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.

Multidisciplinary approach for the management of term pregnancy complicated by Eisenmenger syndrome.

Pregnancy in patients with Eisenmenger syndrome (ES) is associated with high maternal mortality rates of 30%‒50%, or even up to 65% in the case of a cesarean section (Yuan, 2016). Here, we report a case of term pregnancy complicated with ES and severe pulmonary artery hypertension (PAH), which was managed by a multidisciplinary team (MDT) and resulted in an uncomplicated delivery via elective cesarean section. The goal of this study is to emphasize the importance of multidisciplinary approach in the management of pregnancy with ES, which can profoundly improve maternal and infant outcomes.

Abnormal Echocardiographic Findings in Hospitalized Patients with Covid-19: A Systematic Review and Meta-analysis. / Achados Ecocardiográficos Anormais em Pacientes Internados com Covid-19: Uma Revisão Sistemática e Metanálise.

BACKGROUND: Coronavirus disease 2019 (Covid-19) can lead to severe respiratory distress and acute cardiac injury, but it is unclear how often it can cause cardiac dysfunction. OBJECTIVE: In this systematic review, we aimed to summarize the main echocardiographic findings in patients with Covid-19. METHODS: We systematically searched in PUBMED, EMBASE, LILACS and Cochrane databases, in addition MedRxiv and Scielo preprints from inception to July 21st, 2021. Studies reporting echocardiographic data in patients with Covid-19 were included. Demographic characteristics, previous cardiovascular disease (CVD), and echocardiographic findings were extracted. We performed a meta-analysis of proportions to estimate the main echocardiographic findings. The level of significance was p < 0.05. RESULTS: From 11,233 studies, 38 fulfilled inclusion criteria and were included in the meta-analysis. The estimated proportions of left ventricular (LV) systolic dysfunction were 25% (95%CI: 19, 31; I293%), abnormal global longitudinal strain 34% (95% CI 23, 45; I290%), righ ventricular (RV) systolic dysfunction 17% (95%CI 13, 21; I290%), pericardial effusion 17% (95%CI: 9, 26; I297%), and pulmonary hypertension 23% (95%CI: 15, 33, I2 96%). LV systolic dysfunction was directly associated with study-specific prevalence of previous abnormal echocardiogram (p<0.001). The proportion of patients in mechanical ventilation, indicating severity of disease, did not explain the heterogeneity in the proportions of LV dysfunction (p=0.37). CONCLUSION: Among hospitalized patients with Covid-19, LV dysfunction has been reported in one quarter, with smaller proportions of right ventricular dysfunction, pericardial effusion and pulmonary hypertension. However, there was a higher proportion of LV dysfunction among studies reporting the presence of prior heart disease, which suggests that cardiac dysfunction was mostly pre-existing.

FUNDAMENTOS: A doença do coronavírus 2019 (Covid-19) pode levar à insuficiência respiratória grave e lesão cardíaca aguda, mas não está claro com que frequência ela pode causar disfunção cardíaca. OBJETIVOS: Nesta revisão sistemática, nosso objetivo foi resumir os principais achados ecocardiográficos em pacientes com Covid-19. MÉTODOS: Conduzimos uma busca sistemática nos bancos de dados PUBMED, EMBASE, LILACS e Cochrane, além de artigos não pulicados ( preprints ) no MedRxiv e Scielo desde o início até 21 de julho de 2021. Foram incluídos estudos que apresentaram dados ecocardiográficos de pacientes com Covid-19. Características demográficas, doença cardiovascular (DCV) prévia, e achados ecocardiográficos foram extraídos dos estudos. Realizamos uma metanálise de proporções para estimar os principais achados ecocardiográficos. O nível de significância foi p<0,05. RESULTADOS: Do total de 11 233 estudos, 38 preencheram os critérios de inclusão e foram incluídos na metanálise. A proporção estimada de disfunção sistólica do ventrículo esquerdo (VE) foi 25% (IC95%: 19, 31; I2 93%), strain longitudinal global anormal 34% (IC95% 23, 45; I2 90%), disfunção sistólica do ventrículo direito (VD) 17% (IC95% 13, 21; I2 90%), derrame pericárdico 17% (IC95%: 9, 26; I2 97%), e hipertensão pulmonar 23% (IC95%: 15, 33, I2 96%). Disfunção sistólica do VE foi diretamente associada com prevalência de ecocardiograma anormal prévio nos estudos (p<0,001). A proporção de pacientes em ventilação mecânica, indicando gravidade da doença, não explicou a heterogeneidade nas proporções de disfunção do VE (p=0,37). CONCLUSÃO: Entre os pacientes internados com Covid-19, a disfunção ventricular esquerda foi descrita em um quarto dos pacientes, com menores proporções de disfunção do ventrículo direito, derrame pericárdico e hipertensão pulmonar. No entanto, houve uma proporção mais alta de disfunção do VE nos estudos que relataram presença de doença cardíaca prévia, sugerindo que a disfunção cardíaca era predominantemente pré-existente.

Identification of biomarkers and pathways for the SARS-CoV-2 infections that make complexities in pulmonary arterial hypertension patients.

This study aimed to identify significant gene expression profiles of the human lung epithelial cells caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections. We performed a comparative genomic analysis to show genomic observations between SARS-CoV and SARS-CoV-2. A phylogenetic tree has been carried for genomic analysis that confirmed the genomic variance between SARS-CoV and SARS-CoV-2. Transcriptomic analyses have been performed for SARS-CoV-2 infection responses and pulmonary arterial hypertension (PAH) patients' lungs as a number of patients have been identified who faced PAH after being diagnosed with coronavirus disease 2019 (COVID-19). Gene expression profiling showed significant expression levels for SARS-CoV-2 infection responses to human lung epithelial cells and PAH lungs as well. Differentially expressed genes identification and integration showed concordant genes (SAA2, S100A9, S100A8, SAA1, S100A12 and EDN1) for both SARS-CoV-2 and PAH samples, including S100A9 and S100A8 genes that showed significant interaction in the protein-protein interactions network. Extensive analyses of gene ontology and signaling pathways identification provided evidence of inflammatory responses regarding SARS-CoV-2 infections. The altered signaling and ontology pathways that have emerged from this research may influence the development of effective drugs, especially for the people with preexisting conditions. Identification of regulatory biomolecules revealed the presence of active promoter gene of SARS-CoV-2 in Transferrin-micro Ribonucleic acid (TF-miRNA) co-regulatory network. Predictive drug analyses provided concordant drug compounds that are associated with SARS-CoV-2 infection responses and PAH lung samples, and these compounds showed significant immune response against the RNA viruses like SARS-CoV-2, which is beneficial in therapeutic development in the COVID-19 pandemic.

[Position paper of the Italian Society of Cardiology (SIC) on COVID-19 vaccine priority in patients with cardiovascular diseases]. / Position paper della Società Italiana di Cardiologia (SIC): Priorità del vaccino COVID-19 nei pazienti con patologie cardiovascolari.

In over a year, the COVID-19 pandemic caused 2.69 million deaths and 122 million infections. Social isolation and distancing measures have been the only prevention available for months. Scientific research has done a great deal of work, developing in a few months safe and effective vaccines against COVID-19. In the European Union, nowadays, four vaccines have been authorized for use: Pfizer-BioNTech, Moderna, ChAdOx1 (AstraZeneca/Oxford), Janssen (Johnson & Johnson), and three others are currently under rolling review.Vaccine allocation policy is crucial to optimize the advantage of treatment preferring people with the highest risk of contagion. These days the priority in the vaccination program is of particular importance since it has become clear that the number of vaccines is not sufficient for the entire Italian population in the short term. Cardiovascular diseases are frequently associated with severe COVID-19 infections, leading to the worst prognosis. The elderly population suffering from cardiovascular diseases is, therefore, to be considered a particularly vulnerable population. However, age cannot be considered the only discriminating factor because in the young-adult population suffering from severe forms of heart disease, the prognosis, if affected by COVID-19, is particularly ominous and these patients should have priority access to the vaccination program. The aim of this position paper is to establish a consensus on a priority in the vaccination of COVID-19 among subjects suffering from different cardiovascular diseases.

Severe urticarial rash as the initial symptom of COVID-19 infection.

A 54-year-old woman presented with pruritic rash and hives of 3 days' duration followed by shortness of breath for 1 day. SARS-CoV-2 PCR test for COVID-19 was positive. Cutaneous manifestations of COVID-19 include acral lesions, urticarial rash, erythematous maculopapular rash, vascular rashes and vesicular rash. The cutaneous manifestations are mostly described as self-limiting. Urticarial rashes are not reported as the initial presentation symptom of COVID-19 infection but mostly noted to occur at the same time or after the onset of non-cutaneous symptoms. Management of cutaneous manifestations of COVID-19 affecting quality of life has not been well studied. Antihistamine therapy is the primary recommended therapy. Role of antiviral therapy for severe cases of rash needs to be further assessed.

Folic acid as placebo in controlled clinical trials of hydroxychloroquine prophylaxis in COVID-19: Is it scientifically justifiable?

Using folic acid (FA) as placebo complicates the interpretation of the findings of few RCTs evaluating safety and efficacy of hydroxychloroquine prophylaxis in COVID-19. FA is found to bind to furin-protease and spike: ACE2 interface of SARS-CoV-2. In clinical studies, FA level was lowest among severe patients compared to mild and moderate disease. A single controlled study reported the benefit of combination of folic acid with Pyridoxine & cyanocobalamin in terms of clinical and laboratory cure parameters. One hypothesis associates the differences in geographical variation of disease severity with prevalence of methyl tertahydrofolic acid reductase (MTHFR) C677T polymorphism. Other possible domains, where FA is hypothesized to be beneficial are COVID-19 associated pulmonary hypertension and hyper-homocystinemia. So, scientific justification of using folic acid as placebo in COVID-19 trials seems scientifically not credible and this may be one of the major factors for failure of many agents. We need to be more careful in choosing our placebo especially when conducting a placebo controlled trial.

COVID-19 and Pulmonary Hypertension in Children: What Do We Know So Far?

The interplay between coronavirus disease 2019 (COVID-19) and pulmonary hypertension (PH) in children is unknown. Adults with PH are at potential risk for severe complications and high mortality due to associated comorbidities. It is difficult to extrapolate the outcomes of COVID-19 in adults to pediatric PH patients. Overall, a small number of COVID-19 cases is reported in patients with preexisting PH. Several factors may be responsible for the low incidence of COVID-19 in children with PH. Pulmonary hypertension is a rare disease, testing is not universal, and patients may have followed more rigorously the Center for Disease Control's guidelines recommended for personal protection with mask-wearing, social distancing, and hand sanitization through ongoing health education. The small number of COVID-19 cases in patients with preexisting PH does not support that PH is protective for COVID-19. However, medications used to treat PH may have some protection against COVID-19. This review discusses the pathophysiology of PH occurring with COVID-19, differences between children and adults with COVID-19, strategies for management of preexisting PH in children during the ongoing pandemic, and its impact within the field of PH.

Rare case of right ventricular dilatation associated with anomalous pulmonary venous drainage, sinus venosus atrial septal defect and persistent left superior vena cava.

A 34-year-old woman was seen in the emergency department for shortness of breath and chest pain. During a pandemic, it is easy to 'think horses and not zebras', and with a patient presenting with the classic coronavirus symptoms it would have been easy to jump to that as her diagnosis. After a careful history and examination, it became clear that there was another underlying diagnosis. Chest X-ray, echocardiogram and CT scan revealed marked right ventricular dilatation and pulmonary hypertension, alongside a persistent left superior vena cava (PLSVC). Further investigation with cardiac MRI and coronary angiography at a tertiary centre demonstrated that she not only have a PLSVC but also a partial anomalous pulmonary venous drainage and sinus venosus atrial septal defect. This case highlights the importance of considering all differentials and approaching investigations in a logical manner.

High dose folic acid is a potential treatment for pulmonary hypertension, including when associated with COVID-19 pneumonia.

BACKGROUND: Pulmonary hypertension is a significant complication for some patients with COVID-19 pneumonia, especially those requiring intensive care. Tachyphylaxis to the current therapy, inhaled nitric oxide (iNO), is also common. In vitro, folic acid directly increases nitric oxide (NO) production and extends its duration of action; effects which could be of benefit in reversing pulmonary hypertension and severe hypoxaemia. Our work has shown that, in the systemic circulation, folic acid in high dose rapidly improves nitric oxide mediated vasodilation, by activating endothelial nitric oxide synthase (eNOS). HYPOTHESIS: A similar effect of high dose folic acid on pulmonary endothelial function would be expected from the same mechanism and would lead to improvement in pulmonary perfusion. We therefore hypothesise that folic acid, 5 mg or greater, is a useful therapeutic option for pulmonary hypertension and/or refractory severe hypoxaemia, in patients with severe COVID-19 associated pneumonia in whom NO therapy is considered, with a very low risk of adverse effects.

SARS-CoV-2 Infection in Patients with Down Syndrome, Congenital Heart Disease, and Pulmonary Hypertension: Is Down Syndrome a Risk Factor?

With increasing information available about the epidemiology, pathophysiology, and management of patients affected with severe acute respiratory syndrome corona virus-2 infection, patients with Down syndrome, congenital heart disease, airway obstruction, and pulmonary hypertension present a unique challenge. This case series describes 3 patients with Down syndrome and respiratory failure secondary to coronavirus infection.