Pulmonary Hypertension: A Cardiology Perspective

Transcription

1 Pulmonary Hypertension: A Cardiology Perspective Tarek Kashour, MBChB, FRCPC, FACC Head, Cath Lab King Khalid University Hospital Professor, Cardiac Sciences King Saud Unversity, Riyadh

2 The most common cause of PH? PH-LHD accounts for about 65-80% of all cases of PH 1 Heart failure Prevalence in USA 4.9 millions and annual incidence of 378/ 100,000 2,3 1- Rosenkranz et al. Eur Heart J Hunt et al. JACC ger et al. JAMA 2004

3 Definition PH-LHD is increase in mpap 25 mm Hg at rest with increased left sided filling pressures defined as elevated PAWP > 15 mm Hg Constitute group 2 of the WHO PH classification

4 Hemodynamic Classification LHD-PH mpap 25 mm Hg at rest PAWP > 15 mm Hg DPG Normal Isolated Postcapilary PH: <7 mm Hg and /or PVR 3WU elevated Combined pre + Postcapillary 7 mm Hg and/or PVR> 3 WU Reversible Fixed

5 Pathophysiology Rosenkranz et al, Eur H J 2015

6 Degree of PH and histopathology

7 Histopathology and degree of PH Gerges et al, Chest 2013

8 Epidemiology

9 Prevalence Prevalence is variable depending on studied population, HF type, method of assessment and cut off values used In HFpEF: 36% to > 80% In HFrEF: from 40% to 75%

10 Prevalence of PH In HFpEF Olmsted County Lam et al, JACC 2009

11 Prevalence of PH in HFpEF Cath based study 455 patients 239 (52.5%) had PH Predictors of PH: obesity, old age COPD, SOB on exertion and atrial arrhythmias Leung et al Am J Cardiol 2010

12 935 patients Prevalence of PH in HFpEF TOPCAT trial 450 had TR jet assessment PH was defined as TR jet of >2.9 m/sec Prevalence= 36% Shah et al Cir H F 2014

13 2609 patients Prevalence of PH in ADHF HEARTS trial Missing data from 495 patients PH defined as SPAP> 40 mm Hg Prevalence: 34%

14 Effect of PH on survival in HF patients

15 PH and Survival in HF Olmsted County cohort 1049 patients with HF and available PAP measurement Bursi et al, JACC 2012

16 PH and Survival Danish population 388 patients with either HFrEF or HFpEF F/U of up to 5.5 years 9% increase in mortality per 5 mm Hg increase in RVSP Kjaergaardet al, Am J cardiol 2007

17 RVD in HF

18 RV function and PH in HFpEF Melenovsky et al, Eur H J 2014

19 RV function and PH in HFrEF Ghio et al, JACC 2001

20 Prevalence of RVD in HF Variable depending on the method Highest tricuspid annular velocity is used Range from 13% to up to 65%

21 RV dysfunction and mortality in chronic HF

22 RV dysfunction and HF mortality 1547 patients 47% LVEF 45%, 53% LVEF > 45% F/U 63 months (41-75) Mortality= 36% TAPSE was independent predictor of mortality in both groups TAPSE of 15.9 mm had the best prognostic threshold Present in 47% of HFrEF and 20% of HFpEF Damy et al, J card failure 2012

23 RV dysfunction and HFpEF mortality Olmsted County cohort Mohammed et al, Circulation 2014

24 RV dysfunction and HFpEF mortality Melenovsky et al, Eur H J 2014

25 RV dysfunction and HF mortality 140 with HFrEF Ghio et al, Am J cardiol 2000

26 RVD/ PH and HF mortality 377 pts. 1= normal PAP/ RVEF 2= normal PAP/ low RVEF 3= high PAP/ preserved RVEF 4= high PAP/ low RVEF Ghio et al, JACC 2001

27 RV dysfunction and HF mortality 658 with HFrEF EF< 45% TAPSE 14 mm and SPAP 40 mm Hg Ghio et al, Eur J H F 2013

28 RV dysfunction and mortality in ADHF

29 RV dysfunction and ADHF mortality ECHOS trial 817patients admitted with HF (HFrEF) RVD assessed by TAPSE Median F/U= 4.1 years Decreased TAPSE and COPD were associated with decreased survival Kjaergaard et al, Eur J H F 2007

30 RV dysfunction and ADHF mortality ECHOS trial Kjaergaard et al, Eur J H F 2007

31 RV dysfunction and HF mortality HEARTS registry 2 nd World Congress on Acute Heart Failure 2015

32 RV dysfunction and HF mortality HEARTS registry 2 nd World Congress on Acute Heart Failure 2015

33 RV dysfunction and HF mortality HEARTS registry 2 nd World Congress on Acute Heart Failure 2015

34 RV dysfunction and HF mortality 11 studies 4732 patients Metaanalysis RVD present in 2234 (47.2%) RVD was associated with overall mortality and admission for HF Iglesias-Garriz et al, Rev Cardiovasc Med 2012

35 Treatment of PH and/ or RVD in HF

36 Treatment of LHD Lowering left-sided filling pressures Diuretics Titrating up HF medications to target CRT, VADs Mitral valve repair Implantable hemodynamic monitoring

37 CHAMPION Trial Benza et al, J lung heart trasplant 2015

38 RVEF 20% vs < 20% Mortality 33% vs. 43% Adjusted HR= 0.99 ( , p=0.934) BEST Trial RVEF 20% vs < 20% Mortality 28% vs. 49% Adjusted HR= ( , p=0.016) Desai et al, Int J Cardiol 2013

39 Treatment of PH and/ or RVD in HF Can PH targeted therapy improve outcomes in HF patients with PH and/or RVD?

40 PH targeted therapy

41 Targeted therapy FIRST Trial: IV epoprostenol Study prematurely terminated because of increased mortality in the treatment arm Trials with endothelin receptor inhibitors in HFrEF were negative

42 Targeted therapy Sildenafil: Few small single center studies in patients with HFrEF or HFpEF and severe PH, showed improved hemodynamics and exercise capacity 1-3 Metaanalysis of 6 trials revealed that PDE5i improve hemodynamics, exercise capacity and symptoms, and reduce hospitalization 4 1- Lewis et al, Circulation Guazi et al, Circulation Dumetriscu et al, Int J cardiol Wu et al, Eur J H Fn 2014

43 Targeted therapy Sildenafil: Hoendermis et al, Eur Heart J patient with HFpEF and isolated postcapillary PH Randomized double-blind placebo-controlled trial 12 week duration Primary end point: change in PAP 2ndry end points: change in PCWP, CO and VO2 No improvement in primary or 2ndry end points

44 Targeted therapy Sildenafil: Relax Trial (Redfield et al JAMA 2013) Multicenter RCT. 216 patients with HFpEF 24 week study duration. Peak VO2 is the primary endpoint No improvement in peak VO2 with sidlenafil More complications in sildenafil Renal function worsened more in sildenafil Uric acid, NT-proBNP and endothelin increased more in sildenafil

45 Targeted therapy Riociguat: soluble guanylate cyclase stimulator LEPHT trial (Bonderman et al, Circulation 2013) 201 patients with HFrEF and PH Riociguat (05, 1 or 2 mg tid) for 16 weeks Primary end point: change in mpap was not met Riciguat dcreased PVR and SVR, increased CI It also decreased Minnesota living with heart failure score

46 Targeted therapy Riociguat: soluble guanylate cyclase stimulator DILATE-1 trial (Bonderman et al, Chest 2014) Small study (21 patients) with HFpEF and PH Primary end point: reduction in mpap Negative trial

47 Targeted therapy Ongoing trials: Tadalfil (PITCH-HF) terminated SOCRATES (Vericiguat) MELODY (Macitentan) Others

48 Conclusion HF is the most common cause of PH PH and RVD are prevalent in HFrEF and HFpEF and are associated with worse prognosis No effective targeted therapy are available Sildenafil may have potential beneficial effects in HF associated PH Larger RCT with definitive end points and longer follow up are needed to explore the potential of PH specific therapies

49 Thank you

50 Disease Severity and risk Assessment Eur Guidelines, Eur H J 2015

51 PH and Survival in HFpEF Olmsted County Lam et al, JACC 2009

52 Type of PH and Survival Gerges et al, Chest 2013

53 Pathophysiology Abel et al, J thorac Cardiovasc Surg 1967

54 Pathophysiology Guazi et al, Circulation 2012

55 PV relationship in diastolic dysfunction Oudiz Clin Chest med 2007

56 Dobutamine and RV dysfunction Melenovsky et al, Circ H F 2015

57 Back to the Cases:

58 55 year-old man Clinical Case 1 Known to have HTN and DLP Presented with SOB and CP Angio: moderate 2 vessel disease Thallium scan: No ischemia Echo: suggestive of severe PH, dilated RV, RVH with impaired fx and moderate LV dysfunction

59 Heart Cath: Fluid challenge Baseline Post-Fluids RA 4 mpap PCWP TPG LVEDP PA sat 61.4 Ao Sat 95.2 CO/CI 3.6 L/min 2.0 PVR 10 WU

60 Clinical Case 2 61 year-old woman, known to have: Obesity (133 Kg), DM, HTN, AF, HFpEF and PE and PH About 2 years ago, she was seen by a cardiologist Coronary angiogram: No significant CAD Started her on Sildenafil based on echo findings of PH Was referred to our center with class III SOB for further evaluation Meds: Lasix, Perindopril, Rivaroxapan, Atorvastatin, Sildenafil and Pantoprazole Pro-BNP 2730

61 Poor PAWP Tracing Better PAWP Tracing

62 Summary of RHC Results RA= mm Hg RV= 55 64/25 mm Hg. spap= 60-65, dpap= 23-29, mpap= mm Hg PAWP= mm Hg AO= 144/105/119 mm Hg LV= 147/26 mm Hg Restrictive physiology PA sats= 80.9%

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64 Conclusion RHC is essential to confirm diagnosis and should always be obtained before considering PAH targeted therapy RHC should be performed only by experts PH patients should be evaluated and treated in tertiary centers with expertise in PH

65 Thank You

66

67 Clinical parameters PAH vs. HFpEF Echo findings Hemodynamics

68 PAH vs. HFpEF Clinical parameters: Old age HTN Obesity DM AF CAD Congestion on CXR and response to diuretics

69 PAH vs. HFpEF Echo findings: LA enlargement LVH Abnormal LV filling pattern Increase in RV apical angle Notching of the RVOT PW Doppler envelop

70 Angle of the RV apex

71 RVOT Doppler wave shape

72 Echocardiographic score

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75 PAH vs. HFpEF Heart Cath In patients with suspicion of HFpEF and normal PAWP, abnormal LV filling can be uncovered with: Response to fluid challenge Response to exercise

76 Echo/Doppler

77 Echo/Doppler Estimate PAP Assess LV systolic and diastolic function R/O valvular heart disease R/O congenital HD Assess PH consequences on RV May help sort out HFpEF from PAH

78 Problems with current practice Improper assessment of PAP specially in terms of RA pressure assessment Arbitrary grading of PH severity based on PAP Visual assessment of RV size and function Ignoring other important parameters like RVOT acceleration time

79 Estimation of Systolic PAP Using modified Bernoulli equation: P=4V 2 RVSP = 4(TR V Max ) 2 + RA pressure

80 Estimation of Pulmonary Pressure RA pressure IVC size and collapsibility

81 Estimation of Pulmonary Pressure RA pressure RAP: IVC<2.1 cm, >50% inspiratory collapse = 3 mm Hg (0-5) IVC> 2.1 cm, <50% inspiratory collapse with a sniff or >20% with quiet breathing = 15 mm Hg (10-20) Those do not fit either options = 8 mm Hg (5-10)

82 Estimation of Systolic PAP Sources of Error Wrong placement of the measuring caliber Sampling after a PVC Overestimation of RA pressure Atrial fibrillation

83 MPAP utilizing RVOT-AT (acceleration time)- time to peak velocity Normal Pulmonary Hypertension Normal AT > 120 msec AT< 100 msec (PHT) MPAP=80 (AT/2)

84 Echocardiography: Assessment of consequences of PH Structural consequences Functional consequences

85 RA and RV Size PAH Normal

86 RV and RA dilatation RV/LV basal diameter ratio: = Mild RV dilatation = moderate dilatation 1.5 = severe dilatation

87 Flattening of Interventricular septum Very large RV Flattened septum D shaped small LV

88 Pressure Overload Diastole Systole

89 Volume Overload Diastole Systole

90 Assessment of RV function RV is a complex structure Irregular endocardial borders Side view RVOT from above Complex contraction pattern Difficult to measure RV volumes with conventional echo 30 mm RVOT Lack of standardization

91 RV Dysfunction Qualitative visual assessment Fractional area change Tricuspid annular plane systolic excursion (TAPSE) Tricuspid annular velocity

92 RV Function Tricuspid Annular Plane Systolic Excursion (TAPSE)

93 Tricuspid Annular Plane Systolic Excursion (TAPSE) TAPSE mm indicates mild RV dysfx 16-18mm = moderate RV dysfx TAPSE 15 mm indicates severe RV dysfunction and worse outcomes

94 RV Function TDI: Tricuspid Annular Velocity Reduced Normal Severe disease: < 10 cm/ sec Normal > 12 cm/ sec

95 What should be done next? Maximize HF and HTN therapy and continue sildenafil Perform right heart cath V/Q scan to R/O chronic PE CT angio of the pulmonary arteries to R/O chronic PE

96 Determinants of Severity and Risk Milder/Lower Risk Determination of Risk Severe/Higher Risk No Clinical evidence of RV failure Yes I, II WHO Class III, IV Longer (>400 m) 6MW distance Shorter (<300 m) VO2 > 15 CPET VO2 < 12 Normal-minimally elevated BNP Very elevated Minimal RV dysfunction TAPSE 20mm Echocardiographic findings Significant RV Dysfunction TAPSE <15mm Normal/near normal RAP and CI RAP<10 mm. CI>2.5 Hemodynamics High RAP, LOW CI RAP>15 mm. CI 2.0

97 Diagnostic Evaluation Ventilation-Perfusion Lung Scan CT findings in CTEPH may be minimal V/Q scan should always be considered if CTEPH is suspected 1 segmental or larger mismatched perfusion defect Usually several segmental or lobar defects bilaterally Normal V/Q scans in PH: very unlikely to have chronic PE sensitivity 90% to 100%, specificity 94% to 100%

98 Relationship between SPAP, MPAP and DPAP It has been recently shown that the 3 components have constant relationship under varying conditions SPAP = 1.5 MPAP mm Hg Syyed et al Chest 2008;133; At rest: MPAP = 0.6 SPAP + 2 mm Hg Chemla et al, Chest 2004; 126:

99 Estimation of Systolic PAP Tricuspid regurgitation jet velocity

100 RV Size

101 RV Function RV Fractional Area Change (FAC) Weyman A. Practices and principles of echocardiography.2nd ed. Philadelphia: Lippincott, Williams and Wilkins;1994.