Status and Future Directions for Balloon Pulmonary Angioplasty in Chronic Thromboembolic Pulmonary Disease With and Without Pulmonary Hypertension: A Scientific Statement From the American Heart Association.

Balloon pulmonary angioplasty continues to gain traction as a treatment option for patients with chronic thromboembolic pulmonary disease with and without pulmonary hypertension. Recent European Society of Cardiology guidelines on pulmonary hypertension now give balloon pulmonary angioplasty a Class 1 recommendation for inoperable and residual chronic thromboembolic pulmonary hypertension. Not surprisingly, chronic thromboembolic pulmonary hypertension centers are rapidly initiating balloon pulmonary angioplasty programs. However, we need a comprehensive, expert consensus document outlining critical concepts, including identifying necessary personnel and expertise, criteria for patient selection, and a standardized approach to preprocedural planning and establishing criteria for evaluating procedural efficacy and safety. Given this lack of standards, the balloon pulmonary angioplasty skill set is learned through peer-to-peer contact and training. This document is a state-of-the-art, comprehensive statement from key thought leaders to address this gap in the current clinical practice of balloon pulmonary angioplasty. We summarize the current status of the procedure and provide a consensus opinion on the role of balloon pulmonary angioplasty in the overall care of patients with chronic thromboembolic pulmonary disease with and without pulmonary hypertension. We also identify knowledge gaps, provide guidance for new centers interested in initiating balloon pulmonary angioplasty programs, and highlight future directions and research needs for this emerging therapy.

Emerging multimodality imaging techniques for the pulmonary circulation.

Pulmonary hypertension (PH) remains a challenging condition to diagnose, classify and treat. Current approaches to the assessment of PH include echocardiography, ventilation/perfusion scintigraphy, cross-sectional imaging using computed tomography and magnetic resonance imaging, and right heart catheterisation. However, these approaches only provide an indirect readout of the primary pathology of the disease: abnormal vascular remodelling in the pulmonary circulation. With the advent of newer imaging techniques, there is a shift toward increased utilisation of noninvasive high-resolution modalities that offer a more comprehensive cardiopulmonary assessment and improved visualisation of the different components of the pulmonary circulation. In this review, we explore advances in imaging of the pulmonary vasculature and their potential clinical translation. These include advances in diagnosis and assessing treatment response, as well as strategies that allow reduced radiation exposure and implementation of artificial intelligence technology. These emerging modalities hold the promise of developing a deeper understanding of pulmonary vascular disease and the impact of comorbidities. They also have the potential to improve patient outcomes by reducing time to diagnosis, refining classification, monitoring treatment response and improving our understanding of disease mechanisms.

Patterns of myocardial injury in recovered troponin-positive COVID-19 patients assessed by cardiovascular magnetic resonance.

BACKGROUND: Troponin elevation is common in hospitalized COVID-19 patients, but underlying aetiologies are ill-defined. We used multi-parametric cardiovascular magnetic resonance (CMR) to assess myocardial injury in recovered COVID-19 patients. METHODS AND RESULTS: One hundred and forty-eight patients (64 ± 12 years, 70% male) with severe COVID-19 infection [all requiring hospital admission, 48 (32%) requiring ventilatory support] and troponin elevation discharged from six hospitals underwent convalescent CMR (including adenosine stress perfusion if indicated) at median 68 days. Left ventricular (LV) function was normal in 89% (ejection fraction 67% ± 11%). Late gadolinium enhancement and/or ischaemia was found in 54% (80/148). This comprised myocarditis-like scar in 26% (39/148), infarction and/or ischaemia in 22% (32/148) and dual pathology in 6% (9/148). Myocarditis-like injury was limited to three or less myocardial segments in 88% (35/40) of cases with no associated LV dysfunction; of these, 30% had active myocarditis. Myocardial infarction was found in 19% (28/148) and inducible ischaemia in 26% (20/76) of those undergoing stress perfusion (including 7 with both infarction and ischaemia). Of patients with ischaemic injury pattern, 66% (27/41) had no past history of coronary disease. There was no evidence of diffuse fibrosis or oedema in the remote myocardium (T1: COVID-19 patients 1033 ± 41 ms vs. matched controls 1028 ± 35 ms; T2: COVID-19 46 ± 3 ms vs. matched controls 47 ± 3 ms). CONCLUSIONS: During convalescence after severe COVID-19 infection with troponin elevation, myocarditis-like injury can be encountered, with limited extent and minimal functional consequence. In a proportion of patients, there is evidence of possible ongoing localized inflammation. A quarter of patients had ischaemic heart disease, of which two-thirds had no previous history. Whether these observed findings represent pre-existing clinically silent disease or de novo COVID-19-related changes remain undetermined. Diffuse oedema or fibrosis was not detected.

ERS statement on chronic thromboembolic pulmonary hypertension.

Chronic thromboembolic pulmonary hypertension (CTEPH) is a rare complication of acute pulmonary embolism, either symptomatic or not. The occlusion of proximal pulmonary arteries by fibrotic intravascular material, in combination with a secondary microvasculopathy of vessels <500 µm, leads to increased pulmonary vascular resistance and progressive right heart failure. The mechanism responsible for the transformation of red clots into fibrotic material remnants has not yet been elucidated. In patients with pulmonary hypertension, the diagnosis is suspected when a ventilation/perfusion lung scan shows mismatched perfusion defects, and confirmed by right heart catheterisation and vascular imaging. Today, in addition to lifelong anticoagulation, treatment modalities include surgery, angioplasty and medical treatment according to the localisation and characteristics of the lesions.This statement outlines a review of the literature and current practice concerning diagnosis and management of CTEPH. It covers the definitions, diagnosis, epidemiology, follow-up after acute pulmonary embolism, pathophysiology, treatment by pulmonary endarterectomy, balloon pulmonary angioplasty, drugs and their combination, rehabilitation and new lines of research in CTEPH.It represents the first collaboration of the European Respiratory Society, the International CTEPH Association and the European Reference Network-Lung in the pulmonary hypertension domain. The statement summarises current knowledge, but does not make formal recommendations for clinical practice.

Right ventricle in adulthood: CT and MR assessment.

Anatomical complexities coupled with a protracted subclinical disease course, particularly in the early stages, makes the right ventricle (RV) the less studied entity when compared with the left. RV failure is an important predictor of survival in patients with cardiovascular disease. Technological advances have made it possible to visualise and characterise a variety of diseases that affect the RV. This review article will give a broad overview of the main RV pathology to general radiologists in particular those that manifest in adulthood. Congenital heart disease is a vast topic that is beyond the scope of this paper.

Diagnosis of pulmonary hypertension.

A revised diagnostic algorithm provides guidelines for the diagnosis of patients with suspected pulmonary hypertension, both prior to and following referral to expert centres, and includes recommendations for expedited referral of high-risk or complicated patients and patients with confounding comorbidities. New recommendations for screening high-risk groups are given, and current diagnostic tools and emerging diagnostic technologies are reviewed.

Dynamic Risk Stratification of Patient Long-Term Outcome After Pulmonary Endarterectomy: Results From the United Kingdom National Cohort.

BACKGROUND: Chronic thromboembolic pulmonary hypertension results from incomplete resolution of pulmonary emboli. Pulmonary endarterectomy (PEA) is potentially curative, but residual pulmonary hypertension following surgery is common and its impact on long-term outcome is poorly understood. We wanted to identify factors correlated with poor long-term outcome after surgery and specifically define clinically relevant residual pulmonary hypertension post-PEA. METHODS AND RESULTS: Eight hundred eighty consecutive patients (mean age, 57 years) underwent PEA for chronic thromboembolic pulmonary hypertension. Patients routinely underwent detailed reassessment with right heart catheterization and noninvasive testing at 3 to 6 months and annually thereafter with discharge if they were clinically stable at 3 to 5 years and did not require pulmonary vasodilator therapy. Cox regressions were used for survival (time-to-event) analyses. Overall survival was 86%, 84%, 79%, and 72% at 1, 3, 5, and 10 years for the whole cohort and 91% and 90% at 1 and 3 years for the recent half of the cohort. The majority of patient deaths after the perioperative period were not attributable to right ventricular failure (chronic thromboembolic pulmonary hypertension). At reassessment, a mean pulmonary artery pressure of ≥30 mm Hg correlated with the initiation of pulmonary vasodilator therapy post-PEA. A mean pulmonary artery pressure of ≥38 mm Hg and pulmonary vascular resistance ≥425 dynes·s(-1)·cm(-5) at reassessment correlated with worse long-term survival. CONCLUSIONS: Our data confirm excellent long-term survival and maintenance of good functional status post-PEA. Hemodynamic assessment 3 to 6 months and 12 months post-PEA allows stratification of patients at higher risk of dying of chronic thromboembolic pulmonary hypertension and identifies a level of residual pulmonary hypertension that may guide the long-term management of patients postsurgery.

Successful Treatment of Very Early Thrombosis of SAPIEN 3 Valve with Direct Oral Anticoagulant Therapy.

Thrombosis of transcatheter aortic valve implantation (TAVI) is an uncommon complication that commonly occurs weeks to months following the procedure. Herein are described the details of a patient who presented with a recurrence of symptoms days after intervention with a bioprosthesis thrombosis that was successfully treated with direct oral anticoagulant (DOAC) therapy and resulted in hemodynamic improvement and resolution of symptoms. Whilst a previous trial of DOAC therapy with mechanical valves was stopped due to elevated events in comparison to warfarin, a TAVI valve may be different, and the rapid onset of action and reduced bleeding risk may be beneficial in this patient group.

Multimodality cardiac imaging in Turner syndrome.

Congenital and acquired cardiovascular diseases contribute significantly to the threefold elevated risk of premature death in Turner syndrome. A multitude of cardiovascular anomalies and disorders, many of which deleteriously impact morbidity and mortality, is frequently left undetected and untreated because of poor adherence to screening programmes and complex clinical presentations. Imaging is essential for timely and effective primary and secondary disease prophylaxis that may alleviate the severe impact of cardiovascular disease in Turner syndrome. This review illustrates how cardiovascular disease in Turner syndrome manifests in a complex manner that ranges in severity from incidental findings to potentially fatal anomalies. Recommendations regarding the use of imaging for screening and surveillance of cardiovascular disease in Turner syndrome are made, emphasising the key role of non-invasive and invasive cardiovascular imaging to the management of all patients with Turner syndrome.

Absent right common carotid artery with stenting of symptomatic internal carotid artery stenosis.

Absent common carotid artery with independent origin of internal and external carotid arteries from the subclavian artery is a rare but recognized phenomenon. We describe one such case with an associated symptomatic proximal high-grade stenosis of the right internal carotid artery. The abnormal carotid anatomy was not initially well appreciated, resulting in a failed surgical exploration and subsequent successful endovascular carotid stenting. To our knowledge, this is the first reported case of carotid stent in a right internal carotid artery originating from the subclavian artery.

Utility of speckle tracking echocardiography to characterize dysfunctional myocardium in patients with ischemic cardiomyopathy referred for cardiac resynchronization therapy.

BACKGROUND: Assessment of transmural scar at the site of latest mechanical activation is relevant to maximize outcomes in cardiac resynchronization therapy (CRT). Few studies have assessed the ability of speckle tracking echocardiography (STE)-derived short-axis strain to identify segmental myocardial scar, defined by contrast-enhanced cardiac magnetic resonance imaging (CMR), in patients referred for CRT. METHODS: A total of 26 patients with ischemic cardiomyopathy who underwent preprocedure echocardiography and CMR were studied. Extent of transmural scar was assessed using contrast-enhanced CMR and corresponding peak segmental radial and circumferential strains were derived using two-dimensional (2D) STE. Total left ventricle (LV) scar volume was compared with parameters of global strain. CRT response was defined as >15% reduction in LV end systolic volume (LVESV) at 6 months. RESULTS: Speckle tracking short-axis strain analysis was technically possible in over 90% of LV segments. Applying a segmental radial strain cutoff value of 10% distinguished segments with >50% scar area with a high negative predictive value (98%). Global longitudinal strain <-5% predicted CRT response. CONCLUSIONS: Two-dimensional STE offers potential to characterize dysfunctional myocardium and define segmental scar offering an integrated imaging approach to guide LV lead placement for CRT.

Multimodality imaging of acute and chronic pulmonary thromboembolic disease.

Pulmonary embolism (PE) is a pathological entity characterised by venous thromboembolism in the pulmonary arteries. It is a common entity in daily clinical practice and is the third most common cause of cardiovascular death. Correct diagnostic work-up is pivotal to ensure timely institution of appropriate therapy. This requires recognition of the characteristic imaging findings and awareness of the role and peculiarities of the different imaging techniques involved in the diagnostic and therapeutic process. This review aims to showcase the most commonly encountered imaging findings associated with pulmonary thromboembolism for each imaging modality, outline their advantages and disadvantages, and define the specific role of these techniques in the clinical setting. The latest innovations concerning the diagnostic work-up of PE will be also briefly discussed, yielding a perspective on the future developments and challenges that the radiologist will have to face in the coming years.

Pulmonary veno-occlusive disease: illustrative cases and literature review.

Pulmonary veno-occlusive disease (PVOD), also known as "pulmonary arterial hypertension (PAH) with overt features of venous/capillary involvement", is a rare cause of PAH characterised by substantial small pulmonary vein and capillary involvement, leading to increased pulmonary vascular resistance and right ventricular failure. Environmental risk factors have been associated with the development of PVOD, such as occupational exposure to organic solvents and chemotherapy, notably mitomycin. PVOD may also be associated with a mutation in the EIF2AK4 gene in heritable forms of disease. Distinguishing PVOD from PAH is critical for guiding appropriate management. Chest computed tomography typically displays interlobular septal thickening, ground-glass opacities and mediastinal lymphadenopathy. Life-threatening pulmonary oedema is a complication of pulmonary vasodilator therapy that can occur with any class of PAH drugs in PVOD. Early referral to a lung transplant centre is essential due to the poor response to therapy when compared with other forms of PAH. Histopathological analysis of lung explants reveals microvascular remodelling with typical fibrous veno-occlusive lesions. This review covers the main features distinguishing PVOD from PAH and two clinical cases that illustrate the challenges of PVOD management.

Clinical-imaging-pathological correlation in pulmonary hypertension associated with left heart disease.

Pulmonary hypertension (PH) is highly prevalent in patients with left heart disease (LHD) and negatively impacts prognosis. The most common causes of PH associated with LHD (PH-LHD) are left heart failure and valvular heart disease. In LHD, passive backward transmission of increased left-sided filling pressures leads to isolated post-capillary PH. Additional pulmonary vasoconstriction and remodelling lead to a higher vascular load and combined pre- and post-capillary PH. The increased afterload leads to right ventricular dysfunction and failure. Multimodality imaging of the heart plays a central role in the diagnostic work-up and follow-up of patients with PH-LHD. Echocardiography provides information about the estimated pulmonary artery pressure, morphology and function of the left and right side of the heart, and valvular abnormalities. Cardiac magnetic resonance imaging is the gold standard for volumetric measurements and provides myocardial tissue characterisation. Computed tomography of the thorax may show general features of PH and/or LHD and is helpful in excluding other PH causes. Histopathology reveals a spectrum of pre- and post-capillary vasculopathy, including intimal fibrosis, media smooth muscle cell hyperplasia, adventitial fibrosis and capillary congestion. In this paper, we provide an overview of clinical, imaging and histopathological findings in PH-LHD based on three clinical cases.

Use of coronarycomputed tomography for cardiovascular risk assessment in immune-mediated inflammatory diseases.

Immune-mediated inflammatory diseases (IMIDs) are recognised risk factors for accelerated atherosclerotic cardiovascular disease (CVD), particularly in younger individuals and women who lack traditional CVD risk factors. Reflective of the critical role that inflammation plays in the formation, progression and rupture of atherosclerotic plaques, research into immune mechanisms of CVD has led to the identification of a range of therapeutic targets that are the subject of ongoing clinical trials. Several key inflammatory pathways implicated in the pathogenesis of atherosclerosis are targeted in people with IMIDs. However, cardiovascular risk continues to be systematically underestimated by conventional risk assessment tools in the IMID population, resulting in considerable excess CVD burden and mortality. Hence, there is a pressing need to improve methods for CVD risk-stratification among patients with IMIDs, to better guide the use of statins and other prognostic interventions. CT coronary angiography (CTCA) is the current first-line investigation for diagnosing and assessing the severity of coronary atherosclerosis in many individuals with suspected angina. Whether CTCA is also useful in the general population for reclassifying asymptomatic individuals and improving long-term prognosis remains unknown. However, in the context of IMIDs, it is conceivable that the information provided by CTCA, including state-of-the-art assessments of coronary plaque, could be an important clinical adjunct in this high-risk patient population. This narrative review discusses the current literature about the use of coronary CT for CVD risk-stratification in three of the most common IMIDs including rheumatoid arthritis, psoriasis and systemic lupus erythematosus.

Computed tomography pericoronary adipose tissue density predicts coronary allograft vasculopathy and adverse clinical outcomes after cardiac transplantation.

AIMS: To assess pericoronary adipose tissue (PCAT) density on coronary computed tomography angiography (CCTA) as a marker of inflammatory disease activity in coronary allograft vasculopathy (CAV). METHODS AND RESULTS: PCAT density, lesion volumes, and total vessel volume-to-myocardial mass ratio (V/M) were retrospectively measured in 126 CCTAs from 94 heart transplant patients [mean age 49 (SD 14.5) years, 40% female] who underwent imaging between 2010 and 2021; age- and sex-matched controls; and patients with atherosclerosis. PCAT density was higher in transplant patients with CAV [n = 40; -73.0 HU (SD 9.3)] than without CAV [n = 86; -77.9 HU (SD 8.2)], and controls [n = 12; -86.2 HU (SD 5.4)], P < 0.01 for both. Unlike patients with atherosclerotic coronary artery disease (n = 32), CAV lesions were predominantly non-calcified and comprised of mostly fibrous or fibrofatty tissue. V/M was lower in patients with CAV than without [32.4 mm3/g (SD 9.7) vs. 41.4 mm3/g (SD 12.3), P < 0.0001]. PCAT density and V/M improved the ability to predict CAV from area under the receiver operating characteristic curve (AUC) 0.75-0.85 when added to donor age and donor hypertension status (P < 0.0001). PCAT density above -66 HU was associated with a greater incidence of all-cause mortality {odds ratio [OR] 18.0 [95% confidence interval (CI) 3.25-99.6], P < 0.01} and the composite endpoint of death, CAV progression, acute rejection, and coronary revascularization [OR 7.47 (95% CI 1.8-31.6), P = 0.01] over 5.3 (SD 2.1) years. CONCLUSION: Heart transplant patients with CAV have higher PCAT density and lower V/M than those without. Increased PCAT density is associated with adverse clinical outcomes. These CCTA metrics could be useful for the diagnosis and monitoring of CAV severity.

Long-term effects of pulmonary endarterectomy on pulmonary hemodynamics, cardiac function, and exercise capacity in chronic thromboembolic pulmonary hypertension.

BACKGROUND: Long-term changes in exercise capacity and cardiopulmonary hemodynamics after pulmonary endarterectomy (PEA) for chronic thromboembolic pulmonary hypertension (CTEPH) have been poorly described. METHODS: We analyzed the data from 2 prospective surgical CTEPH cohorts in Hammersmith Hospital, London, and Amsterdam UMC. A structured multimodal follow-up was adopted, consisting of right heart catheterization, cardiac magnetic resonance imaging, and cardiopulmonary exercise testing before and after PEA. Preoperative predictors of residual pulmonary hypertension (PH; mean pulmonary artery pressure >20 mm Hg and pulmonary vascular resistance ≥2 WU) and long-term exercise intolerance (VO2max <80%) at 18 months were analyzed. RESULTS: A total of 118 patients (61 from London and 57 from Amsterdam) were included in the analysis. Both cohorts displayed a significant improvement of pulmonary hemodynamics, right ventricular (RV) function, and exercise capacity 6 months after PEA. Between 6 and 18 months after PEA, there were no further improvements in hemodynamics and RV function, but the proportion of patients with impaired exercise capacity was high and slightly increased over time (52%-59% from 6 to 18 months). Long-term exercise intolerance was common and associated with preoperative diffusion capacity for carbon monoxide (DLCO), preoperative mixed venous oxygen saturation, and postoperative PH and right ventricular ejection fraction (RVEF). Clinically significant RV deterioration (RVEF decline >3%; 5 [9%] of 57 patients) and recurrent PH (5 [14%] of 36 patients) rarely occurred beyond 6 months after PEA. Age and preoperative DLCO were predictors of residual PH post-PEA. CONCLUSIONS: Restoration in exercise tolerance, cardiopulmonary hemodynamics, and RV function occurs within 6 months. No substantial changes occurred between 6 and 18 months after PEA in the Amsterdam cohort. Nevertheless, long-term exercise intolerance is common and associated with postoperative RV function.

COVID-19 related myocardial injury is associated with immune dysregulation in symptomatic patients with cardiac MRI abnormalities.

AIMS: While acute cardiovascular complications of COVID-19 are well-described, less is known about longer-term cardiac sequelae. For many individuals with cardiac signs or symptoms arising after COVID-19 infection, the aetiology remains unclear. We examined immune profiles associated with magnetic resonance imaging (MRI) abnormalities in patients with unexplained cardiac injury after COVID-19. METHODS AND RESULTS: Twenty-one participants (mean age 47 [SD 13] years, 71% female) with long COVID (n=17), raised troponin (n=2), or unexplained new-onset heart failure (n=2), who did not have pre-existing heart conditions or recent steroid/immunosuppression treatment were enrolled a mean 346 (SD 191) days after COVID-19 infection in a prospective observational study. Cardiac MRI and blood sampling for deep immunophenotyping using mass cytometry by time of flight and measurement of proteomic inflammatory markers was performed. Nine of 21 (43%) participants had MRI abnormalities (MRI(+)), including non-ischaemic patterns of late gadolinium enhancement and/or visually overt myocardial oedema in 8 people. One patient had mildly impaired biventricular function without fibrosis or oedema, and 2 had severe left ventricular impairment. MRI(+) individuals had higher blood CCL3, CCL7, FGF-23 and CD4 Th2 cells, and lower CD8 T effector memory (TEM) cells, than MRI(-). Cluster analysis revealed lower expression of inhibitory receptors PD1 and TIM3 in CD8 TEM cells from MRI(+) patients than MRI(-) patients, and functional studies of CD8 T αß cells showed higher proportions of cytotoxic granzyme B+ secreting cells upon stimulation. CD8 TEM cells and CCL7 were the strongest predictors of MRI abnormalities in a LASSO regression model (composite AUC 0.96, 95%CI 0.88-1.0). CCL7 was correlated with diffuse myocardial fibrosis/oedema detected by quantitative T1 mapping (r=0.47, p=0.04). CONCLUSION: COVID-19 related cardiac injury in symptomatic patients with non-ischaemic myocarditis-like MRI abnormalities is associated with immune dysregulation, including decreased peripheral CD8 TEM cells and increased CCL7, persisting long after the initial infection.

Mimics of acute coronary syndrome on MDCT.

Acute coronary syndrome (ACS) encompasses a spectrum of unstable coronary artery disease ranging from transmural myocardial infarction to unstable angina. The immediate management of these patients is dictated by the presence/absence of ST segment changes on electrocardiogram. More and more patients with non-ST elevation ACS are bypassing traditional diagnostic pathways to undergo urgent coronary catheter angiography. A proportion of these patients will have normal coronary angiography and an alternative diagnosis is often sought with multi-detector computed tomography (MDCT). It is vital that clinicians and radiologists are aware of the usual and unusual mimics of ACS so they can modify their imaging technique and protocol accordingly. In this review, we present some true mimics of ACS on MDCT, from our practice, and suggest an imaging protocol that can be utilised universally.