TSANZ/ANZSRS meeting 31 Mar Clinical utility of CPET. Bhajan Singh MBBS FRACP PhD

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TSANZ/ANZSRS meeting 31 Mar 2015 Clinical utility of CPET Bhajan Singh MBBS FRACP PhD Head of Department, Pulmonary Physiology & Sleep Medicine, Sir Charles Gairdner Hospital Director, West Australian Sleep Disorders Research Institute Clinical Professor, Faculty of Science, University of Western Australia Overview 1.Management of cardio-pulmonary disease Heart failure Other heart disease PHT Chronic lung disease 2.Evaluation of unexplained breathlessness and exercise limitation 3.Selection of patients for surgery Lung Abdominal 4.Prescription of exercise for rehabilitation 5.Assessment of impairment & disability 1

Heart Failure Peak VO 2 Can peak VO 2 identify patients in whom cardiac transplantation can be safely deferred? N = 114 (103 M) referred for transplantation 46% IHD, 54% dilated CMP Measured: peak VO 2, EF, PCWP Peak VO 2 was best predictor of survival VO 2 > 14 ml/min/kg 1YS 94% VO 2 <14 ml/min/kg 1YS 70% Allows identification of subjects in whom transplantation can be deferred safely. Findings replicated in patients on beta-blockers (O Neill JO et al. Circulation 2005). Mancini DM et al. Circulation 1991; 83;778-786. Heart Failure V E /VCO 2 To develop ventilatory class (VC) system that correlates ventilatory efficiency (V E /VCO 2 ) cut-offs to cardiac-related events. N = 448 subjects with HF underwent CPET followed for 2 years. 81 major cardiac events (64 deaths, 10 Txs, 7 LV assist devices). VC V E /VCO 2 slope Event-free survival, % I 29 97.2 II 30.0-35.9 85.2 III 36-44.9 72.3 IV 45 44.2 May be more predictive of prognosis than peak VO 2. Does not require maximal effort. Arena R et al. Circulation 2007: 115: 2401-17. 2

CPET - Heart Failure Cardiopulmonary predictors of total mortality rate during follow-up of median 644 days in 223 patients with CHF (Gitt AK et al. Circulation. 2002; 106: 3079-84) ACC/AHA CHF Practice Guideline 2005 recommends CPET to Identify high-risk patients presenting with HF who are candidates for cardiac transplantation or other advanced Rxs Determine if HF is the cause of exercise limitation when the contribution of HF is uncertain (expert opinion) Hunt SA et al. ACC/AHA CHF Practice Guideline Circulation 2005; 112(12) Gitt AK et al. Circulation. 2002;106:3079-84. CPET Heart disease other than HF Disorder Congenital HD Clinical utility Assessment Prognosis Findings In non-cyanotic CHD, V E /VCO 2 slope 38 associated with 10x increased risk of mortality (Dimopoulos et al. Circulation 2006) IHD Diagnosis Compared to standard ECG stress test, CPET can detect exercise-induced myocardial ischaemia more accurately (from duration of O 2 pulse flattening & slope of VO 2 / WR) (Belardinelli et al. Eur Heart J 2003) Pacemakers Optimize therapy VO 2 at peak or AT, O 2 pulse & V E /VCO 2 can be used to optimize settings on rate-responsive (e.g. AV delay) and biventricular pacemakers. (Balady et al. Circulation 2010) 3

CPET Pulmonary hypertension Clinical utility Objective functional assessment quantify severity response to Rx Basis Peak VO 2 highly correlated with amount of functional pulmonary vascular bed. V E /VCO 2 correlated with PVR (Janicki et al. ARRD 1984; Ting et al. Chest 2001) Diagnostic - PFO detection of R-to-L shunt Diagnostic chronic lung disease identification of PHT Abrupt and sustained changes in P ET O 2 ( ), P ET CO 2 ( ) and RER ( ), and an associated decline in SpO 2 (Sun et al. Circulation 2002) Patients with chronic lung disease & PHT have higher V E /VCO 2 & lower SaO 2 (Holverda et al. Respiration 2008) CPET Pulmonary hypertension 51 yo F with PPH & R-L shunt 4

10/04/2015 CPET Chronic respiratory diseases CPET also provides prognostic information in patients with chronic lung disease. Palange P. et al. ERJ 2007 Mortality in COPD by peak VO2 quartiles (N=150). (Oga T et al. AJRCCM 2003) CPET unexplained breathlessness & exercise intolerance CPET is under-utilised Lack of published evidence (Eur Resp Task Force 2007 lowest recommendation grade: D) Should be considered if symptoms unexplained from history, exam, ECG, CXR & PFTs. Graphical display (e.g. 9 panel plot) simplifies pattern recognition and interpretation Peripheral circulation CO2 production Pulmonary circulation O2 flow Expired MUSCLE HEART AND BLOOD LUNGS Pyr lac O2 consumption CO2 flow Inspired CAD Heart failure Other HD Anemia Obstructive Restrictive Infiltrative Chest wall Creatine PO 4 VCO2 VO2 Energy Obesity Myopathy Detraining Occlusive Autonomic dysfunction PPH Thromboembolic 1 and 2 PVD Respiratory gas flow from mouth to mitochondria Stringer WW Expert Rev Respir Med 2010 5

CPET unexplained breathlessness Specific diagnoses that can be made using CPET Specific diagnoses Standard test Exercise-induced arrhythmias Chronotropic incompetence Features ECG Low peak HR, AT & VO 2 ; high O 2 pulse PFO with exercise-induced R-L shunt Abrupt changes in V E /VCO 2, RER, P ET CO 2 Myocardial ischaemia ECG, (duration of O 2 pulse flattening, slope of VO 2 / WR) Early pulmonary vascular disease Low peak VO2, AT, P ET CO 2 ; high VE/VCO 2 Diastolic HF Cardiac limitation (with normal ECHO) Chronic hyperventilation Low P ET CO 2 Psychogenic dyspnoea Erratic pattern of breathing Modified test EIA Brief high intensity exercise with post-exercise FEV 1 Exercise-induced laryngeal dysfunction Exercise flow-volume loops or laryngoscopy CPET unexplained breathlessness Directing the diagnostic pathway of breathlessness using CPET: Is exercise capacity normal? Is the pattern of limitation circulatory or ventilatory? Circulatory Ventilatory Peak VO 2 VO 2 at AT Normal or VO 2 / WR Often Normal Peak HR May be May be Peak VO 2 /HR Often May be Breathing reserve >20% <15% Post exercise FEV 1 Unchanged from rest May decrease compared with rest SaO 2 Normal Often V E /VCO 2 May be Often Balady et al. Circulation 2010 6

CPET unexplained dyspnoea Balady et al. Circulation 2010 CPET: suitability for surgery CPET has an important role in pre-op evaluation for 1. Lung resection Lung cancer LVRS in emphysema 2. Abdominal surgery Elderly Bariatric surgery AAA repair CPET directly assesses both cardiac and pulmonary reserves simulates the stress of surgery to an extent ( metabolic rate and O 2 delivery) permits detection of clinically occult heart disease esp. in elderly 7

CPET Lung cancer resection Peak VO 2 is a strong predictor of perioperative morbidity and mortality related to resectional surgery (Bolliger et al AJRCCM 1995; Brunelli et al. Chest 2009). ERS/ESTS Guideline ERJ 2009 ERS/ESTS recommends CPET in all patients with FEV 1 or DLCO <80% predicted. (Brunelli A et al. ERJ 2009) Brunelli et al Chest 2009 N = 204 N Mortality Total morbidity Cardiac morbidity Pulmonary morbidity Bolliger CT et al AJRCCM 1995; Brunelli A et al. Chest 2009 & ERJ 2009 CPET: LVRS N = 1,218 patients with severe emphysema Randomized to LVRS or medical therapy with mean F/U 29.2 mo LVRS group exercise capacity improved by >10 W in more patients (15% vs 3%) survival advantage only in sub-group with predominately UL emphysema + low baseline exercise capacity Low baseline exercise capacity = max. WR <40W for men and <25W for women. Analysis excluded high risk gp= FEV 1 <20% pred. + either homogenous emphysema or DLCO<20% pred. Fishman A et al. (NETT group), NEJM 2003; 348(21): 2059-73 8

CPET - abdominal surgery N = 187, >60 yo, CPET prior to abd surgery 14 deaths 3 surgical; 11 CVS Independent risk factors for mortality: ischaemia, low VO 2 @AT. Prospective study N = 548 VO 2 @ AT ml/min/kg N CVS death % mortality <11 55 10 18* >11 132 1 0.8 *P <0.001 Ischaemia + VO 2 @AT <11: mortality 42% Older P et al. Chest 1993; 104(3): 701-4. Older P et al. Chest 1999; 116: 355-62. CPET abdominal surgery Bariatric surgery (laproscopic) N = 109 (75% F, age 46.0 ± 10.4 yrs, BMI 48.7 ± 7.2 kg/m 2 ) Complications recorded: death, unstable angina, AMI, VTE, renal failure, stroke Patients with peak VO 2 <15.8 ml/kg/min (lowest tertile) had Higher complication rate: 6/37 (16.7%) vs. 2/72 (2.8%) (p = 0.02) Higher LOS & 30 day readmission rate (p = 0.005) AAA repair N = 506, 83% M, age 73.4 (44-90), mostly endovasc repair In-hospital mortality 2.6% CPET thresholds 1. VO 2 @AT >10.2 ml/min/kg 2. Peak VO 2 >15 ml/min/kg 3. AT >42% 3YS worse for 3 vs 0-1 sub-threshold value: - 59.9% for 3 sub-threshold CPET values - 86.4% for 0-1 sub-threshold CPET value McCullogh PA et al. Chest 2006; 130: 517-25. Grant SW et al. Br J Anaesth 2015; 114: 430-6. 9

CPET: exercise prescription Exercise training: integral component of rehabilitation programs - Cardiac - Pulmonary - Stroke Prescription usually based on HR from standard ECG stress test (cardiac), 6MWT (pulmonary). No data to demonstrate superiority of CPET over other methods of prescription. However CPET provides valuable additional information to determine - safety (cardiac disease, O 2 desaturation), - factors contributing to exercise intolerance - optimal training intensity based on VO 2 at AT, peak VO 2, HR, peak RER. - Need for O 2 supplementation - Outcome assessment - need to adjust training intensity. CPET: disability assessment Pulmonary disease Severity of impairment usually based on resting pulmonary function test. But, FEV 1 is a poor predictor of the ventilatory requirement for a given level of work. AMA (American) recommends measuring peak VO 2 in special circumstances: 1. Dyspnoea greater expected from resting PFTs 2. Patient reports inability to perform specific duties due to breathlessness 3. Sub-maximal effort or incorrect performance of pulmonary function tests suspected. 4. Impairment due to ILD AMA (American) assessment of pulmonary dysfunction 2008 Class 0 1 2 3 4 FEV 1, % predicted 80 and 65-799 55-64 45-54 <45 FVC, % predicted 80 and 70-79 60-69 51-59 <50 FEV 1 /FVC, % predicted >LLN or >75% and DLCO, % predicted 75 or 65-74 or 55-64 or 45-54 or <45 or VO 2 max, ml/kg/min >25 22-25 18-21 15-17 <15 10

CPET: disability assessment Compared accuracy of work capacity predicted by physicians based on history, examination, PFT, ABG, CXR, ECG ± CPET. N = 348 shipyard workers who complained of exercise limitation with FEV 1 >40% pred., FEV 1 /FVC >40% and no known cardiac disease. Findings - Work capacity was not accurately predicted without CPET - Exercise is often limited by non-respiratory factors 69% CVS (cardiac/pvd), 18% respiratory Predicted work capacity without CPET N Measured work capacity (CPET) Impaired Not impaired Indeterminate Impaired, (%) 66 (19) 43 (65) 22 (33) 1 (2) Not impaired, (%) 148 (43) 46 (31) 102 (69) 0 (0) Indeterminate, (%) 134 (39) 49 (37) 81 (60) 4 (3) Total 348 138 205 5 Oren A. et al. ARRD 1997; 135(1): 230-5 CPET: disability assessment Cardiovascular disease & stroke Objective and accurate assessment of exercise capacity. Confirms whether effort was maximal (RER>1.10) Identifies the predominant cause for exercise intolerance when several conditions co-exist among patients undergoing CPET for evaluation of impairment due to lung disease, there are high rates of co-existing CV disease deconditioning 11

CPET - Conclusions CPET is a safe and valuable clinical tool for: 1. The management of many cardio-pulmonary diseases 2. Evaluating the cause of exertional breathlessness and exercise limitation 3. Selecting suitable patients for lung and abdominal surgery 4. The prescription of exercise in rehabilitation programs and 5. The assessment of disability It has the potential to reduce health care costs by - streamlining diagnoses, - facilitating treatment decisions, - reducing post-operative complications and - reducing lengths of stay. 12