Luke S Howard

• MA, DPhil, FRCP
• Professor of Practice (Cardiopulmonary Medicine) at Imperial College London

Aims Describe differences in changes in cardiopulmonary exercise testing after surgery for severe primary mitral regurgitation between class I and class II indications for surgery. Methods Prospective observational study of patients who underwent transthoracic echocardiogram and cardiopulmonary exercise testing pre-operatively and six months after...

Background Pulmonary arterial hypertension (PAH) is characterized by high morbidity and mortality despite current vasodilator therapies. Sotatercept, a fusion protein targeting the activin signaling pathway, improved exercise capacity and reduced clinical worsening in PAH patients in the STELLAR randomized controlled trial (RCT). This study explore...

Background The use and effectiveness of parenteral prostanoids in older patients with pulmonary arterial hypertension (PAH) are unknown. We investigated the association of paretenteral prostanoids use with mortality in elderly PAH patients. Methods PAH patients aged ≥65 years enrolled in the FOCUS–PAH registry between 2001 and 2023 were included....

BACKGROUND Patients with pulmonary hypertension (PH) are classified based on disease etiology and hemodynamic drivers. Classification informs treatment. The heart failure biomarker NT-proBNP (N-terminal pro-B-type natriuretic peptide) is used to help inform risk but is not specific to PH or sub-classification groups. There are currently no other bi...

Background Current guidelines recommend a four-strata model based on World Health Organization functional class (WHO-FC), 6-min walk distance (6MWD), and serum levels of brain natriuretic peptide (BNP) or N-terminal pro-BNP (NT-proBNP) for risk stratification in patients with pulmonary arterial hypertension (PAH) during follow-up. We explored the r...

Rationale: Imatinib 400mg daily reduces pulmonary vascular resistance and improves exercise capacity in patients with pulmonary arterial hypertension. Concerns about safety and tolerability limit its use. Objectives: To identify a safe and tolerated dose of oral imatinib between 100mg and 400mg daily and evaluate its efficacy. Methods: Oral im...

Question addressed by the study The clinical and prognostic role of tricuspid valve regurgitation (TR) in patients with pulmonary arterial hypertension (PAH) is still underappreciated. The main objective of the present study was to assess the prognostic value of TR in incident PAH patients. Methods Consecutive incident PAH patients were enrolled f...

Background. Stroke volume index (SVI) is an important prognostic parameter in pulmonary arterial hypertension (PAH). The direct Fick (DF) method represents the gold standard for measuring it. Indirect Fick (IF) and thermodilution (TD) are simpler and widely used alternatives. However, data on the accuracy of these methods in estimating SVI in PAH a...

Evidence for use of pulmonary arterial hypertension targeted-therapies in patients with chronic thromboembolic pulmonary hypertension (CTEPH) is limited. In MERIT-1, the endothelin receptor antagonist macitentan improved hemodynamic and functional parameters versus placebo in patients with inoperable CTEPH over a 24-week double-blind (DB) period. I...

Introduction . Pulmonary hypertension (PH) definition was recently changed and led to a new subset of PH patients with mildly impaired pulmonary hemodynamics, characterized by a mean pulmonary artery pressure of 21–24 mmHg and with a pulmonary vascular resistance >2Wood Units. We evaluated the association of PH-targeted therapy and outcome in mild...

Care of pulmonary hypertension (PH) patients in special situations requires insightful knowledge of the pathophysiology of the cardiopulmonary system and close interaction with different specialists, depending on the situation. The role of this task force was to gather knowledge about five conditions that PH patients may be faced with. These condit...

Background The incidence of Pulmonary Hypertension (PH) and Pulmonary Arterial Hypertension (PAH) is believed to be on the rise and is associated with poor outcomes. Methods We extracted age-standardized mortality rates (ASMRs) for decedents ≥ 18 years of age from the World Health Organization Mortality Database, using International Classification...

Background In patients with COVID-19 requiring supplemental oxygen, dexamethasone reduces acute severity and improves survival, but longer-term effects are unknown. We hypothesised that systemic corticosteroid administration during acute COVID-19 would be associated with improved health-related quality of life (HRQoL) one year after discharge. Met...

Introduction Pulmonary embolism (PE) is a well-recognised complication of COVID-19 infection, and chronic thromboembolic pulmonary disease with and without pulmonary hypertension (CTEPD/CTEPH) are potential life-limiting consequences. At present the burden of CTEPD/CTEPH is unclear and optimal and cost-effective screening strategies yet to be estab...

Aims The use of loop diuretics in pulmonary arterial hypertension (PAH) is less frequent compared with heart failure. The clinical and prognostic characteristics of PAH patients according to loop diuretic use remain unexplored. In this study, we retrospectively analysed the characteristics and survival of PAH patients requiring different doses of l...

A blood test identifying patients at increased risk of pulmonary hypertension (PH) could streamline the investigative pathway. The prospective, multicenter CIPHER study aimed to develop a microRNA‐based signature for detecting PH in breathless patients and enrolled adults with a high suspicion of PH who had undergone right heart catheterization (RH...

Aims Potential loss-of-function variants of ATP13A3, the gene encoding a P5B-type transport ATPase of undefined function, were recently identified in pulmonary arterial hypertension (PAH) patients. ATP13A3 is implicated in polyamine transport but its function has not been fully elucidated. Here, we sought to determine the biological function of ATP...

Aim To obtain real-world evidence about the features and risk stratification of pulmonary arterial hypertension (PAH) with a left heart disease (LHD) phenotype (PAH-LHD). Methods and results By reviewing the records of consecutive incident PAH patients at 7 tertiary centers from 2001 to 2021, we selected 286 subjects with all parameters needed to...

Background With no approved therapies for pulmonary hypertension (PH) associated with interstitial lung disease (PH-ILD) in Europe, we surveyed clinician perceptions on PH-ILD management and unmet need to understand current real-world practices. Methods : An online clinician survey on PH-ILD management was conducted in France, Germany, Italy, Spai...

One in ten severe acute respiratory syndrome coronavirus 2 infections result in prolonged symptoms termed long coronavirus disease (COVID), yet disease phenotypes and mechanisms are poorly understood ¹ . Here we profiled 368 plasma proteins in 657 participants ≥3 months following hospitalization. Of these, 426 had at least one long COVID symptom an...

Background Pulmonary hypertension (PH) is a heterogeneous disease with a poor prognosis. Accurate risk stratification is essential for guiding treatment decisions in pulmonary arterial hypertension (PAH). Although various risk models have been developed for PAH, their comparative prognostic potential requires further exploration. Additionally, the...

Approved therapies for the treatment of patients with pulmonary arterial hypertension (PAH) mediate pulmonary vascular vasodilatation by targeting distinct biological pathways. International guidelines recommend that patients with an inadequate response to dual therapy with a phosphodiesterase type‐5 inhibitor (PDE5i) and endothelin receptor antago...

Rationale: Chronic Thromboembolic Pulmonary Hypertension involves formation and non-resolution of thrombus, dysregulated inflammation, angiogenesis and the development of a small vessel vasculopathy. Objectives: We aimed to establish the genetic basis of chronic thromboembolic pulmonary hypertension to gain insight into its pathophysiological co...

Background The striking increase in COVID-19 severity in older adults provides a clear example of immunesenescence, the age-related remodelling of the immune system. To better characterise the association between convalescent immunesenescence and acute disease severity, we determined the immune phenotype of COVID-19 survivors and non-infected contr...

Chronic thromboembolic pulmonary disease (CTEPD) is a complication of pulmonary embolism (PE). We conducted an online survey of UK PE-treating physicians to understand practices in the follow-up of PE and awareness of CTEPD. The physicians surveyed (N = 175) included 50 each from cardiology, respiratory and internal medicine, plus 25 haematologists...

Pulmonary arterial hypertension (PAH) is characterised by pulmonary vascular remodelling causing premature death from right heart failure. Established DNA variants influence PAH risk, but susceptibility from epigenetic changes is unknown. We addressed this through epigenome-wide association study (EWAS), testing 865,848 CpG sites for association wi...

Background In patients with COVID-19 requiring supplemental oxygen, dexamethasone reduces acute severity and improves survival, but longer-term effects are unknown. We hypothesised that systemic corticosteroid administration during acute COVID-19 would be associated with improved health-related quality of life (HRQoL) one year after discharge. Meth...

Background Use of higher dose of loop diuretics has been associated with worse survival in acute and chronic heart failure. The use of loop diuretics in type 1 pulmonary hypertension (PAH) is generally less frequent compared to heart failure and required doses may be lower. the clinical and prognostic characteristics of patients requiring high dose...

Introduction Subclinical left heart disease (LHD) may impact the management of pulmonary arterial hypertension (PAH) [1]. Purpose To evaluate the influence of a LHD phenotype on PAH risk stratification. Methods We retrospectively reviewed the data of consecutive PAH patients followed at 7 tertiary centers from 2001 to 2021, and selected those wit...

Background Venous thromboembolism is the 3rd commonest acute cardiovascular syndrome. The European Society of Cardiology/European Respiratory Society (ESC/ERS) suggest implementing a Pulmonary Embolism (PE) Response Team (PERT) to guide management of patients with acute PE. Purpose To investigate the implementation of a PERT at a tertiary hospital...

Introduction Our aim is to describe the use of cardiopulmonary exercise testing in watchful waiting for asymptomatic severe primary mitral regurgitation. Methods Between October 2016 and October 2017, ten patients with asymptomatic severe primary mitral regurgitation underwent watchful waiting in a single centre. Baseline assessment included histo...

One in ten SARS-CoV-2 infections result in prolonged symptoms termed long COVID, yet disease phenotypes and mechanisms are poorly understood. We studied the blood proteome of 719 previously hospitalised adults with long COVID grouped by symptoms. Elevated markers of myeloid inflammation and complement activation were associated with long COVID; ele...

Introduction The multiorgan impact of moderate to severe coronavirus infections in the post-acute phase is still poorly understood. We aimed to evaluate the excess burden of multiorgan abnormalities after hospitalisation with COVID-19, evaluate their determinants, and explore associations with patient-related outcome measures. Methods In a prospec...

Aims: Potential loss-of-function variants of ATP13A3, the gene encoding a P5B-type transport ATPase of undefined function, were recently identified in pulmonary arterial hypertension (PAH) patients. ATP13A3 is implicated in polyamine transport but its function has not been fully elucidated. Here, we sought to determine the biological function of AT...

Background and aims: Interventional studies in pulmonary arterial hypertension completed to date have shown to be effective in symptomatic patients with significantly elevated mean pulmonary artery pressure (mPAP) (≥25 mmHg) and pulmonary vascular resistance (PVR) > 3 Wood Unit (WU). However, in health the mPAP does not exceed 20 mmHg and PVR is 2...

Approved therapies for pulmonary arterial hypertension (PAH) mediate pulmonary vascular vasodilatation by targeting distinct biological pathways. Patients identified as intermediate-low risk, according to a four-strata risk assessment model, with an inadequate response to dual therapy with a phosphodiesterase type-5 inhibitor (PDE5i) and endothelin...

Background Data on right ventricular (RV) exercise adaptation following acute intermediate and high-risk pulmonary embolism (PE) remain limited. This study aimed to evaluate the symptom burden, RV functional recovery during exercise and cardiopulmonary exercise parameters in survivors of intermediate and high-risk acute PE. Methods We prospectivel...

Purpose: Pulmonary arterial hypertension (PAH) is a rare, progressive vasculopathy with significant cardiopulmonary morbidity and mortality. Genetic testing is currently recommended for adults diagnosed with heritable, idiopathic, anorexigen-, hereditary hemorrhagic telangiectasia-, and congenital heart disease-associated PAH, PAH with overt featu...

One in ten SARS-CoV-2 infections result in prolonged symptoms termed "long COVID", yet disease phenotypes and mechanisms are poorly understood. We studied the blood proteome of 719 adults, grouped by long COVID symptoms. Elevated markers of monocytic inflammation and complement activation were associated with increased likelihood of all symptoms. E...

Background Chronic Thromboembolic Pulmonary Hypertension (CTEPH) involves formation and non-resolution of thrombus, dysregulated inflammation, angiogenesis and the development of a small vessel vasculopathy. We aimed to establish the genetic basis of CTEPH to gain insight into these pathophysiological contributors. Methods We conducted a genome-wid...

● PHOSP-COVID is a national UK multi-centre cohort study of patients who were hospitalised for COVID-19 and subsequently discharged. ● PHOSP-COVID was established to investigate the medium- and long-term sequelae of severe COVID-19 requiring hospitalisation, understand the underlying mechanisms of these sequelae, evaluate the medium- and long-term...

Background: Activins are novel therapeutic targets in pulmonary arterial hypertension (PAH). We therefore studied whether key members of the activin pathway could be used as PAH biomarkers. Methods: Serum levels of activin A, activin B, α-subunit of inhibin A and B proteins, and the antagonists follistatin and follistatin-like 3 (FSTL3) were mea...

Background: Sleep disturbance is common following hospital admission both for COVID-19 and other causes. The clinical associations of this for recovery after hospital admission are poorly understood despite sleep disturbance contributing to morbidity in other scenarios. We aimed to investigate the prevalence and nature of sleep disturbance after d...

Background: The risk factors for recovery from COVID-19 dyspnoea are poorly understood. We investigated determinants of recovery from dyspnoea in adults with COVID-19 and compared these to determinants of recovery from non-COVID-19 dyspnoea. Methods: We used data from two prospective cohort studies: PHOSP-COVID (patients hospitalised between Mar...

Background: Risk scores are important tools for the prognostic stratification of pulmonary arterial hypertension (PAH). Their performance and the additional impact of comorbidities across age groups is unknown. Methods: Patients with PAH enrolled from 2001 to 2021 were divided in ≥65 years old vs <65 years old patients. Study outcome was 5-year...

Chronic thromboembolic pulmonary hypertension may be cured by pulmonary endarterectomy (PEA). Thromboembolic disease distribution/PEA success primarily determines prognosis but risk scoring criteria may be adjunctive. Right ventriculo‐arterial (RV‐PA) and ventriculo‐atrial (RV‐RA) coupling may be evaluated by cardiac MRI (CMR) feature tracking defo...

Background Most studies of immunity to SARS-CoV-2 focus on circulating antibody, giving limited insights into mucosal defences that prevent viral replication and onward transmission. We studied nasal and plasma antibody responses one year after hospitalisation for COVID-19, including a period when SARS-CoV-2 vaccination was introduced. Methods In t...

BACKGROUND: Most studies of immunity to SARS-CoV-2 focus on circulating antibody, giving limited insights into mucosal defences that prevent viral replication and onward transmission. We studied nasal and plasma antibody responses one year after hospitalisation for COVID-19, including a period when SARS-CoV-2 vaccination was introduced. METHODS: In...

Background Persistence of respiratory symptoms—particularly breathlessness—after acute COVID-19 infection has emerged as a significant clinical problem. We aimed to characterise and identify risk factors for patients with persistent breathlessness following COVID-19 hospitalisation. Methods PHOSP-COVID is a multi-centre prospective cohort study of...

Background Risk scores are important tools for the prognostic stratification of pulmonary arterial hypertension (PAH). Their performance and the additional impact of comorbidities across age groups is unknown. Methods Patients with PAH enrolled from 2001 to 2021 were divided in ≥ 65 years old vs <65 years old patients. Study outcome was 5-year all...

Background Pulmonary arterial hypertension (PAH) is a progressive disease characterized by increased pulmonary artery pressure leading to right ventricular (RV) failure. While current PAH therapies improve patient outlook, they show limited benefit in attenuating RV dysfunction. Recent investigations demonstrated that the thromboxane (TX) A 2 recep...

Background Sleep disturbance is common following hospitalisation both for COVID-19 and other causes. The clinical associations are poorly understood, despite it altering pathophysiology in other scenarios. We, therefore, investigated whether sleep disturbance is associated with dyspnoea along with relevant mediation pathways. Methods Sleep paramete...

Background: Right atrial (RA) imaging has emerged as a promising tool for the evaluation of patients with pulmonary hypertension (PH), albeit without systematic validation. Methods: PubMed, Web of Science and the Cochrane library were searched for studies investigating the prognostic value of RA imaging assessment in patients with PH from 2000 t...

Background Most studies of immunity to SARS-CoV-2 focus on circulating antibody, giving limited insights into mucosal defences that prevent viral replication and onward transmission. We studied nasal and plasma antibody responses one year after hospitalisation for COVID-19, including a period when SARS-CoV-2 vaccination was introduced. Methods In...

COVID-19 infection primarily targets the lungs, which in severe cases progresses to cytokine storm, acute respiratory distress syndrome, multiorgan dysfunction, and shock. Survivors are now presenting evidence of cardiopulmonary sequelae such as persistent right ventricular dysfunction, chronic thrombosis, lung fibrosis, and pulmonary hypertension....