René Gourgon

Prolonged Kinetics of Recovery of Oxygen Consumption After Maximal Graded Exercise in Patients With Chronic Heart Failure Analysis With Gas Exchange Measurements and NMR Spectroscopy

BACKGROUND Patients with chronic heart failure (CHF) often complain of prolonged dyspnea after exercise. The determinants of oxygen consumption after exercise in these patients are unknown. We hypothesized that the kinetics of oxygen consumption recovery after graded exercise was prolonged in parallel with the recovery of muscle energy stores, was not affected by the exercise level, and could be used to assess the circulatory response to exercise. METHODS AND RESULTS Seventy-two patients with CHF in Webers class A (n = 28), B (n = 21), and C/D (n = 23) and 13 healthy subjects performed maximal upright bicycle exercise with breath-by-breath respiratory gas analysis. Kinetics of recovery of ventilation (VE), oxygen consumption (VO2), and CO2 production (VCO2) after exercise were characterized by T1/2, the time to reach 50% of the peak value. T1/2 VO2 (seconds) increased with the severity of CHF (97 +/- 17 for CHF A [P < .05 versus CHF B, P < .05 versus CHF C/D], 119 +/- 22 for CHF B [P < .05 versus control subjects, P < .05 versus CHF A, and P < .05 versus CHF C/D], 155 +/- 55 for CHF C/D [P < .05 versus control subjects, P < .05 versus CHF A, and P < .05 versus CHF B] compared with 77 +/- 17 for control subjects). T1/2 VCO2 and T1/2 VE also increased similarly with the worsening of CHF. T1/2 VO2 was correlated negatively with peak VO2 (r = .65) and was reproducible (r = .96). To study the relation between T1/2 VO2 and the duration of exercise, 10 healthy subjects and 22 patients underwent a second graded test at 75% and/or 50% of peak workload. T1/2 VO2 was minimally shortened, at only 50% of peak workload (P = .02). Finally, 19 patients underwent 31P nuclear magnetic resonance spectroscopy of the anterior compartment of the leg during exercise; the half-time of recovery of the ratio of inorganic phosphate to creatine phosphate (T1/2 Pi/PCr), reflecting the level of involvement of oxidative metabolism in the restoration of energetic metabolites after exercise, was linearly correlated with the half-time of VO2 recovery (r = .70, P < .01). CONCLUSIONS Postexercise T1/2 VO2 increases when CHF worsens, perhaps in part a result of slower kinetics of recovery of muscle energy stores. The time course of oxygen consumption recovery may represent a simple new criterion for measuring the impairment of the circulatory response to exercise in CHF, even submaximal exercise.

Cardiac Metaiodobenzylguanidine uptake in patients with moderate chronic heart failure : Relationship with peak oxygen uptake and prognosis

OBJECTIVES This prospective study was undertaken to correlate early and late metaiodobenzylguanidine (MIBG) cardiac uptake with cardiac hemodynamics and exercise capacity in patients with heart failure and to compare their prognostic values with that of peak oxygen uptake (VO2). BACKGROUND The cardiac fixation of MIBG reflects presynaptic uptake and is reduced in heart failure. Whether it is related to exercise capacity and has better prognostic value than peak VO2 is unknown. METHODS Ninety-three patients with heart failure (ejection fraction <45%) were studied with planar MIBG imaging, cardiopulmonary exercise tests and hemodynamics (n = 44). Early (20 min) and late (4 h) MIBG acquisition, as well as their ratio (washout, WO) were determined. Prognostic value was assessed by survival curves (Kaplan-Meier method) and uni- and multivariate Cox analyses. RESULTS Late cardiac MIBG uptake was reduced (131+/-20%, normal values 192+/-42%) and correlated with ejection fraction (r = 0.49), cardiac index (r = 0.40) and pulmonary wedge pressure (r = -0.35). There was a significant correlation between peak VO2 and MIBG uptake (r = 0.41, p < 0.0001). With a mean follow-up of 10+/-8 months, both late MIBG uptake (p = 0.04) and peak VO2 (p < 0.0001) were predictive of death or heart transplantation, but only peak VO2 emerged by multivariate analysis. Neither early MIBG uptake nor WO yielded significant insights beyond those provided by late MIBG uptake. CONCLUSIONS Metaiodobenzylguanidine uptake has prognostic value in patients with wide ranges of heart failure, but peak VO2 remains the most powerful prognostic index.

Prevalence and significance of left ventricular filling abnormalities determined by Doppler echocardiography in young type I (insulin-dependent) diabetic patients

In 16 insulin-dependent diabetic patients, 36 +/- 8 years old with no microangiopathy, hypertension or coronary artery disease, and 16 healthy control subjects matched for sex, age and body surface area, the following parameters were obtained by Doppler-echocardiography: (1) end-diastolic left ventricular thickness and radius; (2) aortic pulse wave velocity; (3) mitral flow with measurement of early and late (atrial) peak velocities (E and A), pressure half-time and the velocity time integrals of the entire mitral curve and of the atrial wave; and (4) isovolumic relaxation time (i.e., the time between aortic closure and the mitral opening signals recorded simultaneously by continuous-wave Doppler). Heart rate and systolic blood pressure were not different in the 2 groups. Aortic pulse wave velocity and the wall thickness to radius ratio were significantly increased in the diabetic patients compared to the controls. E was significantly reduced whereas A/E, pressure half-time, the atrial contribution to the left ventricular filling (i.e., the ratio of the atrial velocity time integral to the mitral velocity time integral) and the isovolumic relaxation time were significantly increased in the diabetic group versus the control subjects. Lastly, 11 of 16 diabetic patients (69%) had at least 2 of the following abnormalities: A/E greater than 0.71, an atrial contribution to the left ventricular filling greater than 0.25, a pressure half-time greater than 50 ms and an isovolumic relaxation time greater than 88 ms. No correlations were found between the wall thickness to radius ratio, aortic pulse wave velocity and the filling indexes.(ABSTRACT TRUNCATED AT 250 WORDS)

Comparison of oxygen uptake during bicycle exercise in patients with chronic heart failure and in normal subjects

Prediction of oxygen uptake (VO2) during exercise from relations established in normal subjects between VO2 and work load in watts (W) may be inaccurate in patients with chronic heart failure because these patients could manifest delayed VO2 kinetics at final stages of exercise. To test the hypothesis that even at low levels of work, patients exhibit a lower VO2 than do normal subjects, 77 patients with heart failure and 27 control subjects with a normal heart or with disease other than heart failure underwent bicycle exercise with respiratory gas analysis. Work load was increased by 10 W/min from an initial 20 W. VO2 (ml/min per kg) was measured every 15 s. The delta VO2/delta W ratio was significantly reduced only in the most severely impaired patients in heart failure class C-D (8.75 +/- 2.14 versus 11.05 +/- 0.38, p less than 0.05). Class B patients showed a lower ratio at a work load of greater than or equal to 80 W, whereas class C-D patients manifested a lower ratio at greater than or equal to 20 W. Even with a low incremental work rate protocol, compared with sedentary normal subjects or patients without heart failure, patients with heart failure demonstrate impaired oxygen uptake. This observation suggests the presence of anaerobic metabolism or delayed VO2 uptake, or both; accordingly, indirect estimates of VO2 requirements derived from intensity or duration of exercise in such patients are overestimated.

Determinants of stroke volume response to exercise in patients with mitral stenosis: A doppler echocardiographic study

OBJECTIVES The aim of this study was to assess exercise-induced changes in stroke volume and their main determinants in mitral stenosis. BACKGROUND The mechanisms of the stroke volume response to exercise in mitral stenosis are not clearly established. METHODS Twenty-seven patients with mitral stenosis, aged 47 +/- 13 years, and 10 healthy control subjects, aged 46 +/- 11 years, were examined by Doppler echocardiography to obtain stroke volume, mitral velocity-time integral and calculated mitral valve area (by continuity equation) at rest and during submaximal supine bicycle exercise. Measured mitral valve area at rest and total mitral score were also obtained. RESULTS During exercise, stroke volume increased significantly (p < 0.001) in the control subjects (+25 +/- 6%) but remained unchanged in the patients. In 10 patients (Group I), stroke volume increased by > or = 14% (+23 +/- 10%, p < 0.001); in the other 17 (Group II), it decreased or increased by < 14% (-5 +/- 14%, p = NS). Mitral velocity-time integral did not change in the three groups, whereas calculated mitral valve area increased significantly (p < 0.001) and similarly in Group I and the control group but remained unchanged in Group II. The exercise change in calculated mitral valve area correlated significantly with both measured mitral valve area at rest (r = 0.46, p < 0.05) and total mitral score (r - 0.53, p < 0.005). However, at constant mitral score, exercise change in calculated mitral valve area no longer correlated significantly with measured mitral valve area at rest. CONCLUSIONS In mitral stenosis, the change in stroke volume during exercise depends on the change in mitral valve area, which itself depends on the degree of mitral valve damage.

Primary coronary angioplasty for acute myocardial infarction with contraindication to thrombolysis

Patients with acute myocardial infarction (AMI) and contraindication to thrombolysis have a high mortality and morbidity with conventional medical treatment. Among 226 consecutive patients hospitalized within 6 hours of the onset of Q-wave AMI, 45 (20%) had contraindications to thrombolysis. All were treated by emergent primary angioplasty. Mean age of the 45 patients was 60 +/- 11 years and 8 (18%) were > or = 70 years old; 17 (38%) had multivessel disease and 5 (11%) presented with cardiogenic shock. Successful angioplasty was achieved in 42 of the 45 patients (93%) 52 +/- 27 minutes after admission and 238 +/- 100 minutes after the onset of pain. Overall in-hospital mortality was 9% (4 of 45). Neither major bleeding nor stroke occurred. There was 1 case of early symptomatic reocclusion, treated with emergent repeat angioplasty without reinfarction. Predischarge angiography in 33 patients showed only 1 silent reocclusion (3%). Ejection fraction at discharge was 46 +/- 13%. Repeat catheterization at 6 months in 19 patients showed 4 restenoses (21%) and 4 reocclusions (21%) of the infarct-related artery. There were 3 late deaths (2 noncardiac), which gave survival rates of 87 and 85% at 1 and 3 years, respectively, and event-free survival rates of 71 and 69% including in-hospital deaths. There were no cases of late reinfarction. Consequently, in this series, primary coronary angioplasty proved safe and highly effective in rapidly restoring sustained infarct-vessel patency during AMI, and led to a greater improvement in early and late outcomes than that reported in the literature for medically treated subjects in this high-risk subset for which thrombolytic therapy is contraindicated.

Limits of reperfusion therapy for immediate cardiogenic shock complicating acute myocardial infarction

S everal investigators have demonstrated that aggressive reperfusion therapy, particularly emergency coronary angioplasty, effectively improves the poor prognosis of primary cardiogenic shock complicating acute myocardial infarction (AMI) by reducing in-hospital mortality from 80% to 90% to 15 mm Hg) using a Swan-Ganz catheter. In all cases, a mechanical complication was excluded by emergency echocardiography. The baseline clinical and angiographic characteristics of the patients are listed in Table I. Twelve patients (48%) were aged 270 years, 7 (28%) had prior AM, and 15 (60%) required prolonged cardiopulmonary resuscitation for >I5 minutes before or on admission. The location of AM was anterior in 16 patients (64%). In 3 patients, the infarct-related artery (diagnosed on the basis of total or subtotal occlusion and of the presence of intraluminal thrombus) was the left main trunk, and multiple acute coronary occlusions were observed in 2 others. Multivessel disease was present in 20 patients (80%). The emergency therapeutic interventions used are specified in Table II. Successful thrombolysis was defined as reperfusion of the infarct-related artery (grade 3 flow of the Thrombolysis in Myocardial Infarction trial) on

Ventilatory threshold during exercise in patients with mild to moderate chronic heart failure: determination, relation with lactate threshold and reproducibility.

Detection of the ventilatory threshold during exercise has been proposed in order to assess exercise tolerance in patients with chronic heart failure. The relation between the different methods of detecting the ventilatory threshold and the lactate threshold, however, and their reproducibility, have not really been assessed. Forty-three patients with chronic heart failure underwent an exercise test with respiratory gas analysis. A lactate threshold could be determined in 36 patients and a ventilatory threshold in 27 to 38 patients, depending on the method of determination of the ventilatory threshold. The greatest number of determinations (38) and the best correlation coefficient with the lactate threshold (r = 0.87 and 0.88, respectively) were obtained with the method of the ventilatory equivalent for oxygen and by averaging the different methods of determination. Reproducibility of the ventilatory threshold was only moderately good (r = 0.83) and less satisfactory than that of the peak oxygen uptake (r = 0.97). We conclude that unless the way of detecting the ventilatory threshold is improved in patients with chronic heart failure, the peak oxygen uptake will remain more reproducible.

Comparison using dynamic vectorcardiography and MIBI SPECT of ST-segment changes and myocardial MIBI uptake during percutaneous transluminal coronary angioplasty of the left anterior descending coronary artery

The quantitative relation between ST-segment changes and the severity and extent of myocardial ischemia during coronary occlusion remains unclear. This study assesses whether ST-segment changes during percutaneous transluminal coronary angioplasty (PTCA) correlate with the amount of myocardium at risk, measured with technetium-99m hexakis 2-methoxyisobutyl isonitrile (MIBI; also called sestamibi) single-photon emission computed tomography (SPECT). Quantitative continuous dynamic vectorcardiography was performed during PTCA of the left anterior descending coronary artery in 11 patients (mean age 64.3 years) without previous myocardial infarction. Change in the magnitude of the ST vector (STc-VM) was continuously recorded. A standardized protocol of balloon inflations was used and technetium-99m MIBI was injected intravenously at the onset of the third inflation. SPECT imaging was performed 60 minutes later and compared to a rest acquisition. SPECT was quantified by bulls-eye analysis using: (1) the change in the pathologic/normal area count ratio (delta P/N) as an index of the severity of ischemia; and (2) planimetered defect size during PTCA as an indicator of the size of the area at risk. The delta P/N from baseline to balloon occlusion (22 +/- 11%) was correlated, albeit loosely, to the maximum value of STc-VM (245 +/- 186 microV, r = 0.62, p < 0.05), but there was no correlation between the size of the scintigraphic defect and STc-VM. Likewise, the sum of ST-segment elevation was correlated to delta P/N (r = 0.72, p < 0.02), but not to the size of the scintigraphic defect.(ABSTRACT TRUNCATED AT 250 WORDS)

Patterns of myoglobin and MM creatine kinase isoforms release early after intravenous thrombolysis or direct percutaneous transluminal coronary angioplasty for acute myocardial infarction, and implications for the early noninvasive diagnosis of reperfusion.

Early noninvasive detection of reperfusion after thrombolysis for acute myocardial infarction may enable detection of unsuccessful thrombolysis in time for rescue percutaneous transluminal coronary angioplasty (PTCA). It has been suggested that repeated measurement of myoglobin or of MM creatine kinase (CK) isoforms enables early detection of reperfusion. Twenty consecutive patients with acute myocardial infarction treated by intravenous thrombolysis underwent serial determination of myoglobin, MM3 and MM1 CK isoforms every 30 minutes after the beginning of thrombolysis. At 90 minutes, coronary angiography was performed, enabling classification of patients as with (group A) and without (group B) reperfusion. A third group of 7 patients (group C) underwent direct PTCA without antecedent thrombolysis. In all groups, there were increases in myoglobin, percentage of MM3 isoform, and ratio of MM3/MM1. These increases appeared on the average steeper and faster in group B, but the large dispersion of values in this group resulted in a wide overlap with group A. Retrospective analysis suggests that an increase in the MM3/MM1 ratio > 0.35 after 60 minutes is very specific for reperfusion (sensitivity 60% and specificity 100%). In group C, PTCA always led to a sharp increase in all biochemical parameters measured within 30 minutes. Thus, macromolecular markers can be used for very early, noninvasive detection of reperfusion with a high specificity. This could help reduce the need for emergency angiography to select candidates for rescue PTCA. Furthermore, the patterns of biochemical markers of reperfusion differ when reperfusion is initiated by either thrombolysis or PTCA.