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Angiographically assessed plaque morphology, not only plaque severity, may affect myocardial vulnerability to ischemia during stress testing. The aim of this study was to evaluate directly, in a head-to-head comparison, the relation between coronary stenosis severity and morphology and pharmacologic stress echo response. From our inpatients echo databank, we selected 68 patients (62 men, mean age 57 +/- 9 years) who had undergone high-dose dipyridamole and high-dose dobutamine-atropine echocardiography, performed within 1 week and in random order, before coronary angiography that showed significant coronary artery disease by selection. There were altogether 121 vessels with visually assessed stenosis >50% in 68 patients. Thirty-three had complex-type and 56 simple-type lesions (according to the Ambrose classification), whereas 32 vessels were occluded. During dobutamine echocardiography there were 51 dyssynergic regions of the left ventricle fed by different coronary arteries in 50 patients and dipyridamole stress was able to induce ischemia in 45 separate regions in 44 patients. The overall agreement between the 2 tests in recognizing ischemia was 76%. Induced ischemia was associated with greater quantitatively assessed stenosis severity for both dipyridamole (positive, 70 +/- 12% vs negative, 63 +/- 12% area reduction; p <0.05) and dobutamine (positive, 68 +/- 12% vs negative, 63 +/- 12% area reduction; p <0.05). The simple-type stenosis was more frequently identified with dobutamine (46%) versus dipyridamole (21%, [p <0.01]), whereas the complex-type stenosis was associated with a trend toward more frequent positivity of dipyridamole (55%) versus dobutamine (36%), p = 0.13. Adenosinergic stress positivity is affected not only by plaque severity, but also by plaque morphology, whereas adrenergic stress positivity is affected by plaque severity, not by plaque morphology. [ABSTRACT FROM AUTHOR]

Protocols for dipyridamole stress testing have evolved in the last 16 years in the neverending quest of optimal diagnostic accuracy and user friendliness. Higher dipyridamole dose in a shorter infusion time provides higher sensitivity, but concern over safety is still controversial. An accelerated high-dose (0.84 mg/kg in 6 minutes without atropine) dipyridamole stress test was performed on 1,295 patients in 2 echocardiographic laborotories: Institute of Clinical Physiology of Pisa and Niguarda Hospital of Milan. During testing, there were no deaths and no patients had ventricular fibrillation. Major adverse reactions occurred in 3 cases (1 every 431 studies): 1 myocardial infarction, 1 brief cardiac asystole, and 1 transient ischemic attack. Overall feasibility was 97%. In 66 patients with normal function at rest who were evaluated off therapy, with coronary angiography performed independently of test results, the accelerated high-dose protocol showed a sensitivity of 85% (confidence interval [CI] 73% to 92%) and a specificity of 93% (CI 83% to 97%) for angiographically assessed coronary artery disease (quantitatively assessed diameter reduction > or = 50%). Diagnostic accuracy of the accelerated high dose was 89% (CI 79% to 95%). Thus, accelerated high-dose dipyridamole stress echocardiography was reasonably safe and well tolerated. This protocol is especially appealing for its excellent diagnostic accuracy coupled with the short imaging time and no need for drug cocktails. [ABSTRACT FROM AUTHOR]

The aim of this study was to investigate the relation between radioisotopic and echocardiographic markers of myocardial viability and their correlation with functional recovery after coronary revascularization. Myocardial viability can be detected by techniques exploring various aspects of cell physiology: thallium-201 scintigraphy and dobutamine and dipyridamole echocardiography focus on cell membrane integrity, beta-1 and adrenoceptor, and A2-adenosine receptor-mediated inotropic response, respectively. Fifty-seven patients (mean age 60+/-8 years) with previous myocardial infarction (>3 months), angiographically assessed coronary artery disease, and resting regional dysfunction underwent rest-redistribution 201-thallium scintigraphy and low-dose pharmacologic stress echo with dobutamine (up to 10 microg/kg/min), very low dose regimen of dipyridamole (0.28 mg/kg over 4 minutes), and combined dipyridamole-dobutamine. Criteria for viability in a 13-segment model for both techniques were percent peak activity in redistribution images >55% for thallium-201 and a decrease in wall motion score >1 grade (1 [normal] to 4 [dyskinetic]) for stress echo. Thirty patients underwent coronary revascularization (bypass surgery in 8, angioplasty in 22) and were followed up at 4 weeks from intervention with a resting echocardiogram. The rate of agreement between thallium-201 and stress echo was 63% for dipyridamole, 66% for dobutamine, and 74% for combined dipyridamole-dobutamine (p <0.05 vs dipyridamole and dobutamine). In the 30 patients who underwent revascularization, a regional resting dyssynergy was observed in 225 segments, assuming that postrevascularization functional recovery (which occurred in 126 segments) was the gold standard; combined dipyridamole-dobutamine showed a higher sensitivity (90% confidence interval [CI] 85% to 95%) than thallium-201, dobutamine, or dipyridamole (87%, CI 81% to 92%; 82%, CI 76% to 89%; and 82%, CI 76% to 89%, respectively). Specificity was lower for viability recognition with thallium-201 (61%, CI 51% to 71%) than with dobutamine (93%, CI 88% to 98%), dipyridamole (95%, CI 91% to 99%), and combined dipyridamole-dobutamine (92%; CI 87% to 97%). Combined adrenergic and adenosinergic stimulation recruits an inotropic reserve in a significant proportion of segments with preserved thallium uptake that were nonresponders after either dipyridamole or dobutamine. When functional recovery after successful revascularization is considered as the postoperative gold standard, thallium has a higher sensitivity than dipyridamole or dobutamine; this sensitivity gap is filled with combined dipyridamole-dobutamine. The specificity of all forms of pharmacologic stress echo is better than thallium-201. [ABSTRACT FROM AUTHOR]

Subjective interpretation of dobutamine echocardiograms provides only moderate interinstitutional observer agreement if nonunified data acquisition and assessment criteria are applied. The present study was undertaken to evaluate parameters associated with low interinstitutional observer agreement in the interpretation of dobutamine echocardiograms and to analyze whether standardized interpretation criteria improve interinstitutional observer agreement. One hundred fifty dobutamine echocardiograms (dobutamine up to 40 microg/kg/min body weight and atropine up to 1 mg) were evaluated at 5 centers. Clinical, procedural, and echocardiographic parameters were included in the analysis of variables with significant impact on interinstitutional agreement. Standardized interpretative criteria were established, and 90 dobutamine echocardiograms were reanalyzed by 3 observers using a standardized image display. Multivariate analysis demonstrated low image quality (odds ratio [OR] 0.19, 95% confidence interval [CI] 0.08 to 0.45, p=0.0002), low severity of induced wall motion abnormality (OR 0.17, 95% CI 0.07 to 0.40, p <0.0001), and a low peak rate-pressure product (OR 0.93, 95% CI 0.43 to 2.27, p=0.0382) to result in a low interinstitutional agreement. Standardization of image display in cine loop format and of dobutamine stress echo interpretation criteria resulted in improvement in test result categorization as normal or abnormal, with a kappa value of 0.50, compared with 0.39 using the original subjective interpretation. In conclusion, image quality, the severity of induced wall motion abnormalities, and the obtained rate-pressure product have a significant impact on the interpretation homogeneity of dobutamine echocardiograms. Standardization of image display in cine loop format and of reading criteria results in improved interinstitutional agreement in interpretation of stress echocardiograms. [ABSTRACT FROM AUTHOR]

Risk stratification in patients with acute coronary syndromes (ACS) is achieved today by clinical models, "blind" to the prognostic support of imaging methods. To assess the value of simple at rest cardiac chest sonography in predicting the intra- and extrahospital risk of death or myocardial infarction, we enrolled 470 consecutive in-patients (312 men, age 71 ± 12 years) who had been admitted for ACS. On admission, all had received a clinical score using the Global Registry in Acute Coronary Events and Thrombolysis in Myocardial Infarction systems and, within 1 to 12 hours, a comprehensive cardiac-chest ultrasound scan. Each of the 16 echocardiographic parameters evaluating left and right, systolic and diastolic, ventricular function and structure, was scored from 0 (normal) to 3 (severely abnormal). The median follow-up was 5 months (interquartile range 1 to 10). Patients with hard events (n = 102) could be separated from patients without events (n = 368) using the Global Registry in Acute Coronary Events score, Thrombolysis in Myocardial Infarction score, and several echocardiographic parameters. On multivariate Cox analysis, ejection fraction (hazard ratio 1.45, 95% confidence interval 1.02 to 2.08, p = 0.040), tricuspid annular plane systolic excursion (hazard ratio 1.66, 95% confidence interval 1.13 to 2.45, p = 0.010) and ultrasound lung comets (hazard ratio 1.69, 95% confidence interval 1.25 to 2.27, p = 0.001) were independent predictors of cardiac events. The 3-variable echocardiographic score (from 0, normal to 9, severe abnormalities in ejection fraction, ultrasound lung comets, and tricuspid annular plane systolic excursion) effectively stratified patients and added value (hazard ratio 2.52, 95% confidence interval 1.89 to 3.37, p <0.0001) to the Global Registry in Acute Coronary Events score (hazard ratio 1.60, 95% confidence interval 1.07 to 2.39, p = 0.003). In conclusion, for patients with ACS, effective risk stratification can be achieved with cardiac and chest ultrasound imaging parameters, adding prognostic value to the clinical risk scores. [ABSTRACT FROM AUTHOR]

The prognostic value of stress echocardiography in patients with previous percutaneous coronary intervention (PCI) remains undefined. The aim of this study was to investigate the prognostic implication of stress echocardiography after PCI. The study group comprised 1,063 patients (794 men, 65 +/- 10 years of age) who underwent stress echocardiography with exercise (n = 105), dipyridamole (n = 780), or dobutamine (n = 178) after a median of 10 months from a successful PCI. Of these patients, 616 (58%) complained of chest pain and 447 (42%) were asymptomatic. Stress echocardiogram was positive for inducible ischemia in 328 patients (31%). During a median follow-up of 20 months, there were 167 events (61 deaths, 106 infarctions). Independent predictors of mortality were age (hazard ratio [HR] 1.06, 95% confidence interval [CI] 1.03 to 1.09, p <0.0001), wall motion score index at rest (HR 3.91, 95% CI 2.19 to 6.99, p <0.0001), and ischemia at stress echocardiography (HR 1.82, 95% CI 1.05 to 3.16, p = 0.03). Five-year mortalities were 20% in patients with and 9% in those without ischemia (p = 0.006). Independent predictors of hard events were ischemia at stress echocardiography (HR 3.82, 95% CI 2.75 to 5.29, p <0.0001), age (HR 1.02, 95% CI 1.01 to 1.04, p = 0.009), wall motion score index at rest (HR 1.98, 95% CI 1.30 to 3.02, p = 0.002), multivessel disease at time of PCI (HR 1.45, 95% CI 1.05 to 2.02, p = 0.02), and female gender (HR 1.44, 95% CI 1.03 to 2.01, p = 0.03). Five-year hard event rates were 53% in patients with and 16% in those without ischemia (p <0.0001). Stress echocardiographic positivity added prognostic information to clinical and at-rest echocardiographic parameters in symptomatic and asymptomatic patients. Moreover, it identified a subset of patients at higher risk of developing hard events independent of the subtending coronary anatomy (multivessel or single vessel disease). In conclusion, stress echocardiography is effective in risk-stratifying patients with previous PCI. In particular, inducible ischemia is a strong and independent predictor of mortality and hard events. [ABSTRACT FROM AUTHOR]

This study investigated the value of pharmacologic stress echocardiography for risk stratification of patients > or =65 years of age. The study cohort consisted of 2,160 patients > or =65 years of age (1,257 men, mean +/- SD 71 +/- 5 years of age) undergoing dipyridamole (n = 1,521) or dobutamine (n = 639) stress echocardiography for evaluation of known (n = 913) or suspected (n = 1,247) coronary artery disease. Of 2,160 patients, 753 (35%) had a normal test result, whereas 772 (36%) showed a myocardial ischemic pattern and 635 (29%) a scar pattern. During a median follow-up of 26 months, 241 deaths and 87 nonfatal myocardial infarctions occurred. Patients (n = 568) undergoing revascularization were censored. Of 16 analyzed variables, age (hazard ratio [HR] 1.07 per unit increment), wall motion score index at rest (HR 2.63 per unit increment), ischemia at stress echocardiography (HR 1.81), and diabetes (HR 1.57) were multivariable predictors of death, whereas age (HR 1.06 per unit increment), ischemia at stress echocardiography (HR 2.60), wall motion score index at rest (HR 1.98 per unit increment), scar pattern (HR 1.99), and diabetes (HR 1.48) were multivariable predictors of death or myocardial infarction. Using an interactive stepwise procedure, stress echocardiography showed incremental prognostic value over clinical and echocardiographic data at rest, which decreased with increasing age. In addition, the annual hard event rate associated with a normal test result progressively increased with age. In conclusion, pharmacologic stress echocardiography provides useful prognostic information in patients > or =65 years of age. However, its prognostic value decreases with increasing age. [ABSTRACT FROM AUTHOR]

Vasodilator stress echocardiography allows semi-simultaneous imaging of left anterior descending (LAD) coronary flow and regional wall function. To assess the relative (and additive?) value of regional flow and function for noninvasive identification of angiographically assessed LAD disease in patients with chest pain syndrome, we studied 230 consecutive in-hospital patients (134 men, aged 63.5 +/- 11 years) with chest pain syndrome and normal regional and global left ventricular function. All patients underwent stress echocardiography with dipyridamole (up to 0.84 mg/kg over 10 minutes), including wall motion analysis by 2-dimensional echocardiography and coronary flow reserve (CFR) evaluation of the LAD artery by Doppler, with or without contrast injection. A new regional wall motion abnormality in >or=2 contiguous segments was required for 2-dimensional echocardiographic positivity. CFR was evaluated as the ratio of dipyridamole to peak diastolic coronary blood flow velocity at rest. All patients underwent coronary angiography within 60 days; a quantitatively assessed diameter reduction >50% of the LAD artery was considered significant. Of the 230 patients, 70 had LAD disease. A regional wall motion abnormality in LAD territory was present in 52 patients, and reduced CFR (<1.9) in 62 patients. Sensitivity for detecting LAD disease was 74% for 2-dimensional echocardiography (95% confidence interval [CI] 64% to 84%) and 81% for CFR <1.9 (95% CI 72% to 90%); specificity was 91% (95% CI 87% to 96%) for 2-dimensional echocardiography and 84% for CFR (95% CI 79% to 90%). Accuracy was 86% for 2-dimensional echocardiography (95% CI 82% to 91%) and 83.5% for CFR (95% CI 79% to 88%). When 2-dimensional echocardiography and CFR criteria were considered, sensitivity increased to 93% (95% CI 87% to 99%), with 80.6% specificity (95% CI 74.5% to 86.7%). CFR was assessed during vasodilator stress echocardiography. Its diagnostic accuracy for detecting LAD disease was comparable to regional wall motion abnormalities. However, the data for flow and function can be complementary in terms of predicting underlying angiographic anatomy, because abnormal wall motion can include coronary artery disease, and negative CFR can exclude it. [ABSTRACT FROM AUTHOR]

Dobutamine stress echo provides potentially useful information on idiopathic dilated cardiomyopathy (IDC). From February 1, 1997, to October 1, 1999, 186 patients (131 men and 55 women, mean age 56 +/- 12 years) with IDC, ejection fraction <35%, and angiographically normal coronary arteries were studied by high-dose (up to 40 micro/kg/min) dobutamine echo in 6 centers, all quality controlled for stress echo reading. In all patients, wall motion score index (WMSI) (from 1 = normal to 4 = dyskinetic in a 16- segment model of the left ventricle) was evaluated by echo at baseline and peak dobutamine. One hundred eighty-four patients were followed up (mean 15 +/- 13 months) and only cardiac death was considered as an end point. There were 29 cardiac deaths. Significant parameters for survival prediction at univariate analysis are: DeltaWMSI (chi-square 20.1; p <0.0000), New York Heart Association (NYHA) class (chi-square 17.57; p <0.0000), rest ejection fraction (chi-square 10.41; p = 0.0013), angiotensin-converting enzyme inhibitors (chi-square 8.23; p = 0.0041), and hypertension (chi-square 8.08, p = 0.0045). In the multivariate stepwise analysis only DeltaWMSI and NYHA were independent predictors of outcome (DeltaWMSI = hazard ratio 0.02, p < 0.0000; NYHA class = hazard ratio 3.83, p < 0.0000). Kaplan-Meier survival estimates showed a better outcome for patients with a large inotropic response (DeltaWMSI > or =0.44, a cutoff identified by receiver-operating characteristic curves analysis) than for those with a small or no myocardial inotropic response to dobutamine (93.6% vs 69.4%, p = 0.00033). Thus, in patients with IDC, an extensive contractile reserve identified by high-dose dobutamine stress echocardiography is associated with a better survival. [ABSTRACT FROM AUTHOR]

Seventeen patients scheduled for a cardiac procedure necessitating cardiopulmonary bypass underwent serial perioperative assessment of brachial artery flow-mediated dilation. Patients who underwent coronary bypass surgery had a sustained systemic endothelial dysfunction in the perioperative period, whereas those undergoing cardiac valve surgery experienced transient postoperative systemic endothelial dysfunction. [ABSTRACT FROM AUTHOR]

Heart rate reserve (HRR) during physical or pharmacological stress is a sign of cardiac autonomic function and sympathetic reserve, but it can be reduced during exercise for confounders such as poor motivation, drugs or physical fitness. In this study we sought to assess the prognostic meaning of HRR during dipyridamole stress echocardiography (DSE) in patients with abnormal chronotropic response to exercise. From 2004 to 2019, we prospectively acquired and retrospectively analyzed 379 patients (age 62 ± 11 years; ejection fraction 60 ± 5%) with suspected (n = 243) or known (n = 136) chronic coronary syndromes, referred to DSE for chronotropic incompetence during upright bicycle exercise-electrocardiography test defined as HRR used [(peak HR - rest HR) / (220 - age) - rest HR] ≤80% in patients off and ≤62% in patients on beta-blockers. All patients were in sinus rhythm and underwent DSE (0.84 mg/kg) within 3 months of exercise testing. During DSE, age-independent HRR (peak/rest HR) ≤1.22 was considered abnormal. All patients were followed-up. All-cause death was the only outcome measure. HRR during DSE was normal in 275 (73%) and abnormal in 104 patients (27%). During a follow-up of 9.0 ± 4.2 years, 67 patients (18%) died. The 15-year mortality rate was 23% in patients with normal and 61% in patients with abnormal HRR (p < 0.0001). At multivariable analysis a blunted HRR during DSE was an independent predictor of outcome (hazard ratio 2.01, 95% confidence intervals 1.23-3.29; p = 0.005) with age and diabetes, while neither inducible ischemia nor ongoing beta-blocker therapy were significant predictors. In conclusion, a blunted HRR during DSE predicts a worse survival in patients with chronotropic incompetence during exercise test. HRR during DSE is an appealingly simple biomarker of cardiac autonomic dysfunction independent of imaging, exercise and beta-blocker therapy., (Copyright © 2021. Published by Elsevier Inc.)

In patients in sinus rhythm, a blunted heart rate reserve (HRR) during dipyridamole stress echocardiography (SE) is a prognostically unfavorable sign of cardiac autonomic dysfunction. In this study we sought to assess the prognostic meaning of HRR in patients with permanent atrial fibrillation (AF). The study population was made by 301 patients (176 men, age 73 ± 8 years) with suspected (n = 200) or known (n = 101) coronary artery disease and permanent AF who underwent high-dose dipyridamole SE. HRR was calculated on an average of 5 consecutive beats as the peak/rest ratio of HR from 12-lead EKG. During a median follow-up time of 77 months (first quartile 44, third quartile 115 months), 111 (37%) patients died. Receiver operating characteristics analysis identified HRR ≤1.17 as the best predictor of mortality. At multivariable analysis, HRR ≤1.17 (HR 1.75, 95% CI 1.17 to 2.62; p = 0.006) independently predicted mortality together with age (HR 1.09, 95% CI 1.06 to 1.13; p <0.0001), rest wall motion score index (HR 1.69, 95% CI 1.01 to 2.83; p = 0.04), and systemic hypertension (HR 1.76, 95% CI 1.06 to 3.00; p = 0.04). The annual mortality was 5.1% in the overall population, 7.0% in the 140 (46%) patients with abnormal HRR and 3.5% in the 161 (54%) patients with normal HRR. The 8-year mortality was 48% in patients with abnormal HRR and 18% in those with normal HRR (p <0.0001). In conclusion, patients with suspected or known coronary artery disease with permanent AF with a blunted HRR have an increased mortality. HRR outweighs inducible ischemia for prediction of survival. The assessment of HRR should become an integral part of dipyridamole SE reading also in AF., (Copyright © 2020. Published by Elsevier Inc.)

A blunted heart rate (HR) response during dipyridamole myocardial perfusion imaging has been associated with a poor outcome. To assess the value of HR response in patients who underwent high-dose dipyridamole stress echocardiography (SE), we retrospectively selected a sample of 3,059 patients (none with pacemakers or atrial fibrillation; mean age 66 ± 11 years). All underwent high-dose (0.84 mg/kg) dipyridamole SE for evaluation of known or suspected coronary artery disease and/or heart failure in 2 laboratories of Pisa-IFC and Lucca. HR (with 12-lead ECG) was obtained each minute and recorded at rest and peak stress. HR reserve (HRR) was calculated as the peak/rest HR ratio. All patients were followed up. Patients were randomly divided into the modeling and validation group of equal size. During a median follow-up time of 1,004 days, 321 hard events occurred: 231 deaths and 90 nonfatal myocardial infarctions. HRR ≤ 1.22 identified by receiver operating characteristic analysis in the modeling group was an independent predictor of infarction-free survival in the modeling (hazard ratio 1.83, 95% confidence interval [CI] 1.30 to 2.60, p = 0.001), in the validation (hazard ratio 1.47, 95% CI 1.08 to 2.01, p = 0.02), and in the overall group (hazard ratio 1.60, 95% CI 1.27 to 2.02, p <0.0001), either off- or on-β blockers. Five-year event rate increased from 8% to 24 % from the highest (≥1.41) to the lowest (≤1.14) HRR quartile. In conclusion, blunted HRR is a useful nonimaging predictor of adverse events during high-dose dipyridamole SE, independent of inducible ischemia, and beta-blocker therapy., (Copyright © 2019 Elsevier Inc. All rights reserved.)

The aim of this study was to investigate the prognostic effect of coronary flow reserve (CFR) on left anterior descending artery (LAD) in women and men with chest pain of unknown origin and normal stress echocardiogram. The study population consisted of 1,660 patients (906 women, 754 men) with chest pain syndrome, no wall motion abnormality on echocardiogram at rest, and dipyridamole (up to 0.84 mg/kg over 6 minutes) stress echocardiogram negative for wall motion criteria. All had undergone stress echocardiography with combined evaluation of CFR on LAD by Doppler. A CFR value ≤2.0 was considered abnormal. Median duration of follow-up was 19 months (interquartile range 10 to 34). Abnormal CFR was assessed in 171 women (19%) and 147 men (19%, p = 0.80). During follow-up, 80 events (20 deaths, 13 ST-elevation myocardial infarctions, and 47 non-ST-elevation myocardial infarctions) occurred. In addition, 128 patients underwent revascularization and were censored. CFR ≤2.0 on LAD was independently associated with prognosis in women (hazard ratio [HR] 16.48, 95% confidence interval [CI] 7.17 to 37.85, p <0.0001) and in men (HR 6.23, 95% CI 3.42 to 11.33, p <0.0001). Antianginal therapy at time of testing (HR 2.11, 95% CI 1.14 to 3.90, p = 0.02) was also a multivariable prognostic predictor in men. Four-year event rate associated with CFR values ≤2.0 and >2.0 were, respectively, 27% and 2% in women (p <0.0001) and 42% and 8% in men (p <0.0001). In conclusion, decreased CFR on LAD is associated with markedly increased risk in women and men with chest pain syndrome and a normal result of dipyridamole stress echocardiography. Conversely, preserved CFR on LAD predicts excellent survival, particularly in women., (Copyright © 2010 Elsevier Inc. All rights reserved.)

The development of significant intraventricular gradients (IVGs) during exercise has been described anecdotally in athletes. However, the prevalence and clinical effect of this observation are unclear. In addition, the most appropriate exercise technique (upright vs semisupine) for eliciting IVGs also remains unknown. The present study had 2 main aims: (1) to identify the prevalence of exercise IVGs in athletes whose preparticipation cardiovascular screening result for sports practice, according to the European Society of Cardiology guidelines, was positive; and (2) to evaluate the influence of performing exercise echocardiography, as described, on the detection of IVGs. We enrolled 139 consecutive athletes (135 amateurs and 4 professionals, mean age 22 ± 9.9 years; 30 women) who underwent treadmill exercise echocardiography. In each athlete, the IVG was evaluated by continuous wave Doppler during 5 conditions: left lateral decubitus at rest; upright at rest; upright at peak treadmill exercise; upright in the recovery phase; and left lateral decubitus in the recovery phase. All patients had normokinetic regional wall motion at rest and during exercise. According to the detection of IVG during treadmill echocardiography (IVG was considered significant if >30 mm Hg at rest or >50 mm Hg during/after exercise), 2 groups were identified: a group (n = 52), with significant IVG and a group (n = 87) without significant IVG. The IVG was greater in the upright position, both at rest (only 2 athletes from group with IVG) and after exercise (52 athletes, all from group with IVG). The IVG was lower in the recovery phase in the left lateral decubitus position (55 ± 15 mm Hg in 30 athletes, all from group with IVG) than in the upright position in the recovery phase (95 ± 35 mm Hg in 52 athletes, all from group with IVG) and at peak exercise (66 ± 24 mm Hg in 41 athletes from group with IVG). We observed systolic anterior movement of the mitral valve in 33 of the 52 athletes in the group with IVG and in none of the athletes in the group without IVG. In conclusion, in athletes, exercise-induced symptoms and/or ischemia-like electrocardiographic signs are often associated with significant IVG, developing in the absence of wall motion abnormalities. IVG was more evident during post-treadmill upright imaging., (Copyright © 2010 Elsevier Inc. All rights reserved.)

The additive prognostic value of coronary flow reserve (CFR) over regional wall motion has been established, but there is more than a binary (normal-abnormal) response in CFR, which can be continuously titrated. We assessed the prognostic value of quartiles of CFR, evaluated by transthoracic Doppler of the left anterior descending coronary artery (LAD), in patients with known or suspected coronary artery disease (CAD). One thousand six hundred twenty patients (1,006 men, 64 +/- 11 years of age) underwent dipyridamole (up to 0.84 mg/kg over 6 minutes) stress echocardiography with CFR evaluation of LAD by Doppler and coronary angiography. Patients were followed up for a median of 19 months. Mean CFR in the entire population was 2.25 +/- 0.65. Stress echocardiogram was positive for ischemia in 480 patients (30%). Obstructive (>or=70% vessel stenosis) CAD at angiography was present in 650 patients (40%). During follow-up, there were 298 events (42 deaths, 73 ST-elevation myocardial infarctions, and 183 non-ST-elevation myocardial infarctions). Patients (n = 399) undergoing revascularization were censored. With the Kaplan-Meier method, the first quartile of CFR (

In patients with angiographically normal coronary arteries and chest pain, pharmacologic stress echocardiography can identify a subgroup of patients with a less benign prognosis. Coronary flow reserve (CFR) in the left anterior descending artery (LAD) can currently be combined with wall motion analysis during vasodilator stress echocardiography. The aim of this study was to assess the prognostic value of CFR response in patients with normal coronary arteries and normal wall motion during stress. We selected 394 patients (171 men, 61 +/- 11 years of age) who underwent dipyridamole stress echocardiography (0.84 mg/kg over 6 minutes) with 2-dimensional echocardiography and CFR evaluation of the LAD by Doppler. All had angiographically nonsignificant (<50% quantitatively assessed) stenosis in any major vessel, normal left ventricular function (wall motion score index 1), and test negativity for conventional wall motion criteria. Images were independently read by a core laboratory for wall motion and a core laboratory for CFR. Mean CFR was 2.5 +/- 0.6 and 87 patients (22%) had an abnormal CFR <2. During a median follow-up of 51 months, 31 events occurred, namely 4 deaths and 27 nonfatal myocardial infarctions (3 ST-elevated myocardial infarctions and 24 non-ST-elevated myocardial infarctions). Kaplan-Meier survival estimates for hard events showed a better outcome for those patients with a normal CFR compared with those with an abnormal CFR (96% vs 55%, p = 0.001, at 48 months of follow-up). In conclusion, in patients with angiographically normal or near-normal coronary arteries and preserved at-rest regional and global left ventricular function at baseline and during stress, CFR adds incremental value to the prognostic stratification achieved with clinical and angiographic data.

The aim of the study was to prospectively evaluate a cohort of patients with hypertrophic cardiomyopathy (HC) after coronary flow reserve (CFR) assessment of the left anterior descending coronary artery. Sixty-eight patients with HC (40 men, mean +/- SD 58 +/- 12 years of age) underwent dipyridamole (up to 0.84 mg/kg over 6 minutes) echocardiography with CFR evaluation of the left anterior descending coronary artery by Doppler. Seventy-four age- and gender-matched, apparently healthy subjects served as controls. A CFR value <2.0 was considered abnormal. CFR was decreased in patients with HC versus controls (2.12 +/- 0.39 vs 2.78 +/- 0.58, p <0.0001). CFR was abnormal in 26 of 39 symptomatic and in 5 of 29 asymptomatic patients with HC (67% vs 17%, p <0.0001). In addition, patients with HC with left ventricular obstruction had decreased CFR (p <0.0001) compared with those without obstruction. During follow-up (22 +/- 13 months), 27 events occurred: 1 sudden death, 1 nonfatal myocardial infarction, 4 cardioverter-defibrillator implantations, 6 hospitalizations for heart failure, 5 unstable anginas, 2 syncopes, and 8 atrial fibrillations. Three-year event rate was markedly higher in patients with abnormal than in those with normal CFR (79% vs 17%, p <0.0001). Events were more frequent in symptomatic than in asymptomatic patients (62% vs 10%, p <0.0001). However, the latter had a 10-fold increased risk of events in the presence of abnormal CFR (40% vs 4%, p = 0.02). In conclusion, mean CFR is markedly lower in patients with HC than in apparently healthy subjects. Abnormal CFR is a strong and independent predictor of outcome in patients with HC.

The aim of this study was to compare the diagnostic accuracy of perfusion and wall motion (WM) during dipyridamole magnetic resonance in patients with chest pain syndrome. Ninety-three patients with normal baseline left ventricular function were referred for coronary angiography. Additional dipyridamole stress magnetic resonance testing (0.84 mg/kg over 6 minutes; using a Signa Cvi scanner) was performed. Cardiac-gated fast gradient-echo train sequences with a first pass of gadolinium contrast medium were used to assess myocardial perfusion. A perfusion reserve index was calculated as the ratio of dipyridamole to rest upslope. A perfusion reserve index value <1.54 in 2 contiguous myocardial segments was the perfusion positivity criterion. The WM positivity criterion was a segmental score increase of > or =1 grade in > or =2 segments. WM and the perfusion reserve index showed similar diagnostic accuracy for >50% quantitatively assessed coronary diameter reduction (86% for both), with WM having higher specificity (96% vs 66%, p <0.01) and lower sensitivity (82% vs 93%, p <0.05) than the perfusion reserve index. Perfusion had the highest accuracy values for coronary stenoses <75% (cutoff 59%) and WM for coronary stenoses > or =75% (cutoff 84%) (p <0.001). In conclusion, during dipyridamole magnetic resonance stress testing, perfusion and WM abnormalities have similar diagnostic accuracy, with perfusion showing higher sensitivity, particularly in the detection of moderate stenoses, and WM showing higher specificity.

The aim of this study was to compare the prognostic value of pharmacologic stress echocardiography in diabetic and nondiabetic patients with chest pain and intermediate- to high-threshold positive exercise electrocardiographic results. A total of 935 patients with chest pain (131 diabetic patients) with ST-segment depression > or =1 mm on exercise electrocardiography at > or =75-W workload underwent dipyridamole (n = 786) or dobutamine (n = 149) stress echocardiography and were followed up for the occurence of hard (death and infarction) and major events (death, infarction, and late revascularization). During a median follow-up of 26 months, 158 events (51 deaths, 28 myocardial infarctions, and 79 late revascularizations) occurred: 34 in diabetic and 124 in nondiabetic patients (26% vs 15%, p = 0.003). Independent predictors of hard events were age, diabetes, and ischemia at stress echocardiography. Five-year hard event rates were 24% in patients with and 4% in those without ischemia (p <0.0001). Independent predictors of major events were age, diabetes, hypercholesterolemia, smoking habit, antianginal therapy at the time of testing, and ischemia at stress echocardiography. Five-year major event rates were 46% in patients with and 7% in those without ischemia (p <0.0001). Stress echocardiography results yielded effective prognostic information in diabetic and nondiabetic patients. However, the latter had worse outcomes in both the presence and absence of ischemia. Nevertheless, a nonischemic test result predicted an uneventful 6-month period and 2% major event rate at 1-year follow-up in both populations. In conclusion, stress echocardiography was effective in risk stratifying diabetic and nondiabetic patients with intermediate- to high-threshold ischemic exercise electrocardiographic results. However, major event rates associated with a nonischemic test result were similar in diabetic and nondiabetic patients during the first year of follow-up and markedly increased in the former thereafter.

According to American College of Cardiology/American Heart Association/Society for Cardiovascular Angiography and Interventions 2005 guidelines on percutaneous intervention, intracoronary physiologic measurement in the assessment of effects of intermediate coronary stenoses in patients with anginal symptoms is a class IIa indication. This study assessed the additional prognostic value of Doppler echocardiographically derived coronary flow reserve (CFR) in patients with single-vessel disease and intermediate stenosis severity. We enrolled 86 patients (44 men; 66 +/- 10 years of age) with angiographically assessed single-vessel coronary artery disease of the left anterior descending coronary artery (LAD) with quantitatively assessed diameter stenosis severity 50% to 75%. All patients underwent dipyridamole (up to 0.84 mg/kg over 6 minutes) stress echocardiography with wall motion analysis by 2-dimensional echocardiography and CFR evaluation of the affected artery by Doppler. All patients were followed up for a median of 14 months (first quartile 10, third quartile 18) after diagnostic coronary angiography (without percutaneous intervention for a clinically driven decision). Mean diameter stenosis of the LAD was 58 +/- 10%. Mean CFR of the LAD was 2.09 +/- 0.5. Regional wall motion abnormality at peak stress was present in 17 patients. During follow-up, 24 events occurred: 6 nonfatal ST-elevation myocardial infarctions and 18 non-ST-elevation myocardial infarctions. Thirty-month spontaneous event-free survival was higher in patients with normal CFR and lower in patients with decreased CFR (86% vs 30%, p = 0.0001). At Cox analysis, a CFR <2 (hazard ratio 24.2, 95% confidence interval 3.2 to 179.7, p = 0.002) was the only independent prognostic predictor of outcome. In conclusion, in medically treated patients with single-vessel disease of intermediate severity, decreased CFR is associated with a worse outcome.

The aim of this study was to evaluate the prognostic value of Doppler echocardiographically derived coronary flow reserve (CFR) in assessing inotropic response in patients with idiopathic dilated cardiomyopathy (IDC). One hundred thirty-two patients with IDC (90 men; mean age 62 +/- 11 years) were evaluated by transthoracic dipyridamole (0.84 mg/kg in 10 minutes) stress echocardiography. All patients had ejection fractions <40% (mean 33 +/- 7%) and angiographically normal coronary arteries, with New York Heart Association class 0.25. All patients were followed for a median of 24 months. Mean CFR was 2.0 +/- 0.5. On individual patient analysis, 48 patients had normal CFR (>2), and 84 had abnormal CFR. The mean wall motion score index at rest was 2.0 +/- 0.33 and decreased to 1.8 +/- 0.4 at peak dipyridamole dose (p <0.000). Forty-two patients (32%) had inotropic reserve. During follow-up, 19 patients died, and 34 showed worsening of New York Heart Association class. The worst outcomes were observed in those patients with abnormal CFR and no inotropic reserve with high-dose dipyridamole. In a Cox model, mitral insufficiency (hazard ratio [HR] 1.7, 95% confidence interval [CI] 1.1 to 2.8), New York Heart Association class (HR 2.0, 95% CI 1.1 to 3.7), abnormal CFR (HR 2.8, 95% CI 1.0 to 8.5), wall motion score index at rest (HR 3.5, 95% CI 1.3 to 9.8), and the absence of inotropic reserve with high-dose dipyridamole (HR 2.3, 95% CI 1.06 to 5.1) were independent predictors of survival. In conclusion, in patients with IDC, CFR is often impaired. Reduced CFR and the absence of an inotropic response during vasodilator stress are additive in predicting a worse prognosis.

The safety of any diagnostic test is a major issue in deciding its practicability and cost-effectiveness. The aim of this study was to evaluate the safety of various stress echocardiographic modalities in the "real world." From February 1998 to January 2004, a simple written questionnaire was distributed to echocardiography laboratories across the world known to perform stress echocardiography. The following categories of major complications (known to occur during stress testing) were indicated: sustained ventricular tachycardia (> 30 beats/min), ventricular fibrillation, myocardial infarction, third-degree atrioventricular block, severe hypotension requiring therapy, cardiac asystole, cardiac rupture, stroke, and death. Three hundred centers were polled, from which 71 co-investigators responded and reported on 85,997 patient examinations. Exercise was used in 26,295 cases, dobutamine in 35,103, and dipyridamole in 24,599 cases. Life-threatening events occurred in 86 cases: during exercise in 4 patients (event rate 1 in 6,574), during dobutamine infusion (small dose for viability and/or large dose for ischemia) in 63 patients (event rate 1 in 557), and during dipyridamole stress testing in 19 patients (event rate 1 in 1,294). Of the 86 patients with complications, 5 died during dobutamine stress testing (ventricular fibrillation, n = 2; cardiac rupture, n = 3) and 1 after dipyridamole testing (cardiogenic shock). In conclusion, stress echocardiography is a safe method in the real world, but serious complications may occur. Exercise seems safer than pharmacologic stress and dipyridamole safer than dobutamine, possibly because of preselection criteria.

We assessed whether the presence of latent myocardial dysfunction, evaluated by echocardiographic derived force-frequency relationship (FFR) during exercise, predicts the appearance of stress-induced pulmonary hypertension in minimally symptomatic patients with severe mitral regurgitation (MR). Two groups of patients were identified: group I with normal (40 mm Hg) peak stress systemic pulmonary artery pressure. Group I had normal and upsloping FFR and group II had abnormal flat or biphasic FFR. Therefore, in patients with severe MR and apparently normal left ventricular function, the stress-induced pulmonary hypertension seems to be related to the presence of latent left ventricular dysfunction.

Patients with cardiac syndrome X with mild hypercholesterolemia were randomized to placebo (n = 20) or simvastatin 20 mg/day (n = 20). In the simvastatin group, there was a significant (26%; p < 0.0001) decrease in total cholesterol, a 38% (p < 0.0001) decrease in low-density lipoprotein cholesterol levels, and 7% a (p < 0.0001) increase in high-density lipoprotein cholesterol levels, without significant changes in triglyceride levels. Brachial artery flow-mediated dilation increased significantly (52% relative increase, p < 0.0001), and the time to > 1-mm ST-segment depression during stress testing was longer by the end of the study (p < 0.0001)., (Copyright 2004 Excerpta Medica, Inc.)

The "comet-tail" is an ultrasound sign detectable with ultrasound chest instruments; this sign consists of multiple comet-tails fanning out from the lung surface. They originate from water-thickened interlobular septa and would be ideal for nonradiologic bedside assessment of extravascular lung water. To assess the feasibility and value of ultrasonic comet signs, we studied 121 consecutive hospitalized patients (43 women and 78 men; aged 67 +/- 12 years) admitted to our combined cardiology-pneumology department (including cardiac intensive care unit); the study was conducted with commercially available echocardiographic systems including a portable unit. Transducer frequencies (range 2.5 to 3.5 MHz) were used. In each patient, the right and left chest was scanned by examining predefined locations in multiple intercostal spaces. Examiners blinded to clinical diagnoses noted the presence and numbers of lung comets at each examining site. A patient lung comet score was obtained by summing the number of comets in each of the scanning spaces. Within a few minutes, patients underwent chest x-ray, with specific assessment of extravascular lung water score by 2 pneumologist-radiologists blinded to clinical and echo findings. The chest ultrasound scan was obtained in all patients (feasibility 100%). The imaging time per examination was always <3 minutes. There was a linear correlation between echocardiographic comet score and radiologic lung water score (r = 0.78, p <0.01). Intrapatient variations (n = 15) showed an even stronger correlation between changes in echocardiographic lung comet and radiologic lung water scores (r = 0.89; p <0.01). In 121 consecutive hospitalized patients, we found a linear correlation between echocardiographic comet scores and radiologic extravascular lung water scores. Thus, the comet-tail is a simple, non-time-consuming, and reasonably accurate chest ultrasound sign of extravascular lung water that can be obtained at bedside (also with portable echocardiographic equipment) and is not restricted by cardiac acoustic window limitations.

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.

This study assesses the prognostic value of myocardial viability recognized as a contractile response to inotropic stimulation in patients with left ventricular (LV) dysfunction in a large-scale prospective, multicenter, observational study. Four hundred twenty-five patients (mean age 61 +/- 10 years) with angiographically proven coronary artery disease, previous (>3 months) myocardial infarction, and severe LV dysfunction (ejection fraction <35%; mean 28 +/- 6%) were enrolled in the study. Each patient underwent low-dose dobutamine echocardiography (up to 10 microg/kg/min). Myocardial viability was identified as a rest-stress variation (Delta) in the wall motion score index (WMSI), in which each segment was scored from 1 = normal to 4 = dyskinetic in a 16-segment model of the left ventricle. Myocardial viability was identified as an improvement of >/=0.40 in WMSI. All patients were followed for a median of 3.1 years. One hundred eighty-eight were revascularized either by coronary artery bypass grafting (n = 118) or coronary angioplasty (n = 70). The only end point analyzed was cardiac death. In the revascularized group, cardiac death occurred in 4 of the 52 patients with and in 37 of the 136 patients without myocardial viability (7.7% vs 27.2%, p <0.003). Kaplan-Meier survival estimates showed a better outcome for those patients with compared to patients without myocardial viability who underwent coronary revascularization (90.1% vs 62%, p <0.0078). Thus, in severe LV ischemic dysfunction, myocardial viability by low-dose dobutamine echocardiography is associated with improved survival in revascularized patients.

In patients with a major coronary vessel occluded, the presence of good coronary collateral circulation increases vulnerability to myocardial ischemia induced by pharmacologic coronary vasodilation. The presence of good collaterals results in a greater frequency, severity, and extent of dipyridamole-induced regional left ventricular dysfunction, consistent with the hypothesis of angiographically assessed collaterals facilitating "steal phenomena" during dipyridamole-induced coronary vasodilation.

The aims of this study were: (1) to assess whether variations in cyclic echo amplitude might be detected across the human myocardium by videodensitometric analysis of images obtained with epicardial echocardiography; and (2) to explore the possible relation between cyclic gray level variation and left ventricular (LV) hypertrophy and function. Experimental studies show that transmural differences in contractile performance across the normal myocardium are paralleled by differences in the cyclic (diastolic-to-systolic) variation of myocardial echo amplitude. Thirty-three patients (aged 60 +/- 11 years) undergoing cardiac surgery were studied by intraoperative epicardial echocardiography. LV mass index as normal (<110 g/m2 in women, <131 g/m2 in men) in 10 patients and increased in 22. Two-dimensional echocardiographic images were obtained with a 5 MHz transducer and digitized off-line. Videodensitometric analysis was performed at end-diastole and end-systole with regions of interest across the septal and posterior wall. The cyclic variation was more pronounced in the left than in the right septal subendocardium (31% +/- 14% vs 16% +/- 14% <0.01) and higher in the subendocardial than in the subepicardial layer of the posterior wall (30% +/- 21% vs 23 +/- 18%, p <0.01). Cyclic variation of the left septal subendocardium was higher in 11 patients with nonhypertrophic ventricles than in 22 with hypertrophic left ventricles (42% +/- 15% vs 27% +/- 12%; p <0.01). The percent cyclic variation of the left septal subendocardium appeared to be much more tightly related to percent systolic thickening in patients with eccentric LV hypertrophy (r=0.80 p <0.01) than in patients with concentric LV hypertrophy (r=0.27, p=0.9) or normal LV mass (r=0.43, p=0.2). A cyclic gray level variation can be consistently detected in different human myocardial regions and layers. It is more obvious in the subendocardial than in the subepicardial layer, and in nonhypertrophic than hypertrophic ventricles. The cyclic subendocardial variation is tightly related to regional systolic thickening in patients with eccentric LV hypertrophy.

The recognition of coexistent coronary artery disease (CAD) in patients with hypertrophic cardiomyopathy may be difficult by noninvasive testing based upon electrocardiographic changes or perfusion defects. Dipyridamole-stress echocardiography has proved a sensitive and highly specific test for noninvasive diagnosis of CAD in various patient subsets. To establish the feasibility, safety, and diagnostic accuracy of dipyridamole-stress echocardiography in patients with hypertrophic cardiomyopathy, we performed high-dose dipyridamole testing (up to 0.84 mg/kg over 10 minutes) in 88 patients with hypertrophic cardiomyopathy (63 men; mean age +/- SD, 46 +/- 17 years). A subset of 60 patients was referred for coronary angiography independently of test results; CAD was defined as > or = 50% diameter narrowing in at least 1 major coronary vessel. Dipyridamole echocardiography/electrocardiography testing was completed in all patients, with no limiting side effects or adverse reactions. In the subgroup of 60 patients with coronary angiography (14 with and 46 without CAD), chest pain occurred in 18 patients (8 with and 10 without CAD, p = NS); ST-segment depression > or = 2 mm from baseline in 28 (7 with and 21 without CAD, p = NS); and transient dyssynergy in 10 patients (10 with and none without CAD, p < 0.0001). Assuming the transient regional dyssynergy to be the only criterion of positivity, the dipyridamole echocardiography test showed 71% sensitivity, 100% specificity, 100% positive predictive value, and 93% diagnostic accuracy for diagnosis of angiographically assessed CAD. We conclude that high-dose dipyridamole echocardiography testing may be considered a feasible and accurate tool for the noninvasive diagnosis of CAD in patients with hypertrophic cardiomyopathy.

From a population of 2,698 patients (579 evaluated early after an uncomplicated acute myocardial infarction) who underwent dipyridamole echocardiography testing (DET) and subsequent coronary angiography, left main (LM) stenosis > or = 50% was present in 73 (61 men and 12 women, mean age 62 +/- 8 years). These 73 patients were compared with a control group comprising 100 consecutive coronary patients without LM disease. Both groups were similar regarding mean age, sex, incidence of previous myocardial infarction, left ventricular function at rest, and severity of coronary artery disease by the number of diseased vessels excluding the LM. The proportion of patients receiving antianginal therapy during DET was higher in the LM than in the non-LM group (32 vs 14%; p < 0.01). No major complication (severe hypotension, sustained arrhythmia, myocardial infarction or death) occurred during DET. Of 73 patients with LM disease, 68 had positive DET (sensitivity 93%), dipyridamole time was 7.1 +/- 3.8 minutes, and the rest-peak stress variation in dipyridamole wall motion score index (1 = normal to 4 = dyskinesia, in an 11-segment model) was 0.37 +/- 0.23; 14 patients (19%) were resistant to aminophylline and needed nitrates to resolve ischemia. In the non-LM group, DET was positive in 72% (p < 0.001 vs LM), with a longer dipyridamole time (9.6 +/- 5.2 minutes; p < 0.001 vs LM), lower rest-peak stress wall motion score index variation (0.29 +/- 0.25; p < 0.05 vs LM), and less frequent antidote resistance (1%; p < 0.001 vs LM).(ABSTRACT TRUNCATED AT 250 WORDS)

The usefulness of high-dose (< or = 0.84 mg/kg over 10 minutes) dipyridamole echocardiography testing was compared with that of exercise thallium-201 scintigraphy in detecting restenosis (> 70% lumen reduction) in 50 asymptomatic patients with ST-segment depression during maximal exercise testing 3 months after successful coronary angioplasty. Dipyridamole echocardiography testing and exercise thallium scintigraphy showed a similar sensitivity (75 vs 83%; p = NS) and specificity (90 vs 84%; p = NS) for the detection of restenoses, which occurred in 12 patients. It is concluded that dipyridamole echocardiography testing is as accurate as exercise thallium testing for the noninvasive detection of severe restenosis in patients with exercise-induced asymptomatic ST-segment depression after successful angioplasty. Furthermore, the site, extent and severity of the thallium perfusion defects during exercise are correlated to those of the dyssynergy during dipyridamole echocardiography.

The relation between radioisotopic and echocardiographic markers of myocardial viability and postrevascularization recovery of function is still to be defined. To this purpose, 14 patients (11 men, 3 women, aged 35 to 64 years, mean 54 +/- 7) with ventricular dysfunction were studied by a multiparametric approach. Each patient underwent, on separate days, rest thallium-201 and technetium-99m sestamibi scintigraphy, dobutamine echocardiography and coronary angiography. Coronary angiography was analyzed by a quantitative approach. Thallium uptake at rest was quantified from planar early (10-minute) and delayed (16-hour) thallium-201 images and expressed as a percentage of maximal activity in each projection using a 13-segment model. Sestamibi uptake was expressed in the same way. Dobutamine (up to 10 micrograms/kg/min) echocardiography was analyzed using a score index ranging from 1 (normokinesia) to 4 (dyskinesia) and a similar segmental model. Before revascularization 50 segments were grouped as normal (coronary stenosis < 50% and normal function, group 1); of the remaining 132 segments with > 50% coronary stenosis, 57 had normal wall motion (group 2) and 75 showed regional dyssynergies (group 3). Early and delayed thallium-201 regional percent activities did not differ in group 1 and in group 2 but were significantly less in group 3 segments. Sestamibi percent activity was more in group 1 and significantly reduced both in group 2 and 3 segments. Segments with improved wall motion after dobutamine had more early, delayed thallium-201 and sestamibi percent activities than unresponsive segments. Postrevascularization echocardiography was performed in all patients. Delayed thallium-201 scans and dobutamine echocardiography showed good sensitivity and specificity in detecting viable myocardium. (ABSTRACT TRUNCATED AT 250 WORDS)

In patients with coronary artery disease and left ventricular impairment, the distinction between ventricular dysfunction due to myocardial fibrosis and postischemic, viable, although dys-synergic, myocardium has important clinical implications. Experimental studies have shown that dipyridamole can increase myocardial function in stunned segments, outlining a potential role of dipyridamole-induced functional recovery as an ultrasonic marker of myocardial viability. The aim of this study was to assess whether the increase of regional left ventricular function early during dipyridamole infusion in basally asynergic segments could identify viable myocardium recognized by rest injected, delayed (greater than 14 hours from tracer injection) thallium and (in a subset of patients) late functional recovery evaluated by a follow-up echocardiogram at rest. Twenty-two patients with angiographically documented coronary artery disease and regional dysfunction in resting conditions (average left ventricular ejection fraction 43 +/- 8%) were studied by echocardiography. All patients underwent a dipyridamole-echocardiographic test (up to 0.84 mg/kg over 10 minutes) and a delayed planar thallium study. A 13-segment model was used for both techniques. A score index ranging from 1 (normokinesia) to 4 (dyskinesia) was used for echocardiography. Thallium-201 activity was expressed in each segment as the percentage of maximal activity in the corresponding view. After dipyridamole, the wall motion score was assigned to each segment in resting conditions and at peak hyperkinesia before possible mechanical signs of ischemia.(ABSTRACT TRUNCATED AT 250 WORDS)

Clinical data on 10,451 high-dose (up to 0.84 mg/kg over 10 minutes) dipyridamole-echocardiography tests (DET) performed in 9,122 patients were prospectively collected from 33 echocardiographic laboratories, each contributing greater than 100 tests. All patients were studied for documented or suspected coronary artery disease (1,117 early [less than 18 days] after acute myocardial infarction and 293 had unstable angina). Significant side effects including major adverse reactions and minor but limiting side effects occurred in 113 patients (1.2%). Major adverse reactions occurred in 7 cases (0.07%). In 6 of these cases, adverse reactions were associated with echocardiographically assessed ischemia and included 1 prolonged cardiac asystole (complicated by acute myocardial infarction and coma, with death after 23 days), 1 short-lasting cardiac asystole, 2 myocardial infarctions, 1 pulmonary edema and 1 sustained ventricular tachycardia. In all 6 cases, the cardiologist-echocardiographer performing the study had a limited experience (less than 100 tests) with DET, and at off-line reading in 5 cases, the obvious echo-positivity preceded the onset of complications by 1 to 5 minutes. The only ischemia-independent major side effect was a short-lasting cardiac asystole that was reversed by aminophylline and atropine. Significant side effects associated with echocardiographically assessed ischemia occurred in 89 additional cases (21 with and 68 without concomitant echocardiographically assessed myocardial ischemia). The most frequent of these side effects was hypotension or bradycardia, or both, which occurred in 40 patients with negative and 6 with positive DET. In all cases, side effects promptly subsided after aminophylline. In 1,857 cases, the high dose was not given for echo-positivity before the eighth minute.(ABSTRACT TRUNCATED AT 250 WORDS)

The present study compares the relative usefulness of the maximal treadmill exercise electrocardiography test with the high-dose dipyridamole echocardiography test (echocardiographic monitoring during dipyridamole infusion up to 0.84 mg/kg in 10 minutes) in detecting severe restenosis or coronary artery disease progression (greater than 70% stenosis) in asymptomatic patients 12 months after a primary successful coronary angioplasty. Criteria of positivity were: for the exercise electrocardiography test, an ST-segment shift greater than or equal to 0.1 mV from baseline, 0.08 second from the J point; for the dipyridamole echocardiography test, a transient dyssynergy of contraction, absent or of a lesser degree than that in the baseline examination. The exercise electrocardiography and dipyridamole echocardiography tests revealed a similar feasibility (91 vs 87%, difference not significant). Both tests could be performed in 75 patients. For detection of restenosis or disease progression, or both, the exercise electrocardiography test revealed a sensitivity similar to the dipyridamole echocardiography test (71 vs 71%, difference not significant), but a lower specificity (61 vs 90%). It is concluded that the high-dose dipyridamole echocardiography test is equally feasible but more accurate than the exercise electrocardiography test for noninvasive detection of severe asymptomatic restenosis or disease progression at 1 year after successful coronary angioplasty.

Conventional echocardiography provides fundamental information about mitral valve morphology and function but has a relatively low specificity in evaluating valve calcific deposits, which is critical information for the preoperative decision to perform commisurotomy or replacement. In vitro radiofrequency ultrasonic quantitative analysis of the mitral valve has been demonstrated to be a reliable tool in identifying normal, fibrotic and calcific valves. This study evaluates quantitative ultrasound characterization of the mitral valve in vivo. Thirty-three patients, scheduled to undergo mitral valve replacement, and 20 normal subjects (10 young and 10 older control subjects) were studied with a 2.25-MHz transducer. Radiofrequency signal was analyzed by a microprocessor system (used with an M-mode commercially available echocardiograph) for on-line evaluation of ultrasonic backscatter with 8 bits of amplitude resolution, 40-MHz sampling rate and a 1-microsecond acquisition gate. The integrated value of the rectified radiofrequency signal amplitude was deemed the integrated backscatter index. The highest value recorded with the ultrasonic analysis from each valve was taken as representative and expressed as the percent value with respect to the pericardial integrated backscatter index value of that subject. The 33 excised mitral valves underwent histologic examination. Four groups were identified: young controls (group I, n = 10); older controls age-matched with patients (group II, n = 10); patients with fibrotic mitral valves (group III, n = 13); and patients with calcific mitral valves (group IV, n = 20).(ABSTRACT TRUNCATED AT 250 WORDS)

Fourteen consecutive patients with exercise-induced ST-segment elevation in the absence of previous infarction and basal left ventricular asynergy at rest performed a dipyridamole test (infusion of dipyridamole, 0.14 mg/kg/min intravenously for 4 minutes) during 12-lead electrocardiographic (ECG) and 2-dimensional echocardiographic monitoring. In 7 of the 14 patients, dipyridamole infusion consistently induced ST-segment elevation in the leads that showed ST elevation on effort; reversible asynergy (occurring in the region corresponding to the ECG leads with diagnostic changes) could always be documented by echocardiography. In 2 patients dipyridamole induced reversible asynergy in presence of ST-segment depression. In these 9 patients angiography invariably revealed a severe organic stenosis in the coronary artery feeding the region that became transiently asynergic after dipyridamole. In the other 5 patients (all of whom had either spontaneous or ergonovine-induced ST-segment elevation), the dipyridamole test yielded no significant echocardiographic or ECG change; coronary angiography showed absent (2 patients) or significant (3 patients) coronary artery disease. In conclusion, dipyridamole may induce transmural ischemia in humans, as detected by the electrical hallmark of ST elevation; this ECG pattern, in contrast to ST depression, reliably predicts the presence and site of transient regional asynergy. When dipyridamole induces ST-segment elevation, severe basal stenosis is invariably present in the coronary artery supplying the transiently asynergic myocardial region.

Dipyridamole testing represents an alternative to exercise stress testing for documentation of ischemia related to coronary artery disease (CAD). In such a case, ischemia is attributed to maldistribution of coronary flow during dipyridamole-induced vasodilation. The present study evaluated the potential role of dipyridamole testing in producing ischemia through a vasospastic mechanism, following rapid withdrawal of vasodilation induced by aminophylline. The possibility was tested in 36 in-hospital patients with variant angina pectoris who underwent dipyridamole infusion (up to 0.84 mg/kg over 10 minutes) with continuous 12-lead electrocardiographic and 2-dimensional echo monitoring. Medications were withdrawn from all patients. The test was pharmacologically stopped with the dipyridamole antidote (aminophylline, 80 to 240 mg intravenously over 1 to 3 minutes) in all patients. Two to 6 minutes after starting aminophylline infusion, 10 patients (28%) developed (greater than 0.10 mV) ST-segment elevation (2.9 +/- 0.8 mm from baseline), always accompanied by obvious asynergy detected by echocardiography, in the same electrocardiographic leads showing spontaneous or ergonovine-induced ST-segment elevation. Nitrates promptly resolved ischemia in all patients. At coronary angiography, 5 of these 10 patients showed significant CAD (greater than 70% lumen diameter reduction of at least 1 major coronary artery), whereas 5 had nonsignificant CAD. The rate pressure product at the onset of ST-segment elevation (after dipyridamole plus aminophylline) was considerably less than that recorded at peak exercise stress test in these patients (9,600 +/- 2,200 vs 18,400 +/- 4,900, p less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)

Six attacks of variant angina (2 spontaneous, 4 induced by ergonovine) were studied in 6 patients by combined echocardiographic and hemodynamic monitoring. A decrease of percent systolic thickening of the ischemic wall, which occurred as early as the decrease in peak dP/dt of contraction, was detected before the onset of ST-segment elevation ("pre-electrocardiographic phase"). At this stage, no significant change in left ventricular (LV) end-diastolic pressure or end-diastolic diameter was observed. Subsequently, in the presence of clear-cut ST-segment elevation ("electrocardiographic phase"), percent systolic thickening (an index of regional function) reached its nadir, while dP/dt of contraction (an index of global function) was almost back to preischemic values. In this phase, a significant increase in LV end-diastolic diameter and end-diastolic pressure could be also detected. In the recovery phase, when the ST segment had returned to the isoelectric line ("post-electrocardiographic phase"), percent systolic thickening and dP/dt of contraction showed supernormal values, while LV end-diastolic pressure and end-diastolic diameter decreased below basal values. Thus, echocardiographic signs of impairment in LV mechanics are as early and sensitive as hemodynamic indexes during attacks of variant angina. Furthermore, information on morphologic characteristics and regional LV function, not available with hemodynamic monitoring, can be obtained by echocardiography.

Fifty-five patients with effort angina pectoris and technically satisfactory baseline echocardiograms performed a supine exercise-echocardiography test (EET) and a high-dose dipyridamole-echocardiography test (DET, up to 0.84 mg/kg of intravenous dipyridamole in 10 minutes). All underwent coronary arteriography, which showed that at least 1 major artery had more than 70% stenosis in 34 patients. For each patient, the same physician performed both tests, with the same echocardiographic equipment. Detection of new onset or worsening regional asynergy was the only criterion of positivity for both tests. DET yielded interpretable studies in all 55 patients (100%); EET yielded only 40 such studies (73%) (p less than 0.01). In the 40 patients in whom both tests were interpretable, DET showed, compared with EET, a similar sensitivity (72% vs 76%) and specificity (100% vs 87%) (difference not significant for both) for detecting angiographically assessed coronary artery disease. In the 16 patients in whom both DET and EET yielded positive responses for ischemia, the same myocardial region showed reversible asynergy. Thus, independent of all factors that can affect the performance of each test (operator, patient and instrumentation), DET was significantly more feasible than EET, with comparable sensitivity and specificity. Dipyridamole provokes asynergy in the same regions that show ischemia during exercise.