Improved percent-predicted peak VO2 is associated with lower risk of hospitalization in patients with coronary heart disease. Analysis from the FRIEND registry.

BACKGROUND: Normal standards for peak oxygen consumption (VO2peak) are controversial because they tend to be population and protocol specific. This study was undertaken to examine the association between percentage of age-predicted VO2peak and all-cause hospital readmission in cardiac outpatients who were referred to an exercise-based secondary prevention program. METHODS: Hospital readmission was assessed in 1283 male patients with coronary heart disease (CHD) three years after enrolment, and related to the age-predicted VO2peak derived from the Fitness Registry and the Importance of Exercise: A National Data Base equation (FRIEND%PRED). VO2peak was estimated using a moderate perceptually regulated 1-km treadmill-walking test. Readmission was also assessed during the fourth-to-sixth years as function of improvement in FRIEND%PRED in 845 patients who were re-evaluated 3 years after baseline. RESULTS: During the 3-years after baseline, readmission rate was lower across increasing tertiles of FRIEND%PRED. Compared to the lowest tertile, the adjusted hazard ratios (HRs) for the second and third tertile were 0.98 (95% CI 0.76-1.27, p = 0.90) and 0.71 (0.53-0.95, p = 0.002). The rate of readmission from the fourth-to-sixth years after baseline was lower across tertiles of improved FRIEND%PRED, with adjusted HRs 0.78 (0.60-1.03, p = 0.08) and 0.58 (0.42-0.75, p < 0.0001) for the intermediate and high tertiles vs the lowest tertile. After adjustment for confounders, every 1 unit % increase in FRIEND%PRED was associated with a 3% reduction in risk of readmission (HR 0.97, 0.95-0.98, p < 0.0001). CONCLUSIONS: Age-predicted VO2peak estimated by a moderate treadmill-walk predicts hospital readmission in outpatients with CHD undergoing secondary prevention.

Stress echocardiographic results predict risk of reinfarction early after uncomplicated acute myocardial infarction: large-scale multicenter study. Echo Persantine International Cooperative (EPIC) Study Group.

OBJECTIVES: This study sought to assess the value of dipyridamole echocardiography in predicting reinfarction in patients evaluated early after uncomplicated acute myocardial infarction. BACKGROUND: The identification of future nonfatal reinfarction seems an elusive target for physiologic testing. However, a large sample population is needed to detect minor differences in phenomena with a low event rate. METHODS: We assessed the value of dipyridamole echocardiography in predicting reinfarction in 1,080 patients (mean [+/- SD] age 56 +/- 9 years; 926 men, 154 women) evaluated early (10 +/- 5 days) after uncomplicated acute myocardial infarction and followed up for 14 +/- 10 months. RESULTS: Submaximal studies due to limiting side effects occurred in 14 patients (1.3%); these test results were included in the analysis. Results of dipyridamole echocardiography were positive in 475 patients (44%). During follow-up, there were 50 reinfarctions: 45 nonfatal, 5 fatal (followed by cardiac death < or = 4 days after reinfarction). Reinfarction (either nonfatal or fatal) occurred in 30 patients with positive and 20 with negative results (6.3% vs. 3.3%, p < 0.01). Nonfatal reinfarction occurred in 25 patients with positive and 20 with negative results (5% vs. 3.3%, p < 0.05). Reinfarction was fatal in 5 of 30 patients with positive and in none of 20 with negative results (16.6% vs. 0%, p = 0.07). The relative risk of reinfarction was 1.9. CONCLUSIONS: Dipyridamole echocardiographic positivity identifies patients evaluated early after uncomplicated acute myocardial infarction at higher risk of reinfarction, especially fatal reinfarction.

The atropine factor in pharmacologic stress echocardiography. Echo Persantine (EPIC) and Echo Dobutamine International Cooperative (EDIC) Study Groups.

OBJECTIVES: This study sought to compare, head to head, the two most popular pharmacologic stress echocardiographic tests--dipyridamole and dobutamine--with state of the art protocols in a large multicenter prospective study. BACKGROUND: In the continuing quest for ideal diagnostic accuracy, pharmacologic stress echocardiography has quickly moved over the years from low to high dose regimens and is currently performed with atropine coadministration. METHODS: Dobutamine (up to 40 microgram/kg body weight per min) plus atropine (up to 1 mg over 4 h) and dipyridamole (up to 0.84 mg/kg per min over 10 h) plus atropine (up to 1 mg over 4 h) stress echocardiography was performed on different days, in random order and within 1 week in 360 patients with chest pain syndrome. Thirteen different echocardiographic laboratories, all fulfilling quality control criteria for stress echocardiographic reading, contributed to the study. RESULTS: No major complications occurred during either test. The test was interrupted before achievement of predetermined end points for limiting side effects in 37 dobutamine-atropine and 7 dipyridamole-atropine stress echocardiographic studies (feasibility 90% vs. 98%, p < 0.01). Diagnostic accuracy was assessed in a subset of 110 patients with no obvious rest dyssynergy (akinesia or dyskinesia) who underwent coronary angiography independently of test results and within 1 week of testing. Significant coronary artery disease (> or = 50% diameter reduction in at least one major coronary vessel by quantitative coronary angiography) was found in 92 patients. Sensitivity for detection of coronary artery disease was 84% (77 of 92) for dobutamine-atropine and 82% (75 of 92) for dipyridamole-atropine stress echocardiography (p = NS), with a specificity of 89% (16 of 18) for dobutamine-atropine and 94% (17 of 18) for dipyridamole-atropine stress echocardiography (p = NS). A significant correlation was present between peak wall motion score index during dipyridamole-atropine and dobutamine-atropine stress echocardiography (r = 0.83, p < 0.0001). CONCLUSIONS: Dobutamine-atropine and dipyridamole-atropine stress echocardiography are safe and feasible, although submaximal studies are more frequent with dobutamine. The two stresses have comparable accuracy in the detection of angiographically assessed coronary artery disease, although dobutamine is marginally more sensitive and dipyridamole marginally more specific. Stratification of the ischemic response in the space domain is also comparable with the two stresses.

Prognostic value of dipyridamole echocardiography early after uncomplicated myocardial infarction: a large-scale, multicenter trial. The EPIC Study Group.

PURPOSE: To determine the prognostic capability of the dipyridamole echocardiography test (DET) early after an acute myocardial infarction. PATIENTS AND METHODS: On the basis of 11 different echocardiographic laboratories, all with established experience in stress echocardiography and fulfilling quality-control requirements for stress echocardiographic readings, 925 patients were evaluated after a mean of 10 days from an acute myocardial infarction and followed up for a mean of 14 months. RESULTS: During the follow-up, there were 34 deaths and 37 nonfatal myocardial infarctions; 104 patients developed class III or IV angina and 149 had coronary revascularization procedures (bypass or angioplasty). Considering all spontaneous events (angina, reinfarction, and death), the most important univariate predictor was the presence of an inducible wall motion abnormality after dipyridamole administration (chi 2 = 45.8). With a Cox analysis, echocardiographic positivity, age, and male gender were found to have an independent and additive value. Considering survival (and, therefore, death as the only event), age was the most meaningful parameter, followed by the wall motion score index during dipyridamole administration (chi 2 = 12.1). Among other parameters, the resting wall motion score index was a significant predictor of death. In a multivariate analysis, the prognostic contributions of age (relative risk estimate = 1.08) and wall motion score index during dipyridamole administration (relative risk estimate = 4.1) were independent and additive. In particular, considering death only, the event rate was 2% in patients with negative DET results, 4% in patients with positive high-dose DET results, and 7% in patients with positive low-dose DET results. CONCLUSIONS: DET is feasible and safe early after uncomplicated myocardial infarction and allows effective risk stratification on the basis of the presence, severity, extent, and timing of the induced dyssynergy.

Thrombotic markers during myocardial infarction.

The authors carried out a study on the behavior of some thrombotic molecular "markers" in a group of patients suffering from myocardial infarction, just after the first symptoms and after two weeks from the event. The series consists of 12 subjects (6 males, 6 females, mean age 52 +/- 7), suffering from acute myocardial infarction; just after the first symptoms and instrumental signs (before the thrombolysis) and after two weeks a venous blood withdrawal was done; on the plasma of each sample the determination of fibrinogen (F) (coagulative method), tissue plasminogen activator (t-PA), plasminogen activator inhibitor (PAI-1), D-dimer (D-D), fibrinopeptide A (FPA) and betathromboglobulin (BTG) (ELISA methods) was performed. The values of t-PA, FPA and BTG did not show remarkable variations; after two weeks from the myocardial infarction compared to the basal values a significant reduction of PAI-1 (4.6 +/- 0.28 UI/ml vs 5.4 +/- 0.33 UI/ml, p < 0.01), D-D (215 +/- 10 ng/ml, vs 253 +/- 12 ng/ml, p < 0.05) and a significant increase of F (294 +/- 28, vs 218 +/- 16 mg%, p < 0.05) were observed. The authors suggest that a basal reduction of the fibrinolytic activity documented by the enhanced PAI-1, may play a major role, influencing pathogenetically the thrombotic event; the other markers seem to be of lower importance, being only secondarily altered in the first phase and gradually returning to a normal pattern after an adequate elapsed time; a preinfarctual hypofibrinolytic condition, probably enhanced by some triggering factor, actually appears the sole prothrombotic system to be counteracted with adequate diet and drug treatments.

[Fascicular ventricular tachycardia]. / La tachicardia ventricolare fascicolare.

Fascicular tachycardia is an uncommon idiopathic ventricular tachycardia, originating from the left ventricle; it usually occurs in young male patients, with a high prevalence in south-east Asiatic people. Electrocardiographic aspects of this unique ventricular tachycardia (right bundle branch block morphology and left or right-axis deviation, with a moderate QRS widening) and verapamil sensitivity make it often difficult the differential diagnosis with other forms of supraventricular tachycardia. Reentry is believed to be the operative mechanism of fascicular tachycardia, with the reentrant circuit located in the Purkinje network, in the region of the left posterior or anterior fascicle. The slow conduction zone participating in the reentry circuit, made up of partially depolarized Purkinje fibers, seems to be located in a relatively wide area, from the basal to the apical left interventricular septum. Intravenous verapamil is elective in acute treatment; however oral verapamil shows poor efficacy in preventing tachycardia relapses. Ablative approach is very effective; success is achieved in approximately 90% of patients, with rare complications. Recently diastolic potentials during fascicular tachycardia have been reported and these findings have given rise to new electrophysiological hypotheses and new indications about the successful ablation site.

[Epidural spinal stimulation in the treatment of refractory angina pectoris. Its clinical efficacy, complications and long-term mortality. An Italian multicenter retrospective study]. / La stimolazione spinale epidurale nel trattamento dell'angina pectoris refrattaria. Efficacia clinica, complicanze e mortalità a lungo termine. Studio retrospettivo multicentrico Italiano.

BACKGROUND: Spinal cord stimulation has been used for many years in the treatment of refractory angina pectoris. Its anti-anginal and anti-ischemic effect has been well documented in several studies, but the long-term efficacy, safety and survival rate are not well known. The aim of this study was to carry out a retrospective analysis of a series of patients from the Italian Multicenter Registry, the data of which were collected in five centers, by means of a questionnaire. METHODS: One hundred and thirty patients (83 males, 47 females, mean age 74.8 +/- 9.8 years) were submitted to spinal cord stimulator implantation for refractory angina pectoris in the period 1988-1995 and controlled during a mean follow-up of 31.4 +/- 25.9 months. A previous myocardial infarction had already occurred in 69.3% of patients, whereas in 67.6% multivessel coronary artery disease was documented. A left ventricular dysfunction (ejection fraction < 0.40) was present in 34% of patients; bypass surgery and coronary angioplasty were performed in 49.6% and in 27% of patients respectively. In 96.3% of cases revascularization procedures were not advisable. RESULTS: A complete follow-up of 116 patients (89.2%) was available. The spinal cord stimulator induced a significant reduction in NYHA functional class from 2.5 +/- 1.2 to 1.5 +/- 0.9 (p < 0.01). During the follow-up 41 patients (35.3%) died, and in 14.2% a new acute myocardial infarction developed. The total percentage of minor spinal cord stimulation-related complications was 6.8%. No major complications occurred. The annual total mortality rate was 6.5%, whereas the cardiac mortality rate was 5%. Compared to the survivors, patients who died showed a higher incidence of left ventricular dysfunction, previous myocardial infarction and bypass surgery at implantation. CONCLUSIONS: In our experience, spinal cord stimulation is an effective therapy in patients affected by refractory angina pectoris and who cannot undergo revascularization procedure. The complication rate is low, with the total and cardiac mortality showing a trend as that reported for patients with similar coronary disease.

[Usefulness of atrial vulnerability in predicting atrial fibrillation in patients with sick sinus syndrome treated with DDD pacemaker]. / Utilità della vulnerabilità atriale nel prevedere l'insorgenza di fibrillazione atriale in pazienti con malattia del nodo del seno trattata con pacemaker DDD.

BACKGROUND: Atrial fibrillation (AF) is common in patients with sick sinus syndrome (SSS) treated with dual-chamber pacing and it may complicate their management. This study was undertaken to establish the usefulness of atrial vulnerability (AV), determined by means of transesophageal electrophysiological study (TES), in predicting the risk of developing AF and in deciding the type and program of pacemaker (PM) to be implanted in patients with SSS. METHOD: AV was assessed preoperatively using TES in 81 consecutive patients with SSS. AV (AF > 1 min) was divided into "low threshold" (induction with burst < or = 300/min) and "high threshold" (induction with burst > or = 350 min or with incremental ramp). The PM was programmed to ensure constant atrial capture in all patients. Follow-up lasted three years. No patients received antiarrhythmic drugs. RESULT: AV was positive in 52% of patients (Group A) and negative in 48% of patients (Group B). A history of paroxysmal AF was present in 52% of patients in Group A and in 12% of patients in Group B. At follow-up, 38% of Group A and 2% of Group B patients had chronic AF. AV had sensitivity, specificity, positive predictive value (ppv) and negative predictive value (npv) of 94, 59, 38 and 97%, respectively. Thirty-eight percent of patients showed low threshold vulnerability, with sensitivity, specificity, ppv and npv of 87, 92, 87 and 93%, respectively. Sensitivity, specificity, ppv and pnv for history of AF were 93, 100, 98 and 84%, respectively. When the vulnerability threshold and the history of paroxysmal AF were considered together, the sensitivity, specificity, ppv and npv was 94, 100, 100 and 83%, respectively. Multivariate analysis was shown to be an independent predictive value only for history of AF (p = 0.0002). CONCLUSION: AV determined by means of TES, especially with a low induction threshold, shows excellent sensitivity and specificity in evaluating the risk of chronic AF. It could be useful in patients with SSS undergoing cardiac pacing who have never had AF, thus allowing a more accurate choice of the type and program of PM to be implanted. Case histories of paroxysmal AF could represent useful criteria for selecting patients at a high risk of developing chronic AF.

[Prognostic value of the dipyridamole-echocardiography test immediately after a non-complicated myocardial infarct: a large scale multicenter study. Echo Persantine Italian Cooperative Study]. / Valore prognostico del test eco-dipiridamolo subito dopo infarto miocardico recente non complicato: studio multicentrico su larga scala. Ricercatori Dello Studio EPIC.

BACKGROUND: Any new diagnostic test should follow a pathway similar to that of a new drug, from initial studies in highly selected populations under strictly controlled conditions, up to large scale multicenter trials more likely to represent the true performance of the test in the clinical arena. AIM OF THE STUDY: To evaluate the capability of prognostic stratification of high dose (up to 0.84 mg/kg over 10') dipyridamole-echocardiography test (DET) early after an acute myocardial infarction in a "phase IV" study, based upon 11 different echocardiographic laboratories, all with established experience in stress echo and fulfilling quality control requirements for stress echo readings. STUDY POPULATION: Nine-hundred twenty five patients were evaluated after a mean of 10 days from an acute myocardial infarction and followed up for a mean of 14 months. RESULTS: During DET, one major adverse reaction occurred, consisting of a prolonged ischemia resistant to aminophylline and nitrates, and progressing to small uncomplicated reinfarction. In 11 patients the lower dipyridamole dose (0.56 mg/kg over 4') gave limiting side effects. Patients were followed up for 14 +/- 9.9 months (range = 1.53). During the follow-up, there were 34 deaths and 37 non-fatal myocardial infarctions; 104 patients developed class III or IV angina, and 149 had coronary revascularization procedures (bypass or angioplasty). Considering all spontaneous events (angina, reinfarction and death), the most important univariate predictor was the result of DET (chi-square = 45.8). With a Cox analysis, echocardiographic positivity, age and sex were found to have an independent and additive value. Considering survival (and therefore death as the only event) age was the most meaningful parameter, followed by the Wall Motion Score Index during dipyridamole (chi-square = 12.1); among other parameters, the resting Wall Motion Score Index was a significant predictor of death. By Cox analysis, age (relative risk estimate = 1.02) and Wall Motion Score Index during dipyridamole (relative risk estimate = 14) showed an independent and additional prognostic value. In particular, considering death only, the event rate was of 2% in patients with negative DET, 4% in patients with high dose positive DET and 7% in patients with low dose positive DET. CONCLUSIONS: Dipyridamole echocardiography is feasible and safe early after uncomplicated myocardial infarction and allows an effective risk stratification on the basis of the presence, severity, extent and timing of the induced dyssynergy. In particular, the risk of death doubles in patients with high dose positivity and almost quadruples in patients with low dose positivity.

Exercise-electrocardiography and/or pharmacological stress echocardiography for non-invasive risk stratification early after uncomplicated myocardial infarction. A prospective international large scale multicentre study.

AIMS: The aim of the present study was to assess the relative prognostic value of clinical variables, the exercise electrocardiography test and the pharmacological stress echocardiography test either with dipyridamole or dobutamine early after a first uncomplicated acute myocardial infarction in a large, multicentre, prospective study. METHODS AND RESULTS: Seven hundred and fifty-nine in-hospital patients (age=56+/-10 years) with a recent and first clinical uncomplicated myocardial infarction, with baseline echocardiographic findings of satisfactory quality, an interpretable ECG and able to exercise underwent a resting 2D echocardiogram, a pharmacological stress test with either dipyridamole or dobutamine and an exercise electrocardiography test at a mean of 10 days from the infarction; they were followed-up for a median of 10 months. During the follow-up, there were 13 deaths, 23 non-fatal myocardial infarctions and 59 re-hospitalizations for unstable angina. When all spontaneous events were considered, with multivariate analysis, the difference between the wall motion score index at rest and peak stress (delta wall motion score index), and exercise duration were independent predictors of future spontaneous events (relative risk 7.2; 95% CI=2.73-19.1; P=0.000; relative risk 1.1, 95% CI=1.02-1.18; P=0.008, respectively). Kaplan-Meier survival estimates showed a better outcome for those patients with a negative pharmacological stress echocardiography test compared to patients with low dose positivity (94.7 vs 74.8%, P=0.000). CONCLUSION: Stress echocardiography tests provide stronger information than historical and exercise electrocardiography test variables. Pharmacological echocardiography as well as the exercise ECG is able to predict all spontaneously occurring events when the presence as well as the timing, severity, and extension of stress-induced wall motion abnormalities are considered.

The relative value of exercise-electrocardiography and dipyridamole stress echocardiography for risk stratification early after uncomplicated myocardial infarction. The EPIC (Echo Persantine International Cooperative) Study Group.

BACKGROUND: Rational prognostic algorithm should be developed considering the logical progression of the information as it becomes available to the physician, with clinical data first, ECG data second and stress imaging data last. The aim of the present study was to assess in a clinically realistic fashion the relative prognostic value of exercise electrocardiography test (EET) and dipyridamole-echocardiography test (DET) early after first acute uncomplicated myocardial infarction. METHODS AND RESULTS: Five hundred and forty-seven in-hospital patients (age = 56 +/- 9 years) with recent clinically uncomplicated first myocardial infarction, baseline echocardiographic findings of satisfactory quality, interpretable ECG and capability to exercise underwent a resting 2D echocardiogram, a DET and an EET at a mean of 10 days from the infarction and were followed up for 16.2 +/- 11 months. During the follow-up, there were 17 cardiac deaths, 19 non-fatal myocardial infarctions and 49 unstable angina. When cardiac death was considered as the only significant event, with multivariate analysis, peak dipyridamole Wall Motion Score Index was the only significant predictor (chi 2 = 5.66; p = 0.013; relative risk estimate = 4.7; confidence intervals = 1.35-16.08). In presence of a negative exercise electrocardiography test for both chest pain and electrocardiographic criteria, the death rate was 2%. CONCLUSION: DET provides stronger information in comparison with historical and EET variables. However, a negative maximal EET is sufficient to identify a very low risk subset in whom additional testing may not be warranted.