Combination therapy improves vascular volume in female rats with pulmonary hypertension.

Pulmonary arterial hypertension (PAH) is a female predominant disease in which progressive vascular remodeling and vasoconstriction result in right ventricular (RV) failure and death. Most PAH patients utilize multiple therapies. In contrast, the majority of preclinical therapeutic studies are performed in male rats with a single novel drug often markedly reversing disease in the model. We sought to differentiate single drug therapy from combination therapy in female rats with severe disease. One week after left pneumonectomy, we induced PH in young female Sprague-Dawley rats with an injection of monocrotaline (45 mg/kg). Female rats were then randomized to receive combination therapy (ambrisentan plus tadalafil), ambrisentan monotherapy, tadalafil monotherapy, or vehicle. We measured RV size and function on two serial echocardiograms during the development of disease. We measured RV systolic pressure (RVSP) invasively at day 28 after monocrotaline before analyzing the vascular volume with microcomputed tomography (microCT) of the right middle lobe. RVSP was significantly lower in female rats treated with combination therapy, and combination therapy resulted in increased small vessel volume density measured by microCT compared with untreated rats. Combination-treated rats had the smallest RV end-diastolic diameter on echocardiogram as compared with the other groups. In summary, we report a female model of pulmonary hypertension that can distinguish between one and two drug therapies; this model may facilitate better preclinical drug testing for novel compounds.

Low dose monocrotaline causes a selective pulmonary vascular lesion in male and female pneumonectomized rats.

Purpose/Aim: Low doses (30-80 mg/kg) of monocrotaline are commonly used to create experimental models of pulmonary hypertension in rats. At these doses, monocrotaline causes pulmonary endothelial apoptosis and acute lung injury which ultimately results in pulmonary vascular disease. Higher doses of monocrotaline (300 mg/kg) are known to create severe liver injury, but previous investigations with lower doses have not reported histology in other organs to determine whether the vascular injury with monocrotaline is pulmonary-selective or generalized. MATERIALS AND METHODS: We therefore sought to determine whether monocrotaline caused extra-pulmonary injury at doses commonly used in pulmonary hypertension studies. We performed left pneumonectomy on young male and female rats before administering 50-60 mg/kg monocrotaline 7 days later. We monitored serum chemistry and urine dipsticks during the first 3 weeks while the animals developed pulmonary hypertension. After 3 weeks, we sacrificed animals and stained the lungs and highly vascular visceral organs (kidney, liver, and spleen) for elastin to evaluate the degree of vascular injury and remodeling. RESULTS: We did not observe proteinuria or significant transaminitis over the 3 weeks following monocrotaline. As previously published, monocrotaline caused severe pulmonary vascular disease with neointimal lesions and medial hypertrophy. We did not identify significant large or small arterial damage in the kidneys, liver, or spleen. Two external veterinary pathologists did not identify histopathology in the kidneys, liver, or spleen of these rats. CONCLUSIONS: We conclude that 50-60 mg/kg of monocrotaline causes a selective pulmonary vascular lesion and that male and female rats have little non-pulmonary damage over 3 weeks at these doses of monocrotaline.

Nasopharyngeal viral PCR in immunosuppressed patients and its association with virus detection in bronchoalveolar lavage by PCR.

BACKGROUND AND OBJECTIVE: Pulmonary infiltrates are common in immunosuppressed patients. Bronchoscopy with bronchoalveolar lavage (BAL) is often used to evaluate their aetiology. However, it may not always be easily performed. Thus, alternative diagnostic strategies may be needed. There is limited data on the correlation of nasopharyngeal (NP) respiratory viral panel (RVP)-PCR testing compared with BAL. We aimed to identify the predictive value of NP RVP-PCR samples compared with samples obtained from BAL in immunosuppressed patients with pulmonary infiltrates. METHODS: We conducted an observational retrospective study of immunosuppressed adults who underwent bronchoscopy in the Pulmonary Department at the University of Rochester Medical Center between January 2011 and June 2016. We compared the positive and negative predictive values, sensitivity, specificity and false negative rate of NP RVP-PCR and BAL RVP-PCR, as well as identified clinical predictors of positive viral BAL RVP-PCR. RESULTS: Eighty-nine immunosuppressed patients had both NP and bronchoalveolar RVP-PCR testing. Twenty-one patients had NP(+)BAL(+) RVP-PCR testing. Seven patients had false negative (NP(-)BAL(+)) RVP-PCR testing. Three patients had NP(+)BAL(-) RVP-PCR testing. The positive and negative predictive values of NP RVP-PCR testing were 88% and 89%, respectively. Allogeneic bone marrow transplantation and testing performed in the winter and spring months were significantly associated with positive BAL RVP-PCR (OR = 3.3 (1.19-9.12); OR = 4.62 (1.64-12.99), respectively). CONCLUSION: NP RVP-PCR testing has high concordance with testing performed on BAL samples. Repeat testing through BAL is beneficial when there is high concern for viral infection after initial NP RVP-PCR testing is negative.

Cardiac effort and 6-min walk distance correlate with stroke volume measured by cardiac magnetic resonance imaging.

Right ventricular (RV) dysfunction in pulmonary arterial hypertension (PAH) is associated with poor outcomes. Cardiac magnetic resonance imaging (cMRI) is the gold standard for volumetric assessment, and few reports have correlated 6-min walk distance (6MWD) and cMRI parameters in PAH. Cardiac Effort, (the number of heart beats used during 6-min walk test)/(6MWD), incorporates physiologic changes into walk distance and has been associated with stroke volume (SV) measured by nuclear imaging and indirect Fick. Here, we aimed to interrogate the relationship of Cardiac Effort and 6MWD with SV measured by the gold standard, cMRI. This was a single-center, observational, prospective study in Group 1 PAH patients. Subjects completed 6-min walk with heart rate monitoring (Cardiac Effort) and cMRI within 24 h. cMRI was correlated to Cardiac Effort and 6MWD using Spearman Correlation Coefficient. Twenty-five participants with a wide range of RV function completed both cMRI and Cardiac Effort. There was a strong correlation between left ventricle SV index and both Cardiac Effort (r = -0.70, p = 0.0001) and 6MWD (r = 0.67, p = 0.0002). Cardiac Effort and 6MWD were statistically separated in patients at prognostically significant thresholds of left ventricle SV index (>31 ml/m2), RV Ejection Fraction (>35%), and SV/End Systolic Volume ( > 0.53). Cardiac Effort and 6MWD are noninvasive ways to gain insight into those with impaired SV. 6MWD may correlate better with SV than previously thought and heart rate monitoring provides physiologic context to the walk distance obtained.

Pulmonary Hypertension: How to Best Treat the Different Scleroderma Phenotypes?

Pulmonary hypertension (PH) is a leading cause of morbidity and mortality in systemic sclerosis (SSc). PH is a heterogenous condition and several different forms of PH are associated with SSc, including pulmonary arterial hypertension (PAH) resulting from a pulmonary arterial vasculopathy, PH due to interstitial lung disease, PH due to left heart disease, and PH due to thromboembolic disease. Extensive research has led to an improved understanding of the mediators involved in the pathogenesis of SSc-PH. Initial combination therapy is the preferred treatment approach for SSc-PAH and requires coordinated care with a multidisciplinary team including rheumatology, pulmonology, and cardiology.

Evaluation of Clinical Recovery After Surgical Treatment for Hand Ischemia From Vasospastic and Occlusive Disease Using PROMIS.

BACKGROUND: There is a paucity of literature describing the recovery trajectory after surgery for upper extremity ischemia. Using Patient-Reported Outcomes Measurement Information System (PROMIS) Physical Function (PF), Upper Extremity (UE), Pain Interference (PI), and Depression domains, we aimed to describe the postoperative recovery of such patients. METHODS: We queried our PROMIS database for patients undergoing surgery for vasospastic or occlusive disease over a 4.5-year period. Inclusion criteria were preoperative, early (average 3 weeks) and late (average 6 months) postoperative PROMIS PF and/or UE, PI, and Depression scores. The change in PROMIS scores was calculated for each time point. Changes in PROMIS scores were compared with minimal clinically important difference estimates. RESULTS: We identified 13 patients undergoing 13 surgical interventions that met inclusion criteria. More than one-half of our patients were men (n = 7 [54%]), and more than one-half of the surgeries (n = 7 [54%]) were for isolated occlusive diagnoses, with the remainder for vasospastic disease. At short-term postoperative follow-up, the change in PROMIS PF, UE, PI, and Depression scores was -6.34 (SD: 9.13), -6.81 (SD: 9.61), 3.16 (SD: 5.78), and -3.05 (SD: 8.37), respectively. At mid-term postoperative follow-up, the change in PROMIS PF, UE, PI, and Depression scores was 4.45 (SD: 10.33), 8.04 (SD: 13.84), -7.03 (SD: 7.06), and -12.27 (SD: 10.85), respectively. CONCLUSIONS: Our findings suggest patients undergoing surgical treatment for upper extremity ischemia experience a worsening of functional symptoms initially, as expected, followed by notable improvement.

Peak steps: Capacity for activity improves after adding approved therapy in pulmonary arterial hypertension.

Pulmonary arterial hypertension (PAH) patients have low activity. Activity intensity or duration could be a measure of clinical status or improvement. We aimed to determine whether standard or novel actigraphy measures could detect increases in activity after adding therapy. This was a prospective, single-center observational study evaluating activity after adding therapy in Group 1 PAH; we also report a validation cohort. For our study, two different accelerometers were used, a wrist (ActiGraph) and chest (MC10) device. Patients were analyzed in two groups, Treatment Intensification (TI, adding therapy) or Stable. Both groups had baseline monitoring periods of 7 days; the TI group had follow-up at 3 months, while Stables had follow-up within 4 weeks to assess stability. Activity time and steps were reported from both devices' proprietary algorithms. In ActiGraph only, steps in 1-min intervals throughout the day were ranked (not necessarily contiguous). Average values for each week were calculated and compared using nonparametric testing. Thirty patients had paired data (11 Stable and 19 TI). There was no between-group difference at baseline; we did not observe therapy-associated changes on average daily steps or activity time/intensity. The top 5 min of steps (capacity) increased after adding therapy; there was no difference in the stable group. This key finding was validated in a previously reported randomized trial studying a behavioral intervention to increase exercise. Total daily activity metrics are influenced by both disease and non-disease factors, making therapy-associated change difficult to detect. Peak minute steps were a treatment-responsive marker in both a pharmacologic and training intervention.

Transitioning selexipag to oral treprostinil in patients with pulmonary artery hypertension.

There are no prospective studies or guidelines describing transition between selexipag and oral treprostinil. We present two different transition strategies from selexipag to oral treprostinil, one started inpatient and then completed at home, and one completely under outpatient settings. Neither patient experienced worsening prostacyclin-type adverse effects; both were rigorous in their attention to a 7-8 hour administration schedule for oral treprostinil, and both experienced objective clinical benefit at follow-up. Prospective studies are needed to help guide clinical decisions when patients remain intermediate risk after a trial of either drug.

Cardiac Effort to Compare Clinic and Remote 6-Minute Walk Testing in Pulmonary Arterial Hypertension.

BACKGROUND: The SARS-CoV-2 pandemic has limited objective physiologic assessments. A standardized remote alternative is not currently available. "Cardiac effort" (CE), that is, the total number of heart beats divided by the 6-min walk test (6MWT) distance (beats/m), has improved reproducibility in the 6MWT and correlated with right ventricular function in pulmonary arterial hypertension. RESEARCH QUESTION: Can a chest-based accelerometer estimate 6MWT distance remotely? Is remote cardiac effort more reproducible than 6MWT distance when compared with clinic assessment? STUDY DESIGN AND METHODS: This was a single-center, prospective observational study, with institutional review board approval, completed between October 2020 and April 2021. Group 1 subjects with pulmonary arterial hypertension, receiving stable therapy for > 90 days, completed four to six total 6MWTs during a 2-week period to assess reproducibility. The first and last 6MWTs were performed in the clinic; two to four remote 6MWTs were completed at each participant's discretion. Masks were not worn. BioStamp nPoint sensors (MC10) were worn on the chest to measure heart rate and accelerometry. Two blinded readers counted laps, using accelerometry data obtained on the clinic or user-defined course. Averages of clinic variables and remote variables were used for Wilcoxon matched-pairs signed rank tests, Bland-Altman plots, or Spearman correlation coefficients. RESULTS: Estimated 6MWT distance, using the MC10, correlated strongly with directly measured 6MWT distance (r = 0.99; P < .0001; in 20 subjects). Remote 6MWT distances were shorter than clinic 6MWT distances: 405 m (330-464 m) vs 389 m (312-430 m) (P = .002). There was no difference between in-clinic and remote CE: 1.75 beats/m (1.48-2.20 beats/m) vs 1.86 beats/m (1.57-2.14 beats/m) (P = .14). INTERPRETATION: Remote 6MWT was feasible on a user-defined course; 6MWT distance was shorter than clinic distance. CE calculated by chest heart rate and accelerometer-estimated distance provides a reproducible remote assessment of exercise tolerance, comparable to the clinic-measured value.

An untapped resource: characteristics of thrombus recovered from intermediate or high risk pulmonary embolus patients.

INTRODUCTION: Response to anticoagulation varies during management of acute hospitalized pulmonary embolism. We aimed to study thrombus histology in pulmonary embolism samples removed during acute surgical embolectomy to evaluate whether thrombus morphology was similar between patients and whether there was an association with duration of symptoms and/or resolution on follow up imaging. METHODS: This was a retrospective observational single center study at the University of Rochester Medical Center. We evaluated patients that underwent acute surgical embolectomy and followed up in our clinic 2 - 4 months after the event with Ventilation/Perfusion (V/Q) scan obtained for all regardless of symptoms. Thromboemboli were formalin fixed and processed for light microscopy in the hospital histopathology laboratory. Four-micron thick sections were stained with hematoxylin and eosin, Masson trichrome, and Verhoeff elastic tissue stains. Immunohistochemistry was performed using anti-CD31 and anti-CD68. Slides were independently evaluated for time-dependent microscopic changes using Irniger's classification by two blinded pathologists. RESULTS: Sixteen patients underwent embolectomy with fifteen having V/Q imaging at follow up. The majority of patients were female. Samples showed a generally similar overall architecture that included a central core composed primarily of red blood cells and fibrin and an outer layer of platelets and monocytes. Two samples had evidence of fibrosis and recanalization. CONCLUSIONS: We found heterogeneous histopathology in samples obtained during acute embolectomy. Further prospective studies should systematically characterize clot morphology and evaluate treatment response and outcomes. Careful thrombus specimen measurement and consistent sampling for sections will be required to draw firm conclusions.

Comparison of chest- and wrist-based actigraphy in pulmonary arterial hypertension.

Aims: Activity trackers for clinical trials and remote monitoring are appealing as they provide objective data outside of the clinic setting. Algorithms determine physical activity intensity and count steps. Multiple studies show physical inactivity in pulmonary arterial hypertension (PAH). There are no studies comparing different activity trackers worn on different parts of the body in PAH. We had patients with PAH simultaneously wear two different accelerometers, compared measures between the two devices, and correlated the measures with standard clinical metrics in PAH. Methods and results: This was a single-centre, prospective observational study. Daily physical activity and daily total steps were measured using Actigraph GT9X Link and MC10 Biostamp nPoint for 5-10 days. Actigraph was worn on the non-dominant hand and the MC10 Biostamp nPoint was worn on the chest and leg with disposable adhesives. Twenty-two participants wore both accelerometers >12 h/day for an average 7.8 days. The average activity time measured by Actigraph was significantly higher than that measured by MC10 (251 ± 25 min vs. 113 ± 18 min, P = 0.0001). Actigraph's algorithm reported more time in light activity than moderate (190 ± 62 min vs. 60 ± 56 min, P = 0.0001). REVEAL 2.0 scores correlated highly with activity time measured using either device. Invasively measured haemodynamics within 7 days did not correlate with activity time or daily steps. Conclusion: Different activity trackers yield discordant results in PAH patients. Further studies are needed in determining the best device, optimal wear time, and different thresholds for activities in chronic diseases.

Asymptomatic necrotizing myositis in a young male with progressive interstitial lung disease.

Necrotizing autoimmune myopathy (NAM) is a rare inflammatory process characterized by bilateral proximal muscle weakness and elevated creatinine kinase levels. It is one of the idiopathic inflammatory myopathies. It can be associated with anti-signal recognition particle (SRP) antibody which is commonly seen in middle-aged females. Classic findings on muscle biopsy include muscle fiber necrosis without inflammation. Pulmonary manifestations associated with anti-SRP NAM is rare, and often a challenging correlation to make as our understanding of inflammatory myopathies and interstitial lung disease is still evolving. There have been some associations of Anti SRP NAM with NSIP which responds to corticosteroids. We present a 29 year old male with asymptomatic NAM who presented with a combination of NSIP and pulmonary arterial hypertension (PAH). His PAH was responsive to oral vasodilator therapy however his interstitial lung disease (ILD) rapidly progressed to usual interstitial pneumonia (UIP) requiring lung transplantation. This case highlights 1) an extremely rare presentation of rapidly progressive NAM associated ILD in a young man, in which pulmonary manifestations occurred in the absence of myopathy, 2) The importance of doing a complete work up for interstitial lung disease, including diligent examination for myopathic features and obtaining CK levels, 3) Identifying that interstitial lung diseases can progress despite control of the underlying etiology with corticosteroids and immunosuppressives, 4) Recognition of pre capillary PAH in patients with disproportionally elevated pressures relative to their pulmonary findings, 5) The first report of treatment responsive pulmonary vascular disease associated with NAM, and 6) The importance of early lung transplantation evaluation.

Resting heart rate as a surrogate for improvement in intermediate risk pulmonary embolus patients?

BACKGROUND: Pulmonary embolism (PE) response teams (PERT) have been developed to improve in-hospital mortality. Identifying intermediate risk PE patients that will progress despite anticoagulation is difficult, especially because outcomes with modern anticoagulation are quite good. OBJECTIVE: The primary aim of this study was to evaluate the rate of anticoagulation failure (new deep vein thrombosis or PE, right ventricular failure resulting in shock, cardiac arrest, or PE-attributable death) in intermediate risk PE patients managed by PERT. The secondary objective was to determine whether there was a significant decrease in heart rate 24 h after initiation of anticoagulation in intermediate risk PE. METHODS: This was a retrospective observational study of patients treated for acute intermediate risk PE at the University of Rochester Medical Center who also had outpatient followup between November 2016-June 2019. RESULTS: Ninety-two patients presented as intermediate-risk PE and had outpatient followup. Seventy-four patients were initially treated with anticoagulation. None of these patients failed anticoagulation. Of the eighteen intermediate risk patients that underwent advanced intervention, none failed anticoagulation first. There was significant decrease in resting heart rate 24 h after starting therapeutic anticoagulation, 107 beats/min vs 89 beats/min, p = 0.0001. CONCLUSION: We did not observe anticoagulation failure in the management of acute, intermediate risk PE. Reductions in heart rate may reflect improvements in right ventricular function; we hypothesize that those whose heart rate does not fall may be optimal candidates for advanced intervention.

Vasodilator use in precapillary pulmonary hypertension with end stage kidney disease: A single center experience.

BACKGROUND AND OBJECTIVES: Pulmonary hypertension is commonly seen in end stage kidney disease and is most commonly due to elevated left heart pressures. There is limited data about vasodilator use during the management of Group 1 pulmonary arterial hypertension in the context of those who also have or later developed end stage kidney disease. The objective of this study was to determine safety and efficacy of vasodilator therapy in precapillary pulmonary hypertension requiring renal replacement therapy. DESIGN: This was a single-center retrospective case series. Patients were identified from our Pulmonary Hypertension Clinic using a historical roster from 2012 to 2020. Patients were included if they >18 years of age, had Group 1 or Group 4 (precapillary) pulmonary hypertension on right heart catheterization, and also had end stage kidney disease requiring either intermittent hemodialysis or peritoneal dialysis. RESULTS: 18 patients were identified with invasively confirmed Group 1 or Group 4 pulmonary hypertension and end stage kidney disease on renal replacement therapy. Scleroderma was the most common etiology for renal failure. 17 patients were treated with vasodilator therapy. Fifteen patients had paired right heart catheterizations that showed a significant decrease in mean pulmonary artery pressure and pulmonary vascular resistance. Therapy was relatively well tolerated but hypotension was common and midodrine was often helpful. Two patients had successful renal transplantation after starting vasodilator therapy. CONCLUSION: We found vasodilator therapy was reasonably well tolerated and associated with a drop in mean pressure and pulmonary vascular resistance in patients with end stage kidney disease on dialysis.

Direct oral anticoagulant therapy in patients with morbid obesity after intermediate- or high-risk pulmonary emboli.

There is little reported on the efficacy and safety of direct oral anticoagulants (DOACs) in morbid obesity after venous thromboembolism (VTE). In this observational study, patients were followed up after intermediate- or high-risk pulmonary embolism (PE) at the University of Rochester Pulmonary Hypertension Clinic 2-4 months after the initial event. All patients had echocardiography and V/Q imaging regardless of symptoms. Outcomes of interest were the rates of recurrent VTE, thrombus resolution and development of chronic thromboembolic pulmonary hypertension (CTEPH) in patients with morbid obesity treated with a DOAC compared to treatment with vitamin K antagonists and to non-morbidly obese patients after PE. Using the electronic medical record, recurrent events were assessed up to 12 months after the event. 107 patients (body mass index (BMI)>40 kg·m-2, n=32; BMI 30-39.9 kg·m-2, n=39; BMI<30 kg·m-2, n=36) attended follow-up appointments after treatment for PE. A DOAC was used in 70 patients (BMI>40 kg·m-2, n=19; BMI 30-39.9 kg·m-2, n=27; BMI<30 kg·m-2, n=24). There were no recurrent events within the first 12 months of initial diagnosis based on symptoms and imaging in any patient. There was no difference in rate of residual unmatched perfusion defect with DOACs or conventional anticoagulation (49% versus 49%). This finding remained in the subset of morbidly obese patients (47% versus 50%). For the overall cohort, there was no difference in the rate of CTEPH development based on anticoagulation with a DOAC (5% versus 8% with warfarin). There were no major bleeding complications with a DOAC. DOAC therapy appears to be effective and safe in morbid obesity even after intermediate- or high-risk PE. ​.

Heart rate monitoring improves clinical assessment during 6-min walk.

Right ventricular (RV) function is a predictor of outcomes in pulmonary arterial hypertension (PAH). The 6-min walk test (6MWT) is likely an indirect measure of RV function during exercise, but changes in absolute walk distance can also be influenced by factors like effort and musculoskeletal disease. Paired 6MWT with continuous electrocardiogram monitoring was performed in stable PAH patients, patients adding PAH therapies, and healthy controls. Heart rate expenditure (HRE) was calculated (integrating pulse during 6MWT) and then divided by walk distance (HRE/d). We also evaluated changes in peak heart rate, time above age-adjusted maximum predicted heart rate, and heart rate at 6 min. HRE/d was compared to invasive hemodynamic measures in patients who had right heart catheterization performed within seven days, WHO functional class assessment, and Emphasis 10 questionnaire. We measured two 6MWT in 15 stable PAH patients, 13 treatment intensification patients, and 8 healthy controls. HRE/d was reproducible in the stable PAH group (median difference, -0.79%), while it decreased (median difference, 23%, p = 0.0001) after adding vasodilator therapy. In 11 patients with right heart catheterization, HRE/d correlated strongly with stroke volume, r = -0.72, p = 0.01. Peak heart rate decreased after adding vasodilator therapy. HRE/d also correlated with WHO functional class and Emphasis 10 score. Continuous heart rate monitoring during 6MWT provides valuable physiologic data accounting for effort. HRE/d appears to enhance test reproducibility in stable patients while detecting change after adding therapy as compared to walk distance alone.

Clinical and imaging outcomes after intermediate- or high-risk pulmonary embolus.

Long-term outcomes after acute pulmonary embolism vary from complete resolution to chronic thromboembolic pulmonary hypertension (CTEPH). Guidelines after acute pulmonary embolism are generally limited to anticoagulation duration. We assessed patients with estimated prognosis >1 year in our pulmonary hypertension clinic 2-4 months after treatment for intermediate- or high-risk acute pulmonary embolism. At follow-up, ventilation-perfusion scan and echocardiogram were offered. The aim of this study was to assess for recurrent symptomatic disease, residual imaging defects or right ventricular dysfunction, and functional disability after acute management of pulmonary embolism. After treatment for acute intermediate- or high-risk pulmonary embolism, 104 patients followed up in pulmonary hypertension clinic. Of those, 55% of patients had self-reported limitation in activity. No patients had symptomatic recurrence of pulmonary embolism. Forty-eight percent of patients had residual perfusion defects on perfusion imaging, while 91% of patients had either normal or only mildly enlarged right ventricles. We identified heart failure preserved ejection fraction, iron deficiency, and obstructive sleep apnea as significant contributors to breathlessness. Treatment of these conditions was associated with improvement. Surprisingly, we diagnosed CTEPH in nine patients; for some, chronic thrombus may already have been present at the time of index evaluation. Our findings suggest that follow-up in a dedicated pulmonary hypertension clinic 2-4 months after acute intermediate- or high-risk pulmonary embolism may add value to patient care. We identified treatable comorbidities that could be contributing to post-pulmonary embolism syndrome as well as CTEPH.

Chronic therapeutic anticoagulation is associated with decreased thrombotic complications in SARS-CoV-2 infection.

BACKGROUND: Thrombotic disease complicates severe SARS-CoV-2 infection and is associated with increased morbidity and mortality. Various anticoagulation strategies have been evaluated in hospitalized patients to prevent complications. The impact of chronic anticoagulation before SARS-CoV-2 infection on the risk for subsequent thrombosis has not been systematically studied. METHODS: This was a retrospective single-center study. All patients with positive SARS-CoV-2 PCR testing from March 13, 2020, through May 6, 2020, at the University of Rochester Medical Center were identified. We included all patients receiving therapeutic anticoagulation for at least 1 month before COVID diagnosis. We documented the rate of thrombotic complications, type of anticoagulation, bleeding complications, and mortality. RESULTS: A total of 107 SARS-CoV2-infected patients were chronically anticoagulated before SARS-CoV-2 testing with a median age of 78. Of those, 42 required hospital admission, with 17 requiring intensive care. No patients, inpatient or outpatient, were diagnosed with a new symptomatic thrombotic complication. Three patients had minor bleeding in the hospital. Thirteen (12%) patients died (69% male). CONCLUSION: Our uncontrolled findings suggest that chronic anticoagulation at the time of infection may protect against thrombotic complications and decrease disease severity.