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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

0

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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