Role of cardiopulmonary exercise test in the prediction of hemodynamic impairment in patients with pulmonary arterial hypertension.

Periodic repetition of right heart catheterization (RHC) in pulmonary arterial hypertension (PAH) can be challenging. We evaluated the correlation between RHC and cardiopulmonary exercise test (CPET) aiming at CPET use as a potential noninvasive tool for hemodynamic burden evaluation. One hundred and forty-four retrospective PAH patients who had performed CPET and RHC within 2 months were enrolled. The following analyses were performed: (a) CPET parameters in hemodynamic variables tertiles; (b) position of hemodynamic parameters in the peak end-tidal carbon dioxide pressure (PETCO2) versus ventilation/carbon dioxide output (VE/VCO2) slope scatterplot, which is a specific hallmark of exercise respiratory abnormalities in PAH; (c) association between CPET and a hemodynamic burden score developed including mean pulmonary arterial pressure (mPAP), pulmonary vascular resistance (PVR), cardiac index, and right atrial pressure. VE/VCO2 slope and peak PETCO2 significantly varied in mPAP and PVR tertiles, while peak oxygen uptake (peak VO2) and O2 pulse varied in the tertiles of all hemodynamic parameters. PETCO2 versus VE/VCO2 slope showed a strong hyperbolic relationship (R 2 = 0.7627). Patients with peak PETCO2 > median (26 mmHg) and VE/VCO2 slope < median (44) presented lower mPAP and PVR (p < 0.005) than patients with peak PETCO2 < median and VE/VCO2 slope > median. Multivariate analysis individuated peak VO2 (p = 0.0158) and peak PETCO2 (p = 0.0089) as hemodynamic score independent predictors; the formula 11.584 - 0.0925 × peak VO2 - 0.0811 × peak PETCO2 best predicts the hemodynamic score value from CPET data. A significant correlation was found between estimated and calculated scores (p < 0.0001), with a precise match for patients with mild-to-moderate hemodynamic burden (76% of cases). The results of the present study suggest that CPET could allow to estimate the hemodynamic burden in PAH patients.

Surfactant protein B and RAGE increases in the plasma during cardiopulmonary bypass: a pilot study.

Surfactant derived protein B (SPB) and plasma receptor for advanced glycation end products (RAGE) have been proposed as markers of lung injury. The former is produced specifically by pneumocytes while RAGE production is present in several body tissues. Cardiopulmonary bypass (CPB) generates a transient lung injury. We measured SPB and RAGE in plasma before surgery and after CPB, as well as 24 h and 48 h later. We analysed plasma samples from 20 subjects scheduled for elective coronary artery bypass grafting. We performed a quantitative analysis of plasma levels of RAGE and SPB mature form (8 kDa) by ELISA and a semi-quantitative analysis of SPB immature form (~ 40 kDa) by Western blotting. Surgery procedures were uneventful. After CPB RAGE median (75th-25th interquartile difference) increased from 633 (539) pg·mL⁻¹ to 1,362 (557) pg·mL⁻¹ (p < 0.01), while mature SPB increased from 5,587 (3,089) ng·mL⁻¹ to 20,307 (19,873) ng·mL⁻¹ (p < 0.01). RAGE and mature SPB returned to normal values within 48 h. This behaviour was confirmed when RAGE and SPB were normalised for protein content. Parallel changes were observed for immature SPB. Plasma RAGE and SPBs are sensitive and rapid markers of lung distress.

Primary aldosteronism due to adrenocortical adenoma with concurrent ileum carcinoid tumor: case report.

Primary aldosteronism (PA) with synchronous carcinoid syndrome is extremely rare occurrence. In this article, we describe a case of PA due to adrenocortical adenoma ("aldosteronoma") and concurrent malignant carcinoid tumor of ileum. The patient was treated with synchronous right adrenalectomy and resection of the ileum. This case is an example of concomitant presence of two types of tumors, effectively managed surgically. We report a case of a nonclassical form of multiple endocrine neoplasia type 1 (MEN 1) syndrome.

Cushing's syndrome patient who exhibited congestive heart failure.

Cushing's Syndrome (CS) may sometimes lead to dilated cardiomyopathy, even though this condition can be partially or completely reversed after treatment. In this article we report the case of a 28-yr-old woman with CS secondary to adrenal adenoma who exhibited congestive heart failure as an initial symptom. Two weeks before being admitted to our hospital, the patient started complaining of shortness of breath, orthopnea, paroxysmal nocturnal dyspnea and generalized edema. A physical examination did not reveal signs of hypercortisolism. Chest auscultation revealed bilateral diffused crepitation; blood pressure was 180/120 mmHg with heart rate of 90 beats/min. A chest X-ray showed a cardiac shade enlargement due to congestive heart failure. Transthoracic echocardiography demonstrated a dilated left ventricle and an impaired left ventricular systolic function. The patient's urinary cortisol excretion was elevated and circadian rhythm of cortisol was absent. ACTH level was low. In addition, plasma cortisol failed to decrease after administration of dexamethasone. An abdominal magnetic resonance imaging scan showed a 7-cm right adrenal mass. The patient was administered oxygen, spironolactone, ACE-inhibitor and the signs and symptoms of heart failure gradually improved. A laparoscopic right adrenalectomy was performed and pathological examination of the gland showed a benign adrenocortical adenoma. After the adrenalectomy the patient was started on hydrocortisone therapy and 5 months later the wall thickness of the left ventricle was within normal range and the patient's blood pressure was 130/80 mmHg. In conclusion we report the case of heart failure as the main clinical symptom in CS secondary to adrenal adenoma.

Increased plasma levels of adrenomedullin, a vasoactive peptide, in patients with end-stage pulmonary disease.

AIM: To study adrenomedullin (AM) plasma levels in patients with severe lung disease and to analyze the relationship between AM and heart changes, hemodynamics and blood gases. METHODS: Case control study of 56 patients (36 men, 20 women) with severe lung disease and 9 control subjects (7 men, 2 women). Patients with end-stage pulmonary disease, including chronic obstructive pulmonary disease (COPD, n=11), cystic fibrosis (CF, 26), idiopatic pulmonary fibrosis (ILD, n=9), and idiopatic pulmonary arterial hypertension (PAH, n=10), who were evaluated for lung trasplantation between January 1997 and September 2000, and nine patients who underwent lung surgery for a solitary benign nodule. AM plasma levels in pulmonary artery (mixed venous blood, vein) and aorta or femoral artery (arterial, art), art and vein blood gases, pulmonary hemodynamics, systemic hemodynamics, two-dimensional transthoracic echocardiography and echo-Doppler study. RESULTS: Plasma AM (art and ven) levels were higher among patients' group compared to the controls (AMart p<0.02 and AMven p<0.04) for CF, ILD, PAH (AMart, pg ml(-1) Controls 13.7+/-3.6, COPD 22.8+/-6.2, CF 28.1+/-11.4, ILD 34.1+/-14.3, PAH 35.1+/-18.9; AMven, pg ml(-1) Controls 14.2+/-4.8, COPD 28.1+/-12.6, CF 31.7+/-14.1, ILD 38.7+/-16.5, PAH 40.1+/-4.4). We found with a trend towards higher concentration in ILD and PAH patients compared to COPD and CF but no statistical significant differences. Mixed-venous AM was higher than arterial AM in all groups resulting in AM uptake (AMPulmUp pg min(-1) Controls 4.8+/-22.6, COPD 21.1+/-44.9, CF 20.6+/-45.1, ILD 23.7+/-38.5, PAH 29.9+/-49.7). The univariate analysis showed a weak but significant correlation between AMart and mean systemic arterial pressure, heart rate, mean pulmonary arterial pressure and systemic vascular resistance. In the multivariate analysis, four variables emerged as independent factors of AMart including mean pulmonary arterial pressure, heart rate, mean systemic arterial pressure and left ventricular diastolic diameter (F=8.6, p<0.00001, r=0.60, r2=0.32). A similar weak correlation was apparent between AMven, systemic vascular resistance, and mean pulmonary arterial pressure. The results of multivariate analysis identify right atrial enlargement, mean right atrial pressure, heart rate and left ventricular dimensions as the only independent variables related to AMven (F=4.3, p<0.0004 r=0.56, r2=0.26). AM pulmonary uptake was significantly correlated with AMven (r=0.65), but not with hemodynamic, blood gas and echocardiographic variables. CONCLUSIONS: AM plasma levels are elevated in patients with severe lung disease in face of a preserved pulmonary uptake. These results suggest that the high AM plasma levels in patients with severe lung disease are not caused by a reduced pulmonary clearance, instead suggesting a systemic production.

Long term treatment of pulmonary arterial hypertension with beraprost, an oral prostacyclin analogue.

OBJECTIVE: To evaluate the effects of one year's treatment with beraprost, an orally active prostacyclin analogue, in patients with severe pulmonary hypertension. PATIENTS: 13 patients with severe pulmonary hypertension. This was primary in nine, thromboembolic in three, and caused by Eisenmenger syndrome in one. METHODS: All patients underwent right heart catheterisation. Mean (SD) right atrial pressure was 5 (3) mm Hg, mean pulmonary artery pressure was 48 (12) mm Hg, cardiac index was 2.6 (0.8) l/min/m(2), and mixed venous oxygen saturation was 68 (7)%. Beraprost was started at the dose of 20 microgram three to four times a day (1 microgram/kg/day), increasing after one month to 40 microgram three to four times a day (2 microgram/kg/day), with further increases of 20 microgram three to four times a day in case of clinical deterioration. MAIN OUTCOME MEASURES: New York Heart Association (NYHA) functional class, exercise capacity measured by distance walked in six minutes, and systolic pulmonary pressure (by echocardiography) were evaluated at baseline, after one month's treatment, and then every three months for a year. RESULTS: After the first month of treatment, NYHA class decreased from 3.4 (0.7) to 2.9 (0.7) (p < 0.05), the six minute walking distance increased from 213 (64) to 276 (101) m (p < 0.05), and systolic pulmonary artery pressure decreased from 93 (15) to 85 (18) mm Hg (NS). One patient died after 40 days from refractory right heart failure, and another was lost for follow up at six months. The 11 remaining patients had persistent improvements in functional class and exercise capacity and a significant decrease in systolic pulmonary artery pressure in the period from 1-12 months. Side effects were minor. CONCLUSIONS: Oral administration of beraprost may result in long lasting clinical and haemodynamic improvements in patients with severe pulmonary hypertension.

Echocardiography in the coronary care unit: diagnostic and prognostic impact in comparison with clinical and other indicators.

The clinical arena in which we must consider the role of echocardiography is characterized by 2 fundamental findings: (1) most patients with chest pain and suspected acute myocardial infarction (MI) do not present diagnostic electrocardiograms; and (2) an early and correct diagnosis is necessary to match the patient with the most adequate treatment. Echocardiography may be very useful in the coronary care unit, allowing a correct diagnosis of ischemic heart disease when electrocardiography is unclear, even before the rise of cardiac enzymes is detected. It may also play a role in decision-making for thrombolytic therapy. In addition, echocardiography provides useful information for early risk stratification. In fact, although high-risk patients are well identified by simple clinical or instrumental variables (i.e., Killip classification, enzymatic data, blood-gas analysis, electrocardiogram, etc.), most patients (>60%) are identified as low risk, and several subjects classified into the low-risk groups have a poor prognosis and are not detected using a single variable. In our experience, 2-dimensional echocardiography was able to further stratify between patients of low-risk classes. Therefore, echocardiography plays an important role in the early stratification of acute MI patients, especially in those without signs or symptoms of heart failure.

Clinical impact of echocardiography in prognostic stratification after acute myocardial infarction.

Risk stratification is mandatory in the management of the postinfarction period. The identification of high-risk patients, on the basis of clinical data (recurrent angina, overt heart failure, etc.), is quite easy, whereas stratification of uncomplicated subjects needs an accurate noninvasive strategy. In the last 20 years, echocardiography has been gaining an increasing role, allowing increasingly precise evaluation of infarct size. This detection of the extent of infarct size has a definite prognostic value. Since 1980, we have observed that a dysfunctioning left ventricular myocardium >40% marked patients with a poor prognosis. These observations are most important in asymptomatic infarct patients, in whom clinical features may not reflect the amount of left ventricular dysfunction. Our recent results on a large series of patients with acute myocardial infarction (MI) without overt heart failure have shown that the extension of wall motion abnormalities at 2-dimensional (2D) echocardiography was highly predictive of cardiac death or new coronary events in a 3-year follow-up (univariate analysis; p <0.0005). Echocardiography also plays an important role in detecting postinfarct ischemia, as seen by its wide use during stress tests. In our experience, the response to exercise echocardiographic testing has a high prognostic value. In fact, in our series, univariate analysis (Kaplan-Meier) showed that the best predictors of coronary events were the number of markers of ischemia during exercise (p <0.00001), the work load (p <0.00001), a positive exercise echo (p <0.0005), and the echo score at rest (p <0.0005). Multivariate analysis (Cox) confirmed these data: number of markers of ischemia: odds ratio (OR) 4.45, 95% confidence interval (CI) 1.5-13.1; work load: OR 2.46, CI 1.3-4.5; positive exercise echo OR 1.88, CI 1.1-3.2. Thus, serial echocardiography together with predischarge stress echocardiography is recommended for risk stratification after acute MI. In particular, in thrombolytic-treated patients, echo examinations allow the detection of functional recovery of viable reperfused myocardium whereas stress echo may show exercise-induced worsening in the region supplied by the infarct-related vessel, a predictor of a higher rate of coronary events.

Assessment of left ventricular dyssynergy by color kinesis.

Color kinesis is a new echocardiographic technique based on acoustic quantification. It has been developed to facilitate the ability to identify contraction abnormalities and has been incorporated into a commercially available ultrasound imaging system. The potential of this technique to improve the qualitative and quantitative assessment of wall motion abnormalities is described. Evaluation of color-encoded images allows detection of decreased amplitude of endocardial motion in abnormally contracting segments as well as a shorter time of endocardial excursion in segments with severely decreased motion. Compared with off-line quantitative studies, color kinesis has the advantage to be used on-line, without time-consuming manual tracing of endocardial boundaries. In addition, a single end-systolic color image contains the entire picture of spatial and temporal contraction and can be digitally stored and retrieved. In patients with proven coronary artery disease, color kinesis had a sensitivity of 88%, a specificity of 77%, and an overall accuracy of 86% in identifying the presence of segmental dysfunction. The practical application of color kinesis might be to improve our ability to distinguish normal from hypokinesis, something that has always been difficult in clinical echocardiography. Segmental analysis of color kinesis images allows objective detection of dobutamine-induced regional wall motion abnormalities in agreement with conventional visual interpretation of the corresponding 2-dimensional views. A method for objective assessment of wall dynamics during dobutamine stress echocardiography would be of particular clinical value, because these images are even more difficult to interpret than conventional echocardiograms. Quantitative assessment of diastolic function may allow objective evaluation of segmental relaxation abnormalities, especially under conditions of pharmacologic stress testing. Acquisition of color kinesis images during dobutamine stress echocardiography, both transthoracic and transesophageal, may facilitate the assessment of hybernating but viable myocardium and enhance the sensitivity in the detection of coronary artery disease.

[Anatomico-functional changes in the right ventricle of the athlete]. / Modificazioni anatomo-funzionali del ventricolo destro nell'atleta.

The aim of this study was to compare the morpho-functional modifications of the right cardiac sections of the athlete's heart, with those of sedentary healthy control subjects. We studied 24 endurance athletes (mean age 28.17 +/- 7.28 years), 21 power athletes (mean age 25.86 +/- 4.96 years), and 20 sedentary healthy control subjects (mean age 33.22 +/- 6.67 years). We examined the right cavities by standard echocardiographic projections and the following parameters were evaluated: right ventricular longitudinal diameter; under tricuspid valve and medium ventricular transversal diameter immediately under the tricuspid plane and at medium ventricular level; right atrial transversal and longitudinal diameters. All parameters were corrected for body surface area. Our data showed that the right ventricle presents morphological adaptations to endurance exercise; modification is represented mainly by an increase in the mean transversal ventricular diameter with a consequent reduction in the transversal/longitudinal diameter ratio accompanied by modification of the ventricular geometry. In addition the data showed an increase in longitudinal and transversal diameters of the right atrium. On the contrary, the power athletes did not show statistical modification of the right ventricle and atrium. The different modifications of the right heart side diameter are probably due to the different hemodynamic loading, which is involved in the endurance and power training respectively.

Detection of left ventricular systolic and diastolic abnormalities in patients with coronary artery disease by color kinesis.

BACKGROUND: Color kinesis (CK) is a recently developed echocardiographic technique based on acoustic quantification that automatically tracks and displays endocardial motion in real time and has been used in initial studies to improve the evaluation of global and regional wall motion. HYPOTHESIS: For further validation of the use of CK for analysis of segmental ventricular dysfunction, we assessed its sensitivity and specificity for detection of regional systolic and diastolic wall motion abnormalities in patients with coronary artery disease (CAD). METHODS: Two-dimensional (2-D) echocardiography and CK were used to study 15 normal subjects and 63 patients with technically good quality echocardiographic tracings, who underwent coronary arteriography within 1 month of echocardiography. Significant (> 70% luminal diameter stenosis) CAD was present in 50 patients (79%). RESULTS: Color kinesis tracked endocardial motion accurately in 93% of left ventricular segments. Wall motion score, systolic segmental endocardial motion (SEM), and the time of systolic SEM (tSEM) and diastolic (tDEM) segmental endocardial motion were calculated. Intra- and interobserver variability were within narrow limits. SEM and tSEM were significantly lower and tDEM was significantly higher in the patient population than in the control group (p < 0.001). Comparison between CK and 2-D echocardiography showed a correlation coefficient of 0.81 between the two techniques. The score was identically graded in 74% of segments, with concordance of 82% in diagnosing segments as abnormal. Interobserver concordance was 86% for CK (r = 0.85) and 81% for 2-D echocardiography (r = 0.80). The sensitivity and specificity of systolic and diastolic CK parameters for the detection of CAD were 88 and 92% and 77 and 85%, respectively. The positive predictive values were 93 and 96%, respectively, the negative predictive values were 63 and 73%, respectively, and the overall accuracy was 86 and 91%, respectively. CONCLUSIONS: Our data suggest that CK is a feasible and sensitive technique for identifying regional systolic as well as diastolic wall motion abnormalities in patients with CAD.

Clinical and prognostic usefulness of supine bicycle exercise echocardiography in the functional evaluation of patients undergoing elective percutaneous transluminal coronary angioplasty.

BACKGROUND: Supine bicycle exercise echocardiography (SBEE) has never been used before and early after percutaneous transluminal coronary angioplasty (PTCA) for assessing the functional outcome of the procedure and predicting late restenosis. METHODS AND RESULTS: We selected 76 subjects with stable angina, normal wall motion at rest, and exercise-induced wall-motion abnormalities before PTCA. SBEE with peak exercise imaging and the use of a 16-segment, four-grade score model was performed 54 +/- 15 hours after PTCA. No exercise-related adverse events occurred. Patients were grouped according to SBEE results: group 1 (n = 35, 46%) with negative exercise ECG and echo; group 2 (n = 19, 25%) with a positive exercise ECG but normal echo; and group 3 (n = 22, 29%) with a positive exercise echo with either a positive (n = 7, 32%) or negative (n = 15, 68%) ECG. Exercise performance significantly improved in all groups. In group 3, peak wall-motion score index decreased from 1.27 +/- 0.11 before to 1.15 +/- 0.06 after PTCA (P < .05), and duration of wall-motion abnormalities went from 81 +/- 24 to 47 +/- 19 seconds (P < .05). The rate of clinical restenosis (ie, angina recurrence or positive 6-month SBEE in asymptomatic patients, both associated with angiographic restenosis > 50%) was 37%. By multiple logistic regression analysis, clinical restenosis was associated with a positive post-PTCA exercise echo (odds ratio [OR] 3.08, 95% confidence interval [CI] 1.66 to 5.72; P = .0004) and with increasing values of pre-PTCA wall-motion score index (OR 2.86, 95% CI 1.92 to 4.27; P = .005) and duration of wall-motion abnormalities (OR 2.12, 95% CI 1.07 to 4.20; P = .04). CONCLUSIONS: SBEE is a safe and reliable tool to demonstrate changes in exercise-induced wall-motion abnormalities after PTCA and provides prognostic information in the risk assessment of clinical restenosis.

[At risk myocardium after acute infarct treated with fibrinolysis: assessment using exertion echocardiography and clinico-prognostic significance]. / Miocardio a rischio dopo infarto acuto trattato con fibrinolisi: rilevamento mediante ecocardiografia da sforzo e significato clinico-prognostico.

Several studies have been carried out on the role of exercise echocardiography for risk stratification after uncomplicated myocardial infarction. However, the diffusion of thrombolysis has entailed a remarkable change in the characteristics of these patients, with a major incidence of recurrent ischemic events or reinfarction in the follow-up. To test whether the predictive value of exercise echocardiography may be modified by thrombolytic treatment, we have studied 62 patients with acute myocardial infarction undergoing lytic therapy (Group A), compared to 153 conventionally-treated patients (Group B). All patients were asymptomatic at the time of the test, performed by cycloergometer 14 days after hospital admission. In 125 patients (47 Group A and 78 Group B) predischarge coronary angiography was performed. The exercise test showed a lower, but not significant, rate of positive tests in Group A patients (51.6 vs 58.8%). However, a positive test was more frequent in the homozonal area among patients who underwent thrombolytic therapy (50% of positive tests vs 18% in Group B; p < 0.001). Follow-up data (23 +/- 17 months) showed a higher but not significant rate of coronary events (cardiac death, reinfarction, severe angina, coronary bypass or angioplasty) in Group A patients with a positive test (62 vs 39% in Group B); however, in the subgroup with homozonal positive test, the event rate was much higher in Group A (77 vs 18% in Group B; p < 0.01). Furthermore, among patients with negative exercise test, coronary events were observed in 8% Group A and in 10% Group B patients. Therefore, our results show a higher percentage of homozonal exercise-induced ischemia with subsequent higher rate of coronary events in the thrombolyzed patients with respect to controls. This pattern is probably due to a higher rate of significant infarct-related residual stenosis, as coronary angiography have demonstrated. In conclusion, exercise echocardiography is useful in thrombolyzed patients, since it may better explore, rather than ECG, peri-necrotic areas.

Stress echocardiography: comparison of exercise, dipyridamole and dobutamine in detecting and predicting the extent of coronary artery disease.

OBJECTIVES: This study was designed to compare exercise, dipyridamole and dobutamine echocardiography in the same patients and to evaluate, by measuring physiologic and echocardiographic variables, the mechanisms by which exercise and dobutamine induce ischemia. BACKGROUND: The diagnostic value of stress echocardiography has been widely reported, but the specific effects of exercise, dipyridamole and dobutamine have not been directly compared. Furthermore, no echocardiography study has evaluated left ventricular volume changes at ischemic threshold during exercise and dobutamine administration. METHODS: One hundred patients with suspected (Group A, n = 60) or known (Group B, n = 40) coronary artery disease underwent all three tests in random order. RESULTS: In Group A, the sensitivities of exercise (mean 76%, 95% confidence interval [CI] 58% to 94%) and of dobutamine echocardiography (72%, 95% CI 53% to 91%) were higher than that of dipyridamole (52%, 95% CI 31% to 73%; p = 0.01 and p = 0.02, respectively). Specificity did not differ significantly among tests (94% for exercise [95% CI 86% to 100%] and 97% for dipyridamole and dobutamine [95% CI 91% to 100%]). Accuracy was identical for exercise and dobutamine (87%) and higher than that for dipyridamole (78%, p = 0.06). In Group B, the accuracy in predicting coronary disease extent was 71% for exercise, 33% for dipyridamole and 75% for dobutamine. At ischemic threshold, end-systolic volume index and the ratio of systolic blood pressure to end-systolic volume, a variable related to myocardial contractility, were significantly lower and higher, respectively, with dobutamine than during exercise (p < 0.05). CONCLUSIONS: In a clinical setting, exercise echocardiography should represent the first diagnostic approach because it has high diagnostic efficacy and provides additional information on exercise capacity; pharmacologic stress, particularly that of dobutamine, provides a pivotal diagnostic tool when exercise is not feasible or its results are nondiagnostic. Our preliminary data on echocardiographic evaluation at ischemic threshold support the view that myocardial contractility is a major factor in inducing ischemia during dobutamine infusion.