A roadmap for therapeutic discovery in pulmonary hypertension associated with left heart failure. A scientific statement of the Heart Failure Association (HFA) of the ESC and the ESC Working Group on Pulmonary Circulation & Right Ventricular Function.

Pulmonary hypertension (PH) associated with left heart failure (LHF) (PH-LHF) is one of the most common causes of PH. It directly contributes to symptoms and reduced functional capacity and negatively affects right heart function, ultimately leading to a poor prognosis. There are no specific treatments for PH-LHF, despite the high number of drugs tested so far. This scientific document addresses the main knowledge gaps in PH-LHF with emphasis on pathophysiology and clinical trials. Key identified issues include better understanding of the role of pulmonary venous versus arteriolar remodelling, multidimensional phenotyping to recognize patient subgroups positioned to respond to different therapies, and conduct of rigorous pre-clinical studies combining small and large animal models. Advancements in these areas are expected to better inform the design of clinical trials and extend treatment options beyond those effective in pulmonary arterial hypertension. Enrichment strategies, endpoint assessments, and thorough haemodynamic studies, both at rest and during exercise, are proposed to play primary roles to optimize early-stage development of candidate therapies for PH-LHF.

Anaplastic lymphoma kinase-positive pulmonary inflammatory myofibroblastic tumour: a case report.

BACKGROUND: Pulmonary inflammatory myofibroblastic tumour (IMT) is a rare condition that usually presents in young individuals and is associated with anaplastic lymphoma kinase (ALK)-translocation. CASE PRESENTATION: We report a case of an 18-year-old Caucasian man with ALK-translocated pulmonary IMT treated with multimodality therapy. The patient presented with breathlessness and was found to have a collapsed left lung. Further investigations revealed an ALK-translocated pulmonary IMT. This is usually treated with an ALK-inhibitor but patient declined after discussing potential side-effects and had repeated rigid bronchoscopic interventions for local disease control. Due to persistent local recurrence, patient received radical external beam radiotherapy (EBRT) with pulse steroids, and one year later started on Ibuprofen, a non-steroidal anti-inflammatory agent (NSAID). Following multimodality treatment, he developed a complete response. He remains treatment-free for the past seven years. Eleven years on from his diagnosis, he remains in remission with a ECOG performance status of zero. CONCLUSIONS: Achieving long-term local control in pulmonary IMT can be challenging. Multimodality treatment is sometimes needed but the overall outlook remains good.

An ABC approach to cardiothoracic complications and sequelae of COVID-19: a tertiary centre experience.

The Coronavirus disease 2019 (COVID-19) pandemic, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has caused unprecedented challenges to healthcare professionals (HCPs) worldwide. HCPs faced an unknown disease causing many complications, including now well-established acute respiratory distress syndrome (ARDS) and pulmonary artery thromboembolic disease, and some not so well known, for instance, tracheobronchomalacia, tracheal tear or dehiscence, granulation tissue formation and pulmonary hypertension. Many of these complications require highly specialist care warranting early recognition of complications and involvement of appropriately trained professionals. Here, we review the complications and sequelae encountered at our tertiary care centre with follow-up data and potential management strategies using the A (Airway), B (Breathing), C (Circulation) approach. This will not only familiarise HCPs with the different complications of COVID-19, but also arm them with a systematic approach to these complications.

Toxic Shock Syndrome After Orthopaedic Surgery.

Toxic shock syndrome (TSS) is a rare, life-threatening, acute multisystem disorder caused by exotoxin-producing streptococcal or staphylococcal bacteria. It is often characterised by pyrexia, diffuse erythroderma, malaise, confusion, and hypotension which may progress to multiorgan dysfunction and coma. A high index of suspicion along with immediate diagnosis and multidisciplinary management is required to improve the outcome of the disease. A 62-year-old male presented to the hospital a week after an open reduction and internal fixation of a left wrist fracture. He was confused, febrile, and hypotensive with a generalised maculopapular rash on admission. Surgical wound sepsis was a top differential diagnosis; however, other possible sources were considered. Diagnostic imaging and echocardiography effectively ruled out other possible aetiologies. Despite fluids, vasopressor support, and appropriate antibiotics, he showed no significant clinical improvement. Admission blood cultures grew Staphylococcus aureus and after a multidisciplinary meeting, he was taken to the theatre for wound exploration, debridement, and removal of the metal plate. He was eventually weaned off vasopressor support and recovered well. A high index of suspicion is important in recognising TSS in postoperative orthopaedic patients as wounds may appear healthy-looking and the onset of symptoms may be delayed. Early recognition, timely intervention, and multidisciplinary management are vital to the care of these patients.

Case Report: Progressive central conducting lymphatic abnormalities in the RASopathies. Two case reports, including successful treatment by MEK inhibition.

The RASopathies are a group of genetic conditions resulting from mutations within the RAS/mitogen-activated protein kinase (RAS-MAPK) pathway. Lymphatic abnormalities are commonly associated with these conditions, however central conducting lymphatic abnormalities (CCLA) have only recently been described. CCLAs may be progressive and can result in devastating systemic sequelae, such as recurrent chylothoraces, chylopericardium and chylous ascites which can cause significant morbidity and even mortality. Improvements in imaging modalities of the central lymphatics have enhanced our understanding of these complex abnormalities. Management is challenging and have mainly consisted of diuretics and invasive mechanical drainages. We describe two adult males with Noonan syndrome with a severe and progressive CCLA. In one patient we report the therapeutic role of targeted molecular therapy with the MEK inhibitor 'Trametinib', which has resulted in dramatic, and sustained, clinical improvement. The successful use of MEK inhibition highlights the importance of understanding the molecular cause of lymphatic abnormalities and utilising targeted therapies to improve quality of life and potentially life expectancy.

A 12-year experience in endobronchial intervention using rigid bronchoscopy - account of a tertiary referral centre.

We describe our experience of rigid bronchoscopy and endobronchial intervention at a single tertiary centre over a 12-year period. All rigid bronchoscopy procedures between July 2008 and July 2020 (inclusive) were reviewed. All procedures were performed in cardiothoracic theatres by a designated team under general anaesthesia. 2135 rigid bronchoscopies were performed on 1301 patients aged between 18 and 93 years. Complications occurred in 24 (1.12%) procedures. There was one fatality (0.05%). Haemorrhage >100mls occurred in seven (0.33%) all of which were successfully managed endobronchially. Ten procedures (0.5%) were complicated by pneumothorax and an intercostal drain was required for eight. Five patients required intensive care admission post operatively, all of whom were subsequently discharged from hospital. One patient had stent migration. To the best of our knowledge, this is amongst the largest single centre collection of data available for endobronchial intervention using rigid bronchoscopy. We show that rigid bronchoscopy is a safe and effective procedure when performed in a high-volume specialist centre with designated lists involving a specialist multidisciplinary team.

A systematic review of endotracheal stenting in patients with locally advanced thyroid cancer.

OBJECTIVE: Locally aggressive thyroid cancer can result in airway obstruction secondary to tracheal compression or vocal cord palsy. A tracheal stent provides an alternative to surgical resection, tracheostomy or conservative management in patients with compressive symptoms. This systematic review synthesises the current evidence associated with tracheal stenting in locally advanced thyroid cancer. DESIGN, SETTING AND PARTICIPANTS: We conducted a systematic review of tracheal stenting in locally advanced thyroid cancers. We searched MEDLINE, Embase and Web of Science for studies until 22 September 2020. Inclusion criteria were studies involving patients who had received tracheal stents to treat laryngotracheal stenosis secondary to locally advanced thyroid cancer. Single case reports or single cases were not included. MAIN OUTCOME MEASURES: We assessed studies for data on the performance of tracheal stenting; defined as symptomatic relief, spirometry data, complication rates and mortality. We also extracted data pertaining to the use of different types of stent. RESULTS: We identified eight full-text articles from 325 titles found in our search. These were all single-centre retrospective studies that lacked homogeneity of thyroid cancer histotypes. The number of patients in each study ranged from 4 to 35 patients. Stenting improved performance status (two of two studies), symptoms (five of five studies) and spirometry (two of three studies). The most common complications were tracheal granulation, tumour overgrowth, stent migration and sputum retention. CONCLUSION: There is a lack of evidence in the literature of tracheal stents in locally advanced thyroid cancer. However, the evidence available suggests tracheal stenting may be a useful treatment adjunct in advanced thyroid cancer-causing symptomatic airway obstruction.

Undiagnosed Chronic Obstructive Pulmonary Disease is Highly Prevalent in Patients Referred for Dobutamine Stress Echocardiography with Shortness of Breath.

PURPOSE: Shortness of breath (SOB) is a common symptom referral for dobutamine stress echocardiography (DSE). Patients with SOB and a normal DSE have worse long-term outcome than the general population. This suggests multiple aetiologies are involved. The purpose of this study was to assess the prevalence and clinical significance of undiagnosed COPD amongst patients referred for a DSE with SOB. METHODS: We prospectively studied 114 patients referred for DSE with SOB without prior evidence of lung disease (mean age 64.9 ± 18.5 years, 60 male). Respiratory function testing using spirometry was performed on all patients on the day of their DSE. The study end-points were cardiac events and total mortality. RESULTS: Respiratory function testing and DSE was performed in all patients and COPD was highly prevalent (n = 93). Multivariate Cox regression analysis was used to estimate the effect of dyspnoea on non-fatal cardiac events (NFCE) and all-cause mortality. Over a mean follow-up of 4.5 ± 2.6 years, the composite end-point of NFCE and all-cause mortality occurred in 62.7% and 16.7% patients, respectively. COPD (HR 1.27; 95% CI 1.17-1.93), previous myocardial infarction (HR 1.84; 95% CI 1.06-3.2), myocardial ischaemia (HR 2.56; 95% CI 1.48-4.43), peak wall motion score index (HR 4.66; 95% CI 2.26-9.6), and mitral E/E' (HR 1.21; 95% CI 1.1-1.33) were significantly associated with a NFCE. Myocardial ischaemia (HR 4.43; 95% CI 1.24-15.81) was the only independent predictor of all-cause mortality. CONCLUSION: Undiagnosed COPD is highly prevalent and independently associated with worse outcome amongst patients with SOB referred for DSE. Symptom presentation is therefore an important consideration when interpreting DSE results.

A challenging case of tracheal foreign body retrieval following COVID-19 swabbing.

The COVID-19 pandemic has resulted in a significant increase in the number of tracheostomised patients in hospitals requiring ventilatory support. These patients require highly specialist care, but overwhelmed hospital systems with stretched human resources potentially leave these patients cared for by undertrained healthcare professionals. We describe a rare complication where a routine COVID-19 swab done incorrectly via a tracheostomy tube, resulted in a snapped-off swab in the trachea. We outline the events and our method of removal using rigid bronchoscopy through the tracheostomy stoma as endo-tracheal bronchoscopy was impossible due to significant sub-glottic stenosis. This case highlights the paramount importance of the unique care needed to safely manage tracheostomies during this ongoing pandemic.

Large airway complications in COVID-19 pneumonia.

COVID-19 pneumonia can cause respiratory failure which requires specialist management. However the inflammatory nature of the condition and the interventions necessary to manage these patients such as endotracheal intubation and tracheostomy can lead to large airway pathology which may go unrecognised. We describe five of the 44 (11%) consecutive patients referred to our specialist ARDS team between April and June 2020 with confirmed COVID-19 pneumonia who developed diverse large airway pathology which comprised of: supraglottic oedema, tracheal tear, tracheal granulation tissue formation, bronchomalacia, and tracheal diverticulum. Large airway pathology may be underappreciated in severely ill patients with COVID-19 pneumonia and should be considered in patients with unexplained air leak, prolonged need for mechanical ventilatory support, and repeated failed extubation or decannulation. If suspected, such patients should be managed by a team with expertise in large airway intervention and early specialist advice should be sought.

Pulmonary function, computerized tomography features and six-minute walk test at three months in severe COVID-19 patients treated with intravenous pulsed methylprednisolone: a preliminary report.

COVID-19 acute respiratory distress syndrome (ARDS) has a high mortality and few therapeutic options. We present a preliminary report on our experience using high-dose pulsed methylprednisolone in COVID-19 ARDS and three-month outcomes. We performed a retrospective analysis of all patients treated with high-dose methylprednisolone for COVID-19 ARDS and three-month lung function, 6-minutes walking test (6MWT), and computerized tomography (CT) findings. Fifteen patients were treated of which 10 survived to discharge. Reduced diffusion capacity for carbon monoxide (DLCO) was the commonest abnormality in lung function tests and had the lowest mean value. Parenchymal bands were the commonest CT finding and 50% of patients had fibrosis at three months. Mean 6-minutes walk distance (6MWD) was 65.4% predicted and was abnormal in 62.5% of patients. In this cohort of patients with COVID-19 ARDS treated with high-dose methylprednisolone pulses, CT, lung function, and 6MWT abnormalities were unsurprisingly common at three months, although all 10 patients treated early in their disease course survived, a possible therapeutic effect. Further randomised controlled trials are needed to assess the benefits of this treatment.

Prolonged QT predicts prognosis in COVID-19.

BACKGROUND: Coronavirus disease-2019 (COVID-19) causes severe illness and multi-organ dysfunction. An abnormal electrocardiogram is associated with poor outcome, and QT prolongation during the illness has been linked to pharmacological effects. This study sought to investigate the effects of the COVID-19 illness on the corrected QT interval (QTc). METHOD: For 293 consecutive patients admitted to our hospital via the emergency department for COVID-19 between 01/03/20 -18/05/20, demographic data, laboratory findings, admission electrocardiograph and clinical observations were compared in those who survived and those who died within 6 weeks. Hospital records were reviewed for prior electrocardiograms for comparison with those recorded on presentation with COVID-19. RESULTS: Patients who died were older than survivors (82 vs 69.8 years, p < 0.001), more likely to have cancer (22.3% vs 13.1%, p = 0.034), dementia (25.6% vs 10.7%, p = 0.034) and ischemic heart disease (27.8% vs 10.7%, p < 0.001). Deceased patients exhibited higher levels of C-reactive protein (244.6 mg/L vs 146.5 mg/L, p < 0.01), troponin (1982.4 ng/L vs 413.4 ng/L, p = 0.017), with a significantly longer QTc interval (461.1 ms vs 449.3 ms, p = 0.007). Pre-COVID electrocardiograms were located for 172 patients; the QTc recorded on presentation with COVID-19 was longer than the prior measurement in both groups, but was more prolonged in the deceased group (448.4 ms vs 472.9 ms, pre-COVID vs COVID, p < 0.01). Multivariate Cox-regression analysis revealed age, C-reactive protein and prolonged QTc of >455 ms (males) and >465 ms (females) (p = 0.028, HR 1.49 [1.04-2.13]), as predictors of mortality. QTc prolongation beyond these dichotomy limits was associated with increased mortality risk (p = 0.0027, HR 1.78 [1.2-2.6]). CONCLUSION: QTc prolongation occurs in COVID-19 illness and is associated with poor outcome.

Acute tracheal tear - A potential cause of spontaneous pneumomediastinum in patients with COVID-19.

Spontaneous pneumomediastinum following prolonged periods of severe coughing should raise the suspicion of tracheal rupture in COVID-19 patients.

A specialised cardiorespiratory team approach in the intensive care management of COVID-19 patients: benefit on mortality, diagnosis and management.

BACKGROUND: During the coronavirus pandemic, our intensive care units were faced with large numbers of patients with an unfamiliar disease. To support our colleagues and to assist with diagnosis and treatment, we developed a specialist team. METHODS: The acute respiratory disease support team reviewed 44 consecutive patients referred from the intensive care and coordinated therapies for pulmonary hypertension, pulmonary thrombosis, evolving lung fibrosis and large airway intervention. RESULTS: The mortality for this group was significantly lower (34%) than the total group admitted to critical care as a whole (51%) and for those not reviewed by the team (55%; p=0.012). Pulmonary hypertension was present in 84% of the patients and pulmonary thrombosis in 52%. Thirty-two patients received sildenafil therapy and this was associated with improvement in right heart function in survivors. Ten patients with evolving fibrosis and no evidence of sepsis received high-dose steroid therapy with excellent effect. Five patients developed airway complications requiring intervention. Short time on mechanical ventilation was associated with a poorer outcome (p<0.001). INTERPRETATION: A specialised cardiorespiratory team approach contributes significantly to successful management of severely unwell patients with COVID-19 and offers an important platform for continuity of patient care, education and staff well-being.

A rare solitary and endobronchial pulmonary hyalinising granuloma requiring bilobectomy.

Pulmonary hyalinising granuloma is a very rare disease often presenting as multiple smooth rounded nodules within the lung parenchyma and mimicking metastatic disease. Solitary pulmonary hyalinising granuloma is an even rarer subgroup, and to our knowledge, there have been no endoluminal pulmonary hyalinising granulomas reported. A 36-year-old female non-smoker with no significant past medical history presented with a persistent cough and was found to have a right lower lobe bronchial lesion causing lower lobe obstruction. After multiple failed attempts at tissue diagnosis from both percutaneous and endobronchial biopsies, and with worsening haemoptysis, the patient underwent a right thoracotomy and lower bilobectomy. The histopathology was reported as a solitary endobronchial pulmonary hyalinising granuloma. Although benign in nature, tissue diagnosis can be difficult in these lesions, especially when presenting as a solitary mass in a central location. This report demonstrates that these lesions can also be found endobronchially necessitating parenchymal resection for diagnosis and obstructive symptoms.

Vascular and Parenchymal Enhancement Assessment by Dual-Phase Dual-Energy CT in the Diagnostic Investigation of Pulmonary Hypertension.

PURPOSE: To evaluate pulmonary hypertension (PH) determination by dual-phase dual-energy CT pulmonary angiography vascular enhancement and perfused blood volume (PBV) quantification. MATERIALS AND METHODS: In this prospective study, consecutive participants who underwent both right heart catheterization and dual-phase dual-energy CT pulmonary angiography were included between 2012 and 2014. CT evaluation comprised a standard pulmonary arterial phase dual-energy CT pulmonary angiography acquisition (termed series 1) followed 7 seconds after series 1 completion by a second dual-energy CT pulmonary angiography acquisition limited to the central 10 cm of the pulmonary vasculature (termed series 2). In both series, enhancement in the main pulmonary artery (PAenh), the descending aorta (DAenh), and whole-lung PBV (WLenh) was calculated from dual-energy CT pulmonary angiography iodine images. Dual-energy CT pulmonary angiography and standard cardiovascular metrics were correlated to mean pulmonary artery pressure (mPAP) and pulmonary vascular resistance (PVR) with additional receiver operating characteristic curve analysis. RESULTS: A total of 102 participants (median age, 70; range, 58-78 years; 60 women) were included. Sixty-five participants had PH defined by mPAP of greater than or equal to 25 mm Hg, and 51 participants had PH defined by PVR of greater than 3 Wood units. By either definition, participants with PH had higher PAenh/WLenh ratio and lower WLenh and DAenh in series 1 (P < .05) and higher PAenh and WLenh in series 2 (P < .05). Change in WLenh determined highest diagnostic accuracy to define disease by mPAP (area under the receiver operating characteristic curve [AUC], 0.78) and PVR (AUC, 0.79) and the best mPAP correlation (r = 0.62). PAenh series 2 correlated best with PVR (r = 0.49). Multiple linear regression analysis incorporating WLenh and series 1 DAenh improved PVR correlation (r = 0.56). Combining these dual-energy CT pulmonary angiography metrics with main pulmonary artery size and right-to-left ventricular ratio achieved the highest correlations (mPAP, r = 0.71; PVR, r = 0.64). CONCLUSION: Dual-phase dual-energy CT pulmonary angiography enhancement quantification appears to improve mPAP and PVR prediction in noninvasive PH evaluation.Supplemental material is available for this article.See also the commentary by Kay in this issue.© RSNA, 2020.

Cardiac arrest following protamine administration: a case series.

AIMS: Protamine sulfate is commonly used to reverse the action of heparin after catheter ablation procedures. Serious protamine-related adverse effect is rare, but its recognition and appropriate management by electrophysiologists and intensivists is important. Direct ventricular fibrillation (VF) soon after a slow infusion of protamine has not been clearly described. METHODS AND RESULTS: We examined the records of all patients who suffered apparent adverse events after protamine administration in our electrophysiology lab from 2013 to 2018. We describe a series of three patients, all of whom suffered a precipitous fall in arterial pressure followed by VF within minutes after administration of protamine following ablation for atrial fibrillation. The same supplier of protamine was used in all three cases, but they were from different batches. Serum tryptase levels were measured in all cases, immediately post-cardiac arrest and at 2- and 6-h post-event. Immunoglobulin levels were not measured. Two patients recovered after aggressive supportive therapy; the third died despite similar support. CONCLUSION: We have encountered three cases of profound hypotension followed by VF soon after administration of protamine. Although protamine is safe in a large majority of patients, these adverse events have led our centre to exercise greater selectivity and caution in its use.

Evolutional trends in the management of tracheal and bronchial injuries.

Tracheal and Bronchial injuries are potentially life threatening complications which require urgent diagnosis and therapeutic intervention. They typically occur in association with blunt and penetrating chest trauma although they are increasingly being encountered in patients following endobronchial intervention and percutaneous tracheostomy insertion. Their precise incidence is unknown. Presenting features include dyspnoea, stridor, respiratory and haemodynamic compromise, haemoptysis, surgical emphysema, pneumothorax and persistent significant airleak. There may be other additional injuries to consider in trauma patients with large airway injury. Familiarity with the diagnosis and management of large airway injuries is important for medical teams engaged in emergency medicine, thoracic surgery and medicine, anaesthesia and intensive care. Although early surgical intervention is the mainstay of treatment, endobronchial manoeuvres to seal defects are receiving increasing attention particularly for patients with medical co-morbidities which may contraindicate formal surgery or transfer or where local surgical expertise is not available.

Emergency cricothyroidotomy following tracheobronchial stenting.

A man aged 51 years was referred for tracheobronchial stenting after a poorly differentiated oesophageal carcinoma had progressed to cause stridor. Bronchoscopy revealed a left vocal cord palsy and tumour infiltration into the trachea. A tracheobronchial stent was placed, and after distal migration was endoscopically resited. Returning from theatre, the patient developed severe upper airway obstruction that progressed to cause CO2 narcosis and loss of consciousness. A rapid sequence induction was initiated, and a Glidescope revealed bilateral vocal cord palsy with severe oedema causing an inability to pass a tube or stylet. Tracheostomy was attempted above the suprasternal notch but was obstructed by the stent. Oxygen saturations dropped steadily, reaching as low as 38%. Emergency cricothyroidotomy was performed, compliant with DAS guidelines, that proved successful. The stent was removed, which was blocked with blood and secretions, and tracheostomy was placed 2 days later. The patient made a full neurological recovery.

Iatrogenic peripheral pulmonary air embolism following intravenous contrast administration for CT pulmonary angiography: proposal of the "double bronchus sign".

We present a case of iatrogenic extensive air embolism in the peripheral pulmonary arterial tree following intravenous contrast injection for a CT pulmonary angiogram performed to investigate chest pain in a 25-year-old female patient. Small volumes of iatrogenic air embolism following contrast injection are not infrequently encountered incidentally in the central vasculature (brachiocephalic veins, superior vena cava, right cardiac chambers and main pulmonary arteries). To our knowledge, however, this is the only case of extensive peripheral pulmonary arterial air embolism on CT that has been reported in the literature. Despite the extent of peripheral air, this potentially clinically significant complication was relatively inconspicuous at CT interpretation. A new radiological sign, the "double bronchus sign", is proposed as a useful diagnostic tool. In addition to discussing the imaging features, important safety considerations and principles of immediate management, relevant to all radiologists, are addressed.