Pulmonary Vascular Resistance (PVR)

Transcript

1 Ά π π π υ υ υπ υ

2 Eur Respir J 2015

3 Pulmonary Vascular Resistance (PVR) Pulmonary circulation is a low pressure, low resistance circuit During exercise a healthy subject can increase cardiac output 4-5 times while MPAP increases 2-3 times normal (almost doubles the resting lung capillary blood volume) Capillary recruitment Vascular distention

4 PVR and the heart

5 Pulmonary Vascular Resistance (PVR) is a major factor causing exercise limitation PVR increases in diseases that cause obliteration or destruction of the pulmonary vascular bed Symptoms: Dyspnea ( increased VD/VT, wasted ventilation) Fatigue, fainting (ventricular interdependence and systemic cardiovascular effects) Hypoxemia (short transit time in healthy regions, intracardiac (PFO) or intrapulmonary shunt, low SVO2)

6 Determinants of PVR PVR = pulmonary vascular resistance LAP = left atrial pressure Q = cardiac output R0 = total pulmonary vascular resistance = pulmonary vascular distensibility

7 Eur Respir J 2009

8 Mean pulmonary arterial pressure (P pa) during rest and slight supine exercise in healthy subjects aged yrs ( ; n = 144), yrs ( ; n = 169) and 50 yrs ( ; n = 91 The data of this review do not support the current threshold of Ppa during exercise. According to the reviewed data, nearly half of subjects aged>50 yrs are expected to develop a Ppa>30 mmhg during slight exercise and about 20% of subjects aged<50 yrs are expected to exceed this value during maximal exercise G. Kovacs et al. Eur Respir J 2009

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10 Modeled mean pulmonary arterial pressure-cardiac output (mpap-q) relationships during dynamic exercise with progressively increased distensibility coefficients (). Distensibility decreases with age Gregory D. Lewis et al. Circulation. 2013

11 Rajeev Malhotra et al. Circ Heart Fail. 2016

12 Rajeev Malhotra et al. Circ Heart Fail. 2016

13 Rajeev Malhotra et al. Circ Heart Fail. 2016

14 The mpap/co relationship reflects the RV afterload in relation to pulmonary blood flow, integrating the RV capacity and the severity of pulmonary vasculopathy Gregory D. Lewis et al. Circulation. 2013

15 Herve et al, Eur Respir J 2015

16 Herve et al, Eur Respir J 2015

17 Eur Respir J 2017

18 Pulmonary Medicine 2012

19 Ventricular interdependence in COPD- hemodynamic consequences Shujaat et al, Pulmonary Medicine 2012

20 Chest 1992

21 Chest 1992

22 Heart 2009

23 Portillo et al. International Journal of COPD 2015

24 Portillo et al. International Journal of COPD 2015

25 Eur Respr J 2013

26 CHEST 1996

27 Eur Respir Rev 2017

28 π π υπ υ π

29 27 ILD pts, 15 with PVD Degani-Costa et al ERJ 2015

30 Figure 4. Pathophysiology of exercise limitation of PPH patients. Circulation. 2001

31 φυ υ π π π : υπ υγ υ ί PAH υ ε (wasted ventilation) υ υ υ π π π π

32 CPET safety in high risk cardiovascular population 5060 CPETs in 4250 pts 8 adverse effects 0 deaths Skalski et al, Circulation 2012

33 CPET Arena and Sietsema. Circulation, 2011

34 Ventilatory efficiency = Ventilatory equivalent for CO2 (VE/VCO2) Normal value: VE/ VCO2@AT: 34 Increased = inefficient ventilation, perceived as dyspnea disproportionate for the task Increased when: -increased dead space (pulmonary airways, pulmonary vascular disease, heart failure) -hypoxemia -early lactic acidosis -sympathetic stimulation

35 Eur Respir J 2004

36 52 PPH patients vs 9 controls CHEST 2005

37 Pulmonary vasculopathy detection via CPET Yasunobou et al, CHEST 2005

38 π π ESC/ERS, Eur Heart J 2015

39 Cardiopulmonary exercise testing for detecting pulmonary arterial hypertension in systemic sclerosis Dumitrescu et al, Heart 2017

40 Circulation, 2008

41 29 patients with systemic sclerosis without significant lung fibrosis and without known pulmonary arterial hypertension

42 Oliveira et al. Pulmonary Circulation 2017

43 Oliveira et al. Pulmonary Circulation 2017

44 Oliveira et al. Pulmonary Circulation 2017

45 Oliveira et al. Pulmonary Circulation 2017

46 Transplant- free survival of 72 systemic sclerosis patients according to hemodynamic classification Eur Respir J 2016

47 After 24 weeks, 6-minute walking distance significantly improved, by a mean SD of meters. ARTHRITIS & RHEUMATISM 2012

48 Grünig et al. Eur Respir J 2012

49 Individual changes in the 6-min walk distance (6MWD) in pulmonary hypertension subgroups with different aetiologies from baseline to week 3 and 15. Grünig et al. Eur Respir J 2012

50 Arthritis Research & Therapy 2012

51 European Heart Journal 2016

52 European Heart Journal 2016

53 Effects of aerobic training on ventilation during exercise

54 υ π Η Η π υ π υ υ υ π π υ π π φ υπ υ π υ π π, φ, υ, π π φ, φ υ υ υπ π Ηπ υ π υ π π υ π π υ π υ π υ υ φ CPET: peak VO2, AT, π, WR υ υ υ VE/VCO2 PETCO2: Η π π υ υπ π π π π υ υ φ υ π π π π υ π

55 Χ Ω!!!

56 25 COPD patients with deteriorating symptoms (10 with PH and 15 without PH after RHC) (peak VO2, VO2/HR, VO2/ WR similar)

57 Respirology 2011

58 Pulmonary Medicine 2012

59 30 SSc patients not clinically suspected of having significant pulmonary vascular disease PLoS one 2010

60 Respiration 2015

61 π CPET ε πεί

62 McLaughlin et al, JACC 2013

63 20 patients with PPH under inhaled iloprost or oral beraprost alone (baseline) and 3 months after bosentan add-on. Eur Respir J 2003

64 Effect of sildenafil on ventilatory efficiency and exercise tolerance in Pulmonary Hypertension Oudiz et al, Eur J Heart Fail. 2007

65 Iwase et al, Heart 2001

66 Η υ Χ υ Η Η υ1, φ 1, Η: υ2, π π 1, υ Η Η υ 16 π 1, 1, Γ Η Η Ω φ υ1, υ1, Η φ π υ «Γ. π υ π», 2 Δ φ,γ 14,3 0,001 5,8 10,9 0,065 Δ VE/VCO2 at AT -5,1 5,7 0,004 Δ VE/VCO2 peak -3,3 7,7 0,124 4,1 9 0,096-0,9 9,7 0,735 Δ AT Δ PETCO2 at AT Δ PETCO2 peak Συμπέρσμ Σ π φ π υ υπ. π π π. Η CPET π υ VE/ 15,9 p π Δ peak VO2 Θ π, π π π π π φ

67 24 month survival of PAH- CTEPH patients predicted by ventilatory efficiency Schwaiblmair et al, BMC Pulmonary Medicine 2012

68 Chest 2016

69 Conclusions the earliest and often only symptoms of patients with PH manifest during physical activity resting hemodynamics do not correlate well with functional capacity, response to treatment and survival exercise performance has been established as the primary end-point in studies evaluating treatment exercise induced PH may lead to earlier diagnosis and treatment serial exercise testing is an objective and reliable way to evaluate treatment effectiveness over time