Publications by authors named "Palak Shah"

122 Publications

Higher levels of allograft injury in black patients early after heart transplantation.

J Heart Lung Transplant 2021 Dec 23. Epub 2021 Dec 23.

Genomic Research Alliance for Transplantation (GRAfT), Bethesda, Maryland; Laborarory of Applied Precision Omics (APO), Division of Intramural Research, National Heart, Lung and Blood Institute, National Institutes of Health, Bethesda, Maryland; Department of Medicine, Stanford University School of Medicine, Palo Alto, California. Electronic address:

Black patients suffer higher rates of antibody-mediated rejection and have worse long-term graft survival after heart transplantation. Donor-derived cell free DNA (ddcfDNA) is released into the blood following allograft injury. This study analyzed %ddcfDNA in 63 heart transplant recipients categorized by Black and non-Black race, during the first 200 days after transplant. Immediately after transplant, %ddcfDNA was higher for Black patients (mean [SE]: 8.3% [1.3%] vs 3.2% [1.2%], p = 0.001). In the first week post-transplant, the rate of decay in %ddcfDNA was similar (0.7% [0.68] vs 0.7% [0.11], p = 0.78), and values declined in both groups to a comparable plateau at 7 days post-transplant (0.46% [0.03] vs 0.45% [0.04], p = 0.78). The proportion of Black patients experiencing AMR was higher than non-Black patients (21% vs 9% [hazard ratio of 2.61 [95% confidence interval: 0.651-10.43], p = 0.18). Black patients were more likely to receive a race mismatched organ than non-Black patients (69% vs 35%, p = 0.01), which may explain the higher levels of early allograft injury.
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http://dx.doi.org/10.1016/j.healun.2021.12.006DOI Listing
December 2021

Twelfth Interagency Registry for Mechanically Assisted Circulatory Support Report: Readmissions after LVAD.

Ann Thorac Surg 2022 Jan 7. Epub 2022 Jan 7.

Department of Cardiothoracic Surgery, Montefiore Medical Center, Bronx, New York.

The twelfth annual report from the Society of Thoracic Surgeons (STS) Interagency Registry for Mechanically Assisted Circulatory Support (Intermacs) highlights outcomes for 26,688 continuous-flow LVAD patients over the past decade (2011-2020). In 2020, we observed the largest drop in yearly LVAD implant volumes since the registry's inception, which reflects the effects of the COVID-19 pandemic on cardiac surgical volumes in the United States. The 2018 heart transplant allocation policy change in the U.S. continues to affect LVAD implantation volumes and device strategy, with 78.1% of patients now implanted as destination therapy. Despite an older and sicker patient cohort, survival in the recent era (2016-2020) at one- and two-years continues to improve at 82.8% and 74.1%. Patient adverse event profile has also improved in the recent era, with significant reductions in stroke, gastrointestinal bleeding, infection, and device malfunction/pump thrombosis. Finally, we review the burden of readmissions after LVAD implant and highlight an opportunity to improve patient outcomes by reducing this frequent and vexing problem.
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http://dx.doi.org/10.1016/j.athoracsur.2021.12.011DOI Listing
January 2022

Frailty Measures of Patient-reported Activity and Fatigue May Predict 1-year Outcomes in Ambulatory Advanced Heart Failure: A Report From the REVIVAL Registry.

J Card Fail 2021 Dec 25. Epub 2021 Dec 25.

Division of Cardiovascular Medicine, University of Michigan, Ann Arbor, Michigan.

Background: The Fried Frailty Phenotype predicts adverse outcomes in geriatric populations, but has not been well-studied in advanced heart failure (HF). The Registry Evaluation of Vital Information for Ventricular Assist Devices (VADs) in Ambulatory Life (REVIVAL) study prospectively collected frailty measures in patients with advanced HF to determine relevant assessments and their impact on clinical outcomes.

Methods And Results: HF-Fried Frailty was defined by 5 baseline components (1 point each): (1) weakness: hand grip strength less than 25% of body weight; (2) slowness based on time to walk 15 feet; (3) weight loss of more than 10 lbs in the past year; (4) inactivity; and (5) exhaustion, both assessed by the Kansas City Cardiomyopathy Questionnaire. A score of 0 or 1 was deemed nonfrail, 2 prefrail, and 3 or greater was considered frail. The primary composite outcome was durable mechanical circulatory support implantation, cardiac transplant or death at 1 year. Event-free survival for each group was determined by the Kaplan-Meier method and the hazard of prefrailty and frailty were compared with nonfrailty with proportional hazards modeling. Among 345 patients with all 5 frailty domains assessed, frailty was present in 17%, prefrailty in 40%, and 43% were nonfrail, with 67% (n = 232) meeting the criteria based on inactivity and 54% (n = 186) for exhaustion. Frail patients had an increased risk of the primary composite outcome (unadjusted hazard ratio [HR] 2.82, 95% confidence interval [CI] 1.52-5.24; adjusted HR 3.41, 95% CI 1.79-6.52), as did prefrail patients (unadjusted HR 1.97, 95% CI 1.14-3.41; adjusted HR 2.11, 95% CI 1.21-3.66) compared with nonfrail patients, however, the predictive value of HF-Fried Frailty criteria was modest (Harrel's C-statistic of 0.603, P = .004).

Conclusions: The HF-Fried Frailty criteria had only modest predictive power in identifying ambulatory patients with advanced HF at high risk for durable mechanical circulatory support, transplant, or death within 1 year, driven primarily by assessments of inactivity and exhaustion. Focus on these patient-reported measures may better inform clinical trajectories in this population.
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http://dx.doi.org/10.1016/j.cardfail.2021.10.014DOI Listing
December 2021

Noninvasive biomarkers in heart transplant: 2020-2021 year in review.

Curr Opin Organ Transplant 2022 Feb;27(1):7-14

Genomic Research Alliance for Transplantation (GRAfT).

Purpose Of Review: Endomyocardial biopsy (EMB), the current gold standard for cardiac allograft monitoring is invasive, may have a low sensitivity and is associated with significant variability in histopathologic interpretation. Fortunately, on-going research is identifying noninvasive biomarkers that address some of these limitations. This review provides an update on noninvasive blood-based methods for rejection surveillance and diagnosis in heart transplantation.

Recent Findings: Recent studies highlight good test performance to detect acute rejection for donor-derived cell-free DNA (dd-cfDNA) and microRNAs (miR). dd-cfDNA is sensitive, nonspecific, and has a high negative predictive value for acute cellular and antibody-mediated rejection. Clinical utility trials are being planned to test its role as a rule-out test for acute rejection as compared to the EMB. miRs may have an added advantage as it may phenotype the subtypes of rejection alleviating the need for an EMB or permitting the initiation of targeted therapy while awaiting the results of the EMB.

Summary: In this review, we discuss recent advances in the field of noninvasive biomarkers to detect allograft rejection after heart transplant. We provide a perspective of additional studies needed to prove their clinical utility and bring these biomarkers to widescale clinical use.
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http://dx.doi.org/10.1097/MOT.0000000000000945DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8711631PMC
February 2022

Effect of Treatment With Sacubitril/Valsartan in Patients With Advanced Heart Failure and Reduced Ejection Fraction: A Randomized Clinical Trial.

JAMA Cardiol 2022 01;7(1):17-25

Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts.

Importance: The use of sacubitril/valsartan is not endorsed by practice guidelines for use in patients with New York Heart Association class IV heart failure with a reduced ejection fraction because of limited clinical experience in this population.

Objective: To compare treatment with sacubitril/valsartan treatment with valsartan in patients with advanced heart failure and a reduced ejection fraction and recent New York Heart Association class IV symptoms.

Design, Setting, And Participants: A double-blind randomized clinical trial was conducted; a total of 335 patients with advanced heart failure were included. The trial began on March 2, 2017, and was stopped early on March 23, 2020, owing to COVID-19 risk.

Intervention: Patients were randomized to receive sacubitril/valsartan (target dose, 200 mg twice daily) or valsartan (target dose, 160 mg twice daily) in addition to recommended therapy.

Main Outcomes And Measures: The area under the curve (AUC) for the ratio of N-terminal pro-brain natriuretic peptide (NT-proBNP) compared with baseline measured through 24 weeks of therapy.

Results: Of the 335 patients included in the analysis, 245 were men (73%); mean (SD) age was 59.4 (13.5) years. Seventy-two eligible patients (18%) were not able to tolerate sacubitril/valsartan, 100 mg/d, during the short run-in period, and 49 patients (29%) discontinued sacubitril/valsartan during the 24 weeks of the trial. The median NT-proBNP AUC for the valsartan treatment arm (n = 168) was 1.19 (IQR, 0.91-1.64), whereas the AUC for the sacubitril/valsartan treatment arm (n = 167) was 1.08 (IQR, 0.75-1.60). The estimated ratio of change in the NT-proBNP AUC was 0.95 (95% CI 0.84-1.08; P = .45). Compared with valsartan, treatment with sacubitril/valsartan did not improve the clinical composite of number of days alive, out of hospital, and free from heart failure events. Aside from a statistically significant increase in non-life-threatening hyperkalemia in the sacubitril/valsartan arm (28 [17%] vs 15 [9%]; P = .04), there were no observed safety concerns.

Conclusions And Relevance: The findings of this trial showed that, in patients with chronic advanced heart failure with a reduced ejection fraction, there was no statistically significant difference between sacubitril/valsartan and valsartan with respect to reducing NT-proBNP levels.

Trial Registration: ClinicalTrials.gov Identifier: NCT02816736.
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http://dx.doi.org/10.1001/jamacardio.2021.4567DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8567189PMC
January 2022

A Novel Code Team Leader Card to Improve Leader Identification.

J Patient Cent Res Rev 2021 18;8(4):354-359. Epub 2021 Oct 18.

Pediatric Simulation Program, Pediatric Critical Care Medicine, Advocate Children's Hospital, Advocate Aurora Health, Park Ridge, IL.

Prompt and clear code team leader identification is vital in effective cardiopulmonary resuscitation (CPR), and pediatric trainees often have limited experience in these scenarios. This project sought to develop a tangible object that provided clear leader identification and assisted in code team management and simulated team training. A Code Team Leader Card (CTLC) was designed to provide clear leader identification while simultaneously providing a cognitive aid via integration of pediatric advanced life support (PALS) algorithms. Additionally, CTLC served to occupy the leader's hands to limit their ability to intervene on procedural tasks. The CTLC was incorporated into pediatric resident simulation training, and pre- and postintervention survey data were analyzed. Analysis particularly focused on whether "a leader was clearly identified by all team members." The relationship between CTLC implementation and consistent leader recognition was evaluated using chi-squared test, and secondary qualitative data were obtained via debriefing sessions. Pediatric residents completed 131 surveys prior to CTLC implementation and 41 surveys after implementation. Consistent code team leader recognition increased significantly from 61.8% (81 of 131) pre-CTLC to 80.5% (33 of 41) after introduction of CTLC (P=0.027). Participants commented on the benefits of CTLC during debriefing sessions. Use of a CTLC significantly improved leader recognition during simulated CPR. Inclusion of PALS algorithms led to normalization and increased utilization of these adjunct materials. The CTLC provided a secondary benefit of occupying the leader's hands, thereby allowing that person to focus on overseeing the team rather than assisting with procedural tasks.
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http://dx.doi.org/10.17294/2330-0698.1847DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8530241PMC
October 2021

An early relook identifies high-risk trajectories in ambulatory advanced heart failure.

J Heart Lung Transplant 2022 Jan 16;41(1):104-112. Epub 2021 Sep 16.

Cardiovascular Medicine, Brigham and Women's Hospital, Boston, Massachusetts.

Introduction: Patients with ambulatory advanced heart failure (HF) are increasingly considered for durable mechanical circulatory support (MCS) and heart transplantation and their effective triage requires careful assessment of the clinical trajectory.

Methods: REVIVAL, a prospective, observational study, enrolled 400 ambulatory advanced HF patients from 21 MCS/transplant centers in 2015-2016. Study design included a clinical re-assessment of Interagency Registry for Mechanically Assisted Circulatory Support (INTERMACS) profile within 120 days after enrollment. The prognostic impact of a worsening INTERMACS Profile assigned by the treating physician was assessed at 1 year after the Early Relook.

Results: Early Relook was done in 325 of 400 patients (81%), of whom 24% had a worsened INTERMACS Profile, associated with longer HF history and worse baseline INTERMACS profile, but no difference in baseline LVEF (median 0.20), 6-minute walk, quality of life, or other baseline parameters. Early worsening predicted higher rate of the combined primary endpoint of death, urgent MCS, or urgent transplant by 1 year after Early Relook, (28% vs 15%), with hazard ratio 2.2 (95% CI 1.2- 3.8; p = .006) even after adjusting for baseline INTERMACS Profile and Seattle HF Model score. Deterioration to urgent MCS occurred in 14% vs 5% (p = .006) during the year after Early Relook.

Conclusions: Early Relook identifies worsening of INTERMACS Profile in a significant population of ambulatory advanced HF, who had worse outcomes over the subsequent year. Early reassessment of ambulatory advanced HF patients should be performed to better define the trajectory of illness and inform triage to advanced therapies.
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http://dx.doi.org/10.1016/j.healun.2021.09.003DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8742755PMC
January 2022

Fulminant cardiogenic shock due to cardiac sarcoidosis.

J Community Hosp Intern Med Perspect 2021 20;11(5):673-677. Epub 2021 Sep 20.

Division of Cardiology, Inova Heart and Vascular Institute, Falls Church, VA, USA.

This case describes a 57-year-old man with unrecognized cardiac sarcoidosis who presented with progressive heart failure leading to cardiogenic shock. He required extracorporeal membrane oxygenation (ECMO) as a bridge to orthotopic heart transplantation. The case highlights the potential acute and severe electrical and hemodynamic manifestations of cardiac sarcoidosis.
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http://dx.doi.org/10.1080/20009666.2021.1948668DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8462928PMC
September 2021

Response by Shah et al to Letter Regarding Article, "Cell-Free DNA to Detect Heart Allograft Acute Rejection".

Circulation 2021 09 7;144(10):e198-e199. Epub 2021 Sep 7.

Genomic Research Alliance for Transplantation (GRAfT), Bethesda, MD (P.S., S.A-E., I.T., S.H., E.F., K.S., M.E.R., S.S.N., H.K., U.F., A.B., A.M., K.B., Y.Y., M.K.J., C.Marboe, G.J.B., H.A.V.).

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http://dx.doi.org/10.1161/CIRCULATIONAHA.121.055697DOI Listing
September 2021

LVAD decommissioning for myocardial recovery: Long-term ventricular remodeling and adverse events.

J Heart Lung Transplant 2021 12 11;40(12):1560-1570. Epub 2021 Aug 11.

Heart Failure, Mechanical Circulatory Support and Transplantation, Inova Heart and Vascular Institute, Falls Church, Virginia. Electronic address:

Background: Left ventricular assist devices (LVADs) mechanically unload the heart and coupled with neurohormonal therapy can promote reverse cardiac remodeling and myocardial recovery. Minimally invasive LVAD decommissioning with the device left in place has been reported to be safe over short-term follow-up. Whether device retention reduces long-term safety, or sustainability of recovery is unknown.

Methods: This is a dual-center retrospective analysis of patients who had achieved responder status (left ventricular ejection fraction, LVEF ≥40% and left ventricular internal diastolic diameter, LVIDd ≤6.0 cm) and underwent elective LVAD decommissioning for myocardial recovery from May 2010 to January 2020. All patients had outflow graft closure and driveline resection with the LVAD left in place. Emergent LVAD decommissioning for an infection or device thrombosis was excluded. Patients were followed with serial echocardiography for up to 3-years. The primary clinical outcome was survival free of heart failure hospitalization, LVAD reimplantation, or transplant.

Results: During the study period 515 patients received an LVAD and 29 (5.6%) achieved myocardial recovery, 12 patients underwent total device explantation or urgent device decommissioning, 17 patients underwent elective LVAD decommissioning, and were included in the analysis. Median age of patients at LVAD implantation was 42 years (interquartile range, IQR: 25-54 years), all had a nonischemic cardiomyopathy, and 5 (29%) were female. At LVAD implantation, median LVEF was 10% (IQR: 5%-15%), and LVIDd 6.6 cm (IQR: 5.8-7.1 cm). There were 11 hydrodynamically levitated centrifugal-flow (65%), and 6 axial-flow LVADs (35%). The median duration of LVAD support before decommissioning was 28.7 months (range 13.5-36.2 months). As compared to the turndown study parameters, 1-month post-decommissioning, median LVEF decreased from 55% to 48% (p = 0.03), and LVIDd increased from 4.8 cm to 5.2 cm (p = 0.10). There was gradual remodeling until 6 months, after which there was no statistical difference on follow-up through 3-years (LVEF 42%, LVIDd 5.6 cm). Recurrent infections affected 41% of patients leading to 3 deaths and 1 complete device explant. Recurrent HF occurred in 1 patient who required a transplant. Probability of survival free of HF, LVAD, or transplant was 94% at 1-year, and 78% at 3-years.

Conclusions: LVAD decommissioning for myocardial recovery was associated with excellent long-term survival free from recurrent heart failure and preservation of ventricular size and function up to 3-years. Reducing the risk of recurrent infections, remains an important therapeutic goal for this management strategy.
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http://dx.doi.org/10.1016/j.healun.2021.08.001DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8627486PMC
December 2021

RNA sequencing of blood in coronary artery disease: involvement of regulatory T cell imbalance.

BMC Med Genomics 2021 09 3;14(1):216. Epub 2021 Sep 3.

The St. Laurent Institute, Vancouver, WA, USA.

Background: Cardiovascular disease had a global prevalence of 523 million cases and 18.6 million deaths in 2019. The current standard for diagnosing coronary artery disease (CAD) is coronary angiography. Surprisingly, despite well-established clinical indications, up to 40% of the one million invasive cardiac catheterizations return a result of 'no blockage'. The present studies employed RNA sequencing of whole blood to identify an RNA signature in patients with angiographically confirmed CAD.

Methods: Whole blood RNA was depleted of ribosomal RNA (rRNA) and analyzed by single-molecule sequencing of RNA (RNAseq) to identify transcripts associated with CAD (TRACs) in a discovery group of 96 patients presenting for elective coronary catheterization. The resulting transcript counts were compared between groups to identify differentially expressed genes (DEGs).

Results: Surprisingly, 98% of DEGs/TRACs were down-regulated ~ 1.7-fold in patients with mild to severe CAD (> 20% stenosis). The TRACs were independent of comorbid risk factors for CAD, such as sex, hypertension, and smoking. Bioinformatic analysis identified an enrichment in transcripts such as FoxP1, ICOSLG, IKZF4/Eos, SMYD3, TRIM28, and TCF3/E2A that are likely markers of regulatory T cells (Treg), consistent with known reductions in Tregs in CAD. A validation cohort of 80 patients confirmed the overall pattern (92% down-regulation) and supported many of the Treg-related changes. TRACs were enriched for transcripts associated with stress granules, which sequester RNAs, and ciliary and synaptic transcripts, possibly consistent with changes in the immune synapse of developing T cells.

Conclusions: These studies identify a novel mRNA signature of a Treg-like defect in CAD patients and provides a blueprint for a diagnostic test for CAD. The pattern of changes is consistent with stress-related changes in the maturation of T and Treg cells, possibly due to changes in the immune synapse.
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http://dx.doi.org/10.1186/s12920-021-01062-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8414682PMC
September 2021

Prognostic role of anemia in heart failure with preserved ejection fraction: A systematic review and meta-analysis.

Indian Heart J 2021 Jul-Aug;73(4):521-523. Epub 2021 Jun 25.

Department of Critical Care Medicine, St John's Medical College Hospital, Bengaluru, Karnataka, India. Electronic address:

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http://dx.doi.org/10.1016/j.ihj.2021.06.011DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8424263PMC
November 2021

METTL14 facilitates global genome repair and suppresses skin tumorigenesis.

Proc Natl Acad Sci U S A 2021 08;118(35)

Department of Medicine, Section of Dermatology, University of Chicago, Chicago, IL 60637;

Global genome repair (GGR), a subpathway of nucleotide excision repair, corrects bulky helix-distorting DNA lesions across the whole genome and is essential for preventing mutagenesis and skin cancer. Here, we show that METTL14 (methyltransferase-like 14), a critical component of the N-methyladenosine (mA) RNA methyltransferase complex, promotes GGR through regulating mA mRNA methylation-mediated DDB2 translation and suppresses ultraviolet B (UVB) radiation-induced skin tumorigenesis. UVB irradiation down-regulates METTL14 protein through NBR1-dependent selective autophagy. METTL14 knockdown decreases GGR and DDB2 abundance. Conversely, overexpression of wild-type METTL14 but not its enzymatically inactive mutant increases GGR and DDB2 abundance. METTL14 knockdown decreases mA methylation and translation of the DDB2 transcripts. Adding DDB2 reverses the GGR repair defect in METTL14 knockdown cells, indicating that METTL14 facilitates GGR through regulating DDB2 mA methylation and translation. Similarly, knockdown of YTHDF1, an mA reader promoting translation of mA-modified transcripts, decreases DDB2 protein levels. Both METTL14 and YTHDF1 bind to the DDB2 transcript. In mice, skin-specific heterozygous METTL14 deletion increases UVB-induced skin tumorigenesis. Furthermore, METTL14 as well as DDB2 is down-regulated in human and mouse skin tumors and by chronic UVB irradiation in mouse skin, and METTL14 level is associated with the DDB2 level, suggesting a tumor-suppressive role of METTL14 in UVB-associated skin tumorigenesis in association with DDB2 regulation. Taken together, these findings demonstrate that METTL14 is a target for selective autophagy and acts as a critical epitranscriptomic mechanism to regulate GGR and suppress UVB-induced skin tumorigenesis.
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http://dx.doi.org/10.1073/pnas.2025948118DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8536359PMC
August 2021

Cardiovascular implantable electronic device therapy in patients with left ventricular assist devices: insights from TRAViATA.

Int J Cardiol 2021 10 23;340:26-33. Epub 2021 Aug 23.

Department of Cardiology, Clinical Sciences, Lund University and Skåne University Hospital, Lund, Sweden.

Background: There is conflicting observational data on the survival benefit cardiac implantable electronic devices (CIED) in patients with LVADs.

Methods: Patients in whom an LVAD was implanted between January 2008 and April 2017 in the multinational Trans-Atlantic Registry on VAD and Transplant (TRAViATA) registry were separated into four groups based on the presence of CIED prior to LVAD implantation: none (n = 146), implantable cardiac defibrillator (ICD) (n = 239), cardiac resynchronization without defibrillator (CRT-P) (n = 28), and CRT with defibrillator (CRT-D) (n = 111).

Results: A total of 524 patients (age 52 years ±12, 84.4% male) were followed for 354 (interquartile range: 166-701) days. After multivariable adjustment, there were no differences in survival across the groups. In comparison to no device, only CRT-D was associated with late right ventricular failure (RVF) (hazard ratio 2.85, 95% confidence interval [CI] 1.42-5.72, p = 0.003). There was no difference in risk of early RVF across the groups or risk of ICD shocks between those with ICD and CRT-D.

Conclusion: In a multinational registry of patients with LVADs, there were no differences in survival with respect to CIED subtype. However, patients with a pre-existing CRT-D had a higher likelihood of late RVF suggesting significant long-term morbidity in those with devices capable of LV‑lead pacing post LVAD implantation.
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http://dx.doi.org/10.1016/j.ijcard.2021.08.033DOI Listing
October 2021

Long-term survival on LVAD support: Device complications and end-organ dysfunction limit long-term success.

J Heart Lung Transplant 2021 Jul 24. Epub 2021 Jul 24.

Henry Ford Hospitals, Detroit, Michigan. Electronic address:

Background: Preoperative variables can predict short term left ventricular assist device (LVAD) survival, but predictors of extended survival remain insufficiently characterized.

Method: Patients undergoing LVAD implant (2012-2018) in the Intermacs registry were grouped according to time on support: short-term (<1 year, n = 7,483), mid-term (MT, 1-3 years, n = 5,976) and long-term (LT, ≥3 years, n = 3,015). Landmarked hazard analyses (adjusted hazard ratio, HR) were performed to identify correlates of survival after 1 and 3 years of support.

Results: After surviving 1 year of support, additional LVAD survival was less likely in older (HR 1.15 per decade), Caucasian (HR 1.22) and unmarried (HR 1.16) patients (p < 0.05). After 3 years of support, only 3 preoperative characteristics (age, race, and history of bypass surgery, p < 0.05) correlated with extended survival. Postoperative events most negatively influenced achieving LT survival. In those alive at 1 year or 3 years, the occurrence of postoperative renal (creatinine HR MT = 1.09; LT HR = 1.10 per mg/dl) and hepatic dysfunction (AST HR MT = 1.29; LT HR = 1.34 per 100 IU), stroke (MT HR = 1.24; LT HR = 1.42), infection (MT HR = 1.13; LT HR = 1.10), and/or device malfunction (MT HR = 1.22; LT HR = 1.46) reduced extended survival (all p ≤ 0.03).

Conclusions: Success with LVAD therapy hinges on achieving long term survival in more recipients. After 1 year, extended survival is heavily constrained by the occurrence of adverse events and postoperative end-organ dysfunction. The growth of destination therapy intent mandates that future LVAD studies be designed with follow up sufficient for capturing outcomes beyond 24 months.
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http://dx.doi.org/10.1016/j.healun.2021.07.011DOI Listing
July 2021

Association between acute myocardial infarction and death in 386 patients with a thrombus straddling a patent foramen ovale.

Int J Cardiol 2021 Nov 7;342:1-6. Epub 2021 Jul 7.

Department of Clinical Neurological Sciences, Schulich School of Medicine and Dentistry, Western University, London, ON, Canada; Heart & Brain Laboratory, Western University, London, ON, Canada; Department of Epidemiology and Biostatistics, Schulich School of Medicine and Dentistry, Western University, London, ON, Canada; Department of Anatomy and Cell Biology, Schulich School of Medicine and Dentistry, Western University, London, ON, Canada; Robarts Research Institute, Western University, London, ON, Canada; Lawson Research Institute, London, ON, Canada. Electronic address:

Backgorund: Right atrial thrombi are rarely found straddling a patent foramen ovale (PFO). A thrombus straddling a PFO (TSPFO), also known as impending paradoxical embolism, is a medical emergency associated with up to 11.5% risk of death within 24 h of being diagnosed. We hypothesized that acute myocardial infarction (MI) and ischemic stroke (IS) diagnosed upon the admission of patients with TSPFO are associated with increased risk of death. We also investigated if specific acute therapies are associated with reduced in-hospital mortality.

Methods: We performed a systematic search including case reports and series of adult patients with TSPFO published from 1950 to October 30, 2020. We gathered patient-level data and we applied a logistic regression model to evaluate on the risk of in-hospital death. We performed time-trends and several sensitivity analyses.

Results: We included 386 cases with a TSPFO comprised in 359 publications. The median age was 61 years and 51.2% were females. Fifty (13.0%) patients died during hospital stay, 82 (21.2%) had an acute IS, and 18 (4.6%) had an acute MI diagnosed upon admission. Acute MI (OR 7.83, 95%CI 2.70-22.7; P < 0.0001), but not IS, was associated with increased risk of death. Right atrial thrombectomy was associated with a 65% decreased in-hospital mortality (OR 0.35, 95%CI 0.18-0.70, P = 0.003). Results remained unchanged on sensitivity analyses.

Conclusion: In this systematic review of 386 cases of TSPFO, acute MI but not IS was associated with 8-fold increased risk of death, while surgical thrombectomy was associated with a significant 65% reduction of in-hospital mortality.
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http://dx.doi.org/10.1016/j.ijcard.2021.07.007DOI Listing
November 2021

Determinants of in-hospital death in patients with a thrombus straddling a patent foramen ovale: protocol of a systematic review.

F1000Res 2020 10;9:1437. Epub 2020 Dec 10.

Heart & Brain Laboratory, Western University, London, Ontario, N6C1C4, Canada.

Thrombi identified on echocardiography at the time of straddling a patent foramen ovale (PFO) constitute a medical emergency with an associated imminent risk of death.  Ischemic stroke (IS) and myocardial infarction (MI) occurring in patients with a thrombus straddling a PFO (TSPFO) may be associated with increased risk of in-hospital death. Variables associated with increased risk of death in women and men may be different. We will perform a systematic review of case reports and cases series of patients with a TSPFO to assess if IS and MI are associated with increased risk of in-hospital death and we will further stratify analyses by sex. This systematic review will include all case reports and case series of adult patients (18-year-old or older) with echocardiographic or pathological (e.g. at autopsy for older reports) evidence of a TSPFO published between inception and June 30, 2020, in any language. We will search in PubMed and Embase databases. Two reviewers will independently screen titles and abstracts, retrieve full texts, and extract the data in a predesigned form. We will apply a multivariable logistic regression analysis to estimate the association of IS and MI with in-hospital mortality. We will stratify analyses by sex.  IS and MI in patients with TSPFO could potentially be associated with worse outcomes if they are not timely identified or left untreated.  Both acute IS and MI require specific treatment (e.g. thrombolysis, primary coronary intervention, or mechanical thrombectomy) that may be influenced by the therapy instituted for the TSPFO. Knowing the incidence of acute IS and MI among patients diagnosed with TSPFO and whether they are associated with an increased risk of death would help to improve the management of this medical emergency. : CRD42020216118, PROSPERO.
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http://dx.doi.org/10.12688/f1000research.27622.2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8138489PMC
June 2021

Evidence-Based Assessment of Genes in Dilated Cardiomyopathy.

Circulation 2021 07 5;144(1):7-19. Epub 2021 May 5.

Department of Genetics, University Medical Center Utrecht, University of Utrecht, The Netherlands (J.P.v.T.).

Background: Each of the cardiomyopathies, classically categorized as hypertrophic cardiomyopathy, dilated cardiomyopathy (DCM), and arrhythmogenic right ventricular cardiomyopathy, has a signature genetic theme. Hypertrophic cardiomyopathy and arrhythmogenic right ventricular cardiomyopathy are largely understood as genetic diseases of sarcomere or desmosome proteins, respectively. In contrast, >250 genes spanning >10 gene ontologies have been implicated in DCM, representing a complex and diverse genetic architecture. To clarify this, a systematic curation of evidence to establish the relationship of genes with DCM was conducted.

Methods: An international panel with clinical and scientific expertise in DCM genetics evaluated evidence supporting monogenic relationships of genes with idiopathic DCM. The panel used the Clinical Genome Resource semiquantitative gene-disease clinical validity classification framework with modifications for DCM genetics to classify genes into categories on the basis of the strength of currently available evidence. Representation of DCM genes on clinically available genetic testing panels was evaluated.

Results: Fifty-one genes with human genetic evidence were curated. Twelve genes (23%) from 8 gene ontologies were classified as having definitive (, , , , , , , , , , ) or strong () evidence. Seven genes (14%; , , , , , , ) including 2 additional ontologies were classified as moderate evidence; these genes are likely to emerge as strong or definitive with additional evidence. Of these 19 genes, 6 were similarly classified for hypertrophic cardiomyopathy and 3 for arrhythmogenic right ventricular cardiomyopathy. Of the remaining 32 genes (63%), 25 (49%) had limited evidence, 4 (8%) were disputed, 2 (4%) had no disease relationship, and 1 (2%) was supported by animal model data only. Of the 16 evaluated clinical genetic testing panels, most definitive genes were included, but panels also included numerous genes with minimal human evidence.

Conclusions: In the curation of 51 genes, 19 had high evidence (12 definitive/strong, 7 moderate). It is notable that these 19 genes explain only a minority of cases, leaving the remainder of DCM genetic architecture incompletely addressed. Clinical genetic testing panels include most high-evidence genes; however, genes lacking robust evidence are also commonly included. We recommend that high-evidence DCM genes be used for clinical practice and that caution be exercised in the interpretation of variants in variable-evidence DCM genes.
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http://dx.doi.org/10.1161/CIRCULATIONAHA.120.053033DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8247549PMC
July 2021

Framework to Classify Reverse Cardiac Remodeling With Mechanical Circulatory Support: The Utah-Inova Stages.

Circ Heart Fail 2021 05 5;14(5):e007991. Epub 2021 May 5.

Utah Transplant Affiliated Hospitals (U.T.A.H.) Cardiac Transplant Program, University of Utah Health and School of Medicine, Intermountain Medical Center and Salt Lake Veterans Affairs Medical Center (I.T., R.A., O.W.-P., M.Y., J.S., J.C.F., C.P.K., L.B.C., S.S.D., C.H.S., A.K., S.G.D.).

Background: Variable definitions and an incomplete understanding of the gradient of reverse cardiac remodeling following continuous flow left ventricular assist device (LVAD) implantation has limited the field of myocardial plasticity. We evaluated the continuum of LV remodeling by serial echocardiographic imaging to define 3 stages of reverse cardiac remodeling following LVAD.

Methods: The study enrolled consecutive LVAD patients across 4 study sites. A blinded echocardiographer evaluated the degree of structural (LV internal dimension at end-diastole [LVIDd]) and functional (LV ejection fraction [LVEF]) change after LVAD. Patients experiencing an improvement in LVEF ≥40% and LVIDd ≤6.0 cm were termed responders, absolute change in LVEF of ≥5% and LVEF <40% were termed partial responders, and the remaining patients with no significant improvement in LVEF were termed nonresponders.

Results: Among 358 LVAD patients, 34 (10%) were responders, 112 (31%) partial responders, and the remaining 212 (59%) were nonresponders. The use of guideline-directed medical therapy for heart failure was higher in partial responders and responders. Structural changes (LVIDd) followed a different pattern with significant improvements even in patients who had minimal LVEF improvement. With mechanical unloading, the median reduction in LVIDd was -0.6 cm (interquartile range [IQR], -1.1 to -0.1 cm; nonresponders), -1.1 cm (IQR, -1.8 to -0.4 cm; partial responders), and -1.9 cm (IQR, -2.9 to -1.1 cm; responders). Similarly, the median change in LVEF was -2% (IQR, -6% to 1%), 9% (IQR, 6%-14%), and 27% (IQR, 23%-33%), respectively.

Conclusions: Reverse cardiac remodeling associated with durable LVAD support is not an all-or-none phenomenon and manifests in a continuous spectrum. Defining 3 stages across this continuum can inform clinical management, facilitate the field of myocardial plasticity, and improve the design of future investigations.
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http://dx.doi.org/10.1161/CIRCHEARTFAILURE.120.007991DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8137588PMC
May 2021

Autophagy of the mA mRNA demethylase FTO is impaired by low-level arsenic exposure to promote tumorigenesis.

Nat Commun 2021 04 12;12(1):2183. Epub 2021 Apr 12.

Department of Medicine, Section of Dermatology, University of Chicago, Chicago, IL, USA.

Here we show that FTO as an N-methyladenosine (mA) RNA demethylase is degraded by selective autophagy, which is impaired by low-level arsenic exposure to promote tumorigenesis. We found that in arsenic-associated human skin lesions, FTO is upregulated, while mA RNA methylation is downregulated. In keratinocytes, chronic relevant low-level arsenic exposure upregulated FTO, downregulated mA RNA methylation, and induced malignant transformation and tumorigenesis. FTO deletion inhibited arsenic-induced tumorigenesis. Moreover, in mice, epidermis-specific FTO deletion prevented skin tumorigenesis induced by arsenic and UVB irradiation. Targeting FTO genetically or pharmacologically inhibits the tumorigenicity of arsenic-transformed tumor cells. We identified NEDD4L as the mA-modified gene target of FTO. Finally, arsenic stabilizes FTO protein through inhibiting p62-mediated selective autophagy. FTO upregulation can in turn inhibit autophagy, leading to a positive feedback loop to maintain FTO accumulation. Our study reveals FTO-mediated dysregulation of mRNA mA methylation as an epitranscriptomic mechanism to promote arsenic tumorigenicity.
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http://dx.doi.org/10.1038/s41467-021-22469-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8041927PMC
April 2021

Use of Innovative SPECT Techniques in the Presurgical Evaluation of Patients with Nonlesional Extratemporal Drug-Resistant Epilepsy.

Mol Imaging 2021 2;2021:6614356. Epub 2021 Mar 2.

University of Pittsburgh Comprehensive Epilepsy Center (UPCEC), Pittsburgh, USA.

Up to 30% of patients with epilepsy may not respond to antiepileptic drugs. Patients with drug-resistant epilepsy (DRE) should undergo evaluation for seizure onset zone (SOZ) localization to consider surgical treatment. Cases of drug-resistant nonlesional extratemporal lobe epilepsy (ETLE) pose the biggest challenge in localizing the SOZ and require multiple noninvasive diagnostic investigations before planning the intracranial monitoring (ICM) or direct resection. Ictal Single Photon Emission Computed Tomography (i-SPECT) is a unique functional diagnostic tool that assesses the SOZ using the localized hyperperfusion that occurs early in the seizure. Subtraction ictal SPECT coregistered to MRI (SISCOM), statistical ictal SPECT coregistered to MRI (STATISCOM), and PET interictal subtracted ictal SPECT coregistered with MRI (PISCOM) are innovative SPECT methods for the determination of the SOZ. This article comprehensively reviews SPECT and sheds light on its vital role in the presurgical evaluation of the nonlesional extratemporal DRE.
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http://dx.doi.org/10.1155/2021/6614356DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7953581PMC
October 2021

Frequency, Trend, Predictors, and Impact of Gastrointestinal Bleeding in Atrial Fibrillation Hospitalizations.

Am J Cardiol 2021 05 30;146:29-35. Epub 2021 Jan 30.

Department of Internal Medicine, University of Nevada Reno School of Medicine, Reno, Nevada. Electronic address:

Anticoagulation alone or in combination with other treatment strategies are implemented to reduce the risk of stroke in patients with atrial fibrillation (AF). Gastrointestinal bleeding (GIB) is a common complication of oral anticoagulation with a prevalence of 1% to 3% in patients on long term oral anticoagulation. We analyzed the national inpatient sample database from the year 2005 to 2015 to report evidence on the frequency, trends, predictors, clinical outcomes, and economic burden of GIB among AF hospitalizations. A total of 34,260,000 AF hospitalizations without GIB and 1,846,259 hospitalizations with GIB (5.39%) were included. The trend of AF hospitalizations with GIB per 100 AF hospitalizations remained stable from the year 2005 to 2015 (p value = 0.0562). AF hospitalizations with GIB had a higher frequency of congestive heart failure, long term kidney disease, long term liver disease, anemia, and alcohol abuse compared with AF hospitalizations without GIB. AF hospitalizations with GIB had a higher odds of in-hospital mortality (Odds ratio (OR) 1.47; 95% Confidence interval (CI): 1.46 to 1.48, p-value <0.0001), mechanical ventilation (OR 1.69; 95% CI: 1.68 to 1.70, p-value <0.0001), and blood transfusion (OR 7.2; 95% CI: 7.17 to 7.22, P-value <0.0001) compared with AF hospitalizations without GIB. AF hospitalizations with GIB had a lower odds of stroke (OR 0.51; 95% CI: 0.51 to 0.52, p-value <0.0001) compared with AF hospitalizations without GIB. Further, AF hospitalizations with GIB had a higher median length of stay and cost of hospitalization compared with AF hospitalizations without GIB. In conclusion, the frequency of GIB is 5.4% in AF hospitalizations and the frequency of GIB remained stable in the last decade as shown in this analysis. When GIB occurs, it is associated with higher resource utilization. This study addresses a significant knowledge gap highlighting national temporal trends of GIB and associated outcomes in AF hospitalizations.
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http://dx.doi.org/10.1016/j.amjcard.2021.01.020DOI Listing
May 2021

The Society of Thoracic Surgeons Intermacs 2020 Annual Report.

Ann Thorac Surg 2021 03 16;111(3):778-792. Epub 2021 Jan 16.

Division of Cardiovascular Medicine, Henry Ford Hospital, Detroit, Michigan. Electronic address:

The Society of Thoracic Surgeons (STS)-Interagency Registry for Mechanically Assisted Circulatory Support (Intermacs) 2020 Annual Report reviews outcomes on 25,551 patients undergoing primary isolated continuous-flow left ventricular assist device (LVAD) implantation between 2010 and 2019. In 2019, 3198 primary LVADs were implanted, which is the highest annual volume in Intermacs history. Compared with the previous era (2010-2014), patients who received an LVAD in the most recent era (2015-2019) were more likely to be African American (26.8% vs 22.9%, P < .0001) and more likely to be bridged to durable LVAD with temporary mechanical support devices (36.8% vs 26.0%, P < .0001). In 2019, 50% of patients were INTERMACS Profile 1 or 2 before durable LVAD, and 73% received an LVAD as destination therapy. Magnetic levitation technology has become the predominant design, accounting for 77% of devices in 2019. The 1- and 2-year survival in the most recent era has improved compared with 2010 to 2014 (82.3% and 73.1% vs 80.5% and 69.1%, respectively; P < .0001). Major bleeding and infection continue to be the leading adverse events. Incident stroke has declined in the current era to 12.7% at 1 year. STS-Intermacs research publications are highlighted, and the new quality initiatives are introduced.
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http://dx.doi.org/10.1016/j.athoracsur.2020.12.038DOI Listing
March 2021

Meta-Analysis of Transcatheter Aortic Valve Implantation in Patients With Stenotic Bicuspid Versus Tricuspid Aortic Valve.

Am J Cardiol 2021 04 15;145:102-110. Epub 2021 Jan 15.

Department of Cardiovascular Medicine, University of Iowa Hospitals and Clinics, Iowa City, Iowa.

Most of the trials investigating the role of transcatheter aortic valve implantation (TAVI) across various strata of risk categories have excluded patients with bicuspid aortic stenosis (BAS) due to its anatomical complexities. The aim of this study was to perform a meta-analysis with meta-regression of studies comparing clinical, procedural, and after-procedural echocardiographic outcomes in BAS versus tricuspid aortic stenosis (TAS) patients who underwent TAVI. We searched the PubMed and Cochrane databases for relevant articles from the inception of the database to October 2019. Continuous and categorical variables were pooled using inverse variance and Mantel-Haenszel method, respectively, using the random-effect model. To rate the certainty of evidence for each outcome, we used the GRADE (Grading of Recommendations, Assessment, Development, and Evaluations) approach. Nineteen articles were included in the final analysis. There was no difference in the risk of 30-day mortality, 1-year mortality, 30-day cardiovascular mortality, major and/or life-threatening bleeding, major vascular complications, acute kidney injury, permanent pacemaker implantation, device success, annular rupture, after-procedural aortic valve area, and mean pressure gradient between the 2 groups. BAS patients who underwent TAVI had a higher risk of 30-day stroke, conversion to surgery, need for second valve implantation, and moderate to severe paravalvular leak. In conclusion, the present meta-analysis supports the feasibility of TAVI in surgically ineligible patients with BAS. However, the incidence of certain procedural complications such as stroke, conversion to surgery, second valve implantation, and paravalvular leak is higher among BAS patients compared with TAS patients, which must be discussed with the patient during the decision-making process.
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http://dx.doi.org/10.1016/j.amjcard.2020.12.085DOI Listing
April 2021

Cell-Free DNA to Detect Heart Allograft Acute Rejection.

Circulation 2021 03 13;143(12):1184-1197. Epub 2021 Jan 13.

Genomic Research Alliance for Transplantation, Bethesda, MD (S.A.-E., P.S., I.T., S.H., E.F., K.S., M.E.R., S.S.N., H.K., U.F., A.B., A.M., K.B., Y.Y., M.K.J., C.M., G.J.B., H.A.V.).

Background: After heart transplantation, endomyocardial biopsy (EMBx) is used to monitor for acute rejection (AR). Unfortunately, EMBx is invasive, and its conventional histological interpretation has limitations. This is a validation study to assess the performance of a sensitive blood biomarker-percent donor-derived cell-free DNA (%ddcfDNA)-for detection of AR in cardiac transplant recipients.

Methods: This multicenter, prospective cohort study recruited heart transplant subjects and collected plasma samples contemporaneously with EMBx for %ddcfDNA measurement by shotgun sequencing. Histopathology data were collected to define AR, its 2 phenotypes (acute cellular rejection [ACR] and antibody-mediated rejection [AMR]), and controls without rejection. The primary analysis was to compare %ddcfDNA levels (median and interquartile range [IQR]) for AR, AMR, and ACR with controls and to determine %ddcfDNA test characteristics using receiver-operator characteristics analysis.

Results: The study included 171 subjects with median posttransplant follow-up of 17.7 months (IQR, 12.1-23.6), with 1392 EMBx, and 1834 %ddcfDNA measures available for analysis. Median %ddcfDNA levels decayed after surgery to 0.13% (IQR, 0.03%-0.21%) by 28 days. Also, %ddcfDNA increased again with AR compared with control values (0.38% [IQR, 0.31-0.83%], versus 0.03% [IQR, 0.01-0.14%]; <0.001). The rise was detected 0.5 and 3.2 months before histopathologic diagnosis of ACR and AMR. The area under the receiver operator characteristic curve for AR was 0.92. A 0.25%ddcfDNA threshold had a negative predictive value for AR of 99% and would have safely eliminated 81% of EMBx. In addition, %ddcfDNA showed distinctive characteristics comparing AMR with ACR, including 5-fold higher levels (AMR ≥2, 1.68% [IQR, 0.49-2.79%] versus ACR grade ≥2R, 0.34% [IQR, 0.28-0.72%]), higher area under the receiver operator characteristic curve (0.95 versus 0.85), higher guanosine-cytosine content, and higher percentage of short ddcfDNA fragments.

Conclusions: We found that %ddcfDNA detected AR with a high area under the receiver operator characteristic curve and negative predictive value. Monitoring with ddcfDNA demonstrated excellent performance characteristics for both ACR and AMR and led to earlier detection than the EMBx-based monitoring. This study supports the use of %ddcfDNA to monitor for AR in patients with heart transplant and paves the way for a clinical utility study. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT02423070.
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http://dx.doi.org/10.1161/CIRCULATIONAHA.120.049098DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8221834PMC
March 2021

Transcriptomics in transplantation: More than just biomarkers of allograft rejection.

Am J Transplant 2021 06 21;21(6):2000-2001. Epub 2020 Dec 21.

Department of Medicine, Johns Hopkins School of Medicine, Baltimore, MD, USA.

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http://dx.doi.org/10.1111/ajt.16429DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8178244PMC
June 2021

Meta-Analysis of Early Intervention Versus Conservative Management for Asymptomatic Severe Aortic Stenosis.

Am J Cardiol 2021 01 13;138:85-91. Epub 2020 Oct 13.

Department of Cardiovascular Surgery, Marcus Valve Center, Piedmont Heart Institute, Atlanta, Georgia.

The main objective was to determine the optimal strategy for managing asymptomatic severe aortic stenosis between early intervention versus conservative management. We performed a systematic electronic search of the PubMed and Cochrane databases from the inception of the database to May 31, 2020. The Mantel Haenszel method with the Paule-Mandel estimator of Tau and Hartung-Knapp adjustment were used to calculate relative risk (RR) with a 95% confidence interval (CI) and 95% prediction interval. P curve analysis was used to assess publication bias and estimate the true effect of an intervention. All analysis was carried out using R version 3.6.2. A total of 9 studies were included in the final analysis, consisting of 1,775 patients with early intervention and 3,040 patients with conservative management. Early intervention as compared with conservative management was associated with reduced risk of all-cause mortality (RR 0.36, 95% CI 0.24 to 0.53), cardiac mortality (RR 0.36, 95% CI 0.27 to 0.48) and noncardiac mortality (RR 0.40, 95% CI 0.28 to 0.56). There was no difference in the risk of sudden cardiac death (RR 0.46, 95% CI 0.15 to 1.40), stroke (RR 0.79, 95% CI 0.17 to 3.64), myocardial infarction (RR 0.44, 95% CI 0.01 to 16.82) or heart failure hospitalization (RR 0.18, 95% CI 0.01 to 5.29) with early intervention compared with conservative management. In conclusion, early intervention is associated with reduced all-cause, cardiovascular, and noncardiovascular mortality without increasing any procedure-related clinical outcomes among asymptomatic severe AS patients. Hence, this meta-analysis supports early intervention instead of watchful waiting for the management of asymptomatic severe AS. This systematic review and meta-analysis was registered with PROSPERO- CRD42020188439.
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http://dx.doi.org/10.1016/j.amjcard.2020.10.013DOI Listing
January 2021

Navigating COVID-19 Testing: Special Considerations for the Cardiovascular Clinician.

Circulation 2020 12 16;142(24):2293-2295. Epub 2020 Oct 16.

Department of Pathology, University of Maryland School of Medicine, Baltimore (K.E.M.).

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http://dx.doi.org/10.1161/CIRCULATIONAHA.120.051183DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7736133PMC
December 2020

Left Bundle Branch Block: A Reversible Pernicious Effect of Lacosamide.

Cureus 2020 Sep 3;12(9):e10234. Epub 2020 Sep 3.

Department of Internal Medicine, New York Medical College, Metropolitan Hospital Center, New York, USA.

A 95-year-old male with a medical history of focal epilepsy presented with transient ischemic attack (TIA)/pre-syncope like symptoms. He was on lacosamide (LCM) and levetiracetam. On evaluation, he was found to have left bundle branch block (LBBB), sinus pause of three seconds, and 1st degree atrioventricular (AV) block. After holding LCM, electrocardiogram changes were reversed to baseline (before commencing LCM). In conclusion, to the best of our knowledge, this is the first case of reversible LBBB along with sinoatrial (SA) node and AV node dysfunction in an elderly male on LCM therapy.
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http://dx.doi.org/10.7759/cureus.10234DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7535942PMC
September 2020

Outcome of patients on heart transplant list treated with a continuous-flow left ventricular assist device: Insights from the TRans-Atlantic registry on VAd and TrAnsplant (TRAViATA).

Int J Cardiol 2021 02 18;324:122-130. Epub 2020 Sep 18.

University Hospital, Leuven, Belgium.

Background: Geographic variations in management and outcomes of individuals supported by continuous-flow left ventricular assist devices (CF-LVAD) between the United States (US) and Europe (EU) is largely unknown.

Methods: We created a retrospective, multinational registry of 524 patients who received a CF-LVAD (either HVAD or Heartmate II) between January 2008 and April 2017. Follow up spanned from date of CF-LVAD implant to post-HTx period with a median follow up of 44.8 months.

Results: The cohort included 299 (57.1%) EU and 225 (42.9%) US patients. Although the US cohort was significantly older with a higher prevalence of comorbidities, survival was similar between the cohorts (US 63.1%, EU 68.4% at 5 years, unadjusted log-rank test p = 0.43).Multivariate analyses suggested that older age, higher body mass index, elevated creatinine, use of temporary mechanical circulatory support prior CF-LVAD, and implantation of HVAD were associated with increased mortality. Among CF-LVAD patients undergoing HTx, the median time on CF-LVAD support was shorter in the US, meanwhile US donors were younger. Finally, the pattern of adverse events (stroke, gastrointestinal bleedings, late right ventricular failure, and driveline infection) during support differed significantly between US and EU.

Conclusions: Although waitlisted patients in the US on CF-LVAD have higher risk comorbid conditions, the overall outcome is similar in US and EU. Geographic variations with regards to donor characteristics, duration of CF-LVAD support prior to transplant, and adverse events on support can explain the disparity in the utilization of mechanical bridge to transplant strategy between US and EU.
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http://dx.doi.org/10.1016/j.ijcard.2020.09.026DOI Listing
February 2021
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