["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.

Pulmonary hypertension at admission predicts ICU mortality in elderly critically ill with severe COVID-19 pneumonia: retrospective cohort study.

BACKGROUND: Point-of-care ultrasound (POCUS) is a useful diagnostic tool for non-invasive assessment of critically ill patients. Mortality of elderly patients with COVID-19 pneumonia is high and there is still scarcity of definitive predictors. Aim of our study was to assess the prediction value of combined lung and heart POCUS data on mortality of elderly critically ill patients with severe COVID-19 pneumonia. METHODS: This was a retrospective observational study. Data of patients older than 70 years, with severe COVID-19 pneumonia admitted to mixed 25-bed, level 3, intensive care unit (ICU) was analyzed retrospectively. POCUS was performed at admission; our parameters of interest were pulmonary artery systolic pressure (PASP) and presence of diffuse B-line pattern (B-pattern) on lung ultrasound. RESULTS: Between October 2020 and March 2021, 117 patients aged 70 years or more (average age 77 ± 5 years) were included. Average length of ICU stay was 10.7 ± 8.9 days. High-flow oxygenation, non-invasive ventilation and invasive mechanical ventilation were at some point used to support 36/117 (31%), 39/117 (33%) and 75/117 (64%) patients respectively. ICU mortality was 50.9%. ICU stay was shorter in survivors (8.8 ± 8.3 vs 12.6 ± 9.3 days, p = 0.02). PASP was lower in ICU survivors (32.5 ± 9.8 vs. 40.4 ± 14.3 mmHg, p = 0.024). B-pattern was more often detected in non-survivors (35/59 (59%) vs. 19/58 (33%), p = 0.005). PASP and B-pattern at admission, and also mechanical ventilation and development of VAP, were univariate predictors of mortality. PASP at admission was an independent predictor of ICU (OR 1.061, 95%CI 1.003-1.124, p = 0.039) and hospital (OR 1.073, 95%CI 1.003-1.146, p = 0.039) mortality. CONCLUSIONS: Pulmonary artery systolic pressure at admission is an independent predictor of ICU and hospital mortality of elderly patients with severe COVID-19 pneumonia.

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.

Inference following multiple imputation for generalized additive models: an investigation of the median p-value rule with applications to the Pulmonary Hypertension Association Registry and Colorado COVID-19 hospitalization data.

BACKGROUND: Missing data prove troublesome in data analysis; at best they reduce a study's statistical power and at worst they induce bias in parameter estimates. Multiple imputation via chained equations is a popular technique for dealing with missing data. However, techniques for combining and pooling results from fitted generalized additive models (GAMs) after multiple imputation have not been well explored. METHODS: We simulated missing data under MCAR, MAR, and MNAR frameworks and utilized random forest and predictive mean matching imputation to investigate a variety of rules for combining GAMs after multiple imputation with binary and normally distributed outcomes. We compared multiple pooling procedures including the "D2" method, the Cauchy combination test, and the median p-value (MPV) rule. The MPV rule involves simply computing and reporting the median p-value across all imputations. Other ad hoc methods such as a mean p-value rule and a single imputation method are investigated. The viability of these methods in pooling results from B-splines is also examined for normal outcomes. An application of these various pooling techniques is then performed on two case studies, one which examines the effect of elevation on a six-minute walk distance (a normal outcome) for patients with pulmonary arterial hypertension, and the other which examines risk factors for intubation in hospitalized COVID-19 patients (a dichotomous outcome). RESULTS: In comparison to the results from generalized additive models fit on full datasets, the median p-value rule performs as well as if not better than the other methods examined. In situations where the alternative hypothesis is true, the Cauchy combination test appears overpowered and alternative methods appear underpowered, while the median p-value rule yields results similar to those from analyses of complete data. CONCLUSIONS: For pooling results after fitting GAMs to multiply imputed datasets, the median p-value is a simple yet useful approach which balances both power to detect important associations and control of Type I errors.

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.

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 arterial hypertension: achievements and realities of modern treatment, a look into the future].

The paper summarizes the most important aspects of modern treatment of patients with pulmonary arterial hypertension (PAH): the goals of therapy are indicated, the issues of risk stratification of PAH progression/mortality, the place of combination specific therapy and switching strategies are considered, as well as new promising approaches to therapy; features of the course of the new coronavirus infection COVID-19 in this category of patients are discussed.

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.

Angiotensin-Converting Enzyme 2 (ACE2) as a Potential Diagnostic and Prognostic Biomarker for Chronic Inflammatory Lung Diseases.

Chronic inflammatory lung diseases are characterized by uncontrolled immune response in the airways as their main pathophysiological manifestation. The lack of specific diagnostic and therapeutic biomarkers for many pulmonary diseases represents a major challenge for pulmonologists. The majority of the currently approved therapeutic approaches are focused on achieving disease remission, although there is no guarantee of complete recovery. It is known that angiotensin-converting enzyme 2 (ACE2), an important counter-regulatory component of the renin-angiotensin-aldosterone system (RAAS), is expressed in the airways. It has been shown that ACE2 plays a role in systemic regulation of the cardiovascular and renal systems, lungs and liver by acting on blood pressure, electrolyte balance control mechanisms and inflammation. Its protective role in the lungs has also been presented, but the exact pathophysiological mechanism of action is still elusive. The aim of this study is to review and discuss recent findings about ACE2, including its potential role in the pathophysiology of chronic inflammatory lung diseases:, i.e., chronic obstructive pulmonary disease, asthma, and pulmonary hypertension. Additionally, in the light of the coronavirus 2019 disease (COVID-19), we will discuss the role of ACE2 in the pathophysiology of this disease, mainly represented by different grades of pulmonary problems. We believe that these insights will open up new perspectives for the future use of ACE2 as a potential biomarker for early diagnosis and monitoring of chronic inflammatory lung diseases.

Right Ventricular Dysfunction in Patients With COVID-19: A Systematic Review and Meta-analysis.

OBJECTIVE: This systematic review and meta-analysis aimed to describe the features of right ventricular impairment and pulmonary hypertension in coronavirus disease (COVID-19) and assess their effect on mortality. DESIGN: The authors carried out a systematic review and meta-analysis of observational studies. SETTING: The authors performed a search through PubMed, the International Clinical Trials Registry Platform, and the Cochrane Library for studies reporting right ventricular dysfunction in patients with COVID-19 and outcomes. PARTICIPANTS: The search yielded nine studies in which the appropriate data were available. INTERVENTIONS: Pooled odds ratios were calculated according to the random-effects model. MEASUREMENTS AND MAIN RESULTS: Overall, 1,450 patients were analyzed, and half of them were invasively ventilated. Primary outcome was mortality at the longest follow-up available. Mortality was 48.5% versus 24.7% in patients with or without right ventricular impairment (n = 7; OR = 3.10; 95% confidence interval [CI] 1.72-5.58; p = 0.0002), 56.3% versus 30.6% in patients with or without right ventricular dilatation (n = 6; OR = 2.43; 95% CI 1.41-4.18; p = 0.001), and 52.9% versus 14.8% in patients with or without pulmonary hypertension (n = 3; OR = 5.75; 95% CI 2.67-12.38; p < 0.001). CONCLUSION: Mortality in patients with COVID-19 requiring respiratory support and with a diagnosis of right ventricular dysfunction, dilatation, or pulmonary hypertension is high. Future studies should highlight the mechanisms of right ventricular derangement in COVID-19, and early detection of right ventricular impairment using ultrasound might be important to individualize therapies and improve outcomes.

COVID-19 in Adults With Congenital Heart Disease.

BACKGROUND: Adults with congenital heart disease (CHD) have been considered potentially high risk for novel coronavirus disease-19 (COVID-19) mortality or other complications. OBJECTIVES: This study sought to define the impact of COVID-19 in adults with CHD and to identify risk factors associated with adverse outcomes. METHODS: Adults (age 18 years or older) with CHD and with confirmed or clinically suspected COVID-19 were included from CHD centers worldwide. Data collection included anatomic diagnosis and subsequent interventions, comorbidities, medications, echocardiographic findings, presenting symptoms, course of illness, and outcomes. Predictors of death or severe infection were determined. RESULTS: From 58 adult CHD centers, the study included 1,044 infected patients (age: 35.1 ± 13.0 years; range 18 to 86 years; 51% women), 87% of whom had laboratory-confirmed coronavirus infection. The cohort included 118 (11%) patients with single ventricle and/or Fontan physiology, 87 (8%) patients with cyanosis, and 73 (7%) patients with pulmonary hypertension. There were 24 COVID-related deaths (case/fatality: 2.3%; 95% confidence interval: 1.4% to 3.2%). Factors associated with death included male sex, diabetes, cyanosis, pulmonary hypertension, renal insufficiency, and previous hospital admission for heart failure. Worse physiological stage was associated with mortality (p = 0.001), whereas anatomic complexity or defect group were not. CONCLUSIONS: COVID-19 mortality in adults with CHD is commensurate with the general population. The most vulnerable patients are those with worse physiological stage, such as cyanosis and pulmonary hypertension, whereas anatomic complexity does not appear to predict infection severity.

New onset severe right ventricular failure associated with COVID-19 in a young infant without previous heart disease.

We present our recent experience with a 6-month-old infant with a personal history of short bowel syndrome that presented with fever, cyanosis, and cardiogenic shock secondary to severe pulmonary hypertension and right ventricular failure without pulmonary thromboembolism. He did not present signs of toxin-mediated disease or Kawasaki disease. He was finally diagnosed with SARS-CoV-2 infection. If this presentation is confirmed in future research, the severe cardiovascular impairment in children with COVID-19 could be also attributable to the primary pulmonary infection, not only to a multisystem inflammatory syndrome but also in children without heart disease.

An Update on Pulmonary Hypertension in Coronavirus Disease-19 (COVID-19).

Coronavirus 19 disease (COVID-19) continues to be a pandemic with global implications.  Respiratory system involvement is the most common manifestation in symptomatic patients.  In this literature review, we describe the diagnosis, management, and implications of pulmonary hypertension (PH) among patients with COVID-19.  We defined pulmonary hypertension as increasing mean pulmonary artery pressure (mPAP) of ≥ 25 mm Hg at rest.  In our literature search, we identified 4 articles with details on pulmonary hypertension.  Among these, two reported various echocardiographic details for diagnosing pulmonary hypertension.  In 1 study evidence of pulmonary hypertension was noted in 13.4% of patients.  Patients with severe COVID-19 were reported to have a higher proportion of pulmonary hypertension as compared to mild COVID-19 disease [22% vs 2%].  Elevated pulmonary artery systolic pressure was significant in predicting mortality.  COVID-19 patients with chronic obstructive pulmonary disease, congestive heart failure, myocardial injury, pulmonary embolism, and prior pulmonary hypertension were at a higher risk of worsening pulmonary hypertension.  Multiple mechanisms for developing pulmonary hypertension that have been postulated are i) concomitant worsening myocardial injury, ii) cytokine storm, endothelial injury, hypercoagulability attributing to development of venous thromboembolism, iii) and the presence of thrombotic microangiopathy.  Among patients with severe COVID-19 disease and pulmonary hypertension, complications including acute respiratory distress syndrome, acute myocardial injury, the requirement of intensive care unit admission, the requirement of mechanical ventilation, and mortality are higher.

COVID-19-Related Potential Multisystem Inflammatory Syndrome in Childhood in a Neonate Presenting as Persistent Pulmonary Hypertension of the Newborn.

A term infant with persistent pulmonary hypertension of newborn developed clinical and laboratory features of multisystem inflammatory syndrome in childhood (MIS-C) between days 12 and 14. Mother and baby were anti-SARS-Coronavirus-2 (SARS-CoV-2) IgG positive and anti-SARS-CoV-2 IgM negative on day 18, with negative COVID-19 PCR on repeated testing; possible first documentation of neonatal MIS-C following passive transfer of maternal antibodies.

Addressing Reduced Laboratory-Based Pulmonary Function Testing During a Pandemic.

To reduce the spread of the severe acute respiratory syndrome coronavirus 2, many pulmonary function testing (PFT) laboratories have been closed or have significantly reduced their testing capacity. Because these mitigation strategies may be necessary for the next 6 to 18 months to prevent recurrent peaks in disease prevalence, fewer objective measurements of lung function will alter the diagnosis and care of patients with chronic respiratory diseases. PFT, which includes spirometry, lung volume, and diffusion capacity measurement, is essential to the diagnosis and management of patients with asthma, COPD, and other chronic lung conditions. Both traditional and innovative alternatives to conventional testing must now be explored. These may include peak expiratory flow devices, electronic portable spirometers, portable exhaled nitric oxide measurement, airwave oscillometry devices, and novel digital health tools such as smartphone microphone spirometers and mobile health technologies along with integration of machine learning approaches. The adoption of some novel approaches may not merely replace but could improve existing management strategies and alter common diagnostic paradigms. With these options comes important technical, privacy, ethical, financial, and medicolegal barriers that must be addressed. However, the coronavirus disease 19 pandemic also presents a unique opportunity to augment conventional testing by including innovative and emerging approaches to measuring lung function remotely in patients with respiratory disease. The benefits of such an approach have the potential to enhance respiratory care and empower patient self-management well beyond the current global pandemic.

A Survey-based Estimate of COVID-19 Incidence and Outcomes among Patients with Pulmonary Arterial Hypertension or Chronic Thromboembolic Pulmonary Hypertension and Impact on the Process of Care.

Rationale: Patients with pulmonary arterial hypertension (PAH) and chronic thromboembolic pulmonary hypertension (CTEPH) typically undergo frequent clinical evaluation. The incidence and outcomes of coronavirus disease (COVID-19) and its impact on routine management for patients with pulmonary vascular disease is currently unknown.Objectives: To assess the cumulative incidence and outcomes of recognized COVID-19 for patients with PAH/CTEPH followed at accredited pulmonary hypertension centers, and to evaluate the pandemic's impact on clinic operations at these centers.Methods: A survey was e-mailed to program directors of centers accredited by the Pulmonary Hypertension Association. Descriptive analyses and linear regression were used to analyze results.Results: Seventy-seven center directors were successfully e-mailed a survey, and 58 responded (75%). The cumulative incidence of COVID-19 recognized in individuals with PAH/CTEPH was 2.9 cases per 1,000 patients, similar to the general U.S. population. In patients with PAH/CTEPH for whom COVID-19 was recognized, 30% were hospitalized and 12% died. These outcomes appear worse than the general population. A large impact on clinic operations was observed including fewer clinic visits and substantially increased use of telehealth. A majority of centers curtailed diagnostic testing and a minority limited new starts of medical therapy. Most centers did not use experimental therapies in patients with PAH/CTEPH diagnosed with COVID-19.Conclusions: The cumulative incidence of COVID-19 recognized in patients with PAH/CTEPH appears similar to the broader population, although outcomes may be worse. Although the total number of patients with PAH/CTEPH recognized to have COVID-19 was small, the impact of COVID-19 on broader clinic operations, testing, and treatment was substantial.