Deep phenotyping of cardiac function in heart transplant patients using cardiovascular systems models

Heart transplant patients are followed with periodic right heart catheterizations (RHCs) to identify post-transplant complications and guide treatment. Post-transplant positive outcomes are associated with a steady reduction of right ventricular and pulmonary arterial pressures, toward normal levels of right-side pressure (about 20mmHg) measured by RHC. This study shows more information about patient progression is obtained by combining standard RHC measures with mechanistic computational cardiovascular systems models. This study shows: to understand how cardiovascular system models can be used to represent a patient's cardiovascular state, and to use these models to track post-transplant recovery and outcome. To obtain reliable parameter estimates comparable within and across datasets, we use sensitivity analysis, parameter subset selection, and optimization to determine patient specific mechanistic parameter that can be reliably extracted from the RHC data. Patient-specific models are identified for ten patients from their first post-transplant RHC and longitudinal analysis is done for five patients. Results of sensitivity analysis and subset selection show we can reliably estimate seven non-measurable quantities including ventricular diastolic relaxation, systemic resistance, pulmonary venous elastance, pulmonary resistance, pulmonary arterial elastance, pulmonary valve resistance and systemic arterial elastance. Changes in parameters and predicted cardiovascular function post-transplant are used to evaluate cardiovascular state during recovery in five patients. Of these five patients, only one patient showed inconsistent trends during recovery in ventricular pressure-volume relationships and power output. At a four-year recovery time point this patient exhibited biventricular failure along with graft dysfunction while the remaining four exhibited no cardiovascular complications.Comment: 53 Pages (including supplement), 9 figures in manuscript, 9 figures in supplemen

Deep phenotyping of cardiac function in heart transplant patients using cardiovascular system models

Heart transplant patients are followed with periodic right heart catheterizations (RHCs) to identify post‐transplant complications and guide treatment. Post‐transplant positive outcomes are associated with a steady reduction of right ventricular and pulmonary arterial pressures, toward normal levels of right‐side pressure (about 20 mmHg) measured by RHC. This study shows that more information about patient progression is obtained by combining standard RHC measures with mechanistic computational cardiovascular system models. The purpose of this study is twofold: to understand how cardiovascular system models can be used to represent a patient’s cardiovascular state, and to use these models to track post‐transplant recovery and outcome. To obtain reliable parameter estimates comparable within and across datasets, we use sensitivity analysis, parameter subset selection, and optimization to determine patient‐specific mechanistic parameters that can be reliably extracted from the RHC data. Patient‐specific models are identified for 10 patients from their first post‐transplant RHC, and longitudinal analysis is carried out for five patients. Results of the sensitivity analysis and subset selection show that we can reliably estimate seven non‐measurable quantities; namely, ventricular diastolic relaxation, systemic resistance, pulmonary venous elastance, pulmonary resistance, pulmonary arterial elastance, pulmonary valve resistance and systemic arterial elastance. Changes in parameters and predicted cardiovascular function post‐transplant are used to evaluate the cardiovascular state during recovery of five patients. Of these five patients, only one showed inconsistent trends during recovery in ventricular pressure–volume relationships and power output. At the four‐year post‐transplant time point this patient exhibited biventricular failure along with graft dysfunction while the remaining four exhibited no cardiovascular complications.Key pointsRight heart catheterization data from clinical records of heart transplant patients are used to identify patient‐specific models of the cardiovascular system.These patient‐specific cardiovascular models represent a snapshot of cardiovascular function at a given post‐transplant recovery time point.This approach is used to describe cardiac function in 10 heart transplant patients, five of which had multiple right heart catheterizations allowing an assessment of cardiac function over time.These patient‐specific models are used to predict cardiovascular function in the form of right and left ventricular pressure‐volume loops and ventricular power, an important metric in the clinical assessment of cardiac function.Outcomes for the longitudinally tracked patients show that our approach was able to identify the one patient from the group of five that exhibited post‐transplant cardiovascular complications.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/156242/2/tjp14120.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/156242/1/tjp14120_am.pd

Challenges facing early career academic cardiologists

Early career academic cardiologists currently face unprecedented challenges that threaten a highly valued career path. A team consisting of early career professionals and senior leadership members of American College of Cardiology completed this white paper to inform the cardiovascular medicine profession regarding the plight of early career cardiologists and to suggest possible solutions. This paper includes: 1) definition of categories of early career academic cardiologists; 2) general challenges to all categories and specific challenges to each category; 3) obstacles as identified by a survey of current early career members of the American College of Cardiology; 4) major reasons for the failure of physician-scientists to receive funding from National Institute of Health/National Heart Lung and Blood Institute career development grants; 5) potential solutions; and 6) a call to action with specific recommendations

Accuracy of risk models used for public reporting of heart transplant center performance.

BACKGROUND: Heart transplant programs and regulatory entities require highly accurate performance metrics to support internal quality improvement activities and national oversight of transplant programs, respectively. We assessed the accuracy of publicly reported performance measures. METHODS: We used the United Network for Organ Sharing registry to study patients who underwent heart transplantation between January 1, 2016 and June 30, 2018. We used tests of calibration to compare the observed rate of 1-year graft failure to the expected risk of 1-year graft failure, which was calculated for each recipient using the July 2019 method published by the Scientific Registry of Transplant Recipients (SRTR). The primary study outcome was the joint test of calibration, which accounts for both the total number of events predicted (calibration-in-the-large) and dispersion of risk predictions (calibration slope). RESULTS: 6,528 heart transplants were analyzed. The primary test of calibration failed (p CONCLUSIONS: Risk models employed for publicly-reported graft survival at U.S. heart transplant centers lack accuracy in general and in all subgroups tested. The use of disease-specific models may improve the accuracy of program performance metrics

Patterns of Hospital Bypass and Interhospital Transfer Among Patients With Heart Failure.

BACKGROUND: We describe how patient characteristics influence hospital bypass, interhospital transfer, and in-hospital mortality in patients with heart failure in Washington. Rural patients with heart failure may bypass their nearest hospital or be transferred for appropriate therapies. The frequency, determinants, and outcomes of these practices remain uncharacterized. METHODS AND RESULTS: Mean excess travel times based on hospital and patient residence ZIP codes were calculated using published methods. Hospitals and servicing areas were coded based on bed size and ZIP code, respectively. Transfer patterns were analyzed using bootstrap inference for clusters. Analysis of mortality and transfer-associated factors was performed using logistic regression with generalized estimating equations. There were 48,163 patients, representing 1106 instances of transfer, studied. The mean excess travel time increased 7.14 minutes per decrease in population density (metropolitan, micropolitan, small town, rural; P \u3c .0001). The rural mean excess travel time was greatest at 28.56 minutes. Transfer likelihood increased with younger age, male gender, admitting hospital rurality, higher Charlson Comorbidity Index, and stroke. Transfer was less likely among women (odds ratio [OR], 0.82; 95% confidence interval [CI], 0.72-0.94) and patients over 70 years old (OR, 0.15-0.46; 95% CI, 0.10-0.65). Adjusting for comorbidities and transfer propensity, transfer exhibited a stronger association with mortality than any other measured patient risk factor (OR, 2.15; 95% CI, 1.69-2.73), excluding stroke (OR, 7.09; 95% CI, 4.99-10.06). CONCLUSIONS: Rural hospital bypass is prevalent among patients with heart failure, although its clinical significance is unclear. Female and older patients were found to have a lesser likelihood of transfer adjusted for other factors. Interhospital transfer is associated with increased mortality when adjusted for comorbidities

Long-term adult congenital heart disease survival after heart transplantation: A restricted mean survival time analysis.

BACKGROUND: Adult Congenital Heart Disease (ACHD) heart transplant recipients may have lower post-transplant survival resulting from higher peri-operative mortality than non-ACHD patients. However, the late risk of mortality appears lower in ACHD recipients. This study seeks to establish whether long-term heart transplant survival is reduced among ACHD recipients relative to non-ACHD recipients. METHODS: Adult patients who received a heart transplant between January, 2000 and December, 2019 in the United Network for Organ Sharing database were stratified by the presence of ACHD. Propensity-matched cohorts (1:4) were created to adjust for differences between groups. Graft survival at time points from 1 to 18 years was compared between groups using restricted mean survival time (RMST) analysis. RESULTS: The matched cohort included 1,139 ACHD and 4,293 non-ACHD patients. Median age was 35 years and 61% were male. Average survival time at 1 year was 0.85 years for ACHD patients and 0.93 years for non-ACHD patients (average difference: -0.08 years, 95% Confidence Interval [CI] -0.10 to -0.06, p \u3c 0.001), reflecting higher immediate post-transplant mortality. Average survival time at 18 years was not clinically or statistically different: 11.14 years for ACHD patients and 11.40 years for non-ACHD patients (average difference: -0.26 years, 95% CI: -0.85 to + 0.32 years, p = 0.38). CONCLUSIONS: Despite increased medium-term mortality among ACHD patients after heart transplant, differences in long-term survival are minimal. Allocation of hearts to ACHD patients results in acceptable utility of donor hearts

Outcomes of external repair of HeartMate II™ LVAD percutaneous leads

Background: The HeartMate II Left Ventricular Assist Device (LVAD) receives power via a percutaneous lead connected to an external controller and batteries. At times, this lead can be damaged during normal wear, as well as by traumatic fracture, which may jeopardize the functionality of the LVAD. If there is significant internal damage, surgical replacement of the LVAD is required. However it is possible to repair externally damaged leads by replacing the distal portion of the lead to avoid pump replacement. We report the overall experience and outcomes in patients with external lead repairs. Methods: A procedure for full external lead replacement has been developed and is approved for implementation by the FDA. Pre-procedural steps include examination of high resolution x-rays of the driveline and analysis of pump log files. Efficacy and outcomes of all attempted external lead repairs were evaluated between initiation of repairs in 2008 through 2014. Results: A total of 321 repairs were attempted in 297 patients with suspected isolated external lead damage after a median of 2.0 yr [range: 7d to 8.7 yr] of support. Of 297 patients, 37 (12.5%) had attempts at external repair that were unsuccessful due to concomitant internal lead damage. 31 patients (10.4%) had additional serious malfunctions after lead repair resulting in 17 with repeat repairs and 14 who continued on ungrounded cables, and ultimately 14 of these 31 patients required pump exchanges. 27 of the 297 patients (9.1%) with lead repairs had only minor additional problems, including cuts or abrasion in the insulation which was fixed with tape or external reinforcement. There was one catastrophic failure during attempted lead repair requiring emergent pump exchange, and there were three deaths within 14 days of attempted repair related to continued percutaneous lead damage. One of these patients refused pump exchange, and two were not candidates for other clinical reasons. 202 of the 297 patients (68%) have had no recurrence of lead problems after a median follow-up of 189 days [n=11 over 2 years, longest 5.8 yr]. Conclusions: HeartMate II dysfunction due to percutaneous lead damage is uncommon but is of serious concern due to potential abrupt pump stoppage. Lead repair by replacement of the external distal percutaneous lead can be performed by trained personnel in a standardized fashion and may provide a durable solution in select patients with isolated external lead damage, thus avoiding the need for surgical pump exchange. We provide an algorithm for evaluating potential lead damage