Markers of thrombin generation are associated with myocardial necrosis and left ventricular impairment in patients with ST-elevation myocardial infarction.

INTRODUCTION: Platelet activation, thrombin generation and fibrin formation play important roles in intracoronary thrombus formation, which may lead to acute myocardial infarction. We investigated whether the prothrombotic markers D-dimer, pro-thrombin fragment 1 + 2 (F1 + 2) and endogenous thrombin potential (ETP) are associated with myocardial necrosis assessed by Troponin T (TnT), and left ventricular impairment assessed by left ventricular ejection fraction (LVEF) and N-terminal pro b-type natriuretic peptide (NT-proBNP). MATERIALS/METHODS: Patients (n = 987) with ST-elevation mycardial infarction (STEMI) were included. Blood samples were drawn at a median time of 24 h after onset of symptoms. RESULTS: Statistically significant correlations were found between both peak TnT and D-dimer (p < 0.001) and F1 + 2 (p < 0.001), and between NT-proBNP and D-dimer (p = 0.001) and F1 + 2 (p < 0.001). When dividing TnT and NT-proBNP levels into quartiles there were significant trends for increased levels of both markers across quartiles (all p < 0.001) D-dimer remained significantly associated with NT-proBNP after adjustments for covariates (p = 0.001) whereas the association between NTproBNP and F1 + 2 was no longer statistically significant (p = 0.324). A significant inverse correlation was found between LVEF and D-dimer (p < 0.001) and F1 + 2 (p = 0.013). When dichotomizing LVEF levels at 40 %, we observed significantly higher levels of both D-dimer (p < 0.001) and F1 + 2 (p = 0.016) in the group with low EF (n = 147). SUMMARY/CONCLUSION: In our cohort of STEMI patients we demonstrated that levels of D-dimer and F1 + 2 were significantly associated with myocardial necrosis as assessed by peak TnT. High levels of these coagulation markers in patients with low LVEF and high NTproBNP may indicate a hypercoagulable state in patients with impaired myocardial function.

Tissue Doppler imaging describes diastolic function in men prone to develop hypertension over twenty years.

AIMS: Hypertension is one of several risk factors of cardiovascular disease and is associated with left ventricular (LV) systolic and diastolic dysfunction. A method for reliably detecting the onset of LV dysfunction before transition to irreversible damage of the myocardium would be of crucial importance in subjects with essential hypertension. METHODS AND RESULTS: Subjects with clear differences in BP level, development and duration of the hypertensive disease were examined at the age of 60 yrs: normotensives (n = 17), new hypertensives who developed hypertension over a 20 year period (n = 15) and hypertensives (n = 19). Relationships between conventional echocardiographic and tissue velocities imaging (TVI) parameters compared to LV parameters, and TVI as an estimate of LV function were explored. E'(Lat) (TVI peak early diastolic velocity) (P = 0.006) and E/E'(Lat) (P = 0.002) demonstrated differences in diastolic function between the groups. There were no significant differences regarding systolic myocardial velocities. E'(Lat) correlated to S'(Lat) (TDI peak systolic velocity) (r = 0.32, P = 0.026) and was independently predicted by S'(Lat) (R(2) = 0.24, P = 0.025) in multivariate analysis. E'(Lat) correlated negatively to LV mass index (r = -0.34, P = 0.012), also in multivariate regression analysis (R(2) = 0.12, P = 0.032). CONCLUSIONS: Myocardial diastolic velocities and mitral flow to annulus velocity ratio differentiated LV function between the hypertensive and normotensive groups. The parameters probably reflect changes in relaxation, recoil and contraction and parallel changes in LV mass index.

Effects of preload alterations on peak early diastolic mitral annulus velocities evaluated by tissue Doppler echocardiography.

BACKGROUND AND OBJECTIVE: Tissue Doppler echocardiography is proposed to be a relatively preload independent tool for assessment of diastolic function. No data exist on anaesthetized patients in whom myocardial contractility, vascular tone and baroreceptor reflexes are depressed. The aim of this study was to evaluate the effects of preload alterations on tissue velocities in patients during general anaesthesia for coronary arterial bypass surgery. METHODS: Fifteen patients referred for elective aorto-coronary bypass surgery were examined by tissue Doppler echocardiography. Early diastolic velocities in the septal and lateral portion of the mitral annulus were measured during preload interventions induced by tilting of the operating table in patients during general anaesthesia both before surgery and after chest closure. To verify changes in preload we used right atrial pressure and pulmonary artery occlusion pressure. RESULTS: Tissue velocities in both the septal and lateral portion of the mitral annulus were significantly higher when preload was increased, compared to when it was decreased. Alterations in diastolic velocities in the septal portion of the mitral annulus prior to surgery: 0.8 +/- 0.2 cm s-1, P < 0.001, after surgery: 1.1 +/- 0.2 cm s-1, P < 0.001. Alterations in diastolic velocities in the lateral portion of the mitral annulus prior to surgery: 1.4 +/- 0.2 cm s-1, P < 0.001, after surgery: 1.1 +/- 0.3 cm s-1, P < 0.01. Concomitant changes in right atrial pressure and pulmonary artery occlusion pressure were 11 +/- 1 and 12 +/- 1 mmHg before surgery and 13 +/- 1 and 12 +/- 1 mmHg after surgery (P < 0.001 for all), respectively. CONCLUSION: These results show that tissue velocities of the mitral annulus are preload dependent in patients during general anaesthesia both before and after coronary surgery.

Effects of treatment with a 5-HT4 receptor antagonist in heart failure.

BACKGROUND AND PURPOSE: Positive inotropic responses (PIR) to 5-hydroxytryptamine (5-HT) are induced in the left ventricle (LV) in rats with congestive heart failure (CHF); this is associated with upregulation of the G(s)-coupled 5-HT(4) receptor. We investigated whether chronic 5-HT(4) receptor blockade improved cardiac function in CHF rats. EXPERIMENTAL APPROACH: Rats were given either the 5-HT(4) antagonist SB207266 (0.5 mg kg(-1) 24h(-1); MI(int)) or placebo (MI(pl)) through mini-osmotic pumps for 6 weeks subsequent to induction of post-infarction CHF. In vivo cardiac function and ex vivo responses to isoprenaline or 5-HT were evaluated using echocardiography and isolated LV papillary muscles, respectively. mRNA levels were investigated using real-time quantitative RT-PCR. KEY RESULTS: LV diastolic function improved, with 4.6% lower LV diastolic diameter and 24.2% lower mitral flow deceleration in MI(int) compared to MI(pl). SB207266 reduced LV systolic diameter by 6.1%, heart weight by 10.2% and lung weight by 13.1%. The changes in posterior wall thickening and shortening velocity, cardiac output, LV systolic pressure and (dP/dt)(max), parameters of LV systolic function, did not reach statistical significance. The PIR to isoprenaline (10 microM) increased by 36% and the response to 5-HT (10 microM) decreased by 57% in MI(int) compared to MI(pl). mRNA levels for ANP, 5-HT(4(b)) and 5-HT(2A) receptors, MHCbeta, and the MHCbeta/MHCalpha -ratio were not significantly changed in MI(int) compared to MI(pl). CONCLUSIONS AND IMPLICATIONS: Treatment with SB207266 to some extent improved in vivo cardiac function and ex vivo myocardial function, suggesting a possible beneficial effect of treatment with a 5-HT(4) receptor antagonist in CHF.

Defective excitation-contraction coupling in hearts of rats with congestive heart failure.

AIM: We examined the cellular basis for depressed cardiac contractility in rats with congestive heart failure (CHF) secondary to myocardial infarction. METHODS: Six weeks after ligation of the left coronary artery, CHF was confirmed by haemodynamic measures and echocardiographic demonstration of reduced myocardial contractility in vivo. Papillary muscles from CHF animals developed less force than those from sham operated (SHAM) animals. Cell shortening was measured in isolated ventricular myocytes voltage-clamped with high resistance electrodes. Ca2+ transients were measured in fluo-4 loaded myocytes. RESULTS: Contractions triggered by depolarizing test steps from a post conditioning potential of -70 mV were significantly smaller and had significantly reduced velocity of shortening in CHF compared with SHAM myocytes. However, contractions initiated from -40 mV, were similar in amplitude and velocity of shortening in CHF and SHAM cells. L-type Ca2+ current was not significantly different between CHF and SHAM cells, whether activated from -70 or -40 mV. Therefore, in SHAM cells, excitation-contraction coupling exhibited higher gain when contractions were initiated from negative (-70 mV), as compared with depolarized potentials (-40 mV). However, in CHF myocytes, excitation-contraction coupling gain was selectively depressed with steps from -70 mV. This depression of gain in CHF was not accompanied by a significant reduction in sarcoplasmic reticulum Ca2+ content. Isoproterenol increased Ca2+ transients less in CHF than SHAM myocytes. CONCLUSION: In this post-infarction model of CHF, the contractile deficit was voltage dependent and the gain of excitation-contraction coupling was selectively depressed for contractions initiated negative to -40 mV.

Natriuretic peptides in patients with aortic stenosis.

BACKGROUND: Whereas atrial natriuretic peptide (ANP) is secreted mainly from cardiac atria, brain natriuretic peptide (BNP) is produced to a larger extent in ventricles. Their relative importance as markers of cardiac function and myocardial hypertrophy is not yet clarified. This study evaluated circulating BNP and ANP and the N-terminal part of their propeptides (NT-proBNP and NT-proANP) as markers of left ventricular hypertrophy and atrial pressure increase in patients with aortic stenosis. METHODS: The plasma concentrations of BNP, NT-proBNP, ANP, and NT-proANP were measured by radioimmunoassay in 67 patients with aortic stenosis. Peptide plasma concentrations were related to measurements obtained by cardiac catheterization and echocardiography. RESULTS: Receiver operating characteristic curves indicated that BNP and NT-proBNP performed best in the detection of increased left ventricular mass and NT-proANP in the detection of increased left atrial pressure. NT-proBNP was significantly increased in mild left ventricular hypertrophy (left ventricular mass index, 78 to 139 g/m(2)), whereas NT-proANP was not increased until left ventricular mass index was 141 to 180 g/m(2). CONCLUSIONS: Plasma BNP and NT-proBNP may serve as early markers of left ventricular hypertrophy, whereas ANP and NT-proANP reflect left atrial pressure increase. The repeated and combined measurements of natriuretic peptides might provide diagnostic information relevant to the evaluation of the stage of aortic stenosis.

High frame rate Doppler echocardiography in the rat: an evaluation of the method.

AIMS: In small animal models, two-dimensional (2D) and Doppler echocardiography should provide more information than M-mode, especially in animals with infarcted and distorted left ventricles, but has been limited by low frame rates and poor near field resolution. New, high frame rate echo-Doppler equipment with digital processing was tested for accuracy of measurements. METHODS AND RESULTS: Fourteen normal Wistar rats (232-328 g) were examined under halothane anaesthesia. Pulsed Doppler recordings from both left ventricular outflow tract(LVOT) and right ventricular outflow tract (RVOT) cor-responded well with simultaneous ultrasound transit time measurements of aortic flow (LVOT: v=0.99x+4.8, min R=0.93. Standard error of estimate (SEE)=8.3 ml x min(-1), and RVOT: v=0.97x -4.3. R=0.93. SEE =8.4 ml x min(-1). No systematic differences were observed over a flow range of 20-90 ml x min(-1). Left ventricular (LV) dimensions assessed by 2D parasternal long-axis and short-axis views were equal to M-mode measurements with LV diameter 6.6 + 0.44 mm, anterior wall 1.8 +/- 0.18 mm, and posterior wall 1.5 + 0.56 mm. Mean absolute difference 4.4-8.5%. Intra- and interobserver variability was 4.6 +/- 4.1% and 6.7 +/- 7.0% for Doppler measurements, and 4.3 +/- 3.8% and 3.8 +/- 4.6% for dimensions, respectively. CONCLUSION: High frame rate Doppler echocardiography provides accurate non-invasive measurements of cardiac structure and function in the rat.

Echocardiographic criteria for detection of postinfarction congestive heart failure in rats.

We evaluated postinfarction myocardial function in rats and determined echocardiographic criteria for congestive heart failure (CHF) using high performance echocardiography. Extensive myocardial infarction (MI) was induced in rats by left coronary occlusion. Sham-operated animals served as controls. Five weeks later, high-frame rate ( approximately 200 Hz), fully digitized, shallow-focus (10-25 mm), two-dimensional, M-mode and Doppler echocardiography was performed. A J-tree cluster analysis was performed using parameters indicative of CHF. Reproducibility was examined. The cluster analysis joined the animals into one Sham and two MI clusters. One of the MI clusters had clinical characteristics of CHF and elevated left ventricular end diastolic pressure. Among the echocardiographic variables, only posterior wall shortening velocity separated the failing and nonfailing MI clusters. We conclude that, by high frame rate echocardiography, it is possible to obtain high- quality recordings in rats. It is feasible to distinguish MI rats with CHF due to myocardial dysfunction from those without failure and to perform longitudinal studies on myocardial function.

Cyclosporin A inhibits cardiac hypertrophy and enhances cardiac dysfunction during postinfarction failure in rats.

Calcineurin has recently been implicated as a mediator in the signaling pathways that transform intracellular calcium signals to the phenotype of myocardial hypertrophy. The present study was conducted to examine the effects of cyclosporin A (CsA), an inhibitor of calcineurin, on myocardial hypertrophy and remodeling during congestive heart failure (CHF) in rats. After ligation of the left coronary artery, rats were randomized to treatment with CsA or vehicle for 14 days. Compared with vehicle, CsA substantially attenuated myocardial hypertrophy in the CHF rats as assessed by alterations in ventricular weight-to-tibial length ratios (P < 0.05). Myocardial gene expression of skeletal alpha-actin was also reduced in the failing left ventricle (LV) after treatment with CsA (P < 0. 05), although the mRNA levels were still substantially elevated relative to those of sham rats. CsA-induced inhibition of compensatory myocardial hypertrophy in the CHF rats led to increased dilatation of the LV cavity and reduced fractional shortening and peak positive and negative first derivatives of LV pressure (P < 0. 05). Plasma renin and endothelin-1 levels were increased in the CHF-CsA rats, providing humoral cues of aggravated cardiac function. Thus this study supports a crucial role of calcineurin-dependent pathways in the mechanisms of compensatory myocardial hypertrophy during CHF. In addition, our data indicate that inhibition of compensatory myocardial hypertrophy exerts detrimental effects on cardiac remodeling and function after myocardial infarction.

Left atrial volumes assessed by three- and two-dimensional echocardiography compared to MRI estimates.

OBJECTIVES: The aim of the present study was to establish the accuracy and reproducibility of left atrial volume measurements by three-dimensional (3D) echocardiography compared to 2D biplane and monoplane measurements. BACKGROUND: No echocardiographic technique is generally accepted as optimal for estimation of left atrial size. METHODS: Left atrial volumes of 18 unselected cardiac patients were obtained with magnetic resonance imaging (MRI) (volumes 145 +/- 58 ml). These volumes were compared with those obtained with different echocardiographic methods: a multiplane 3D method based on 90 images acquired by apical probe rotation, a simplified 3D method using only the three standard apical views, and 2D biplane and monoplane methods based on area-length, disc summation and spherical formulas. RESULTS: The echocardiographic methods significantly underestimated maximum left atrial volumes as obtained by MRI by 14-37% (p < 0.001). Accuracy, expressed as 1 SD of individual estimates around this systematic underestimation, was 25 to 27% for all methods, except for the 2D 2-chamber monoplane method (37%). Interobserver coefficient of variation was between 14 and 20% for all methods (n.s.). CONCLUSION: All echocardiographic methods significantly underestimated left atrial volumes as obtained by MRI. A minor non-significant improvement in individual echocardiographic estimates by the 3D methods was obtained at the cost of more time consumption. In unselected patients ultrasound image quality precludes significant improvement of left atrial volume measurements by the applied 3D methods.

Reversal of intraventricular flow propagation during isovolumic relaxation: A marker of anterior wall dysfunction.

BACKGROUND: Myocardial infarction induces left ventricular (LV) wall motion abnormalities during isovolumic relaxation (IVR) and may potentially alter intraventricular flow during this period. This study evaluated whether 2-dimensional color Doppler measurements of intraventricular flow during IVR were able to identify LV dysfunction caused by coronary artery disease. METHODS: Patients with single-vessel coronary artery disease and posterior wall infarction (21 patients) or anterior wall infarction (27 patients) were included. Eighteen healthy persons served as a control group. LV function was examined by 2-dimensional echocardiography, 2-dimensional color Doppler, and pulsed Doppler techniques. RESULTS: All normal persons (23.6 +/- 10.9 cm/s) and patients with posterior infarction (19.6 +/- 9.3 cm/s) had flow propagation towards LV apex during IVR. Patients with anterior wall infarction had reversed flow direction (-12.2 +/- 8.7 cm/s, P <.001). The echocardiographic wall motion score index of the 4 apical segments correlated well with flow velocities (r = -0.78, P <.001). CONCLUSION: Reversed flow propagation during IVR may become a sensitive clinical marker of regional ischemia.

Diastolic flow pattern in the normal left ventricle.

OBJECTIVES: This study sought to clarify the diastolic flow pattern in the normal left ventricle. BACKGROUND: During left ventricular filling, basally directed (retrograde) velocities are seen in the outflow compartment. These velocities may represent blood returned from the apical region or a shortcut at a more basal level. METHODS: Left ventricular flow patterns were identified in 18 healthy individuals (age 47 +/- 12 years) with the use of high frame-rate two-dimensional color Doppler and color M-mode Doppler echocardiography techniques. Intraventricular velocities were measured with single pulsed Doppler at 3 levels in both inflow and outflow compartments (posterolateral and anteroseptal parts of the left ventricle). RESULTS: During early transmitral flow acceleration, all intraventricular velocities were directed towards the apex. However, after peak early and late inflow velocities and during diastasis, retrograde velocities were identified in the outflow compartment. These retrograde velocities occurred earlier, and were higher, at the level of the deflected anterior mitral leaflet tip compared with more apical levels (P <.001). A velocity pattern was established, consistent with early intraventricular vortex formation behind both mitral leaflets. The vortex adjacent to the anterior leaflet subsequently enlarged to include a major part of the left ventricle. CONCLUSION: Uniform diastolic flow patterns were identified in the normal left ventricles. The findings suggest that both early and late diastolic filling start with an initial motion of a fluid column, succeeded by vortex formation, which explains retrograde flow in the outflow compartment.

[Current use of beta-blockers in coronary artery disease]. / Aktuell bruk av beta-blokkere ved koronar hjertesykdom.

This article presents the results of a retrospective analysis of the use of beta-blockers and current dosing of these agents in patients with coronary artery disease. While 70 to 78% of patients admitted to Norwegian university hospitals during 1990-1997 for angiographic evaluation of chest pain used beta-blockers, only 43-60% of patients with stable coronary artery disease enrolled in the 4S study in Norway received such treatment. High risk groups such as diabetics and patients with peripheral artery disease were less likely to receive beta-blockers during the early period, but were not treated differentially compared to low risk patients during recent years. Only 15% of patients with congestive heart failure received oral beta-blockers, and only 10.5% intravenous beta-blockade during acute myocardial infarction. The dosing of the most common beta-blockers were low, approximately 50% of doses shown to improve survival after acute myocardial infarction.

Left ventricular volumes assessed by different new three-dimensional echocardiographic methods and ordinary biplane technique.

UNLABELLED: Three-dimensional (3D) echocardiography may overcome the problems with inadequate accuracy and reproducibility of 2D volume measurements of the left ventricle. AIMS: To establish the in vitro accuracy and reproducibility of two new methods for 3D echocardiographic volume determination as compared to biplane measurements. METHODS: Validation of volume measurements by a multiplane 3D method was performed on asymmetric latex phantoms (n = 8, true volumes 45-304 ml) using rotational acquisition of 90 image planes. Porcine agarose-filled asymmetrical left ventricles (n = 7, true volumes 34-280 ml) were measured by the same multiplane 3D method based on images acquired by probe rotation axis perpendicular (A) and parallel (B) to the ventricular long axis. Ventricular volumes were also obtained by a simplified 3D system using only the three standard apical views (C) and by the ordinary biplane Simpson's method (D). RESULTS: On latex phantoms systematic deviation from true volumes by multiplane 3D was less than 2%, and 95% variability of individual measurements from this mean was +/- 4.9%. For accuracy on left ventricles, systematic bias was small with all the methods (< 5%), but 95% variability of individual measurements was +/- 9.0%, 15.4%, 18.8% and 41.3% of true volumes for methods A-D respectively. Corresponding results in the same range were obtained for inter- and intraobserver variability. CONCLUSION: Individual in vitro volume estimates of left ventricles are of similar quality using apical multiplane or apical triplane 3D echocardiography. Both methods were superior to the ordinary apical biplane method, but inferior to multiplane 3D method with the probe directed perpendicular to the ventricular long axis.

[Mortality and morbidity after coronary bypass surgery in high-risk patients]. / Dødelighet og sykelighet etter koronar bypasskirurgi hos høyrisikopasienter.

A total of 113 women and 912 men were submitted to coronary artery bypass surgery at Surgical Department A, Rikshospitalet between August 1982 and December 1986 and followed till January 1993. We found no difference in early mortality, recurrent angina pectoris or non-fatal myocardial infarction in diabetic patients compared to nondiabetic patients. However, total mortality was 1.87 times higher in the diabetic group. For patients with ejection fraction < or = 40%, early mortality was 10.2 times higher than for the reference group. For total mortality we found a practically linear relationship between increased mortality and falling ejection fraction values. We found no relationship between ejection fraction and recurrent angina and non-fatal myocardial infarction, neither did we find any difference in mortality and morbidity between women and men. Although a somewhat higher mortality and morbidity rate must be expected for high-risk patients, they seem to profit to the same extent from the favourable effects of coronary bypass surgery as other patients.

Left ventricular mass assessed by three-dimensional echocardiography using rotational acquisition.

BACKGROUND: The reproducibility of left ventricular (LV) mass measurement by two-dimensional (2-D) echocardiography is inadequate for individual assessments. HYPOTHESIS: This study was undertaken to evaluate the potential of LV mass determination with a new three-dimensional (3-D) echocardiographic method compared with 2-D measurements. METHODS: Porcine agarose-filled left ventricles (n = 15, true mass 61-511 g) of different shapes were measured by a multiplane 3-D method based on 90 images acquired by probe rotation axis (1) perpendicular and (2) parallel to the ventricular long axis ["parasternal" (the left sternal border was not present as a reference point in this study) and apical views]. Mass was also obtained using (3) the biplane truncated ellipsoid and (4) area-length methods, as well as (5) the modified cube formula. Five hearts were not analyzed with the apical 3-D technique because of insufficient image quality. RESULTS: Systematic deviation from true mass was small with all methods (< 5.3%). Accuracy, expressed as 1 standard deviation of individual estimates around this systematic bias, was 7.7, 13.6, 8.2, 11.9, and 11.9% of true mass for the methods 1-5, respectively. Interobserver reproducibility, expressed as the coefficient of variation, was 4.7, 8.8, 8.1, 8.9, and 9.4% for the same methods. CONCLUSION: Limits for individual accuracy and reproducibility of LV mass estimates are nearly doubled using apical compared with "parasternal" 3-D echocardiography in vitro. A main advantage of "parasternal" 3-D compared with 2-D LV mass estimates is better reproducibility, but at the expense of greater time consumption. Apical 3-D technique is not superior to simpler 2-D methods based on "parasternal" short axis imaging.

Gas exchange and neurohumoral response to exercise: influence of the exercise protocol.

Maximal oxygen uptake varies with the exercise protocol, but the extent to which hormonal and metabolic responses to exercise are influenced by the exercise protocol has not been precisely defined. Twelve healthy subjects underwent maximal exercise testing using two incremental bicycle tests with individualized, identical work rate increments between 40 and 70 W. One protocol employed a 1-min and the other a 3-min duration per stage. Expiratory gas and venous blood were sampled at regular intervals for metabolic and hormonal analysis. Exercise duration for the 1-min and 3-min protocols was 6.0 +/- 0.1 and 14.3 +/- 0.3 min, respectively (P < 0.001). Significantly higher values were observed for peak VO2 and maximal ventilation during the 3-min protocol compared with the 1-min protocol (41.1 +/- 1.8 vs 38.3 +/- 1.6 ml.kg-1.min-1, P < 0.001; and 104.9 +/- 8.0 vs 97.2 + 5.7 l.min-1, P < 0.05, for peak VO2 and peak ventilation, respectively). However, the maximal workload achieved was higher during the 1-min versus the 3-min protocol (330 + 24 vs 280 + 21 W, P < 0.01). No differences were observed for maximal heart rate or blood pressure, whereas maximal plasma lactate was roughly twice as high during the 3-min compared with the 1-min protocol (7.5 +/- 0.8 vs 3.8 +/- 0.5 mmol.l-1, P < 0.001). Norepinephrine, epinephrine, dopamine, and growth hormone levels were generally higher throughout exercise during the 3-min compared with the 1-min protocol. When expressed as a percentage of peak VO2, however, differences in catecholamine levels were not observed. Endothelin levels did not change. We conclude that the exercise protocol profoundly influences exercise capacity as well as the metabolic and hormonal response to exercise and should be considered when using these variables to evaluate an intervention.

Hemodynamic characterization of the CarboMedics mitral valve prosthesis.

BACKGROUND AND AIMS OF THE STUDY: The hemodynamic function of the CarboMedics bileaflet mitral valve prosthesis was evaluated by Doppler echocardiography and by heart catheterization. The clinical state of the invasively examined patients was evaluated before and after surgery. METHODS: Doppler echocardiography was performed in 54 patients at six months after surgery. Further, combined right and left heart catheterization was performed in 22 of these patients before surgery and at six months thereafter. RESULTS: The Doppler mean gradients were small (3.6 +/- 1.2 mmHg), and corresponded well with Doppler mean gradients in the subgroup examined with both methods (3.5 +/- 1.1 mmHg) and with the invasive gradients (3.4 +/- 1.9 mmHg); there was also no difference between the different valve sizes. Clinically, pressure recovery distal to the valve is probably so small that no systematic difference between the two techniques of measurement is present. Only physiological regurgitation was found, and no case of valve dysfunction. The patients improved from functional NYHA class 3.1 +/- 0.4 to 1.4 +/- 0.6, regardless of preoperative diagnosis, with most pronounced improvement in those with mitral stenosis. Pulmonary artery pressure was normalized. Pulmonary vascular resistance and cardiac index improved slightly. CONCLUSIONS: In conclusion, the valvular prostheses demonstrated excellent hemodynamic function. There was striking agreement between the small invasive and non-invasive gradients. Finally, the functional status of the patients improved considerably, most distinctly in those patients with prior mitral stenosis.

Exercise capacity of heart transplant recipients: the importance of chronotropic incompetence.

BACKGROUND: Maximal exercise capacity is limited in patients after heart transplantation. The extent to which chronotropic incompetence contributes to this intolerance has not been well defined. METHODS: This prospective cross-sectional study examined the heart rate response to exercise and its relation to exercise capacity in 159 heart transplant recipients during progressive, symptom-limited, upright exercise. All prior exercise studies of heart transplant recipients that reported peak oxygen uptake and peak heart rate were also evaluated. RESULTS: Peak oxygen uptake was closely correlated with peak heart rate (r = 0.39, p < 0.001) and maximum increase in heart rate (r = 0.49, p < 0.001) during exercise by our patients. Similar correlations were found in the published studies for peak oxygen uptake versus maximal heart rate (r = 0.54, p < 0.05) and peak oxygen uptake versus increase in heart rate (r = 0.63, p < 0.02). The current study showed that the increase in heart rate from rest to peak exercise was significantly higher and the decline in heart rate after exercise significantly faster for patients 2 or more years after transplantation than for patients less than 2 years after transplantation (46 +/- 2 versus 38 +/- 1.9 beats/min, p < 0.05); the decline in heart rate 4 minutes after exercise was 27 +/- 1.8 versus 16 +/- 1.8 beats/min, respectively ( p < 0.001). CONCLUSION: The reduction in peak oxygen consumption, particularly during the first 2 years, appears to be related in part to chronotropic incompetence. Late after transplantation the heart rate response to exercise is greater and the decline in heart rate after exercise faster, suggesting possible autonomic reinnervation in some patients. Chronotropic incompetence may be an inadequate explanation of oxygen uptake impairment seen late after transplantation, when other factors such as myocardial dysfunction and intrinsic skeletal muscle abnormalities are of increasing importance.

Influence of the exercise protocol on hemodynamic, gas exchange, and neurohumoral responses to exercise in heart transplant recipients.

BACKGROUND: A gradual accommodation to increasing exercise loads has been recommended for exercise testing in denervated posttransplantation heart recipients. However, how the exercise protocol influence the hemodynamic, gas exchange, and hormonal response to exercise in this not been studied. METHODS: Nine heart transplant recipients tests incremental maximal bicycle ergometry tests in random order. Exercise stages of 1 and 3 minute durations were compared with matched work rate increments ranging between 30 and 40 W. Expiratory gas was measured continuously and arterial blood was sampled at each of the matched work rates. RESULTS: Total exercise duration was 6.4 +/- and 15.3 +/- 0.7 minutes for the 1-minute and 3-minute protocols, respectively. Maximal workload was significantly higher during the 1-minute versus the 3-minute protocol (238 +/- 9 versus 200 +/- 11 W, p < 0.001), but maximal oxygen uptake was not significantly different (25.5 +/- 1.1 versus 26.5 +/- 1.2 ml. min-1.kg-1). Hemodynamic, metabolic, and some hormonal parameters showed marked differences between the two protocols, with significantly higher responses observed during the 3-minute protocol for heart rate, ventilation, lactate, atrial natriuretic factor, and growth hormone. Catecholamine (epinephrine and norepinephrine) and insulin responses did not differ between the two tests. If expressed as a relative exercise intensity (percentage of maximal oxygen uptake) no differences in hormonal responses were observed between the two protocols, except for growth hormone response which remained higher during the 3-minute protocol. CONCLUSIONS: Although maximal oxygen uptake was independent of the exercise protocol in these heart transplant recipients, the exercise protocol has a major influence on the hormonal and metabolic response. The delayed response observed for oxygen uptake and hormonal responses suggests a significant physiologic lag time during the more rapidly incremental protocol. These differences should be taken into account when exercise is used as a method to evaluate the heart transplant recipient.