CPX and Prognosis in Cardiovascular Disease

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CPX and Prognosis in Cardiovascular Disease Anselm K. Gitt, Piergiuseppe Agostoni Herzzentrum Ludwigshafen, Germany Instituto di Cardiologia Università di Milano, Milan, Italy Cardiopulmonary exercise testing (CPX): an introduction ESC Congress, Munich, Germany, August 25, 2012

Disclosure Declaration Declaration of Interest: Anselm K. Gitt: None Piergiuseppe Agostoni: None

Heart Failure in Clinical Practice - Facts U.S.A - Heart Failure Fact Sheet 2010

CPX in Cardiac Disease Determination of cardiopulmonary exercise capacity Differential diagnosis of exercise limitation Therapy control in heart failure Riskstratification in heart failure Decision for HTX

Cardiac Index - VO 2 Weber et al., Am. J. Cardiol., 1985

Weber-Classification Cardiopulmonary Exercise Capacity in Heart Failure Class Severity max. VO 2 [ml/kg/min] VO 2 AT [ml/kg/min] A mild to none > 20 > 14 B C mild to moderate moderate to severe 16-20 11 14 10-16 8-11 D severe 6-10 4-8 E very severe < 6 < 4 Weber et al., Am. J. Cardiol., 1985

ESC-Guidelines - Exercise Testing in CHF- Exercise tests only in stable heart failure Measured VO 2 better than estimated METs Individual exercise protocols (Ramp, Naughton) Work load increase by 1 MET 12.5% increase of increment (treadmill) 10-15 watt increase (bicycle) Optimal test duration 8-12 min. Walking test for submaximal exercise Eur Heart J, 21, 2001: 37-45

ESC-Guidelines - Exercise Testing in CHF - Risk-Stratification Peak VO 2 > 14 ml/kg/min: same prognosis as HTX Increase of peak VO 2 by 2.0 ml/kg/min < 6 months 2 years survival 100% * No influence on prognosis ** V E /VCO 2 -Slope < 35: good" prognosis * Stevenson et al., JACC 1995, 25: 163-70 Eur Heart J, 21, 2001: 37-45 ** Gullestad et al., Am Heart J 1998, 135: 221-9

Physiology of Exercise Peripheral Circulation Pulmonary Circulation Parameter of cardiopulmonary exercise capacity Obesity Myopathy Deconditioning CAD Dilative CMP Hypert. HD Valvular D. Anemia Obstructive LD Restrictive LD Infiltrative LD Wasserman et al., 2012

Exercise Limitation Impaired Exercise Capacity (Peak VO 2 / VO 2 AT)

Peak VO 2 and LV-EF L V - E F ( % ) Correlation in Chronic Heart Failure L V - E F ( % ) V - H e F T I V - H e F T P e a k V O P e a 2 k ( Vm O l / k g 2 ( m l / k g / m i n ) Cohn et al., Circ. 87, Suppl. VI, 1993, VI 5 - VI 16

Y e a r l y M o r t a l i t y 1-Year-Mortality in CHF V - H e F T I V - H e F T I V - H e F T I I Y e a r l y M o r t a l i t y LV-EF and peak VO 2 V - H e F T I I L V - E F ( % ) P e a k V O 2 ( m l / k g / Cohn et al., Circ. 87, Suppl. VI, 1993, VI 5 - VI 16

Risk-Stratification in CHF Peak VO 2 Pea k VO 2 (m l/kg /m in) Peak VO 2 (%predmax) Survival (%) > 1 8 1 4-1 8 1 0-1 4 < 1 0 * *p<0. 05 Event-free Survival (%) p<0.0001 > 50% predmax < 50% predmax Mo nths Follow-up (Months) Mancini et al., Circulation, 1991 Stelken et al., JACC 27, 1996: 349

Population Changes over time Agostoni et al., Int. J. Cardiology, 2012

Survival rate by years Agostoni et al., Int. J. Cardiology, 2012

MECKI score Research group Agostoni et al., Int. J. Cardiology, 2012

Population Agostoni et al., Int. J. Cardiology, 2012

Multivariable analysis Agostoni et al., Int. J. Cardiology, 2012

Survival rate by peak VO 2 (VO 2 <8, 10<VO 2 <8, VO 2 >10) VO2 CAT Total Failed Censored Percent Censored VO2<8 87 38 49 56.32 8<VO2<10 230 62 168 73.04 VO2>10 398 80 318 79.9 Total 715 180 535 74.83 Agostoni et al., Int. J. Cardiology, 2012

Lung Function in CHF 190 pts with HF O = p<0.01 o o o o o o o o o Agostoni PG, et al. Eur Heart J 2006; 27: 2538-43.

Ventilation in CHF Minuteventilation versus VO 2 Wasserman et al., Circ 96, 1997: 2221-2227

Ventilation in CHF Tidal volume versus V E Wasserman et al., Circ 96, 1997: 2221-2227

Cardiac Limitation Perfusion-Ventilation- Mismatch Hyperventilation V E vs VCO 2 -Slope

Ventilatory Efficiency V E CHF: Slope 59.9* "Threshold": 35 Therapy Training Normal: Slope 21.5* VCO 2 *Metra et al., Am J Cardiol, 70: 622, 1992 Chua et al. JACC,29: 1585-1590, 1997 Kleber et al., Circulation 101: 2803-09, 2000

Risk-Stratification in CHF Ventilatory Efficiency V E -vs-vco 2 -Slope 1 0.8 0.6 0.4 0.2 Cumulative Survival Low V E /VCO 2 -Slope High V E /VCO 2 -Slope 1 0.8 0.6 0.4 0.2 Cumulative Survival V E /VCO 2 -Slope <=130% V E /VCO 2 -Slope > 130% Days 540 Months 30 Chua et al., JACC,29: 1585-1590, 1997 Kleber et al., Circulation 101: 2803-09, 2000

Peak VO 2 - Prognostic Value - 1 Survival 0,9 0,8 Peak VO 2 > 14ml/kg/min (n=126) p < 0.001 0,7 0,6 Peak VO 2 < 14ml/kg/min (n=97) 0,5 0 6 12 18 24 Follow-up (Months) Gitt et al., Circulation 2002, 106: 3079-3084

VO 2 AT - Prognostic Value - 1 Survival VO 2 AT > 11ml/kg/min 0,9 0,8 (n=100) p < 0.001 0,7 VO 2 AT < 11ml/kg/min (n=106) 0,6 0,5 0 6 12 18 24 Follow-up (Months) Gitt et al., Circulation 2002, 106: 3079-3084

Prognostic Value - Median Follow-up 644 Days - Peak VO2 <= 14ml/kg/min Peak VO2 <= 50% pred 2.5 3.9 VE/VCO2-Slope > 34 VO2 AT < 11ml/kg/min 3.0 3.7 Peak VO2+VO2 AT Peak VO2+VE/VCO2-Slope VO2 AT+VE/VCO2-Slope 4.5 6.1 7.0 Lower Mortality 0,5 1 5 50 Higher Mortality Odds Ratio Gitt et al., Circulation 2002, 106: 3079-3084

Prognostic Value Early Mortality < 6 Months Peak VO2 <= 14ml/kg/min Peak VO2 <= 50% pred 1.5 3.4 VE/VCO2-Slope > 34 VO2 AT < 11ml/kg/min 4.8 5.3 Peak VO2 + VO2 AT Peak VO2+VE/VCO2-Slope VO2 AT+VE/VCO2-Slope 5.5 6.1 9.6 Lower Mortality 0,5 1 5 50 Higher Mortality Odds Ratio Gitt et al., Circulation 2002, 106: 3079-3084

CPX and Prognosis of CVD Reproducible test to estimate prognosis Old parameter VO 2 max with limitations Newer parameter VO 2 AT and V E /VCO 2 -Slope Independent on patient motivation Combination of VO 2 AT and V E /VCO 2 -Slope Determined in one exercise test Identifies CHF patients at high risk