Exercise stress echocardiography for the study of the pulmonary circulation.

Exercise stress tests have been used for the diagnosis of pulmonary hypertension, but with variable protocols and uncertain limits of normal. The pulmonary haemodynamic response to progressively increased workload and recovery was investigated by Doppler echocardiography in 25 healthy volunteers aged 19-62 yrs (mean 36 yrs). Mean pulmonary artery pressure ((Ppa)) was estimated from the maximum velocity of tricuspid regurgitation. Cardiac output (Q) was calculated from the aortic velocity-time integral. Slopes and extrapolated pressure intercepts of (Ppa)-Q plots were calculated after using the adjustment of Poon for individual variability. A pulmonary vascular distensibility alpha was calculated from each (Ppa)-Q plot to estimate compliance. (Ppa) increased from 14+/-3 mmHg to 30+/-7 mmHg, and decreased to 19+/-4 mmHg after 5 min recovery. The slope of (Ppa)-Q was 1.37+/-0.65 mmHg x min(-1) x L(-1) with an extrapolated pressure intercept of 8.2+/-3.6 mmHg and an alpha of 0.017+/-0.018 mmHg(-1). These results agree with those of previous invasive studies. Multipoint (pa)-Q plots were well described by a linear approximation, from which resistance can be calulated. We conclude that exercise echocardiography of the pulmonary circulation is feasible and provides realistic resistance and compliance estimations. Measurements during recovery are unreliable because of rapid return to baseline.

Influence of atenolol on the relationship between heart rate and QT interval in patients with exercise-induced myocardial ischemia.

The aim of this study was to analyze the relationship between heart rate and QT interval (HR-QT) during exercise in control subjects (Group A) and in patients with coronary artery disease (CAD) with effort angina and without previous myocardial infarction (MI) (Group B). The diagnosis of CAD was confirmed by coronarographic examination. The correlation HR-QT was significant (p < 0.001) in both groups on effort and at recovery. The analysis of the regression HR-QT was carried out separately, both on effort in upright position and at rest in supine position, to avoid the influence of posture on QT length. During effort, the regression line showed lower slope and intercept values in Group B (p < 0.001) than those for Group A. A similar behavior was also observed at rest. Thus, at the highest heart rate, where ECG signs of ischemia (ST depression > 1 mm) frequently occurred, a longer QT interval was present in Group B. Moreover, in Group B, the QT interval in the presence of ECG signs of ischemia was significantly longer (p < 0.01) than in Group A at comparable heart rates both on effort and at rest, thereby confirming the result obtained by comparing both regression lines. The same effort protocol was repeated in Group B patients after acute administration of atenolol 100 mg per os. After atenolol administration, the analysis of the regression HR-QT in Group B clearly showed a shorter QT interval than that obtained in washout period during the baseline test at the highest heart rates where the ECG frequently showed signs of ischemia.(ABSTRACT TRUNCATED AT 250 WORDS)

Long term effects of bosentan treatment in adult patients with pulmonary arterial hypertension related to congenital heart disease (Eisenmenger physiology): safety, tolerability, clinical, and haemodynamic effect.

BACKGROUND: Oral bosentan is an established treatment for pulmonary arterial hypertension (PAH). OBJECTIVE: To evaluate safety, tolerability, and clinical and haemodynamic effects of bosentan in patients with PAH related to congenital heart disease (CHD). PATIENTS: 22 patients with CHD related PAH (8 men, 14 women, mean (SD) age 38 (10) years) were treated with oral bosentan (62.5 mg x 2/day for the first 4 weeks and then 125 mg x 2/day). MAIN OUTCOME MEASURES: Clinical status, liver enzymes, World Health Organisation (WHO) functional class, resting oxygen saturations and 6-min walk test (6MWT) were assessed at baseline and at 1, 3, 6, and 12 months. Haemodynamic evaluation with cardiac catheterisation was performed at baseline and at 12 month follow-up. RESULTS: 12 patients had ventricular septal defect, 5 atrioventricular canal, 4 single ventricle, and 1 atrial septal defect. All patients tolerated bosentan well. No major side effects were seen. After a year of treatment, an improvement was seen in WHO functional class (2.5 (0.7) v 3.1 (0.7); p<0.05), oxygen saturation at rest (87 (6%) v 81 (9); p<0.001), heart rate at rest (81 (10) v 87 (14) bpm; p<0.05), distance travelled in the 6MWT (394 (73) v 320 (108) m; p<0.001), oxygen saturation at the end of the 6MWT (71 (14) v 63 (17%); p<0.05), Borg index (5.3 (1.8) v 6.5 (1.3); p<0.001), pulmonary vascular resistances index (14 (9) v 22 (12) WU m(2); p<0.001), systemic vascular resistances index (23 (11) v 27 (10) WU.m(2); p<0.01), pulmonary vascular resistances index/systemic vascular resistances index (0.6 (0.5) v 0.9 (0.6); p<0.05); pulmonary (4.0 (1.3) v 2.8 (0.9) l/min/m2; p<0.001) and systemic cardiac output (4.2 (1.4) v 3.4 (1.1) l/min/m2; p<0.05). CONCLUSIONS: Bosentan was safe and well tolerated in adults with CHD related PAH during 12 months of treatment. Clinical status, exercise tolerance, and pulmonary haemodynamics improved considerably.

[The usefulness of bioimpedance in patient monitoring in an intensive-therapy heart-surgery unit: a comparison with thermodilution]. / Utilità della bioimpedenza nel monitoraggio del paziente in unità di terapia intensiva di cardiochirurgia: comparazione con la termodiluizione.

Haemodynamic monitoring of intensive care unit (ICU) patients can be carried out by thermodilution system. This method is invasive, does not give a continuous monitoring and complications can occur. Thoracic electrical bioimpedance (TB), a non invasive, fast, easily repeatable method, is able to measure some important haemodynamic parameters: end diastolic volume (EDV), stroke volume, cardiac output (CO), ejection fraction (EF), some contractility indexes, systemic vascular resistances (SVR) and cardiac work. The aim of the present study is to compare CO and SVR obtained by thermodilution with the same indexes obtained by TB. Therefore, 20 ICU patients (12 males and 8 females, mean age 54 +/- 11 years) were studied. Out of them, 16 had been submitted to cardiac surgery in the previous 7 days and 4 were waiting for cardiac surgery. The patients were divided in 2 groups: Group A (N 4) included patients with valvular malfunction and/or cardiac arrhythmias and Group B (N 16) included patients with normal valvular function and sinus rhythm. CO obtained by TB was well related with the one obtained by invasive (INV; r = 0.878; p < 0.001). The mean value of difference of the 2 methods was 12.29 +/- 11.83 for the whole group of 20 patients but it was 26.07 +/- 14.16 in the Group A and 8.84 +/- 8.09 in the Group B confirming the less reliability of the method in patients with abnormal valvular function or in the presence of cardiac arrhythmias. As a consequence, SVR obtained by TB and INV resulted well related (r = 0.752; p < 0.001). The mean value of differences was 11.14 +/- 9.01 in the group of 20 patients and particularly 19.55 +/- 10.87 in the Group A and 9.04 +/- 7.07 in the Group B. In a subgroup of 9 patients, CO was measured at successive times (0, 30, 60, 90 min) by both TB and INV; when comparing the 2 CO values a significant correlation was observed. In conclusion, TB represents a valid method in haemodynamic monitoring of the ICU patients.

[Cardiac performance during insulin clamp: its evaluation by bioimpedance measurement]. / Performance cardiaca durante "clamp" insulinico: valutazione mediante bioimpedenzometria.

Ten patients with dilated cardiomyopathy, 7 ischemic heart disease and 3 idiopathic (7 males and 3 females, mean age 54.8 +/- 11 years), were studied. An insulin euglycemic clamp was performed to evaluate the influence of insulin infusion on cardiac performance. All the subjects were in NYHA functional class II-III and had an ejection fraction < 60% at a previous echocardiographic examination. They were submitted to a noninvasive continuous cardiac output monitoring by variations of thoracic impedance at three stops: a basal evaluation (T0); 1.2 mU/kg/min insulin infusion (T1); 5 mU/kg/min insulin infusion (T2). Moreover at the same times Na+, K+, hematocrit (Hct) and catecholamines were measured in the plasma. The total time required for the study was about 4 hours. Cardiac performance improved as shown by a significant increase in T1 and T2 with respect to the basal condition (T0), of ejection fraction: 57.87 +/- 11.3% (T1) vs 52.25 +/- 14.1% (T0; p < 0.01); 59.5 +/- 10.7% (T2) vs 52.25 +/- 14.1% (T0; p < 0.005); stroke volume: 2.61 +/- 0.5 l/min/m2 (T1) vs 2.01 +/- 0.75 l/min/m2 (T0; p < 0.001); 3.35 +/- 0.66 l/min/m2 (T2) vs 2.01 +/- 0.75 l/min/m2 (T0; p < 0.001) and cardiac output: 41.14 +/- 9.1 ml/m2 (T1) vs 38.83 +/- 7.1 ml/m2 (T0; p < 0.01); 46.45 +/- 8.56 ml/m2 (T2) vs 38.83 +/- 7.1 ml/m2 (T0; p < 0.001). This improvement in cardiac function was not due to an increase in preload because end diastolic volume, Hct, Na+ did not differ through the study. Similarly, afterload measured as mean blood pressure did not decrease. Cardiac function improvement was obtained in the presence of increased catecholamines. In conclusion, exogenous insulin infusion was able, in the presence of euglycemic condition, to improve cardiac performance. This improvement could be due to a direct inotropic effect of insulin perhaps mediated by its metabolic properties on cardiac muscular cells and/or by increasing the cellular intake of Ca+2.

Right ventricular myocardial activation delay in adult patients with right bundle branch block late after repair of Tetralogy of Fallot.

Electromechanical interaction, with prolonged QRS duration due to right ventricular (RV) overload, has been described as a predictor of unfavorable outcome in patients late after correction of Tetralogy of Fallot (TOF). Aim of our study was to evaluate myocardial function and activation delay of both left and right ventricles in TOF patients. Doppler echo, treadmill test and pulsed Tissue Doppler (TD) were performed in 25 healthy subjects and in 30 adult patients who had undergone surgery for TOF, all with right bundle branch block on ECG. Exclusion criteria were evidence of residual pulmonary either stenosis or regurgitation. By use of TD, the level of both LV mitral and RV tricuspid annulus were measured: systolic (Sm), early- and late-diastolic (Em and Am) regional peak velocities. The indexes of myocardial systolic activation were calculated: precontraction time (PCTm) and interventricular activation delay (InterV-del) (difference of PCTm between RV and LV segments). The two groups were comparable for LV diameters and for Doppler indexes, while QRS duration was prolonged and RV end-diastolic diameter was increased in TOF. By TD analysis, only at the level of tricuspid annulus TOF patients had lower Sm and Em, and increased RV PCTm ( p<0.001 ) and InterV-del ( p<0.0001 ), even after adjustment for heart rate (HR) and QRS duration. By treadmill test, TOF showed reduced cardiac functional reserve. In seven patients non-sustained ventricular tachycardia was documented during physical effort. By multivariate analysis, RV Em ( p<0.001 ), and InterV-del ( p<0.01 ) were independently associated to maximal workload at peak effort. The same InterV-del was an independent determinant of risk of ventricular arrhythmias during effort ( p<0.01 ). A cut-off point of Em peak velocity of tricuspid annulus <0.13 m/s at rest showed a sensitivity of 91% and a specificity of 88% in identifying TOF patients with submaximal exercise test. A cut-off point of InterV-del >55 ms showed 87% sensitivity and 88% specificity to detect increased risk of ventricular arrhythmias during effort. In TOF patients, TD analysis at rest may be taken into account as a non-invasive and easy-repeatable tool to predict cardiac performance during physical effort, and to select subgroups of patients at increased risk of ventricular arrhythmias.

Left ventricular systolic and diastolic function in severe obesity: a radionuclide study.

To verify the impact of sever obesity (defined as body mass index > 31 kg/m2) on left ventricular (LV) function, 32 asymptomatic obese but otherwise healthy subjects (16 men; age 38 +/- 11 years) voluntarily underwent first-pass and equilibrium 99mTc radionuclide angiography at rest and, in 22 of them, during bicycle supine exercise. Data were compared to those obtained from 10 normal volunteers (age 48 +/- 13; p < 0.05, vs. obeses). End-diastolic and stroke volumes did not differ between the two groups, whereas end-systolic volume was significantly higher in obese subjects (67 +/- 20 vs. 49 +/- 20 ml; p < 0.05), and, as a consequence, LV ejection fraction at rest was decreased in obese subjects (59 +/- 7%) compared to normals (65 +/- 6%; p < 0.05). Due to the higher heart rate in obese subjects (81 +/- 13 vs. 69 +/- 10 pbm, respectively; p < 0.05) cardiac output was significantly greater compared to normals (7.1 +/- 0.8 vs. 6.2 +/- 0.2 liters/min, respectively; p < 0.01). During exercise, ejection fraction normally increased in normals (70 +/- 7%; p < 0.001, vs. baseline) but not in obese subjects (60 +/- 9%; p = nonsignificant vs. baseline). In addition, systolic blood pressure/end-systolic volume ratio was significantly decreased in obese subjects (23 +/- 1.3) compared to normals (2.8 +/- 1.6; p < 0.05). Peak filling rate, normalized to end-diastolic counts per second, was significantly lower in obese subjects (2.2 +/- 1.3) compared to normals (2.8 +/- 1.6; P < 0.05). This difference was also true when peak filling rate was computed in stroke counts per second (3.8 +/- 0.8 in obeses vs. 4.4 +/- 0.4 in normals; p < 0.05). Repeat analysis in a subgroup of 10 young obese subjects (age < or = 30 years) confirmed decreased ejection fraction at rest (60 +/- 4%; p < 0.05) and peak filling rate (2.4 +/- 0.4 end-diastolic counts/s; p < 0.05), as well as the lack of ejection fraction increase during exercise (59 +/- 9%). Thus, these data indicate a subclinical impairement of LV systolic and diastolic function at rest and during exercise in asymptomatic severely obese but otherwise healthy subjects.

[Evaluation of left ventricular function in patients with mammary carcinoma after treatment with epidoxorubicin using a high-dose, short-term protocol]. / Valutazione della funzione ventricolare sinistra in pazienti con carcinoma mammario sottoposti a terapia con epidoxorubicina secondo il protocollo "high-dose short-term".

Anthracyclines are effective chemotherapeutic agents against various malignancies but their therapeutic value is limited by well-known dose-related cardiotoxicity, mainly induced by oxygen free radicals. Left ventricular diastolic and systolic functional abnormalities precede the clinical evidence of cardiotoxicity. The aim of this study was to evaluate the possible cardiotoxicity of epidoxorubicin administered as "high-dose short-term" protocol. Twenty patients (mean age 50.4 +/- 7.9 years) without cardiac disease, affected by advanced breast cancer were studied. All patients were treated with epidoxorubicin as neoadjuvant chemotherapy according to the new protocol "high-dose short-term" (cumulative dose 475.8 +/- 35.6 mg/m2, range 450-600 mg/m2, in 4-6 weeks). The effectiveness of cancer chemotherapy was monitored by clinical evaluation and mammography performed before and after treatment. All patients underwent color Doppler echocardiography and resting radionuclide angiocardiography in baseline condition and 30 +/- 10 days after the last cycle of chemotherapy. All patients showed a significant reduction of tumor lesion after chemotherapy. Left ventricular systolic and diastolic function parameters obtained by echocardiography (fractional shortening 33.1 +/- 4.5% vs 32.4 +/- 4.8%; ejection fraction 63.6 +/- 6.2% vs 62.9 +/- 5.7%; E/A ratio 1.73 +/- 0.64 vs 1.82 +/- 0.67; E wave deceleration time 204 +/- 24.6 ms vs 208.5 +/- 31.7 ms;isovolumetric relaxation time 79 +/- 15.7 ms vs 80 +/- 17.8 ms) and radionuclide angiocardiography (ejection fraction 62.4 +/- 7% vs 61.8 +/- 5.9; peak ejection rate 2.87 +/- 0.44 VTD/s vs 2.74 +/- 0.46 VTD/s; peak filling rate 2.72 +/- 0.54 VTD/s vs 2.6 +/- 0.58 VTD/s) did not show significant changes after treatment. In conclusion, our results suggest that epidoxorubicin administration using the "high-dose short-term" protocol in patients with breast cancer does not induce early significant abnormalities of left ventricular systolic and diastolic function.

[The short- and medium-term ambulatory radionuclide study of left ventricular function (VEST) after aortocoronary bypass]. / Studio ambulatoriale radionuclidico della funzione ventricolare sinistra (VEST) a breve e medio termine dopo bypass aortocoronarico.

The aim of the present study was to evaluate the variation in left ventricular function at 15 and 120 days after bypass surgery. Ten male patients (mean age 59.6 +/- 7 years) with previous myocardial infarction and coronary stenosis of at least two main vessels, underwent a radionuclide ambulatory monitoring of left ventricular function (VEST) during: handgrip test, mental stress test, walking, climbing stairs. These tests were carried out 8 +/- 2 days before (T0), 15 +/- 3 days (T1) and 120 +/- 11 days after coronary bypass; heart rate (HR), ejection fraction (EF), stroke volume (SV), and cardiac output (CO) were evaluated beat by beat before and during the test until the maximal HR was reached. Handgrip and mental stress tests did not induce significant variations in cardiac indices both before and after cardiac surgery. No variation in HR was observed before and after the test. During walking, at T0, HR increased from rest to maximal effort (p < 0.01) with a significant decrease in EF (p < 0.05); at T1 HR, EF, SV and CO increased with respect to rest (p < 0.01); AT T2 HR, EF (p < 0.05) and CO (p < 0.01) increased with respect to rest. Climbing stairs, at T0, HR increased (p < 0.01) and EF decreased (p < 0.05); at T1 HR, EF, CO (p < 0.05) and SV (p < 0.01) increased with respect to rest. At T2 an increase in HR (p < 0.01) and CO (p < 0.05) was observed at maximal effort with respect to rest. The statistical analysis on the percentage variations between baseline and maximal effort (climbing stairs) showed a significant increase in SV at T2 compared to T0 (p < 0.01). In conclusion, VEST during daily normal activities 15 days and 4 months after bypass surgery showed a significant increase in cardiac function indices. The best results obtained at T1 can be explained with the transient increase in adrenergic tone at the time of early postoperative period.

[The heterogeneity of myocardial sympathetic innervation in normal subjects: an assessment by iodine-123 metaiodobenzylguanidine scintigraphy]. / Eterogeneità dell'innervazione simpatica del miocardio in soggetti normali: valutazione mediante scintigrafia con iodio-123 metaiodobenzilguanidina.

123I-radiolabeled metaiodobenzylguanidine (123I-MIBG) cardiac imaging has been used to evaluate the distribution of sympathetic nervous system (SNS) in the heart. Different heart diseases have shown impaired cardiac SNS distribution as reflected by MIBG activity. The aim of this study was to assess the cardiac distribution of SNS in normal subjects, using MIBG imaging. Ten normal subjects (1 male and 9 females, mean age 46 +/- 9 years) with no cardiac abnormalities underwent myocardial 123I-MIBG scintigraphy, Tc-99m methoxyisobutylisonitrile (MIBI) cardiac perfusion imaging and equilibrium radionuclide angiography (RNA). Regional myocardial MIBG and MIBI activities were quantitatively evaluated using a region of interest analysis. For this purpose, the left ventricle was divided into 6 myocardial regions as anterior, apical, inferior, septum, lateral and posterolateral. In particular, myocardial MIBG and MIBI activities were measured as myocardium to mediastinum ratio. Regional left ventricular function was assessed by RNA. Myocardial MIBG uptake was homogeneous in anterior (2.2 +/- 0.5), inferior (2.5 +/- 0.7), septal (2.4 +/- 0.4), lateral (2.3 +/- 0.4), and posterolateral (2.3 +/- 0.4) regions. Conversely, MIBG uptake was significantly lower in the apical region (1.9 +/- 0.3) compared to all other left ventricular segments (p < 0.05). Regional myocardial perfusion, as measured by MIBI uptake, was homogeneous in all regions. No regional left ventricular wall motion abnormalities were observed by RNA. In conclusion, our data suggest that a decreased MIBG uptake may be observed in the left ventricular apical region of normal subjects reflecting reduced sympathetic innervation of the apex. This finding is not related to myocardial perfusion or wall motion abnormalities. The knowledge of cardiac sympathetic innervation in normal subjects may be helpful to assess SNS abnormalities in heart disease.