Publications by authors named "Ryan J Tedford"

153 Publications

The Right Ventricular-Pulmonary Arterial Coupling and Diastolic Function Response to Therapy in Pulmonary Arterial Hypertension.

Chest 2021 Oct 9. Epub 2021 Oct 9.

Department of Medicine, University of Arizona, Tucson, AZ; Division of Pulmonary, Critical Care, Sleep, and Allergy Medicine, University of Arizona, Tucson, AZ. Electronic address:

Background: Multiparametric risk assessment is used in pulmonary arterial hypertension (PAH) to target therapy. However, this strategy is imperfect as most patients remain in intermediate or high risk after initial treatment with low risk being the goal. Metrics of right ventricular (RV) adaptation are promising tools that may help refine our therapeutic strategy.

Research Question: Does RV adaptation predict therapeutic response over time?

Study Design And Methods: We evaluated 52 incident treatment naïve patients with advanced PAH by catheterization and cardiac imaging longitudinally at baseline, follow-up 1 (∼3 mo.) and follow-up 2 (∼18 mo.). All patients were placed on goal-directed therapy with parenteral treprostinil and/or combination therapy with treatment escalation if functional class I-II was not achieved. Therapeutic response was evaluated at follow-up 1 as non-responders (died) or responders and again at follow-up 2 as super-responders (low risk) or partial-responders (high/intermediate risk). Multiparametric risk was based on a simplified ERS/ESC guideline score. RV adaptation was evaluated with the single-beat coupling ratio (Ees/Ea) and diastolic function with diastolic elastance (Eed). Data are expressed as mean±SD or odds ratio [95%CI].

Results: Nine patients (17%) were non-responders. PAH-directed therapy improved ERS low risk from 1 (2%) at baseline to 23 (55%) at follow-up 2. Ees/Ea at presentation was non-significantly higher in responders (0.9±0.4) versus non-responders (0.6±0.4, p=0.09) but was unable to predict super-responder status at follow-up 2 (odds ratio 1.40 [0.28-7.0], p=0.84). Baseline RVEF and change in Eed successfully predicted super-responder status at follow-up 2 (odds ratio 1.15 [1.0-1.27], p=0.009 and 0.29 [0.86-0.96], p=0.04, respectively).

Interpretation: In patients with advanced PAH, RV-PA coupling could not discriminate irreversible RV failure (non-responders) at presentation but showed a late trend to improvement by follow-up 2. Early change in Eed and baseline RVEF were the best predictors of therapeutic response.
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http://dx.doi.org/10.1016/j.chest.2021.09.040DOI Listing
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

Evaluation of aspirin platelet inhibition in left ventricular assist device population.

J Card Surg 2021 Sep 21. Epub 2021 Sep 21.

Department of Pharmacy, Medical University of South Carolina, Charleston, South Carolina, USA.

Introduction: Aspirin therapy is recommended in durable left ventricular assist device (LVAD) patients to prevent thromboembolic complications. Up to 30% of patients treated with aspirin may demonstrate aspirin resistance, which has been related to thrombotic complications. However, it is unknown whether individual patients exhibit temporal alterations in aspirin sensitivity during LVAD support. We hypothesized that aspirin platelet inhibition would wane after the initial postimplant period.

Methods: This was a retrospective, observational, single center study conducted at an academic medical center. This study evaluated changes in aspirin platelet inhibition over the first 6 months of LVAD support. Patients who underwent placement of centrifugal LVAD with aspirin platelet sensitivity assays were included for analysis. Aspirin responsiveness was assessed postimplant after 5 days, 3 months, and 6 months.

Results: A total of 28 patients were included for analysis of which 7% of patients were aspirin resistant initially. At 3 months, 32% (odds ratio [OR], 6.1, p = .03) of patients were aspirin resistant and 28% (OR, 4.1, p = .1) at 6 months. Over the first 3 months postimplant, the odds of aspirin resistance increased sixfold and remained relatively constant at 6 months. Patients who were aspirin resistant and received an increase in aspirin dose at 3 months subsequently had a sensitive ARU at 6 months.

Conclusion: Aspirin responsiveness not only varies between patients but can significantly wane within individual LVAD patients over time. Additional study is needed to determine if monitoring aspirin resistance may prevent thrombotic complications after LVAD implantation.
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http://dx.doi.org/10.1111/jocs.16003DOI Listing
September 2021

Right Heart Catheterization in Cardiogenic Shock Is Associated With Improved Outcomes: Insights From the Nationwide Readmissions Database.

J Am Heart Assoc 2021 Sep 21;10(17):e019843. Epub 2021 Aug 21.

Department of Cardiovascular Medicine The University of Kansas Health SystemUniversity of Kansas School of Medicine Kansas City KS.

Background The usefulness of right heart catherization (RHC) has long been debated, and thus, we aimed to study the real-world impact of the use of RHC in cardiogenic shock. Methods and Results In the Nationwide Readmissions Database using (), we identified 236 156 patient hospitalizations with cardiogenic shock between 2016 and 2017. We sought to evaluate the impact of RHC during index hospitalization on management strategies, complications, and outcomes as well as on 30-day readmission rate. A total 25 840 patients (9.6%) received RHC on index admission. The RHC group had significantly more comorbidities compared with the non-RHC group. During the index admission, the RHC group had lower death (25.8% versus 39.5%, <0.001) and stroke rates (3.1% versus 3.4%, <0.001). Thirty-day readmission rates (18.7% versus 19.7%, =0.04) and death on readmission (7.9% versus 9.3%, =0.03) were also lower in the RHC group. After adjustment, RHC was associated with lower index admission mortality (odds ratio, 0.69; 95% CI, 0.66-0.72), lower stroke rate (odds ratio, 0.81; 95% CI, 0.72-0.90), lower 30-day readmission (odds ratio, 0.83; 95% CI, 0.78-0.88), and higher left ventricular assist device implantations/orthotopic heart transplants (odds ratio, 6.05; 95% CI, 4.43-8.28) during rehospitalization. Results were not meaningfully different after excluding patients with cardiac arrest. Conclusions RHC use in cardiogenic shock is associated with improved outcomes and increased use of downstream advanced heart failure therapies. Further blinded randomized studies are required to confirm our findings.
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http://dx.doi.org/10.1161/JAHA.120.019843DOI Listing
September 2021

Diagnosis and Treatment of Right Heart Failure in Pulmonary Vascular Diseases: A National Heart, Lung, and Blood Institute Workshop.

Circ Heart Fail 2021 Jun 15;14(6). Epub 2021 Jun 15.

Division of Lung Diseases, National Heart, Lung, and Blood Institute, NIH, Bethesda, MD.

Right ventricular dysfunction is a hallmark of advanced pulmonary vascular, lung parenchymal, and left heart disease, yet the underlying mechanisms that govern (mal)adaptation remain incompletely characterized. Owing to the knowledge gaps in our understanding of the right ventricle (RV) in health and disease, the National Heart, Lung, and Blood Institute (NHLBI) commissioned a working group to identify current challenges in the field. These included a need to define and standardize normal RV structure and function in populations; access to RV tissue for research purposes and the development of complex experimental platforms that recapitulate the environment; and the advancement of imaging and invasive methodologies to study the RV within basic, translational, and clinical research programs. Specific recommendations were provided, including a call to incorporate precision medicine and innovations in prognosis, diagnosis, and novel RV therapeutics for patients with pulmonary vascular disease.
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http://dx.doi.org/10.1161/CIRCHEARTFAILURE.120.007975DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8375628PMC
June 2021

Heart Transplantation in Adriamycin-Associated Cardiomyopathy in the Contemporary Era of Advanced Heart Failure Therapies.

JACC CardioOncol 2021 Jun 15;3(2):294-301. Epub 2021 Jun 15.

Division of Cardiology, Department of Medicine, University of Minnesota, Minneapolis, Minnesota, USA.

Background: Adriamycin-associated cardiomyopathy (ACM) can lead to end-stage heart failure requiring advanced heart failure therapies.

Objectives: This study sought to provide post-cardiac transplant survival data in patients with ACM in the contemporary era of mechanical circulatory support and cardiac transplantation.

Methods: Adults (≥18 years of age) who underwent first-time, single-organ heart transplantation were identified from the United Network for Organ Sharing between October 18, 2008, and October 18, 2018. Cardiomyopathy subtypes that could have been supported with a left ventricular assist device (LVAD) including ACM, dilated cardiomyopathy (DCM), and ischemic cardiomyopathy (ICM) were included. A multivariable Cox regression analysis was performed to determine the association between cardiomyopathy subtype and post-cardiac transplant survival.

Results: This analysis included 18,270 patients (357 with ACM; 10,662 with DCM; and 7,251 with ICM). Heart transplant recipients with ACM were younger, included more women, and had higher pulmonary vascular resistance at the time of listing. Patients with ACM had a lower percentage of durable LVADs at the time of transplant across all years of the study period. Patients with ACM did not experience an increase in post-cardiac transplant mortality compared to those with DCM (adjusted hazard ratio: 0.96; 95% confidence interval: 0.79 to 1.40; p = 0.764) or ICM (adjusted hazard ratio: 0.85; 95% confidence interval: 0.6 to 1.2; p = 0.304).

Conclusions: Patients with ACM who received heart transplants between 2008 and 2018 had similar post-cardiac transplant survival to those with dilated and ischemic cardiomyopathy. Bridge-to-transplant LVAD use remains lower compared to other cardiomyopathy subtypes.
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http://dx.doi.org/10.1016/j.jaccao.2021.02.010DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8352281PMC
June 2021

Pulmonary Hypertension in the Context of Heart Failure With Preserved Ejection Fraction.

Chest 2021 Aug 12. Epub 2021 Aug 12.

Division of Cardiology, Department of Medicine, Medical University of South Carolina, Charleston, SC. Electronic address:

Heart failure with preserved ejection fraction (HFpEF) is the most common form of heart failure and frequently is associated with pulmonary hypertension (PH). HFpEF associated with PH may be difficult to distinguish from precapillary forms of PH, although this distinction is crucial because therapeutic pathways are divergent for the two conditions. A comprehensive and systematic approach using history, clinical examination, and noninvasive and invasive evaluation with and without provocative testing may be necessary for accurate diagnosis and phenotyping. After diagnosis, HFpEF associated with PH can be subdivided into isolated postcapillary pulmonary hypertension (IpcPH) and combined postcapillary and precapillary pulmonary hypertension (CpcPH) based on the presence or absence of elevated pulmonary vascular resistance. CpcPH portends a worse prognosis than IpcPH. Despite its association with reduced functional capacity and quality of life, heart failure hospitalizations, and higher mortality, therapeutic options focused on PH for HFpEF associated with PH remain limited. In this review, we aim to provide an updated overview on clinical definitions and hemodynamically characterized phenotypes of PH, pathophysiologic features, therapeutic strategies, and ongoing challenges in this patient population.
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http://dx.doi.org/10.1016/j.chest.2021.08.039DOI Listing
August 2021

Coronavirus disease 2019 in heart transplant recipients: Risk factors, immunosuppression, and outcomes.

J Heart Lung Transplant 2021 09 19;40(9):926-935. Epub 2021 May 19.

The Zena and Michael A. Wiener Cardiovascular Institute, Icahn School of Medicine at Mount Sinai, New York, New York.

Background: COVID-19 continues to inflict significant morbidity and mortality, particularly on patients with preexisting health conditions. The clinical course, outcomes, and significance of immunosuppression regimen in heart transplant recipients with COVID-19 remains unclear.

Methods: We included the first 99 heart transplant recipients at participating centers with COVID-19 and followed patients until resolution. We collected baseline information, symptoms, laboratory studies, vital signs, and outcomes for included patients. The association of immunosuppression regimens at baseline with severe disease were compared using logistic regression, adjusting for age and time since transplant.

Results: The median age was 60 years, 25% were female, and 44% were white. The median time post-transplant to infection was 5.6 years. Overall, 15% died, 64% required hospital admission, and 7% remained asymptomatic. During the course of illness, only 57% of patients had a fever, and gastrointestinal symptoms were common. Tachypnea, oxygen requirement, elevated creatinine and inflammatory markers were predictive of severe course. Age ≥ 60 was associated with higher risk of death and the use of the combination of calcineurin inhibitor, antimetabolite, and prednisone was associated with more severe disease compared to the combination of calcineurin inhibitor and antimetabolite alone (adjusted OR = 7.3, 95% CI 1.8-36.2). Among hospitalized patients, 30% were treated for secondary infection, acute kidney injury was common and 17% required new renal replacement therapy.

Conclusions: We present the largest study to date of heart transplant patients with COVID-19 showing common atypical presentations and a high case fatality rate of 24% among hospitalized patients and 16% among symptomatic patients.
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http://dx.doi.org/10.1016/j.healun.2021.05.006DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8131557PMC
September 2021

Associations of Angiopoietins With Heart Failure Incidence and Severity.

J Card Fail 2021 Jul 17;27(7):786-795. Epub 2021 Apr 17.

University of Washington, Department of Medicine, Seattle, WA; University of Washington, Department of Epidemiology, Seattle, WA. Electronic address:

Background: Angiopoietin-1 and 2 (Ang1, Ang2) are important mediators of angiogenesis. Angiopoietin levels are perturbed in cardiovascular disease, but it is unclear whether angiopoietin signaling is causative, an adaptive response, or merely epiphenomenon of disease activity.

Methods And Results: In a cohort free of cardiovascular disease at baseline (Multi-Ethnic Study of Atherosclerosis [MESA]), relationships between angiopoietins, cardiac morphology, and subsequent incidence of heart failure or cardiovascular death were evaluated. In cohorts with pulmonary arterial hypertension or left heart disease, associations between angiopoietins, invasive hemodynamics, and adverse clinical outcomes were evaluated. In MESA, Ang2 was associated with a higher incidence of heart failure or cardiovascular death (hazard ratio 1.21 per standard deviation, P < .001). Ang2 was associated with increased right atrial pressure (pulmonary arterial hypertension cohort) and increased wedge pressure and right atrial pressure (left heart disease cohort). Elevated Ang2 was associated with mortality in the pulmonary arterial hypertension cohort.

Conclusions: Ang2 was associated with incident heart failure or death among adults without cardiovascular disease at baseline and with disease severity in individuals with existing heart failure. Our finding that Ang2 is increased before disease onset and that elevations reflect disease severity, suggests Ang2 may contribute to heart failure pathogenesis.
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http://dx.doi.org/10.1016/j.cardfail.2021.04.001DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8277723PMC
July 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

Levosimendan Improves Hemodynamics and Exercise Tolerance in PH-HFpEF: Results of the Randomized Placebo-Controlled HELP Trial.

JACC Heart Fail 2021 05 7;9(5):360-370. Epub 2021 Apr 7.

Northwestern University, Chicago, Illinois, USA.

Objectives: The purpose of this study was to evaluate the effects of intravenous levosimendan on hemodynamics and 6-min walk distance (6MWD) in patients with pulmonary hypertension and heart failure with preserved ejection fraction (PH-HFpEF).

Background: There are no proven effective treatments for patients with PH-HFpEF.

Methods: Patients with mean pulmonary artery pressure (mPAP) ≥35 mm Hg, pulmonary capillary wedge pressure (PCWP) ≥20 mm Hg, and LVEF ≥40% underwent 6MWD and hemodynamic measurements at rest, during passive leg raise, and supine cycle exercise at baseline and after an open-label 24-h levosimendan infusion (0.1 μg/kg/min). Hemodynamic responders (those with ≥4 mm Hg reduction of exercise-PCWP) were randomized (double blind) to weekly levosimendan infusion (0.075 to 0.1 ug/kg/min for 24 h) or placebo for 5 additional weeks. The primary end point was exercise-PCWP, and key secondary end points included 6MWD and PCWP measured across all exercise stages.

Results: Thirty-seven of 44 patients (84%) met responder criteria and were randomized to levosimendan (n = 18) or placebo (n = 19). Participants were 69 ± 9 years of age, 61% female, and with resting mPAP 41.0 ± 9.3 mm Hg and exercise-PCWP 36.8 ± 11.3 mm Hg. Compared with placebo, levosimendan did not significantly reduce the primary end point of exercise-PCWP at 6 weeks (-1.4 mm Hg; 95% confidence interval [CI]: -7.8 to 4.8; p = 0.65). However, levosimendan reduced PCWP measured across all exercise stages (-3.9 ± 2.0 mm Hg; p = 0.047). Levosimendan treatment resulted in a 29.3 m (95% CI: 2.5 to 56.1; p = 0.033) improvement in 6MWD compared with placebo.

Conclusions: Six weeks of once-weekly levosimendan infusion did not affect exercise-PCWP but did reduce PCWP incorporating data from rest and exercise, in tandem with increased 6MWD. Further study of levosimendan is warranted as a therapeutic option for PH-HFpEF. (Hemodynamic Evaluation of Levosimendan in Patients With PH-HFpEF [HELP]; NCT03541603).
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http://dx.doi.org/10.1016/j.jchf.2021.01.015DOI Listing
May 2021

Characteristics and Outcomes of COVID-19 in Patients on Left Ventricular Assist Device Support.

Circ Heart Fail 2021 Apr 5;14(4):e007957. Epub 2021 Apr 5.

Zena and Michael A. Wiener Cardiovascular Institute, Icahn School of Medicine at Mount Sinai, NY (J.A.-G., D.M.M., N.M.).

Background: The coronavirus disease 2019 (COVID-19) pandemic continues to afflict millions of people worldwide. Patients with end-stage heart failure and left ventricular assist devices (LVADs) may be at risk for severe COVID-19 given a high prevalence of complex comorbidities and functional impaired immunity. The objective of this study is to describe the clinical characteristics and outcomes of COVID-19 in patients with end-stage heart failure and durable LVADs.

Methods: The Trans-CoV-VAD registry is a multi-center registry of LVAD and cardiac transplant patients in the United States with confirmed COVID-19. Patient characteristics, exposure history, presentation, laboratory data, course, and clinical outcomes were collected by participating institutions and reviewed by a central data repository. This report represents the participation of the first 9 centers to report LVAD data into the registry.

Results: A total of 40 patients were included in this cohort. The median age was 56 years (interquartile range, 46-68), 14 (35%) were women, and 21 (52%) were Black. Among the most common presenting symptoms were cough (41%), fever, and fatigue (both 38%). A total of 18% were asymptomatic at diagnosis. Only 43% of the patients reported either subjective or measured fever during the entire course of illness. Over half (60%) required hospitalization, and 8 patients (20%) died, often after lengthy hospitalizations.

Conclusions: We present the largest case series of LVAD patients with COVID-19 to date. Understanding these characteristics is essential in an effort to improve the outcome of this complex patient population.
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http://dx.doi.org/10.1161/CIRCHEARTFAILURE.120.007957DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8059761PMC
April 2021

Turning Pressure Into Success: Preload Restriction in HFpEF?

JACC Basic Transl Sci 2021 Mar 22;6(3):199-201. Epub 2021 Mar 22.

Division of Cardiology, Department of Medicine, Medical University of South Carolina, Charleston, South Carolina, USA.

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http://dx.doi.org/10.1016/j.jacbts.2021.01.008DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7987539PMC
March 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

Ventricular septal defect complicating delayed presentation of acute myocardial infarction during COVID-19 lockdown: a case report.

Eur Heart J Case Rep 2021 Feb 16;5(2):ytab027. Epub 2021 Feb 16.

Division of Cardiology, Medical University of South Carolina, 30 Courtenay Drive, 326/MSC 592, Charleston, SC 29425, USA.

Background : Post-myocardial infarction ventricular septal defects (VSDs) have become rare in the reperfusion era but remain associated with very high morbidity and mortality. As patients defer prompt evaluation and management of acute coronary syndromes during the COVID-19 global pandemic, the incidence of these and other post-infarction mechanical complications is expected to increase.

Case Summary : A 37-year-old gentleman with multiple coronary artery disease risk factors presented with intermittent chest discomfort and 1 week of heart failure symptoms. An echocardiogram demonstrated a large muscular VSD and coronary angiography confirmed the presence of an anterior wall infarction. He was subsequently referred for transcatheter VSD repair and showed rapid clinical improvement in his symptoms.

Discussion : Post-infarction VSDs remain associated with a high degree of morbidity and mortality. Surgical repair of acutely ruptured myocardium can be technically challenging, and transcatheter repair has emerged as a safe and effective alternative.
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http://dx.doi.org/10.1093/ehjcr/ytab027DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7953949PMC
February 2021

Elevated Pulmonary Pressure Noted on Echocardiogram: A Simplified Approach to Next Steps.

J Am Heart Assoc 2021 04 15;10(7):e017684. Epub 2021 Mar 15.

Cardiovascular Medicine University of Michigan Ann Arbor MI.

An elevated right ventricular/pulmonary artery systolic pressure suggestive of pulmonary hypertension (PH) is a common finding noted on echocardiography and is considered a marker for poor clinical outcomes, regardless of the cause. Even mild elevation of pulmonary pressure can be considered a modifiable risk factor, informing the trajectory of patients' clinical outcome. Although guidelines have been published detailing diagnostic and management algorithms, this echocardiographic finding is often underappreciated or not acted upon. Hence, patients with PH are often diagnosed in clinical practice when hemodynamic abnormalities are already moderate or severe. This results in delayed initiation of potentially effective therapies, referral to PH centers, and greater patient morbidity and mortality. This mini-review presents a succinct, simplified case-based approach to the "next steps" in the work-up of PH, once elevated pulmonary pressures have been noted on an echocardiogram. Our goal is for clinicians to develop a good overview of diagnostic approach to PH and recognition of high-risk features that may require early referral.
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http://dx.doi.org/10.1161/JAHA.120.017684DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8174323PMC
April 2021

Response by Viray et al to Letter Regarding Article, "Role of Pulmonary Artery Wedge Pressure Saturation During Right Heart Catheterization: A Prospective Study".

Circ Heart Fail 2021 03 12;14(3):e008304. Epub 2021 Mar 12.

Division of Cardiology, Department of Medicine, Medical University of South Carolina, Charleston.

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http://dx.doi.org/10.1161/CIRCHEARTFAILURE.121.008304DOI Listing
March 2021

A novel non-invasive and echocardiography-derived method for quantification of right ventricular pressure-volume loops.

Eur Heart J Cardiovasc Imaging 2021 Feb 28. Epub 2021 Feb 28.

Department of Internal Medicine, Justus-Liebig-University Giessen, Universities of Giessen and Marburg Lung Center (UGMLC), Member of the German Center for Lung Research (DZL), Klinikstrasse 32, Giessen 35392, Germany.

Aims: We sought to assess the feasibility of constructing right ventricular (RV) pressure-volume (PV) loops solely by echocardiography.

Methods And Results: We performed RV conductance and pressure wire (PW) catheterization with simultaneous echocardiography in 35 patients with pulmonary hypertension. To generate echocardiographic PV loops, a reference RV pressure curve was constructed using pooled PW data from the first 20 patients (initial cohort). Individual pressure curves were then generated by adjusting the reference curve according to RV isovolumic and ejection phase duration and estimated RV systolic pressure. The pressure curves were synchronized with echocardiographic volume curves. We validated the reference curve in the remaining 15 patients (validation cohort). Methods were compared with correlation and Bland-Altman analysis. In the initial cohort, echocardiographic and conductance-derived PV loop parameters were significantly correlated {rho = 0.8053 [end-systolic elastance (Ees)], 0.8261 [Ees/arterial elastance (Ea)], and 0.697 (stroke work); all P < 0.001}, with low bias [-0.016 mmHg/mL (Ees), 0.1225 (Ees/Ea), and -39.0 mmHg mL (stroke work)] and acceptable limits of agreement. Echocardiographic and PW-derived Ees were also tightly correlated, with low bias (-0.009 mmHg/mL) and small limits of agreement. Echocardiographic and conductance-derived Ees, Ees/Ea, and stroke work were also tightly correlated in the validation cohort (rho = 0.9014, 0.9812, and 0.9491, respectively; all P < 0.001), with low bias (0.0173 mmHg/mL, 0.0153, and 255.1 mmHg mL, respectively) and acceptable limits.

Conclusion: The novel echocardiographic method is an acceptable alternative to invasively measured PV loops to assess contractility, RV-arterial coupling, and RV myocardial work. Further validation is warranted.
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http://dx.doi.org/10.1093/ehjci/jeab038DOI Listing
February 2021

Acute Hemodynamic Effects of Cardiac Resynchronization Therapy Versus Alternative Pacing Strategies in Patients With Left Ventricular Assist Devices.

J Am Heart Assoc 2021 03 5;10(6):e018127. Epub 2021 Mar 5.

Division of Cardiology Department of Medicine Medical University of South Carolina Charleston SC.

Background The hemodynamic effects of cardiac resynchronization therapy in patients with left ventricular assist devices (LVADs) are uncharacterized. We aimed to quantify the hemodynamic effects of different ventricular pacing configurations in patients with LVADs, focusing on short-term changes in load-independent right ventricular (RV) contractility. Methods and Results Patients with LVADs underwent right heart catheterization during spontaneous respiration without sedation and with pressures recorded at end expiration. Right heart catheterization was performed at different pacemaker configurations (biventricular pacing, left ventricular pacing, RV pacing, and unpaced conduction) in a randomly generated sequence with >3 minutes between configuration change and hemodynamic assessment. The right heart catheterization operator was blinded to the sequence. RV maximal change in pressure over time normalized to instantaneous pressure was calculated from digitized hemodynamic waveforms, consistent with a previously validated protocol. Fifteen patients with LVADs who were in sinus rhythm were included. Load-independent RV contractility, as assessed by RV maximal change in pressure over time normalized to instantaneous pressure, was higher in biventricular pacing compared with unpaced conduction (15.7±7.6 versus 11.0±4.0 s; =0.003). Thermodilution cardiac output was higher in biventricular pacing compared with unpaced conduction (4.48±0.7 versus 4.38±0.8 L/min; =0.05). There were no significant differences in heart rate, ventricular filling pressures, or atrioventricular valvular regurgitation across all pacing configurations. Conclusions Biventricular pacing acutely improves load-independent RV contractility in patients with LVADs. Even in these patients with mechanical left ventricular unloading via LVAD who were relative pacing nonresponders (required LVAD support despite cardiac resynchronization therapy), biventricular pacing was acutely beneficial to RV contractility.
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http://dx.doi.org/10.1161/JAHA.120.018127DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8174219PMC
March 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

Nonresponse to Acute Vasodilator Challenge and Prognosis in Heart Failure With Pulmonary Hypertension.

J Card Fail 2021 Aug 5;27(8):869-876. Epub 2021 Feb 5.

Department of Medicine, Division of Cardiology, Medical University of South Carolina, Charleston, South Carolina.

Background: An acute vasodilator challenge is recommended in patients with heart failure and pulmonary hypertension during heart transplant evaluation. The aim of the study was to assess which hemodynamic parameters are associated with nonresponsiveness to the challenge.

Methods And Results: This study is a retrospective analysis of 402 patients with heart failure with pulmonary hypertension who underwent right heart catheterization and a pulmonary vasodilator challenge. Among the 140 who fulfilled the transplant guidelines eligibility criteria for the vasodilator challenge, 38 were responders and 102 nonresponders. At multivariable analysis, a diastolic blood pressure of <70 mm Hg, pulmonary vascular resistance of >5 Woods units, and pulmonary artery compliance of <1.2 mL/mm Hg were independently associated with poor response to vasodilator challenge (all P < .001). The presence of any 2 of these 3 conditions was associated with a 90% probability of being a nonresponder. The covariate-adjusted hemodynamic predictors of death in the entire population were a low baseline systolic blood pressure (P = .0017) and a low baseline right ventricular stroke work index (P = .0395).

Conclusions: In patients with heart failure and pulmonary hypertension, low pulmonary arterial compliance, high pulmonary vascular resistance, and low diastolic blood pressure predict the nonresponsiveness to acute vasodilator challenge whilst a poor right ventricular function predicts a dismal prognosis.
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http://dx.doi.org/10.1016/j.cardfail.2021.01.021DOI Listing
August 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

Phosphodiesterase-5 Inhibitors and Outcomes During Left Ventricular Assist Device Support: A Systematic Review and Meta-Analysis.

J Card Fail 2021 04 29;27(4):477-485. Epub 2020 Dec 29.

Division of Cardiology, Duke University Medical Center, Durham, North Carolina. Electronic address:

Background: Phosphodiesterase-5 inhibitors (PDE5i) have been used to treat pulmonary hypertension and right ventricular failure in patients with left ventricular assist devices (LVAD). The effects of PDE5i on post-LVAD outcomes including hemocompatibility-related adverse events are not well-established. This systematic review and meta-analysis aims to evaluate the effects of PDE5i on post-LVAD outcomes.

Methods And Results: A comprehensive literature search was conducted using Pubmed and Embase databases from inception through November 25, 2020, to compare post-LVAD outcomes in patients with or without PDE5i use. Pooled odds ratio (OR) with 95% confidence intervals (CI) and I statistic were calculated. Thirteen observational studies were included in this analysis. The use of PDE5i was not significantly associated with lower postoperative right ventricular failure (OR 0.38, 95% CI 0.02-5.96, P = .41). There was no significant association between PDE5i and gastrointestinal bleeding (OR 1.23, 95% CI 0.76-1.98, P = .2), overall stroke (OR 0.60, 95% CI 0.21-1.68, P = .17), ischemic stroke (OR 0.61, 95% CI 0.09-4.07, P = .38), or pump thrombosis (OR 0.71, 95% CI 0.14-3.54, P = .46).

Conclusions: Our meta-analysis showed no significant association between PDE5i and post-LVAD right ventricular failure. Despite the antiplatelet effects of PDE5i, there was no significant association between PDE5i and gastrointestinal bleeding, overall stroke, ischemic stroke, or pump thrombosis. Randomized controlled studies are warranted to evaluate the net benefits or harms of PDE5i in the LVAD population.
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http://dx.doi.org/10.1016/j.cardfail.2020.12.018DOI Listing
April 2021

Cardiopulmonary Hemodynamics in Pulmonary Hypertension and Heart Failure: JACC Review Topic of the Week.

J Am Coll Cardiol 2020 12;76(22):2671-2681

Division of Cardiology, Department of Medicine, Medical University of South Carolina, Charleston, South Carolina. Electronic address:

Pulmonary hypertension (PH) is an independent risk factor for adverse clinical outcome, particularly in left heart disease (LHD) patients. Recent advances have clarified the mean pulmonary artery pressure (mPAP) range that is above normal and is associated with clinical events, including mortality. This progress has for the first time resulted in a new clinical definition of PH that is evidenced-based, is inclusive of mPAP >20 mm Hg, and emphasizes early diagnosis. Additionally, pulmonary vascular resistance (PVR) 2.2 to 3.0 WU, considered previously to be normal, appears to associate with elevated clinical risk. A revised approach to classifying PH patients as pre-capillary, isolated post-capillary, or combined pre-/post-capillary PH now guides point-of-care diagnosis, risk stratification, and treatment. Exercise hemodynamic or confrontational fluid challenge studies may also aid decision-making for patients with PH-LHD or otherwise unexplained dyspnea. This collective progress in pulmonary vascular and heart failure medicine reinforces the critical importance of accurate hemodynamic assessment.
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http://dx.doi.org/10.1016/j.jacc.2020.10.007DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7703679PMC
December 2020

Treatment of right ventricular dysfunction and heart failure in pulmonary arterial hypertension.

Cardiovasc Diagn Ther 2020 Oct;10(5):1659-1674

Division of Cardiology, Department of Medicine, Vanderbilt University Medical Center and Vanderbilt Translational and Clinical Cardiovascular Research Center, Nashville, TN, USA.

Right heart dysfunction and failure is the principal determinant of adverse outcomes in patients with pulmonary arterial hypertension (PAH). In addition to right ventricular (RV) dysfunction, systemic congestion, increased afterload and impaired myocardial contractility play an important role in the pathophysiology of RV failure. The behavior of the RV in response to the hemodynamic overload is primarily modulated by the ventricular interaction and its coupling to the pulmonary circulation. The presentation can be acute with hemodynamic instability and shock or chronic producing symptoms of systemic venous congestion and low cardiac output. The prognostic factors associated with poor outcomes in hospitalized patients include systemic hypotension, hyponatremia, severe tricuspid insufficiency, inotropic support use and the presence of pericardial effusion. Effective therapeutic management strategies involve identification and effective treatment of the triggering factors, improving cardiopulmonary hemodynamics by optimization of volume to improve diastolic ventricular interactions, improving contractility by use of inotropes, and reducing afterload by use of drugs targeting pulmonary circulation. The medical therapies approved for PAH act primarily on the pulmonary vasculature with secondary effects on the right ventricle. Mechanical circulatory support as a bridge to transplantation has also gained traction in medically refractory cases. The current review was undertaken to summarize recent insights into the evaluation and treatment of RV dysfunction and failure attributable to PAH.
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http://dx.doi.org/10.21037/cdt-20-348DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7666956PMC
October 2020

Pulmonary Artery Wedge Pressure Respiratory Variation Increases With Sodium Nitroprusside Vasodilator Challenge.

J Card Fail 2020 Dec 7;26(12):1096-1099. Epub 2020 Oct 7.

Division of Cardiology, Department of Medicine, Medical University of South Carolina, Charleston, South Carolina. Electronic address:

Background: The physiologic factors leading to pulmonary arterial wedge pressure respiratory variation (PAWP) are underexplored. We hypothesized that PAWP is associated with baseline PAWP and would predict response to sodium nitroprusside (SNP).

Methods And Results: We performed a retrospective study of right heart catheterization studies in 51 subjects with SNP challenge at our institution from 2012 to 2019. PAWP was defined as expiratory minus inspiratory PAWP. Baseline %PAWP was inversely correlated with baseline PAWP (R = -0.5). SNP administration led to increased %PAWP (+27%, P < .01). Subjects with low baseline PAWP (less than the median) had an increase in PAWP with SNP (3 ± 4 mm Hg), whereas those with a high baseline PAWP (greater than the median) did not (-0.6 ± 4 mm Hg, P = .003). Those who had a greater than the median PAWP increase with SNP had greater cardiac output augmentation compared with those who had less than a median increase in PAWP (1.7 ± 1.5 L/min vs 0.9 ± 0.7 L/min, P = .02). An increasing PAWP after SNP was associated with significant discrepancy in the number of subjects achieving transplant-acceptable pulmonary vascular resistance (<2.5 Wood units) when calculated by expiratory versus mean PAWP (37 vs 27 subjects, 20% discrepancy rate). Subjects with a higher PAWP after SNP were more likely to demonstrate discrepant transplant-acceptable pulmonary vascular resistance calculations comparing expiratory versus mean PAWP than those with lower PAWP post-SNP (47% vs 13%, odds ratio 5.5, P = .03).

Conclusions: Our findings indicate that PAWP is a meaningful physiologic parameter that is influenced by the compliance of the left heart/pulmonary vascular system and its relative preload and afterload states.
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http://dx.doi.org/10.1016/j.cardfail.2020.09.476DOI Listing
December 2020

Role of Pulmonary Artery Wedge Pressure Saturation During Right Heart Catheterization: A Prospective Study.

Circ Heart Fail 2020 11 3;13(11):e007981. Epub 2020 Oct 3.

Division of Cardiology, Department of Medicine, Medical University of South Carolina, Charleston (M.C.V., E.L.B., N.D.G., J.A., N.S.A., V.L.C.F., A.M., C.D.N., E.R.P., D.H.S., T.M.T., T.G.D.S., G.R.J., B.A.H., R.J.T.).

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http://dx.doi.org/10.1161/CIRCHEARTFAILURE.120.007981DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7674188PMC
November 2020
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