Pulmonary Hypertension and Left Heart Disease: What s good for the goose is not necessary good for the gander

Transcription

1 Pulmonary Hypertension and Left Heart Disease: What s good for the goose is not necessary good for the gander Jacqueline Fearon-Clarke, MA, ACNP-BC Heart Failure and Pulmonary Hypertension Nurse Practitioner Heart Success Program Morristown Medical Center

2 Learning Objectives Review PAH disease process, risk factors and associated conditions, disease classification and treatment options Discuss key assessment and diagnostic tools to differentiate PAH from pulmonary hypertension related to left heart disease Discuss management strategies of PH related to left heart disease

3 Pulmonary Arterial Hypertension Pulmonary arterial hypertension refers to elevation of vascular resistance specifically within pulmonary arteries, as opposed to capillaries and veins. The resulting increase in right ventricular afterload impairs blood flow Right ventricular remodeling from chronic pressure overload leads to progressive right heart failure and death Left ventricle is limited to the inflow received from the right ventricle. As right heart failure progresses it becomes harder and harder for the left side of the heart to supply sufficient oxygen to the rest of the body, especially during physical activity PAH: the disease is in the pulmonary arteries RA LA RV

4 Pathogenesis PAH NORMAL REVERSIBLE DISEASE IRREVERSIBLE DISEASE Gaine S. JAMA. 2000;284:

5 Pathogenesis PAH Hemodynamic impairment CO mpap Decreasing mean PAP may not reflect improvement PVR Adapted from Gaine S. JAMA. 2000;284:

6 Percent of patients FC III/IV at diagnosis Advanced Functional Class at Diagnosis Common and Indicates Delayed Recognition 100 Approximate prevalence: 15 cases/million 80 More common in women Spans 60 broad age range Delay in diagnosis persists 40 Most patients diagnosed with late symptoms 20 Poor prognosis if untreated (median survival <3 yr) 0 REVEAL Registry (N=1831) NIH Registry (N=187) French Registry (N=674) Badesch DB et al. Circulation. 2010;137: D Alonzo GE. Ann Intern Med. 1991;115: Humbert M et al. Am J Respir Crit Care Med. 2006;173:

7 5 th World Symposium on PAH: Modified Classification of PAH 1. Pulmonary arterial hypertension 1.1 Idiopathic PAH 1.2 Heritable PAH BMPR ALK1, ENG, SMAD9, CAV1, KCNK Unknown 1.3 Drug- and toxin-induced 1.4 Associated with Connective tissue diseases HIV infection Portal hypertension Congenital heart disease (update) Schistosomiasis Chronic hemolytic anemia 1. Pulmonary veno-occlusive disease and/or pulmonary capillary hemangiomatosis 1. PPHN 2. PH due to LHD 2.1 LV systolic dysfunction 2.2 LV diastolic dysfunction 2.3 Valvular disease 2.4 Congenital/acquired left heart inflow/outflow obstruction 3. PH due to lung diseases and/or hypoxia 3.1 COPD 3.2 Interstitial lung disease 3.3 Other pulmonary diseases with mixed restrictive and obstructive pattern 3.4 Sleep-disordered breathing 3.5 Alveolar hypoventilation disorders 3.6 Chronic exposure to high altitude 3.7 Developmental lung diseases (update) 4. CTEPH 5. PH with unclear multifactorial mechanisms 5.1 Hematological disorders: chronic hemolytic anemia, myeloproliferative disorders, splenectomy 5.2 Systemic disorders: sarcoidosis, pulmonary Langerhans cell histiocytosis, lymphangioleiomyomatosis, neurofibromatosis, vasculitis 5.3 Metabolic disorders: glycogen storage disease, Gaucher disease, thyroid disorders 5.4 Others: tumoral obstruction, fibrosing mediastinitis, chronic renal failure, segmental PH Simonneau G et al. JACC 2013;62:D34-41.

8 WHO Functional Class of PAH CLASS DESCRIPTION I Patients with PH but without resulting limitation of physical activity. Ordinary physical activity does not cause undue dyspnea, chest pain, or near syncope. II Patients with PH resulting in slight limitation of physical activity. They are comfortable at rest. Ordinary physical activity causes undue dyspnea or fatigue, chest pain, or near syncope. III Patients with PH resulting in marked limitation of physical activity. They are comfortable at rest. Less than ordinary activity causes undue dyspnea or fatigue, chest pain, or near syncope. IV Patients with PH with inability to carry out any physical activity without symptoms. These patients manifest signs of right-heart failure. Dyspnea and/or fatigue may even be present at rest. Discomfort is increased by any physical activity. Rubin LJ. Chest. 2004;2004:7S-10S

9 Right Heart Catheterization Gold standard Exclude congenital heart disease Measure wedge pressure or LVEDP (via LHC) Establish severity and prognosis Test vasodilator therapy Guide Treatment

10 Drugs to Treat PAH (FDA Approved) Bosentan Ambrisentan Macitentan Sildenafil Tadalafil Riociguat Epoprostenol (IV, inhaled) Treprostinil (IV, SQ, Oral, inhaled) Endothelin Receptor Antagonist PDE-5 Inhibitor Soluble guanylate cyclase stimulator Prostanoids

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14 Pulmonary Hypertension related to Left Heart Disease (PH-LHD) Pathogenesis in pulmonary venous hypertension differs from pulmonary arterial hypertension, in that there is no obstruction to blood flow in the lung; instead, an elevation in left ventricular end diastolic pressure leads to an increase in left atrial pressure which leads to an increase in pulmonary venous pressure which results in pulmonary congestion/edema Presence of intravascular circulatory congestion with elevation of diastolic and pulmonary venous pressures causes fluid transudation from pulmonary capillaries into interstitial spaces Pulmonary edema develops if transudation exceeds lymphatic drainage PVH: the disease is from the left heart Pressure gets transmitted backwards and makes the RV fail too

15 Epidemiology of PH by Echo PAH, 2.7% Unknown, 15.4% CTEPH, 2.0% Lung disease, Sleep-related hypoventilation, 9.3% Miscellaneous, 2.7% Left heart disease, 67.9% N=936 of 10,314 patients with echo PASP >40 mm Hg. Strange G et al. Heart. 2012;98:

16 Epidemiology of PH-LHD Recognized to be the most common form of PH seen clinically The precise incidence and prevalence of PH-LHD in heart failure is not known widely due to: reliance on echo assessment of PA pressure to identify affected pts, inconsistent definitions cutoff to diagnose PH-LHD well done invasive studies that only provide data at a single time point (pt resting, sedated, fasting) which affect hemodynamics sicker population referred for RHC Left sided valvular heart disease assoc with PH MS 73%, MR 23%-44%, AS 29%-47%

17 Survival rates among patients with CHF and systolic dysfunction 1. normal PAP/preserved RVEF Normal PAP/ Preserved RVEF Normal PAP/ low RVEF High PAP/ low RVEF 4. high PAP/low RVEF Figure 1. Survival Rates Among Patients With CHF With Systolic and left ventricular ejection fraction less than 35% are lower among patients with high pulmonary arterial pressures (PAPs) and low right ventricular ejection fraction (RVEF). Group 1: normal PAP/preserved RVEF (n = 73). Group 2: normal PAP/low RVEF (n = 68). Group 3: low PAP/low RVEF (n = 21). Group 4: high PAP/low RVEF (n = 215). Ghio, A. Gavazzi and C. Campana et al., Independent and additive prognostic value of right ventricular systolic function and pulmonary artery pressure in patients with chronic heart failure, J Am Coll Cardiol 37 (2001), pp

18 Differentiating PAH from PH-LHD 1. Pulmonary Arterial Hypertension Idiopathic (IPAH) Familial (FPAH) Associated with (APAH) Collagen Vascular disease Congenital systemic-to-pulmonary shunt Portal hypertension HIV infection Drugs and toxins Anorectic agents (appetite surpressants) Others 2. Pulmonary Venous Hypertension Left-sided atrial or ventricular heart disease Left-sided valvular disease Associated with significant venous or capillary involvement Pulmonary veno-venous occlusive disease Pulmonary capillary hemangiomatosis Persistent pulmonary hypertension of the newborn Extrinsic compression of central pulmonary veins Fibrosing mediastinitis Adenopathy and/or tumors others

19 Hemodynamic Definition of PH/PAH PH Mean PAP 25 mm Hg at rest during RHC PAH Mean PAP 25 mm Hg plus PAWP 15 mm Hg plus PVR >3 Wood Units Hoeper MM et al. J Am Coll Cardiol. 2013;62:D42-D50.

20 PH: The Importance of Hemodynamics Pulmonary venous hypertension Elevated PCWP, normal PVR VC RA RV PA PV PC LA LV Ao PAH PH with respiratory disease CTEPH Normal PCWP, elevated PVR Other high CO

21 Chronic LVD Elevated LVEDP Pulmonary Venous Hypertension Pulmonary Vascular Endothelial Dysfunction Endothelin Nitric Oxide Reactive Pulmonary Vascular Remodeling Fixed Pulmonary Vascular Resistance Pulmonary Artery Hypertension RV Afterload RV Systolic Failure Adapted from: Zakir RM, Al-Dehneh A. et al Right Ventricular Failure in Patients with Preserved Ejection Fraction and Diastolic Dysfunction: An Under-recognized and Increasingly Prevalent Clinical Entity. Congestive heart failure, May 2007, 13: issue 3

22 DIAGNOSING PH-LHD Challenging nonspecific symptoms, difficult to interpret diagnostics, PH may be multifactorial PH-LHD is often incorrectly diagnosed and treated as PAH, especially in elderly patients Comprehensive approach so that appropriate treatment can be chosen

23 History and Physical Examination Known LV structural disease MI, CM Presence of comorbidities associated with LHD older age, DM, obesity, HTN Orthopnea and PND Left sided S3 or S4 gallop Left sided Murmurs Displaced apical pulse Coarse crackles Ascites

24 Diagnostic Studies Chest x-ray evidence of congestion, absence of parynchemal lung disease ECG Q waves, LVH, LAE, LBBB, AF, inducible myocardial ischemia during exercise Echo host of echo finding suggestive of LV systolic and diastolic dysfunction, LVH, MV disease ex MR >1+ favors PH-LHD over PAH, EF <50% Cardiac MRI useful to detect structural abnormalities of the LV, LA, systolic function, congenital heart disease, myocardial fibrosis and infiltrative disease RV enlargement, hypertrophy, and systolic function are best determined by CMR

25 Right Heart Catheterization Data from optimally performed RHC must be incorporated together with clinical findings and echo data to arrive at final diagnosis of PH-LHD Useful to optimize medical management Assess risk in patients being evaluated for transplant and mechanical circulatory support Crucial that the procedure is performed correctly and that the data are properly collected and interpreted PCWP/LVEDP > 15 mmhg, abrupt increase in PCWP with exercise or volume loading

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27 Management of PH-LHD Despite its prevalence, significant clinical data directed at treatment of PH-LHD is lacking Goals of care are focused on: Differentiate the cause of heart failure and treat HFrEF, HFpEF, valvular disease Volume management is first line therapy Normalization of PCWP Guided hemodynamic therapy Aggressive management of the underlying condition and comorbidities that may worsen disease and cause disease progression.

28 Management of PH-LHD Are PAH meds beneficial in PH-LHD? Prostanoids FIRST flolan in HFrEF Stopped early due to trend towards increased mortality in the flolan group ERAs Multiple trials of ERAs in HFrEF Showed no improvement, worsening edema, hospitalization PDE5I Small studies showed benefit in hemodynamics, 6mwd, peak VO2 Considered the only safe PH med for heart failure

29 Use of PDE-5 Inhibition in HFrEF and HFpEF Has been used pre-transplant to lower PAP prior to transplant as well as post transplant and LVAD Few small randomized trials add to observational and mechanistic evidence in favor of adding PDE-5 inhibitors, to standard drug therapy in patients with heart failure These small placebo-controlled studies were consistent with each other in suggesting that patients with systolic heart failure who take a PDE-5 inhibitor in addition to their other HF medications have less dyspnea and have improved exercise performance In systolic heart failure patients enrolled in these studies Peak VO 2 increased over months of 3x daily sildenafil in both studies along with improvements in pulmonary-artery pressures and other hemodynamic measures. 1. Lewis GD, Shah R, Shahzad K, et al. Sildenafil improves exercise capacity and quality of life in patients with systolic heart failure and secondary pulmonary hypertension. Circulation 2007; 116: Guazzi M, Samaja M, Arena R, et al. Long-term use of sildenafil in the therapeutic management of heart failure. J Am Coll Cardiol 2007; 50:

30 RELAX trial - PhosphodiesteRasE-5 Inhibition to Improve Quality of Life And Exercise Capacity in Diastolic Heart Failure Primary Hypothesis: As compared to placebo, chronic PDE-5 inhibition will result in greater improvement in exercise performance as measured by peak VO 2 in DHF after 24 weeks of double blinded therapy. Study Design: double-blind, placebo controlled trial Sample size: 216 patients with DHF. Primary endpoint: Change in exercise capacity, as determined by peak oxygen uptake at 12 wks. Secondary endpoints: Change in submaximal exercise capacity, as determined by 6-minute walk test at Weeks 12 and 24 Change in a composite score reflective of clinical status Conclusion and Relevance Among patients with HFPEF, phosphodiesterase-5 inhibition with administration of sildenafil for 24 weeks, compared with placebo, did not result in significant improvement in exercise capacity or clinical status.

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32 Management of PH-LHD HFrEF HFpEF GDMT neurohormonal blockade, diuretics, vasodilators, inotropes, MCS Lifestyle changes Remote monitoring technology cardiomems, ICDs No medication approved to treat Waiting for results of PARAGON-HF (Entresto vs Valsartan on morbidity and mortality) Aggressively treat underlying conditions htn, obesity, DM, sleep apnea Lifestyle changes Valvular pathology Open heart surgery to repair or replace valves Minimally invasive approaches TAVR, COAPT

33 Case study #1 62 year old white male referred to our program for PH evaluation Hx of morbid obesity, htn, DM type 2, pulmonary fibrosis, cirrhosis (NASH) with evidence of varices on CT skan, no GI bleed C/o 2 months nonproductive cough, decreased exercise tolerance and shortness of breath, left sided chest pain at rest and with walking He denied pre-syncope, syncope, hemoptysis, family hx of PAH, use of wt reduction medications, ETOH and tobacco use

34 Case Study #1 Vitals b/p 110/62, HR 72, BMI 55.2 PE - NAD, S1S2 RRR, no murmurs/rubs, no RV heave Increased JVD, 2 3+ pretibial edema Diagnostics EKG LFB vs LVH, non spec ST changes Echo nml LVEF, pulm veins c/w Increased LAP, mod RV dilation, no TR to estimate RVSP A/P HFpEF given increased dose of diuretic for a couple of months, lost 10 lbs Referred for R/LHC due to further determine etiology of his HF

35 Case study #1 Right heart cath normal RA/RV/Pa saturations, RA 23 PCWP 20 PAM 26 CO/CI 8/3 Left heart cath LVEDP 26 normal coronaries Confirms HFpEF Continued aggressive diuresis and referred to metabolic specialist for bariatric surgery (ongoing, pt doesn t think he has a problem)

36 Questions?