Luca Lanzarini

Comparison of Dobutamine Stress Echocardiography, Dipyridamole Stress Echocardiography and Exercise Stress Testing for Diagnosis of Coronary Artery Disease

To compare the value of dobutamine and dipyridamole stress echocardiography with exercise stress testing for the diagnosis of coronary artery disease (CAD), 80 patients with chest pain of suspected myocardial ischemic origin (57 with CAD and 23 without significant CAD) underwent dobutamine stress echocardiography (5 to 40 micrograms/kg/min), dipyridamole echocardiography (0.84 mg/kg over 10 minutes) and bicycle exercise electrocardiography after discontinuation of antianginal treatment. Dobutamine echocardiography and exercise testing revealed a higher overall sensitivity than dipyridamole echocardiography (79 vs 60%, p < 0.005; 77 vs 60%, p < 0.05, respectively); this finding was due to a higher dobutamine and exercise sensitivity in 1-vessel CAD (62 vs 33%, p < 0.05 for both tests), whereas sensitivity of the 3 tests was similar in multivessel CAD. Dobutamine and dipyridamole showed a higher specificity than exercise (83 vs 43%, p < 0.01; 96 vs 43%, p < 0.005, respectively). Diagnostic accuracy of dobutamine echocardiography was higher than that of exercise (80 vs 67%, p < 0.05), whereas the difference with dipyridamole (80 vs 70%) was not significant. In the tests that yielded positive results, double product during exercise was significantly higher than that during dobutamine and dipyridamole echocardiography. No major complications occurred during the tests, but adverse effects were more frequent during dobutamine testing. Thus, dobutamine echocardiography may be superior to dipyridamole echocardiography and exercise electrocardiography for the diagnosis of CAD.

Dobutamine stress echocardiography for assessment of myocardial viability and ischemia in acute myocardial infarction treated with thrombolysis

To evaluate the role of dobutamine echocardiography for early assessment of myocardial viability and ischemia in acute myocardial infarction (MI), 59 patients with thrombolyzed acute MI underwent low- (5-10 micrograms/kg/min, 8 patients) and high-dose (20-40 micrograms/kg/min, 51 patients) dobutamine echocardiography at a mean of 8 +/- 4 days after acute MI. Myocardial viability in the infarct zone was documented in 43 of 59 (73%) patients (group 1), in whom mean asynergy score index decreased from 1.6 +/- 0.3 at baseline to 1.3 +/- 0.2 (p < 0.001), after low-dose dobutamine. No viability was present in 16 of 59 (27%) patients (group 2). At follow-up, recovery of regional contractile function was observed in group 1 (asynergy score index decreased from 1.6 +/- 0.3 to 1.4 +/- 0.3; p < 0.001), but not in group 2 patients. Sensitivity, specificity, and negative and positive predictive values of low-dose dobutamine echocardiography in predicting spontaneous recovery of function were 79%, 68%, 50%, and 89%, respectively. Of the 51 patients who underwent high-dose dobutamine, 26 of 36 (72%) group 1 patients showed a deterioration of contractility in the infarct zone indicative of myocardial ischemia compared with only 1 of 15 (7%) group 2 patients. At follow-up, recovery of regional function was greater in patients with no evidence of myocardial ischemia at high doses than in those with an ischemic response.(ABSTRACT TRUNCATED AT 250 WORDS)

Two novel and one known mutation of the TGFBR2 gene in Marfan syndrome not associated with FBN1 gene defects

TGF-β-receptor 2 (TGFBR2) gene defects have been recently associated with Marfan syndrome (MFS) with prominent cardio-skeletal phenotype in patients with negative fibrillin-1 (FBN1) gene screening. Four mutations have been identified to date in five unrelated families. We screened TGFBR2 gene by direct automated sequencing in two adult patients diagnosed with MFS according to Ghent criteria, and in one girl clinically suspected as affected on the basis of a major cardiovascular criterion and skeletal involvement, all proven not to carry mutations in the exon–intron boundaries of FBN1 gene. We identified two novel and one known TGFBR2 gene mutations in the three unrelated probands. The D446N was identified in a 4-year-old girl with de novo disease characterized by severe cardiovascular disease and skeletal involvement. The M425V and R460H mutations were identified in two familial, autosomal dominant MFSs, both characterized by major cardio-skeletal signs and absence of major ocular signs. The mutation R460H has been recently reported in a family with thoracic aortic aneurysms and dissection. The three mutations are absent in 192 controls and affect evolutionarily conserved residues of the serine/threonine kinase domain (exon 5). Our data support the recently reported association between TGFBR2 gene and MFS without major ocular signs (MFS2). The number of genotyped cases however is too low to confirm that major ocular signs are characteristically absent in MFS2. Accordingly, all patients proven or suspected to be affected by MFS with negative FBN1 gene screening could benefit from rapid investigation of the TGFBR2 gene.

Hemodynamics of volume loading compared with dobutamine in severe right ventricular infarction

To compare the hemodynamic effect of volume loading with that of dobutamine infusion in severe ischemic right ventricular (RV) dysfunction, 11 patients with inferior and RV infarction complicated by low cardiac output syndrome and important hemodynamic derangement (systolic blood pressure < 100 mm Hg, cardiac index < 2.0 liters/min/m2, right atrial pressure > 10 mm Hg) were prospectively studied within 48 hours of symptom onset. After right heart catheterization, volume loading (mean 400 ml saline solution) and dobutamine infusion (5 and 10 micrograms/kg/min over 10 minutes) were performed according to a randomized, crossover design. Volume loading resulted in increased right atrial (from 15 +/- 2 to 19 +/- 3 mm Hg, p < 0.05) and pulmonary capillary (from 15 +/- 2 to 19 +/- 3 mm Hg, p < 0.05) pressures, without increasing cardiac index, heart rate, aortic pressure, or right and left ventricular stroke work index. Dobutamine (5 micrograms/kg/min) increased cardiac index (from 1.5 +/- 0.3 to 1.9 +/- 0.5 liters/min/m2, p < 0.05), incrementing both heart rate (from 61 +/- 12 to 70 +/- 13 beats/min, p < 0.05) and stroke volume index (from 25 +/- 6 to 27 +/- 5 ml/beat/m2, p < 0.05), as well as right (from 1.4 +/- 1.6 to 2.3 +/- 2.2 g.m/m2, p < 0.05) and left (from 21 +/- 7 to 27 +/- 10 g.m/m2, p < 0.05) stroke work indexes; right and left ventricular filling pressures did not decrease. Dobutamine (10 micrograms/kg/min) significantly improved myocardial performance.(ABSTRACT TRUNCATED AT 250 WORDS)

Prognostic value of myocardial viability and ischemia detected by dobutamine stress echocardiography early after acute myocardial infarction treated with thrombolysis

OBJECTIVES The aim of the study was to assess the prognostic value of myocardial viability and ischemia detected by dobutamine stress echocardiography (DSE) in patients with acute myocardial infarction (AMI) treated with thrombolysis. BACKGROUND DSE can detect myocardial viability and ischemia early after AMI, but the prognostic importance of viability and ischemia in these patients has yet to be assessed. METHODS DSE was performed in 152 patients at a mean of 9 +/- 5 days after a first AMI treated with thrombolysis to evaluate myocardial viability and ischemia. The patients were followed up for 15 +/- 19 months. RESULTS On the basis of DSE results three groups of patients were identified: group 1 (95 patients, 62.5%) with myocardial viability and ischemia, group 2 with myocardial viability without ischemia (32 patients, 21%) and group 3 (25 patients, 16.5%) with no myocardial viability. During follow-up 10 patients (6.5%) had hard events, 53 (35%) developed unstable angina and 67 (44%) underwent myocardial revascularization. The rate of hard events was 10% in group 1 and 0% in group 2 and 3 patients (p < 0.05 group 1 versus group 2); group 1 patients with viability and ischemia showed a significantly higher rate of recurrence of unstable angina and myocardial revascularization procedures (40% and 60%) compared to group 2 (22% and 16%) and group 3 patients (20% and 20%). Using the Cox multivariate stepwise model, only the extent of ischemic myocardium (hazard ratio (HR) = 21.7, p = 0.02) and angina during DSE (HR = 4.45, p = 0.03) were significant predictors of hard events; an ischemic response to DSE (HR = 2.92, p = 0.001) was the most important predictor of spontaneous events, followed by ST-segment depression during DSE (HR = 1.71, p = 0.04), angina during DSE (HR = 1.53, p = 0.19) and age (HR = 0.96, p = 0.05). CONCLUSIONS In patients with a first AMI treated with thrombolysis the presence and extent of myocardial ischemia during DSE is the most important predictor of both hard and spontaneous cardiac events, whereas myocardial viability does not have an independent prognostic value.

Comparison of dobutamine stress echocardiography with dipyridamole stress echocardiography for detection of viable myocardium after myocardial infarction treated with thrombolysis

OBJECTIVE: To compare the ability of dobutamine and dipyridamole stress echocardiography to detect functional recovery of stunned but viable myocardial regions early after acute myocardial infarction, and to predict late functional recovery of the reperfusion salvaged myocardium within the infarct area. METHODS: Within 10 d of acute myocardial infarction, 51 patients--30 anterior and 21 inferior, 44 Q wave and seven non-Q-wave infarction--were submitted to a dobutamine echocardiography test at low dose (5-10 micrograms/kg/min over 5 min) and high dose (20-40 micrograms/kg/min over 3 min) and to dipyridamole echocardiography test (0.56 mg/kg over 4 min + 0.28 mg/kg over 2 min) on different days and in random order, after interruption of any vasoactive drug. Resting echocardiography was repeated at two months in 41 of 51 patients (80%). Regional wall motion of the left ventricle was analysed in a semiquantitative manner on a 14-segment model. Viability was defined as improvement of one grade or more of at least two basally asynergic segments in the infarcted area. RESULTS: Regional functional recovery was detected by low dose dobutamine in 38/51 patients (75%) and in 147/308 (48%) of basally asynergic segments, compared to 25/51 patients (49%; P < 0.001) and 78/308 segments (25%; P < 0.001) only identified by dipyridamole. Late spontaneous functional recovery was detected in 24/41 patients (59%) and in 78/254 basally asynergic segments (31%). The sensitivity of dobutamine and dipyridamole echocardiography for predicting spontaneous functional recovery was 72% and 51% respectively (P < 0.001), specificity 68% and 82% (P < 0.001), positive predictive value 50% and 56%, and negative predictive value 85% and 79%. CONCLUSIONS: In comparison with dipyridamole in patients with thrombolysed myocardial infarction, dobutamine induces regional functional recovery. This suggests that dobutamine is more sensitive in showing the presence of viable myocardium within the infarct zone, though it has a lower specificity in predicting delayed spontaneous functional recovery of non-contractile but still viable areas.

Analysis of ENG and ACVRL1 genes in 137 HHT Italian families identifies 76 different mutations (24 novel). Comparison with other European studies.

AbstractHereditary hemorrhagic telangiectasia (HHT) is an autosomal dominant disorder causing vascular dysplasias. About 70-80% of HHT patients carries mutations in ENG or ACVRL1 genes, which code for a TGFβ receptor type III and I respectively. Molecular data on a large cohort of Italian HHT patients are presented, discussing the significance of missense and splice site mutations. Mutation analysis in ENG and ACVRL1 genes was performed using single strand conformation polymorphisms (SSCP), denaturing high performance liquid chromatography (DHPLC) and subsequent direct sequencing. Overall, 101 mutations were found, with ACVRL1 involved in 71% of cases. The highest number of mutations (28/101 subjects, 14/76 different mutations referring to both genes) was in ACVRL1, exon 3. Mutation analysis was then extended to a total of 356 family members, and 162 proven to carry the mutation. New polymorphisms were identified in both genes, and evidence that ENG P131L change is not a disease-causing mutation was also provided. An in silico analysis was performed in order to characterize splice-site mutations. These results were compared to other European national studies and data from Italy, France and Spain were consistent for an higher incidence of ACVRL1 mutations.

Aortic dimensions in Turner's syndrome: Two-dimensional echocardiography versus magnetic resonance imaging

Background Patients with Turners syndrome have an increased risk of cardiac death caused by aortic disease. Consensus has not been reached about the best method to image the aorta in this syndrome. Aim This present study aimed: (i) to evaluate thoracic and abdominal aortic dimensions by two-dimensional echo (2-DE) and magnetic resonance imaging (MRI) and (ii) to assess agreement between 2-DE and MRI measurements. Material and methods Among 75 kariotypically proven Turners syndrome patients, 59 (79%) (mean age: 22 ± 7 years) underwent a 2-DE and an MRI study of the thoracic and proximal abdominal aorta. The aortic root (AR), the sino-tubular aortic junction (STJ), the first part of the ascending thoracic aorta (AscTA), the aortic arch (AArch), the descending thoracic aorta (DTAp) a few centimetres below the isthmus and the abdominal aorta (AbA) were analysed. The Bland and Altman method and Lins concordance correlation coefficient were utilized to compare 2-DE and MRI aortic dimensions. Results Compared to MRI, feasibility of aortic imaging by 2-DE was identical at AR level, but lower when measuring distal aorta (88% at DTAp and 91.5% at AbA level versus 100%). The 2-DE and MRI showed a very slight difference between measurements and a high concordance correlation coefficient at the level of AR and AscTA; correlations were weaker at the other aortic levels. Absolute differences calculated at each measurement level showed that concordance (defined as differences within 1 mm between 2-DE and MRI absolute measures) was highest at AR (45.6%) and AscTA (28%) level and lowest at STJ (12.2%) level. The 2-DE overestimated aortic arch diameters in approximately 70% of cases, whereas at the remaining aortic levels MRI measurements were usually 1 mm higher compared to the corresponding 2-DE values. Conclusions Concordance between 2-DE and MRI was found to be very good at the AR and AscTA levels. Because the risk of aortic complication is higher when AR and proximal thoracic aorta are dilated, 2-DE may be considered a useful method to screen for aortic disease and a good choice to follow proximal aortic dimensions over time in Turners syndrome patients.

Results of dobutamine stress echocardiography in patients with Syndrome X

This study describes the results of Dobutamine stress echocardiography in 10 patients with Syndrome X. The diagnosis of Syndrome X was made on the basis of the presence of exertional angina, positive exercise stress test, negative ergonovine stress test and normal coronary arteries at angiography. All patients underwent Dobutamine stress echocardiography after interruption of any antianginal therapy. Dobutamine was infused starting with a dose of 5 mcg/kg/min over 3 minutes with incremental steps of 5 mcg/kg/min every 3 minutes up to a maximal dose of 40 mcg/kg/min. Two-dimensional echocardiography and 12-lead electrocardiography was monitored during the infusion of the drug. Nine patients received the maximal dose while one patient prematurely stopped the test for the occurrence of side effects. None of the ten patients developed segmental left ventricular wall motion abnormalities indicative of myocardial ischemia; ST-segment depression diagnostic for ischemia developed in 30% of patients; angina was elicited in one of these patients and in two additional patients. A hyperkinetic response to Dobutamine infusion involving all the segments of the left ventricle was observed both in patients with and without chest pain or electrocardiographic changes.In patients with Syndrome X Dobutamine induces a hyperkinetic left ventricular response indicative of normal contractile reserve despite the presence in some cases of angina and electrocardiographic signs of ischemia.

Dobutamine-induced ST-segment elevation in patients without myocardial infarction

During dobutamine stress echocardiography, ST-segment elevation developed in 20 of 372 patients (5%) without previous myocardial infarction and was associated with a transient severe asynergy of the myocardial region corresponding to the site of ST elevation. In 17 of 19 patients, ST-segment elevation was associated with a critical stenosis of the ischemia-related coronary artery, whereas in 2 of 19 patients with no critical lesions of the ischemia-related artery, coronary vasospasm was the most likely mechanism of myocardial ischemia.