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Edema nelle fasi avanzate della BPCO: cuore polmonare cronico o scompenso cardiaco?

Stefano CarloneDirettore UOC Malattie Apparato Respiratorio

Roma

Caso clinico A

• Paziente di 65 anni, con diagnosi certa di BPCO

• Dispnea di 3°-4° grado

• Ortopnea – Turgore delle giugulari – Epatomegalia

• Edema agli arti inferiori

• Insufficienza respiratoria ipossiemica

pO2 48 pCO2 34 mmHg pH 7.47

• PFR = Deficit ventilatorio di tipo misto

• ECG = FA ad alta frequenza – segni di ischemia antero-laterale

• BNP = 1350 pg/ml

Diagnosi: Scompenso cardiaco congestizio in cardiopatia dilatativa ischemica in paziente affetto da BPCO

Caso clinico B

• Paziente di 71 anni con diagnosi certa di BPCO

• Dispnea di 4° grado

• Turgore delle giugulari – Epatomegalia

• Edema agli arti inferiori

• Insufficienza respiratoria ipossiemica e ipercapnica

pO2 44 pCO2 78 mmHg pH 7.31

• PFR = Deficit ventilatorio di tipo ostruttivo di grado severo (VEMS 40% del valore teorico, Indice di Tiffenau 60%)

• ECG = Tachicardia sinusale, P polmonare

• BNP = 285 pg/ml

Diagnosi: “Cuore polmonare” in paziente affetto da BPCO

COPD: a multi-component airway disease

Systemic effects

Muco-ciliarydysfunction

Airway remodelling(chronic bronchitis)

Loss of elastic recoil(emphysema)

Inflammation

Reducedexercise toleranceDyspnea

Hyperinflation

Eventi cardiovascolari prevalenti nella BPCO

Coronaropatie 15.2%Aritmie 25-30%

FA e fibrillo-flutterExtrasistolia sopra e ventricolareTachicardia sinusaleTachiaritmieFibrillazione ventricolare

Ipertensione arteriosa 39.6%Scompenso cardiaco 20%Ipertensione polmonare 90%

al III stadioEdema (cuore polmonare) 48%

al III stadio

INDACO StudyComorbidity prevalence in 547 COPD pts

51.3

18,5

8.4

18.722.1

12.2

2.8

7.3

15.4

Hypertension

Metabolic syndrome

Cancers(All)

Diabetes

Heart failure

Cardiacischemia

Lung cancer

AnxietyDepression

None

Cardiovascularcomorbidities

Ageing of the population increases the prevalence of chronic diseases, including cardiovascular diseases, cancer, chronic respiratory diseases and metabolic syndrome in developed countries with a substantial economic and social burden. Almost half of all elderly people (> 65 yrs) have at least three chronic medical conditions and one fifth have five or more.

Comorbidities affect health outcomes in COPD

Patients with COPD mainly die of nonrespiratory diseases such as cardiovascular diseases (25%), cancer (mainly lung cancer, 20-33%) and other causes (30%).Respiratory diseases (mainly respiratory failure due to COPD excerbations) account for 4-35% of deaths.

COPD e CV risk

• In mild to moderate COPD three times as many hospital admissions in this patient group are for cardiovascular than for pulmonary causes.

• In the Lung Health Study, 25% of deaths were due to CV disease

• In the TORCH study the proportion was 27%

• In a systematic review of the literature (>80.000 pts) reduced FEV1 nearly doubles the risk for CV mortality independent of confounders as age, smoking, etc

• For every 10% decrease of FEV1, CV mortality increased by 28%, and nonfatal coronary event increased by almost 20%, after adjustments for confounders as age, sex, smoking status, cholesterol and hypertension

Sin Proc Am Thor Soc 2005

Anthonisen AJCRCM 2002

COPD is frequently associated with chronic heart failure (CHF) (> 20%)and metabolic syndrome (hypertension, diabetes, dyslipidemia, obesity, insulin resistance, proinflammatory state ( CRP) and a prothrombotic state

Major risk factors for chronic disease expecially COPD and CHF:

Cigarette smoking Obesity

Cigarette smoking is associated with:•Lung and systemic inflammation•Systemic oxidative stress•Marked changes of vasomotor and endothelial function•Enhanced circulating concentrations of several procoagulant factors

Obesity is associated with:•Insulin resistance•Oxidative stress•Increased concentrations of various (adipo) cytokines and inflammatory markers (CRP)•Endothelial dysfunction

Eur Respir J 2009

Caso B: Terapia

• Broncodilatazione: beta agonisti short acting e long acting, anticolinergici (riduzione della CO2)

• Ossigeno terapia

• Diuretici?

• Digitale?

• Riabilitazione

Adverse cardiovascular events by b2 agonist use in COPD patients

• Myocardial infarction• Congestive hearth failure• Cardiac arrest and acute cardiac death

Increase of heart rate and decrease of potassium concentration, associated with other effect of b-adrenergic stimulation may precipitate ischemia, congestive heart failure, arrythmias and sudden death

S.R. Salpeter, Chest 2004, 125: 2309-2321

Caso A: Terapia

• Diuretici

• Digitale?

• ACE inibitori

• Ossigeno terapia

• Beta bloccanti cardioselettivi

β-Blockers

• The ßB has traditionally beencontraindicated in COPDmainly because of anecdotalevidence and case reportsciting acute bronchospasmafter their administration

BMJ 2011;342:d2549

Assessing the effects (mortality, hospital admissions, and COPD exacerbations) of BB therapy on 5977COPD patients on top of standard therapy with a mean follow-up of 4.35 years.

Kaplan-Meier survival curves among patients with COPD by use of β blockers

BMJ 2011;342:d2549

22% overall reduction in all cause mortality

for COPD patients taking BB in addition to standard therapy for

COPD.

Why BB may improve outcomes in HF and COPD patients?

• Up-regulation of β2 adrenoceptors by chronic β blockade may improve the effectiveness of β2 agonists (cardioselective β blockers such as bisoprolol, have been shown to exert significant β2 adrenoceptor antagonism, resulting in β2 adrenoceptor up-regulation).

• Cardioprotective effects of β blockade (decrease in oxygen consuption, increase diastolic filling, antioxidant properties)