Quantitative general theory for periodic breathing in chronic heart failure and its clinical implications

Background-in patients with chronic heart failure (CHF), periodic breathing (PB) predicts poor prognosis. Clinical studies have identified numerous ri sk factors for PB (which also includes Cheyne-Stokes respiration). Computer simulations have shown that oscillations can arise from delayed negative f eedback. However, no simple general theory quantitatively explains PB and i ts mechanisms of treatment using widely-understood clinical concepts. There fore, we introduce a new approach to the quantitative analysis of the dynam ic physiology governing cardiorespiratory stability in CHF. Methods and Results-An algebraic formula was derived (presented as a simple 2D plot), enabling prediction from easily acquired clinical data to determ ine whether respiration will be unstable. Clinical validation was performed in 20 patients with CHF (10 with PB and 10 without) and 10 healthy normal subjects. Measurements, including chemoreflex sensitivity (S) and delay (de lta), alveolar volume (V-L), and end-tidal CO2 fraction ((C) over bar), wer e applied to the stability formula. The breathing pattern was correctly pre dicted in 28 of the 30 subjects. The principal combined parameter ((C) over barS)X(delta /V-L) was higher in patients with PB (14.2+/-3.0) than in tho se without PB (3.1+/-0.5; P=0.0005) or in normal controls (2.4+/-0.5; P=0.0 003). This was because of differences in both chemoreflex sensitivity (1749 +/-235 versus 620+/-103 and 526+/-104 L/min per atm CO2; P=0.0001 and P<0.0 001, respectively) and chemoreflex delay (0.53+/-0.06 vs 0.40+/-0.06 and 0. 30+/-0.03 min; P=NS and P=0.02). zConclusion-This analytical approach identifies the physiological abnormali ties that are important in the genesis of PB and explicitly defines the reg ion of predicted instability. The clinical data identify chemoreflex gain a nd delay time (rather than hyperventilation or hypocapnia) as causes of PB.