Lower peak VO(2)implies poorer prognosis across a range of values from 10 to 20 ml. kg(-1)min(-1), without a unique threshold. Gradations of elevation of the VE/VCO(2)slope also carry prognostic information over a wide range (30-55). The two parameters are comparable in terms of prognostic power, and contribute complementary prognostic information.

Background-In patients with chronic heart failure (CHF) and preserved exercise tolerance, the value of cardiopulmonary exercise testing for risk stratification is not known. Elevated slope of ventilatory response to exercise (V E/V CO 2 ) predicts poor prognosis in advanced CHF. Derangement of cardiopulmonary reflexes may trigger exercise hyperpnea. We assessed the relationship between cardiopulmonary reflexes and V E/V CO 2 and investigated the prognostic value of V E/V CO 2 in CHF patients with preserved exercise tolerance. Methods and Results-Among 344 consecutive CHF patients, we identified 123 with preserved exercise capacity, defined as a peak oxygen consumption (peak V O 2 ) Ն18 mL · kg Ϫ1 · min Ϫ1 (age 56 years; left ventricular ejection fraction 28%; peak V O 2 23.5 mL · kg Ϫ1 · min Ϫ1 ). Hypoxic and hypercapnic chemosensitivity (nϭ38), heart rate variability (nϭ34), baroreflex sensitivity (nϭ20), and ergoreflex activity (nϭ20) were also assessed. We identified 40 patients (33%) with high V E/V CO 2 (ie, Ͼ34.0). During follow-up (49Ϯ22 months, Ͼ3 years in all survivors), 34 patients died (3-year survival 81%). High V E/V CO 2 (hazard ratio 4.3, PϽ0.0001) but not peak V O 2 (Pϭ0.7) predicted mortality. In patients with high V E/V CO 2 , 3-year survival was 57%, compared with 93% in patients with normal V E/V CO 2 (PϽ0.0001). Patients with high V E/V CO 2 demonstrated impaired reflex control, as evidenced by augmented peripheral (Pϭ0.01) and central (Pϭ0.0006) chemosensitivity, depressed low-frequency component of heart rate variability (PϽ0.0001) and baroreflex sensitivity (Pϭ0.03), and overactive ergoreceptors (Pϭ0.003) compared with patients with normal V E/V CO 2 . Conclusions-In CHF patients with preserved exercise capacity, enhanced ventilatory response to exercise is a simple marker of a widespread derangement of cardiovascular reflex control; it predicts poor prognosis, which peak V O 2 does not. (Circulation. 2001;103:967-972.)

Objectives To develop prediction models that better estimate the pretest probability of coronary artery disease in low prevalence populations.Design Retrospective pooled analysis of individual patient data.Setting 18 hospitals in Europe and the United States.Participants Patients with stable chest pain without evidence for previous coronary artery disease, if they were referred for computed tomography (CT) based coronary angiography or catheter based coronary angiography (indicated as low and high prevalence settings, respectively). Main outcome measuresObstructive coronary artery disease (≥50% diameter stenosis in at least one vessel found on catheter based coronary angiography). Multiple imputation accounted for missing predictors and outcomes, exploiting strong correlation between the two angiography procedures. Predictive models included a basic model (age, sex, symptoms, and setting), clinical model (basic model factors and diabetes, hypertension, dyslipidaemia, and smoking), and extended model (clinical model factors and use of the CT based coronary calcium score). We assessed discrimination (c statistic), calibration, and continuous net reclassification improvement by cross validation for the four largest low prevalence datasets separately and the smaller remaining low prevalence datasets combined. ResultsWe included 5677 patients (3283 men, 2394 women), of whom 1634 had obstructive coronary artery disease found on catheter based coronary angiography. All potential predictors were significantly associated with the presence of disease in univariable and multivariable analyses. The clinical model improved the prediction, compared with the basic model (cross validated c statistic improvement from 0.77 to 0.79, net reclassification improvement 35%); the coronary calcium score in the extended model was a major predictor (0.79 to 0.88, 102%). Calibration for low prevalence datasets was satisfactory.Conclusions Updated prediction models including age, sex, symptoms, and cardiovascular risk factors allow for accurate estimation of the pretest probability of coronary artery disease in low prevalence populations. Addition of coronary calcium scores to the prediction models improves the estimates. IntroductionIn the United States, about 10.2 million people have chest pain complaints each year, 1 and more than 1.1 million diagnostic procedures of catheter based coronary angiography are performed on inpatients each year. 2 In a recent report based on the national cardiovascular data registry of the American College of Cardiology, 3 only 41% of patients undergoing elective procedures of catheter based coronary angiographies are diagnosed with obstructive coronary artery disease. The report's authors concluded that better risk stratification was needed, underlined by decision analyses showing that the choice of further diagnostic investigation in patients with chest pain depends primarily on the pretest probability of coronary artery disease. [4][5][6] The American College of Cardiology/American Heart Associatio...

OUES provides an effective, independent measure of pathological exercise physiology. Its numerical value is relatively insensitive to the duration of exercise data from which it is calculated. Its prognostic value seems to be stronger than the best available existing measures of exercise physiology.

Background-In patients with chronic heart failure (CHF), periodic breathing (PB) predicts poor prognosis. Clinical studies have identified numerous risk factors for PB (which also includes Cheyne-Stokes respiration). Computer simulations have shown that oscillations can arise from delayed negative feedback. However, no simple general theory quantitatively explains PB and its mechanisms of treatment using widely-understood clinical concepts. Therefore, we introduce a new approach to the quantitative analysis of the dynamic 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 determine 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 (␦), alveolar volume (V L ), and end-tidal CO 2 fraction (C ), were applied to the stability formula. The breathing pattern was correctly predicted in 28 of the 30 subjects. The principal combined parameter (C S)ϫ(␦/V L ) was higher in patients with PB (14.2Ϯ3.0) than in those without PB (3.1Ϯ0.5; Pϭ0.0005) or in normal controls (2.4Ϯ0.5; Pϭ0.0003). This was because of differences in both chemoreflex sensitivity (1749Ϯ235 versus 620Ϯ103 and 526Ϯ104 L/min per atm CO 2 ; Pϭ0.0001 and PϽ0.0001, respectively) and chemoreflex delay (0.53Ϯ0.06 vs 0.40Ϯ0.06 and 0.30Ϯ0.04 min; PϭNS and Pϭ0.02). Conclusion-This analytical approach identifies the physiological abnormalities that are important in the genesis of PB and explicitly defines the region of predicted instability. The clinical data identify chemoreflex gain and delay time (rather than hyperventilation or hypocapnia) as causes of PB.