Statement on Disability: Pulmonary Hypertension Ronald J. Oudiz, MD and Robyn J. Barst, MD on behalf of Pulmonary Hypertension Association The Scientific Leadership Council of the Pulmonary Hypertension Association (PHA) drafted this document to provide guidance for the development of disability criteria for patients with pulmonary hypertension by the Institute of Medicine (IOM) for the Social Security Administration (SSA). Pulmonary hypertension (PH) is defined as an abnormal elevation of pulmonary arterial pressure, and can result in progressive enlargement and dysfunction of the right ventricle (the right side of the heart), often leading to rapidly progressive clinical heart failure and death 1. Disability due to PH is multifactorial, and can depend on factors such as the PH patient s degree of aerobic impairment, functional limitation, compensatory physiologic mechanisms, psychological impact of the disease, as well as the burden and side effects of the treatments used to treat the PH. It should be noted that to date, while there is an abundance of data from the literature demonstrating the physiologic impact of PH and poor outcomes in patients with PH, there have been no studies specifically evaluating the impact of PH on work ability. 1. Definition of PH a. Pulmonary hypertension (PH) is defined as an abnormal elevation of pulmonary arterial pressure. The hemodynamic definition of PH requires cardiac catheterization demonstrating a mean pulmonary artery pressure (PAP) > 25 mmhg and pulmonary vascular resistance (PVR) >3 Wood units 1. 2. Etiology of PH a. PH can be the result of various disorders of the cardiovascular and/or respiratory systems. The table below shows the current PH classification, grouped by similar clinical symptoms and similar pathology/pathobiology 2.
3. Impact of PH on disability a. Decreased exercise capacity in PH One of the hallmarks of the physical impairment due to PH is reduced exercise capacity with breathlessness, (i.e. dyspnea) with exertion being the most common symptom reported. Patients with PH cannot increase cardiac output sufficiently to meet the demands of the exertion, whether it is the activities of daily living or exercise. Both the inability to increase the blood flow through the lungs due to the diseased lung vessels (which by definition causes the same lack of needed increase in blood flow to the body, i.e. cardiac output) and the impairment in the ability of pulmonary blood flow to perfuse ventilated lung (resulting in poor ventilation/perfusion matching) contribute to the impaired
exercise capacity and dyspnea and fatigue experienced by patients with PH. i. Measurement of exercise capacity in PH Decreased exercise capacity can be quantitated using various standardized measures of exercise capacity, including treadmill and cycle testing 3 (measures of exercise tolerance), as well as the commonly used 6 minute walk test 4 (measure of exercise endurance). When measurements of gas exchange are also measured (such as oxygen uptake and carbon dioxide output), more precise physiologic assessments of the cause(s) of the reduced exercise capacity can often be made 3. ii. Degree of impairment in exercise capacity The degree of impairment in exercise capacity has been best quantified using 6 minute walk testing and cardiopulmonary exercise testing (CPET). Studies have shown that these measures are prognostic parameters for survival in PH patients 5 6 and that the degree of their impairment correlates with other clinical measures of PH severity including the modified New York Heart Association (NYHA) functional classification for PH, quality of life, and hemodynamic severity. b. Reduced functional capacity in PH The NYHA functional class (and World Health Organization [WHO] functional class, modified for PH) correlates with hospitalization and survival in patients with PH. As in heart failure associated with other cardiovascular disorders, patients with functional class III and IV are limited to the extent that they must modify their daily activities due to their underlying illness. c. Compensatory mechanisms in PH i. Hemodynamic considerations The degree of elevation in pulmonary artery pressure (PAP) does not correlate with functional PH severity as well as other markers of PH severity 7. Adaptation of the cardiopulmonary system in response to the impairment of pulmonary blood flow is variable, with some patients able to compensate via an increased right ventricular (RV) response (RV hypertrophy with preserved RV systolic function), and others who develop rapid decrements in RV function. Fluid retention and impaired renal handling of sodium directly affect the RV response to PH. Higher right atrial pressure and lower cardiac output, correlate well survival in PH, as these measures evaluate the physiologic effects of the impaired pulmonary circulation. Physical examination may be revealing in PH patients with RV failure, with neck vein distension, enlarged liver (i.e. hepatomegaly, and peripheral swelling (i.e. edema, however many PH patients only manifest symptoms during exercise, when the demand for increased blood pulmonary and
systemic blood flow cannot be met due to the diseased blood vessels in the lungs 8. These patients may not manifest the typical findings of RV failure, but exercise capacity may be severely limited. Conversely, patients with overt signs of RV failure may in fact have relatively minor symptoms owing to physiologic adaptations, however these patients should still avoid workday stresses because of their propensity for sudden decompensation, which occurs frequently in the PH population. ii. Neurohormonal considerations A variable neurohormonal response may also play a role in the variable clinical response to PH. Circulating vasoconstrictor (i.e. constricting and narrowing of the blood vessels) and vasodilator (i.e. relaxing and opening of the blood vessels) responses mediate detrimental and adaptive responses, respectively to PH. iii. Metabolic and organ systems considerations Responses to PH including increased oxidative stress and impaired renal perfusion contribute to the above neurohormonal and hemodynamic changes that modulate the clinical presentation of PH. The common use of diuretics used to treat the fluid retention in PH patients also contributes to renal impairment. A particularly common abnormality seen in patients with PH is hypoxemia (i.e. decreased oxygen in the blood supplying the body). Patients with underlying parenchymal lung disease and/or pulmonary venous hypertension due to left sided heart disease may develop hypoxemia. In addition, patients without these conditions can develop hypoxemia. In many patients, shunting of deoxygenated blood (i.e. right to left shunting of blood bypassing the lungs resulting in inadequate oxygen in the blood) results in systemic desaturation, (i.e. low oxygen in the blood going to the body), due to increased right sided pressure that forces blood through a patent foramen ovale (i.e. a small hole in the heart that remains open in ~30 40% of individuals) 9. d. Treatment side effects and burden of treatment i. PH treatments The treatments for PH vary, and include supportive interventions and medications such as continuous oxygen and diuretics (i.e. to decrease swelling from fluid retention). Some PH patients benefit from medications used to improve symptoms and exercise capacity. These medications range from oral (taken one to three times per day) and inhaled treatments (four to 9 times per day) to continuous (24/7) parenteral (subcutaneous or intravenous) treatments.
ii. PH treatment side effects Common side effects of PH treatments include, but are not limited to: increased thirst and urination, dry mouth, hypokalemia with muscle cramping, flushing, hypotension (i.e. low blood pressure), dizziness, headache, jaw pain, leg and back pain, diarrhea, and rash. iii. Burden of PH treatment and associated effects Depending on the medications, the burden of PH treatments can include the daily need for preparing PH medications under sterile conditions, carrying ice packs to keep medication in the infusion pump refrigerated, carrying and maintaining two infusion pumps (one pump is needed for backup due to the short half life of the medication, which can be as short as 2 minutes, thereby necessitating the 24/7 treatment), cleaning, protecting and maintaining an indwelling central venous or subcutaneous catheter, and carrying, maintaining and preparing a nebulizer for inhalation 4 9 times daily with inhaled treatment delivery times ranging from 2 15 minutes per treatment. Being off of the 24/7 therapies, even for a few minutes, can be life threatening. The burden of continuous oxygen therapy includes the need for transporting a continuous supply of oxygen (i.e. not infrequently large and heavy tanks) and use of nasal cannula. Additional side effects associated with some PH treatments include pain at the medication injection site (which in itself can be debilitating), frequent catheter infection and sepsis, requiring hospitalization and catheter removal, and coughing after inhalation of PH medications. Replacement of central venous catheters are not without significant risk in part due to limited number of veins that the catheter can be inserted into.
Disability criteria and scoring system for patients with pulmonary hypertension (PH) Weighted Criteria Score Syncope 3 WHO Functional Class IV 3 Mean RAP > 14 or SVO2 < 70% 3 Clinical right-sided heart failure 3 WHO Functional Class III (do not count if NYHA IV; see above) 2 Troponin elevation 2 Resting SBP <100 mmhg or 2 Resting HR >100 bpm Pericardial Effusion 2 Mild or greater echo RV enlargement or mild or worse echo RV dysfunction 2 6MWD < 300 m or peak VO2 < 14 ml/kg/min 2 BNP > 180 pg/ml or NT-proBNP > 450 pg/ml 2 Serum sodium <130 meq/l 2 Continuous parenteral PH Therapy 2 Hypoxia (SaO2<92% at rest) requiring supplemental O2 or Hypoxia (SaO2<90% with exertion) requiring supplemental O2 2 WHO Functional Class II (do not count if NYHA III or IV; see above) 1 Pleural Effusion 1 6MWD < 400 m (do not count if <300 m; see above) 1 Peak exercise SBP <120 mmhg 1 Medication side effects preventing work outside of home 1 IF PVR >12 IF PVR >8, 12 IF PVR >3, 8 AND AND AND weighted score > 3 weighted score > 8 weighted score > 12 THEN Disability THEN Disability THEN Disability
Tabular Listing of Impairments in pulmonary hypertension (PH) Patients Risk Factor Modifier Rationale Syncope Recurrent Poor survival; predictor of sudden death Right ventricular heart failure Late stage of decompensation; lack of cardiac reserve*** WHO functional class** III, IV Late stage of decompensation; lack Resting systolic blood pressure of cardiac reserve*** <100 mmhg Denotes low cardiac output; late stage of decompensation; lack of cardiac reserve*** Resting heart rate > 90 bpm Late stage of decompensation; lack of cardiac reserve*** CXR Pleural effusions Denotes right ventricular heart failure ; late state of decompensation ; lack of cardiac reserve*** Echocardiography Pericardial effusion not otherwise explained (any size); RV dilation/ dysfunction; decreased right sided clearance with cavitation study Independent predictor of poor survival; late stage of decompensation; lack of cardiac reserve*** 6 minute walk distance*+ <425 meters Significant functional limitation; independent predictor of poor survival CPET+ Peak VO 2 < 18 ml/kg/min; Peak systolic blood pressure during exercise < 130 mm Hg Significant functional limitation; independent predictor of poor survival Platelet count <50,000/μl Late state of decompensation Serum sodium < 135 meq/l Predictor of poor survival with or without right heart failure Total bilirubin 2.5 mg/dl Denotes severe right heart failure Hospitalization for worsening PH Independent predictor of poor survival Uric acid >11 mg/dl Independent predictor of poor survival; marker of severe oxidative stress Renal insufficiency Denotes low cardiac output; Late stage of decompensation; lack of cardiac reserve*** BNP > 180 pg/ml Marker of right ventricular heart failure Troponin Positive Right ventricular ischemia Hemodynamics mrap>14 mmhg CI<2.2L/min/m2; PVR > 12 Wood units; SVO2 < 70% Late stage of decompensation; lack of cardiac reserve***
Disease Severity necessitating Parenteral Therapy Disease Severity necessitating Supplemental Oxygen Therapy for SaO2 < 92% at rest or with exertion Memory Loss/Learning Disabilities Denotes advanced disease and/or inadequate responses to nonparenteral therapies. Burden of medication delivery systems, indwelling catheters is high; increased risk of life threatening bacteremia, sepsis and/or thromboembolic events, e.g. CVA, PE Denotes advanced disease. Burden delivery system is high. Related to inadequate cerebral perfusion, i.e. inadequate cardiac output; increases burden of parenteral and/or inhaled PAH medications Medication side effects Diarrhea, foot pain, back pain Prevents work outside the home Note regarding disability in patients with PH: While FDA approved therapies are indicated for patients with WHO Group 1 PAH, the disability and associated morbidity (and mortality) of PH resulting from any underlying etiology is significant, and is the result of the same cardiovascular consequences (i.e. right ventricular [RV] failure) as PAH. In addition, in order to fully address a disability claim of a patient with congenital heart disease (CHD, discussed separately on 05 April, 2010), cross referencing this document with the CHD guidelines is suggested. *6 MWD is affected by age, gender, and height **WHO class is the functional classification for PH (modification of the New York Heart Association functional classification for PH) + limits to sustain performance on a daily basis as required in order to work ***Lack of cardiac reserve can progress to severe heart failure with not infrequently insignificant stresses (that are tolerated by subjects with adequate cardiopulmonary reserve), e.g. upper respiratory tract infection, bronchitis, clinical pneumonia, flu; anemia; hyperthyroid state. PVR reflects the impact of both the elevated pulmonary artery pressure and the reduced cardiac output upon the cardiovascular system. Abbreviations: PVR = pulmonary vascular resistance; RV = right ventricle; WHO = World Health Organization; 6MWD = 6 minute walk distance; peak VO 2 = peak oxygen uptake during exercise; CPET = cardiopulmonary exercise testing; RAP = right atrial pressure; CI = cardiac index; SVO2
mixed venous oxygen saturation; BNP = brain natriuretic peptide; RHC right heart catheterization REFERENCES 1 McLaughlin VV, Archer SL, Badesch DB, et al. American College of Cardiology Foundation Task Force on Expert Consensus Documents; American Heart Association; American College of Chest Physicians; American Thoracic Society, Inc; Pulmonary Hypertension Association. J Am Coll Cardiol 2009;53:1573 619. 2 Simonneau G, Robbins IM, Beghetti M, et al. Updated clinical classification of pulmonary hypertension. J Am Coll Cardiol 2009;54:S43 54. 3 Sun XG, Hansen JE, Oudiz RJ, Wasserman K. Exercise pathophysiology in patients with primary pulmonary hypertension. Circulation 2001;104:429 35. 4 Guyatt GH, Sullivan MJ, Thompson PJ, et al. The 6 minute walk: a new measure of exercise capacity in patients with chronic heart failure. Can Med Assoc J 1985;132:919 23. 5 Sitbon O, Humbert M, Nunes H, et al. Long term intravenous epoprostenol infusion in primary pulmonary hypertension: prognostic factors and survival. J Am Coll Cardiol 2002;40:780 8. 6 Wensel R, Opitz CF, Anker SD, et al. Assessment of survival in patients with primary pulmonary hypertension: importance of cardiopulmonary exercise testing. Circulation 2002;106:319 24. 7 McLaughlin VV, Shillington A, Rich S. Survival in primary pulmonary hypertension: the impact of epoprostenol therapy. Circulation 2002;106:1477 82. 8 Rubin LJ, Badesch DB. Evaluation and management of the patient with pulmonary arterial hypertension. Ann Intern Med 2005;143:282 92. 9 Sun XG, Hansen JE, Oudiz RJ, Wasserman K. Gas exchange detection of exercise induced right to left shunt in patients with primary pulmonary hypertension. Circulation 2002;105:54 60.