European Respiratory Society

Cardiovascular Complications of Respiratory Disorders

Edited by Miguel Ángel Martínez-García, Jean-Louis Pépin and Mario Cazzola
Cardiovascular Complications of Respiratory Disorders

This Monograph provides an update on cardiovascular disease complications and treatment implications for respiratory diseases, based on current scientific evidence and considered from an epidemiological, pathophysiological and clinical point of view. This book also discusses the future challenges when studying the complex relationship between these two groups of disorders.

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  4. Page 1
    Abstract
    Joan B. Soriano, Servicio de Neumología, Hospital Universitario La Princesa, Madrid, Spain. E-mail: jbsoriano2@gmail.com

    It is often a clinical challenge to perform a differential diagnosis of individual patients suffering from CVDs and respiratory diseases, as their causes can be coincidental, their symptoms may overlap and case definitions are often not straightforward. They are often under- or misdiagnosed and co-occur in ageing individuals with multiple comorbidities. Similar or even greater problems occur when establishing their population epidemiology. Furthermore, as global diagnostic practices and medical access are highly heterogeneous, comparing national and international epidemiology estimators is not easy. In this chapter, we aim to describe the current epidemiology and future burden of CVDs and respiratory diseases, as well as their occurrence as comorbidities.

    Cite as: Soriano JB, Elosua R. Epidemiological aspects of cardiovascular and respiratory diseases. In: Martínez-García MÁ, Pépin J-L, Cazzola M, eds. Cardiovascular Complications of Respiratory Disorders (ERS Monograph). Sheffield, European Respiratory Society, 2020; pp. 1–11 [https://doi.org/10.1183/2312508X.10027019].

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    Abstract
    Renaud Tamisier, Laboratoire du Sommeil, CHU de Grenoble, BP217X 38043 Grenoble cedex 09, France. E-mail: rtamisier@chu-grenoble.fr

    Respiratory disorders such as OSA and COPD are associated with an increased risk of CVDs in which the sympathetic system of the autonomic nervous system is pivotal. These disorders share an autonomic nervous system dysregulation that promotes high cardiovascular sympathetic tone. Different stimuli, such as hypoxia (intermittent or chronic), sleep fragmentation, increased respiratory effort, systemic inflammation and carbon dioxide accumulation, may all initiate the pathophysiological cascade leading to sympathetic overactivity. In this chapter, we describe the pathways in different respiratory conditions leading to sympathetic overactivity as a potent important role in the development of CVDs. We also present arguments as to how sympathetic overactivity may contribute to the metabolic dysregulation associated with these chronic respiratory disorders.

    Cite as: Viglino D, Maltais F, Tamisier R. Common pathophysiological pathways of the autonomic nervous system. In: Martínez-García MÁ, Pépin J-L, Cazzola M, eds. Cardiovascular Complications of Respiratory Disorders (ERS Monograph). Sheffield, European Respiratory Society, 2020; pp. 12–30 [https://doi.org/10.1183/2312508X.10027119].

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    Abstract
    Mireia Dalmases, Hospital Universitari Arnau de Vilanova, Rovira Roure, 80, 25198 Lleida, Spain. E-mail: mdalmases.lleida.ics@gencat.cat

    Numerous animal models have been developed to mimic the clinical characteristics and biological changes encountered in human diseases. These models make it possible to study the mechanisms and cardiovascular consequences of respiratory diseases without confounding factors and permit the study of parameters that are difficult or impossible to assess in humans. Moreover, animal models can evaluate causality and either exclude or add comorbidities in a controlled fashion. Experimental models could enhance our knowledge of the mechanisms involved in cardiovascular damage in lung diseases and could be helpful for developing future treatment options that are more precise and adapted to the pathophysiology of each individual.

    Cite as: Almendros I, Blanco I, Marquina M, et al. Murine models of cardiovascular damage in lung diseases. In: Martínez-García MÁ, Pépin J-L, Cazzola M, eds. Cardiovascular Complications of Respiratory Disorders (ERS Monograph). Sheffield, European Respiratory Society, 2020; pp. 31–46 [https://doi.org/10.1183/2312508X.10027219].

    1. Page 47
      Abstract
      Paola Rogliani, Dept of Experimental Medicine, Via Montpellier 1, 00133, Rome, Italy. E-mail: paola.rogliani@uniroma2.it

      COPD is a serious public health concern and is frequently associated with CVD. When COPD is associated with CVD, there is reduced health status and increased hospitalisation rate and mortality. CVD and COPD share a common background chronic low-grade systemic inflammation, triggered by several stimuli including air pollutants and cigarette smoke. The teleological activities and paradoxical effects of polypeptide cardiac hormones further support the intimate relationship between CVD and COPD. COPD exacerbations play a pivotal role in COPD progression, and early identification of cardiac problems could help to better phenotype COPD exacerbators and ameliorate disease prognosis. In this scenario, novel predictive tools and biomarkers of cardiovascular risk specifically validated in COPD populations may help to identify pre-symptomatic subjects. Current recommendations for the management of CVD in COPD patients are limited and therefore pulmonologists and cardiologists should work together in order to reach a correct and complementary diagnosis and identify tailored therapy.

      Cite as: Rogliani P, Calzetta L. Cardiovascular disease in COPD. In: Martínez-García MÁ, Pépin J-L, Cazzola M, eds. Cardiovascular Complications of Respiratory Disorders (ERS Monograph). Sheffield, European Respiratory Society, 2020; pp. 47–65 [https://doi.org/10.1183/2312508X.10027319].

    2. Page 66
      Abstract
      Josuel Ora, Respiratory Diseases Unit, “Tor Vergata” University Hospital, viale Oxford 81, Rome 00133, Italy. E-mail: josuel78@gmail.com

      Asthma or COPD and CVDs often coexist. In such circumstances, these diseases must be considered in an integrated way because there is evidence that treatment for one condition may influence the other. Therefore, therapy should be optimised in order to take advantage of the beneficial effects that each therapy could exert on both organs, but making every effort to reduce the possibility of deleterious effects on the lungs and heart.

      Cite as: Ora J, Cavalli F, Cazzola M. Management of patients with asthma or COPD and cardiovascular disease: risks versus benefits. In: Martínez-García MÁ, Pépin J-L, Cazzola M, eds. Cardiovascular Complications of Respiratory Disorders (ERS Monograph). Sheffield, European Respiratory Society, 2020; pp. 66–81 [https://doi.org/10.1183/2312508X.10027419].

    3. Page 82
      Abstract
      Diego J. Maselli, Division of Pulmonary Diseases and Critical Care, UT Health San Antonio, 7400 Merton Minter, MC111E, San Antonio, TX, 78249, USA. E-mail: masellicacer@uthscsa.edu

      Chronic obstructive lung diseases and CVD are common conditions with a significant prevalence worldwide and substantial morbidity. There is a growing body of evidence that associates asthma as a potential risk factor for CVD, in particular, CAD, acute myocardial infarction and stroke. These observations appear to be stronger in patients with uncontrolled asthma and in women. Moreover, asthma that appears later in life has been also linked to CVD. The associations between asthma and CVD are incompletely understood, but chronic and systemic inflammation derived from the airways may have a role in the development of the atherosclerosis and hypercoagulable states. Additionally, eosinophils, smooth muscle factors, endothelial dysfunction and haemodynamic stress may be important factors that link asthma and CVD. These observations have raised clinical awareness and may identify asthmatics with a higher risk profile for CVD, opening an opportunity for potential interventions in the earlier stages of the disease.

      Cite as: Argueta FA, Alviar CL, Peters JI, Maselli DJ. Chronic asthma and the risk of cardiovascular disease. In: Martínez-García MÁ, Pépin J-L, Cazzola M, eds. Cardiovascular Complications of Respiratory Disorders (ERS Monograph). Sheffield, European Respiratory Society, 2020; pp. 82–95 [https://doi.org/10.1183/2312508X.10027519].

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      Abstract
      Wei-jie Guan, State Key Laboratory of Respiratory Disease, National Clinical Research Center for Respiratory Disease, Guangzhou Institute of Respiratory Disease, First Affiliated Hospital of Guangzhou Medical University, 151 Yanjiang Road, Guangzhou, Guangdong, China. E-mail: battery203@163.com

      CVDs are common comorbidities seen in bronchiectasis. There is a significantly increased risk of CVDs in patients with bronchiectasis than in those without. The mechanisms are poorly understood but may include heightened neutrophilic inflammation, uncontrolled neutrophil elastase activity, oxidative stress and endothelial dysfunction. Comorbid CVDs are correlated with poor clinical outcomes and certain bronchiectasis phenotypes. Comorbid diseases are an important aspect of bronchiectasis disease severity grading. However, the current diagnostic criteria have been based on a comparison of the diameter of bronchi and the accompanying pulmonary artery, and may have certain limitations. Nevertheless, aberrant findings for pulmonary vessels have been linked to a greater risk of haemoptysis. Identification of CVDs in at-risk bronchiectasis patients with modern point-of-care testing such as ultrasonography, computed tomography and blood biomarkers may provide an important opportunity for early intervention.

      Cite as: Guan W-j, Gao Y-h, de la Rosa-Carrillo D, et al. Cardiovascular implications in bronchiectasis. In: Martínez-García MÁ, Pépin J-L, Cazzola M, eds. Cardiovascular Complications of Respiratory Disorders (ERS Monograph). Sheffield, European Respiratory Society, 2020; pp. 96–107 [https://doi.org/10.1183/2312508X.10027619].

    5. Page 108
      Abstract
      Damian G. Downey, Centre for Experimental Medicine, Queen's University Belfast, Belfast, UK. E-mail: d.downey@qub.ac.uk

      Cystic fibrosis (CF) is an autosomal-recessive disease caused by mutations in the gene that encodes the CF transmembrane conductance regulator (CFTR) protein. This results in progressive lung damage, respiratory failure and premature death. Recent development of therapies to modulate CFTR has resulted in significant improvements in lung function. As people with CF (PWCF) live longer, there will be a rise in nonpulmonary complications. CVD is the leading cause of death worldwide, with increasing recognition that inflammatory respiratory tract conditions have been linked to a higher risk of CVD. Although right heart changes are established consequences of severe lung disease, left ventricular dysfunction and arterial stiffness have been identified in young PWCF. CFTR loss has also been implicated in impaired endothelial cell function and systemic inflammation, which can lead to CVD. Further research is required for PWCF with increasing risk factors for CVD; this should inform screening recommendations and risk-reduction strategies in the era of CFTR modulation.

      Cite as: Downey DG, Elborn JS. Cardiovascular complications of cystic fibrosis. In: Martínez-García MÁ, Pépin J-L, Cazzola M, eds. Cardiovascular Complications of Respiratory Disorders (ERS Monograph). Sheffield, European Respiratory Society, 2020; pp. 108–117 [https://doi.org/10.1183/2312508X.10000920].

    6. Page 118
      Abstract
      Maria R. Bonsignore, Sleep and Respiratory Failure Clinic, PROMISE Dept, University of Palermo, Piazza delle Cliniche, 2, 90100 Palermo, Italy. E-mail: marisa.bonsignore@irib.cnr.it

      CPAP treatment decreases BP in OSA patients, especially in severe OSA, and in patients with poorly controlled BP. OSA adversely affects heart function and remodelling, but its role in the pathogenesis of HF remains unclear. Similarly, the impact of CPAP is uncertain, and results of the ongoing ADVENT-HF trial will provide more information. Several experimental studies in animals and humans indicate a central role of intermittent hypoxia in atherogenesis through multiple mechanisms. However, randomised controlled trials (RCTs) in patients with CAD and OSA found no difference in outcomes between CPAP-treated and untreated patients. The negative results of secondary prevention RCTs may be the result of exclusion of severely sleepy patients and poor compliance with CPAP treatment. In addition, room for improvement after substantial cardiac interventions may be very limited. Knowledge on arrhythmias in OSA has expanded in recent years, especially regarding AF and ventricular arrhythmias including sudden cardiac death. However, studies on the effects of CPAP are limited and controversial.

      Cite as: Bonsignore MR, Gallina S, Drager LF. Cardiovascular consequences of sleep disordered breathing: the role of CPAP treatment. In: Martínez-García MÁ, Pépin J-L, Cazzola M, eds. Cardiovascular Complications of Respiratory Disorders (ERS Monograph). Sheffield, European Respiratory Society, 2020; pp. 118–142 [https://doi.org/10.1183/2312508X.10027819].

    7. Page 143
      Abstract
      Babak Mokhlesi, Section of Pulmonary and Critical Care, Sleep Disorders Center, University of Chicago, 5841 S. Maryland Avenue, MC6076/Room M630, Chicago, IL 60637, USA. E-mail: bmokhles@medicine.bsd.uchicago.edu

      Obesity hypoventilation syndrome (OHS) is defined by obesity, daytime hypercapnia and sleep-disordered breathing after excluding other aetiologies of hypoventilation. When left untreated, patients with OHS experience increased morbidity and mortality, largely due to cardiovascular conditions. PH is probably linked directly to chronic hypoventilation and sleep-disordered breathing; it is highly prevalent, with about half of patients with OHS exhibiting PH. The main cause of death is from CVD, including PH and right-sided HF. Weight loss is the ideal treatment as it can improve respiratory failure, PH and sleep-disordered breathing. In the majority of patients with OHS who also have severe OSA, improvements in PH and left ventricular diastolic dysfunction can be similarly achieved with noninvasive ventilation and CPAP.

      Cite as: Ramírez Molina VR, Masa JF, de Terreros Caro FJG, et al. The heart in obesity hypoventilation syndrome. In: Martínez-García MÁ, Pépin J-L, Cazzola M, eds. Cardiovascular Complications of Respiratory Disorders (ERS Monograph). Sheffield, European Respiratory Society, 2020; pp. 143–153 [https://doi.org/10.1183/2312508X.10027919].

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      Abstract
      Anne-Claire Toffart, Service Hospitalo-Universitaire Pneumologie et Physiologie, CHU Grenoble Alpes, Boulevard de la Chantourne, CS10217, 38043 Grenoble Cedex 9, France. E-mail: AToffart@chu-grenoble.fr

      Over recent decades, new therapeutic options for the treatment of lung cancer have emerged. These may be responsible for new toxicities, particularly CVEs. This chapter focuses on CVEs of targeted cancer therapies: anti-angiogenesis agents and immune checkpoint inhibitors (ICIs). While kinase inhibitors may be associated with bradycardia and QT-interval prolongation requiring monitoring of drug–drug interactions, anti-angiogenic agents are frequently responsible for hypertension and proteinuria. Myocarditis is an infrequent but life-threatening side-effect of ICIs. Thus, oncologists have to consider (prevent, anticipate, detect, treat and monitor) these cardiovascular toxicities with the help of the cardiology team.

      Cite as: Toffart A-C, Pluchart H, Girard N. Cardiovascular effects of innovative therapies in lung cancer. In: Martínez-García MÁ, Pépin J-L, Cazzola M, eds. Cardiovascular Complications of Respiratory Disorders (ERS Monograph). Sheffield, European Respiratory Society, 2020; pp. 154–166 [https://doi.org/10.1183/2312508X.10028019].

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      Abstract
      Etienne-Marie Jutant, Service de Pneumologie, Hôpital Bicêtre, 78 Rue du Général Leclerc, 94275 Le Kremlin-Bicêtre, France. E-mail: etiennemarie.jutant@aphp.fr

      PH is a common complication of chronic respiratory diseases and a marker of poor prognosis (group 3 of the PH classification). PH is suspected on the basis of clinical signs and Doppler echocardiography; confirmation requires RHC demonstrating pre-capillary PH with mPAP >20 mmHg, pulmonary artery wedge pressure ≤15 mmHg and elevated pulmonary vascular resistance ≥3 Wood units. Most patients present with mild-to-moderate PH. However, a small subset display severe PH and right HF. Treatment of underlying respiratory disease is recommended and administration of oxygen therapy in cases of hypoxaemia and noninvasive ventilation if there is an indication of hypoventilation. Drugs approved for PAH are not recommended in group 3 PH. Severe cases should be referred to expert centres and included in clinical trials and registries; lung transplantation should be discussed.

      Cite as: Jutant E-M, Ghigna M-R, Montani D, et al. Cardiovascular implications of pulmonary hypertension due to chronic respiratory diseases. In: Martínez-García MÁ, Pépin J-L, Cazzola M, eds. Cardiovascular Complications of Respiratory Disorders (ERS Monograph). Sheffield, European Respiratory Society, 2020; pp. 167–183 [https://doi.org/10.1183/2312508X.10028119].

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      Abstract
      David Jiménez, Respiratory Dept and Medicine Dept, Ramón y Cajal Hospital, IRYCIS and Universidad de Alcalá, 28034 Madrid, Spain. E-mail: djimenez.hrc@gmail.com

      Pulmonary embolism (PE) is a common, life-threatening disease, with the majority of deaths occurring early after diagnosis due to haemodynamic instability, deterioration of a previous medical illness or complications from PE therapies. Short-term nonfatal morbidities include recurrent venous thromboembolism (VTE) and new-onset AF. Appropriate triage of the level of care, anticoagulation and guideline-recommended use of advanced therapies are necessary to reduce short-term cardiovascular complications. Long-term mortality after a PE event is mainly due to comorbidities (including advanced cancer), recurrent fatal PE or chronic thromboembolic pulmonary hypertension. Long-term nonfatal complications include recurrent VTE, post-PE syndrome, arterial atherosclerosis and thrombosis. Appropriate risk assessment for consideration of long-term anticoagulation is the cornerstone to reducing the risk of long-term PE complications. Use of an integrated model of patient care is key for accurate and individualised patient counselling to identify the treatment choice and duration, and for early detection of complications that might benefit from timely management.

      Cite as: Bikdeli B, Rodríguez C, García-Ortega A, Jiménez D. Cardiovascular mortality and morbidity in pulmonary embolism. In: Martínez-García MÁ, Pépin J-L, Cazzola M, eds. Cardiovascular Complications of Respiratory Disorders (ERS Monograph). Sheffield, European Respiratory Society, 2020; pp. 184–197 [https://doi.org/10.1183/2312508X.10028219].

    11. Page 198
      Abstract
      Martin R.J. Kolb, Division of Respirology, Firestone Institute for Respiratory Health, McMaster University, 50 Charlton Avenue East, Room T2120, Hamilton, ON, L8N 4A6, Canada. E-mail: kolbm@mcmaster.ca

      The incidence and prevalence of ILDs, especially IPF, is on the rise. Despite improved clinical management, IPF still remains a challenging disease, especially with regard to its cardiovascular comorbidity. This chapter provides readers with recent updates regarding cardiovascular involvement in IPF. There is a significant association between CAD and IPF, and this may be due to a combination of common shared risk factors, hypoxia and oxidative stress. The mechanism behind the development of PH in IPF is incompletely understood; comparison with other ILDs may offer clarification. Importantly, arrhythmias are present in a significant portion of the daily activities of IPF patients, as well as post-lung transplant IPF patients. Antifibrotics such as pirfenidone and nintedanib are generally safe from the cardiac point of view. The impact of cardiovascular comorbidities on the survival of IPF patients is discussed before we explore the challenges faced in managing this vulnerable patient population.

      Cite as: Chong SG, Yanagihara T, Kolb MRJ. The cardiovascular system in idiopathic pulmonary fibrosis. In: Martínez-García MÁ, Pépin J-L, Cazzola M, eds. Cardiovascular Complications of Respiratory Disorders (ERS Monograph). Sheffield, European Respiratory Society, 2020; pp. 198–211 [https://doi.org/10.1183/2312508X.10028319].

    12. Page 212
      Abstract
      Rosario Menéndez, Servicio de Neumología, Hospital Universitario y Politécnico La Fe, Av. Fernando Abril Martorell 106, 46026 Valencia, Spain. E-mail: rosmenend@gmail.com

      Pulmonary infections, such as community-acquired pneumonia (CAP), and CVDs, are highly prevalent worldwide health problems. Pulmonary infections predispose patients to short- and long-term cardiovascular complications, even in those without prior chronic comorbid conditions. These events are more frequent during the first days of infection, but the risk is sustained for up to 10 years. Various pathophysiological mechanisms underlie this interplay, including inflammation, endothelial injury, platelet activation, neutrophil extracellular traps and direct organ damage. Identifying clinical risk factors and the use of biomarkers are useful to address this cardiovascular risk. Prevention and therapeutic strategies for cardiovascular risk in CAP are limited. Some of the approaches to be evaluated are vaccinations and treatments such as statins and antiplatelet drugs. Several studies with CVEs in CAP as the primary end-point are ongoing. CAP should be considered an independent cardiovascular risk factor.

      Cite as: Méndez R, González-Jiménez P, Feced L, et al. Cardiovascular consequences of community-acquired pneumonia and other pulmonary infections. In: Martínez-García MÁ, Pépin J-L, Cazzola M, eds. Cardiovascular Complications of Respiratory Disorders (ERS Monograph). Sheffield, European Respiratory Society, 2020; pp. 212–228 [https://doi.org/10.1183/2312508X.10028419].

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      Abstract
      Maria Gabriella Matera, Experimental Medicine, University of Campania Luigi Vanvitelli, via Costsntinopoli 16, Naples, 80135, Italy. E-mail: mariagabriella.matera@unicampania.it

      COPD and chronic CVDs often coexist and pharmacological modulation of β2-adrenoceptor (β2-AR) function remains a critical issue in the management of these diseases. Activation of the β2-AR, a requisite mechanism of action, promotes bronchodilation that improves COPD-related health-outcome measures, such as quality of life, dyspnoea, exercise capacity and, mainly, the number and severity of exacerbations. Nevertheless, recent findings suggest that β2-AR stimulation induces physiological and pathological signals in the lung. β-AR found in the heart play an important role in the control of the cardiovascular system, but the changes in cardiac autonomic function in CVDs may contribute to an increased cardiac risk associated with inhaled β2-AR agonist treatment. New insights on the mechanism of action of β2-AR agonists have engendered rethinking of the efficacy and safety of β2-AR activation in the management of CVD and COPD. The future development of novel synthetic β2-AR agonists could avoid adverse reactions by modulating tertiary and quaternary conformations that alter β2-AR phosphorylation and desensitisation.

      Cite as: Matera MG, Panettieri RA Jr. β2-adrenoceptor modulation in COPD and its potential impact on cardiovascular comorbidities. In: Martínez-García MÁ, Pépin J-L, Cazzola M, eds. Cardiovascular Complications of Respiratory Disorders (ERS Monograph). Sheffield, European Respiratory Society, 2020; pp. 229–237 [https://doi.org/10.1183/2312508X.10028519].

    2. Page 238
      Abstract
      Daiana Stolz, Clinic of Respiratory Medicine and Pulmonary Cell Research, University Hospital Basel and University Basel, Petersgraben 4, Basel, Switzerland. E-mail: Daiana.Stolz@usb.ch

      Long-acting muscarinic receptor (mAChR) antagonists (LAMAs) are likely to be the main drugs used to treat patients with COPD. They are generally considered “safe” but concerns have been raised about the possible association of their use with cardiovascular morbidity and mortality. Evidence suggests that suppressed parasympathetic nervous system function can lead to tachycardia and arrhythmia. In effect, when cardiac vagal tone is blocked, β2-adrenergic-mediated increases in heart rate are greater. A review of the available literature on the cardiovascular adverse events of LAMAs indicates that they must be considered safe even in cardiac patients when compared with other active therapies or placebo. However, much of the available information has been generated through pivotal clinical trials and the adverse event rates of a drug observed in a clinical trial may not reflect the rates observed in daily practice. There is a need for studies in a real-world setting to identify high-risk patients that may benefit from ECG surveillance because there may be a different cardiovascular response to mAChR blockages in individual patients.

      Cite as: Stolz D, Cazzola M. Characterising the cardiovascular safety profile of inhaled muscarinic receptor antagonists. In: Martínez-García MÁ, Pépin J-L, Cazzola M, eds. Cardiovascular Complications of Respiratory Disorders (ERS Monograph). Sheffield, European Respiratory Society, 2020; pp. 238–250 [https://doi.org/10.1183/2312508X.10028619].

    3. Page 251
      Abstract
      Nicola Hanania, Baylor College of Medicine, 1504 Taub Loop, Houston, TX 77 030, USA. E-mail: Hanania@bcm.edu

      CVDs often complicate the course of asthma and COPD. ICSs constitute a cornerstone of the management of asthma and have an important role in the management of high-risk patients with COPD when used in combination with long-acting bronchodilators. Knowledge of the risk/benefit ratio of the effects of ICSs on the cardiovascular system has emerged from a number of observational studies and clinical trials. Current evidence does not show an increased risk of CVEs with ICS treatment for either asthma or COPD. While observational studies suggest beneficial effects of these medications on the cardiovascular system, evidence from large clinical trials including those performed in patients at high cardiovascular risk is not as conclusive. Emerging data demonstrate the beneficial effects of ICSs in the context of triple therapy on cardiovascular risk and mortality, but, while these are encouraging, they need further exploration.

      Cite as: Narendra D, Hanania NA. Impact of inhaled corticosteroids in patients with cardiovascular disease. In: Martínez-García MÁ, Pépin J-L, Cazzola M, eds. Cardiovascular Complications of Respiratory Disorders (ERS Monograph). Sheffield, European Respiratory Society, 2020; pp. 251–263 [https://doi.org/10.1183/2312508X.10028719].

    4. Page 264
      Abstract
      Stefano Aliberti, Dept of Pathophysiology and Transplantation, University of Milan, Respiratory Unit and Cystic Fibrosis Adult Center, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Via Francesco Sforza 35, 20122, Milan, Italy. E-mail: stefano.aliberti@unimi.it

      Two of the most prescribed classes of antibiotic in respiratory medicine, macrolides and fluoroquinolones, are associated with cardiovascular side-effects. The antibiotic-related cardiovascular morbidity and mortality are linked to arrhythmia, ischaemic events, and aortic dissection or bleeding. However, the cardiovascular risk of antibiotics is higher in the subgroup of patients with risk factors for arrhythmia, ischaemic CVEs and aortic dissection. Therefore, identifying this subgroup of patients at high risk is of paramount importance. The aim of this chapter is to review antibiotic-induced adverse CVEs, particularly in high-risk patients. The mechanisms inducing these events and the gaps in real-life data are also explored. Finally, we propose an algorithm to identify patients at risk for CVEs and to monitor those undergoing macrolide and fluoroquinolone treatment.

      Cite as: Amati F, Di Pasquale M, Restrepo MI, et al. Cardiovascular side-effects of common antibiotics. In: Martínez-García MÁ, Pépin J-L, Cazzola M, eds. Cardiovascular Complications of Respiratory Disorders (ERS Monograph). Sheffield, European Respiratory Society, 2020; pp. 264–278 [https://doi.org/10.1183/2312508X.10028819].

    5. Page 279
      Abstract
      Salvatore Cuzzocrea, Dept of Chemical, Biological, Pharmaceutical and Environmental Sciences, University of Messina, Viale Ferdinando Stagno D'Alcontres, n 31, Messina 98166, Italy. E-mail: salvator@unime.it

      Xanthines have been employed in the treatment of respiratory disorders since 1937, for the treatment of respiratory diseases such as COPD and asthma. However, xanthines, although effective, have a relatively narrow therapeutic window that has limited their wider use. Xanthines can also have important effects on the cardiovascular system. However, more recently, there has been the introduction of a number of selective phosphodiesterase 4 (PDE4) inhibitors for the treatment of inflammatory conditions, in particular roflumilast for the treatment of severe COPD. In addition, a number of PDE3 inhibitors have been approved for the treatment of a range of conditions, as PDE3 is widely expressed in cardiovascular tissues. The dual PDE3/4 inhibitor ensifentrine is also under development for the treatment of COPD. Here, we discuss the cardiovascular actions of xanthines and selective PDE inhibitors.

      Cite as: Fusco R, Di Paola R, Cuzzocrea S, et al. The cardiovascular effects of xanthines and selective PDE inhibitors: a risk–benefit analysis. In: Martínez-García MÁ, Pépin J-L, Cazzola M, eds. Cardiovascular Complications of Respiratory Disorders (ERS Monograph). Sheffield, European Respiratory Society, 2020; pp. 279–286 [https://doi.org/10.1183/2312508X.10028919].

  7. Page 287
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      Abstract
      Don D. Sin, Room 385, Centre for Heart Lung Innovation, St Paul's Hospital, Vancouver, BC, Canada, V6Z 1Y6. E-mail: don.sin@hli.ubc.ca

      Cardiovascular comorbidities are common in patients with COPD, fibrotic lung diseases and other chronic lung conditions, and contribute to patients’ morbidity and mortality. Wearable and home-monitoring devices are rapidly advancing and are ready for prime-time clinical use in the diagnosis and management of cardiovascular conditions such as AF, HF and acute coronary syndromes. Imaging modalities are also rapidly evolving. Soon, advanced three- and four-dimensional imaging techniques involving echocardiography, cardiac magnetic resonance imaging and computed tomography will be available for patient care. Multi-omics technology will lead to novel blood biomarkers and therapeutic targets. These technologies will be supported by artificial intelligence methods that will enable the development of diagnostic and predictive algorithms derived from “big data” collected through these modalities. Future therapeutics will most likely be based on a “treatable traits” approach rather than on canonical diagnoses, and will be precise and effective.

      Cite as: Sin DD. Future challenges. In: Martínez-García MÁ, Pépin J-L, Cazzola M, eds. Cardiovascular Complications of Respiratory Disorders (ERS Monograph). Sheffield, European Respiratory Society, 2020; pp. 287–299 [https://doi.org/10.1183/2312508X.10029019].

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