Publications by authors named "Steven Hsu"

98 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

Future Directions for Investigating Sacubitril-Valsartan in Left Ventricular Assist Device Patients.

ASAIO J 2021 Dec 22. Epub 2021 Dec 22.

Division of Cardiology, Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD.

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http://dx.doi.org/10.1097/MAT.0000000000001637DOI Listing
December 2021

Invasive Right Ventricular Pressure-Volume Analysis: Basic Principles, Clinical Applications, and Practical Recommendations.

Circ Heart Fail 2022 Jan 29;15(1):e009101. Epub 2021 Dec 29.

Division of Cardiology, Columbia University Medical Center, New York, NY (M.I.B., A.M., V.G.N., R.T.H., S.K.K., G.T.S., N.U., D.B.).

Right ventricular pressure-volume (PV) analysis characterizes ventricular systolic and diastolic properties independent of loading conditions like volume status and afterload. While long-considered the gold-standard method for quantifying myocardial chamber performance, it was traditionally only performed in highly specialized research settings. With recent advances in catheter technology and more sophisticated approaches to analyze PV data, it is now more commonly used in a variety of clinical and research settings. Herein, we review the basic techniques for PV loop measurement, analysis, and interpretation with the aim of providing readers with a deeper understanding of the strengths and limitations of PV analysis. In the second half of the review, we detail key scenarios in which right ventricular PV analysis has influenced our understanding of clinically relevant topics and where the technique can be applied to resolve additional areas of uncertainty. All told, PV analysis has an important role in advancing our understanding of right ventricular physiology and its contribution to cardiovascular function in health and disease.
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http://dx.doi.org/10.1161/CIRCHEARTFAILURE.121.009101DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8766922PMC
January 2022

Heart transplantation strategies in arrhythmogenic right ventricular cardiomyopathy: a tertiary ARVC centre experience.

ESC Heart Fail 2021 Dec 24. Epub 2021 Dec 24.

Division of Cardiac Surgery, Department of Surgery, Johns Hopkins School of Medicine, Baltimore, MD, USA.

Aims: End-stage heart failure necessitating evaluation for heart transplantation is increasingly recognized in arrhythmogenic right ventricular cardiomyopathy (ARVC). These patients present unique challenges in pre-transplant and peri-transplant management given their predominantly right ventricular (RV) failure and propensity for ventricular arrhythmias. We sought to utilize a tertiary ARVC referral and heart transplant centre experience to describe management of a series of patients with ARVC undergoing heart transplantation at our centre.

Methods And Results: We queried the Johns Hopkins ARVC Registry for all patients who underwent heart transplantation and further studied the subset undergoing transplantation at the Johns Hopkins Hospital. Patient demographics, clinical characteristics, and pre-transplant clinical course were obtained from the registry and electronic medical records. Of the 532 patients in the ARVC Registry, 63 (12%) underwent heart transplantation. Nine (six male) of these patients both had known ARVC prior to transplant and were transplanted at Johns Hopkins Hospital between 2006 and 2020 at a mean age of 42 ± 14 years old. Pathogenic ARVC genetic variants were identified in six (67%) patients, all of whom had variants in the plakophilin-2 (PKP2) gene. RV failure was universal with median right atrial to pulmonary capillary wedge pressure (RA/PCWP) ratio of 1.4 [interquartile range (IQR) 1.2-1.5] and median right ventricular stroke work index (RVSWI) of 0 g·m/m /beat (IQR 0-0.3). Six had a history of catheter ablation for ventricular arrhythmia with five of the six having at least three ablations. Transplant evaluation was initiated an average of 344 ± 407 days after first developing heart failure symptoms. The most common bridge to transplant support included inotropes (n = 3) and extracorporeal membrane oxygenation (ECMO) (n = 2). Contraindication to inotropes or mechanical support was common due to ventricular arrhythmia and RV predominant cardiomyopathy.

Conclusions: Heart transplantation is a curative treatment for ARVC, but due to frequent ventricular arrhythmias and RV predominant pathology, patients require unique considerations in regard to timing of evaluation, haemodynamic support options, and wait listing qualification.
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http://dx.doi.org/10.1002/ehf2.13757DOI Listing
December 2021

A disposable envelope for video-assisted intubating stylet during tracheal intubation in COVID-19 pandemic.

J Chin Med Assoc 2022 01;85(1):136

Department of Anesthesiology, Mennonite Christian Hospital, Hualien, Taiwan, ROC.

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http://dx.doi.org/10.1097/JCMA.0000000000000671DOI Listing
January 2022

Simulation and evaluation of the protective barrier enclosure for cardiopulmonary resuscitation.

Resusc Plus 2021 Dec 13;8:100180. Epub 2021 Nov 13.

Department of Anesthesiology, Mennonite Christian Hospital, Hualien, Taiwan.

Introduction: The COVID-19 pandemic has presented a significant challenge for infection prevention and control during airway management in anaesthesia and critical care. The protective barrier enclosure has been described and studied particularly for perioperative anaesthesia use. The potential use of the protective barrier enclosure during cardiopulmonary resuscitation has been poorly explored in the current literature. This work aims to demonstrate the potential of protective barrier enclosure in limiting aerosol dispersion during cardiopulmonary resuscitation delivery.

Methods: A proof-of-concept simulation study was conducted to evaluate the protective properties of the protective barrier enclosure during cardiopulmonary resuscitation. Aerosol was simulated using a fluorescent dye trapped within the manikin. Three different methods of cardiopulmonary resuscitation delivery with a protective barrier enclosure applied over the manikin's head were conducted. The first method simulated a chest compression only cardiopulmonary resuscitation, the second method also used chest compressions only, with a face mask fitted on the victim, while the third method, the victim was given chest compression and bag-valve-mask ventilation by two rescuers.

Results: In the first method, release of aerosol from the manikin's mouth was observed during chest compression, while in second method, most of the aerosol was trapped within the face mask, with only minor leaking. However, when bag-valve-mask ventilation was delivered, the aerosol leaked out at high speed around the bag-valve-mask seal. No aerosol condensation was found outside of the protective barrier enclosure in all scenes.

Conclusion: Protective barrier enclosure may reduce aerosol exposure to the rescuers during out-of-hospital cardiac arrest.
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http://dx.doi.org/10.1016/j.resplu.2021.100180DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8590516PMC
December 2021

Posttransplant Long-Term Outcomes for Patients with Ventricular Assist Devices on the Heart Transplant Waitlist.

ASAIO J 2021 Nov 3. Epub 2021 Nov 3.

Johns Hopkins School of Medicine, Baltimore, Maryland Cardiac Surgery, Johns Hopkins Hospital, Baltimore, Maryland Department of Surgery, University of Colorado School of Medicine, Aurora, Colorado Division of Cardiology, Johns Hopkins School of Medicine, Baltimore, Maryland.

Ventricular assist devices (LVADs) are commonly used in end-stage heart failure for mechanical circulatory support as a bridge to heart transplantation. However, LVADs' long-term effects on posttransplant survival are unknown. We sought to compare long-term mortality after transplantation for patients with and without LVADs. Using the Organ Procurement and Transplantation Network database, we investigated LVADs' impact on long-term (3 month, 1 year, 2 years, 5 years, and 8 years) posttransplant mortality risk for all heart transplant recipients between 2010 and 2019. Time-to-event regression analysis quantified mortality risk by LVAD status in both unconditional and conditional survival analyses. Of 20,113 transplant recipients, 8,999 (45%) had a LVAD while on the waitlist. Among those who died after transplantation, patients with LVADs on average died sooner (1.8 years) than patients without LVADs (3.0 years; p < 0.01). On multivariable analysis, patients with LVADs had a 44% higher mortality risk within the first 3 months posttransplant (HR = 1.44, p = 0.03). There was no significant difference in mortality risk between patients who did and did not have pretransplant LVADs after 1, 2, and 5 years of posttransplant conditional survival. While LVAD patients have a survival disadvantage in the first year posttransplant, conditional survival analysis demonstrated no difference in mortality risk between patients with and without LVADs beyond 1 year of follow up. Of the patients who died posttransplant, patients with LVADs on average died sooner than patients without LVADs.
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http://dx.doi.org/10.1097/MAT.0000000000001611DOI Listing
November 2021

Quality of Heart Failure Care in the Intensive Care Unit.

J Card Fail 2021 10;27(10):1111-1125

The Division of Cardiology, Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland.

Patients with heart failure (HF) who are seen in an intensive care unit (ICU) manifest the highest-risk, most complex and most resource-intensive disease states. These patients account for a large relative proportion of days spent in an ICU. The paradigms by which critical care is provided to patients with HF are being reconsidered, including consideration of various multidisciplinary ICU staffing models and the development of acute-response teams. Traditional HF quality initiatives have centered on the peri- and postdischarge period in attempts to improve adherence to guideline-directed therapies and reduce readmissions. There is a compelling rationale for expanding high-quality efforts in treating patients with HF who are receiving critical care so we can improve outcomes, reduce preventable harm, improve teamwork and resource use, and achieve high health-system performance. Our goal is to answer the following question: For a patient with HF in the ICU, what is required for the provision of high-quality care? Herein, we first review the epidemiology of HF syndromes in the ICU and identify relevant critical care and quality stakeholders in HF. We next discuss the tenets of high-quality care for patients with HF in the ICU that will optimize critical care outcomes, such as ICU staffing models and evidence-based management of cardiac and noncardiac disease. We discuss strategies to mitigate preventable harm, improve ICU culture and conduct outcomes review, and we conclude with our summative vision of high-quality of ICU care for patients with HF; our vision includes clinical excellence, teamwork and ICU culture.
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http://dx.doi.org/10.1016/j.cardfail.2021.08.001DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8514052PMC
October 2021

Right ventricular function as assessed by cardiac magnetic resonance imaging-derived strain parameters compared to high-fidelity micromanometer catheter measurements.

Pulm Circ 2021 Oct-Dec;11(4):20458940211032529. Epub 2021 Sep 24.

Division of Pulmonary and Critical Care Medicine, Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD, USA.

Right ventricular function has prognostic significance in patients with pulmonary hypertension. We evaluated whether cardiac magnetic resonance-derived strain and strain rate parameters could reliably reflect right ventricular systolic and diastolic function in precapillary pulmonary hypertension. End-systolic elastance and the time constant of right ventricular relaxation tau, both derived from invasive high-fidelity micromanometer catheter measurements, were used as gold standards for assessing systolic and diastolic right ventricular function, respectively. Nineteen consecutive precapillary pulmonary hypertension patients underwent cardiac magnetic resonance and right heart catheterization prospectively. Cardiac magnetic resonance data were compared with those of 19 control subjects. In pulmonary hypertension patients, associations between strain- and strain rate-related parameters and invasive hemodynamic parameters were evaluated. Longitudinal peak systolic strain, strain rate, and early diastolic strain rate were lower in PAH patients than in controls; peak atrial-diastolic strain rate was higher in pulmonary hypertension patients. Similarly, circumferential peak systolic strain rate was lower and peak atrial-diastolic strain rate was higher in pulmonary hypertension. In pulmonary hypertension, no correlations existed between cardiac magnetic resonance-derived and hemodynamically derived measures of systolic right ventricular function. Regarding diastolic parameters, tau was significantly correlated with peak longitudinal atrial-diastolic strain rate ( = -0.61), deceleration time ( = 0.75), longitudinal systolic to diastolic time ratio ( = 0.59), early diastolic strain rate ( = -0.5), circumferential peak atrial-diastolic strain rate ( = -0.52), and deceleration time ( = 0.62). Strain analysis of the right ventricular diastolic phase is a reliable non-invasive method for detecting right ventricular diastolic dysfunction in PAH.
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http://dx.doi.org/10.1177/20458940211032529DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8481729PMC
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

Prognostic Value of Peak Oxygen Uptake in Patients Supported With Left Ventricular Assist Devices (PRO-VAD).

JACC Heart Fail 2021 10 11;9(10):758-767. Epub 2021 Aug 11.

Department of Cardiology, Rigshospitalet, Copenhagen, Denmark; Department of Clinical Medicine, Rigshospitalet, Copenhagen, Denmark. Electronic address: https://twitter.com/FinnGustafsson.

Objectives: The purpose of this study was to examine whether peak oxygen uptake (pVO) and other cardiopulmonary exercise test (CPET)-derived variables could predict intermediate-term mortality in stable continuous flow LVAD recipients.

Background: pVO is a cornerstone in the selection of patients for heart transplantation, but the prognostic power of pVO obtained in patients treated with a left ventricular assist device (LVAD) is unknown.

Methods: We collected data for pVO and outcomes in adult LVAD recipients in a retrospective, multicenter study and evaluated cutoff values for pVO including: 1) values above or below medians; 2) grouping patients in tertiles; and 3) pVO ≤14 ml/kg/min if the patient was not treated with beta-blockers (BB) or pVO ≤12 ml/kg/min if the patient was taking BB therapy.

Results: Nine centers contributed data from 450 patients. Patients were 53 ± 13 years of age; 78% were male; body mass index was 25 ± 5 kg/m with few comorbidities (stroke: 11%; diabetes: 18%; and peripheral artery disease: 4%). The cause of heart failure (HF) was most often nonischemic (66%). Devices included were the HeartMate II and 3 (Abbott); and Heartware ventricular assist devices Jarvik and Duraheart (Medtronic). The index CPET was performed at a median of 189 days (154-225 days) after LVAD implantation, and mean pVO was 14.1 ± 5 ml/kg/min (47% ± 14% of predicted value). Lower pVO values were strongly associated with poorer survival regardless of whether patients were analyzed for absolute pVO in ml/kg/min, pVO ≤12 BB/14 ml/kg/min, or as a percentage of predicted pVO values (P ≤ 0.001 for all). For patients with pVO >12 BB/14 and ventilation/carbon dioxide relationship (VE/VCO) slope <35, the 1-year survival was 100%.

Conclusions: Even after LVAD implantation, pVO has prognostic value, similar to HF patients not supported by mechanical circulatory support devices. (PROgnostic Value of Exercise Capacity Measured as Peak Oxygen Uptake [pVO] in Recipients of Left Ventricular Assist Devices [PRO-VAD]; NCT04423562).
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http://dx.doi.org/10.1016/j.jchf.2021.05.021DOI Listing
October 2021

Hemodynamics for the Heart Failure Clinician: A State-of-the-Art Review.

J Card Fail 2022 Jan 10;28(1):133-148. Epub 2021 Aug 10.

Division of Cardiology, Department of Medicine, Mayo Clinic, Rochester, Minnesota. Electronic address:

Heart failure (HF) fundamentally reflects an inability of the heart to provide adequate blood flow to the body without incurring the cost of increased cardiac filling pressures. This failure occurs first during the stressed state, but progresses until hemodynamic derangements become apparent at rest. As such, the measurement and interpretation of both resting and stressed hemodynamics serve an integral role in the practice of the HF clinician. In this review, we discuss conceptual and technical best practices in the performance and interpretation of both resting and invasive exercise hemodynamic catheterization, relate important pathophysiologic concepts to clinical care, and discuss updated, evidence-based applications of hemodynamics as they pertain to the full spectrum of HF conditions.
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http://dx.doi.org/10.1016/j.cardfail.2021.07.012DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8748277PMC
January 2022

Characteristics of viral pneumonia in non-HIV immunocompromised and immunocompetent patients: a retrospective cohort study.

BMC Infect Dis 2021 Aug 6;21(1):767. Epub 2021 Aug 6.

Department of Pulmonary and Critical Care Medicine, Tianjin First Central Hospital, Tianjin, 300192, China.

Background: Concerning viral pneumonia, few large-scale comparative studies have been published describing non-HIV immunocompromised and immunocompetent patients, but the epidemiological characteristics of different viruses or underlying diseases in immunocompromised hosts are lacking.

Methods: We retrospectively recruited patients hospitalised with viral pneumonia from six academic hospitals in China between August 2016 and December 2019. We measured the prevalence of comorbidities, coinfections, nosocomial infections, and in-hospital mortalities.

Results: Of the 806 patients, 370 were immunocompromised and 436 were immunocompetent. The disease severity and in-hospital mortality of immunocompromised patients were higher than those of immunocompetent patients. During the influenza season, an increased number of cases of influenza virus (IFV) infection were found in the immunocompromised group, followed by cases of cytomegalovirus (CMV) and respiratory syncytial virus (RSV) infection. During the non-influenza season, CMV was the main virus detected in the immunocompromised group, while RSV, adenovirus (AdV), parainfluenza virus (PIV), and rhinovirus (HRV) were the main viruses detected in the immunocompetent group. Pneumonia caused by Pneumocystis jirovecii (22.4%), Aspergillus spp. (14.1%), and bacteria (13.8%) were the most frequently observed coinfections in immunocompromised patients but not in immunocompetent patients (Aspergillus spp. [10.8%], bacteria [7.1%], and Mycoplasma spp. [5.3%]). CMV infection and infection with two-or-more viruses were associated with a higher in-hospital mortality rate than non-IFV infection. However, patients with IFV and non-IFV infection in immunocompromised patients had similar disease severity and prognosis.

Conclusions: Immunocompromised patients have a high frequency of coinfections, and a higher mortality rate was observed among those infected with CMV and two-or-more viruses. In addition, patients with IFV and non-IFV infection in immunocompromised patients had similar same disease severity and prognosis. The type of viral infection varied with seasons.
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http://dx.doi.org/10.1186/s12879-021-06437-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8343364PMC
August 2021

Natriuretic Peptide Levels and Clinical Outcomes Among Patients Hospitalized With Coronavirus Disease 2019 Infection.

Crit Care Explor 2021 Jul 16;3(7):e0498. Epub 2021 Jul 16.

Division of Cardiology, Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD.

Objectives: There is increasing evidence of cardiovascular morbidity associated with severe acute respiratory syndrome coronavirus 2 (coronavirus disease 2019). Pro-B-type natriuretic peptide is a biomarker of myocardial stress, associated with various respiratory and cardiac outcomes. We hypothesized that pro-B-type natriuretic peptide level would be associated with mortality and clinical outcomes in hospitalized coronavirus disease 2019 patients.

Design: We performed a retrospective analysis using adjusted logistic and linear regression to assess the association of admission pro-B-type natriuretic peptide (analyzed by both cutoff > 125 pg/mL and log transformed pro-B-type natriuretic peptide) with clinical outcomes. We additionally treated body mass index, a confounder of both pro-B-type natriuretic peptide levels and coronavirus disease 2019 outcomes, as an ordinal variable.

Setting: We reviewed hospitalized patients with coronavirus disease 2019 who had a pro-B-type natriuretic peptide level measured within 48 hours of admission between March 1, and August 31, 2020, from a multihospital U.S. health system.

Patients: Adult patients (≥ 18 yr old; = 1232) with confirmed coronavirus disease 2019 admitted to the health system.

Interventions: None.

Measurements And Main Results: After adjustment for demographics, comorbidities, and troponin I level, higher pro-B-type natriuretic peptide level was significantly associated with death and secondary outcomes of new heart failure, length of stay, ICU duration, and need for ventilation among hospitalized coronavirus disease 2019 patients. This significance persisted after adjustment for body mass index as an ordinal variable. The adjusted hazard ratio of death for log transformed pro-B-type natriuretic peptide was 1.56 (95% CI, 1.23-1.97; < 0.0001).

Conclusions: Further investigation is warranted on the utility of pro-B-type natriuretic peptide for clinical prognostication in coronavirus disease 2019 as well as implications of abnormal pro-B-type natriuretic peptide in the underlying pathophysiology of coronavirus disease 2019-related myocardial injury.
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http://dx.doi.org/10.1097/CCE.0000000000000498DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8288900PMC
July 2021

Improved Mechanical Properties of Ultra-High Shear Force Mixed Reduced Graphene Oxide/Hydroxyapatite Nanocomposite Produced Using Spark Plasma Sintering.

Nanomaterials (Basel) 2021 Apr 12;11(4). Epub 2021 Apr 12.

Department of Applied Materials and Optoelectronic Engineering, National Chi Nan University, Nantou 54561, Taiwan.

The addition of nanomaterials, such as graphene and graphene oxide, can improve the mechanical properties of hydroxyapatite (HA) nanocomposites (NCPs). However, both the dispersive state of the starting materials and the sintering process play central roles in improving the mechanical properties of the final HA NCPs. Herein, we studied the mechanical properties of a reduced graphene oxide (r-GO)/HA NCP, for which an ultra-high shear force was used to achieve a nano-sized mixture through the dispersion of r-GO. A low-temperature, short-duration spark plasma sintering (SPS) process was used to realize high-density, non-decomposing r-GO/HA NCPs with an improved fracture toughness of 97.8% via the addition of 0.5 wt.% r-GO. Greater quantities of r-GO improve the hardness and the fracture strength. The improved mechanical properties of r-GO/HA NCPs suggest their future applicability in biomedical engineering, including use as sintered bodies in dentistry, plasma spray-coatings for metal surfaces, and materials for 3D printing in orthopedics.
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http://dx.doi.org/10.3390/nano11040986DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8069644PMC
April 2021

Angiotensin Receptor-Neprilysin Inhibition Improves Blood Pressure and Heart Failure Control in Left Ventricular Assist Device Patients.

ASAIO J 2021 12;67(12):e207-e210

From the Division of Cardiology, Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland.

Angiotensin receptor-neprilysin inhibitors (ARNIs) greatly benefit functional capacity and longevity in heart failure with reduced ejection fraction (HFrEF). Angiotensin receptor-neprilysin inhibitors remain underutilized and unstudied, however, in left ventricular assist device (LVAD) recipients, in spite of their underlying HFrEF. In this case series, we studied the feasibility and short-term efficacy of ARNI utilization in 21 LVAD patients. Angiotensin receptor-neprilysin inhibitor initiation was successful in most, resulting in significant consolidation of blood pressure (BP) medical management and marked improvements in both functional capacity and diuretic requirements. Angiotensin receptor-neprilysin inhibitors are safe, feasible, and within a short timeframe benefit BP and heart failure control in LVAD recipients.
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http://dx.doi.org/10.1097/MAT.0000000000001435DOI Listing
December 2021

Assessment of right ventricular reserve utilizing exercise provocation in systemic sclerosis.

Int J Cardiovasc Imaging 2021 Jul 16;37(7):2137-2147. Epub 2021 Apr 16.

Division of Rheumatology, Johns Hopkins University, Baltimore, MD, USA.

Right ventricular (RV) capacity to adapt to increased afterload is the main determinant of outcome in pulmonary hypertension, a common morbidity seen in systemic sclerosis (SSc). We hypothesized that supine bicycle echocardiography (SBE), coupled with RV longitudinal systolic strain (RVLSS), improves detection of limitations in RV reserve in SSc. 56 SSc patients were prospectively studied during SBE with RV functional parameters compared at rest and peak stress. We further dichotomized patients based on resting RV systolic pressure (RVSP) to determine the effects of load on contractile response. Our pooled cohort analysis revealed reduced global RVLSS at rest (-16.2 ± 3.9%) with normal basal contractility (-25.6 ± 7.7%) and relative hypokinesis of the midventricular (-14.1 ± 6.0%) and apical (-8.9 ± 5.1%) segments. With exercise, global RVLSS increased significantly (p = 0.0005), however despite normal basal contractility at rest, there was no further augmentation with exercise. Mid and apical RVLSS increased with exercise suggestive of RV contractile reserve. In patients with resting RVSP < 35 mmHg, global and segmental RVLSS increased with exercise. In patients with resting RVSP ≥ 35 mmHg, global and segmental RVLSS did not increase with exercise and there was evidence of exertional RV dilation. Exercise provocation in conjunction with RVLSS identified differential regional contractile response to exercise in SSc patients. We further demonstrate the effect of increased loading conditions on RV contractile response exercise. These findings suggest subclinical impairments in RV reserve in SSc that may be missed by resting noninvasive 2DE-based assessments alone.
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http://dx.doi.org/10.1007/s10554-021-02237-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8292174PMC
July 2021

Exercise right ventricular ejection fraction predicts right ventricular contractile reserve.

J Heart Lung Transplant 2021 06 17;40(6):504-512. Epub 2021 Feb 17.

Division of Cardiology, Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland. Electronic address:

Background: Right ventricular (RV) contractile reserve shows promise as an indicator of occult RV dysfunction in pulmonary vascular disease. We investigated which measure of RV contractile reserve during exercise best predicts occult RV dysfunction and clinical outcomes.

Methods: We prospectively studied RV contractile reserve in 35 human subjects referred for right heart catheterization for known or suspected pulmonary hypertension. All underwent cardiac magnetic resonance imaging, echocardiography, and supine invasive cardiopulmonary exercise testing with concomitant RV pressure-volume catheterization. Event-free survival was prospectively adjudicated from time of right heart catheterization for a 4-year follow-up period.

Results: RV contractile reserve during exercise, as measured by a positive change in end-systolic elastance (Ees) during exertion, was associated with elevation in pulmonary pressures but preservation of RV volumes. Lack of RV reserve, on the other hand, was tightly coupled with acute RV dilation during exertion (R = 0.76, p< 0.001). RV Ees and dilation changes each predicted resting RV-PA dysfunction. RV ejection fraction during exercise, which captured exertional changes in both RV Ees and RV dilation, proved to be a robust surrogate for RV contractile reserve. Reduced exercise RV ejection fraction best predicted occult RV dysfunction among a variety of resting and exercise RV measures, and was also associated with clinical worsening.

Conclusions: RV ejection fraction during exercise, as an index of RV contractile reserve, allows for excellent identification of occult RV dysfunction, more so than resting measures of RV function, and may predict clinical outcomes as well.
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http://dx.doi.org/10.1016/j.healun.2021.02.005DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8169559PMC
June 2021

Right ventricular pressure-volume loop shape and systolic pressure change in pulmonary hypertension.

Am J Physiol Lung Cell Mol Physiol 2021 05 3;320(5):L715-L725. Epub 2021 Mar 3.

Department of Internal Medicine, Justus-Liebig-University Giessen, Universities of Giessen and Marburg Lung Center (UGMLC), German Center for Lung Research (DZL), Giessen, Germany.

Right ventricular (RV) function determines outcome in pulmonary arterial hypertension (PAH). RV pressure-volume loops, the gold standard for measuring RV function, are difficult to analyze. Our aim was to investigate whether simple assessments of RV pressure-volume loop morphology and RV systolic pressure differential reflect PAH severity and RV function. We analyzed multibeat RV pressure-volume loops (obtained by conductance catheterization with preload reduction) in 77 patients with PAH and 15 patients without pulmonary hypertension in two centers. Patients were categorized according to their pressure-volume loop shape (triangular, quadratic, trapezoid, or notched). RV systolic pressure differential was defined as end-systolic minus beginning-systolic pressure (ESP - BSP), augmentation index as ESP - BSP/pulse pressure, pulmonary arterial capacitance (PAC) as stroke volume/pulse pressure, and RV-arterial coupling as end-systolic/arterial elastance (Ees/Ea). Trapezoid and notched pressure-volume loops were associated with the highest afterload (Ea), augmentation index, pulmonary vascular resistance (PVR), mean pulmonary arterial pressure, stroke work, B-type natriuretic peptide, and the lowest Ees/Ea and PAC. Multivariate linear regression identified Ea, PVR, and stroke work as the main determinants of ESP - BSP. ESP - BSP also significantly correlated with multibeat Ees/Ea (Spearman's ρ: -0.518, < 0.001). A separate retrospective analysis of 113 patients with PAH showed that ESP - BSP obtained by routine right heart catheterization significantly correlated with a noninvasive surrogate of RV-arterial coupling (tricuspid annular plane systolic excursion/pulmonary arterial systolic pressure ratio; ρ: -0.376, < 0.001). In conclusion, pressure-volume loop shape and RV systolic pressure differential predominately depend on afterload and PAH severity and reflect RV-arterial coupling in PAH.
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http://dx.doi.org/10.1152/ajplung.00583.2020DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8174826PMC
May 2021

Decreased Nutritional Risk Index is associated with mortality after heart transplantation.

Clin Transplant 2021 05 25;35(5):e14253. Epub 2021 Feb 25.

Division of Cardiac Surgery, Department of Surgery, Johns Hopkins University School of Medicine, Baltimore, MD, USA.

Introduction: Validated scoring tools, such as the Nutritional Risk Index (NRI), can aid clinicians in quantifying the degree of malnourishment in patients prior to an operation. We evaluated the association between NRI and outcomes after heart transplantation.

Methods: The United Network for Organ Sharing (UNOS) database was used to identify adult patients (age > 18) undergoing heart transplantation between 1987 and 2016. NRI was calculated and categorized into previously established groupings representing severity of malnutrition. Multivariate Cox proportional hazards modeling were used to assess the primary outcome of all-cause mortality.

Results: A total of 25,236 patients were included in the analysis. Most patients (75.4%) were male. Malnourishment was absent (NRI ≥ 100) in 11,022 (44%) patients, while 2,898 (12%) were mildly malnourished (97.5 ≤ NRI < 100), 8,685 (34%) were moderately malnourished (83.5 ≤ NRI < 97.5), and 2,631 (10%) were severely malnourished (NRI < 83.5). Moderate-to-severe malnutrition was associated with increased mortality (HR = 1.18, p < .001, 95%CI: 1.13-1.24), and post-transplant renal failure requiring dialysis (OR: 1.13, p < .001, 95%CI: 1.03-1.23).

Conclusion: Malnourishment determined by NRI is independently associated with mortality and post-transplant dialysis after heart transplant. This is the largest study of NRI in heart transplant recipients.
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http://dx.doi.org/10.1111/ctr.14253DOI Listing
May 2021

High rates of de novo malignancy compromise post-heart transplantation survival.

J Card Surg 2021 Apr 10;36(4):1401-1410. Epub 2021 Feb 10.

Division of Cardiac Surgery, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.

Background: Transplant patients are known to have increased risk of developing de novo malignancies (DNMs). As post-transplant survival increases, DNM represents an obstacle to further improving survival. We sought to examine the incidence, types, and risk factors for post-transplant DNM.

Methods: We studied adult heart transplant recipients from the Organ Procurement and Transplantation Network database (1987-2018). Kaplan-Meier survival analysis was performed to determine annual probabilities of developing DNM, excluding squamous and basal cell carcinoma. Rates were compared to the general population in the Surveillance, Epidemiology, and End Results database. Cox proportional hazards regression was performed to calculate hazard ratios for risk factors of DNM development, all-cause, and cancer-specific mortality.

Results: Over median follow-up of 6.9 years, 18% of the 49,361 patients developed DNM, which correlated with an incidence rate 3.8 times that of the general population. The most common malignancies were lung, post-transplant lymphoproliferative disorder, and prostate. Risk was most increased for female genital, tongue/throat, and renal cancers. Male gender, older age, smoking history, and impaired renal function were risk factors for developing DNM, whereas the use of MMF for immunosuppression was protective. Cigarette use, increasing age, the use of ATG for induction and calcineurin inhibitors for maintenance were risk factors for cancer-specific mortality. The development of a DNM increased the risk of death by 40% (p < .001).

Conclusions: Heart transplant patients are at increased risk of malignancy, particularly rare cancers, which significantly increases their risk of death. Strict cancer surveillance and attention to immunosuppression are critical for prolonging post-transplant survival.
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http://dx.doi.org/10.1111/jocs.15416DOI Listing
April 2021

Less invasive surgical implant strategy and right heart failure after LVAD implantation.

J Heart Lung Transplant 2021 04 12;40(4):289-297. Epub 2021 Jan 12.

Medical University of South Carolina, Charleston, South Carolina. Electronic address:

Background: Conventional median sternotomy (CMS) is still the standard technique utilized to implant left ventricular assist devices (LVADs). Recent studies suggest that less invasive surgery (LIS) may be beneficial; however, robust data on differences in right heart failure (RHF) are lacking. This study aimed to determine the impact of LIS compared with that of CMS on RHF outcomes after LVAD implantation.

Methods: An international multicenter retrospective cohort study was conducted across 5 centers. Patients were grouped according to their implantation technique (LIS vs CMS). Only centrifugal devices were included. RHF was defined as severe or severe acute RHF according to the 2013 Interagency Registry for Mechanically Assisted Circulatory Support (INTERMACS) definition. Logistic multivariate regression and propensity score‒matched analyses were performed to account for confounding.

Results: Overall, 427 implantations occurred during the study period, with 305 patients implanted using CMS and 122 using LIS. Pre-operative extracorporeal membrane oxygenation (ECMO) and intra-aortic balloon pump (IABP) use was more common in the CMS group; off-pump implantation was more common in the LIS group. Other pre-implant variables, including age, creatinine, hemodynamics, and tricuspid regurgitation, did not differ between the 2 groups. Post-operative RHF was less common in the patients who underwent LIS than in those who underwent CMS as was post-operative right ventricular assist device (RVAD) use. LIS remained associated with less RHF in the multivariate analysis. After propensity score matching conditional for age, sex, INTERMACS profile, ECMO, and IABP use in a ratio of 2:1 (CMS to LIS), RHF (29.9% vs 18.6%, p = 0.001) and the need for post-operative RVAD (18.6% vs 8.2%; p = 0.009) remained more common in the CMS group than in the LIS group. There were no significant differences in survival up to 1 year between the groups.

Conclusions: LIS may be associated with less RHF after LVAD implantation compared with CMS. Despite the possible reduction in RHF, there was no difference in 1-year survival. LIS is an alternative to traditional CMS.
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http://dx.doi.org/10.1016/j.healun.2021.01.005DOI 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

Reduced Right Ventricular Sarcomere Contractility in Heart Failure With Preserved Ejection Fraction and Severe Obesity.

Circulation 2021 03 2;143(9):965-967. Epub 2020 Dec 2.

Division of Cardiology, Department of Medicine (M.I.A., V.S.H., S.H., K.S., D.A.K.), The Johns Hopkins University, The Johns Hopkins School of Medicine, Baltimore, MD.

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http://dx.doi.org/10.1161/CIRCULATIONAHA.120.052414DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7920934PMC
March 2021

Disposable protective barrier enclosure prevent aerosol contamination during aerosol-generating procedures.

J Chin Med Assoc 2021 01;84(1):119-120

Department of Anesthesiology, Mennonite Christian Hospital, Hualien, Taiwan, ROC.

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http://dx.doi.org/10.1097/JCMA.0000000000000471DOI Listing
January 2021

New-Onset Seizures in Three COVID-19 Patients: A Case Series.

J Clin Neurophysiol 2021 Mar;38(2):e5-e10

Weill Cornell Medical College, New York City, New York, U.S.A.

Summary: Neurological manifestations of coronavirus disease 2019 most commonly present in severe cases and range from mild complications, such as headache and dizziness, to severe complications, such as encephalopathy and acute cerebrovascular disease. Seizures, however, are an underreported neurological manifestation of this disease. We present three critically ill coronavirus disease 2019 patients with EEG monitoring who developed new-onset seizures and encephalopathy up to three-and-a-half weeks after symptom onset. There are several speculated etiologies for the development of new-onset seizures; however, the pathogenic mechanism remains unknown. Testing of coronavirus disease 2019 in the cerebrospinal fluid in addition to extensive research on neurological manifestations is warranted.
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http://dx.doi.org/10.1097/WNP.0000000000000783DOI Listing
March 2021

An Analysis of Waitlist Inactivity Among Patients With Ventricular Assist Devices.

J Surg Res 2021 04 28;260:383-390. Epub 2020 Nov 28.

Division of Cardiac Surgery, Johns Hopkins Hospital, Cardiac Surgery, Baltimore, Maryland. Electronic address:

Background: Ventricular assist devices (VADs) are commonly used mechanical circulatory support for bridge to transplant therapy in end-stage heart failure; however, it is not understood how VADs influence incidence of waitlist inactive status. We sought to characterize and compare waitlist inactivity among patients with and without VADs.

Methods: Using the Organ Procurement and Transplantation Network database, we investigated the VAD's impact on incidence and length of inactive periods for heart transplant candidates from 2005 through 2018. We compared median length of inactivity between patients with and without VADs and investigated inactivity risk with time-to-event regression models.

Results: Among 46,441 heart transplant candidates, 32% (n = 14,636) had a VAD. Thirty-eight percent (n = 17,873) of all patients experienced inactivity, of which 42% (7538/17,873) had a VAD. Median inactivity length was 31 d for patients without VADs and 62 d for VAD patients (P < 0.0005). Multivariable analysis showed no significant difference in risk of inactivity for deteriorating conditions between patients with and without VADs after controlling for demographic and baseline clinical variables. A larger proportion of patients without VADs were inactive for deteriorating conditions than VAD patients (54%, n = 8242/15,221 versus 32%, n = 3583/11,086, P < 0.001). Ten percent (1155/11,086) of VAD patients' inactive periods were for VAD-related complications.

Conclusions: Although VAD patients were inactive longer and had an overall increased risk of any-cause inactivity, their risk of inactivity for deteriorating condition was not significantly different from patients without VADs. Furthermore, VAD patients had a smaller proportion of inactivity periods due to deteriorating conditions. Thus, VADs are protective from morbidity for waitlist patients.
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http://dx.doi.org/10.1016/j.jss.2020.11.010DOI Listing
April 2021

Aetiology and prognostic risk factors of mortality in patients with pneumonia receiving glucocorticoids alone or glucocorticoids and other immunosuppressants: a retrospective cohort study.

BMJ Open 2020 10 27;10(10):e037419. Epub 2020 Oct 27.

Department of Pulmonary and Critical Care Medicine, Laboratory of Clinical Microbiology and Infectious Diseases; Institute of Respiratory Medicine, Chinese Academy of Medical Science; Tsinghua University-Peking University Joint Center for Life Sciences, China-Japan Friendship Hospital, Beijing, China

Objectives: Long-term use of high-dose glucocorticoids can lead to severe immunosuppression and increased risk of treatment-resistant pneumonia and mortality. We investigated the aetiology and prognostic risk factors of mortality in hospitalised patients who developed pneumonia while receiving glucocorticoid therapy alone or glucocorticoid and other immunosuppressant therapies.

Design: Retrospective cohort study.

Setting: Six secondary and tertiary academic hospitals in China.

Participants: Patients receiving glucocorticoids who were hospitalised with pneumonia between 1 January 2013 and 31 December 2019.

Main Outcomes: We analysed the prevalence of comorbidities, microbiology, antibiotic susceptibility patterns, 30-day and 90-day mortality and prognostic risk factors.

Results: CONCLUSIONS: A total of 716 patients were included, with pneumonia pathogens identified in 69.8% of patients. Significant morbidities occurred, including respiratory failure (50.8%), intensive care unit transfer (40.8%) and mechanical ventilation (36%), with a 90-day mortality of 26.0%. Diagnosis of pneumonia occurred within 6 months of glucocorticoid initiation for 69.7% of patients with (CMV) pneumonia and 79.0% of patients with pneumonia (PCP). Pathogens, including , CMV and multidrug-resistant bacteria, were identified more frequently in patients with persistent lymphocytopenia and high-dose glucocorticoid treatment (≥30 mg/day of prednisolone or equivalent within 30 days before admission). The 90-day mortality was significantly lower for non-CMV viral pneumonias than for PCP (p<0.05), with a similar mortality as CMV pneumonias (24.2% vs 38.1% vs 27.4%, respectively). Cox regression analysis indicated several independent negative predictors for mortality in this patient population, including septic shock, respiratory failure, persistent lymphocytopenia, interstitial lung disease and high-dose glucocorticoid use.Patients who developed pneumonia while receiving glucocorticoid therapy experienced high rates of opportunistic infections, with significant morbidity and mortality. These findings should be carefully considered when determining treatment strategies for this patient population.
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http://dx.doi.org/10.1136/bmjopen-2020-037419DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7592294PMC
October 2020
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