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Long-term follow-up of acute and chronic rejection in heart transplant recipients from hepatitis C viremic (NAT+) donors

Stachel, Maxine W; Alimi, Marjan; Narula, Navneet; Flattery, Erin E; Xia, Yuhe; Ramachandran, Abhinay; Saraon, Tajinderpal; Smith, Deane; Reyentovich, Alex; Goldberg, Randal; Kadosh, Bernard S; Razzouk, Louai; Katz, Stuart; Moazami, Nader; Gidea, Claudia G
The long-term safety of heart transplants from hepatitis C viremic (NAT+) donors remains uncertain. We conducted a prospective study of all patients who underwent heart transplantation at our center from January 2018 through August 2020. Routine testing was performed to assess for donor-derived cell-free DNA, acute cellular rejection (ACR), antibody-mediated rejection (AMR), and cardiac allograft vasculopathy (CAV). Allograft dysfunction and mortality were also monitored. Seventy-five NAT- recipients and 32 NAT+ recipients were enrolled in the study. All NAT+ recipients developed viremia detected by PCR, were treated with glecaprevir/pibrentasvir at the time of viremia detection, and cleared the virus by 59 days post-transplant. Patients who underwent NAT testing starting on post-operative day 7 (NAT+ Group 1) had significantly higher viral loads and were viremic for a longer period compared with patients tested on post-operative day 1 (NAT+ Group 2). Through 3.5 years of follow-up, there were no statistically significant differences in timing, severity, or frequency of ACR in NAT+ recipients compared with the NAT- cohort, nor were there differences in noninvasive measures of graft injury, incidence or severity of CAV, graft dysfunction, or mortality. There were five episodes of AMR, all in the NAT- group. There were no statistically significant differences between Group 1 and Group 2 NAT+ cohorts. Overall, these findings underscore the safety of heart transplantation from NAT+ donors.
PMID: 36053676
ISSN: 1600-6143
CID: 5332222

Missed opportunities in medical therapy for patients with heart failure in an electronically-identified cohort

Mukhopadhyay, Amrita; Reynolds, Harmony R; Nagler, Arielle R; Phillips, Lawrence M; Horwitz, Leora I; Katz, Stuart D; Blecker, Saul
BACKGROUND:National registries reveal significant gaps in medical therapy for patients with heart failure and reduced ejection fraction (HFrEF), but may not accurately (or fully) characterize the population eligible for therapy. OBJECTIVE:We developed an automated, electronic health record-based algorithm to identify HFrEF patients eligible for evidence-based therapy, and extracted treatment data to assess gaps in therapy in a large, diverse health system. METHODS:In this cross-sectional study of all NYU Langone Health outpatients with EF ≤ 40% on echocardiogram and an outpatient visit from 3/1/2019 to 2/29/2020, we assessed prescription of the following therapies: beta-blocker (BB), angiotensin converting enzyme inhibitor (ACE-I)/angiotensin receptor blocker (ARB)/angiotensin receptor neprilysin inhibitor (ARNI), and mineralocorticoid receptor antagonist (MRA). Our algorithm accounted for contraindications such as medication allergy, bradycardia, hypotension, renal dysfunction, and hyperkalemia. RESULTS:We electronically identified 2732 patients meeting inclusion criteria. Among those eligible for each medication class, 84.8% and 79.7% were appropriately prescribed BB and ACE-I/ARB/ARNI, respectively, while only 23.9% and 22.7% were appropriately prescribed MRA and ARNI, respectively. In adjusted models, younger age, cardiology visit and lower EF were associated with increased prescribing of medications. Private insurance and Medicaid were associated with increased prescribing of ARNI (OR = 1.40, 95% CI = 1.02-2.00; and OR = 1.70, 95% CI = 1.07-2.67). CONCLUSIONS:We observed substantial shortfalls in prescribing of MRA and ARNI therapy to ambulatory HFrEF patients. Subspecialty care setting, and Medicaid insurance were associated with higher rates of ARNI prescribing. Further studies are warranted to prospectively evaluate provider- and policy-level interventions to improve prescribing of these evidence-based therapies.
PMID: 35927632
ISSN: 1471-2261
CID: 5285842

Pre-transplant immune cell function assay as a predictor of early cardiac allograft rejection

Maidman, Samuel D; Gidea, Claudia; Reyentovich, Alex; Rao, Shaline; Saraon, Tajinderpal; Kadosh, Bernard S; Narula, Navneet; Carillo, Julius; Smith, Deane; Moazami, Nader; Katz, Stuart; Goldberg, Randal I
INTRODUCTION/BACKGROUND:ImmuKnow, an immune cell function assay that quantifies overall immune system activity can assist in post-transplant immunosuppression adjustment. However, the utility of pre-transplant ImmuKnow results representing a patient's baseline immune system activity is unknown. This study sought to assess if pre-transplant ImmuKnow results are predictive of rejection at the time of first biopsy in our cardiac transplant population. METHODS:This is a single center, retrospective observational study of consecutive patients from January 1, 2018 to October 1, 2020 who underwent orthotopic cardiac transplantation at NYU Langone Health. Patients were excluded if a pre-transplant ImmuKnow assay was not performed. ImmuKnow results were categorized according to clinical interpretation ranges (low, moderate, and high activity), and patients were divided into two groups: a low activity group versus a combined moderate-high activity group. Pre-transplant clinical characteristics, induction immunosuppression use, early postoperative tacrolimus levels, and first endomyocardial biopsy results were collected for all patients. Rates of clinically significant early rejection (defined as rejection ≥ 1R/1B) were compared between pre-transplant ImmuKnow groups. RESULTS:Of 110 patients who underwent cardiac transplant, 81 had pre-transplant ImmuKnow results. The low ImmuKnow activity group was comprised of 15 patients, and 66 patients were in the combined moderate-high group. Baseline characteristics were similar between groups. Early rejection occurred in 0 (0%) patients with low pre-transplant ImmuKnow levels. Among the moderate- high pre-transplant ImmuKnow group, 16 (24.2%) patients experienced early rejection (P = .033). The mean ImmuKnow level in the non-rejection group was the 364.9 ng/ml of ATP compared to 499.3 ng/ml of ATP for those with rejection (P = .020). CONCLUSION/CONCLUSIONS:Patients with low pre-transplant ImmuKnow levels had lower risk of early rejection when compared with patients with moderate or high levels. Our study suggests a possible utility in performing pre-transplant ImmuKnow to identify patients at-risk for early rejection who may benefit from intensified upfront immunosuppression as well as to recognize those where slower calcineurin inhibitor initiation may be appropriate.
PMID: 35678734
ISSN: 1399-0012
CID: 5279542

An Evaluation of Alternative Technology-Supported Counseling Approaches to Promote Multiple Lifestyle Behavior Changes in Patients With Type 2 Diabetes and Chronic Kidney Disease

St-Jules, David E; Hu, Lu; Woolf, Kathleen; Wang, Chan; Goldfarb, David S; Katz, Stuart D; Popp, Collin; Williams, Stephen K; Li, Huilin; Jagannathan, Ram; Ogedegbe, Olugbenga; Kharmats, Anna Y; Sevick, Mary Ann
OBJECTIVES/OBJECTIVE:Although technology-supported interventions are effective for reducing chronic disease risk, little is known about the relative and combined efficacy of mobile health strategies aimed at multiple lifestyle factors. The purpose of this clinical trial is to evaluate the efficacy of technology-supported behavioral intervention strategies for managing multiple lifestyle-related health outcomes in overweight adults with type 2 diabetes (T2D) and chronic kidney disease (CKD). DESIGN AND METHODS/METHODS:, age ≥40 years), T2D, and CKD stages 2-4 were randomized to an advice control group, or remotely delivered programs consisting of synchronous group-based education (all groups), plus (1) Social Cognitive Theory-based behavioral counseling and/or (2) mobile self-monitoring of diet and physical activity. All programs targeted weight loss, greater physical activity, and lower intakes of sodium and phosphorus-containing food additives. RESULTS:Of 256 randomized participants, 186 (73%) completed 6-month assessments. Compared to the ADVICE group, mHealth interventions did not result in significant changes in weight loss, or urinary sodium and phosphorus excretion. In aggregate analyses, groups receiving mobile self-monitoring had greater weight loss at 3 months (P = .02), but between 3 and 6 months, weight losses plateaued, and by 6 months, the differences were no longer statistically significant. CONCLUSIONS:When engaging patients with T2D and CKD in multiple behavior changes, self-monitoring diet and physical activity demonstrated significantly larger short-term weight losses. Theory-based behavioral counseling alone was no better than baseline advice and demonstrated no interaction effect with self-monitoring.
PMID: 35752400
ISSN: 1532-8503
CID: 5282392

A Randomized Open Label Clinical Trial of Lipid-Lowering Therapy in Psoriasis to Reduce Vascular Endothelial Inflammation

Garshick, Michael S; Drenkova, Kamelia; Barrett, Tessa J; Schlamp, Florencia; Fisher, Edward A; Katz, Stuart; Jelic, Sanja; Neimann, Andrea L; Scher, Jose U; Krueger, James; Berger, Jeffrey S
PMID: 34808233
ISSN: 1523-1747
CID: 5063372

Missed Opportunities in Identifying Cardiomyopathy Aetiology Prior to Advanced Heart Failure Therapy

Aiad, Norman; Elnabawai, Youssef A; Li, Boyangzi; Narula, Navneet; Gidea, Claudia; Katz, Stuart D; Rao, Shaline D; Reyentovich, Alex; Saraon, Tajinderpal; Smith, Deane; Moazami, Nader; Pan, Stephen
BACKGROUND:Specific aetiologies of cardiomyopathy can significantly impact treatment options as well as appropriateness and prioritisation for advanced heart failure therapies such as ventricular assist device (VAD) or orthotopic heart transplantation (OHT). We reviewed the tissue diagnoses of patients who underwent advanced therapies for heart failure (HF) to identify diagnostic discrepancies. METHODS:This study presents a retrospective cohort of the aetiology of cardiomyopathy in 118 patients receiving either durable VAD or OHT. Discrepancies between the preoperative aetiological diagnosis of cardiomyopathy with the pathological diagnosis were recorded. Echocardiographic and haemodynamic data were reviewed to examine differences in patients with differing aetiological diagnoses. RESULTS:Twelve (12) of 118 (12/118) (10.2%) had a pathological diagnosis that was discordant with pre-surgical diagnosis. The most common missed diagnoses were infiltrative cardiomyopathy (5) and hypertrophic cardiomyopathy (3). Patients with misidentified aetiology of cardiomyopathy had smaller left ventricular (LV) dimensions on echocardiography than patients with dilated cardiomyopathy (5.8±0.9 vs 6.7±1.1 respectively p=0.01). CONCLUSIONS:Most HF patients undergoing VAD and OHT had a correct diagnosis for their heart failure prior to treatment, but a missed diagnosis at time of intervention (VAD or OHT) was not uncommon. Smaller LV dimension on echocardiogram in a patient with a non-ischaemic cardiomyopathy warrants further workup for a more specific aetiology.
PMID: 35165053
ISSN: 1444-2892
CID: 5163352

Vascular endothelium as a target for perfluroalkyl substances (PFAs)

Wittkopp, Sharine; Wu, Fen; Windheim, Joseph; Robinson, Morgan; Kannan, Kurunthachalam; Katz, Stuart D; Chen, Yu; Newman, Jonathan D
INTRODUCTION/BACKGROUND:Perfluoroalkyl substances (PFAs) are ubiquitous, anthropogenic organic compounds that have been linked with cardiovascular disease and cardiovascular risk factors. Older, long-chain PFAs have been phased out due to adverse cardiometabolic health effect and replaced by newer short-chain PFAs. However, emerging research suggests that short-chain PFAs may also have adverse cardiovascular effects. Non-invasive measures of vascular function can detect preclinical cardiovascular disease and serve as a useful surrogate for early CVD risk. We hypothesized that serum concentrations of PFAs would be associated with noninvasive measures of vascular function, carotid-femoral pulse wave velocity (PWV) and brachial artery reactivity testing (BART), in adults with non-occupational exposure to PFAs. METHODS:We measured serum concentrations of 14 PFAs with hybrid solid-phase extraction and ultrahigh-performance liquid chromatography-tandem mass spectrometry in 94 adult outpatients with no known cardiovascular disease. We collected clinical and demographic data; and measured vascular function, PWV and BART, using standard protocols. We assessed associations of individual PFAs with log-transformed BART and PWV using linear regression. We used weighted quantile sum regression to assess effects of correlated PFA mixtures on BART and PWV. RESULTS:Ten PFAs were measured above the limit of detection in >50% of participants. Each standard deviation increase in concentration of perfluoroheptanoic acid (PFHpA) was associated with 15% decrease in BART (95% CI: -28.5, -0.17). The weighted index of a mixture of PFAs with correlated concentrations was inversely associated with BART: each tertile increase in the weighted PFA mixture was associated with 25% lower BART, with 73% of the effect driven by PFHpA. In contrast, no PFAs or mixtures were associated with PWV. CONCLUSIONS:Serum concentration of PFHpA, a new, short-chain PFA, was associated with impaired vascular function among outpatients without CVD. Our findings support a potential adverse cardiovascular effect of newer, short-chain PFAs.
PMID: 35447152
ISSN: 1096-0953
CID: 5218522

A Qualitative Study Eliciting Patient Preferences For Cabg Vs Pci [Meeting Abstract]

Dickson, V V; Langford, A; Katz, S
Eliciting patient preferences and goals of care are foundational to the shared decision-making process and are also important to consider in clinical trial design. This qualitative study was part of formative work of a planning study to determine optimal design for a future randomized clinical trial comparing revascularization with coronary artery bypass grafting vs. percutaneous coronary intervention in patients with ischemic cardiomyopathy.
Objective(s): To elicit patient preferences for CABG vs. PCI among ischemic heart disease patients for use in refining study design and methods.
Method(s): We conducted individual interviews and focus groups with 20 subjects (>age 18) with ischemic cardiomyopathy to elicit patient attitudes and descriptions of patient preferences for treatment option. A semi-structured interview guide that included open-ended questions "What is the most important thing you consider when" provided structure but allowed participants to communicate attitudes and patient preferences. All interviews and focus groups were audiotaped and transcribed verbatim; and analyzed using Atlas ti v 8.0 to identify attributes and levels of attributes that influence decision making.
Result(s): Among this sample of patients with ischemic cardiomyopathy (85% male; 80% non-hispanic White); patients described that they are most likely to take the advice of their trusted provider "he's the expert and he knows my caseI do what he says". Five attributes of patient preferences emerged: invasiveness, quality of life, sustainability, complications and recovery period. In each category, subjects described 3 levels of attributes they deemed as influential (e.g., critical, major or minor complication). They also described preferences as a trade off or balancing of attributes. For example trading a longer recovery period for sustainability "If I'm in the hospital longer, I'll manageI prefer one and done!" Or balancing procedure invasiveness with impact to quality of life "I don't want to crack my chest but if it means I will play tennis again".
Conclusion(s): Preferences for CABG vs. PCI among ischemic heart disease patients provide important data for determination of study feasibility, entry criteria and recruitment strategies to support planning of a future clinical trial.
Copyright
EMBASE:2017884879
ISSN: 1532-8414
CID: 5252542

Prevalence and Cumulative Risk of Familial Idiopathic Dilated Cardiomyopathy

Huggins, Gordon S; Kinnamon, Daniel D; Haas, Garrie J; Jordan, Elizabeth; Hofmeyer, Mark; Kransdorf, Evan; Ewald, Gregory A; Morris, Alanna A; Owens, Anjali; Lowes, Brian; Stoller, Douglas; Tang, W H Wilson; Garg, Sonia; Trachtenberg, Barry H; Shah, Palak; Pamboukian, Salpy V; Sweitzer, Nancy K; Wheeler, Matthew T; Wilcox, Jane E; Katz, Stuart; Pan, Stephen; Jimenez, Javier; Aaronson, Keith D; Fishbein, Daniel P; Smart, Frank; Wang, Jessica; Gottlieb, Stephen S; Judge, Daniel P; Moore, Charles K; Mead, Jonathan O; Ni, Hanyu; Burke, Wylie; Hershberger, Ray E
Importance:Idiopathic dilated cardiomyopathy (DCM) aggregates in families, and early detection in at-risk family members can provide opportunity to initiate treatment prior to late-phase disease. Most studies have included only White patients, yet Black patients with DCM have higher risk of heart failure-related hospitalization and death. Objective:To estimate the prevalence of familial DCM among DCM probands and the age-specific cumulative risk of DCM in first-degree relatives across race and ethnicity groups. Design, Setting, and Participants:A family-based, cross-sectional study conducted by a multisite consortium of 25 US heart failure programs. Participants included patients with DCM (probands), defined as left ventricular systolic dysfunction and left ventricular enlargement after excluding usual clinical causes, and their first-degree relatives. Enrollment commenced June 7, 2016; proband and family member enrollment concluded March 15, 2020, and April 1, 2021, respectively. Exposures:The presence of DCM in a proband. Main Outcomes and Measures:Familial DCM defined by DCM in at least 1 first-degree relative; expanded familial DCM defined by the presence of DCM or either left ventricular enlargement or left ventricular systolic dysfunction without known cause in at least 1 first-degree relative. Results:The study enrolled 1220 probands (median age, 52.8 years [IQR, 42.4-61.8]; 43.8% female; 43.1% Black and 8.3% Hispanic) and screened 1693 first-degree relatives for DCM. A median of 28% (IQR, 0%-60%) of living first-degree relatives were screened per family. The crude prevalence of familial DCM among probands was 11.6% overall. The model-based estimate of the prevalence of familial DCM among probands at a typical US advanced heart failure program if all living first-degree relatives were screened was 29.7% (95% CI, 23.5% to 36.0%) overall. The estimated prevalence of familial DCM was higher in Black probands than in White probands (difference, 11.3% [95% CI, 1.9% to 20.8%]) but did not differ significantly between Hispanic probands and non-Hispanic probands (difference, -1.4% [95% CI, -15.9% to 13.1%]). The estimated prevalence of expanded familial DCM was 56.9% (95% CI, 50.8% to 63.0%) overall. Based on age-specific disease status at enrollment, estimated cumulative risks in first-degree relatives at a typical US advanced heart failure program reached 19% (95% CI, 13% to 24%) by age 80 years for DCM and 33% (95% CI, 27% to 40%) for expanded DCM inclusive of partial phenotypes. The DCM hazard was higher in first-degree relatives of non-Hispanic Black probands than non-Hispanic White probands (hazard ratio, 1.89 [95% CI, 1.26 to 2.83]). Conclusions and Relevance:In a US cross-sectional study, there was substantial estimated prevalence of familial DCM among probands and modeled cumulative risk of DCM among their first-degree relatives. Trial Registration:ClinicalTrials.gov Identifier: NCT03037632.
PMID: 35103767
ISSN: 1538-3598
CID: 5153502

Factors Associated With Cognitive Impairment in Heart Failure With Preserved Ejection Fraction

Faulkner, Kenneth M; Dickson, Victoria Vaughan; Fletcher, Jason; Katz, Stuart D; Chang, Patricia P; Gottesman, Rebecca F; Witt, Lucy S; Shah, Amil M; DʼEramo Melkus, Gail
BACKGROUND:Cognitive impairment is prevalent in heart failure and is associated with higher mortality rates. The mechanism behind cognitive impairment in heart failure with preserved ejection fraction (HFpEF) has not been established. OBJECTIVE:The aim of this study was to evaluate associations between abnormal cardiac hemodynamics and cognitive impairment in individuals with HFpEF. METHODS:A secondary analysis of Atherosclerosis Risk in Communities (Atherosclerosis Risk in Communities) study data was performed. Participants free of stroke or dementia who completed in-person assessments at visit 5 were included. Neurocognitive test scores among participants with HFpEF, heart failure with reduced ejection fraction (HFrEF), and no heart failure were compared. Sociodemographics, comorbid illnesses, medications, and echocardiographic measures of cardiac function that demonstrated significant (P < .10) bivariate associations with neurocognitive test scores were included in multivariate models to identify predictors of neurocognitive test scores among those with HFpEF. Multiple imputation by chained equations was used to account for missing values. RESULTS:Scores on tests of attention, language, executive function, and global cognitive function were worse among individuals with HFpEF than those with no heart failure. Neurocognitive test scores were not significantly different among participants with HFpEF and HFrEF. Worse diastolic function was weakly associated with worse performance in memory, attention, and language. Higher cardiac index was associated with worse performance on 1 test of attention. CONCLUSIONS:Cognitive impairment is prevalent in HFpEF and affects several cognitive domains. The current study supports the importance of cognitive screening in patients with heart failure. An association between abnormal cardiac hemodynamics and cognitive impairment was observed, but other factors are likely involved.
PMID: 32649377
ISSN: 1550-5049
CID: 4552572