Heart and kidney transplant: should they be combined or subsequent?

AIMS: End-stage heart failure patients often present with severe kidney failure and have limited treatment options. We compared the clinical characteristics and outcomes among end-stage heart and kidney failure patients who underwent combined heart and kidney transplant (HKTx) with those who underwent kidney transplant after heart transplant (KAH). METHODS AND RESULTS: All patients from 2007-2016 who underwent combined HKTx (n = 715) and those who underwent KAH (n = 130) using the United Network for Organ Sharing database were included. Kaplan-Meier curves and Cox models compared survivals and identified predictors of death. Number of combined HKTx performed annually in United States increased from 59 in 2007 to 146 in 2016 whereas KAH decreased from 34 in 2007 to 6 in 2016. Among KAH patients, average wait time for kidney transplant was 3.0 years, time to dialysis or to kidney transplant after heart transplant did not differ with varying severity of kidney disease at baseline (P for both >0.05). Upon follow-up (mean 3.5 ± 2.7 years), 151 patients died. In multivariable models, patients who underwent combined HKTx had 4.7-fold greater risk of death [95% confidence interval (CI) 2.4-9.4) than KAH patients upon follow up. A secondary analysis using calculation of survival only after kidney transplant for KAH patients still conferred higher risk for combined HKTx patients [hazard ratio (HR) 2.6 95% CI 1.33-5.15]. In subgroup analyses after excluding patients on dialysis (HR 3.99 95% CI 1.98-8.04) and analysis after propensity matching for age, gender, and glomerular filtration rate (HR 3.01 95% CI 1.40-6.43) showed similar and significantly higher risk for combined HKTx patients compared with KAH patients. Lastly, these results also remained unchanged after excluding transplant centres who performed only one type of procedure preferentially, i.e. HKTx or KAH (HR 4.70 95% CI 2.35-9.42). CONCLUSIONS: National registry data show continual increase in combined HKTx performed annually in the United States but inferior survival compared with KAH patients. Differences in patient characteristics or level of kidney dysfunction at baseline do not explain these poor outcomes among HKTx patients compared with KAH patients. Consensus guidelines are greatly needed to identify patients who may benefit more from dual organ transplants.

Evaluation for Heart Transplantation and LVAD Implantation: JACC Council Perspectives.

Timely referrals for transplantation and left ventricular assist device implantation play a key role in favorable outcomes in patients with advanced heart failure. Nonetheless, evaluation usually occurs at advanced heart failure centers and is obscured from referring physicians. The purposes of this review are to explain the decision-making process for candidacy for advanced therapies and to describe the potential impact of the new organ allocation algorithm on center decision making. The document first addresses the signs of advanced heart failure, specifically focusing on the importance of the syndrome of low cardiac output as a key feature of advanced heart failure, and then summarizes the evaluation as a 3-step process addressing the following questions: 1) Is transplantation or durable assist device placement indicated? 2) Are there contraindications to either intervention? 3) How can one choose between transplantation and left ventricular assist device implantation if advanced therapies are indicated and not contraindicated?

Activities and Compensation of Advanced Heart Failure Specialists: Results of the Heart Failure Society of America (HFSA) Survey.

BACKGROUND: In the current era, where advanced heart failure (AHF) has become an American Board of Internal Medicine-certified subspecialty, new data are needed to benchmark and value levels of clinical effort performed by AHF specialists (AHFMDs). METHODS AND RESULTS: A 36-question survey was sent to 728 AHFMDs, members of the Heart Failure Society of America, and 224 (31%) responded. Overall, 56% worked in academic medical centers (AMCs) and were younger (48 ± 9 y vs 52 ± 10 y; P < .01) and were represented by a higher proportion of women (34% vs 21%, P < .01) compared with non-AMCs. The percentage of time in clinical care was lower in AMCs (64 ± 19% vs 78 ± 18%; P = .002), with similar concentration on evaluation and management services (79 ± 18% in AMCs vs 72 ± 18 % in non-AMCs; P = NS). The majority of nonclinical time was spent in program administration (10% in both AMCs and non-AMCs) and education/research (15% in AMC vs 5% in non-AMCs). Although 69% of respondents were compensated by work-relative value units (wRVUs), only a small percentage knew their target or the amount of RVUs generated. The mean annual wRVUs generated were lower in AMCs compared to non-AMCs (5,452 ± 1,961 vs 9,071 ± 3,484; P < .001). The annual compensation in AMCs was lower than in non-AMCs (45% vs 10% <$250,000 and 17% vs 61% >$350,000; P < .001) and the satisfaction with compensation was higher in non-AMCs. CONCLUSIONS: AHFMDs' compensation is largely dependent by practice type (AMC vs non-AMC) and clinical productivity as measured by wRVUs. These data provide an opportunity for benchmarking work effort and compensation for AHFMDs, allowing distinction from segments of cardiologists with greater opportunity to accrue procedural wRVUs. They also show several differences between AMCs and non-AMCs that should be considered when formulating work assignment and compensation for AHFMDs.

A novel approach to prevent post-operative ileus after continuous-flow left ventricular assist device implantation: A retrospective cohort study.

INTRODUCTION: Patients with postoperative ileus (POI), a common post-surgical event, experience intense discomfort. Various treatments targeting prevention of POI have shown to have an unpredictable effect. We introduced a novel postoperative bowel management protocol in patients implanted with a continuous-flow left ventricular assist device (CF-LVAD). The effect of this protocol on POI was evaluated. METHODS: Patients receiving an old bowel management protocol (OBMP; 01/2007-03/2009) were compared with those receiving a new bowel management protocol (NBMP; 04/2009-12/2013). The OBMP consisted of advancing the diet as tolerated, bisacodyl suppositories and enemas with the goal of a bowel movement (BM) every 3 days. The NBMP consisted of clear liquids until first BM is achieved, then full liquids until the second BM, then advancing to goal diet. Docusate is given on postoperative day (POD) 1 and bisacodyl PR on POD2 with enemas if ileus develops. Enemas are added POD3 if no BM has occurred. Polyethylene glycol is considered daily for patients prone to constipation. The goal is a BM every 2 days. Patients were made nil per os (NPO) with any signs of ileus. RESULTS: One hundred eighteen patients were implanted with CF-LVADs during the study period. The incidence of ileus significantly decreased from 19% in the OBMP group to 4% percent in the NBMP group (p < 0.05). In-hospital mortality was not different between the two groups (6% vs. 2% p = 0.35). CONCLUSIONS: A novel postoperative bowel management protocol successfully decreased the incidence of POI following CF-LVAD implant surgery at our institution.

A case series of real-time hemodynamic assessment of high output heart failure as a complication of arteriovenous access in dialysis patients.

Congestive heart failure (CHF) is an important source of morbidity and mortality in end-stage renal disease patients. Although CHF is commonly associated with low cardiac output (CO), it may also occur in high CO states. Multiple conditions are associated with increased CO including congenital or acquired arteriovenous fistulae or arteriovenous grafts. Increased CO resulting from permanent AV access in dialysis patients has been shown to induce structural and functional cardiac changes, including the development of eccentric left ventricle hypertrophy. Often, the diagnosis of high output heart failure requires invasive right heart monitoring in the acute care setting such as a medical or cardiac intensive care unit. The diagnosis of an arteriovenous access causing high output heart failure is usually confirmed after the access is ligated surgically. We present for the first time, a case for real-time hemodynamic assessment of high output heart failure due to AV access by interventional nephrology in the cardiac catheterization suite.

Lack of persistence of influenza vaccine antibody titers in patients with heart failure.

BACKGROUND: Patients with heart failure (HF) have lower initial antibody responses to the influenza vaccine compared with healthy individuals. Whether antibody titers wane faster in this population remains unknown. METHODS AND RESULTS: We studied 62 HF patients (18 ischemic, 44 idiopathic) and 40 healthy control subjects (HC) during the 2006-2007 and 2007-2008 influenza seasons. Antibody titers were measured before and 2-4 weeks and 11-12 months after vaccination. Serum antibody production was measured by hemagglutination inhibition assay, and antibody titers to individual vaccine viral strains between the HF and HC groups were compared after the influenza season to measure persistence of antibody response. All participants demonstrated early antibody seroprotection (titers 40 hemmaglutination inhibition units to 1 strain). Although antibody titers waned over time in both groups, titers to A/H3N2 and A/H1N1 strains decreased more in HF than in HC participants (P = .004 and P = .04, respectively). Titers to the B-type strain decreased to below seroprotective levels in both groups. CONCLUSIONS: Antibody titers to influenza A vaccine strains wane to below seroprotective levels in HF patients compared with HC, despite similar rates of initial seroprotection and seroconversion. These findings suggest that HF patients may remain at increased risk for influenza infection despite annual vaccination.

Double dose vs. standard dose influenza vaccination in patients with heart failure: a pilot study.

AIMS: Influenza infection leads to increased morbidity and mortality in those with heart failure, and individuals with heart failure exhibit reduced antibody responses to influenza vaccine. We hypothesized that patients with heart failure randomized to double dose (DD) influenza vaccine will mount more vigorous humoral immune responses compared with those given standard dose (SD) vaccine. METHODS AND RESULTS: We randomized 28 heart failure patients to DD (30 µg/strain) or SD (15 µg/strain) influenza vaccine. We assessed antibody production by haemagglutination inhibition assay (reported as log haemagglutination units) prior to, at 2-4 weeks and at 4-6 months following vaccination. Baseline antibody titres between DD (n = 12, mean age 64 ± 10 years) and SD (n = 16, mean age 63 ± 9 years) did not differ significantly. At 2-4 weeks, DD haemagglutination unit changes were significantly higher than those of SD (3.3 vs. 1.6 for A/H3N2, P < 0.001; 1.9 and 1.1 for A/H1N1, P = 0.009; and 1.7 and 1 for B-type, P = 0.02). At 4-6 weeks, there were no differences in titres in any of the virus types between treatment groups and, although titres decreased, levels remained above the seroprotective threshold. CONCLUSIONS: Higher influenza vaccine doses may elicit increased antibody-mediated responses in patients with heart failure; further studies should assess whether clinical outcomes are improved with this strategy.

The potential of cardiac allografts from donors after cardiac death at the University of Wisconsin Organ Procurement Organization.

OBJECTIVE: The purpose of this study is to investigate the potential availability of hearts from adult donation after cardiac death (DCD) donors within an acceptable hypoxic period. METHODS: We retrospectively reviewed a donor database from the University of Wisconsin Organ Procurement Organization Donor Tracking System between 2004 and 2006. The DCD population (n=78) was screened using our inclusion criteria for DCD cardiac donor suitability, including warm ischaemic time (WIT) limit of 30 min. In the same period, 70 hearts were donated from brain-dead donors. RESULTS: Of 78 DCD donors, 12 (15%) met our proposed DCD cardiac donor criteria. The mean WIT of these 12 DCD donors was 21 min (range 14-29 min). When inclusion criteria are further narrowed to (1) age <30 years, (2) WIT <20 min and (3) male gender, only two out of 12 met the criteria. CONCLUSIONS: Based on our proposed DCD cardiac donor criteria, the potential application of DCD cardiac donors would represent an increase in cardiac donation of 17% (12/70) during the 3-year period. When the criteria were narrowed to the initial 'ideal' case, only two donors met such criteria, suggesting that such 'ideal' DCD donors are rare but they do exist.

Decreased T-cell responses to influenza vaccination in patients with heart failure.

STUDY OBJECTIVE: To determine whether T-cell immune responses to influenza vaccination in patients with chronic heart failure (CHF) are less vigorous than the responses of healthy control subjects. DESIGN: Prospective, single-center study. SETTING: University hospital and research laboratory. PARTICIPANTS: Eighteen adults with stable CHF receiving optimal treatment and 16 healthy control subjects. INTERVENTION: Participants were immunized with the 2006-2007 trivalent inactivated (killed) influenza vaccine during October-December of 2006. MEASUREMENTS AND MAIN RESULTS: Blood samples were taken from the participants before and 2-4 weeks after vaccination to measure antibody titers, which were measured with a hemagglutination inhibition assay, then 3-4 months after vaccination to assess T-cell responses, measured by using the trans vivo delayed-type hypersensitivity method. As part of this method, which mimics physiologic conditions, peripheral blood mononuclear cells were isolated from the blood samples. The cells were mixed with influenza vaccine antigens A/H1N1, A/H3N2, and B type and injected into the footpads of SCID mice (mice with severe combined immunodeficiency), as their resulting swelling is an index of human T-cell sensitization. Median T-cell-mediated immune responses to A/H3N2 were less vigorous in patients with CHF than in control subjects (62.5 vs 87.5 microm, unadjusted p=0.031, age-adjusted p=0.006). Median responses to A/H1N1 were not significantly different between the groups (56.3 vs 75 microm, p=0.11). Median responses to B type were also similar between the groups (62.5 vs 75 microm, p=0.47). All participants mounted an antibody response to the influenza vaccine. CONCLUSION: Patients with CHF had reduced T-cell responses to the influenza vaccine compared with healthy control subjects, as demonstrated by a lower response to A/H3N2, the newest antigen in the 2006-2007 vaccine. However, differences in T-cell immune responses to the A/H1N1 and B type strains were not found to be significant between the two groups, which suggests that patients with CHF can mount an appropriate response to vaccine antigens to which they have been previously exposed, but less so to new antigens. These findings suggest that patients with CHF may be at increased risk for influenza infection, and clinicians may want to investigate other or additional strategies for influenza vaccination.

Management of allosensitized cardiac transplant candidates.

Cardiac transplantation remains the best treatment in patients with advanced heart failure with a high risk of death. However, an inadequate supply of donor hearts decreases the likelihood of transplantation for many patients. Ventricular assist devices (VADs) are being increasingly used as a bridge to transplantation in patients who may not survive long enough to receive a heart. This expansion in VAD use has been associated with increasing rates of allosensitization in cardiac transplant candidates. Anti-HLA antibodies can be detected before transplantation using different techniques. Complement-dependent lymphocytotoxicity assays are widely used for measurement of panel-reactive antibody (PRA) and for crossmatch purposes. Newer assays using solid-phase flow techniques feature improved specificity and offer detailed information concerning antibody specificities, which may lead to improvements in donor-recipient matching. Allosensitization prolongs the wait time for transplantation and increases the risk of post-transplantation complications and death; therefore, decreasing anti-HLA antibodies in sensitized transplant candidates is of vital importance. Plasmapheresis, intravenous immunoglobulin, and rituximab have been used to decrease the PRA before transplantation, with varying degrees of success. The most significant post-transplantation complications seen in allosensitized recipients are antibody-mediated rejection (AMR) and cardiac allograft vasculopathy (CAV). Often, AMR manifests with severe allograft dysfunction and hemodynamic compromise. The underlying pathophysiology is not fully understood but appears to involve complement-mediated activation of endothelial cells resulting in ischemic injury. The treatment of AMR in cardiac recipients is largely empirical and includes high-dose corticosteroids, plasmapheresis, intravenous immunoglobulin, and rituximab. Diffuse concentric stenosis of allograft coronary arteries due to intimal expansion is a characteristic of CAV. Its pathophysiology is unclear but may involve chronic complement-mediated endothelial injury. Sirolimus and everolimus can delay the progression of CAV. In some nonsensitized cardiac transplant recipients, the de novo formation of anti-HLA antibodies after transplantation may increase the likelihood of adverse clinical outcomes. Serial post-transplantation PRAs may be advisable in patients at high risk of de novo allosensitization.