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Noninvasive estimation of systolic pulmonary artery pressure (SPAP) during exercise stress echocardiography (ESE) is recommended for pulmonary hemodynamics evaluation but remains flow-dependent. Our aim was to assess the feasibility of pulmonary vascular reserve index (PVRI) estimation during ESE combining SPAP with cardiac output (CO) or exercise-time and compare its value in three group of patients: with invasively confirmed pulmonary hypertension (PH), at risk of PH development (PH risk) mainly with systemic sclerosis and in controls (C) without clinical risk factors for PH, age-matched with PH risk patients. We performed semisupine ESE in 171 subjects: 31 PH, 61 PH at risk and 50 controls as well as in 29 young, healthy normals. Rest and stress assessment included: tricuspid regurgitant flow velocity (TRV), pulmonary acceleration time (ACT), CO (Doppler-estimated). SPAP was calculated from TRV or ACT when TRV was not available. We estimated PVRI based on CO (peak CO/SPAP*0.1) or exercise-time (ESE time/SPAP*0.1). During stress, TRV was measurable in 44% patients ACT in 77%, either one in 95%. PVRI was feasible in 65% subjects with CO and 95% with exercise-time (p < 0.0001). PVRI was lower in PH compared to controls both for CO-based PVRI (group 1 = 1.0 ± 0.95 vs group 3 = 4.28 ± 2.3, p < 0.0001) or time-based PVRI estimation (0.66 ± 0.39 vs 3.95 ± 2.26, p < 0.0001). The proposed criteria for PH detection were for CO-based PVRI ≤ 1.29 and ESE-time based PVRI ≤ 1.0 and for PH risk ≤ 1.9 and ≤ 1.7 respectively. Noninvasive estimation of PVRI can be obtained in near all patients during ESE, without contrast administration, integrating TRV with ACT for SPAP assessment and using exercise time as a proxy of CO. These indices allow for comparison of pulmonary vascular dynamics in patients with varied exercise tolerance and clinical status.

Background: A blunted heart rate reserve (HRR) during dipyridamole stress echocardiography (DSE) is a prognostically unfavorable sign of cardiac autonomic dysfunction. Short-term adjustments of heart rate (HR) are thought to rise from changes in neural input to the heart. DSE is applied in potential heart donors to rule out underlying coronary artery disease and left ventricular dysfunction. The aim of this study is to assess HRR during DSE in brain death., Methods: We enrolled two groups: group 1 (N.=49, 22 men, 54.6±8.8 years) with patients in brain death enrolled in the nationwide marginal donor heart recruiting program; group 2 (N.=49, 18 men, 66.4±12.0 years) referred to DSE for suspected or known coronary artery disease. All underwent DSE (0.84 mg/kg in 6') by quality-controlled readers certified via web-based training (1487/CE Lazio-1). We assessed left ventricular contractile reserve (LVCR) as stress/rest ratio of force (systolic blood pressure/end-systolic volume). HRR was calculated as the peak/rest HR ratio from 12-lead EKG., Results: The two study groups were similar for prevalence of inducible ischemia (4/49 vs. 9/49, P=NS). Group 1 showed higher resting HR (group 1: 88.1±15.5 bpm vs. group 2: 66.5±11.5 bpm, P<0.01) and similar peak HR (group 1: 94.7±15.3 bpm vs. group 2: 89.5±19.3 bpm, P=0.144), with blunted HRR (group 1: 1.08±0.10 bpm vs. group 2: 1.36±0.31 bpm, P<0.01). HRR was unrelated to LVCR., Conclusions: HRR is almost abolished and unrelated to LVCR in brain-dead patients during DSE. The modulation of neural input to the heart is essential to determine HRR, and plays no significant role in determining the inotropic response during DSE.

Current guidelines recommend the use of exercise stress echocardiography (ESE) in patients with unexplained dyspnoea. SE was recently reshaped with the ABCDE protocol: A for asynergy, B for B-lines (4-site simplified scan), C for contractile reserve based on force, D for Doppler-based coronary flow velocity reserve (CFVR) in left anterior descending coronary artery; and E for EKG-based heart rate reserve (HRR, defined as peak/rest HR < 1.62). Aim of the study was to define the ESE response in patients with dyspnoea as the main symptom. From the initial population of patients referred in 2018 in a single center for semi-supine ESE, we selected two groups (without history of previous myocardial infarction or coronary revascularization) on the basis of the main presenting symptom: dyspnoea (Group 1, n = 100, 62 men, 63 ± 10 years) or chest pain (Group 2, n = 100, 58 men, age 61 ± 8 years). All underwent ESE with ABCDE protocol. Success rate was 100% for steps A, B, C, E, and 88% for step D. Positivity for A criterion occurred in 56 patients of Group 1 and 24 of Group 2 (p < 0.0001). B-lines positivity (stress > rest for ≥ 2 points) occurred in 40 patients of Group 1 and 28 of Group 2 (p = 0.07). LVCR positivity (< 2.0) occurred in 60 patients of Group 1 and 42 of Group 2 (p < 0.05). A reduced CFVR occurred in 56 of Group 1 and 22 of Group 2 (p < 0.0001). A blunted HRR was present in 44 patients of Group 1 and 22 of Group 2 (p < 0.001). In conclusion, in patients with unexplained dyspnoea, SE with ABCDE protocol is useful to document the cardiac origin of dyspnoea with a comprehensive assessment focused not only on ischemia (A) but also pulmonary congestion (B), myocardial scar or necrosis (C), coronary microvascular dysfunction (D) or chronotropic incompetence (E).

To investigate the role of right ventricular free wall strain (RVFWSL) to predict low functional capacity in repaired tetralogy of Fallot (rTOF). We prospectively enrolled 33 patients with rTOF with moderate to severe PR who underwent rest and peak exercise echocardiography on a semisupine cycloergometer. Conventional function and strain imaging parameters of both ventricles were measured. Patients performing < 7 METS were defined to have low functional capacity. Logistic regression was used to identify parameters associated with low functional capacity. Eleven patients (33.3%) had low functional capacity. These patients were shorter (height 155 ± 7 vs 163 ± 9 cm, p = 0.023), more frequently female (27.3 vs 72.7%, p = 0.024) and had history of Blalock-Taussig shunt (45.5 vs 9.1%, p = 0.027). On multivariate analysis RVFWSL was the only predictor of low functional capacity OR 1.39 (CI 95%, 1.06-1.83., p = 0.018) per % change. A RVFWSL < 17% (absolute value) had an AUC of 0.785, sensitivity of 81.8% and specificity of 77.3% to predict low functional capacity. Right ventricular free wall strain is an independent predictor of low functional capacity in repaired tetralogy of Fallot with moderate to severe PR. A value < 17% might be useful in deciding when to perform pulmonary valve replacement, when functional capacity cannot be objectively measured.

Various lung ultrasound (LUS) scanning modalities have been proposed for the detection of B-lines, also referred to as ultrasound lung comets, which are an important indication of extravascular lung water at rest and after exercise stress echo (ESE). The aim of our study was to assess the lung water spatial distribution (comet map) at rest and after ESE. We performed LUS at rest and immediately after semi-supine ESE in 135 patients (45 women, 90 men; age 62 ± 12 y, resting left ventricular ejection fraction = 41 ± 13%) with known or suspected heart failure or coronary artery disease. B-lines were measured by scanning 28 intercostal spaces (ISs) on the antero-lateral chest, 2nd-5th IS, along with the midaxillary (MA), anterior axillary (AA), mid-clavicular (MC) and parasternal (PS) lines. Complete 28-region, 16-region (3rd and 4th IS), 8-region (3rd IS), 4-region (3rd IS, only AA and MA) and 1-region (left 3rd IS, MA) scans were analyzed. In each space, the B-lines were counted from 0 = black lung to 10 = white lung. Interpretable images were obtained in all spaces (feasibility = 100 %). B-lines (>0 in at least 1 space) were present at ESE in 93 patients (69%) and absent in 42. More B-lines were found in the 3rd IS and along AA and MA lines. The B-line cumulative distribution was symmetric at rest (right/left = 1.10) and asymmetric with left lung predominance during stress (right/left = 0.67). The correlation of per-patient B-line number between 28-S and 16-S (R 2  = 0.9478), 8-S (R 2  = 0.9478) and 4-S scan (R 2  = 0.9146) was excellent, but only good with 1-S (R 2  = 0.8101). The average imaging and online analysis time were 5 s per space. In conclusion, during ESE, the comet map of lung water accumulation follows a predictable spatial pattern with wet spots preferentially aligned with the third IS and along the AA and MA lines. The time-saving 4-region scan is especially convenient during stress, simply dismissing dry regions and focusing on wet regions alone., (Copyright © 2017 World Federation for Ultrasound in Medicine & Biology. Published by Elsevier Inc. All rights reserved.)

Background: The presence of left ventricular contractile reserve (LVCR) during stress echo (SE) may provide favorable response to cardiac resynchronization therapy (CRT) in heart failure patients. The aim of the study was to perform a meta-analysis of available SE data in this set of patients., Methods: From a Pubmed and Advance Google Scholar database web based search scan up to December 2016, we initially identified 5906 records. From this initial set, we removed that did not include SE and duplicate studies. We assessed for eligibility 71 full-text articles assessed for eligibility, and 60 of them did not meet the inclusion criteria as follow: 1) heart failure patients with NYHA class III and IV, depressed ejection fraction (EF <35%) and QRS duration ≥120 ms at study entry; 2) SE with assessment of LVCR; 3) Follow-up data. LVCR during SE was identified as reduction in wall motion score index and/or an increase in EF., Results: Eleven studies with 861 patients (mean age 67 ± 9 years, ejection fraction 25 ± 6%) were included in the meta-analysis. The type of stress was either exercise (n = 2) or dobutamine (n = 9), the latter with low-dose (10 mcg) in two, intermediate-dose (20 mcg) in five, and high-dose (40 mcg) protocol in two studies. LVCR was detected in 555 patients (63%) and CRT-response was present in 584 (66%). The overall odds ratio for LVCR to predict a favorable CRT response was 2.06 (95%, CI 1.70-2-43), Z score: 11.055, p < 0.001., Conclusion: The presence of LVCR during SE with either dobutamine or exercise is associated with a greater chance of response to CRT. This parameter is now ready to be tested in a prospective multicenter trial to select patients more likely to benefit from CRT.

Background: Stress echo (SE) may have a role in the outcome in patients with hypertrophic cardiomyopathy (HCM)., Objectives: The aim was to assess the prognostic value of SE in a retrospective multicenter study in HCM., Methods: We enrolled 706 HCM patients. The employed stress was exercise (n=608) and/or vasodilator (n=146, dipyridamole in 98 and adenosine in 48). We defined SE positivity according to clinical/hemodynamic criteria including: symptoms (all stress modalities), exercise-induced hypotension (failure to increase or fall >20mmHg, exercise) and exercise-induced left ventricular outflow tract obstruction (left ventricular outflow tract obstruction >50mmHg); and ischemic criteria, such as new wall motion abnormalities (new wall motion abnormality) and/or reduction of coronary flow reserve velocity (CFVR≤2.0) on left anterior descending coronary artery with vasodilator stress assessed in 116 patients. All patients completed the clinical follow-up., Results: Positive SE showed more frequently CFVR reduction, exercise-induced hypotension, left ventricular outflow tract obstruction, and symptoms (38, 23, 20 and 15% respectively), but new wall motion abnormality only in 6%. During a median follow-up of 49months 180 events were observed, including 40 deaths. Clinical/hemodynamic criteria did not predict outcome (X2 0.599, p=0.598), whereas ischemia-related SE criteria (X2: 111.120, p<0.0001) was significantly related to outcome. Similarly, mortality was predicted with SE ischemic-criteria (X2 16.645, p<0.0001)., Conclusions: SE has an important prognostic significance in HCM patients, with ischemia-related end-points showing greater predictive accuracy than hemodynamic endpoints. New wall motion abnormalities and impairment of CFVR should be specifically included in SE protocols for HCM., (Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.)

Background: Patients with systemic sclerosis (SSc) are at risk for developing pulmonary hypertension, which is associated with a poor prognosis. Exercise Doppler echocardiography enables the identification of exercise-induced increase in pulmonary artery systolic pressure (PASP) and may provide a thorough noninvasive hemodynamic evaluation., Aim: The aim of this study was to evaluate the clinical and echocardiographic determinants of exercise-induced increase in PASP in a large population of patients with SSc., Methods: We selected 164 patients with SSc (age 58 ± 13 years, 91% female) with normal resting PASP (<40 mm Hg) who underwent a comprehensive 2-dimensional and Doppler echocardiography and graded bicycle semisupine exercise Doppler echocardiography. Pulmonary artery systolic pressure, cardiac output, and pulmonary vascular resistance (PVR) were estimated noninvasively. Cutoff values of PASP ≥50 mm Hg and PVR ≥3.0 Wood Units at peak exercise were considered a significant exercise-induced increase in PASP and PVR, respectively., Results: Sixty-nine (42%) patients showed a significant exercise-induced increase in PASP. Among them, peak PVR ≥3 Wood Units was present only in 11% of patients, about 5% of the total population. Univariate analysis showed that age, presence of interstitial lung disease, and both right and left diastolic dysfunction are predictors of peak PASP ≥50 mm Hg, but none of these parameters predict elevated peak PVR., Conclusions: Exercise-induced increase in PASP occurs in almost one-half of patients with SSc with normal resting PASP. Peak exercise PASP is affected by age, interstitial lung disease, and right and left ventricular diastolic dysfunction and, only in 5% of the patients, is associated with an increase in PVR during exercise, suggesting heterogeneity of the mechanisms underlying exercise-induced pulmonary hypertension in SSc., (Copyright © 2013 Mosby, Inc. All rights reserved.)

Objectives: The aim of the study was to assess the prognostic value of stress echocardiography after surgical revascularization., Methods: We evaluated 500 (100 women) patients who had undergone exercise or pharmacological SE after a median of 69 months after coronary artery by-pass grafting (CABG). Of these, 351 (70%) complained of symptoms suggestive of ischemic origin while 149 (30%) were tested for asymptomatic progression of the disease., Results: SE was positive for ischemia in 196 (39%) patients. During a median follow-up of 25 months, 61 patients died, 33 had a nonfatal myocardial infarction, and 112 underwent late (>3 months) revascularization. Multivariable Cox' regression analysis indicated age (HR=1.04; 95% CI 1.01-1.06; p<0.003), and peak WMSI (HR=3.07; 95% CI 1.96-4.81; p=0.0001) as independent predictors of hard (total mortality and myocardial infarction) events. SE information provided a significant improvement in predictive power of the statistical model (chi-square increase 34%, p<0.0001 for hard and 91%, p<0.0001 for major events, respectively). Survival analysis showed ischemia at SE to be associated with significantly higher hard and major event rate in both symptomatic and asymptomatic patients., Discussion: SE represents an effective tool for the risk stratification of patients with previous CABG independently of the presence of symptoms suggestive of ischemic origin., (Copyright © 2009 Elsevier Ireland Ltd. All rights reserved.)

Background: Upright exercise stress echocardiography (SE) induces significant intraventricular gradient (IVG) and systolic anterior motion (SAM) in a large proportion of symptomatic athletes, who may therefore benefit from a negative inotropic therapy.The purpose of the present study was to assess the effect of chronic oral β blocker therapy on the occurrence of exercise-induced IVG and mitral valve SAM, in symptomatic athletes., Methods: We enrolled 35 symptomatic athletes (age = 23 ± 11 years) with IVG (>30 mmHg) during SE off therapy. All repeated SE on chronic oral beta-blocker therapy (atenolol up to 50 mg, bisoprolol up to 10 mg, or metoprolol up to 100 mg daily according to physician-driven choice)., Results: On therapy, there was during SE a reduction in IVG (35 off vs 17 on beta blocker, p < 0.01), decrease of IVG (102 ± 34 mmHg off vs 69 ± 24 mmHg on beta blocker, p < 0.01), peak heart rate (178 ± 15 bpm off vs 157 ± 9 bpm on beta blocker), SAM (24 off vs 9 on beta blocker, p < 0.001), symptoms during SE (17 off vs 2 on beta blocker p < 0.001), ST segment depression (13 off vs 2 on beta blocker, p < 0.001)., Conclusions: In athletes with positive screening on medical evaluation for sports practice and IVG on exertion, treatment with oral beta blockers improved symptoms in the large majority of patients. Symptomatic benefit was mirrored by objective evidence of improvement of echocardiographic signs of obstruction (IVG and SAM) and reduction of ischemia-like electrocardiographic changes.

Exercise testing has an established role in the evaluation of patients with valvular heart disease and can aid clinical decision making. Because symptoms may develop slowly and indolently in chronic valve diseases and are often not recognized by patients and their physicians, the symptomatic, blood pressure, and electrocardiographic responses to exercise can help identify patients who would benefit from early valve repair or replacement. In addition, stress echocardiography has emerged as an important component of stress testing in patients with valvular heart disease, with relevant established and potential applications. Stress echocardiography has the advantages of its wide availability, low cost, and versatility for the assessment of disease severity. The versatile applications of stress echocardiography can be tailored to the individual patient with aortic or mitral valve disease, both before and after valve replacement or repair. Hence, exercise-induced changes in valve hemodynamics, ventricular function, and pulmonary artery pressure, together with exercise capacity and symptomatic responses to exercise, provide the clinician with diagnostic and prognostic information that can contribute to subsequent clinical decisions. Nevertheless, there is a lack of convincing evidence that the results of stress echocardiography lead to clinical decisions that result in better outcomes, and therefore large-scale prospective randomized studies focusing on patient outcomes are needed in the future.

Objective: Patients undergoing radiologic and nuclear medicine examination often receive little, if any, information related to the radiologic dose and consequent potential long-term cancer risk. This "economical with the truth" communication may violate basic patients' rights. We assessed the information perceived by patients on the radiation dose exposure during nuclear medicine examinations., Methods: We recruited 109 consecutive patients (66 male; aged 66 +/- 10 years) who were referred to the Nuclear Medicine laboratory of Sant'Orsola-Malpighi Hospital (Bologna University, Bologna, Italy) for a cardiac rest-stress technetium-99m sestamibi scan. This scan gives an effective dose of approximately 10 mSv, corresponding to a dose equivalent of 500 chest x-rays (European Commission Medical Imaging Guidelines 2001) and an estimated extra lifetime attributable risk of 1 cancer in 1,000 exposed subjects (Biological Effects of Ionizing Radiation VII Committee 2005)., Results: Radiation dose exposure was correctly identified by 21% of patients, with the remaining 79% underestimating the exposure by at least 500 times, considered to be zero by 11%, one-half of a chest x-ray by 23%, 1 chest x-ray by 35%, and "don't know" by 10%. The long-term cancer risk was correctly estimated by 27% of patients, with the remaining substantially underestimating the risk, considered to be "zero" by 30%, 1 in 1 million by 19%, 1 in 100,000 by 9%, and "don't know" by 10%., Conclusion: Patients undergoing common cardiac stress scintigraphy examinations involving significant radiation exposure have little or no awareness about nuclear medicine dose (and corresponding risk). This ineffective communication poses significant ethical concerns and possible vulnerability to legal suits against practitioners and prescribers, especially in case of inappropriate examinations.

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.

Ultrasound lung comet images (ULC) are useful for the noninvasive assessment of extravascular lung water (EVLW). We investigated the modification of EVLW, its relation to indices of left ventricular systolic and diastolic function, and noninvasively determined pulmonary capillary wedge pressure (PCWP) (PCWP = 1.24 ratio of early diastolic mitral inflow velocity to early diastolic velocity of the mitral annulus [E/Em] + 1.9) at rest and its variation during exercise echocardiography. A total of 72 patients (mean age 66.4 +/- 8.4 years) with mean ejection fraction of 41.2 +/- 14.4% underwent symptoms-limited exercise echocardiography. The sum of the ULC yielded a score of EVLW. The ULC increased significantly from baseline to postexercise (5.9 +/- 14.9 vs 11 +/- 20.7, P = .0001). Positive linear correlations were found between baseline ULC score and baseline ejection fraction (r = -0.37, P = .002), systolic pulmonary artery pressure (r = 0.69, P = .0001), E/Em (r = 0.70, P = .0001), and estimated PCWP (r = 0.69, P = .0001). The variation between postexercise and baseline ULC score correlated significantly with the variation between peak stress and rest PCWP (r = 0.62, P = .0001), systolic pulmonary artery pressure (r = 0.44, P = .0001), wall-motion score index (r = 0.30, P = .01), and peak stress E/Em (r = 0.71, P = .0001), whereas no significant correlations were found between variations of ULC score and ejection fraction. This study shows that ULC represents a simple way to assess the presence of excess EVLW. Increased EVLW is associated with estimated PCWP and indices of left ventricular systolic and diastolic dysfunction. The additional exercise-induced increase of PCWP, the worsening of left ventricular diastolic function, and extensive wall-motion abnormalities correlate with variations of EVLW.

Background: Stress echocardiography is a cost-effective tool for the modern noninvasive diagnosis of coronary artery disease. Several physical and pharmacological stresses are used in combination with echocardiographic imaging, usually exercise, dobutamine and dipyridamole. The safety of a stress is (or should be) a major determinant in the choice of testing. Although large scale single center experiences and multicenter trial information are available for both dobutamine and dipyridamole stress echo testing, complications or side effects still can occur even in the most experienced laboratories with the most skilled operators., Case Presentation: We decided to present a case collection of severe complications during pharmacological stress echo testing, including a ventricular tachycardia, cardiogenic shock, transient ischemic attack, torsade de pointe, fatal ventricular fibrillation, and free wall rupture., Conclusion: We believe that, in this field, every past complication described is a future complication avoided; what happens in your lab is more true of what you read in journals; and Good Clinical Practice is not "not having complications", but to describe the complications you had.

Objectives: Studies on the diagnostic value of exercise electrocardiography in right bundle branch block produced controversial results, and data on the accuracy of stress echo are still lacking. The aim of the study was to compare the diagnostic value of exercise electrocardiography and dipyridamole stress echo in chest pain patients with right bundle branch block, and to verify whether stress testing accuracy is affected by history of hypertension., Methods: The study group was made up of 71 patients (56 men, aged 63 +/- 8 years) with chest pain of unknown origin and complete right bundle branch block. Of them, 35 were hypertensives and 36 normotensives. Patients performed, on different days and in random order, exercise electrocardiography and dipyridamole stress echo and underwent coronary angiography., Results: Significant (> or = 70% diameter stenosis) coronary artery disease was found in 34 patients (17 hypertensives and 17 normotensives). Positive exercise electrocardiography (ST-segment shift > 1 mm at 80 ms after the J point in leads V5 and V6 or leads II and Vf) and dipyridamole stress echo (new wall motion abnormalities) were observed in 38 and 30 patients, respectively. The result of tests was concordant in 69% of hypertensives and 92% of normotensives. The two tests shared the same sensitivity in hypertensives (82%) and normotensives (71%). Of 37 patients without coronary artery disease, 12 had a false-positive result during exercise electrocardiography and four during stress echo. The specificity was lower for exercise electrocardiography than for stress echo in hypertensives (50 versus 89%, P = 0.0006), while no difference was evidenced in normotensives (84 versus 89%, P = 0.4). In hypertensives, the accuracy, positive, and negative predictive values were 66, 61, and 75% for exercise electrocardiography, and 86, 87, and 84% for stress echo. Corresponding figures in normotensives were 78, 80, and 76% for exercise electrocardiography, and 81, 86, and 77% for stress echo., Conclusions: In chest-pain patients with right bundle branch block, dipyridamole stress echo was effective to diagnose coronary artery disease in both normotensives and hypertensives. Moreover, it exhibited superior diagnostic information than exercise electrocardiography in hypertensives, due to significantly higher specificity. However, the two tests had similar diagnostic value in normotensives.

Stress echocardiography is a popular cardiac imaging technique that provides similar diagnostic and prognostic accuracy as radionuclide stress perfusion imaging. Similar accuracy, however, should not be synonymous with being "clinically interchangeable." Because of economic cost, environmental impact, and individual biohazard exposure, a nuclear examination should be performed only when it cannot be replaced by other techniques that do not employ ionizing radiation. Nuclear medical imaging procedures, of which cardiological procedures are an important part, account for 4% of the annual effective radiation dose received by the average person in the United States. At the individual level, the radiological exposure of a single nuclear cardiology procedure conveys a low, but measurable, risk of fatal cancer, which varies from 1 in 1000 to 1 in 10,000, depending on the type of examination (higher for thallium scans; lower for technetium 99m methoxyisobutylisonitrile scans). Because the information provided by stress echocardiography and stress radionuclide perfusion imaging are similar, the choice of test should be made in the context of the environmental, biological, and economic effects of that choice.

Background: In the stress imaging era, ECG positivity is regarded as a frequent source of false-positive responses. However, it is known that normal coronary arteries frequently coexist with abnormal endothelial function in patients with chest pain., Aim: To evaluate the anatomical coronary epicardial, and functional systemic endothelial determinants of wall motion and electrocardiographic responses during stress testing., Method: Sixty-eight in-hospital patients with chest pain syndrome, no previous myocardial infarction, and off nitrate therapy at the time of testing underwent, on different days, in random order and within 1 month: (1) stress ECG echo testing (with dipyridamole in 43, dobutamine in 3, and exercise in 22 patients); (2) coronary angiography; (3) endothelium-dependent, flow-mediated dilation of the brachial artery during reactive hyperaemia using high-resolution ultrasound. Criteria of positivity were: ST segment depression >0.1mm in the stress ECG; regional dysfunction >2 segments demonstrated by stress-echo; diameter reduction >50% on coronary angiography; and <5% flow-mediated dilation as revealed by endothelial function., Results: Significant coronary artery disease was present in 39 patients, and was predicted on multivariate analysis by stress-induced wall motion abnormalities (OR=108.8; 95% CI=8.5-1,389.4, P=0.0003), but not by either ST segment depression (P=0.13; OR=0.47; 95% CI=0.7-1.3) or reduced flow-mediated dilation (P=0.81; OR=0.87; 95% CI=0.27-2.8). Abnormal flow-mediated dilation was present in 53 patients (78%), and was predicted by stress-induced ST segment depression (P=0.023; OR=6.2; 95% CI=1.3-30.5), but not by either stress echo positivity (P=0.66; OR=0.77; 95% CI=0.23 to 2.5) or angiographically assessed coronary artery disease. There was no correlation between flow-mediated dilation and extent of coronary artery disease as assessed by the angiographic Duke score (from 0=normal to 100=most severe disease): r=-0.13, P=0.91., Conclusion: Epicardial coronary artery anatomy affects wall motion abnormalities, and systemic endothelial dysfunction affects ST segment depression during stress. However, echocardiographic positivity is unrelated to endothelial dysfunction, and electrocardiographic positivity is an inaccurate predictor of coronary stenosis. An integration of ECG and functional markers is warranted in the stress testing lab.

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., (Copyright 2002 The European Society of Cardiology. Published by Elsevier Science Ltd. All rights reserved.)

Unlabelled: INTRODUCTION. There are few studies that evaluate the safety of stress echocardiography with discordant results. They are done in well-trained centers with highly selected populations leading to selection bias., Objective: To assess the safety of the different modalities of stress echocardiography in Spain and Portugal., Method: Severe complications were retrospectively analyzed during the stress echocardiography performed in 29 hospitals in Portugal and Spain, from the beginning of their activity to September, 1999. In this period 22,105 stress echocardiograms were performed: 10,975 exercise echos, 2,969 low dose dobutamine echos, 6,832 high dose dobutamine echocardiograms, 1,276 dypiridamole echocardiograms, 41 paced echocardiograms and 12 with adenosine. A complication was defined as severe when it was life-threatening or led to hospital admission., Results: We registered 26 complications, one death, 3 ventricular fibrillations, 10 sustained ventricular tachycardias, 2 complete atrioventricular blocks, 6 acute myocardial infarctions, 2 ruptures of the free wall or ventricular septal defects, 1 transient ischemic attack and 1 severe symptomatic hypotension. We had one severe complication for every 2,743 exercise stress, 1 every 1,231 dypiridamole, 1 every 325 high dose dobutamine without any complications with low dose dobutamine stress. We found a relationship between experience in dobutamine stress echocardiography and the frequency of complications. Three complications appeared once the test was finished., Conclusions: The stress echocardiography is a safe technique, but not harmless. The exercise stress echo is the safest of all the modalties of stress echocardiography. There is a relation between experience and the number of complications.

Objectives: Many different stress echocardiographic and radionuclide perfusion imaging tests have been proposed for detecting epicardial coronary artery disease (CAD) in hypertensive patients. Their relative diagnostic and prognostic value has not been exactly established., Background: A positive exercise electrocardiography test has a low diagnostic specificity in hypertensive patients and warrants for a complementary imaging test to confirm the diagnosis of coronary artery disease., Methods: Hypertensive patients (n = 53), (29 males, aged 58 +/- 10 years) with normal left ventricular function detected by echocardiography and previous positive exercise test ( > or = 0.15 mV of ST segment depression on 12 lead electrocardiogram) underwent dipyridamole-atropine stress echocardiography (DASE) and thallium-201 stress/ rest myocardial single-photon emission computed tomography (SPECT). All patients had coronary angiography within 15 days and independently of imaging test results., Results: Coronary angiogram showed significant ( > or = 50% qualitatively assessed diameter reduction) epicardial coronary artery disease in 23 (43%) patients. Sensitivity for detection of coronary artery disease was significantly higher for scintigraphy (DASE = 78% versus SPECT = 100%, P < 0.05) while specificity was higher for echo (DASE = 100% versus SPECT = 47%, P < 0.00001). Diagnostic accuracy was also higher for echo (DASE = 91% versus SPECT = 70%, P < 0.01)., Conclusion: In patients with exercise-nduced ST segment depression, dipyridamole stress echo and SPECT perfusion scintigraphy are both good diagnostic options, with DASE characterized by higher specificity, lower sensitivity, and at least comparable diagnostic accuracy than SPECT.

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.

Stress echo has become the preferred theater where innovative technologies are first tested. The new technologies address, in different ways, various physiological targets: more quantitative assessment of the regional wall thickening (by anatomical M-mode); operator-independent assessment of global and regional systolic function (by anatomic boundary detection and color kinesis); tissue composition and physiologic state (by tissue characterization); transmural stratification of myocardial (subendocardial) function (by tissue Doppler imaging); more quantitative evaluation of contrast-enhanced myocardial perfusion (by harmonic imaging). All new emerging techniques aim to improve display and communication among physicians by translating the description of function into numbers and/or colors. However, cardiologists have to be aware that due the pro-technology bias of modern medicine, we, as physicians, are encouraged to trust, to use (and to buy) technologies far before their clinical incremental value has been shown.

Objectives: The aim of this study was to assess whether endogenous accumulation of adenosine, induced by low-dose dipyridamole infusion, protects from exercise-induced ischemia., Background: Adenosine is a recognized mediator of ischemic preconditioning in experimental settings., Methods: Ten patients (all men: mean age 63.4 +/- 7.3 years) with chronic stable angina, angiographically assessed coronary artery disease (n = 7) or previous myocardial infarction (n = 3) and exercise-induced ischemia underwent on different days two exercise-stress echo tests after premedication with placebo or dipyridamole (15 mg in 30 min, stopped 5 min before testing) in a double-blind, placebo controlled, randomized crossover design., Results: In comparison with placebo, dipyridamole less frequently induced chest pain (20% vs. 100%, p = 0.001) and >0.1 mV ST segment depression (50% vs. 100%, p < 0.05). Wall motion abnormalities during exercise-stress test were less frequent (placebo = 100% vs. dipyridamole = 70%, p = ns) and significantly less severe (wall motion score index at peak stress: placebo = 1.55 +/- 0.17 vs. dipyridamole = 1.27 +/- 0.2, p < 0.01) following dipyridamole, which also determined an increase in exercise time up to echocardiographic positivity (placebo = 385.9 +/- 51.4 vs. dipyridamole = 594.4 +/- 156.9 s, p < 0.01)., Conclusions: Low-dose dipyridamole infusion increases exercise tolerance in chronic stable angina, possibly by endogenous adenosine accumulation acting on high affinity A1 myocardial receptors involved in preconditioning or positively modulating coronary flow through collaterals.

Dipyridamole stress is the forerunner and prototype of pharmacological stress echo tests in the diagnosis of coronary artery disease. The safety of this test has been conclusively demonstrated as a result of extensive experience in large-scale multicenter projects. The diagnostic accuracy of dipyridamole stress echo is comparable to dobutamine and largely a function of the employed dose. Higher dosages (up to 0.84 mg/kg) are being required to achieve good sensitivity. The prognostic value has been shown to be independent and additive to clinical, exercise echocardiogram, and angiographic data. The test positive response should be titrated on the basis of severity, extent, and timing of induced dyssynergy with low positivity being associated to more anatomically and functionally severe forms of disease. Multicenter, randomized, prospective, international studies on cost-effectiveness directly comparing a noninvasive strategy centered on stress echo versus an invasive strategy centered on coronary angiography are currently ongoing.

Objectives: This study sought to verify the effectiveness of pharmacologic stress echocardiography in risk stratification of patients with single-vessel disease., Background: Noninvasive prognostic assessment of single-vessel disease is an unresolved issue to date., Methods: The study evaluated prospectively collected data from 754 patients with angiographic single-vessel disease who underwent either dipyridamole (n = 576) or dobutamine (n = 178) stress echocardiography. Invasive treatment (coronary revascularization within 3 months of stress testing) was performed in 260 patients and medical treatment in 494., Results: Echocardiographic positivity was observed in 421 patients (56%). Patients treated invasively had a higher incidence of stress test positivity (69% vs. 49%, p < 0.001) and left anterior descending coronary artery involvement (60% vs. 46%, p < 0.001) than patients maintained with medical therapy. During a mean follow-up of 37 months, 54 hard cardiac events occurred (14 deaths, 40 nonfatal infarctions): 37 in medically and 17 in invasively treated patients (7.5% vs. 6.5%, p = NS). On Cox analysis, a positive result on stress testing was the only independent prognostic predictor in medically treated patients (relative risk 2.92, 95% confidence interval 1.29 to 6.59). The 4-year infarction-free survival rate was higher for a negative than a positive stress test result in medically (93.9% vs. 87.3%, p = 0.009) but not invasively treated patients (92.7% vs. 97.1%, p = 0.545). Moreover, a significantly higher 4-year infarction-free survival rate was found in invasively versus medically treated patients with a positive (p = 0.012), but not in those with a negative, stress test result (p = 0.853)., Conclusions: Pharmacologic stress echocardiography is effective in risk stratification of single-vessel disease and can accurately discriminate patients in whom coronary revascularization can have the maximal beneficial effect. These findings have a potential favorable impact on the cost-effectiveness of invasive procedures.

When new technologies are added to the previously existing ones, the latter can be prematurely discarded and judged obsolete not only on the basis of rational scientific facts, but also on irrational trends. Old techniques, like electrocardiography, suffer from diagnostic ambiguities that can be solved by combination with a cardiac imaging technique, like stress echocardiography. ECG monitoring during all forms of stress testing can still offer surprising dividends for a better understanding of the complex physiology of coronary artery disease, a better clinical characterization of patients with microvascular angina, and may serve as an important adjunct marker to cardiac imaging techniques.

Dipyridamole stress is the forerunner and prototype of pharmacological stress echo tests in the diagnosis of coronary artery disease. Among the various stress echo tests, it is probably the least technically demanding to perform and the easiest to interpret. Its accuracy is similar to dobutamine stress echocardiography but its feasibility is higher. The prognostic impact of dipyridamole stress echo has also been proven for presentation of hard end-points such as cardiac death. The safety and prognostic value of this test has been conclusively demonstrated as a result of extensive experience in large scale multicentre projects. Dipyridamole stress is many different tests in one: dipyridamole atropine is best for diagnosis; dipyridamole dobutamine or dipyridamole-exercise is highly sensitive for the detection of minor forms of coronary artery disease; low and high dose dipyridamole is best suited for prognostic stratification; infra-low dipyridamole with low dose dobutamine administration is probably best suited for selective myocardial viability identification. Each patient should have their own test, tailored on the basis of the clinical picture and the diagnostic issue.

Resting and stress echocardiography is a 'one-stop shop', which enables a wide range of information to be collected on resting function, myocardial viability, and induced ischaemia, all of which are useful for prognostic stratification. Large scale, multicentre, prospectively collected data show the prognostic failure of resting function and inducible ischaemia, both independently and combined, which are especially effective in predicting cardiac death. The GISSI data show that the increment of risk as a result of reduction in ventricular function has a hyperbolic trend, with a relatively moderate increase in mortality for ejection fraction values between 50 and 30%, but with marked increases below 30%. The EPIC data show that the 1-year risk of cardiac death is as low as 2% in patients with negative dipyridamole stress echocardiography: it doubles if the test is positive at a high dose, and is almost four times higher if it is positive at a low dose. In the field of prognostic stratification, in the absence of carefully controlled studies, the choice between coronary angiography as the only essential study, or use of a non-invasive test to discriminate access to catheterization currently reflect alternate philosophical approaches rather than scientifically based decisions. In the invasive approach, stress echocardiography offers relief from the vicious circle of chest pain-coronary angiography revascularization. In the non-invasive and physiological approach, stress echo is capable of offering, in one sitting, an insight into the main determinants of survival: function, viability, and ischaemia.

Background: Anti-ischaemic therapy with nitrates and/or calcium channel blockers profoundly affects the results of pharmacological stress echocardiography with coronary vasodilators but the influence on catecholamine stress testing remains unsettled., Aims: The present study aimed to assess the effects of non-beta-blocker antianginal therapy on dobutamine (up to 40 micrograms.kg-1.min-1)-atropine (up to 1 mg) stress. echo-cardiography and to evaluate whether drug-induced changes in the dobutamine atropine stress echocardiography response may predict variations in exercise tolerance., Methods: Twenty six patients with angiographically assessed coronary artery disease (seven patients with single-, 10 with double-, and nine with triple-vessel disease) performed a dobutamine atropine stress echocardiography and an exercise electrocardiography test in random order both off and on antianginal drugs (nitrates and calcium antagonists). In doubtamine-atropine stress echocardiography, we evaluated: dobutamine time (i.e. the time from initiation of the dobutamine infusion to obvious dyssynergy), wall motion score index (in a 16-segment model of the left ventricle, each segment ranging from 1 = normal, to 4 = dyskinetic), and rate-pressure product at peak stress., Results: Dobutamine-atropine stress echocardiography positivity occurred in 26 out of 26 patients off and in 23 patients on therapy (100 vs 88%, P = ns). Atropine coadministration was needed to evoke echo positivity in no patient off and in five out of 26 on therapy (0 vs 19% P < 0.01). The achieved rate pressure product during dobutamine-atropine stress echocardiography was comparable on and off therapy (17 +/- 4 vs 19 +/- 5 x 10(3) mmHg x heart rate. min-1, P = ns). Therapy induced an increase in dobutamine time (on = 16 +/- 3 vs of = 13 +/- 3 min, P < 0.01) and a decrease in peak wall motion score index (on = 1.3 +/- 0.2 vs off = 1.5 +/- 0.3, P < 0.01). The therapy induced changes in exercise time during the exercise electrocardiography test were not significantly correlated to dobutamine-atropine stress echocardiography variations in either dobutamine time (r = 0.07, P = ns), or peak rate pressure product (r = 0.24, P = ns), or peak wall motion score index (r = 0.02, P = ns)., Conclusions: (1) non-beta-blocker antianginal therapy only modestly reduces dobutamine-atropine stress echocardiography sensitivity, although atropine coadministration is more often required to reach stress echo positivity under therapy; (2) therapy reduces the severity of dobutamine atropine stress echocardiography ischaemia stratified in the time and space domain, but these changes are only poorly correlated to variations in exercise tolerance.

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.

The basic aspect of cell behaviour that is the clue for viability recognition by stress echo is regional function. By definition, the function is depressed both in viable and in necrotic segments. However, only viable segments retain a contractile reserve; which can be evoked by an inotropic challenge, either cathecolaminic or flow-mediated, as consistently shown by several experimental studies. This is the basis of viability recognition by pharmacological stress echocardiography. Both dobutamine and dipyridamole exploit the same pathophysiological principle: viable tissue has a residual contractile reserve, which can be elicited by an appropriate inotropic stimulus. With dobutamine, the stimulus is a beta-receptor mediated effect on myocardial cell, which is later matched by an increase in flow. With dipyridamole, the primary stimulus is an adenosine A2-receptor mediated effect on the coronary arteriole smooth muscle cell, leading to an increase in flow. At that point, the increase in function is to be expected on the basis of the known relationship between myocardial contractility and coronary perfusion. From the technical point of view, the "viability window" is dose-related with dobutamine, and time-related with dipyridamole--where the same dose is associated to an early inotropic phase followed by a later ischemic response. In spite of the different pathophysiological background and technical modalities, dobutamine and and dipyridamole have shown a similar sensitivity and specificity for prediction of viability, with an overall accuracy only marginally lower than resting thallium. The practical, clinical impact of these observations is still blunted by relatively small numbers of observations in highly selected populations including a limited number of patients and studies in very few centers.(ABSTRACT TRUNCATED AT 250 WORDS)

Background: Before any new diagnostic test is accepted in clinical practice, such a test should be compared with established diagnostic tools in an appropriately large series of patients encompassing the complete spectrum of challenges to which the test is exposed. The aim of the present study was to assess the relative diagnostic and prognostic accuracies of high-dose dipyridamole echocardiography (two-dimensional echocardiographic monitoring during dipyridamole infusion up to 0.84 mg/kg over 10 hours) versus maximal symptom-limited bicycle exercise ECG test in patients with angina., Methods and Results: We studied 429 consecutive in-hospital patients who met the following inclusion criteria: history of chest pain, off antianginal therapy for at least 2 days (1 week for beta-blockers), no previous myocardial infarction and/or obvious regional left ventricular dyssynergy of contraction (akinesis or dyskinesis) at baseline, and acceptable acoustic window under resting conditions. All patients underwent dipyridamole echocardiography and exercise ECG--on different days and in random order--within 1 week of coronary angiography (which was performed independent of test results) and were followed up for 37.8 +/- 14 months (range, 1 to 73 months). Criteria of positivity were for dipyridamole echocardiography, a transient regional dyssynergy absent in the baseline examination; for exercise ECG, an ST-segment shift of > or = 0.1 mV from baseline; and for coronary angiography, a luminal reduction of > or = 75% in at least one major coronary vessel (50% for left main). There were 183 patients without and 246 with coronary artery disease; 132 had one-, 70 had two-, and 44 had three- and/or left main vessel disease. The specificity was higher for dipyridamole echocardiography than for exercise ECG (90% versus 51%, P < .001). The overall sensitivity of dipyridamole echocardiography was similar to that of exercise ECG (75% versus 74%, P = NS), with no significant differences in the subset with one- (67% versus 69%, P = NS), two- (79% versus 77%, P = NS), or three- (93% versus 86%, P = NS) vessel disease. During the follow-up, there were 20 deaths, 13 nonfatal myocardial infarctions, and 126 revascularization procedures. In the univariate analysis, dipyridamole resulted in higher chi 2 values than did exercise stress testing. A Cox forward stepwise survival analysis identified the dipyridamole time as the most powerful prognostic predictor of death (chi 2 = 19.4, P < .0001) of all invasive and noninvasive parameters. The dipyridamole time also provided independent and additional prognostic information when it was adjusted for age, diabetes, resting ECG, and exercise stress test according to a modified, interactive stepwise procedure. This is true when death only, death and myocardial infarction, and death, myocardial infarction, and revascularization procedures were considered end points., Conclusions: In patients with no previous myocardial infarction and good resting left ventricular function, compared with exercise ECG, dipyridamole echocardiography has a similar sensitivity and a higher specificity for the noninvasive detection of angiographically assessed coronary artery disease. Dipyridamole echocardiography also provides information in addition to that provided by exercise ECG for predicting death, infarction, and all events when the presence as well as the timing, severity, and extension of dipyridamole-induced wall motion abnormalities are considered.

Regional wall motion impairment incurred by means of dipyridamole-induced ischemia, is regarded with higher sensitivity and specificity than the conventional findings in the ECG. Based on the latter considerations, a new test, the dipyridamole echocardiogram has been introduced in which the development of regional wall motion impairment is designated as the positive diagnostic criterion. Dipyridamole is a vasodilator of coronary arterioles. During the course of the examination, three consecutively occurring mechanisms are considered responsible for the appearance of dipyridamole-induced ischemia in the presence of coronary stenosis. The ischemia is initially attributed to a steal-effect, then to reflex-induced rise in rate-pressure product and, lastly, to a vasospastic component. In 680 patients with thoracic pain, on use of 0.84 mg/kg over ten minutes, there was a sensitivity of 74% in detection of angiographically-documented coronary artery disease, defined as greater than 70% stenosis in at least one major coronary artery, and a specificity of 95%. The onset of regional wall motion impairment after dipyridamole infusion was correlated with the severity of the disease, the localization of the wall motion impairment enabled delineation of the localization of the stenosis in the coronary vascular system. By means of the dipyridamole echocardiogram, the effectiveness of therapeutic measures such as PTCA, ACVB, medical antianginal treatment and thrombolysis can be assessed. Lastly, the dipyridamole echocardiogram provides important information with regard to prognosis.

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.

The aim of the study was to assess the relative diagnostic and prognostic accuracy of high-dose dipyridamole echocardiography test (DET: 2D-echo monitoring during dipyridamole infusion up to 0.84 mg/kg over 10') vs maximal symptom limited bicycle exercise electrocardiography test (EET) in patients with chest pain addressed to coronary angiography. We initially considered 477 consecutive patients, meeting the following inclusion criteria: 1) history of chest pain; 2) off antianginal therapy; 3) no previous myocardial infarction and/or obvious regional left ventricular dyssynergy of contraction. All patients were submitted to a DET and EET--on different days and in random order--within 1 week of coronary angiography (which was performed independently of test results). DET could not be performed in 32 patients for a poor acoustic window in resting conditions (n = 31) or for asthmatic disease requiring xanthine therapy (n = 1); EET could not be performed in 54 patients for inability to exercise, or resting electrocardiographic abnormalities making the EET interpretable. The overall feasibility was of 445/477 for DET and 423/477 for EET (93 vs 89%, p = ns). Criteria for positivity were: transient regional dyssynergy absent in the baseline examination for DET; ST segment shift greater than .15 m V from baseline for EET. Angiographically assessed coronary artery disease (CAD) was considered present when a luminal reduction greater than or equal to 50% occurred in at least 1 major coronary vessel. There were 135 pts with no significant CAD and 256 with CAD; 137 had single, 70 double, 49 triple and/or left main (15) vessel disease. The specificity was higher in DET vs EET (96 vs 59%, p less than .01). The overall sensitivity of DET was similar to EET (67 vs 69%, p = ns), with no significant differences in the subset with single (56 vs 63%, p = ns), double (74 vs 69%, p = ns) or triple (88 vs 86%, p = ns) vessel disease. Patients were followed-up for 26 +/- 22 (range 1 to 73) months considering only death and myocardial infarction as end-points. A Cox stepwise survival analysis identified the Wall Motion Score Index (an integrated semiquantitative measure of extent and severity of the dyssynergy) at peak dipyridamole as the most powerful prognostic predictor (X2 = 18.5, p less than 0001) of all invasive (number of stenotic coronary vessels, X2 = 5.8, p less than .05) and noninvasive (exercise electrocardiography positivity, p = ns) parameters.(ABSTRACT TRUNCATED AT 400 WORDS)

Background: Dipyridamole echocardiography test (DET: two-dimensional echocardiographic monitoring with dipyridamole infusion up to 0.84 mg/kg in 10 minutes) is a useful tool for the noninvasive diagnosis of coronary artery disease. Aims of the present study were to assess the effects of antianginal drugs on dipyridamole-induced ischemia and to evaluate whether drug-induced changes in DET response may predict variations in exercise tolerance., Methods and Results: Fifty-seven patients with angiographically assessed significant coronary artery disease (greater than 70% lumen reduction in at least one major coronary vessel) performed a DET and an exercise electrocardiography test (EET) in random order both off treatment and on antianginal drugs (beta-blockers, calcium antagonists and nitrates, alone or in various combinations). The criterion for DET positivity was a transient dyssynergy of contraction absent or of a lesser degree in the baseline examination. In DET, two parameters were evaluated: the dipyridamole time (i.e., the time from onset of dipyridamole infusion to obvious dyssynergy) and the wall motion score index. DET sensitivity was 91% off therapy and fell to 65% under therapy (p less than 0.01). In the 37 patients who had a positive DET both off and on therapy, the dipyridamole time increased from 6 +/- 3 (off therapy) to 8 +/- 3 minutes (on therapy) (p less than 0.01). The wall motion score index at peak dipyridamole went from 1.38 +/- 0.14 to 1.31 +/- 0.14 (p less than 0.01). EET and DET yielded concordant (positive versus negative) results in 41 of 57 (71%) patients off and in 35 of 57 (61%) on therapy (p = NS). In the subgroup of 38 patients with both positive DET and EET without treatment, the therapy-induced variations in exercise time were significantly correlated with the variations in dipyridamole time (r = 0.5; p less than 0.01), not with variations in wall motion score index (r = 0.3; p = NS)., Conclusions: 1) Antianginal therapy can protect from dipyridamole-induced ischemia and 2) the therapy-induced changes in DET response parallel variations in exercise tolerance and might be useful for the objective, exercise-independent assessment of the therapy efficacy.

The short term reproducibility of exercise testing in 25 patients who had exercise induced ST segment elevation without baseline regional asynergy or a previous myocardial infarction, who had different responses to the dipyridamole test, was assessed. The patients performed a dipyridamole echocardiography test and a second exercise stress test. All underwent coronary arteriography. Seventeen patients had transient regional asynergy after dipyridamole (group 1) and either ST segment elevation (14 patients) or depression (three patients); a second group of eight had no asynergy and no electrocardiographic changes (group 2). The repeated exercise stress test was positive in 16 of the 17 patients of group 1 (11 with ST elevation and five with ST depression) and in two patients of group 2 (both had ST depression and one had coronary artery disease). The dipyridamole echocardiography test was positive in 17 of the 19 patients with coronary artery disease and was negative in all six patients without coronary artery disease. The repeated exercise stress test was positive in 17 of the 19 patients with coronary artery disease and in one patient without. The dipyridamole echocardiography test and a repeated exercise stress test, but not a single exercise stress test, identified coronary artery disease causing exercise induced ST segment elevation.

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.

To test the hypothesis that a dipyridamole infusion might sensitize the myocardium to exercise-induced ischemia, 33 patients with effort chest pain syndrome--including 24 with and 9 without angiographically documented coronary artery disease (CAD)--and 10 control subjects were studied. As inclusion criterion, all enrolled subjects had a negative resting high-dose dipyridamole-echocardiography test result for both mechanical (development of a transient asynergy) and electrocardiographic (greater than 0.1 mV ST-segment shift) changes. All performed 2 supine exercises during 2-dimensional echocardiography and 12-lead electrocardiography monitoring, immediately after high-dose (0.84 mg/kg over 10 minutes) dipyridamole (dipyridamole-exercise stress test) or placebo (exercise stress test) infusion. The overall sensitivity (by electrocardiographic, echocardiographic or combined criteria) for CAD detection was 10 of 24 for exercise stress test and 21 of 24 for dipyridamole-exercise stress test (42 vs 88%, p less than 0.01). The specificity was 19 of 19 for exercise stress test and 18 of 19 for dipyridamole-exercise stress test (100 vs 95%, difference not significant). Both exercise stress test and dipyridamole-exercise stress test yielded negative results in the 10 control subjects, with a similar peak rate-pressure product (X 1/100) reached in the 2 tests (287 +/- 55 vs 274 +/- 42, difference not significant). Eight patients (all with significant CAD) had positive results of their exercise stress test and all 8 had also positive dipyridamole-exercise stress test results, at a significantly lower rate-pressure product with respect to the exercise stress test (253 +/- 49 vs 204 +/- 35, p less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

The value of the exercise-electrocardiography test in detecting coronary artery disease in women is limited. Recently, the high dose dipyridamole-echocardiography test (two-dimensional echocardiographic monitoring during intravenous dipyridamole infusion, up to 0.84 mg/kg body weight over 10 min) was proposed as an alternative to exercise testing for the diagnosis of coronary artery disease. To establish the diagnostic usefulness of the exercise-electrocardiography and dipyridamole-echocardiography tests in this disease, the two tests were performed--on different days and in random order--in 83 consecutive women evaluated for a chest pain syndrome. All 83 women had taken no medications for greater than 48 h, and 15 had had a previous myocardial infarction. Positivity of the dipyridamole-echocardiography test was based on detection of a transient asynergy of contraction that was absent or of lesser degree at rest; the exercise-electrocardiography test (by upright cycloergometer) was considered positive when the ST segment was shifted greater than 0.1 mV 0.08 s after the J point. Coronary angiography showed significant coronary artery disease (greater than 70% luminal reduction of at least one major coronary vessel) in 39 women. No significant complications occurred in any patient during either test. Sensitivity and predictive value of a negative test were similar for the dipyridamole-echocardiography and the exercise-electrocardiography test (79 versus 72% and 84 versus 68%, respectively, whereas the dipyridamole-echocardiography test had greater specificity (93 versus 52%, p less than 0.001), accuracy (87 versus 62%, p less than 0.001) and a higher predictive value of a positive test (91 versus 57%, p less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)