Publications by authors named "Kevin Clerkin"

49 Publications

Chronic intermittent intravenous immunoglobulin in heart transplant recipients with elevated donor-specific antibody levels.

Clin Transplant 2021 Oct 27:e14524. Epub 2021 Oct 27.

Department of Medicine, Division of Cardiology, Columbia University Irving Medical Center, New York, New York, USA.

Donor-specific antibodies (DSA) are associated with antibody-mediated rejection (AMR) and poor patient survival. In heart transplant, the efficacy of intermittent intravenous immunoglobulin (IVIg) in reducing de novo DSA levels and treating AMR has not been characterized. We retrospectively studied a cohort of 19 patients receiving intermittent IVIg for elevated DSA and examined changes in DSA levels and graft function. Intermittent IVIg infusions were generally safe and well tolerated. Overall, 23 of 62 total DSA (37%) were undetectable after treatment, 21 DSA (34%) had MFI decrease by more than 25%, and 18 (29%) had MFI decrease by less than 25% or increase. The average change in MFI was -51% ± 71% (P < .001). Despite reductions in DSA, among the six patients (32%) with biopsy-confirmed AMR, left ventricular ejection fraction (LVEF) decreased in five (83%) and cardiac index (CI) decreased in three (50%). Conversely, LVEF increased in 91% and CI increased in 70% of biopsy-negative patients. All six AMR patients were readmitted during treatment, four for confirmed or suspected rejection. IVIg infusions may stabilize the allograft in patients with elevated DSA and negative biopsies, but once AMR has developed does not appear to improve allograft function despite decreasing DSA levels.
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http://dx.doi.org/10.1111/ctr.14524DOI Listing
October 2021

Understanding the link between obesity and severe COVID-19 outcomes: Causal mediation by systemic inflammatory response.

J Clin Endocrinol Metab 2021 Sep 2. Epub 2021 Sep 2.

Division of Cardiology, Columbia University, New York, NY USA.

Background: Obesity is an established risk factor for severe COVID-19 outcomes. The mechanistic underpinnings of this association are not well-understood.

Objective: To evaluate the mediating role of systemic inflammation in obesity-associated COVID-19 outcomes.

Design: Hospital-based, observational.

Setting: Massachusetts General Hospital (MGH) or Columbia University Irving Medical Center/NewYork-Presbyterian Hospital (CUIMC/NYP).

Patients Or Other Participants: N=3828 SARS-CoV-2-infected patients hospitalized February to May 2020.

Main Outcome Measures: Mediation analysis is used to evaluate whether peak inflammatory biomarkers [C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), D-dimer, ferritin, white blood cell count and interleukin-6] are in the causal pathway between obesity (BMI ≥ 30) and mechanical ventilation or death within 28 days of presentation to care.

Results: In the MGH cohort (n=1202), obesity was associated with greater likelihood of ventilation or death [OR=1.73, 95% CI=(1.25, 2.41), p=0.001] and higher peak CRP (p<0.001) compared to non-obese patients. The estimated proportion of the association between obesity and ventilation or death mediated by CRP was 0.49 (p<0.001). Evidence of mediation was more pronounced in patients <65 years [proportion mediated=0.52 (p<0.001) versus 0.44 (p=0.180)]. Findings were more moderate but consistent for peak ESR. Mediation by other inflammatory markers was not supported. Results were replicated in CUIMC/NYP cohort (n=2626).

Conclusions: Findings support systemic inflammatory pathways in obesity-associated severe COVID-19 disease, particularly in patients <65 years, captured by CRP and ESR. Contextualized in clinical trials findings, these results reveal therapeutic opportunity to target systemic inflammatory pathways and monitor interventions in high-risk subgroups and particularly obese patients.
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http://dx.doi.org/10.1210/clinem/dgab629DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8499919PMC
September 2021

Transcriptomic heterogeneity of antibody mediated rejection after heart transplant with or without donor specific antibodies.

J Heart Lung Transplant 2021 11 8;40(11):1472-1480. Epub 2021 Jul 8.

Columbia Center for Translational Immunology, Columbia University Medical Center, New York, New York. Electronic address:

Background: Antibody mediated rejection (AMR) is an increasingly studied cause of graft failure after heart transplantation. AMR diagnosis previously required the detection of circulating donor specific antibodies (DSA); however, the most recent criteria only require pathological findings. This classification defined a subset of patients with AMR, yet without known antibodies. Here, we sought to evaluate differences in the transcriptome profile associated with different types of AMR.

Methods: RNA sequencing was used on endomyocardial biopsies to analyze and compare transcriptomic profiles associated with different subtypes of AMR defined by immunopathological and histopathological findings, as well as the presence or absence of DSA. Gene expression profiles were characterized for each diagnostic group.

Results: The most divergent gene expression profiles were observed between patients with or without DSA. AMR subtypes associated with DSA showed expression of signature genes involved in monocyte activation and response to interferon. There was also substantial difference between the transcriptomic profiles of AMR defined by histopathological and immunopathological findings, the latter being associated with expression of mucin genes. In contrast, there was no differential RNA expression between patients with pAMR1i without DSA and those without AMR. Likewise, no differential expression was observed between patients with pAMR1h with DSA and pAMR2.

Conclusions: Overall, our studies reveal different expression profiles in endomyocardial biopsies in relation to some key criteria used to diagnose AMR. These findings support the view that the diagnosis of AMR encompasses several phenotypes that may rely on distinct mechanisms of injury.
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http://dx.doi.org/10.1016/j.healun.2021.06.012DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8571048PMC
November 2021

A Rare Case of Disseminated Tuberculosis and Hematological Malignancy in a Heart Transplant Recipient.

Transplant Proc 2021 Oct 13;53(8):2626-2629. Epub 2021 Aug 13.

Division of Cardiology, Columbia University Irving Medical Center, New York, New York, USA. Electronic address:

A 77-year-old man who underwent a heart transplant 7 years ago presented with multiple bloody bowel movements. Endoscopic and histologic evaluation revealed chronic active ileitis, granulomatous inflammation, multinucleated giant cells, and a rare, equivocal acid-fast bacterium in the terminal ileum. Positive sputum cultures for Mycobacterium tuberculosis and acid-fast bacilli established a diagnosis of intestinal tuberculosis, and RIPE (rifabutin, isoniazid, pyrazinamide, ethambutol) therapy was initiated. Elevated IgG levels on quantitative immunoglobulin testing and a bone marrow biopsy specimen of ≥60% plasma cells confirmed the diagnosis of multiple myeloma that later transformed into its aggressive form, plasma cell leukemia. Induction chemotherapy was initiated; however, the patient experienced retroperitoneal bleeding and pancytopenias, limiting the continuation of chemotherapy, and as a result, the patient was transitioned to palliative care.
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http://dx.doi.org/10.1016/j.transproceed.2021.07.037DOI Listing
October 2021

How can we better inform our patients about post-heart transplantation survival? A conditional survival analysis.

Clin Transplant 2021 Nov 12;35(11):e14449. Epub 2021 Sep 12.

Department of Medicine, Milstein Division of Cardiology, Columbia University Vagelos College of Physicians and Surgeons, New York, New York, USA.

Background: Conditional survival (CS) is a dynamic method of survival analysis that provides an estimate of how an individual's future survival probability changes based on time post-transplant, individual characteristics, and post-transplant events. This study sought to provide post-transplant CS probabilities for heart transplant recipients based on different prognostic variables and provide a discussion tool for the providers and the patients.

Methods: Adult heart transplant recipients from January 1, 2004, through October 18, 2018, were identified in the UNOS registry. CS probabilities were calculated using data from Kaplan-Meier survival estimates.

Results: CS probability exceeded actuarial survival probability at all times post-transplant. Women had similar short-term, but greater long-term CS than men at all times post-transplant (10-year CS 1.8-11.5% greater [95% CI 1.2-12.9]). Patients with ECMO or a surgical BiVAD had decreased survival at the time of transplant, but their CS was indistinguishable from all others by 1-year post-transplant. Rejection and infection requiring hospitalization during the first year were associated with a persistently decreased CS probability.

Conclusions: In this study, we report differential conditional survival outcomes based on time, patient characteristics, and clinical events post-transplant, providing a dynamic assessment of survival. The survival probabilities will better inform patients and clinicians of future outcomes.
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http://dx.doi.org/10.1111/ctr.14449DOI Listing
November 2021

Exception Status Listing in the New Adult Heart Allocation System: A New Solution to an Old Problem?

Circ Heart Fail 2021 06 28;14(6):e007916. Epub 2021 May 28.

Division of Cardiology, Department of Medicine, Weill Cornell Medicine, New York, NY (E.H., G.S., N.U.).

Background: One of the goals of the revised 6-tiered US adult heart allocation policy was to improve risk stratification of patients to lower exception status utilization for transplant listing. We sought to define the characteristics and outcomes of waitlisted patients using exception status and to examine region- and center-level differences in utilization of exception status in the new heart allocation system.

Methods: This retrospective cohort analysis of the United Network for Organ Sharing database included adult waitlisted patients for heart transplant between October 18, 2018, and June 30, 2020, in the United States, stratified by use of exception status versus standard criteria.

Results: Out of 6351 patients, 1907 (30.0%) were waitlisted under exception status. Patients using exception status were more likely to have a nonischemic cause of heart failure, blood type O, United Network for Organ Sharing status 2 at listing and were less likely to have a durable left ventricular assist device at listing. Exception status utilization varied significantly between and within United Network for Organ Sharing regions. Listing by exception criteria was associated with a significantly higher incidence of heart transplantation compared with listing by standard criteria (hazard ratio, 1.25 [1.15-1.38], <0.001), without increased risk of death or delisting for worsening clinical status (hazard ratio, 0.83 [0.65-1.05], =0.12) after multivariable adjustment.

Conclusions: The status tiers of the new heart allocation system may not fully capture medical urgency and complexity of waitlisted patients as assessed by transplant physicians and review committees and may limit the ability to develop a heart allocation score.
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http://dx.doi.org/10.1161/CIRCHEARTFAILURE.120.007916DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8218576PMC
June 2021

Extracorporeal photopheresis and its role in heart transplant rejection: prophylaxis and treatment.

Clin Transplant 2021 07 27;35(7):e14333. Epub 2021 May 27.

Division of Cardiology, Department of Medicine, Columbia University, New York, NY, USA.

Heart transplantation is the gold standard therapeutic option for select patients with end-stage heart failure. Unfortunately, successful long-term outcomes of heart transplantation can be hindered by immune-mediated rejection of the cardiac allograft, specifically acute cellular rejection, antibody-mediated rejection, and cardiac allograft vasculopathy. Extracorporeal photopheresis is a cellular immunotherapy that involves the collection and treatment of white blood cells contained in the buffy coat with a photoactive psoralen compound, 8-methoxy psoralen, and subsequent irradiation with ultraviolet A light. This process is thought to cause DNA and RNA crosslinking, ultimately leading to cell destruction. The true mechanism of therapeutic action remains unknown. In the last three decades, extracorporeal photopheresis has shown promising results and is indicated for a variety of conditions. The American Society for Apheresis currently recommends the use of extracorporeal photopheresis for the treatment of cutaneous T-cell lymphoma, scleroderma, psoriasis, pemphigus vulgaris, atopic dermatitis, graft-versus-host disease, Crohn's disease, nephrogenic systemic fibrosis, and solid organ rejection in heart, lung, and liver transplantation. In this review, we aim to explore the proposed effects of extracorporeal photopheresis and to summarize published data on its use as a prophylactic and therapy in heart transplant rejection.
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http://dx.doi.org/10.1111/ctr.14333DOI Listing
July 2021

De Novo Human Leukocyte Antigen Allosensitization in Heartmate 3 Versus Heartmate II Left Ventricular Assist Device Recipients.

ASAIO J 2021 Apr 19. Epub 2021 Apr 19.

From the Division of Cardiology, Department of Medicine, Columbia University Irving Medical Center, New York, New York Columbia Center for Translational Immunology, Columbia University Irving Medical Center, New York, New York Division of Cardiothoracic Surgery, Department of Surgery, Columbia University Irving Medical Center, New York, New York.

Left ventricular assist devices (LVADs) are associated with the development of antihuman leukocyte antigen (HLA) antibodies, which can create a challenge for future transplantation in these patients. The differential effects of Heartmate 3 (HM3) versus Heartmate II (HMII) on de novo HLA allosensitization remain unknown. Patients who underwent HMII or HM3 implantation and had no prior HLA antibodies by solid-phase assay (Luminex) testing were included in this study. Complement-dependent cytotoxicity (CDC) panel reactive antibody (PRA) levels and Luminex antibody profiles were followed until cardiac transplantation, device explantation, or death. Electronic medical records were reviewed to examine posttransplant outcomes. Thirty-eight HM3 and 34 HMII patients with complete data were followed for 1.5 ± 1.1 years on device support. HM3 and HMII groups had similar age at implant, female gender, ischemic heart failure etiology, bridge strategy at implant, as well as intraoperative and postoperative transfusion requirements. 39.5% of HM3 and 47.1% of HMII patients developed detectable HLA antibodies by Luminex testing (p = 0.516). Development of high-level (mean fluorescence intensity >10,000) antibodies was significantly lower in HM3 than HMII patients (5.3 vs. 20.6%, p = 0.049). CDC PRA testing showed fewer HM3 patients with a positive result (PRA > 0%) than HMII patients (39.4 vs. 70.0%, p = 0.015). Among transplanted patients, those who had developed de novo sensitization on LVAD support showed a trend toward incidence of moderate to severe grade rejection compared with unsensitized patients (23.8 vs. 4.8%, p = 0.078). HM3 is associated with lower risk of de novo HLA sensitization compared with HMII.
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http://dx.doi.org/10.1097/MAT.0000000000001451DOI Listing
April 2021

ECMO as a Bridge to Left Ventricular Assist Device or Heart Transplantation.

JACC Heart Fail 2021 04 10;9(4):281-289. Epub 2021 Mar 10.

Milstein Division of Cardiology, Department of Medicine, New York Presbyterian - Columbia University Irving Medical Center, New York, New York, USA. Electronic address:

Objectives: The purpose of this study was to compare outcomes between patients on extracorporeal membrane oxygenation (ECMO) bridged to left ventricular assist device (LVAD) versus heart transplantation (HT) using registry data.

Background: Patients with heart failure supported with ECMO represent the highest priority in the new HT allocation system. For patients on ECMO, bridging to LVAD may be non-inferior compared with bridging to HT.

Methods: Adult patients in the Interagency Registry for Mechanically Assisted Circulatory Support (INTERMACS) from 2006 to 2017 and United Network for Organ Sharing (UNOS) database from 2006 to June 2019 requiring ECMO were included. Cause-specific hazard models were created and cumulative incidence functions were calculated with mortality, transplantation, and re-transplantation as competing events.

Results: A total of 906 patients received ECMO as bridge to VAD (n = 587, 64.8%) or as bridge to HT (n = 319, 35.2%). Patients bridged directly to HT were younger (age 46.3 ± 15.4 years vs. 52.1 ± 13.2 years; p < 0.001) and more likely to be female (93 [29.2%] vs. 139 [23.7%]; p = 0.022). Patients bridged directly to HT were more likely to have a nonischemic cardiomyopathy, restrictive physiologies, and allograft failure; (p < 0.05 for all). ECMO use increased over time in both UNOS and INTERMACS. There was no significant difference in mortality between groups (Gray's p = 0.581). This remained true even when the analysis was restricted to transplant-listed or eligible patients as well as patients with dilated phenotypes (excluding patients with congenital heart disease, restrictive phenotypes, and allograft failure).

Conclusions: There was no difference in mortality on pump support compared with posttransplant mortality among those bridged from ECMO to LVAD or HT.
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http://dx.doi.org/10.1016/j.jchf.2020.12.012DOI Listing
April 2021

Donor-derived cell-free DNA is associated with cardiac allograft vasculopathy.

Clin Transplant 2021 03 6;35(3):e14206. Epub 2021 Feb 6.

Department of Medicine, Milstein Division of Cardiology, Columbia University Vagelos College of Physicians and Surgeons, New York, NY, USA.

Background: The role of donor-derived cell-free DNA (dd-cfDNA) in screening for cardiac allograft vasculopathy (CAV) is unknown. We hypothesized that dd-cfDNA correlates with CAV, markers of inflammation, and angiogenesis in stable heart transplant (HT) recipients.

Methods: Sixty-five HT recipients ≥2 years post-transplant, without recent rejection, were stratified by high (≥0.12%) versus low levels (<0.12%) of dd-cfDNA. A targeted amplification, next-generation sequencing assay (AlloSure ; CareDx, Inc.) was used to detect dd-cfDNA. Peripheral blood inflammatory and angiogenesis markers were assessed using a multiplex immunoassay system (Bioplex ).

Results: Of 65 patients, 58 patients had a known CAV status and were included. Thirty had high levels of dd-cfDNA (≥0.12%), and 28 had low levels (<0.12%). CAV was present in 63% of patients with high dd-cfDNA vs. 35% with low dd-cfDNA (p = .047). Donor-specific antibodies were present in 25% of patients with high dd-cfDNA vs. 3.8% in those with low dd-cfDNA (p = .03). There were no differences in rejection episodes, inflammatory, or angiogenesis markers. Importantly, dd-cfDNA levels were not different when stratified by time post-transplant.

Conclusions: Higher dd-cfDNA levels were associated with CAV in stable chronic HT recipients. Further studies are warranted to investigate a possible association between dd-cfDNA levels and CAV severity and whether dd-cfDNA can predict CAV progression.
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http://dx.doi.org/10.1111/ctr.14206DOI Listing
March 2021

Admission Cardiac Diagnostic Testing with Electrocardiography and Troponin Measurement Prognosticates Increased 30-Day Mortality in COVID-19.

J Am Heart Assoc 2021 01 10;10(1):e018476. Epub 2020 Nov 10.

Seymour, Paul, and Gloria Milstein Division of Cardiology Department of Medicine Columbia University Irving Medical Center New York NY.

Background Cardiovascular involvement in coronavirus disease 2019 (COVID-19) is common and leads to worsened mortality. Diagnostic cardiovascular studies may be helpful for resource appropriation and identifying patients at increased risk for death. Methods and Results We analyzed 887 patients (aged 64±17 years) admitted with COVID-19 from March 1 to April 3, 2020 in New York City with 12 lead electrocardiography within 2 days of diagnosis. Demographics, comorbidities, and laboratory testing, including high sensitivity cardiac troponin T (hs-cTnT), were abstracted. At 30 days follow-up, 556 patients (63%) were living without requiring mechanical ventilation, 123 (14%) were living and required mechanical ventilation, and 203 (23%) had expired. Electrocardiography findings included atrial fibrillation or atrial flutter (AF/AFL) in 46 (5%) and ST-T wave changes in 306 (38%). 27 (59%) patients with AF/AFL expired as compared to 181 (21%) of 841 with other non-life-threatening rhythms (<0.001). Multivariable analysis incorporating age, comorbidities, AF/AFL, QRS abnormalities, and ST-T wave changes, and initial hs-cTnT ≥20 ng/L showed that increased age (HR 1.04/year), elevated hs-cTnT (HR 4.57), AF/AFL (HR 2.07), and a history of coronary artery disease (HR 1.56) and active cancer (HR 1.87) were associated with increased mortality. Conclusions Myocardial injury with hs-cTnT ≥20 ng/L, in addition to cardiac conduction perturbations, especially AF/AFL, upon hospital admission for COVID-19 infection is associated with markedly increased risk for mortality than either diagnostic abnormality alone.
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http://dx.doi.org/10.1161/JAHA.120.018476DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7955502PMC
January 2021

Comparing outcomes for infiltrative and restrictive cardiomyopathies under the new heart transplant allocation system.

Clin Transplant 2020 12 28;34(12):e14109. Epub 2020 Oct 28.

Milstein Division of Cardiology, Department of Medicine, Columbia University Vagelos College of Physicians and Surgeons, New York, NY, USA.

The new heart transplantation (HT) allocation policy was introduced on 10/18/2018. Using the UNOS registry, we examined early outcomes following HT for restrictive cardiomyopathy, hypertrophic cardiomyopathy, cardiac sarcoidosis, or cardiac amyloidosis compared to the old system. Those listed who had an event (transplant, death, or waitlist removal) prior to 10/17/2018 were in Era 1, and those listed on or after 10/18/2018 were in Era 2. The primary endpoint was death on the waitlist or delisting due to clinical deterioration. A total of 1232 HT candidates were included, 855 (69.4%) in Era 1 and 377 (30.6%) in Era 2. In Era 2, there was a significant increase in the use of temporary mechanical circulatory support and a reduction in the primary endpoint, (20.9 events per 100 PY (Era 1) vs. 18.6 events per 100 PY (Era 2), OR 1.98, p = .005). Median waitlist time decreased (91 vs. 58 days, p < .001), and transplantation rate increased (119.0 to 204.7 transplants/100 PY for Era 1 vs Era 2). Under the new policy, there has been a decrease in waitlist time and waitlist mortality/delisting due to clinical deterioration, and an increase in transplantation rates for patients with infiltrative, hypertrophic, and restrictive cardiomyopathies without any effect on post-transplant 6-month survival.
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http://dx.doi.org/10.1111/ctr.14109DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7755228PMC
December 2020

The Prognostic Value of Electrocardiogram at Presentation to Emergency Department in Patients With COVID-19.

Mayo Clin Proc 2020 10 15;95(10):2099-2109. Epub 2020 Aug 15.

Seymour, Paul, and Gloria Milstein Division of Cardiology, Department of Medicine, Columbia University Irving Medical Center, New York, NY; Department of Medicine, Columbia University Irving Medical Center, New York, NY.

Objective: To study whether combining vital signs and electrocardiogram (ECG) analysis can improve early prognostication.

Methods: This study analyzed 1258 adults with coronavirus disease 2019 who were seen at three hospitals in New York in March and April 2020. Electrocardiograms at presentation to the emergency department were systematically read by electrophysiologists. The primary outcome was a composite of mechanical ventilation or death 48 hours from diagnosis. The prognostic value of ECG abnormalities was assessed in a model adjusted for demographics, comorbidities, and vital signs.

Results: At 48 hours, 73 of 1258 patients (5.8%) had died and 174 of 1258 (13.8%) were alive but receiving mechanical ventilation with 277 of 1258 (22.0%) patients dying by 30 days. Early development of respiratory failure was common, with 53% of all intubations occurring within 48 hours of presentation. In a multivariable logistic regression, atrial fibrillation/flutter (odds ratio [OR], 2.5; 95% CI, 1.1 to 6.2), right ventricular strain (OR, 2.7; 95% CI, 1.3 to 6.1), and ST segment abnormalities (OR, 2.4; 95% CI, 1.5 to 3.8) were associated with death or mechanical ventilation at 48 hours. In 108 patients without these ECG abnormalities and with normal respiratory vitals (rate <20 breaths/min and saturation >95%), only 5 (4.6%) died or required mechanical ventilation by 48 hours versus 68 of 216 patients (31.5%) having both ECG and respiratory vital sign abnormalities.

Conclusion: The combination of abnormal respiratory vital signs and ECG findings of atrial fibrillation/flutter, right ventricular strain, or ST segment abnormalities accurately prognosticates early deterioration in patients with coronavirus disease 2019 and may assist with patient triage.
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http://dx.doi.org/10.1016/j.mayocp.2020.07.028DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7428764PMC
October 2020

Indications for and Findings on Transthoracic Echocardiography in COVID-19.

J Am Soc Echocardiogr 2020 10 17;33(10):1278-1284. Epub 2020 Jun 17.

Department of Medicine, Division of Cardiology, Columbia University Irving Medical Center, New York, New York.

Background: Despite growing evidence of cardiovascular complications associated with coronavirus disease 2019 (COVID-19), there are few data regarding the performance of transthoracic echocardiography (TTE) and the spectrum of echocardiographic findings in this disease.

Methods: A retrospective analysis was performed among adult patients admitted to a quaternary care center in New York City between March 1 and April 3, 2020. Patients were included if they underwent TTE during the hospitalization after a known positive diagnosis for COVID-19. Demographic and clinical data were obtained using chart abstraction from the electronic medical record.

Results: Of 749 patients, 72 (9.6%) underwent TTE following positive results on severe acute respiratory syndrome coronavirus-2 polymerase chain reaction testing. The most common clinical indications for TTE were concern for a major acute cardiovascular event (45.8%) and hemodynamic instability (29.2%). Although most patients had preserved biventricular function, 34.7% were found to have left ventricular ejection fractions ≤ 50%, and 13.9% had at least moderately reduced right ventricular function. Four patients had wall motion abnormalities suggestive of stress-induced cardiomyopathy. Using Spearman rank correlation, there was an inverse relationship between high-sensitivity troponin T and left ventricular ejection fraction (ρ = -0.34, P = .006). Among 20 patients with prior echocardiograms, only two (10%) had new reductions in LVEF of >10%. Clinical management was changed in eight individuals (24.2%) in whom TTE was ordered for concern for acute major cardiovascular events and three (14.3%) in whom TTE was ordered for hemodynamic evaluation.

Conclusions: This study describes the clinical indications for use and diagnostic performance of TTE, as well as findings seen on TTE, in hospitalized patients with COVID-19. In appropriately selected patients, TTE can be an invaluable tool for guiding COVID-19 clinical management.
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http://dx.doi.org/10.1016/j.echo.2020.06.009DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7298489PMC
October 2020

Myocardial Injury in COVID-19 Patients: The Beginning or the End?

J Am Coll Cardiol 2020 08;76(5):547-549

Division of Cardiology, Department of Medicine, Columbia University Vagelos College of Physicians and Surgeons, New York, New York.

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http://dx.doi.org/10.1016/j.jacc.2020.06.045DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7384775PMC
August 2020

The cardiac intensive care unit and the cardiac intensivist during the COVID-19 surge in New York City.

Am Heart J 2020 09 3;227:74-81. Epub 2020 Jul 3.

Department of Medicine, Seymour, Paul, and Gloria Milstein Division of Cardiology, Columbia University Irving Medical Center, New York, NY. Electronic address:

Critical care cardiology has been impacted by the coronavirus disease-2019 (COVID-19) pandemic. COVID-19 causes severe acute respiratory distress syndrome, acute kidney injury, as well as several cardiovascular complications including myocarditis, venous thromboembolic disease, cardiogenic shock, and cardiac arrest. The cardiac intensive care unit is rapidly evolving as the need for critical care beds increases. Herein, we describe the changes to the cardiac intensive care unit and the evolving role of critical care cardiologists and other clinicians in the care of these complex patients affected by the COVID-19 pandemic. These include practical recommendations regarding structural and organizational changes to facilitate care of patients with COVID-19; staffing and personnel changes; and health and safety of personnel. We draw upon our own experiences at NewYork-Presbyterian Columbia University Irving Medical Center to offer insights into the unique challenges facing critical care clinicians and provide recommendations of how to address these challenges during this unprecedented time.
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http://dx.doi.org/10.1016/j.ahj.2020.06.018DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7332920PMC
September 2020

United network for organ sharing outcomes after heart transplantation for al compared to ATTR cardiac amyloidosis.

Clin Transplant 2020 10 24;34(10):e14028. Epub 2020 Jul 24.

Center for Advanced Cardiac Care, Division of Cardiology, Columbia College of Physicians & Surgeons, New York, NY, USA.

Light-chain (AL) cardiac amyloidosis (CA) has a worse prognosis than transthyretin (ATTR) CA. In this single-center study, we compared post-heart transplant (OHT, orthotopic heart transplantation) survival for AL and ATTR amyloidosis, hypothesizing that these differences would persist post-OHT. Thirty-nine patients with CA (AL, n = 18; ATTR, n = 21) and 1023 non-amyloidosis subjects undergoing OHT were included. Cox proportional hazards modeling was used to evaluate the impact of amyloid subtype and era (early era: from 2001 to 2007; late era: from 2008 to 2018) on survival post-OHT. Survival for non-amyloid patients was greater than ATTR (P = .034) and AL (P < .001) patients in the early era. One, 3-, and 5-year survival rates were higher for ATTR patients than AL patients in the early era (100% vs 75%, 67% vs 50%, and 67% vs 33%, respectively, for ATTR and AL patients). Survival in the non-amyloid cohort was 87% at 1 year, 81% at 3 years, and 76% at 5 years post-OHT. In the late era, AL and ATTR patients had unadjusted 1-year, 3-year, and 5-year survival rates of 100%, which was comparable to non-amyloid patients (90% vs 84% vs 81%). Overall, these findings demonstrate that in the current era, differences in post-OHT survival for AL compared to ATTR are diminishing; OHT outcomes for selected patients with CA do not differ from non-amyloidosis patients.
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http://dx.doi.org/10.1111/ctr.14028DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7744118PMC
October 2020

Case 18-2020: A 73-Year-Old Man with Hypoxemic Respiratory Failure and Cardiac Dysfunction.

N Engl J Med 2020 Jun;382(24):2354-2364

From the Departments of Medicine (D.S.K., L.M.M., D.S.P., P.J.Z.) and Radiology (D.L.), Beth Israel Deaconess Medical Center, the Departments of Medicine (D.S.K., L.M.M., D.S.P., P.J.Z., D.M.D.) and Radiology (D.L.), Harvard Medical School, and the Department of Medicine, Massachusetts General Hospital (D.M.D.) - all in Boston; and the Department of Medicine, New York Presbyterian-Columbia University Medical Center, and the Department of Medicine, Columbia University Vagelos College of Physicians and Surgeons - both in New York (K.J.C.).

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http://dx.doi.org/10.1056/NEJMcpc2002417DOI Listing
June 2020

Pharmacological Agents Targeting Thromboinflammation in COVID-19: Review and Implications for Future Research.

Thromb Haemost 2020 Jul 30;120(7):1004-1024. Epub 2020 May 30.

New York-Presbyterian Hospital/Columbia University Irving Medical Center, New York, New York, United States.

Coronavirus disease 2019 (COVID-19), currently a worldwide pandemic, is a viral illness caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The suspected contribution of thrombotic events to morbidity and mortality in COVID-19 patients has prompted a search for novel potential options for preventing COVID-19-associated thrombotic disease. In this article by the Global COVID-19 Thrombosis Collaborative Group, we describe novel dosing approaches for commonly used antithrombotic agents (especially heparin-based regimens) and the potential use of less widely used antithrombotic drugs in the absence of confirmed thrombosis. Although these therapies may have direct antithrombotic effects, other mechanisms of action, including anti-inflammatory or antiviral effects, have been postulated. Based on survey results from this group of authors, we suggest research priorities for specific agents and subgroups of patients with COVID-19. Further, we review other agents, including immunomodulators, that may have antithrombotic properties. It is our hope that the present document will encourage and stimulate future prospective studies and randomized trials to study the safety, efficacy, and optimal use of these agents for prevention or management of thrombosis in COVID-19.
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http://dx.doi.org/10.1055/s-0040-1713152DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7516364PMC
July 2020

Local competition influences donor heart acceptance practice.

J Heart Lung Transplant 2020 08 27;39(8):835-838. Epub 2020 Apr 27.

Division of Cardiology, Department of Medicine, Columbia University College of Physicians and Surgeons, New York, New York.

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http://dx.doi.org/10.1016/j.healun.2020.04.018DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7721478PMC
August 2020

Characteristics and Outcomes of Recipients of Heart Transplant With Coronavirus Disease 2019.

JAMA Cardiol 2020 10;5(10):1165-1169

Division of Cardiology, Department of Medicine, Columbia University Vagelos College of Physicians and Surgeons, New York, New York.

Importance: Recipients of heart transplant (HT) may be at increased risk of adverse outcomes attributable to infection with coronavirus disease 2019 (COVID-19) because of multiple comorbidities and clinically significant immunosuppression.

Objective: To describe the characteristics, treatment, and outcomes of recipients of HT with COVID-19.

Design, Setting, And Participants: This case series from a single large academic heart transplant program in New York, New York, incorporates data from between March 1, 2020, and April 24, 2020. All recipients of HT followed up by this center who were infected with COVID-19 were included.

Interventions: Heart transplant and a confirmed diagnosis of COVID-19.

Main Outcomes And Measures: The primary measure was vital status at end of study follow-up. Secondary measures included patient characteristics, laboratory analyses, changes to immunosuppression, and treatment administered for COVID-19.

Results: Twenty-eight patients with HT received a confirmed diagnosis of COVID-19. The median age was 64.0 (interquartile range [IQR], 53.5-70.5) years, 22 (79%) were men, and the median time from HT was 8.6 (IQR, 4.2-14.5) years. Comorbid conditions included hypertension in 20 patients (71%), diabetes in 17 patients (61%), and cardiac allograft vasculopathy in 16 patients (57%). Twenty-two participants (79%) were admitted for treatment, and 7 (25%) required mechanical ventilation. Most (13 of 17 [76%]) had evidence of myocardial injury (median high-sensitivity troponin T, 0.055 [IQR, 0.0205-0.1345] ng/mL) and elevated inflammatory biomarkers (median peak high-sensitivity C-reactive protein, 11.83 [IQR, 7.44-19.26] mg/dL; median peak interleukin 6, 105 [IQR, 38-296] pg/mL). Among patients managed at the study institution, mycophenolate mofetil was discontinued in 16 patients (70%), and 6 (26%) had a reduction in the dose of their calcineurin inhibitor. Treatment of COVID-19 included hydroxychloroquine (18 patients [78%]), high-dose corticosteroids (8 patients [47%]), and interleukin 6 receptor antagonists (6 patients [26%]). Overall, 7 patients (25%) died. Among 22 patients (79%) who were admitted, 11 (50%) were discharged home, 4 (18%) remain hospitalized at the end of the study, and 7 (32%) died during hospitalization.

Conclusions And Relevance: In this single-center case series, COVID-19 infection was associated with a case fatality rate of 25% in recipients of HT. Immunosuppression was reduced in most of this group of patients. Further study is required to evaluate the optimal approach to management of COVID-19 infection in the HT population.
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http://dx.doi.org/10.1001/jamacardio.2020.2159DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7221850PMC
October 2020

Current Perspectives on Coronavirus Disease 2019 and Cardiovascular Disease: A White Paper by the Editors.

J Am Heart Assoc 2020 06 29;9(12):e017013. Epub 2020 Apr 29.

Division of Cardiovascular Medicine Department of Medicine University of Iowa Carver College of Medicine Iowa City IA.

Coronavirus Disease 2019 (COVID-19) has infected more than 3.0 million people worldwide and killed more than 200,000 as of April 27, 2020. In this White Paper, we address the cardiovascular co-morbidities of COVID-19 infection; the diagnosis and treatment of standard cardiovascular conditions during the pandemic; and the diagnosis and treatment of the cardiovascular consequences of COVID-19 infection. In addition, we will also address various issues related to the safety of healthcare workers and the ethical issues related to patient care in this pandemic.
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http://dx.doi.org/10.1161/JAHA.120.017013DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7429024PMC
June 2020

COVID-19 and Cardiovascular Disease.

Circulation 2020 May 21;141(20):1648-1655. Epub 2020 Mar 21.

Department of Medicine, Division of Cardiology, Columbia University Vagelos College of Physicians and Surgeons, New York.

Coronavirus disease 2019 (COVID-19) is a global pandemic affecting 185 countries and >3 000 000 patients worldwide as of April 28, 2020. COVID-19 is caused by severe acute respiratory syndrome coronavirus 2, which invades cells through the angiotensin-converting enzyme 2 receptor. Among patients with COVID-19, there is a high prevalence of cardiovascular disease, and >7% of patients experience myocardial injury from the infection (22% of critically ill patients). Although angiotensin-converting enzyme 2 serves as the portal for infection, the role of angiotensin-converting enzyme inhibitors or angiotensin receptor blockers requires further investigation. COVID-19 poses a challenge for heart transplantation, affecting donor selection, immunosuppression, and posttransplant management. There are a number of promising therapies under active investigation to treat and prevent COVID-19.
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http://dx.doi.org/10.1161/CIRCULATIONAHA.120.046941DOI Listing
May 2020

Profiling non-HLA antibody responses in antibody-mediated rejection following heart transplantation.

Am J Transplant 2020 09 26;20(9):2571-2580. Epub 2020 Apr 26.

Columbia Center for Translational Immunology, Columbia University Irving Medical Center, New York, New York, USA.

Antibody-mediated rejection (AMR) driven by the development of donor-specific antibodies (DSA) directed against mismatched donor human leukocyte antigen (HLA) is a major risk factor for graft loss in cardiac transplantation. Recently, the relevance of non-HLA antibodies has become more prominent as AMR can be diagnosed in the absence of circulating DSA. Here, we assessed a single-center cohort of 64 orthotopic heart transplant recipients transplanted between 1994 and 2014. Serum collected from patients with ≥ pAMR1 (n = 43) and non-AMR (n = 21) were tested for reactivity against a panel of 44 non-HLA autoantigens. The AMR group had a significantly greater percentage of patients with elevated reactivity to autoantigens compared to non-AMR (P = .002) and healthy controls (n = 94, P < .0001). DSA-positive AMR patients exhibited greater reactivity to autoantigens compared to DSA-negative (P < .0001) and AMR patients with DSA and PRA > 10% were identified as the subgroup with significantly elevated responses. Reactivity to 4 antigens, vimentin, beta-tubulin, lamin A/C, and apolipoprotein L2, was significantly different between AMR and non-AMR patients. Moreover, increased reactivity to these antigens was associated with graft failure. These results suggest that antibodies to non-HLA are associated with DSA-positive AMR although their specific role in mediating allograft injury is not yet understood.
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http://dx.doi.org/10.1111/ajt.15871DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8117249PMC
September 2020

Continuous-flow mechanical circulatory support is not associated with early graft failure: An analysis of the International Society for Heart and Lung Transplantation registry.

Clin Transplant 2019 12 26;33(12):e13752. Epub 2019 Nov 26.

Department of Medicine, Karolinska Institutet & Heart and Vascular Theme, Karolinska University Hospital, Stockholm, Sweden.

Background: Continuous-flow mechanical circulatory support (CF-MCS) is associated with impaired vascular function and increased risk of vasoplegia. One contributing factor to early graft failure (EGF) is severe vasoplegia. We tested the hypothesis that CF-MCS is associated with increased risk of EGF.

Methods: Adult primary heart transplant recipients in the ISHLT Registry from 2005 to 2013 were stratified into three groups based on pre-transplant MCS: No MCS (n = 11 748), pulsatile (P)-MCS (n = 718), and CF-MCS (n = 3818). EGF was defined as death/retransplantation due to graft failure within 30 days after HT. Comparisons were made using descriptive statistics and associations. EGF was assessed with multivariable Cox proportional hazard regression.

Results: The incidence of EGF within 30 days was similar between groups (No MCS 2.2%, P-MCS 3.3%, CF-MCS 2.1%, P = .10). Following multivariable adjustment, the risk of EGF was not statistically different for those with CF-MCS compared with P-MCS (HR 0.75, 95% CI 0.46-1.21, P = .24). The risk of EGF was numerically, but not statistically significantly higher for CF-MCS compared with No MCS (HR 1.24, 95% CI 0.92-1.67, P = .16).

Conclusion: CF-MCS use was not associated with a statistically significant increased risk of EGF resulting in death or retransplantation in the first 30 days after transplant.
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http://dx.doi.org/10.1111/ctr.13752DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6933077PMC
December 2019

Severe coronary artery spasm presenting as Prinzmetal's angina following cardiac transplantation.

Cardiovasc Revasc Med 2018 12 22;19(8S):13-15. Epub 2018 Jun 22.

Columbia University Medical Center/New York-Presbyterian Hospital and the Cardiovascular Research Foundation, New York, NY, United States of America. Electronic address:

We report the case of a 63-year-old woman who presented with typical angina (crushing chest pain) and recurrent frank syncope two years after her heart transplant. She was observed to have transient ST-elevations on continuous ST-segment monitoring that correlated with her symptoms, and coronary angiography revealed severe and transient spasm of the right coronary artery concurrent with her symptoms and ST-segment changes. The observed spasm completely resolved following administration of intracoronary nitroglycerin in the cardiac cathetherization laboratory. Although rare (occurring in ~5% of patients following cardiac transplantation), coronary artery spasm can occur in post-transplanted hearts and is occasionally diagnosed by coronary angiography.
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http://dx.doi.org/10.1016/j.carrev.2018.06.019DOI Listing
December 2018

Clinical and hemodynamic effects of intra-aortic balloon pump therapy in chronic heart failure patients with cardiogenic shock.

J Heart Lung Transplant 2018 11 20;37(11):1313-1321. Epub 2018 Mar 20.

Division of Cardiology, Department of Medicine, Columbia University Medical Center-New York Presbyterian, New York, New York, USA. Electronic address:

Background: The role of the intra-aortic balloon pump (IABP) in acute decompensated heart failure (HF) with cardiogenic shock (CS) is largely undefined. In this study we sought to assess the hemodynamic and clinical response to IABP in chronic HF patients with CS and identify predictors of response to this device.

Methods: We retrospectively reviewed all patients undergoing IABP implantation from 2011 to 2016 at our institution to identify chronic HF patients with acute decompensation and CS (cardiac index <2.2 liters/min/m and systolic blood pressure <90 mm Hg or need for vasoactive medications to maintain this level). Clinical deterioration on IABP was defined as failure to bridge to either discharge on medical therapy or durable heart replacement therapy (HRT; durable left ventricular assist device or heart transplant) with IABP alone.

Results: We identified 132 chronic HF patients with IABP placed after decompensation with hemodynamic evidence of CS. Overall 30-day survival was 84.1%, and 78.0% of patients were successfully bridged to HRT or discharge without need for escalation of device support. The complication rate during IABP support was 2.3%. Multivariable analysis identified ischemic cardiomyopathy (odds ratio [OR] 3.24, 95% confidence interval [CI] 1.16 to 9.06; p = 0.03) and pulmonary artery pulsatility index (PAPi) <2.0 (OR 5.04, 95% CI 1.86 to 13.63; p = 0.001) as predictors of clinical deterioration on IABP.

Conclusions: Overall outcomes with IABP in acute decompensated chronic HF patients are encouraging, and IABP is a reasonable first-line device for chronic HF patients with CS. Baseline right ventricular function, as measured by PAPi, is a major predictor of outcomes with IABP in this population.
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http://dx.doi.org/10.1016/j.healun.2018.03.011DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6148415PMC
November 2018
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