Comorbidities in HF COPD Chronic Obstructive Pulmonary Disease Gerasimos Filippatos Athens, Greece

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Comorbidities in HF COPD Chronic Obstructive Pulmonary Disease Gerasimos Filippatos Athens, Greece

Epidemiology of heart failure in chronic obstructive pulmonary disease (COPD) patients and vice versa. Diagnostic, prognostic and treatment challenges of the co-existence of both syndromes.

Definition of COPD COPD is characterized by airflow limitation that is not fully reversible. The airflow limitation is usually progressive and associated with an abnormal inflammatory response of the lung. It has significant extrapulmonary effects that may contribute to the severity in individual patients.

Classification of COPD Severity by Spirometry Stage I: Mild FEV 1 /FVC < 0.70 FEV 1 > 80% predicted Stage II: Moderate FEV 1 /FVC < 0.70 50% < FEV 1 < 80% predicted Stage III: Severe FEV 1 /FVC < 0.70 30% < FEV 1 < 50% predicted Stage IV: Very Severe FEV 1 /FVC < 0.70 FEV 1 < 30% predicted or FEV 1 < 50% predicted plus chronic respiratory failure

Percent Change in Age-Adjusted Death Rates, U.S., 1965-1998 Proportion of 1965 Rate 3.0 3.0 2.5 2.5 2.0 2.0 Coronary Heart Disease Stroke Other CVD COPD All Other Causes 1.5 1.5 1.0 1.0 0.5 0.5 0.00 59% 64% 35% +163% 7% 1965-1998 1965-1998 1965-1998 1965-1998 1965-1998 Source: NHLBI/NIH/DHHS

Number Deaths x 1000 COPD Mortality by Gender 1980-2000 70 60 50 40 30 Men Women 20 10 0 1980 1985 1990 1995 2000 Source: US Centers for Disease Control and Prevention, 2002

COPD and Heart Failure Heart Failure 5.000.000 COPD 14.000.000 Filippatos G 2010

Prevalence of COPD in patients with heart failure The reported prevalence of COPD ranges from 11 to 52% in North American patients with HF, and from 9 to 41% in European cohorts Hawkins NM et al. EJHF 2009

Prevalence of COPD in heart failure trials Hawkins NM et al EJHF 2009 Reference n Prevalence COPD (%) LVEF (%) Trial Population Parker 6797 7 35 SOLVD Community Sharma 3044 9 40 ELITE II Community Staszewsky 5010 13 <40 Val-HeFT Community Massie 1587 8 35 WATCH Community Grancelli 1518 9 Any DIAL Community NETWORK Investigators 1532 7 NETWORK Mixed Gheorghiade 319 10 40 ACTIV-CHF Cuffe 949 23 <40 OPTIME-CHF HF hospitalization HF hospitalization

Prevalence of COPD in HF Clinic Data Presented by Stainacher, AT

Prevalence of heart failure in patients with COPD

0,6 Normal LV LVD 0,4 0,2 0 LVD Normal LV Distance walked on the flat without stopping LVD was found in 32% of patients with COPD presenting with symptomatic deterioration

Problems diagnosing heart failure in patients with COPD Clinical features Radiology Imaging (Echocardiography, CMR, Νuclear) Νatriuretic Peptides European Journal of Heart Failure (2009) 11, 130 139 J Am Coll Cardiol 2007;49:171 80

Problems diagnosing heart failure in patients with COPD Clinical features. Pulmonary disease may produce or obscure every symptom and sign defined by Framingham Criteria Radiology. Imaging (Echo, CMR, Νuclear) Νatriuretic Peptides European Journal of Heart Failure (2009) 11, 130 139 J Am Coll Cardiol 2007;49:171 80

Exam Variables by Diagnosis J Am Coll Cardiol 2010

Problems diagnosing heart failure in patients with COPD Clinical features Radiology Chest hyperinflation spuriously reduces the cardiothoracic ratio. Pulmonary vascular remodelling and radiolucent lung fields mask the typical alveolar shadowing of pulmonary oedema Asymmetric, regional, and reticular patterns of pulmonary oedema are common Emphysematous vascular bed loss causes upper lobe venous diversion, mimicking HF Imaging (Echo, CMR, Νuclear) Νatriuretic Peptides J Am Coll Cardiol 2007;49:171 80 European Journal of Heart Failure (2009) 11, 130 139

Relationship between LVEF and heart size on chest radiograph in patients with COPD. Chest 1995

A chest radiograph of a 50-year-old woman with chronic cough. Gehlbach B K, Geppert E Chest 2004;125:669-682

Active transport is important for edema clearance Filippatos et al. In Vitro 1997 Voelker et al

Problems diagnosing heart failure in patients with COPD Clinical features Radiology Imaging (Echo, CMR, Νuclear) Echo images unsatisfactory in 10 to 50 % Νatriuretic Peptides

Problems diagnosing heart failure in patients with COPD Clinical features Radiology Imaging (Echo, CMR, Νuclear) Νatriuretic Peptides Natriuretic peptides are elevated in both primary pulmonary hypertension and right HF secondary to chronic respiratory disease

ESC Guidelines for the Diagnosis and Treatment of Acute and Chronic Heart Failure

Problems diagnosing COPD in patients with heart failure Airflow obstruction is common in ADHF and restriction in CHF Disparities in confirmatory testing. In a recent study among patients with both HF and COPD, 82% had echo vs 36% LFT. Respir Care 2006;51:1120 1124

Cardiopulmonary abormalities responsible for restrictive and obstructive defects JACC 2004

The percentage of fibrosis (stained blue) in the right venticle was significantly greater in CPD patients with right ventricular hypertrophy

Boudestein L C et al. Eur J Heart Fail 2009;11:1182 Kaplan Meier survival curves of 404 patients with a general practitioner's diagnosis of chronic obstructive pulmonary disease.

J Card Fail 2010

Challenges in management

Utilization of Evidence-based Therapies in Heart Failure History of HF and LVEF Documented and 0.40* *Excludes patients with documented contraindications. 2300/7883 Patients hospitalized with HF; prior known dx of systolic dysfunction HF; outpatient medical regimen. ADHERE Registry Report Q1 2002 (4/01-3/02) of 180 US Hospitals Presented by GC Fonarow at the Heart Failure Society of America Satellite Symposium, September 23, 2002.

Therapeutic implications Pulmonary medication influencing cardiac function Oral and inhaled short-acting β2- adrenoreceptor agonists do seem to increase the risk of mortality and number of heart failure exacerbations in LVSD F. Rutten. Heart failure in COPD, Thesis 2005

Hawkins N M et al. Eur J Heart Fail 2010;12:557-565 Adjusted survival rate according to bronchodilator and beta-blocker use.

Therapeutic implications Cardiovascular medication influencing pulmonary function I Angiotensin-II is a potent pulmonary airway constrictor. Therefore, ACE-inhibitors and ARBs confer potential benefit in COPD. ACE-inhibitors may have additional beneficial effects because they can also decrease pulmonary inflammation Aldosterone antagonists can also have possibly positive effects on gas exchange, because aldosterone can damage the alveolar-capillary membrane F. Rutten. Heart failure in COPD, Thesis 2005

Changes in exercise tolerance measured in placebo and losartan groups by the mean number of shuttles completed in the shuttle walk test.

Therapeutic implications Cardiovascular medication influencing pulmonary function II High dosages of diuretics can cause acidbase disturbances (metabolic alkalosis) in COPD patients and this may blunt the respiratory drive Digitalis may reduce lung function because it can cause pulmonary vasoconstriction F. Rutten. Heart failure in COPD, Thesis 2005

Therapeutic implications Cardiovascular medication influencing pulmonary function III Until recently, experts advised not to use β- blockers in COPD, specially in the presence of bronchospasm. However, recent analyses have shown that cardioselective β-blockers do not produce clinically significant adverse respiratory effects in patients with mild to moderate reactive airway disease. The results were similar for patients with concomitant chronic airways obstruction

Rutten et al. Arch Intern Med 2010; 170:880-

Differences Between B-Blockers in Patients With CHF Failure and COPD: A Randomized Crossover Trial Switching between β1-selective beta-blockers and the nonselective beta-blocker carvedilol is well tolerated but results in demonstrable changes in airway function, most marked in patients with COPD. Switching from β1-selective beta-blockers to carvedilol causes short-term reduction of central augmented pressure and NT-proBNP. JACC 2010

Public Health would benefit more from application of what is already known than from scientific breakthroughs. Lord Rosenheim

There are, in truth, no specialties in medicine, since to know fully many of the most important diseases a man must be familiar with their manifestations in many organs. William Osler, The Army Surgeon, Medical News, Philadelphia, 1894

WORLD COPD DAY November 14, 2007 Raising COPD Awareness Worldwide

IS YOUR HEART FAILING? Do you have unexplained shortness of breath, swollenankles? Go to www.heartfailurematters.org If thisdoes not answeryour questions, please contact yourdoctor