Pulmonary Hypertension: Evolution and

Transcription

1 Management of Pulmonary Hypertension: Evolution and Controversies VERMONT CARDIAC NETWORK SPRING CONFERENCE MAY 10, 2018 MARYELLEN ANTKOWIAK, MD, PULMONARY & CRITICAL CARE MEDICINE, UVMMC

2 WHO classification I: Pulmonary Arterial Hypertension (PAH) II: Pulmonary Hypertension due to Left Heart Disease III: Pulmonary Hypertension due to Lung Disease and/or hypoxia IV: Pulmonary Hypertension due to chronic thrombotic / embolic disease V: Pulmonary Hypertension due to unclear or multifactorial mechanisms

3 Subclasses and etiologies of PH? WHO Group V Systemic S t i Circulation Pulmonary Circulation Pulmonary Arteries Systemic Arteries LA WHO Group I, IV RA WHO OG Group oup III Body Lung Systemic Veins RV WHO Group II LV Pulmonary Vi Veins

4 Classification of PH What determines pulmonary artery pressure? Pressure = Resistance x Flow Mean pulmonary pressure left atrial pressure = Resistance x Flow Mean pulmonary artery pressure = (Resistance x Flow) + left atrial pressure High cardiac output state WHO Group II WHO Group I G WHO Group III WHO Group IV

5 Pathophysiology and Pathogenesis

6 Pulmonary Hypertension: Historical Perspective Dr. Ernst von Romberg describes autopsy fi di findings off pulmonary l vascular l sclerosis l i 1960 s- Epidemic of PAH in western Europe attributed to aminorex fumarate st World Symposium Definition of elevated pulmonary artery pressure Dr. Robyn Barst publishes RCT of epoprostenol for PAH

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8 And since : Macitentan Riociguat Oral (Endothelin Receptor Antagonist) (Soluble Guanylate Cyclase Stimulator) Treprostinil (Prostacylin) 2015: Selexipag (Selective IP Prostacyclin Agonist)

9 Prior to 1995 No therapies Median survival 2.8 years from diagnosis 34% Five year survival

10 1995 Prostacylin / camp Pathway IV V Epoprostenol pop oste o Vasoreactive Patients Diltiazem Dihydropyridine CCB

11 Vasodilator testing Inhaled NO, IV prostacyclin, adenosine IPAH patients only* Positive challenge: mpap decrease by > 10 mmhg AND to < 40 mmhg Preserved or increased cardiac output Associated with much better prognosis Evaluates p patients who are candidates for CCB therapy py

12 Today Prostacylin / camp Pathway Endothelin Pathway Oral Bosentan Oral Ambrisentan Oral Macitentan IV Epoprostenol IV Treprostinil p SC Treprostinil Combination Therapy INH Treprostinil Nitric Oxide / cgmp INH Iloprost Il t Pathway Oral Treprostinil Oral Sildenafil Oral Selexipag Oral Tadalafil Oral Riociguat

13 Pathophysiology and Pathogenesis Epoprostenol Treprostinil Iloprost Selexipag Riociguat Ri i t Ambrisentan Sildenafil Tadalafil Bosentan Macitentan

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15 Updates in the Management p g of Chronic Thromboembolic Pulmonary Hypertension (CTEPH) Curable form of pulmonary hypertension Only group of PH outside of WHO I f which for hi h pulmonary l vasodilator dil t therapy is approved

16 Updates in the Management of g Chronic Thromboembolic Pulmonary Hypertension (CTEPH) Curable form of pulmonary hypertension Only l group off PH outside id off WHO I for f which hi h pulmonary vasodilator therapy is approved

17 Thromboendarterectomyy Determining surgical candidacy Disease Classification Comobidities: CAD Lung disease difficulty Body habitus Prior sternotomy NYHA IV I: Major vessel clot II: Main, lobar or segmental g III: Segmental / subsegmental IV: Intrinsic small vessel Hemodynamics Pre-op Pre op Post-op

18 Balloon Pulmonary y Angioplasty g p y ((BPA)) Inoperable CTEPH O l small, Only ll non RCT studies t di Multiple sessions, avg 3 vessel dilations / session Improvements p in mpap,, CO,, NYHA functional class,, biomarkers Persisted at 2 years Survival: % 2 yr survival % i l llarger studies t di 85-90% yr survival smaller studies Complications: Reperfusion edema % Vascular perforation- 1% Ref: Mizoguchi et al. Circ Cardiovasc Interv. 2012, Kataoka et al. Circ Cardiovasc Interv. 2012, Andreassen et al, Heart 2013

19 BPA Outcomes Post-BPA + Medical tx: PAP: 47/19 (27) RA 6 CO / CI: 6.7 / 3.4 PVR: 2.8 WU Pre-BPA + Medical tx: PAP: 97/32 (58) RA 12 CO / CI: 3.1 / 1.6 PVR: 15 WU

20 Riociguat Soluable guanylate cyclase stimulator Does not rely on endogenous NO prod ction production CHEST-1: 261 pts w/ Inoperable (~75%) or persistent ((~25%) 25%) CTEPH ~45 m difference in 6MWD, improved HD, WHO FC, FC QOL scores Ghofrani et al. NEJM. 2013

21 To anticoagulate or not to anticoagulate? Physiologic basis established early after recognition of PPH 8 major j trials All data observational, mostly retrospective 6 pos trials, 2 neg

22 COMPERA I P A H s s C P A H REVEAL

23 Exercise Initial treatment algorithms recommended avoidance of exercise Early 2000 s Recognition that exercise capacity correlates well with quality of life and p g prognosis Investigations into the safety and benefit of exercise in PH began g

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25 Reported benefits of exercise in PH Increased 6 minute walk distance (~50-70 meters!) Improved quality of life scores Improved functional capacity Improved pain and depression scores? IImproved dh hemodynamic d i ((right i ht heart catheterization) measurements Improvements in VO2max

26 As a result of these trials Treatment algorithm updated from avoidance of exercise to avoidance of strenuous exercise European respiratory society guidelines changed to recommendation to include an exercise plan in treatment of PH

27 Critically ill patients with Pulmonary Hypertension Rhythm management: Highly susceptible to atrial arrhythmias May dramatically worsen hemodynamics Rhythm control / restoration favored over rate control Lacking data to support this Respiratory failure: Avoid intubation: Can be poorly tolerated from hemodynamic standpoint Some data that NIPPV may be better tolerated Pulmonary artery catheters: No societal guidelines recommending routine use

28 The Preload Controversy PH patients are preload dependent Fluid Fl id administration d i i t ti can result in: Worsened LV filling 2/2 to septal bowing bowing, increased RV ejection time Increased RV wall stress, decreased coronary perfusion RV ischemia perfusion,

29 Vasopressors and Ionotropes Phenylephrine- both SVR and PVR increased, reflexive bradycardia may worsen HDs V Vasopressini att doses d currently tl used d iin ICU is i a pulmonary l vasodilator dil t Dopamine- At </= 16mcg/kg/min increased CO w/o increasing PVR Take Home: Epinephrinep p more ((increased CO)) and 2 ((decreases PVR)) No 1great evidence to Norepinephrine- Probably a good choice extrapolating from acute favor vs.pvr others RV failure data but known one to increase Dobutamine- decreases PVR Dobutamine PVR, but complicated by arrhythmia risks and decreased SVR, may be a good adjunct Milrinone- theoretically more pulmonary vasodilation but otherwise similar risks of dobutamine with a less predictable half life, life caution in renal failure

30 On the Horizon? Implantable delivery system for IV prostacyclin? UVMMC? Advanced RV hemodynamic y support?

31 Vasoreactive Patients Treat comorbidities Today Diltiazem (Actually) Pregnancy? Dihydropyridine CCB Anticoagulation? Endothelin Pathway Prostacylin / Nutritional Exercise Programs goral Bosentan camp Pathway counseling Oral Ambrisentan IV Epoprostenol Oral Macitentan Supplemental pp O2 Lung g Transplant p IV Treprostinil p SC Treprostinil Long term INH Treprostinil Management Oxide / cgmp g Nitric in complications INH Iloprost Diuretics CriticalPathway Illness of therapy? Oral Treprostinil Oral Sildenafil Sele ipag Oral Selexipag Oral Tadalafil Up front combination? Vaccinations Oral Riociguat

32 In Conclusion Therapeutic options for PAH have increased d dramatically i ll When and how to use the therapies we have has b become increasingly i i l complicated li d Adjuvant therapies remain controversial As A patients i live li longer l andd function f i better, b we have additional considerations regarding comorbidities bidi i andd lifestyle lif l Optimum management of decompensation is unclear l