Impact of Age of Heart Transplant Program on Patient Survival and Post-Transplant Outcomes.

BACKGROUND: The relationship between age of a heart transplant (HT) program and outcomes has not been explored. METHODS: We performed a retrospective cohort analysis of the United Network for Organ Sharing database of all adult HTs between 2009 and 2019. For each patient, we created a variable that corresponded to program age: new (<5), developing (≥5 but <10) and established (≥10) years. RESULTS: Of 20 997 HTs, 822 were at new, 908 at developing, and 19 267 at established programs. Patients at new programs were significantly more likely to have history of cigarette smoking, ischemic cardiomyopathy, and prior sternotomy. These programs were less likely to accept organs from older donors and those with a history of hypertension or cigarette use. As compared to patients at new programs, transplant patients at established programs had less frequent rates of treated rejection during the index hospitalization (HR 0.43 [95% CI, 0.36-0.53] p < 0.001) and at 1 year (HR 0.58 [95% CI, 0.49-0.70], p < 0.001), less frequently required pacemaker implantations (HR 0.50 [95% CI, 0.36-0.69], p < 0.001), and less frequently required dialysis (HR 0.66 [95% CI, 0.53-0.82], p < 0.001). However, there were no significant differences in short- or long-term survival between the groups (log-rank p = 0.24). CONCLUSION: Patient and donor selection differed between new, developing, and established HT programs but had equivalent survival. New programs had increased likelihood of treated rejection, pacemaker implantation, and need for dialysis. Standardized post-transplant practices may help to minimize this variation and ensure optimal outcomes for all patients.

Clinical Utility of the Molecular Microscope Diagnostic System in a Real-World Transplant Cohort: Moving Towards a New Paradigm.

Objectives: To evaluate the clinical implications of adjunctive molecular gene expression analysis (MMDx ) of biopsy specimens in heart transplant (HT ) recipients with suspected rejection. Introduction: Histopathological evaluation remains the standard method for rejection diagnosis in HT. However, the wide interobserver variability combined with a relatively common incidence of "biopsy-negative" rejection has raised concerns about the likelihood of false-negative results. MMDx, which uses gene expression to detect early signs of rejection, is a promising test to further refine the assessment of HT rejection. Methods: Single-center prospective study of 418 consecutive for-cause endomyocardial biopsies performed between November 2022 and May 2024. Each biopsy was graded based on histology and assessed for rejection patterns using MMDx. MMDx results were deemed positive if borderline or definitive rejection was present. The impact of MMDx results on clinical management was evaluated. Primary outcomes were 1-year survival and graft dysfunction following MMDx-guided clinical management. Secondary outcomes included changes in donor-specific antibodies, MMDx gene transcripts, and donor-derived cell-free DNA (dd-cfDNA) levels. Results: We analyzed 418 molecular samples from 237 unique patients. Histology identified rejection in 32 cases (7.7%), while MMDx identified rejection in 95 cases (22.7%). Notably, in 79 of the 95 cases where MMDx identified rejection, histology results were negative, with the majority of these cases being antibody-mediated rejection (62.1%). Samples with rejection on MMDx were more likely to show a combined elevation of dd-cfDNA and peripheral blood gene expression profiling than those with borderline or negative MMDx results (36.7% vs 28.0% vs 10.3%; p<0.001). MMDx results led to the implementation of specific antirejection protocols or changes in immunosuppression in 20.4% of cases, and in 73.4% of cases where histology was negative and MMDx showed rejection. 1-year survival was better in the positive MMDx group where clinical management was guided by MMDx results (87.0% vs 78.6%; log rank p=0.0017). Conclusions: In our cohort, MMDx results more frequently indicated rejection than histology, often leading to the initiation of antirejection treatment. Intervention guided by positive MMDx results was associated with improved outcomes.

Long-term outcomes of heart transplantation in adults with congenital heart disease: The impact of single-ventricle versus biventricular physiology.

Objective: Congenital heart disease is a risk factor for mortality after orthotopic heart transplantation; however, the impact of preoperative circulation type and primary congenital heart disease diagnosis remains poorly delineated. Methods: We retrospectively reviewed patients with adult congenital heart disease aged 16 years or more who underwent orthotopic heart transplantation at our institution between 2008 and 2022. Patients were categorized as having single-ventricle or biventricular circulation. The primary end point was 5-year post-transplant survival. Results: Sixty-one patients with adult congenital heart disease (single-ventricle: n = 26 [42.6%], biventricular: n = 35 [57.4%]) underwent orthotopic heart transplantation at 33.7 [interquartile range, 19.1-48.7] years. The most common congenital heart disease diagnosis was hypoplastic left heart syndrome (n = 11, 42.3%) in the single-ventricle group and congenitally corrected transposition of the great arteries (n = 7, 20.0%) in the biventricular group. Twenty-four patients previously underwent Fontan palliation. At transplant, patients in the single-ventricle group were younger (18.5 [interquartile range, 17.6-32.3] years vs 45.0 [interquartile range, 33.0-52.2] years, P < .001) and more likely to have biopsy-proven cirrhosis (46.2% vs 14.3%, P = .01) and protein-losing enteropathy (42.3% vs 2.9%, P < .001). Patients in the single-ventricle group also had longer bypass times (223.4 ± 65.3 minutes vs 187.4 ± 59.5 minutes, P = .03) and longer durations of mechanical ventilatory support (3.5 [interquartile range, 2.0-6.0] days vs 1.0 [interquartile range, 1.0-2.0] days, P < .001). Operative mortality was comparable (11.5% vs 8.6%, P = 1). Median follow-up was 6.0 [interquartile range, 2.4-10.0] years. Five-year survival was worse in the single-ventricle group (66.0% ± 10.0% vs 91.3% ± 4.8%, P = .03), as was freedom from major rejection (58.3% ± 10.2% vs 84.0% ± 6.6%, P = .02). In univariable analysis, hypoplastic left heart syndrome and Fontan circulation were risk factors for post-transplant mortality (hypoplastic left heart syndrome: hazard ratio, 5.0, P < .001; Fontan: hazard ratio, 3.5, P = .03). Conclusions: Adult patients with congenital heart disease undergoing heart transplant with single-ventricle physiology experienced a more complicated post-transplant course, with worse long-term survival and freedom from rejection. Multicenter studies are required to guide orthotopic heart transplantation decision-making in this complex cohort.

Medium-Term Outcomes of Concomitant Aortic Valve Repair in Patients with Continuous-Flow Left Ventricular Assist Device.

OBJECTIVE: Our objective was to analyze the development of aortic insufficiency in patients who received central aortic valve repair when undergoing continuous-flow left ventricular assist device implantation. METHODS: We conducted a retrospective review of patients who underwent HeartMate II or 3 (Abbott Lab) implantation between 2004 and 2022. Ninety-four patients were excluded from analysis for history of aortic valve procedures, a bicuspid aortic valve, baseline trace aortic insufficiency, or other concomitant aortic valve procedure. Patients who had ≥ mild aortic insufficiency had concomitant aortic valve repair. Clinical characteristics, serial echocardiograms, and outcomes were determined. RESULTS: Of the 656 patients who underwent HeartMate II or 3 implantation, 105 patients (59 HeartMate II and 46 HeartMate 3) met study criteria. Median age was 68 years [60-74 years], 91.4% [n=96] were male, 54.4% [n=56] were white, and 68.6% [n=72] received support as destination therapy. Preoperative aortic insufficiency degree was 54.3% (n=57) mild, 23.8% (n=25) mild-to-moderate, 20.0% (n=21) moderate, 1.0% (n=1) moderate-to-severe, 1.0% (n=1) severe. In hospital mortality was 5.7% [n=6]. Freedom from ≥ moderate aortic insufficiency was 96.4% (95%CI: 92.5%-100%), 93.3% (95%CI: 87.6%-99.2%), and 91.0% (95%CI: 84.1%-98.5%) at 1-year, 2-year, and 3-year post-implantation, respectively. One HeartMate II patient experienced severe aortic insufficiency and was treated with a heart transplant. Three-year survival was 63.4% [95%CI: 52.9%-75.9%]. CONCLUSIONS: Central aortic valve repair may be an effective technique to mitigate aortic insufficiency in HeartMate II and 3. A larger cohort study with longer duration of follow up is warranted to further investigate the clinical impact.

Alterations in the sarcopenia index are associated with inflammation, gut, and oral microbiota among heart failure, left ventricular assist device, and heart transplant patients.

BACKGROUND: Sarcopenia, characterized by loss of muscle mass and function, is prevalent in heart failure (HF) and predicts poor outcomes. We investigated alterations in sarcopenia index (SI), a surrogate for skeletal muscle mass, in HF, left ventricular assist device (LVAD), and heart transplant (HT), and assessed its relationship with inflammation and digestive tract (gut and oral) microbiota. METHODS: We enrolled 460 HF, LVAD, and HT patients. Repeated measures pre/post-procedures were obtained prospectively in a subset of LVAD and HT patients. SI (serum creatinine/cystatin C) and inflammatory biomarkers (C-reactive protein, interleukin-6, tumor necrosis factor-alpha) were measured in 271 and 622 blood samples, respectively. Gut and saliva microbiota were assessed via 16S ribosomal ribonucleic acid sequencing among 335 stool and 341 saliva samples. Multivariable regression assessed the relationship between SI and (1) New York Heart Association class; (2) pre- versus post-LVAD or HT; and (3) biomarkers of inflammation and microbial diversity. RESULTS: Median (interquartile range) natural logarithm (ln)-SI was -0.13 (-0.32, 0.05). Ln-SI decreased across worsening HF class, further declined at 1 month after LVAD and HT, and rebounded over time. Ln-SI was correlated with inflammation (r = -0.28, p < 0.01), gut (r = 0.28, p < 0.01), and oral microbial diversity (r = 0.24, p < 0.01). These associations remained significant after multivariable adjustment in the combined cohort but not for all individual cohorts. The presence of the gut taxa Roseburia inulinivorans was associated with increased SI. CONCLUSIONS: SI levels decreased in symptomatic HF and remained decreased long-term after LVAD and HT. In the combined cohort, SI levels covaried with inflammation in a similar fashion and were significantly related to overall microbial (gut and oral) diversity, including specific taxa compositional changes.

Impact of Interventricular Interaction on Ventricular Function: Insights From Right Ventricular Pressure-Volume Analysis.

BACKGROUND: Interventricular interactions may be responsible for the decline in ventricular performance observed in various disease states that primarily affect the contralateral ventricle. OBJECTIVES: This study sought to quantify the impact of such interactions on right ventricular (RV) size and function using clinically stable individuals with left ventricular assist devices (LVADs) as a model for assessing RV hemodynamics while LV loading conditions were acutely manipulated by changing device speed during hemodynamic optimization studies (ie, ramp tests). METHODS: The investigators recorded RV pressure-volume loops with a conductance catheter at various speeds during ramp tests in 20 clinically stable HeartMate3 recipients. RESULTS: With faster LVAD speeds and greater LV unloading, indexed RV end-diastolic volume increased (72.28 ± 15.07 mL at low speed vs 75.95 ± 16.90 at high speed; P = 0.04) whereas indexed end-systolic volumes remained neutral. This resulted in larger RV stroke volumes and shallower end-diastolic pressure-volume relationships. Concurrently, RV end-systolic pressure decreased (31.58 ± 9.75 mL at low speed vs 29.58 ± 9.41 mL at high speed; P = 0.02), but contractility, as measured by end-systolic elastance, did not change significantly. The reduction in RV end-systolic pressure was associated with a reduction in effective arterial elastance from 0.65 ± 0.43 mm Hg/mL at low speed to 0.54 ± 0.33 mm Hg/mL at high speed (P = 0.02). CONCLUSIONS: Interventricular interactions resulted in improved RV compliance, diminished afterload, and did not reduce RV contractility. These data challenge the prevailing view that interventricular interactions compromise RV function, which has important implications for the understanding of RV-LV interactions in various disease states, including post-LVAD RV dysfunction.

Increasing waiting times for status 2 patients in new United Network for Organ Sharing allocation system: Impact on waitlist and posttransplant outcomes.

OBJECTIVE: Since the heart transplant allocation policy change in 2018, there has been an increase in temporary mechanical circulatory support for Status 2 patients. We sought to examine the temporal pattern of waitlist and posttransplant outcomes for Status 2 patients. METHODS: Adult patients in the United Network for Organ Sharing registry who were listed as Status 2 from January 2019 to June 2022 were included. Temporal trends in waitlist time, waitlist events, and posttransplant outcomes were assessed. Probability of transplant or death after being listed was compared over time. Multivariable regression was performed to identify risk factors for mortality after transplant. RESULTS: A total of 6310 patients were included. From 2019 to 2022, the number of Status 2 patients listed increased from 4.2 to 5.9 per day. Microaxial ventricular assist devices at Status 2 listing increased over time (P < .001). During the study period, median waitlist time (18 days vs 23 days, P < .001) as well as Status 2 days (8 days vs 12 days, P < .001) increased. Waitlist mortality remained stable (5.5%); however, probability of transplant within 90 days of Status 2 listing progressively declined (P < .001). Finally, longer waitlist duration was independently associated with 30-day posttransplant mortality (odds ratio, 1.01; 95% confidence interval, 1.00-1.01, P = .02). CONCLUSIONS: Since the allocation policy change there has been a steady rise in the number of patients listed for Status 2. This has led to increasing waitlist times and lower probability of transplantation for Status 2 patients, which may have negative consequences for posttransplant outcomes.

Reverse Remodeling Effects of Sacubitril-Valsartan: Structural and Functional Optimization in Stage C Heart Failure.

Sacubitril-valsartan, an angiotensin receptor-neprilysin inhibitor, reduces all-cause mortality and the rate of heart failure hospitalizations in patients with heart failure with reduced ejection fraction. This study aimed to elucidate the benefits of initiating sacubitril-valsartan on ventricular remodeling in patients previously optimized on guideline-directed medical therapy. In this prospective, single-arm longitudinal study, 40 patients with heart failure with reduced ejection fraction who were optimized on guideline-directed medical therapy were transitioned to sacubitril-valsartan. The primary end point was the change in left ventricular (LV) volume at 1 year as assessed by 3-dimensional transthoracic echocardiography. Other echocardiographic end points included change in LV-function and change in right ventricular (RV) size and function. The mean age was 55 ± 12 years, and 63% were male. At 1 year, LV end-diastolic volume decreased from 242 ± 71 to 157 ± 57 ml (p <0.001) with a corresponding increase in LV ejection fraction from 32 ± 7% to 44 ± 9% (p <0.001). RV end-diastolic volume decreased from 151 ± 51 to 105 ±45 ml (p <0.001). Although RV ejection fraction did not change (51 ± 8 vs 51 ± 10; p = 0.35), RV global longitudinal strain improved from -14.9 ± 3.4 % to -19.3 ± 4.3% (p <0.001). When added to standard medical therapy for heart failure, sacubitril-valsartan induces significant remodeling of both the right and left ventricles as assessed by 3-dimensional echocardiography.

Comparing 3-year survival and readmissions between HeartMate 3 and heart transplant as primary treatment for advanced heart failure.

OBJECTIVE: To compare 3-year survival and readmissions of patients who received the HeartMate 3 (HM3) left ventricular assist device (LVAD) or underwent orthotopic heart transplantation (OHT) as primary treatment for advanced heart failure. METHODS: We retrospectively analyzed 381 adult patients who received an HM3 LVAD or were listed for OHT between January 2014 and March 2021 at our center. To minimize crossover bias, OHT recipients with a prior LVAD were excluded, and HM3 patients were censored at the time of transplant. Cohorts were propensity score-matched to reduce confounding variables. The primary outcome was 3-year survival, and the secondary outcome was mean cumulative all-cause unplanned readmission. RESULTS: The study population comprised 185 HM3 patients (49%) and 196 OHT patients (51%), with 104 propensity score-matched patients in each group. After propensity score matching, there was no statistical difference in 3-year survival (83.7% for HM3 vs 87.0% for OHT; P = .91; relative risk [RR], 1.00; 95% confidence interval [CI], 0.45-2.20). In the unmatched cohorts, patients age 18 to 49 years had comparable survival with HM3 and OHT (96.9% vs 95.9%; N = 91; P = 1.00; RR, 0.92; 95% CI, 0.09-9.78). Patients age 50+ years had slightly inferior survival with HM3 (75.0% vs 83.9%; N = 290; P = .60; RR, 1.51; 95% CI, 0.85-2.68). The mean number of readmissions at 3 years was higher in the HM3 group (3.89 vs 2.05; P < .001). CONCLUSIONS: This exploratory analysis suggests that for similar patients, HM3 may provide comparable 3-year survival to OHT as a primary treatment for heart failure but may result in more readmissions.

The utilization of molecular microscope in management of heart transplant recipients in the era of noninvasive monitoring.

INTRODUCTION: Monitoring for graft rejection is a fundamental tenet of post-transplant follow-up. In heart transplantation (HT) in particular, rejection has been traditionally assessed with endomyocardial biopsy (EMB). EMB has potential complications and noted limitations, including interobserver variability in interpretation. Additional tests, such as basic cardiac biomarkers, cardiac imaging, gene expression profiling (GEP) scores, donor-derived cell-free DNA (dd-cfDNA) and the novel molecular microscope diagnostic system (MMDx) have become critical tools in rejection surveillance beyond standard EMB. METHODS: This paper describes an illustrative case followed by a review of MMDx within the context of other noninvasive screening modalities for rejection. CONCLUSIONS: We suggest MMDx be used to assist with early detection of rejection in cases of discordance between EMB and other noninvasive studies.

Does lateral approach preserve the right ventricular function after HeartMate 3 insertion?

OBJECTIVES: Lateral thoracotomy (LT) approach may preserve the right ventricular (RV) function after left ventricular assist device (LVAD) implantation. This study evaluated the short- and long-term RV function using echocardiography after LVAD implantation via LT or median sternotomy (sternotomy). METHODS: The patients who underwent HeartMate 3 implantation were retrospectively reviewed. The RV function was assessed before and 1 month and 1 year after LVAD implantation. The primary and secondary outcomes were all-cause mortality and a composite of death or readmission due to RV failure, respectively. RESULTS: Of the 195 patients, 55 (28%) underwent LT and 140 (72%) underwent sternotomy. There were no significant differences in the preoperative RV geometry or function. One month after the LVAD implantation, the LT group had a smaller RV end-diastolic dimension [42 (29-48) vs 47 (42-52) mm; P = 0.003] and RV end-diastolic area [25 (21-28) vs 29 (24-36) cm2; P < 0.001] and a greater RV fractional area change [30 (25-34)% vs 28 (23-31)%; P = 0.04] and peak systolic tissue velocity [8 (7-9) vs 7 (6-8) cm/s; P = 0.01]. Twenty-four patients died and 46 met the composite end point. Kaplan-Meier curve analysis did not reveal significant differences between LT and sternotomy in the 2-year survival (93% vs 83%; log-rank test, P = 0.28) and adverse event rate (76% vs 71%; log-rank test, P = 0.65). CONCLUSIONS: LT approach yielded a better-preserved RV function at 1 month; however, there were no significant differences in the 2-year survival and adverse event rates.

Preoperative left ventricular diastolic dimension index is associated with outcomes after HeartMate 3 implantation.

OBJECTIVES: We investigated the association between indexed left ventricular diastolic dimension and clinical outcomes after HeartMate 3 implantation. METHODS: We retrospectively reviewed patients implanted with the HeartMate 3 at our centre between November 2014 and September 2021. Left ventricular diastolic dimension was assessed via preoperative transthoracic echocardiography and left ventricular diastolic dimension index was calculated as left ventricular diastolic dimension/body surface area. The primary outcome was a composite of death or readmission due to right heart failure or stroke. The cut-off left ventricular diastolic dimension index value most closely associated with outcomes was determined by receiver-operating characteristic curve and restricted cubic spline analyses. RESULTS: Left ventricular diastolic dimension index measurements were available for 252 of 253 (99.6%) patients. Using a left ventricular diastolic dimension index cut-off value of 33.5 mm/m2, the cohort was divided: left ventricular diastolic dimension index ≤ (n = 131) or > (n = 121) 33.5 mm/m2. While there were no significant differences in age, INTERMACS level and preoperative haemodynamics between groups, patients with smaller left ventricular diastolic dimension index were more likely to have a larger body surface area (2.1 vs 1.9 m2, P < 0.001), ischaemic cardiomyopathy [64 (49%) vs 40 (33%), P = 0.01] and smaller left atrium volume index [40.5 (32.3-54.0) ml/m2 vs 54.0 (43.0-66.8) ml/m2, P < 0.001]. Smaller left ventricular diastolic dimension index patients had significantly worse survival (74% vs 88%, log-rank P = 0.009) and freedom from adverse events (55% vs 73%, log-rank P = 0.005) at 3-year follow-up. Smaller left ventricular diastolic dimension index was independently associated with the composite outcome (Hazard ratio 2.24, P = 0.002). CONCLUSIONS: Smaller preoperative left ventricular diastolic dimension index is associated with worse outcomes in patients undergoing HeartMate 3 implantation.

Association of Angiopoetin-2 and TNF-α With Bleeding During Left Ventricular Assist Device Support: Analysis From the PREVENT Biorepository.

The purpose of this study was to describe the changes in plasma levels of angiogenic and inflammatory biomarkers, specifically Ang-2 and TNF-α, in patients receiving HeartMate II (HMII) left ventricular assist device (LVAD) and correlate them with nonsurgical bleeding. It has been shown that angiopoietin-2 (Ang-2) and tissue necrosis factor-α (TNF-α) may be linked to bleeding in LVAD patients. This study utilized biobanked samples prospectively collected from the PREVENT study, a prospective, multicenter, single-arm, nonrandomized study of patients implanted with HMII. Paired serum samples were obtained in 140 patients before implantation and at 90 days postimplantation. Baseline demographics were as follows: age 57 ± 13 years, 41% had ischemic etiology, 82% male, and 75% destination therapy indication. In the 17 patients with baseline elevation of both TNF-α and Ang-2, 10 (60%) experienced a significant bleeding event within 180 days postimplant compared with 37 of 98 (38%) patients with Ang-2 and TNF-α below the mean ( p = 0.02). The hazard ratio for a bleeding event was 2.3 (95% CI: 1.2-4.6) in patients with elevated levels of both TNF-α and Ang-2. In the PREVENT multicenter study, patients with elevations in serum Angiopoietin-2 and TNF-α at baseline before LVAD implantation demonstrated increased bleeding events after LVAD implantation.

The Difference Between Cystatin C- and Creatinine-Based Estimated GFR in Heart Failure With Reduced Ejection Fraction: Insights From PARADIGM-HF.

RATIONALE & OBJECTIVE: The clinical implications of the discrepancy between cystatin C (cysC)- and serum creatinine (Scr)-estimated glomerular filtration rate (eGFR) in patients with heart failure (HF) and reduced ejection fraction (HFrEF) are unknown. STUDY DESIGN: Post-hoc analysis of randomized trial data. SETTING & PARTICIPANTS: 1,970 patients with HFrEF enrolled in PARADIGM-HF with available baseline cysC and Scr measurements. EXPOSURE: Intraindividual differences between eGFR based on cysC (eGFRcysC) and Scr (eGFRScr; eGFRdiffcysC-Scr). OUTCOMES: Clinical outcomes included the PARADIGM-HF primary end point (composite of cardiovascular [CV] mortality or HF hospitalization), CV mortality, all-cause mortality, and worsening kidney function. We also examined poor health-related quality of life (HRQoL), frailty, and worsening HF (WHF), defined as HF hospitalization, emergency department visit, or outpatient intensification of therapy between baseline and 8-month follow-up. ANALYTICAL APPROACH: Fine-Gray subdistribution hazard models and Cox proportional hazards models were used to regress clinical outcomes on baseline eGFRdiffcysC-Scr. Logistic regression was used to investigate the association of baseline eGFRdiffcysC-Scr with poor HRQoL and frailty. Linear regression models were used to assess the association of WHF with eGFRcysC, eGFRScr, and eGFRdiffcysC-Scr at 8-month follow-up. RESULTS: Baseline eGFRdiffcysC-Scr was higher than +10 and lower than-10mL/min/1.73m2 in 13.0% and 35.7% of patients, respectively. More negative values of eGFRdiffcysC-Scr were associated with worse outcomes ([sub]hazard ratio per standard deviation: PARADIGM-HF primary end point, 1.18; P=0.008; CV mortality, 1.34; P=0.001; all-cause mortality, 1.39; P<0.001; worsening kidney function, 1.31; P=0.05). For a 1-standard-deviation decrease in eGFRdiffcysC-Scr, the prevalences of poor HRQoL and frailty increased by 29% and 17%, respectively (P≤0.008). WHF was associated with a more pronounced decrease in eGFRcysC than in eGFRScr, resulting in a change in 8-month eGFRdiffcysC-Scr of-4.67mL/min/1.73m2 (P<0.001). LIMITATIONS: Lack of gold-standard assessment of kidney function. CONCLUSIONS: In patients with HFrEF, discrepancies between eGFRcysC and eGFRScr are common and are associated with clinical outcomes, HRQoL, and frailty. The decline in kidney function associated with WHF is more marked when assessed with eGFRcysC than with eGFRScr. PLAIN-LANGUAGE SUMMARY: Kidney function assessment traditionally relies on serum creatinine (Scr) to establish an estimated glomerular filtration rate (eGFR). However, this has been challenged with the introduction of an alternative marker, cystatin C (cysC). Muscle mass and nutritional status have differential effects on eGFR based on cysC (eGFRcysC) and Scr (eGFRScr). Among ambulatory patients with heart failure enrolled in PARADIGM-HF, we investigated the clinical significance of the difference between eGFRcysC and eGFRScr. More negative values (ie, eGFRScr>eGFRcysC) were associated with worse clinical outcomes (including mortality), poor quality of life, and frailty. In patients with progressive heart failure, which is characterized by muscle loss and poor nutritional status, the decline in kidney function was more pronounced when eGFR was estimated using cysC rather than Scr.

Impact of preheart transplant spirometry and DCLO measurement on post-transplant pulmonary outcomes.

BACKGROUND: Pulmonary function tests (PFT) are a frequent component of heart transplant evaluation. In cardiac surgery abnormal PFTs, especially reduced DLCO, have been associated with poor outcomes. We sought to evaluate the impact of pretransplant PFTs on post-transplant pulmonary outcomes and patient survival. METHODS: Among the 652 adult heart transplant recipients between January 1, 2010 and July 31, 2021, 462 had PFTs and constituted the patient cohort. Obstructive ventilatory defects (OVD), restrictive ventilatory defects (RVD), and reduced DLCO were defined according to established criteria. The primary outcome was the combined endpoint of a post-transplant pulmonary complication defined as reintubation, postoperative pneumonia, prolonged intubation, or tracheostomy. Secondary outcomes included 90-day all-cause mortality, length of stay, and the odds of individual pulmonary complications. Kaplan-Meier survival analysis, multivariable Cox proportional-hazards regression, and multivariable logistic regression were performed to compare outcomes between the groups. RESULTS: Patients with severe OVD (OR 1.48, 95% CI 1.18-5.23, p = 0.02) or severely reduced DLCO (OR 1.95, 95% CI 1.19-3.20, p = 0.008) had increased odds of post-transplant pulmonary complications. Following multivariable adjustment, severe OVD (aOR 2.67, 95% CI 1.15-6.19, p = 0.02) and severely reduced DLCO (aOR 1.79, 95% CI 1.05-3.04) remained strongly associated with post-transplant pulmonary complications. Patients with any degree of extrinsic RVD, moderate or less OVD, or moderately reduced DLCO or less did not have increased odds of post-transplant pulmonary complications. Ninety-day post-transplant survival was significantly reduced for both severe OVD (97.2% vs 86.5%, p = 0.04) and severely reduced DLCO (97.3% vs 90.4%, p = 0.004). Post-transplant ICU and hospital length of stay were nominally longer for both groups as well. CONCLUSIONS: Severe OVD or severely reduced DLCO on preheart transplant PFTs were associated with increased odds of post-transplant pulmonary complications and early mortality.

Combined heart and liver transplantation in a patient supported by left ventricular assist device (LVAD) with propionic acidemia.

Propionic acidemia (PA) is a rare inherited metabolic disease due to inborn errors of metabolism. PA results in the accumulation of abnormal organic acid metabolites in multiple systems, mainly the central nervous system and the heart. Cardiac complications include dilated cardiomyopathy (DCM) and carry a 40-50% increased mortality risk. Liver transplantation (LT) is required in PA patients when medical treatment fails and may prevent or slow down the cardiomyopathy progression. However, severe heart disease may be a serious contraindication to LT. We present a complicated case of a PA patient, supported with a Left Ventricular Assist Device, who underwent a heart and Liver transplant. PA patients are at increased risk for metabolic acidosis during surgery, with increased anion gap and hyperammonemia. A strict multi-disciplinary approach is needed to prevent and treat metabolic decompensation. The patient had a successful heart and liver transplant after a strict treatment protocol in the pre, intra, and post-operative periods. His case highlights the complexity of PA patients and the increased risk for metabolic decompensation during surgery and provides an insight into how to manage such complicated patients.

Outflow Graft Narrowing of the HeartMate 3 Left Ventricular Assist Device.

BACKGROUND: In patients with the HeartMate 3 (HM3, Abbott) left ventricular (LV) assist device (LVAD), outflow graft narrowing has been reported as a result of accumulation of biodebris either internal or external to the graft. This study describes the prevalence, imaging findings, and clinical outcomes associated with HM3 LVAD outflow graft narrowing. METHODS: A single-center retrospective cohort study was performed in patients who received an HM3 LVAD between November 2014 and July 2019. All patients with a computed tomographic (CT) angiogram or a CT scan with intravenous contrast sufficient to evaluate the outflow graft lumen were included. Narrowing was defined as a hypodensity of ≥3 mm. RESULTS: Of 165 HM3 LVAD recipients, 46 (28%) had qualifying imaging. Outflow graft narrowing was present in 33% (15/46). One patient had complete obstruction requiring emergency surgery, whereas 14 patients had a median hypodensity of 4.5 mm (interquartile range, 3.3-5.8 mm). The presence of outflow graft narrowing was significantly associated with a longer duration of LVAD support (588.2 ± 277.5 days vs 131.5 ± 170.9 days; P < .0001). One-year survival after identification of narrowing was 93%, with death occurring in 1 patient with complete obstruction. LV unloading (mean percent decrease in LV end-diastolic diameter at time of CT imaging vs pre-LVAD) was 16.7% vs 17.7% in patients with and without narrowing, respectively (P = .86). CONCLUSIONS: Among patients with adequate imaging, one-third have evidence of narrowing. Outflow graft narrowing secondary to biodebris was more likely to be found in HM3 LVAD recipients with longer duration of LVAD support. There was no significant difference in LV unloading between patients with and without narrowing.

National outcomes of bridge to multiorgan cardiac transplantation using mechanical circulatory support.

BACKGROUND: Little is known regarding the profile of patients with multiorgan failure listed for simultaneous cardiac transplantation and secondary organ. In addition, few studies have reported how these patients are bridged with mechanical circulatory support (MCS). In this study, we examined national data of patients listed for multiorgan transplantation and their outcomes after bridging with or without MCS. METHODS: United Network for Organ Sharing data were reviewed for adult multiorgan transplantations from 1986 to 2019. Post-transplant patients and total waitlist listings were examined and stratified according to MCS status. Survival was assessed via Cox regression in the post-transplant cohort and Fine-Gray competing risk regression with transplantation as a competing risk in the waitlist cohort. RESULTS: There were 4534 waitlist patients for multiorgan transplant during the study period, of whom 2117 received multiorgan transplants. There was no significant difference in post-transplant survival between the MCS types and those without MCS in the whole cohort and heart-kidney subgroup. Fine-Gray competing risk regression showed that patients bridged with extracorporeal membrane oxygenation had significantly greater waitlist mortality compared with those without MCS when controlling for preoperative characteristics (subdistribution hazard ratio, 2.27; 95% confidence interval, 1.48-3.47; P < .001), whereas those bridged with a ventricular assist device had a decreased incidence of death compared with those without MCS (subdistribution hazard ratio, 0.78; 95% confidence interval, 0.63-0.96; P = .017). CONCLUSIONS: MCS, as currently applied, does not appear to compromise the survival of multiorgan heart transplant patients. Waitlist data show that extracorporeal membrane oxygenation patients have profoundly worse survival irrespective of preoperative factors including organ type listed. Survival on the waitlist for multiorgan transplant has improved across device eras.

The impact of pre-transplant weight loss on survival following cardiac transplantation.

BACKGROUND: Significant weight loss due to cardiac cachexia is an independent predictor of mortality in many heart failure (HF) clinical trials. The impact of significant weight loss while on the waitlist for heart transplant (HT) has yet to be studied with respect to post-transplant survival. METHODS: Adult HT recipients from 2010 to 2021 were identified in the UNOS registry. Patients who experienced an absolute weight change from the time of listing to transplant were included and classified into two groups by percent weight loss from time of listing to time of transplant using a cut-off of 10%. The primary endpoint was 1-year survival following HT. RESULTS: 5951 patients were included in the analysis, of whom 763 (13%) experienced ≥10% weight loss from the time of listing to transplant. Weight loss ≥ 10% was associated with reduced 1-year post-transplant survival (86.9% vs. 91.0%, long-rank p = .0003). Additionally, weight loss ≥ 10% was an independent predictor of 1-year mortality in a multivariable model adjusting for significant risk factors (adjusted HR 1.23, 95% CI 1.04-1.46). In secondary analyses, weight loss ≥ 10% was associated with reduced 1-year survival independent of hospitalized status at time of transplant as well as obesity status at listing (i.e., body mass index [BMI] < 30 kg/m2 and BMI ≥ 30 kg/m2 ). CONCLUSIONS: Preoperative weight loss ≥ 10% is associated with reduced survival in patients listed for HT. Nutrition interventions prior to transplant may prove beneficial in this population.

Letermovir for cytomegalovirus prophylaxis in high-risk heart transplant recipients.

Letermovir is a novel agent for the prevention of cytomegalovirus (CMV) infection and disease that, unlike traditional CMV DNA polymerase inhibitors, does not carry the risk of myelosuppression. The purpose of this study was to evaluate the safety, efficacy, and clinical application of letermovir for CMV prophylaxis in heart transplant (HT) recipients. Between November 1, 2019, and October 1, 2021, at a single, tertiary care hospital, 17 HT recipients were initiated on letermovir due to leukopenia while on valganciclovir. Fifteen (88%) had high-risk mismatch (CMV D+/R-). Median time on letermovir was 5 months (interquartile range, 2-8 months.) At the end of the study period, nine of 17 patients (52.9%) were still on letermovir and four of the 17 (23.5%) had successfully completed the prophylaxis window on letermovir and been switched to the pre-emptive strategy. One patient developed clinically significant CMV viremia in the setting of being unable to obtain medication due to insurance barriers but was later successfully restarted on letermovir. One patient was unable to tolerate letermovir due to symptoms of headache and myalgias. Two patients developed low-level non-clinically significant CMV viremia and were switched back to valacyclovir. All patients had tacrolimus dosages reduced at time of letermovir initiation to minimize the risk of supratherapeutic tacrolimus concentration. One patient required hospitalization due to symptomatic tacrolimus toxicity. For HT recipients who cannot tolerate valganciclovir, letermovir presents an alternative for CMV prophylaxis. Close monitoring for breakthrough CMV and calcineurin inhibitor levels is necessary. Larger studies are required to further delineate its use and help provide further evidence of its safety and efficacy.