Post on 12-Jul-2020
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Pulmonary Hypertension Due to Left Heart DiseaseDiagnosis and Management
James C. Fang, MD
University of Utah Health Sciences
Salt Lake City, UT
Pulmonary HypertensionSome definitions
ISHLT 2012;31:913–33
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Pathophysiology of PH-LHD
Moraes, Colucci, Givertz Circulation 2000
Highest risk associated with
PVR >4 Wood units
PAsys >35 mmHg
PCW >25 mmHg
PAC <2.0 cc/mmHg
‘Mixed’ Pulmonary Hypertension in Heart Failure
Miller WL, et al. JACC-HF 2013
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When to Suspect PVH
Robbins IM, et al. CircHF 2013
RAP <1546/207 (22%) PCW >15 after 0.5L NS over 5-10”
PH suspected by history and exam
PH on echocardiography
1) Age > 60 years?2) Comorbidities (DM, HTN, CAD, obesity)3) Valvular heart disease?4) LV systolic dysfunction?5) Echo abnormalities (LAE, LVH, or significant DD)6) BNP markedly elevated?
PAH Probable PH from LHD
All no 1-2 yes
PH from LHD
≥3 yes
ISHLT 2012;31:913–33
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PA Pressures by DE and RHCPoor correlation
Fisher MR, Forfia P, et al. AJRCCM 2009
Sharifov OF, et al. JAHA 2016
“E/e’ had poor to mediocre linear correlation with LVFP”
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PH secondary to LHDPathophysiology
ISHLT 2012;31:913–33
B
Ryan JJ, et al. AHJ 2012
20 mmHg
10 mmHg
50
16
20 mmHg
10 mmHg
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PCW may not = LVEDP
Halperin and Taichman, Chest 2009
Of the 4320 with PH,580 (15%) had PCW<15,But310 (54%) of them had EDP>15
Particularly when1)PVR >32)PH was indication
N=11.523 mPA => 4320 (37%)
Bland-Altman limits of agreement, -15.2 to 9.5 mm Hg
EL Brittain, et al. PLoS ONE 8(10): e76461
PA Diastolic Pressure GradientPAD - PCW
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PH at catheterization
1) LVEDP >18 mmHg?2) PCW > 15 mmHg?3) LAP >15 mmHg?
no yes
PH from LHD1) Exercise2) Leg lift3) Volume challenge4) Nitric oxide
Consider Vasodilator challenge<18 mmHg
PAH
>24 mmHg
PH from LHD
PH suspected by history and exam
18-24 mmHg
Intermediate Group
ISHLT 2012;31:913–33
Systolic PA Pressure and PVRLimitations
• Does not entirely describe afterload on RV
• PA compliance not accounted for
• Does not directly describe RV performance
• Has not emerged as predictor of RVF post LVAD in multivariate models
• PVR is calculated measure
• Low PASP is very late stage of RVF
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Pulmonary Artery Pulsatility Index
Kang et al., JHLT 2015
OR 95%CIOn inotropes 0.21 0.02-0.97Off inotropes 0.49 0.01-1.94
>2.0
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E
Tedford R, et al. Circulation 2012
PA 55/20/33PCW 10CO 5.0PVR 4.6 (=0.33 mmHg-s-mL-1)
VADs decrease pulmonary hypertension in HFREF
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10
20
30
40
50
60
70
PA sys PA mean PCW CO PVR
Baseline Testing 3 days 6 wks
Zimpfer D, et al. JTCS 2007;133:689-695
N = 3527 continuous flow pump24 bridged to transplant210 +/- 83 days
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Agent PVR PAm PCW CI SVR Notes
Nitroprusside 36% 23% 27% 30% 31% Titrated in 25-50 mcg/min increments
Milrinone 31% 12% 16% 42% 30% 50 mcg/kg iv bolus
Nitric Oxide 47% NC 24% 9% NC 80 ppm over 10 minutes
Prostaglandin E1
47% 21% 13% 23% 31% Titrated in doses of 0.02, 0.05, 0.10, 0.20, 0.30
mcg/kg/min
Adenosine 41% NC 12% 9% NC 100 mcg/kg/min
ISHLT 2012;31:913–33
PH, LVAD, and Sildenafil
Tedford RJ, et al. Circulation – HF 2008
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RELAX trialPDE5i in HFpEF
Redfield MM, et al. JAMA 2013
PAH specific drugs in PH-LHDTrials and tribulations
Drug Trial Patients Endpoint Outcome
Epoprostenol FIRST 471 ACM Neutral
Tezosentan RITZ-1 669 Dyspnea Neutral
Bosentan ENABLE 1613 ACM/HFH Neutral
Darusentan EARTH-2 642 LVESVI Neutral
Milrinone PROMISE 1088 ACM Neutral
Enoximone ESSENTIAL 1854 ACM/CVH Neutral
PDE5i PITCH-HF xxxx CVD/HFH Suspended
ISHLT 2012;31:913–33
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Nitric Oxide, PVR, and PCW
Loh E, et al. Circulation 1994
Inhaled Nitrites for HFpEF
Borlaug B, et al. Circulation Research 2016
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Stasch JP, et al. Circulation 2011
LEPHT study - RiociguatSoluble guanylate cyclase stimulator
Bonderman D, et al. Circulation 2013
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Haddad, F. et al. Circulation 2008
RVSWI (mmHg-ml/m2) = (mPAP – mCVP) x CI/HR
Summary
• PH in LHD should always be distinguished from PAH
• Treatment starts with establishing euvolemia
• PH specific drugs have yet to improve outcomes
• New paradigms are being sought
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