Pulmonary hypertension, pulmonary embolism and COVID-19: A district general hospital experience from the UK.

BACKGROUND: Preliminary data suggest that the prevalence of pulmonary hypertension (PH) in patients with COVID-19 is around 13%, but its prognostic role remains unclear. Approximately 3% of patients develop chronic thrombo-embolic pulmonary hypertension (CTEPH) following diagnosis of acute pulmonary embolism (PE). It is recommended that patients are screened for CTEPH if they remain symptomatic 3 months following diagnosis of PE. The primary aim of the study was to assess the chances of persistent PH following PE secondary to COVID-19. METHODS: We conducted a retrospective cohort study at a District General Hospital (DGH) in the United Kingdom. All patients diagnosed with COVID-19 and PE between April 2020 and October 2021 were examined. Patients were divided into two groups:·COVID-19 and PE with comorbidities (excluding pre-existing PH) and·COVID-19 and PE without comorbidities. We compared the ECHO features suggestive of PH between the two groups at the time of diagnosis of PE and at 3 months following treatment. RESULTS: 80 patients were included in the study (49 with comorbidities and 31 with no comorbidities). Average age of comorbidities and no comorbidities groups were 73 years and 70 years, respectively. Average PaO2/FiO2 ratio for comorbidities and no comorbidities groups were 170 and 195, respectively. Fourteen patients (13 with comorbidities and 1 with no comorbidities) died in total. Results showed that risk of persistent PH and subsequent mortality following PE in COVID-19 is 4.17 times and 1.32 times more in comorbidity group as compared to no comorbidity group, respectively (p < 0.001). CONCLUSION: Patients with comorbidities are at high risk of persistent PH and mortality due to PE secondary to COVID-19.

["Guiding lights" for the diagnosis of chronic thromboembolic pulmonary hypertension in the flow of patients with pulmonary embolism].

On December 13, 2021, an expert council was held to determine the position of experts of different specialties regarding the reasons for the low level of diagnosis of chronic thromboembolic pulmonary hypertension (CTEPH) in real clinical practice in a pandemic of a new coronavirus infection and possible ways to improve detection in patients with pulmonary embolism (PE) ) in history. The reasons for the low level of diagnosis of CTEPH are the insufficient level of knowledge of specialists, especially primary care physicians; lack of clear regulatory documents and expert centers for the management of this category of patients. Primary diagnosis of CTEPH in a pandemic can be strengthened through the widespread use of telemedicine for consultations of primary care physicians with specialists from expert centers; to maximize the role of echocardiography and computed tomography (CT) as differential diagnostic tools for dyspnea, in particular in patients with COVID-19. To increase the detection rate of CTEPH, diagnostic vigilance is required in patients with risk factors and episodes of venous thromboembolism. To improve the screening of CTEPH, it is necessary to create an algorithm for monitoring patients who have had PE; provide educational activities, including through the media; create materials for patients with accessible information. The regulatory documents should designate the circle of responsible specialists who will be engaged in long-term monitoring of patients with PE. Educational programs are needed for primary care physicians, cardiologists, and other physicians who come into the field of view of patients with CTEPH; introduction of a program to create expert centers for monitoring and managing patients with the possibility of performing ventilation-perfusion lung scintigraphy, cardiopulmonary stress test, CT, right heart catheterization. It seems important to build cooperation with the Ministry of Health of Russia in order to create special protocols, procedures for managing patients with PE and CTEPH.

Outcomes of COVID-19 in patients vaccinated and unvaccinated against SARS-CoV-2 and suffering from pulmonary arterial hypertension and chronic thromboembolic pulmonary hypertension.

INTRODUCTION: Pulmonary arterial hypertension (PAH) and chronic thromboembolic pulmonary hypertension (CTEPH) lead to progressive right heart failure. The mortality rates in PAH and CTEPH patients due to COVID­19 are high, and vaccination against COVID­19 is recommended in this group. OBJECTIVES: We analyzed the incidence and outcomes of COVID­19in the PAH/CTEPH patients for 2 years of the pandemic, as well as the predictors of worse outcomes of COVID­19 in this group. PATIENTS AND METHODS: PAH/CTEPH patient data for this observational, cohort study were obtained from 3 pulmonary hypertension centers between March 11, 2020 and March 11, 2022. RESULTS: A total of 364 consecutive patients with PAH/CTEPH (248/122; 232 women [64%]; median [interquartile range] age, 61 years [18-92]) were included in the study. All the patients had advanced pulmonary hypertension at baseline. Eighty­five patients (23%) suffered from COVID­19. Seven of them (8%), all of whom were unvaccinated, died of COVID­19. The unvaccinated patients suffered from COVID­19 more often than the vaccinated ones (46% vs 9%; P <0.001). As many as 31% of the PAH/CTEPH patients with COVID­19 needed hospitalization, in 8% of cases in the intensive care unit. Age equal to or above 65 years and severe pulmonary hypertension defined as a World Health Organization functional class 3 or 4 were associated with severe COVID­19 in the PAH/CTEPH patients. CONCLUSIONS: The vaccinated PAH/CTEPH patients suffered from COVID­19 less frequently than the unvaccinated ones. The mortality rate and hospitalization due to COVID­19 were higher in the PAH/CTEPH patients than in the general population. All efforts should be made to convince the PAH/CTEPH patients to vaccinate against COVID­19.

Inhaled Nitric Oxide in Acute Severe Pulmonary Hypertension and Severe Acute Respiratory Distress Syndrome Secondary to COVID-19 Pneumonia: A Case Report.

BACKGROUND Inhaled nitric oxide (iNO) is used as a treatment for pulmonary arterial hypertension (PAH). Severe hypoxia with hypoxic vasoconstriction caused by severe acute respiratory distress syndrome (ARDS) can induce pulmonary hypertension with hemodynamic implications, mainly secondary to right ventricle (RV) systolic function impairment. We report the case of the use of iNO in a critically ill patient with bilateral SARS-CoV-2 pneumonia and severe ARDS and hypoxemia leading to acute severe PAH, causing a ventilation/perfusion mismatch, RV pressure overload, and RV systolic dysfunction. CASE REPORT A 36-year-old woman was admitted to the Intensive Care Unit with a severe ARDS associated with SARS-CoV-2 pneumonia requiring invasive mechanical ventilation. Severe hypoxia and hypoxic vasoconstriction developed, leading to an acute increase in pulmonary vascular resistance, severe to moderate tricuspid regurgitation, RV pressure overload, RV systolic function impairment, and RV dilatation. Following 24 h of treatment with iNO at 15 ppm, significant oxygenation and hemodynamic improvement were noted, allowing vasopressors to be stopped. After 24 h of iNO treatment, echocardiography showed very mild tricuspid regurgitation, a non-dilated RV, no impairment of transverse free wall contractility, and no paradoxical septal motion. iNO was maintained for 7 days. The dose of iNO was progressively decreased with no adverse effects and maintaining an improvement of oxygenation and hemodynamic status, allowing respiratory weaning. CONCLUSIONS Sustained acute hypoxia in ARDS secondary to SARS-CoV-2 pneumonia can lead to PAH, causing a ventilation/perfusion mismatch and RV systolic impairment. iNO can be considered in patients with significant PAH causing hypoxemia and RV dysfunction.

Pulmonary artery pressures and right ventricular dimensions of post-COVID-19 patients without previous significant cardiovascular pathology.

BACKGROUND: Pulmonary hypertension is a significant complication of COVID-19, but follow-up data on pulmonary artery pressure after recovery from COVID-19 are limited. OBJECTIVES: To investigate pulmonary artery pressure and heart dimensions in post-COVID-19 patients without a history of significant cardiac pathology. METHODS: Data for 91 eligible adult patients were subjected to 2 analyses. First, patients were grouped according to where they received COVID-19 treatment: the ICU, COVID-19 ward, or outpatient clinic. Second, the severity of COVID-19 was grouped as no pulmonary involvement, non-severe pulmonary involvement, or severe pulmonary involvement based on thoracic computed tomography scores. Heart dimensions were measured and pulmonary artery pressure was estimated using transthoracic echocardiography. The correlation between transthoracic echocardiography findings and COVID-19 severity was assessed. RESULTS: Pulmonary artery pressure and right-heart dimensions were significantly elevated in the post-COVID-19 patients without a history of risk factors for pulmonary hypertension that presented to the cardiology outpatient clinic with cardiac complaints. Both of these findings were correlated with the severity of COVID-19 and the extent of lung involvement based on thoracic computed tomography. CONCLUSION: The present findings confirm that increases in systolic pulmonary artery pressure and right ventricular dimensions persist 2-3 months after recovery from COVID-19 in patients without a history of risk factor for pulmonary hypertension. Furthermore, the increase in pulmonary artery pressure and right ventricular dimensions correlate with the severity of COVID-19 and the extent of lung involvement based on thoracic computed tomography.

Management of COVID-19 in Patients with Pulmonary Arterial Hypertension.

In this review, we discuss the evidence regarding the course and management of COVID-19 in patients with pulmonary arterial hypertension (PAH), the challenges in PAH management during the pandemic and, lastly, the long-term complications of COVID-19 in relation to pulmonary vascular disease. The inherent PAH disease characteristics, as well as age, comorbidities, and the patient's functional status act synergistically to define the prognosis of COVID-19 in patients with PAH. Management of COVID-19 should follow the general guidelines, while PAH-targeted therapies should be continued. The pandemic has caused a shift toward telemedicine in the chronic care of patients with PAH. Whether COVID-19 could predispose to the development of chronic pulmonary hypertension is a subject of future investigation.

An expert opinion of the Polish Cardiac Society Working Group on Pulmonary Circulation on screening for chronic thromboembolic pulmonary hypertension patients after acute pulmonary embolism: Update.

Chronic thromboembolic pulmonary hypertension (CTEPH) is a rare complication of acute pulmonary embolism (APE). Both pharmacological and invasive treatments for CTEPH are available in Poland, and awareness of the disease among physicians is growing. It has been suggested that the COVID-19 pandemic may increase the incidence of CTEPH and facilitate disease detection during more advanced stages of the illness. Thus, the Polish Cardiac Society's Working Group on Pulmonary Circulation, in cooperation with independent experts in this field, launched the updated statement on the algorithm to guide a CTEPH diagnosis in patients with previous APE. CTEPH should be suspected in individuals after APE with dyspnea, despite at least 3 months of effective anticoagulation, particularly when specific risk factors are present. Echocardiography is the main screening tool for CTEPH. A diagnostic workup of patients with significant clinical suspicion of CTEPH and right ventricular overload evident on echocardiography should be performed in reference centers. Pulmonary scintigraphy is a safe and highly sensitive screening test for CTEPH. Computed tomography pulmonary angiography with precise detection of thromboembolic residues in the pulmonary circulation is important for the planning of a pulmonary thromboendarterectomy. Right heart catheterization definitively confirms the presence of pulmonary hypertension and direct pulmonary angiography allows for the identification of lesions suitable for thromboendarterectomy or balloon pulmonary angioplasty. In this document, we propose a diagnostic algorithm for patients with suspected CTEPH. With an individualized and sequential diagnostic strategy, each patient can be provided with suitable and tailored therapy provided by a dedicated CTEPH Heart Team.

COVID-19 in Patients with Pulmonary Hypertension: A National Prospective Cohort Study.

Rationale: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection is associated with pulmonary endothelial dysfunction. There are limited data available on the outcomes of coronavirus disease (COVID-19) in patients with pulmonary hypertension (PH), a disease characterized by pulmonary endothelial dysfunction. Objectives: To describe characteristics and outcomes of patients with precapillary PH and COVID-19. Methods: We prospectively collected characteristics, management, and outcomes of adult patients with precapillary PH in the French PH network who had COVID-19 between February 1, 2020, and April 30, 2021. Clinical, functional, and hemodynamic characteristics of PH before COVID-19 were collected from the French PH registry. Measurements and Main Results: A total of 211 patients with PH (including 123 with pulmonary arterial hypertension, 47 with chronic thromboembolic PH, and 41 with other types of PH) experienced COVID-19, and 40.3% of them were outpatients, 32.2% were hospitalized in a conventional ward, and 27.5% were in an ICU. Among hospitalized patients (n = 126), 54.0% received corticosteroids, 37.3% high-flow oxygen, and 11.1% invasive ventilation. Right ventricular and acute renal failure occurred in 30.2% and 19.8% of patients, respectively. Fifty-two patients (all hospitalized) died from COVID-19. Overall mortality was 24.6% (95% CI [confidence interval], 18.8-30.5) and in-hospital mortality 41.3% (95% CI, 32.7-49.9). Nonsurvivors were significantly older, more frequently male and suffering comorbidities (diabetes, chronic respiratory diseases, systemic hypertension, chronic cardiac diseases, and/or chronic renal failure), and had more severe PH at their most recent evaluation preceding COVID-19 diagnosis (in terms of functional class and 6-minute-walk distance; all P < 0.05). Use of pulmonary arterial hypertension therapy was similar between survivors and nonsurvivors. Conclusions: COVID-19 in patients with precapillary PH was associated with a high in-hospital mortality. The typical risk factors for severe COVID-19 and severity of PH were associated with mortality in this population.

Chronic thromboembolic pulmonary hypertension secondary to Behçet's disease: an extremely rare pediatric case.

Chronic thromboembolic pulmonary hypertension is an uncommon condition in the children. It almost always accompanies a hypercoagulable state. We described a rare case of Behçet's disease presenting with chronic thromboembolic pulmonary hypertension and initially misdiagnosed as coronavirus disease 2019 pneumonia.

Nitric oxide: Clinical applications in critically ill patients.

Inhaled nitric oxide (iNO) acts as a selective pulmonary vasodilator and it is currently approved by the FDA for the treatment of persistent pulmonary hypertension of the newborn. iNO has been demonstrated to effectively decrease pulmonary artery pressure and improve oxygenation, while decreasing extracorporeal life support use in hypoxic newborns affected by persistent pulmonary hypertension. Also, iNO seems a safe treatment with limited side effects. Despite the promising beneficial effects of NO in the preclinical literature, there is still a lack of high quality evidence for the use of iNO in clinical settings. A variety of clinical applications have been suggested in and out of the critical care environment, aiming to use iNO in respiratory failure and pulmonary hypertension of adults or as a preventative measure of hemolysis-induced vasoconstriction, ischemia/reperfusion injury and as a potential treatment of renal failure associated with cardiopulmonary bypass. In this narrative review we aim to present a comprehensive summary of the potential use of iNO in several clinical conditions with its suggested benefits, including its recent application in the scenario of the COVID-19 pandemic. Randomized controlled trials, meta-analyses, guidelines, observational studies and case-series were reported and the main findings summarized. Furthermore, we will describe the toxicity profile of NO and discuss an innovative proposed strategy to produce iNO. Overall, iNO exhibits a wide range of potential clinical benefits, that certainly warrants further efforts with randomized clinical trials to determine specific therapeutic roles of iNO.

Pulmonary Hypertension and COVID-19.

Coronavirus disease 2019 (COVID-19) is a primary respiratory infectious disease, which can result in pulmonary and cardiovascular complications. From its first appearance in the city of Wuhan (China), the infection spread worldwide, leading to its declaration as a pandemic on March 11, 2020. Clinical research on SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2) suggests that the virus may determine changes in the pulmonary hemodynamics through mechanisms of endothelial dysfunction, vascular leak, thrombotic microangiopathy, and venous thromboembolism that are similar to those leading to pulmonary hypertension (PH). Current available studies report echocardiographic signs of PH in approximately 12 to 13% of hospitalized patients with COVID-19. Those with chronic pulmonary obstructive disease, congestive heart failure, pulmonary embolism, and prior PH are at increased risk to develop or worsen PH. Evidence of PH seems to be associated with increased disease severity and poor outcome. Because of the importance of the pulmonary hemodynamics in the pathophysiology of COVID-19, there is growing interest in exploring the potential therapeutical benefits of inhaled vasodilators in patients with COVID-19. Treatment with inhaled nitric oxide and prostacyclin has shown encouraging results through improvement of systemic oxygenation, reduction of systolic pulmonary arterial pressure, and prevention of right ventricular failure; however, data from randomized control trials are still required.

Pulmonary Hypertensive Changes Secondary to COVID-19 Pneumonia in a Chronically SARS-CoV-2-Infected Bilateral Lung Explant.

COVID-19, the syndrome caused by the novel coronavirus SARS-CoV-2, has spread throughout the world, causing the death of at least three million people. For the over 81 million who have recovered, however, the long-term effects are only beginning to manifest. We performed a bilateral lung transplant on a 31-year-old male patient for chronic hypoxic respiratory failure, severe pulmonary hypertension and radiographically identified pulmonary fibrosis five months after an acute COVID-19 infection. The explant demonstrated moderate pulmonary vascular remodeling with intimal thickening and medial hypertrophy throughout, consistent with pulmonary hypertension. The parenchyma demonstrated an organizing lung injury in the proliferative phase, with severe fibrosis, histiocytic proliferation, type II pneumocyte hyperplasia, and alveolar loss consistent with known COVID-19 pneumonia complications.This report highlights a novel histologic finding in severe, chronic COVID-19. Although the findings in acute COVID-19 pneumonia have been well-examined at autopsy, the chronic course of this complex disease is not yet understood. The case presented herein suggests that COVID-induced pulmonary hypertension may become more common as more patients survive severe SARS-CoV-2-related pneumonia. Pulmonologists and pulmonary pathologists should be aware of this possible association and look for the clinical, radiographic, and histologic criteria in the appropriate clinical setting.

Giant Pulmonary Artery Thrombotic Material, Due to Chronic Thromboembolic Pulmonary Hypertension, Mimics Pulmonary Artery Sarcoma.

In this article, we present the case of a 38-year-old female who suffered from serious respiratory distress. After an extensive pulmonary artery imaging diagnostic work-up (CTPA, MRA and PET), we were unable to differentiate between chronic thromboembolic pulmonary hypertension (CTEPH) vs. pulmonary artery sarcoma (PAS) due to extensive filling defects and extraluminal findings. Although surgery was postponed for nine months due to the COVID-19 pandemic, CTEPH diagnosis, due to a high-thrombus burden, was finally confirmed after pulmonary endarterectomy (PEA). Conclusively, imaging findings of rare cases of CTEPH might mimic PAS and the surgical removal of the lesion are both needed for a final diagnosis. What is Already Known about This Topic? Pulmonary artery sarcoma (PAS) is a rare but aggressive malignancy, which originates from the intimal layer of the pulmonary artery (PA); Chronic thromboembolic pulmonary hypertension (CTEPH) is based on chronic, organized flow-limiting thrombi inside PA circulation and subsequent pulmonary hypertension. What Does This Study Contribute? Since radiological findings of CTEPH cases might rarely mimic PAS, pulmonary artery endarterectomy and subsequent histopathologic study are needed for a final diagnosis.

Whooping cough complicating pulmonary hypertension in pregnancy.

We report a case of a previously fit woman who presented at 26 weeks into her fourth pregnancy with a dry cough. Following a nasopharyngeal swab, she was diagnosed with a pertussis infection, and treated with antibiotics. A chest X-ray showed right atrial dilatation and an echocardiogram was scheduled outpatient. However, after re-presenting with worsening cough and dyspnoea, an inpatient echocardiogram was performed which suggested elevated pulmonary pressures with significant tricuspid regurgitation, as confirmed by subsequent cardiac catheterisation. She had an elective caesarean section at 34 weeks and underwent repeat right heart catheterisation which revealed persistent, and likely pre-existing, pulmonary arterial hypertension. This case highlights the importance of thorough assessment of non-obstetric symptoms in pregnancy in formulating alternative differentials, even after a diagnosis has been made, to prevent potentially life-threatening conditions from being missed. It also shows that although often associated, respiratory and cardiac causes may coexist separately.

Outcomes of COVID-19 infection in pediatric pulmonary hypertension: A single-center experience.

BACKGROUND: The global COVID-19 pandemic was particularly concerning for the pediatric pulmonary hypertension (PH) population due to immature immune systems and developmental comorbidities. This study aims to describe a single-center experience of pediatric PH patients diagnosed with COVID-19 disease. METHODS: A retrospective cohort study of all pediatric patients followed by the PH Center at Texas Children's Hospital diagnosed with COVID-19 infection from April 2020 to February 2021. RESULTS: We identified 23 patients with a median age of 58 months (interquartile range [IQR]: 25-75th, 21-132 months), 48% being Hispanics. Eight patients (35%) required hospitalization; median length of stay was 6 days (IQR: 25-75th, 5-8 days). Only three of these eight patients required increased respiratory support. Targeted PH therapy was escalated in four patients (two in dual and two in triple therapy). There was one mortality in a patient with failing Fontan physiology. Ninety-one percent of patients have had post-COVID outpatient follow-up, median of 101 days (IQR: 25-75th, 50-159 days) from diagnosis. Of the five patients with 6 min walk test (6MWT) data, three (60%) children walked less distance, median of -12 m (IQR: 25-75th, -12 to +49 m) compared to pre-COVID testing. Postinfection pulmonary function testing (PFT) was notable for decrease in predicted forced vital capacity (FVC; median -6%, range -11% to +6%) and forced expiratory volume in one second (FEV1; median -14%, range -12% to -18%) in 75% of the patients with PFT data. CONCLUSION: In our institution, COVID-19 was found more frequently in Hispanics and associated with low mortality.

The Oxygen Transport Triad in High-Altitude Pulmonary Edema: A Perspective from the High Andes.

Acute high-altitude illnesses are of great concern for physicians and people traveling to high altitude. Our recent article "Acute Mountain Sickness, High-Altitude Pulmonary Edema and High-Altitude Cerebral Edema, a View from the High Andes" was questioned by some sea-level high-altitude experts. As a result of this, we answer some observations and further explain our opinion on these diseases. High-Altitude Pulmonary Edema (HAPE) can be better understood through the Oxygen Transport Triad, which involves the pneumo-dynamic pump (ventilation), the hemo-dynamic pump (heart and circulation), and hemoglobin. The two pumps are the first physiologic response upon initial exposure to hypobaric hypoxia. Hemoglobin is the balancing energy-saving time-evolving equilibrating factor. The acid-base balance must be adequately interpreted using the high-altitude Van Slyke correction factors. Pulse-oximetry measurements during breath-holding at high altitude allow for the evaluation of high altitude diseases. The Tolerance to Hypoxia Formula shows that, paradoxically, the higher the altitude, the more tolerance to hypoxia. In order to survive, all organisms adapt physiologically and optimally to the high-altitude environment, and there cannot be any "loss of adaptation". A favorable evolution in HAPE and pulmonary hypertension can result from the oxygen treatment along with other measures.

Clinical observations of COVID-19 infection in patients with chronic thromboembolic pulmonary hypertension.

Aim    To present clinical observations of the novel coronavirus infection (COVID-19) in patients with chronic thromboembolic pulmonary hypertension (CTEPH) after a surgical intervention in the form of thromobendarterectomy from pulmonary artery branches.Material and methods    The Acad. E.N. Meshalkin National Medical Research Center performed 127 open surgical interventions for CTEPH in the form of thromobendarterectomy from 2016 through 2020. The present study enrolled 113 patients included into the follow-up care group and into the Center Registry who were followed up for more than 6 months after the surgery. Clinical and functional features of COVID-19 were evaluated in the studied group.Results    In the follow-up care group, 5 (4.4%) postoperative CTEPH patients had COVID-19. One patient had asymptomatic disease, and others had typical clinical symptoms and bilateral polysegmental pneumonia. There were no cases requiring artificial ventilation and no lethal outcomes. All patients with COVID-19 received anticoagulants as a basis therapy for CTEPH, and two patients who had residual pulmonary arterial hypertension (PAH) additionally received a PAH-specific therapy. During the treatment of COVID-19, no adjustment of the anticoagulant or PAH-specific therapy was required.Conclusion    The group of patients with CTEPH is a unique pathophysiological model for studying the effect of COVID-19 under the conditions of compromised pulmonary circulation. In the studied follow-up care group, the COVID-19 morbidity was 4.4 % without fatal outcomes. Evaluation of the role of chronic anticoagulant and PAH-specific therapy in COVID-19 postoperative patients as well as evaluation of the role of COVID-19 in CTEPH progression merit further investigation.