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Aim: Aim of the study was to evaluate if brain natriuretic peptide (BNP) levels, a cardiac neurohormone well correlated with prognosis in chronic heart failure (CHF), are associated with enhanced ventilatory response to exercise, in ambulatory patients with intermediate peak oxygen uptake (PVO2)., Methods: Resting BNP was measured in 129 consecutive stable CHF patients with mild to moderate heart failure (90% New York Heart Association (NYHA) class II or III) and intermediate (10-18 mL/kg/min) PVO2, assessed during cardiopulmonary exercise test. Mean (SD) left ventricular ejection fraction (EF) and pulmonary systolic pressure (PAP) were 41 +/- 3% and 47 +/- 14 mmHg, respectively. The enhanced ventilatory response to exercise (EVR) was assessed as a slope of the relation between minute ventilation and carbon dioxide production (VE/VCO2 slope) > 35., Results: Thirty-three over 129 patients (26%) had EVR. Mean BNP plasma level was 394 +/- 347 pg/mL. A significant correlation between BNP and EVR (r = 0.310; p < 0.01), was observed. In the logistic multivariate model, a BNP plasma level > 100 pg/mL had an independent predictive value for EVR (95% IC 1.68 to 10.5, Odds Ratio 4.23, p = 0.02). We found a significant correlation between BNP and PAP (r = 0.390; p < 0.001), and between PAP and EVR (r = 0.511; p < 0.01)., Conclusions: In CHF patients with intermediate PVO2, plasma BNP is clearly related to the enhanced ventilatory response to exercise. In this subset, BNP levels could represent an effective alternative tool for the clinical assessment in patients with unreliable cardiopulmonary exercise test.

Right bundle branch block (RBBB) is independently associated with all-cause mortality in patients referred for noninvasive evaluation of coronary artery disease. However, further stratification of risk in these patients has not been specifically addressed. The aim of this study was to risk stratify patients with RBBB who were referred for stress echocardiography. The study population was comprised of 343 patients (267 men; age 66 +/- 9 years) with RBBB who underwent pharmacologic stress echocardiography (231 dipyridamole, 112 dobutamine) for evaluation of suspected or known coronary artery disease. Overall mortality was the only end point. Stress echocardiography was positive for ischemia in 109 patients (32%). During follow-up (38 +/- 32 months), 36 deaths occurred. Seventy-three patients underwent revascularization and were censored. Ischemia at stress echocardiography (hazard ratio [HR] 2.9, 95% confidence interval [CI] 1.5 to 5.5, p=0.002), left anterior fascicular block (LAFB) (HR 2.8, 95% CI 1.4 to 5.6, p = 0.002), age >65 years (HR 2.1, 95% CI 1.0 to 4.3, p=0.047), and wall motion score index at rest (HR 2.5, 95% CI 1.0 to 6.5, p=0.057) were multivariate predictors of mortality. On the basis of stress echocardiographic result and presence and/or absence of LAFB, 3 levels of risk were identified: (1) low-risk, in cases of no ischemia and no LAFB (49% of the entire study population); (2) intermediate-risk, in cases of ischemia or LAFB only; and (3) high-risk, in cases of ischemia and LAFB. Clinical data, electrocardiography at rest, and stress echocardiographic results can provide effective stratification of risk in patients with RBBB.

Purpose: To investigate the prognostic implications of conduction defects in subjects without proven coronary artery disease who had been referred for stress echocardiography., Methods: The study sample consisted of 1230 patients (574 men and 656 women; mean [+/- SD] age, 63 +/- 10 years) who underwent stress echocardiography with dipyridamole (n = 780) or dobutamine (n = 450) to evaluate suspected coronary artery disease. A summary wall motion score (on a 1 to 4 scale) was calculated. Patients were followed for a mean of 41 +/- 27 months; mortality was the only endpoint., Results: Four hundred and twenty patients (34%) had intraventricular conduction defects on a resting electrocardiogram (173 with complete left bundle branch block, 98 with isolated right bundle branch block, 43 with right bundle branch block with left anterior hemiblock, and 106 with left anterior hemiblock). Ischemia at stress echo (new or worsening of preexisting wall motion abnormality) was found in 250 patients (20%). There were 56 deaths during follow-up; 138 patients underwent revascularization and were censored. Multivariate predictors of mortality were resting wall motion score index (hazard ratio [HR] = 6.0 per unit increase; 95% confidence interval [CI]: 2.3 to 16; P <0.0001), ischemia at stress echo (HR = 3.9; 95% CI: 2.2 to 6.7; P <0.0001), age >65 years (HR = 3.2; 95% CI: 1.7 to 5.9; P <0.0001), hypertension (HR = 1.8; 95% CI: 1.1 to 3.2; P = 0.03), and right bundle branch block with left anterior hemiblock (HR = 3.7; 95% CI: 1.8 to 7.5; P <0.0001). The other three forms of intraventricular conduction defects (left bundle branch block, isolated complete right bundle branch block, and left anterior hemiblock) were not associated with mortality in multivariate analyses, or among the 980 patients who did not have ischemia., Conclusion: Right bundle branch block with left anterior hemiblock is an independent predictor of mortality in patients with suspected coronary artery disease undergoing stress echocardiography, whereas isolated right bundle branch block is associated with outcomes similar to those observed in patients with no conduction defects.

Background: Recovery of function following stroke plateaus in about 1 year, typically leaving upper arm function better than that in the hand. Since there is competition among body parts for territory in the sensorimotor cortex, even limited activity of the upper arm might prevent the hand from gaining more control, particularly when the territory is reduced in size because of the stroke. Deafferentation of a body part in a healthy brain enhances cortical representations of adjacent body parts, and this effect is markedly increased by voluntary activity of the adjacent part., Objective: To explore whether deafferentation of the upper arm, produced by a new technique of regional anesthesia during hand motor practice, helps recovery of hand function in patients with long-term stable weakness of their hand following stroke., Methods and Results: Deafferentation, produced by a new technique of regional anesthesia of the upper arm during hand motor practice, dramatically improved hand motor function including some activities of daily living. The improvement was associated with an increase in transcranial magnetic stimulation-evoked motor output to the practice hand muscles., Conclusion: This is a novel therapeutic strategy that may help improve hand function in patients with long-term weakness after stroke.

Background: The purpose of this study was to evaluate efficacy and safety of biphasic shock for atrial fibrillation cardioversion to sinus rhythm. A second endpoint was to evaluate myocardial damage by means of cardiac troponin I dosage., Methods: We studied 164 patients, with drug-resistant atrial fibrillation (208 episodes). Group A patients underwent biphasic shock normalized with respect to weight: 50 J (weight < 60 kg), 70 J (weight 61-84 kg) and 100 J (weight > 84 kg; the second and third shocks were 2 and 3 times higher than the first. Group B underwent sequential monophasic shock of 200, 300 and 360 J. Troponin I was evaluated at baseline, and 6, 12 and 24 hours after cardioversion., Results: Total efficacy was 92% for biphasic shock and 89% for monophasic shock. First-shock efficacy with biphasic waveform (57.3%) was significantly greater than with first monophasic waveform (21.5%) (p = 0.000). Cardiac troponin I increased from 0.4 +/- 1.1 to 0.8 +/- 2.2 compared to a normal value of 2 ng/ml., Conclusions: For transthoracic cardioversion of atrial fibrillation, biphasic shock has a greater efficacy requiring less energy compared to monophasic shock. Normal mean values of cardiac troponin I proved the absence of myocardial damage.

Objective: Forty-seven patients with long-term mental illness were transferred to the community following the closure of a psychiatric hospital in Sydney. This 6-year evaluation is an extension of a detailed clinical, ethnographic and economic study of the initial 2-years of community transition., Method: Quantitative evaluation was conducted using the Brief Psychiatric Rating Scale, Life Skills Profile, Social Behaviour Scale, Montgomery Asberg Depression Rating Scale and Quality Of Life measures. Assessments were completed prior to discharge and at two- and 6-year intervals following community transfer. Repeated measures analysis was utilized to determine changes in outcome variables over time. The residents' perception of 6-years of community living was explored in qualitative semistructured interviews. Details of accommodation, level of care, readmissions, incidents and medication were also documented., Results: During the 6 years following community relocation a total of seven residents returned to hospital for long-term care, three residents died from medical causes and one resident required detention in a corrective services facility. The 36 residents who remained in the community at the 6-year follow-up no longer required intensive 24-h supervision. Living semi-independently, 23 residents resided in two to three person accommodation with either daily or weekly case manager visits. Clinically, community residents remained stable over the 6 years without significant changes in psychiatric symptoms, depression, living skills or social behaviour problems. Clinical stability was achieved with significant reduction in medication levels over the 6 years. Community-based residents continued to experience improved quality of life and reported their marked preference for living in the community., Conclusion: The residents maintained community tenure with significant improvement in quality of life and a reduction in medication, supported by a mental health system with adequate community resources. Issues regarding continuing rehabilitation and social integration need to be addressed. Further deinstitutionalization will require 24-h supervision for most initially and for some on a continuing basis. An ageing population will require specific age related medical and psychiatric services.

Background: beta-Blockers improve clinical outcome after acute myocardial infarction (AMI), but few data are available on their effectiveness in preventing left ventricular remodeling. The aim of the study was to assess the relative effects of captopril, metoprolol, and their combination on left ventricular remodeling after uncomplicated AMI., Methods: Two hundred fifty consecutive patients with a first AMI were randomly allocated to receive for 6 months captopril (up to 75 mg/d, group 1), metoprolol (up to 200 mg/d, group 2), or both (group 3) starting within 24 hours from symptom onset. Of these, 130 patients (group 1, 46; group 2, 47; group 3, 37) completed the study; all patients underwent 2-dimensional echocardiography at baseline and after 2 weeks and 3 and 6 months from AMI., Results: At 6 months, in comparison with baseline values, left ventricular end-diastolic area index (LVEDI) significantly increased in group 3 (P =.013) and wall motion score index significantly decreased in group 1 (P =.038). At any follow-up evaluation, the covariance analysis showed significantly greater interval changes in LVEDI in group 3 than in group 1 (P =.0077 at 2 weeks, P =.0108 at 3 months, and P = 0.0155 at 6 months). No significant differences were observed between group 1 and group 2 and between group 2 and group 3., Conclusions: After uncomplicated first AMI, early and long-term treatment with captopril alone attenuates left ventricular remodeling better than its combination with metoprolol. In the head-to-head captopril versus metoprolol therapy strategy comparison, captopril alone seems more effective in reducing postinfarction enlargement, but a definite difference was not demonstrated.

Purpose: Although coronary artery disease is a frequent cause of left bundle branch block, the prognostic value of myocardial ischemia in patients with this conduction abnormality has not been defined. We investigated the value of pharmacologic stress echocardiography in risk stratification of patients with left bundle branch block., Patients and Methods: Three hundred eighty-seven patients [230 men and 157 women, mean (+/- SD) age, 64 +/- 9 years] with complete left bundle branch block on the resting electrocardiogram underwent dobutamine (n = 217) or dipyridamole (n = 170) stress echocardiography to evaluate suspected or known coronary artery disease. A summary wall motion score (on a one to four scale) was calculated. The primary end points were cardiac death and nonfatal myocardial infarction., Results: A positive echocardiographic result (evidence of ischemia) was detected in 109 (28%) patients. During a mean follow-up of 29 +/- 26 months, there were 21 cardiac deaths and 20 myocardial infarctions, 63 patients underwent coronary revascularization, and 1 patient received a heart transplant. In a multivariate analysis, four clinical and echocardiographic variables were associated with increased risk of cardiac death: resting wall motion score index [hazard ratio (HR) = 7.5 per unit; 95% confidence interval (CI), 2.8 to 20; P = 0.001], previous myocardial infarction (HR = 2.9; 95% CI, 1.1 to 7.3; P = 0.02), diabetes (HR = 2.7; 95% CI, 1.1 to 6.6; P = 0.03), and the change in wall motion score index from rest to peak stress (HR = 3.0 per unit; 95% CI, 1.0 to 8.6; P = 0.04). The 5-year survival was 77% in the ischemic group and 92% in the nonischemic group (P = 0.02). Four variables were associated with increased risk of cardiac death or infarction: previous myocardial infarction (HR = 3.4; 95% CI, 1.7 to 6.8; P = 0.0005), diabetes (HR = 2.4; 95% CI, 1.2 to 4.6; P = 0.01), resting wall motion score index (HR = 2.2 per unit; 95% CI, 1.1 to 4.1; P = 0.02), and positive echocardiographic result (HR = 2.2; 95% CI, 1.1 to 4.5; P = 0.03). The 5-year infarction-free survival was 60% in the ischemic group and 87% in the nonischemic group (P < 0.0001). Stress echocardiography significantly improved risk stratification in patients without previous myocardial infarction (P = 0.0001), but not in those with previous myocardial infarction (P = 0.08). In particular, it provided additional value over clinical and resting echocardiographic findings in predicting cardiac events among patients without previous infarction., Conclusions: Myocardial ischemia during pharmacologic stress echocardiography is a strong prognostic predictor in patients with left bundle branch block, particularly in those without previous myocardial infarction.

Background: The outpatient prognostic assessment of coronary artery disease (CAD) by exercise electrocardiography has limitations, including the feasibility of the test and its low positive predictive value in several clinical conditions. In the current study we investigated the safety, feasibility, and prognostic value of pharmacologic stress echocardiography in a large cohort of ambulatory patients., Methods: The study group was made of 1482 ambulatory patients (969 men, aged 60 +/- 10 years) who underwent stress echocardiography with either dipyridamole (n = 846) or dobutamine (n = 636) for evaluation of suspected or known stable CAD. The pretest likelihood of CAD was intermediate (<70%) in 709 patients and high (> or =70%) in 773 patients., Results: There was no complication during the dipyridamole test, whereas 2 ischemia-dependent, sustained ventricular tachycardias occurred during the dobutamine test. Limiting side effects were observed in 2% of dipyridamole and in 3% of dobutamine stresses. The echocardiogram was positive in 459 patients. During a mean follow-up of 28 +/- 24 months, 58 patients died, 33 had a nonfatal myocardial infarction, and 158 underwent early (< or =3 months) and 64 late (>3 months) revascularization. Multivariate predictors of hard events (death, infarction) were positive echocardiographic results (hazard ratio [HR] 2.9) and resting wall motion score index (WMSI) (HR 2.3). In considering major events (death, infarction, late revascularization) as end points, positive echocardiographic result (HR 4.3), scar (HR 2.2), and resting WMSI (HR 1.7) were independent prognostic predictors. The 5-year survival rates for the ischemic and nonischemic groups were, respectively, 80% and 91% (HR 3.6, 95% confidence interval [CI] 3.8-8.4; P <.0001) considering hard cardiac events and 65% and 88% (HR 2.6, 95% CI 2.1-5.9; P <.0001) considering major events. Multivariate predictors of major events were positive echocardiographic results (HR 8.2) and male sex (HR 2.5) for the intermediate-risk group and positive echocardiographic results (HR 2.9), resting WMSI (HR 1.8), and prior Q-wave myocardial infarction (HR 1.8) for the high-risk group., Conclusions: Pharmacologic stress echocardiography is safe, highly feasible, and effective in prognostic assessment of ambulatory patients when both a general population and groups selected on the basis of pretest likelihood of CAD are analyzed. It represents a valid complementary tool to exercise electrocardiography for prognostic purposes in outpatients.

We have found that certain tetrasubstituted pyrazoles are high-affinity ligands for the estrogen receptor (ER) (Fink et al. Chem. Biol. 1999, 6, 205-219) and that one pyrazole is considerably more potent as an agonist on the ERalpha than on the ERbeta subtype (Sun et al. Endocrinology 1999, 140, 800-804). To investigate what substituent pattern provides optimal ER binding affinity and the greatest enhancement of potency as an ERalpha-selective agonist, we prepared a number of tetrasubstituted pyrazole analogues with defined variations at certain substituent positions. Analysis of their binding affinity pattern shows that a C(4)-propyl substituent is optimal and that a p-hydroxyl group on the N(1)-phenyl group also enhances affinity and selectivity for ERalpha. The best compound in this series, a propylpyrazole triol (PPT, compound 4g), binds to ERalpha with high affinity (ca. 50% that of estradiol), and it has a 410-fold binding affinity preference for ERalpha. It also activates gene transcription only through ERalpha. Thus, this compound represents the first ERalpha-specific agonist. We investigated the molecular basis for the exceptional ERalpha binding affinity and potency selectivity of pyrazole 4g by a further study of structure-affinity relationships in this series and by molecular modeling. These investigations suggest that the pyrazole triols prefer to bind to ERalpha with their C(3)-phenol in the estradiol A-ring binding pocket and that binding selectivity results from differences in the interaction of the pyrazole core and C(4)-propyl group with portions of the receptor where ERalpha has a smaller residue than ERbeta. These ER subtype-specific interactions and the ER subtype-selective ligands that can be derived from them should prove useful in defining those biological activities in estrogen target cells that can be selectively activated through ERalpha.

Background: The aim of this study was to verify the changes in the autonomic balance by means of heart rate variability assessment in patients with myocardial infarction referred for cardiac rehabilitation., Methods: We studied 122 patients (79 males, 43 females, mean age 56 +/- 5 years), with a first uncomplicated myocardial infarction (anterior 48, thrombolysis 72), Killip class 1, preserved left ventricular function (ejection fraction 49 +/- 6%). All patients were free of inducible residual ischemia. Four weeks after myocardial infarction, patients were randomized into two groups; Group 1 (n = 58) referred for an 8 week cardiac rehabilitation program (scheduled: 24 sessions); Group 2 (n = 64): normal daily physical activity. During a 24-hour Holter ECG monitoring the following parameters were calculated in pharmacological wash-out at randomization (T0) and at the end of cardiac rehabilitation/control period (T1): mean value of RR intervals (RR), its standard deviation (SDNN), pNN50, rMSSD in the time domain; low frequency (LF) and high frequency (HF) value and the LF/HF ratio in the frequency domain. T1-T0 changes in percent values (delta %) were considered and compared between the two groups., Results: Thirty-one patients were excluded from the study either for insufficient adhesion to the cardiac rehabilitation program (< 13 sessions, 22 patients) or recurrent ischemia (3 Group 1 patients and 3 Group 2 patients) and non-assessable 24-hour Holter ECG monitoring (3 patients). Thirty-one Group 1 patients and 60 Group 2 patients completed the study with a first and a second 24-hour Holter ECG monitoring performed at 30 +/- 3 days and 60 +/- 4 days respectively. At the same time an ergospirometric test was performed to evaluate cardiopulmonary function by means of exercise time, maximum oxygen consumption, anaerobic threshold, exercise time at the anaerobic threshold, and maximum oxygen consumption at the anaerobic threshold. Twenty-eight Group 1 patients and 44 Group 2 patients completed the study with a first and a second ergospirometric test. Baseline heart rate variability parameters were comparable in the two groups. During the observation period only in Group 1 patients heart rate variability parameters changed significantly: RR (Group 1 = +18.3 +/- 21.3; Group 2 = +4.2 +/- 5.2, p = 0.000), pNN50 (Group 1 = 45.0 +/- 38.9; Group 2 = +24.2 +/- 34.7, p = 0.011), HF (Group 1 = +81.6 +/- 124; Group 2 = -28.7 +/- 75.4, p = 0.014) and LF/HF ratio (Group 1 = -26.0 +/- 16.1; Group 2 = -4.9 +/- 6.1, p = 0.062). There were no significant differences in SDNN, rMSSD and LF. A linear correlation between delta LF/HF ratio and baseline LF/HF ratio values was found in Group 1 (r = 0.489, p = 0.006), whereas no correlation was found between this parameter and age, ejection fraction, creatine phosphokinase, and infarct localization. Group 1 patients had a significant improvement in exercise tolerance compared to Group 2 patients., Conclusions: A cardiac rehabilitation program positively modifies the sympatho-vagal balance in patients with uncomplicated myocardial infarction, increasing the parasympathetic tone and exercise tolerance.

Unlabelled: The RIMA (Rimodellamento Infarto Miocardico Acuto) study was designed to assess the relative effects of angiotensin-converting enzyme (ACE) inhibition by captopril, beta-blocker therapy by metoprolol, and their combination in patients with a first acute myocardial infarction on: 1. echocardiographically detected left ventricular remodeling; 2. prognosis. The second goal will be the argument of the present paper. Two-hundred fifty < or = 75 years consecutive patients (mean age: 58 yrs, males = 203) with acute myocardial infarction were randomly allocated to receive for > or = 3 months captopril (up to 75 mg/day, Group 1), metoprolol (up to 200 mg/day, Group 2) or captopril + metoprolol (Group 3) starting in the first 24 hours after the onset of symptoms. Intravenous beta-blockers in the acute phase of myocardial infarction and all other cardioactive drugs were allowed. The effect of the randomized therapy at six months from admission to the coronary care unit was considered in relation to: 1. recurrence of spontaneous cardiac events and of elective revascularization procedures; 2. adverse reactions (hypotension, atrioventricular block, cough, allergy, need of beta-blockers in Group 1, need for ACE inhibition in Group 2) requiring treatment modification based on physician's decision., Results: Definite follow-up data were available in 226 patients and 195/226 patients (86%) had a complete treatment period. In these patients (per protocol analysis), 37 spontaneous cardiac events occurred: cardiac death = 6, non-fatal reinfarction = 9, unstable angina requiring hospitalization = 16, congestive heart failure = 6. Moreover, seven patients received a coronary revascularization procedure. Events occurred in 11/67 patients from Group 1, 16/63 patients from Group 2, 10/65 patients from Group 3 (16% vs 25% vs 15%, p = 0.28). The multiple logistic regression analysis demonstrated an increased odds ratio (OR) for spontaneous cardiac events in patients from Group 2 (OR = 2.82, 95% Cl: 1.16-6.87: p < 0.05). Elective revascularization procedures were statistically less frequent in patients treated with metoprolol (Group 1 = 9%, Group 2 = 1.6%, Group 3 = 0%; Group 1 vs Groups 2 and 3; p = 0.03). The intention-to-treat analysis on the overall population (226 patients) confirmed the presence of a trend towards a higher risk in patients from Group 2 (OR = 2.1, 95% Cl: 0.96-4.59; p = 0.06). Adverse reactions were observed in 16 patients from Group 1, 6 patients from Group 2 and 15 patients from Group 3 (22% vs 10% vs 23%; Group 2 vs Groups 1 and 3; p = 0.08). At the multivariate regression analysis, a trend towards less adverse reactions in patients assigned to the beta-blocker therapy alone was confirmed (OR = 0.41, 95% Cl: 0.15-1.13; p = 0.07)., Conclusions: In a randomized early post-infarction treatment strategy, ACE inhibition with captopril alone or in combination with metoprolol demonstrated an increased protection against spontaneous cardiac events at six months in comparison with metoprolol alone. On the other hand, the beta-blocker treatment was associated with a lower number of elective revascularization procedures and appeared better tolerated than ACE inhibition.

Background: Residual viable myocardium identified by dobutamine stress after myocardial infarction may act as an unstable substrate for further events such as subsequent angina and reinfarction. However, in patients with severe global left ventricular dysfunction, viability might be protective rather than detrimental. The aim of this study was to assess the impact on survival of echocardiographically detected viability in medically treated patients with global left ventricular dysfunction evaluated after acute uncomplicated myocardial infarction., Methods and Results: The data bank of the large-scale, prospective, multicenter, observational Echo Dobutamine International Cooperative (EDIC) study was interrogated to select 314 medically treated patients (271 men; age, 58+/-9 years) who underwent low-dose (1.6). Patients were followed up for 9+/-7 months. Low-dose dobutamine stress echocardiography identified myocardial viability in 130 patients (52%). Dobutamine-atropine stress echocardiography was positive for ischemia in 148 patients (47%) and negative in 166 patients (53%). During the follow-up, there were 12 cardiac deaths (3.8% of the total population). With the use of Cox proportional hazards model, delta low-dose WMSI (the variation between rest WMSI and low-dose WMSI) was shown to exert a protective effect by reducing cardiac death by 0.8 for each decrease in WMSI at low-dose dobutamine (coefficient, -0.2; hazard ratio, 0.8; P<0.03); WMSI at peak stress was the best predictor of cardiac death in this set of patients (hazard ratio, 14.9; P<0.0018)., Conclusions: In medically treated patients with severe global left ventricular dysfunction early after acute uncomplicated myocardial infarction, the presence of myocardial viability identified as inotropic reserve after low-dose dobutamine is associated with a higher probability of survival. The higher the number of segments showing improvement of function, the better the impact is of myocardial viability on survival. The presence of inducible ischemia in this set of patients is the best predictor of cardiac death.

Background: Thrombolysis has reduced early and longterm mortality by about 20%; sometimes, however, there is a re-occlusion of the infarct related artery or an unsuccessful thrombolysis. In these situations, there is a possible increase in detrimental events in the follow-up., Objectives: The aim of the study was to compare the prognostic value of dobutamine echocardiography (DET) and ECG exercise test (EET) in pts submitted to thrombolysis., Methods: One hundred and fifty-one pts, with acute uncomplicated myocardial infarction, were enrolled. The pts were able to perform EET and had a sufficient echocardiographic window; 58 had anterior myocardial infarction (38%), 79 had inferior (52%), 2 had lateral (1%), 12 had non-Q (8%). EET was performed with an initial load of 25 Watt, and thereafter, 25 W every two minutes. DET was performed with step-wise infusion every three minutes (5, 10, 20, 30 and 40 mcg/kg/min.). If the target heart rate was not reached, a further dose of 40 mcg/kg/min. together with atropine 0.25-1 mg was administered, in the absence of signs and symptoms of ischemia., Results: During a mean (+/- SD) follow-up period of 8 +/- 4.5 months (range 1-23), 16 spontaneous events happened (4 deaths, 5 non-fatal re-infarctions, 7 unstable angina). One-hundred and three EET (68%) were negative for ongoing ischaemia, while 48 were positive, 79 DET (52%) were negative for ongoing ischaemia and 72 were positive (48%). Statistical results: DET and EET had a sensitivity of 41% and 54%, a specificity of 57% and 74%, a positive predictive value of 7% and 14%, a negative predictive value of 91% and 95%, an accuracy of 56% and 73%. Kaplan-Maier survival curves demonstrated that patients with Peak Wall motion > 1.8 and EET score > 3, had the higher risk of spontaneous events., Conclusion: A few spontaneous events happened in the follow-up. These data demonstrate that patients treated with thrombolysis are not at high risk of spontaneous events. DET and EET, therefore, have had a high negative predictive value. For this reason, we can conclude that pts with negative tests can be considered at low risk and do not need any further investigations.

Unlabelled: Recent reports suggest a relationship between ECG changes and myocardial viability during dobutamine stress echocardiography in patients with myocardial infarction. The aim of the study was to analyze the predictive value of T-wave normalization and ST segment elevation during low- (10 mucg/Kg/m') and high-dose (40 mucg/Kg/m') dobutamine stress test for late spontaneous recovery of function in patients with a first uncomplicated Q-wave myocardial infarction., Methods: Seventy eight consecutive patients (59 +/- 9 yrs; males = 67; anterior MI = 41, inferoposterior MI = 37 pts) underwent baseline 2D echo and dobutamine stress test at 9 +/- 2 days from onset of symptoms and they were free of cardiac events during the first three months after myocardial infarction. T-wave normalization (negative T-wave becoming > or = 1 mm upright in > or = 2 leads) and ST segment elevation (> or = 0.1 mm in > or = 2 leads) at low- and high-dose dobutamine infusion were compared with an improvement of contractility in the infarct area detected echocardiographically at three months. A wall motion score decrease in infarct area > or = 2 was the criterion for recovery of contractility., Results: ST segment elevation occurred in 19/78 patients at low dose (24%) and in 45/78 patients at high dose (58%). Late recovery of contractility in the infarct area was observed in 38/78 patients (49%). The positive and negative predictive values of ST segment elevation for late recovery of contractility were, respectively, 63-56% at low dose and 47-48% at high dose. A baseline negative T-wave in > or = 2 leads was present in 56 patients, and 27 (48%) showed recovery of contractility at three months. T-wave normalization occurred in 14 patients at low-dose (25%) and in 29 patients at high-dose dobutamine infusion (52%). The positive and negative predictive values of T-wave normalization were, respectively, 71-59% at low dose and 62-67% at high dose. Both ECG markers were present in 10/56 patients at low dose and in 19 patients at high dose. The positive and negative predictive values, respectively, were 70-57% at low dose and 58-57% at high dose. At univariate analysis, neither the ECG changes alone nor their combination during dobutamine stress testing were shown to be significant predictors of recovery of function., Conclusions: Our study demonstrates that in patients with a first uncomplicated Q-wave myocardial infarction, the T-wave normalization and/or the ST segment elevation occurring during early dobutamine stress testing are not reliable predictors of late spontaneous recovery of contractility in the infarct area.

We analyzed the relation between dobutamine-induced Q-wave ST-segment elevation and regional contraction during low (5 to 10 microg/kg/min) and high doses (20 to 40 microg/kg/min) of dobutamine in a series of 391 dobutamine echocardiographic tests performed 10 +/- 2 days after a first uncomplicated acute myocardial infarction (AMI). ST-segment elevation was defined as > or = 1 mm new or additional J-point elevation with a horizontal or upsloping ST segment lasting 80 ms. Wall motion score index at rest was derived using a 16 segment-4 grade score model. Patients with dobutamine-induced ST-segment elevation had a higher wall motion score index at rest (anterior wall AMI: 1.67 +/- 0.27 vs 1.43 +/- 0.30, p = 0.0001; inferior wall AMI: 1.44 +/- 0.27 vs 1.30 +/- 0.18, p = 0.0001) and similar incidence and extent of myocardial viability and homozonal ischemia in comparison with those without ST-segment elevation. The sensitivity, specificity, and accuracy of dobutamine-induced ST-segment elevation for detecting residual homozonal ischemia were 51%, 55%, and 54%, respectively, in patients with anterior wall AMI, and 42%, 68%, and 58%, respectively, in patients with inferior wall AMI. In conclusion, dobutamine-induced ST-segment elevation is not associated with higher incidence and extent of viable or jeopardized myocardium but rather to a greater extent of wall motion abnormalities at rest. Thus, this finding does not represent a clinically reliable discriminator for selecting patients for coronary angiography and possible revascularization procedures.

Background: There is no written data about the efficacy of transesophageal electropharmacologic test (TEPT) to guide antiarrhythmic therapy in the prophylaxis of paroxysmal atrial fibrillation (PAF) recurrences. Aim of this study was to assess the efficacy of TEPT compared to empiric treatment in the prophylaxis of PAF., Methods: One-hundred-sixty patients (pts) with previous episodes of PAF were randomized in two groups: Gr A (90 pts) was submitted to basal transesophageal electrophysiologic study (BTES); Gr B (70 pts) was submitted to randomized empiric antiarrhythmic therapy with flecainide (F), propafenone (P) and sotalol (S). The end-points of stimulation protocol in Gr A were the induction of sustained atrial fibrillation (SAF)- > or = 1 min duration- or the end of protocol. SAF was inducible in 68/90 pts (Gr A1) while it was not in 22/90 pts (Gr A2). Pts in Gr A1 were subsequently submitted to TEPT at steady-state of F, P or S randomized in first choice. Pts responders (R) (SAF non inducible) were submitted to TEPT with other antiarrhythmic drugs randomized in second choice: R were followed-up with the same drug in chronic oral assumption, while non responders (NR) were submitted to TEPT with the last drug and followed-up with the same drug both in R and NR case. The same stimulation protocol was employed in TEPT as in BTES. Pts in Gr A2 withdrew from the study. During follow-up all-pts were submitted to periodic specialist examinations every three months. In case of PAF recurrence pts withdrew from the study., Results: Mean follow-up duration in the study population was 17.5 +/- 8.5 months. One-hundred-eight TEPT were performed in Gr A1: 36 tests with F, 40 with P and 32 with S. Twenty pts were R with F (55% of tests) and 17 finished the follow-up, 22 pts were R with P (55% of tests) and 16 finished the follow-up, 19 pts were R with S (59% of tests) and 15 finished the follow-up; 3 pts with F, 2 pts with P and 2 pts with S were NR in last choice and finished the follow-up. In Gr A1 61/68 pts (90%) were R and 55/68 (81%) finished the follow-up (13 pts withdrew from the study). In Gr B (70 pts) 23 pts were randomized to F and 20 finished the follow-up, 24 pts were randomized to P and 20 finished the follow-up, 23 pts were randomized to S and 20 finished the follow-up (10 pts withdrew from the study). PAF recurrences during follow-up in Gr A1 were in 15/55 pts (27%): 9/48 pts (19%) R and 6/7 pts (86%) NR, and in Gr B in 41/60 pts (68%). Gr A1 vs Gr B p < 0.001. Univariate and multivariate statistical analysis showed the empiric treatment as the only variable with high predictive value for PAF recurrences (risk ratio 1.53). PPV and NPV of TEPT were respectively 86 and 81%., Conclusions: TEPT-guided antiarrhythmic therapy in the prophylaxis of PAF recurrences seems to be an effective method in predicting the efficacy of the chronic antiarrhythmic therapy, when compared to the empiric treatment. The non inducibility of SAF at TEPT would have a high predictive value for event-free follow-up.

Objectives: The aim of this multicenter, multinational, prospective, observational study was to assess the relative value of myocardial viability and induced ischemia early after uncomplicated myocardial infarction., Background: Dobutamine-atropine stress echocardiography allows evaluation of rest function (at baseline), myocardial viability (at low dose) and residual ischemia (peak dose, up to 40 micrograms with atropine up to 1 mg) in one test., Methods: Dobutamine-atropine stress echocardiography was performed 12 +/- 5 days (mean +/- SD) after a first uncomplicated acute myocardial infarction in 778 patients (677 men; mean age 58 +/- 10 years) with technically satisfactory rest echocardiographic study results. Patients were followed-up for 9 +/- 7 months., Results: Dobutamine-atropine stress echocardiographic findings were positive for myocardial ischemia in 436 of patients (56%) and negative in 342 (44%). During follow-up, there were 14 cardiac-related deaths (1.8% of the total cohort), 24 (2.9%) nonfatal myocardial infarctions and 63 (8%) hospital readmissions for unstable angina. One hundred seventy-four patients (22%) underwent coronary revascularization (bypass surgery or coronary angioplasty). Spontaneous events occurred in 61 of 436 patients with positive and 40 of 342 patients with negative findings on dobutamine-atropine stress echocardiography (14% vs. 12%, p = 0.3). When only spontaneously occurring events were considered, the most important predictor was myocardial viability (chi-square 9.7). Using the Cox proportional hazards model, only the presence of myocardial viability (hazard ratio [HR] 2.0, p < 0.002) and age (HR 1.03, p < 0.001) were predictive of spontaneously occurring events. When only hard cardiac events were considered, age was the strongest predictor (chi-square 3.6, p = 0.056), followed by wall motion score index (WMSI) at peak dose (chi-square 3.3, p = 0.06) and remote ischemia (chi-square 2.25, p = 0.1). When cardiac death was considered, WMSI at peak dose was the best predictor (HR 9.2, p < 0.0001)., Conclusions: During dobutamine stress, echocardiographic recognition of myocardial viability is more prognostically important than echocardiographic recognition of myocardial ischemia for predicting unstable angina, whereas WMSI at peak stress was the best predictor of cardiac-related death. Different events can be recognized with different efficiency by various stress echocardiographic variables.

Backgrounds: The aim of the study was to assess the relative prognostic accuracy of dobutamine echocardiography (TED) vs maximal bicycle exercise electrocardiography (TE) in patients with proven coronary artery disease., Methods: One hundred and thirty consecutive patients (70 patients with uncomplicated recent myocardial infarction, 19 asymptomatic patients with previous myocardial infarction and 41 patients with stable angina pectoris and previous myocardial infarction or previous myocardial revascularization procedure) underwent TED (incremental dobutamine infusion: 5 to 40 ncg/kg/min, continued with atropine 0.25 to 1 mg iv if necessary) and TE on different days and in random order. Criteria for positivity were: new or worsening regional dyssynergy for TED; ST segment shift > or = 1 mm from baseline for TE. End points were defined as spontaneous events (cardiac death, myocardial infarction and unstable angina) and total events (spontaneous events plus myocardial revascularization procedures)., Results: During 15.4 +/- 7.9 (range 1-33) months of follow-up, 33 events occurred: cardiac death (1), myocardial infarction (4) unstable angina (21) myocardial revascularization (7). Sensitivity, specificity, positive and negative predictive value, prognostic accuracy were similar for TED and TE (P = NS). Cumulative event-free survival curves as a function of TED and TE results were both statistically significant. A Cox stepwise regression analysis identified TED positivity obtained without atropine administration as the best predictor of spontaneous and total events (Odds ratio 5.33 and 4.38, respectively). Cumulative survival curves obtained by the combination of TED and TE results were statistically different (P < 0.05 and P < 0.001 for spontaneous and total events, respectively) and showed a poor clinical outcome in patients with both tests or only TED positive. TED correctly predicted clinical outcome in 24/39 patients in whom there was disagreement between the two tests., Conclusions: In patients with proven coronary artery disease, TED and TE have a similar accuracy for predicting clinical outcome. Where a discrepancy is seen between the two tests, TED appears to have a slightly higher prognostic value.

Background: Coronary blood reserve is the capacity of coronary vessels to vasodilate and thereby to increase the blood flow, when the heart needs more energy. However, when a coronary stenosis occurs, the capacity to vasodilate is reduced or completely diminished. It is then necessary to use all the tools useful in evaluating the functional conditions of the coronary vessels. Above all, the intracoronary Doppler technique is used to measure the velocity of blood flow. Our purpose was to evaluate a non-invasive tool "Multiplane Transesophageal Echocardiography" in the study of velocity of the anterior descendent artery before and after adenosine infusion., Methods: At first, we studied 28 patients (pts), which we divided in two groups: Group A, 18 pts 59.38 +/- 8.23 mean age, 15 M. and 3 F., with anterior descending disease; Group B 10 pts, 59.20 +/- 8.48 mean age, 7 M. and 3 F, without significant stenosis (> 75%). Echocardiography examinations were performed with a 5 MHz multiplane probe, connected to a 1000 Hewlett Parkard echocardiography. Before the test, Diazepam 1 mg i.v. and Lidocaine spray were administered to the patients. We introduced the transesophageal probe and after choosing the best position of the aortic short axis view, we studied the anterior descending artery and measured the maximum and mean diastolic and sistolic velocities (V.MAX D., V.MN.D., V.MAX S., V.MN.S.)., Results: Transesophageal echocardiography allowed us to study the anterior descending artery in 95% of pts. There were no side effects, except for one pt affected by severe bradicardia. In Group B there was an increase of the diastolic and sistolic velocity after adenosine infusion, resulting twice greater they the rest values. The adenosine/rest velocities ratios were statistically significant (V.MAX D. p < 0.02) (V.MN.D. p < 0.03)., Conclusion: Our results demonstrated an higher capacity of the Multiplane Transesophageal Echocardiography in studiing coronary blood reserve. We used adenosine, as a vasodilator drug, because of its short half-life and because it can be replatedly infused. The flow velocity values increased up to more than twice the rest values only in normal subjects.

Background: Recent reports demonstrated an increased accuracy of dipyridamole echocardiography test with the intravenous infusion of 0.25 to 1 mg of atropine in 1-4 consecutive administrations at the end of the test. The effect of higher doses of atropine during dipyridamole echocardiography, potentially able to further increase heart rate and myocardial oxygen consumption, has not been evaluated. The aim of the study was to evaluate the effect of high doses of atropine during dipyridamole echocardiography and to investigate the possible pharmacological interference between dipyridamole and atropine., Methods: One-hundred consecutive patients (M = 81, F = 19; mean age 58 yrs) without inducible wall motion abnormalities at 14th minute of a high-dose (0.84 mg/Kg in 10') dipyridamole echocardiography test were studied. Seventy-five patients referred to the test in pharmacological wash-out were randomly divided in three groups: 25 patients (Group 1) received 10 mcg/Kg of atropine in 60"; 25 patients (Group 2) received 15 mcg/Kg of atropine in 120"; 25 patients (Group 3) received 20 mcg/Kg of atropine in 120"; moreover, 25 patients with a full-dose oral beta-blocker therapy (Group 4) received 20 mcg/Kg of atropine in 120". Atropine was infused during the 15th and 16th minute of the test. Heart rate (HR) changes and new wall motion abnormalities induced by atropine were considered and compared for each Group. In 60 patients (15 randomly selected from each Group) the effect on mean HR and R-R interval (msec) of the same dose of atropine infused during dipyridamole echocardiography was evaluated in resting conditions 24 hours apart., Results: The dipyridamole-atropine test was well tolerated and accomplished in all patients. HR increased significantly in all Groups of patients in comparison with pre-atropine HR values (Group 1: +14 +/- 8 b/m', p < 0.0001; Group 2: +19 +/- 8 b/m', p < 0.0001; Group 3: +22 +/- 9 b/m', p < 0.0001; Group 4: +19 +/- 8 b/m', p < 0.0001; Groups 2, 4 vs Group 1: p = 0.03, Group 3 vs Group 1: p = 0.002). No patients in Group 1 (0%), 3 patients in Groups 2 and 3 (12%), and 5 patients in Group 4 (20%) showed new wall motion abnormalities after atropine infusion (Group 4 vs Group 1: p = 0.06). Effects of atropine on HR and mean R-R interval were significantly more pronounced in resting conditions than during dipyridamole test (HR: +25 +/- 11 vs +18 +/- 9 b/m', p < 0.001; R-R: -256 +/- 122 vs -127 +/- 68 msec, p < 0.0001)., Conclusions: High doses of atropine during dipyridamole echocardiography test are safe and more effective for induction of new wall motion abnormalities than usual doses, particularly in patients tacking beta-blockers. The likelihood of an antagonistic mechanism between atropine and endogenous, dipyridamole-induced adenosine on sinus node is supported from our results.

Objectives: The prognostic value of dipyridamole echocardiography was assessed in patients with chronic coronary artery disease and preserved left ventricular function., Background: Few data are available on the prognostic value of dipyridamole echocardiography in patients with a low risk of cardiac events., Methods: Two hundred sixty-eight consecutive patients with stable, proven or suspected coronary artery disease and ejection fraction > or = 0.40 underwent high dose (up to 0.84 mg/kg body weight) dipyridamole echocardiography. In 204 patients definite exercise electrocardiographic (ECG) results were also available., Results: During a mean (+/- SD) follow-up period of 16 +/- 8 months (range 6 to 36), 33 spontaneous events occurred: 15 "hard" events (cardiac death [n = 6], myocardial infarction [n = 9]) and 18 "soft" events (unstable angina). Events occurred more frequently in patients with positive findings on dipyridamole echocardiography (59% vs. 3%, p < 0.001; hard events 24% vs. 2%, p < 0.01). A positive response at the low dose (up to 0.56 mg/kg) identified patients with a high incidence of hard events (7 of 16 patients, sensitivity 50%, specificity 96%). In patients with an exercise ECG, a comparable sensitivity for cardiac events was found (89% vs. 93%, p = NS), but dipyridamole echocardiography was more specific (91% vs. 61%, p < 0.01). A positive response on the low work load exercise ECG (< 8 min) and a positive response to low dose dipyridamole echocardiography had similar accuracy (82% vs. 90%, p = NS). Cox analysis identified dipyridamole echocardiography as the best predictor of cardiac events (odds ratio [OR] 20.9, 95% confidence interval [CI] 10.8 to 37.9); the highest risk of hard events was found in patients with a positive response to low dose dipyridamole echocardiography (OR 25.4, 95% CI 12.2 to 54.1)., Conclusions: In patients with chronic coronary artery disease and a low incidence of cardiac events, dipyridamole echocardiography was effective in prognostic stratification, and positive low work load exercise ECG results were a reliable predictor of subsequent events. Consequently, dipyridamole echocardiography should be considered a complementary tool in the presence of high work load positivity or ambiguous exercise ECG results.

Subungual exostosis in the digit is an uncommon benign tumor. Only 21 (10%) of 203 cases reported in the literature occurred in the hand. We present a recent case, detailing diagnosis, pathologic findings, and management.

The effect of vasodilator Molsidomine (M) vs placebo on left ventricular dimensions and function measured by echocardiography was evaluated in a randomized study on 23 patients (pts) with refractory congestive heart failure (R CF) (NYHA class III-IV). The pts were randomized in two groups: group A (12 pts) received M, group B received an identical appearing placebo. Adequate echocardiograms were obtained before and one hour after 2 tablets of M (4 mg) or P; left ventricular end-diastolic and end-systolic diameters (LVEDD and LVESD), mean rate of circumferential shortening and left ventricular fractional shortening were calculated on the echocardiograms obtained. At the same time mean arterial pressure (MAP) and heart rate were measured. In group A, the single-dose test induced a significant reduction in LVEDD (74.1 +/- 7.2 to 72.1 +/- 7.1 mm; p less than 0.01), in LVESD (64.4 +/- 8.4 to 61.6 +/- 7.4 mm; p less than 0.01) and in MAP (96.5 +/- 8.3 to 85.4 +/- 7.2 mmHg; p less than 0.05). No significant changes were noted in the other parameters. Moreover, changes of parameters evaluated in group A between pts with idiopathic cardiomyopathy and pts with ischemic heart disease showed no statistical differences. Thus, acute Molsidomine therapy is effective in reducing left ventricular diameters and MAP in pts with RCF without changes of echocardiographic contractility indexes.

A histometry system has been developed to measure bone ingrowth into porous hydroxyapatite implants utilizing the backscattered electron image of thick sections. The system consists of a scanning electron microscope (SEM) with backscattered electron detector, digital beam controller, minicomputer based image digitization, and microcomputer based image processing, point counting, and lineal analysis. The SEM backscattered electron imaging mode yields high tissue contrast and sharp tissue boundaries, substantially reducing the lost cap and projection effect errors of thick sections. High-resolution digitization of the image substantially reduces the standard error of the estimates. By using the digitized image the tedious process of filtering artifacts and recording actual point counts, intersections, and intercept lengths is delegated to computer software. Performance of this system in a recent study demonstrated substantial ease of operator use and speed of measurement. In the absence of a digital beam controller an inexpensive video digitizer circuit board may be used to digitize photographic prints of the SEM images. The combination of increased accuracy, precision, operator ease, and speed suggests that this system can be useful for soft tissue-bone-implant histometry.

The value of pulsed Doppler echocardiography in assessing the presence and severity of tricuspid regurgitation (TR) has been studied in three groups of subjects, 12 without cardiovascular disease (Group I), 38 with TR (Group II) and 16 patients with aortic and mitral valve disease but no TR (Group III). The presence and severity of TR was also independently evaluated by clinical examination, jugular vein pulse recording and/or hemodynamic investigation. Left parasternal, sub-xyphoid and apical views were adapted for the pulsed Doppler echocardiographic examination. The sample volume was placed in the right atrium at varying distances from the tricuspid valve. We tried to quantitate the degree of TR according to: 1) the diameter and maximal distance from the tricuspid valve of the regurgitant stream, 2) the duration of reguritation through systole, and 3) the degree of turbolence as demonstrated by the time interval histograms. On the basis of above mentioned criteria, three subgroups of subjects with TR, i.e. mild, moderate and severe were recognised. These results were compared to hemodynamic and/or clinical-poligraphic evaluation. In 34 Group II subjects (89%), the Doppler study revealed the presence of TR and allowed an acceptable quantitative assessment. Falsely positive diagnoses were not made in any of the subjects of Group I. Identification of organic TR in patients with atrial fibrillation was possible only when regurgitation was moderate or severe.

Tremors of the isoelectric line in routine electrocardiograms have been described in patients with spinal muscular atrophy and have been interpreted as fasciculations of denervated muscles. In order to evaluate this phenomenon, 13 patients with spinal muscular atrophy have been studied (average age: 37.3 months). A first electrocardiogram was recorded routinely; a second tracing was then recorded with double sensitivity and double speed. In addition, all patients were evaluated clinically and had M-mode and cross-sectional echocardiography. Regular and constant spikes on the isoelectric electrocardiographic line were recorded in 12 patients (93.4%); their frequency ranged from 39 to 48 cycles/sec (average: 42.08 +/- 2.64). Contrary to previous reports, we found an "abnormal" electrocardiogram in all our patients with severe spinal muscular atrophy. The only patient with a normal electrocardiogram had a mild and clinically stable form of spinal muscular atrophy. We did not find any significant structural cardiac abnormality by clinical and echocardiographic evaluation. We conclude that continuous tremor on the isoelectric line of electrocardiogram represents a characteristic of spinal muscular atrophy in these patients. It is a result of muscle fasciculations and does not imply any abnormality of the heart.