACT exhibited improved accuracy. A reclassification table was developed, and the net reclassification index was 0.32. The percentage of patients incorrectly classified for social risk decreased from 27% with the PACT to 8% with the mPACT. Patients with higher mPACT scores had decreased 30-day readmission rates (26% vs 67%, p = 0.045) after device implantation. CONCLUSIONS: By emphasizing social support, psychologic health, lifestyle factors, and device understanding, the mPACT showed improved performance in risk-stratifying candidates for LVAD therapy. Prospective validation is warranted.

Living with a total artificial heart: patients' perspectives.

BACKGROUND: Advances in mechanical circulatory support have reduced morbidity and mortality in end-stage heart failure. To date, there have been no published studies examining the psychosocial impact on patients who are supported with a total artificial heart (TAH-t). PURPOSE: The purpose of this study was to describe the lived experience of patients currently supported by the TAH-t awaiting transplant. METHODS: A qualitative method using Giorgi's modification of phenomenologic inquiry guided the investigation, which was conducted at a transplant center located in the mid-Atlantic region of the United States. A purposive sample was selected to reflect participants currently supported by the TAH-t. All participants (9 men, 1 woman; mean age, 48.2 years; nonischemic etiology, 80%) were in-patients on the progressive care unit at the time of the interview and had been supported for at least 30 days. The mean length of device therapy was 84.7 days (range, 33-245 days). FINDINGS: Hope for the future was the overarching theme. Subthemes included reflections, for better or for worse, the secret club, and coping and adaptation. The patients reflected on severity of illness, progress, and expressed optimism. For better or for worse described how symptoms improved but were offset by restrictions imposed by the technology. The secret club described the support provided to help deal with their life situation. Coping and adaptation suggested that the patients came to terms with and accepted their circumstances. CONCLUSIONS: The findings will help clinicians understand patients experiencing a life-changing situation and implications for psychosocial interventions.

Persistent anemia after implantation of the total artificial heart.

BACKGROUND: The total artificial heart (TAH) replaces the heart with 2 pneumatic pumps and 4 tilting disk mechanical valves. It was hypothesized that patients receiving TAH support have persistent hemolysis that resolves after heart transplantation (HT). METHODS AND RESULTS: Hematocrit (HCT) was compared in patients on TAH to left ventricular assist device (LVAD) support for bridge to HT. Data were compared with t tests. The TAH (n = 36; mean age 47 ± 13 years) and LVAD patients (n = 14; mean age 53 ± 12 years) were supported for a median of 83 (interquartile range [IQR] 43-115) and 106 days (IQR 84-134), respectively. Hematocrit was similar between the TAH and LVAD patients (34 ± 6% vs 37 ± 5%; P = .07) at baseline. After placement, TAH patients had lower HCT at 2 (20 ± 2% vs 24 ± 3%), 4 (22 ± 3% vs 26 ± 3%), 6 (22 ± 4% vs 30 ± 4%), and 8 weeks (23 ± 4% vs 33 ± 5%; P < .001 for all). There were no differences in HCT at 1 (30 ± 4% vs 29 ± 7%; P = .42) and 3 months (35 ± 7% vs 35 ± 4%; P = .98) after removal of the devices for HT. TAH patients had undetectable haptoglobin in 96% of assessments, increased lactate dehydrogenase (1,128 ± 384 units/L), and detectable plasma free hemoglobin in 40% of measurements (21 ± 15 mg/dL). High sensitivity C-reactive protein (52 ± 50 mg/dL) was elevated, and reticulocyte production index was decreased (1.6 ± 0.6). CONCLUSIONS: Patients implanted with a TAH have persistent anemia that resolves only after HT. The association of hemolysis, ineffective erythropoiesis, and inflammation with the TAH warrants further study.

Exercise blood pressure response during assisted circulatory support: comparison of the total artificial [corrected] heart with a left ventricular assist device during rehabilitation.

BACKGROUND: The total artificial heart (TAH) consists of two implantable pneumatic pumps that replace the heart and operate at a fixed ejection rate and ejection pressure. We evaluated the blood pressure (BP) response to exercise and exercise performance in patients with a TAH compared to those with a with a continuous-flow left ventricular assist device (LVAD). METHODS: We conducted a single-center, retrospective study of 37 patients who received a TAH and 12 patients implanted with an LVAD. We measured the BP response during exercise, exercise duration and change in tolerated exercise workload over an 8-week period. RESULTS: In patients with a TAH, baseline BP was 120/69 ± 13/13, exercise BP was 118/72 ± 15/10 and post-exercise BP was 120/72 ± 14/12. Mean arterial BP did not change with exercise in patients with a TAH (88 ± 10 vs 88 ± 11; p = 0.8), but increased in those with an LVAD (87 ± 8 vs 95 ± 13; p < 0.001). Although the mean arterial BP (MAP) was negatively correlated with metabolic equivalents (METs) achieved during exercise, the association was not statistically significant (ß = -0.1, p = 0.4). MAP correlated positively with METs achieved in patients with LVADs (MAP: ß = 0.26, p = 0.04). Despite the abnormal response to exercise, patients with a TAH participated in physical therapy (median: 5 days; interquartile range [IQR] 4 to 7 days) and treadmill exercise (19 days; IQR: 13 to 35 days) early after device implantation, with increased exercise intensity and duration over time. CONCLUSIONS: During circulatory support with a TAH, the BP response to exercise was blunted. However, aerobic exercise training early after device implantation was found to be safe and feasible in a supervised setting.

Implantable mechanical circulatory support: demystifying patients with ventricular assist devices and artificial hearts.

Engineering advancements have expanded the role for mechanical circulatory support devices in the patient with heart failure. More patients with mechanical circulatory support are being discharged from the implanting institution and will be seen by clinicians outside the immediate surgical or heart-failure team. This review provides a practical understanding of device design and physiology, general troubleshooting, and limitations and complications for implantable left ventricular assist devices (pulsatile-flow and continuous-flow pumps) and the total artificial heart.

Caregiving for patients requiring left ventricular assistance device support.

BACKGROUND: The responsibility of caregiving for patients requiring left ventricular assistance device (LVAD) support may be significant. However, little is known about their experience. Data from the Interagency Registry for Mechanically Assisted Circulatory Support (2006-2009) reported that 1722 patients had received LVADs as a bridge to transplantation, recovery, or destination therapy. The use of this advanced technology in the management of endstage heart failure is expected to continue, suggesting increased involvement of family members and significant others. The purpose of this qualitative study was to describe the experiences of caregivers of patients who received LVAD therapy as a bridge to transplantation. METHODS: Semistructured interviews allowed participants to describe their experiences as caregivers. Interviews were audiotape-recorded and transcribed verbatim. An analysis was conducted using Sandelowski's three-step process for the analysis of phenomenological data: data dwelling, open coding, and data reduction. RESULTS: Participants (n=5 women and 1 man; age, 51 years; range=44 to 66 years; duration of caregiving, 183.9 days; range, 26 to 372 days; relationship to patient: spouse=3, parent=1, significant other=1, and friend=1) were designated caregivers of patients discharged home with an LVAD. Two themes emerged: sacrifice and moving beyond. Caregivers sacrificed relationships with friends and family, jobs and livelihood, health, and peace of mind in their roles as caregivers. "Moving beyond" reflected coping and adaptation to the sacrifices of being a caregiver. CONCLUSIONS: Experiences described by caregivers suggest that they successfully incorporated the role of caregiver for patients with a complex therapeutic regimen into their daily lives. The specific findings should guide healthcare professionals in their efforts to support caregivers.

Psychosocial factors, quality of life, and psychological distress: ethnic differences in patients with heart failure.

Advances in treatment have prolonged life in heart failure (HF) patients, leading to increased attention to quality of life (QOL) and psychological functioning. It is not clear if ethnic differences exist in factors associated with psychological well-being. We examined psychosocial factors associated with depression and anxiety in 97 HF patients. Medical records were reviewed and patients (M age 53, 50% African American) completed surveys examining social support, coping, spirituality, and QOL for their association with depression and anxiety. Multiple regressions suggested that psychosocial factors were associated with psychological health. Patients with lower social support, lower meaning/peace and more negative coping reported greater depression; positive coping, and lower meaning/peace were associated with higher anxiety. Ethnicity stratified models suggested that spiritual well-being was associated with depression only among African Americans and QOL partially mediated this relationship. Findings suggest the importance of considering the unique psychosocial needs of diverse populations to appropriately target clinical interventions.