Familial evaluation reveals a distinct genetic cause in a large Spanish family with neurofibromatosis 1 and hypertrophic cardiomyopathy.

Neurofibromatosis 1 (NF1) is an autosomal dominant disorder characterized by café-au-lait spots, intertriginous freckling, and multiple neurofibromas. Classically, it has been described that hypertrophic cardiomyopathy (HCM) may be a cardiovascular manifestation of neurofibromatosis 1, although the relationship between these two entities has not been fully established. We report a large Spanish family carrying a pathogenic truncating variant in NF1 (p.Arg2258Ter) causing neurofibromatosis 1, and a pathogenic missense variant in MYH7 (p. Arg453Cys), causing hypertrophic cardiomyopathy independently. A complete penetrance was observed in both genetic diseases, reinforcing the notion of deleterious effects of both rare variants. According to our report, hypertrophic cardiomyopathy in patients with NF1 should not be considered as part of the clinical spectrum in all cases. A careful and comprehensive assessment, including family evaluation and genetic testing for HCM should be considered as part of the diagnostic work-up in individuals presenting with both phenotypes.

Registro informatizado de la telangiectasia hemorrágica hereditaria (Registro RiHHTa) en España: objetivos, métodos y resultados preliminares / Computerized registry of patients with hemorrhagic hereditary telangiectasia (RiHHTa Registry) in Spain: Objectives, methods, and preliminary results

Introducción: La telangiectasia hemorrágica hereditaria (HHT, por sus siglas en inglés) es una enfermedad minoritaria con herencia autosómica dominante que provoca una afectación vascular sistémica. Material y método: Tras la elaboración de un registro nacional español multicéntrico, denominado RiHHTa, se describen las principales manifestaciones clínicas y procedimientos diagnósticos de los primeros pacientes introducidos. Resultados: Se han introducido datos de 141 pacientes, de los que 91 (64,5%) eran mujeres. La edad media al diagnóstico fue de 42 años. Las mutaciones en el gen ACVRL1 predominaron sobre el gen ENG. El síntoma inicial fue la epistaxis recurrente en 130 (92,2%) pacientes y en 3 (2,1%), el absceso cerebral. Se detectaron fístulas arteriovenosas (AV) pulmonares en 36 (45%) de los 79 pacientes a los que se les practicó una angio-TC torácica. En 36 (45%) de estos 79 afectados no se había detectado paso de contraste en la ecocardiografía o este era grado 1. En 43 (67,2%) de los 64 pacientes con una angio-TC abdominal se detectaron malformaciones vasculares hepáticas, mayoritariamente telangiectasias, fístulas AV y arterio-portales, y extrahepáticas en 14 (10%) sujetos. Se realizó cribado de malformación AV cerebral a más de la mitad de los pacientes, detectándose en un 3,9%. La parte del tubo digestivo más afectada fue la superior (95%). Conclusión: El Registro RiHHTa permite identificar puntos de mejora en el manejo de los pacientes con HHT. Se ha detectado un uso inadecuado de la angio-TC torácica y la utilidad de la angio-TC abdominal para definir los subtipos de afectación vascular hepática y detectar afectación vascular extrahepática

Introduction: Hereditary hemorrhagic telangiectasia (HHT) is a rare disease with autosomal dominant inheritance that causes systemic vascular affectation. Material and method: After development a multicentric Spanish national registry, called RiHHTa, main clinical manifestations and diagnostic procedures of the first patients introduced are described. Results: 141 patients were included, of which 91 (64.5%) were women. The mean age at diagnosis was 42 years. Mutations in the ACVRL1 gene predominated over the ENG gene. The initial symptom was recurrent epistaxis in 130 (92.2%) patients and in three (2.1%), brain abscess. Pulmonary arteriovenous (AV) fistula were detected in 36 (45%) of the 79 patients who underwent thoracic CT angiography. The contrast echocardiography detected very few bubbles (grade I) or none, in 36 (45%) of these 79 affected patients. In 43 (67.2%) of the 64 patients with an abdominal CT angiography, hepatic vascular malformations were detected, mostly telangiectasias, AV and arterio-portal fistula, and extrahepatic in 14 (10%) subjects. More than half of the patients were screened for the presence of brain arteriovenous malformations which was found in 3.9% of them. The upper part of the intestinal tube was the most (95%) affected region. Conclusion: The RiHHTa Registry allows improving the management of patients with HHT. An inadequate use of thoracic CT angiography and the usefulness of abdominal CT angiography has been detected in order to define subtypes of hepatic vascular involvement and detect extrahepatic vascular involvement

Computerized registry of patients with hemorrhagic hereditary telangiectasia (RiHHTa Registry) in Spain: Objectives, methods, and preliminary results. / Registro informatizado de la telangiectasia hemorrágica hereditaria (Registro RiHHTa) en España: objetivos, métodos y resultados preliminares.

INTRODUCTION: Hereditary hemorrhagic telangiectasia (HHT) is a rare disease with autosomal dominant inheritance that causes systemic vascular affectation. MATERIAL AND METHOD: After development a multicentric Spanish national registry, called RiHHTa, main clinical manifestations and diagnostic procedures of the first patients introduced are described. RESULTS: 141 patients were included, of which 91 (64.5%) were women. The mean age at diagnosis was 42 years. Mutations in the ACVRL1 gene predominated over the ENG gene. The initial symptom was recurrent epistaxis in 130 (92.2%) patients and in three (2.1%), brain abscess. Pulmonary arteriovenous (AV) fistula were detected in 36 (45%) of the 79 patients who underwent thoracic CT angiography. The contrast echocardiography detected very few bubbles (grade I) or none, in 36 (45%) of these 79 affected patients. In 43 (67.2%) of the 64 patients with an abdominal CT angiography, hepatic vascular malformations were detected, mostly telangiectasias, AV and arterio-portal fistula, and extrahepatic in 14 (10%) subjects. More than half of the patients were screened for the presence of brain arteriovenous malformations which was found in 3.9% of them. The upper part of the intestinal tube was the most (95%) affected region. CONCLUSION: The RiHHTa Registry allows improving the management of patients with HHT. An inadequate use of thoracic CT angiography and the usefulness of abdominal CT angiography has been detected in order to define subtypes of hepatic vascular involvement and detect extrahepatic vascular involvement.

Corrigendum: Effect of age on pro-inflammatory miRNAs contained in mesenchymal stem cell-derived extracellular vesicles.

This corrects the article DOI: 10.1038/srep43923.

Effect of age on pro-inflammatory miRNAs contained in mesenchymal stem cell-derived extracellular vesicles.

Stem cells possess significant age-dependent differences in their immune-response profile. These differences were analysed by Next-Generation Sequencing of six age groups from bone marrow mesenchymal stem cells. A total of 9,628 genes presenting differential expression between age groups were grouped into metabolic pathways. We focused our research on young, pre-pubertal and adult groups, which presented the highest amount of differentially expressed genes related to inflammation mediated by chemokine and cytokine signalling pathways compared with the newborn group, which was used as a control. Extracellular vesicles extracted from each group were characterized by nanoparticle tracking and flow cytometry analysis, and several micro-RNAs were verified by quantitative real-time polymerase chain reaction because of their relationship with the pathway of interest. Since miR-21-5p showed the highest statistically significant expression in extracellular vesicles from mesenchymal stem cells of the pre-pubertal group, we conducted a functional experiment inhibiting its expression and investigating the modulation of Toll-Like Receptor 4 and their link to damage-associated molecular patterns. Together, these results indicate for the first time that mesenchymal stem cell-derived extracellular vesicles have significant age-dependent differences in their immune profiles.

A mutation in the Z-line Cypher/ZASP protein is associated with arrhythmogenic right ventricular cardiomyopathy.

Arrhythmogenic right ventricular cardiomyopathy (ARVC) is an important cause of malignant arrhythmia and sudden death particularly in young people. Although it is considered a desmosomal disease, mutations in non-desmosomal genes have also been identified. We report on a family where a mutation in LDB3 is associated with this condition. The index case and first and second degree relatives underwent a complete clinical evaluation: physical examination, electrocardiography (ECG), signal-averaged ECG, 2D echocardiogram, cardiac magnetic resonance and 24-h monitoring. After ruling out mutations in the five desmosomal genes, genetic testing by means of Next Generation Sequencing was carried out on the proband. A heterozygous missense mutation in LDB3 c.1051A>G was identified. This result was confirmed by subsequent Sanger DNA sequencing. Another six carriers were identified amongst her relatives. Three subjects fulfilled the criteria for a definitive diagnosis of ARVC and one reached a borderline diagnosis. In conclusion, this is the first family with ARVC where a mutation in LDB3 is associated with ARVC. Next generation sequencing arises as a particular useful tool to point to new causative genes in ARVC.

Effects of weaning and finishing feeding treatment on fatty acids, especially cis and trans C18:1 isomers, in the Longissimus thoracis muscle of Galician Blond calves.

Seven- to 10-month-old calves are the typical production of Galician Blond (GB), the most important bovine local beef breed in Spain. As meat lipid repercussions on human health depend on their fatty acid (FA) profile, this study aimed at analysing the individual FA at weaning and at the end of the feeding finishing period, especially trans and cis 18:1 isomers in total lipids of the Longissimus thoracis muscle in GB male calves. Distribution of main FA in veal lipids was characterized by gas-liquid chromatography (GLC) analysis on a high polar glass capillary column. Total trans and cis 18:1 isomers were purified, from total FA (TFA) methyl esters, by preparative reversed-phase high-performance liquid chromatography, to allow subsequent specific analysis of their different isomers by GLC. Calves stayed with their mothers at pasture for 2 or 5 months in intensive or semi-extensive systems, followed by an indoor feeding period. The weaned (W) group was finished on concentrate and hay, whereas the non-weaned (NW) group was finished on concentrate and hay and it continued suckling until slaughter. The studied effects did not present interactions. The duration of the indoor finishing period hardly had a significant influence on the parameters analysed. Compared to W calves, NW calves had higher proportions (% TFA) of 18:3n-3 (+38%, P < 0.0001), 20:5n-3 (+22%, P = 0.005), 22:5n-3 (+13%, P = 0.042), cis monounsaturated FA (MUFA; +8%, P = 0.032), total MUFA (+8%, P = 0.013), n-3 polyunsaturated FA (PUFA; +25%, P = 0.0001) and conjugated linoleic acid (CLA; +48%, P < 0.0001) to the detriment of 18:0 (-10%, P = 0.002), 18:2n-6 (-25%, P = 0.004) and n-6 PUFA (-20%, P = 0.011). With regard to cis and trans 18:1 isomers, NW calves had higher proportions (% total cis or trans 18:1) of Δ11trans and Δ16trans (+25% and +22%, respectively, P < 0.01) and Δ13 + 14trans (+13%, P < 0.05) and lower proportions of Δ6 to 8 and Δ10trans (-28% and 58%, respectively, P < 0.001). NW calves' meat might be more suitable for human health than W calves' meat due to the increase of anti-atherogenous FA such as n-3 PUFA, CLA and 18:1 Δ11trans.

Cardiac challenges in patients with Fabry disease.

Fabry disease, an X-linked lysosomal storage disorder affecting both men and women, is a relatively prevalent cause of hypertrophic cardiomyopathy (HCM) and is associated with significant morbidity and early death due to heart failure or ventricular arrhythmias. Fabry cardiomyopathy results from progressive build-up of glycosphingolipids in cardiac structures, but the underlying complex pathophysiologic mechanisms remain poorly understood. Disease-specific enzyme replacement therapy (ERT) is available for Fabry disease and, therefore, attention should be focused on early diagnosis of this progressive, life-threatening disease. Selected cardiology patients at high risk for Fabry disease can be tested using simple enzymatic assays, and diagnosis is confirmed by demonstration of a Fabry mutation. Testing cardiology patients with HCM of unknown etiology may identify previously unrecognized Fabry patients and allow genetic mapping to be carried out to identify other affected family members at a relatively early stage of the disease. Timely intervention early on in the disease is a key, as the best responses to ERT are seen in patients with the lowest degree of cardiac hypertrophy and fibrosis at the start of treatment.

Diagnóstico electrocardiográfico de los síndromes coronarios agudos / Electrocardiographic diagnosis of the coronary syndromes

After clinical history, the electrocardiogram (ECG) is the study of greater relevance for diagnose, treatment and pursuit of the patients who undergo some of the presentations of the Acute Coronary Syndrome. The diagnoses sensitivity it is conditional one at the moment in which it is made and by the presence of symptomatology; whereas the foretell value it is support by the type of electrocardiographic alteration, magnitude and location. The objective of the present revision is to analize on one's infirmary the importance of the valuation of the assessment of the electrocardiogram, that orient to us towards an opportune and truthful planning of the specific cares of the patient with acute coronary syndrome. With which future complications can be limited. The concepts of ischemia, injury and necrosis, as well as electrocardiographic examples of some clinical forms of the ischemic cardiopathy appear.

[Electrocardiographic diagnosis of the coronary syndromes]. / Diagnóstico electrocardiográfico de los síndromes coronarios agudos.

After clinical history, the electrocardiogram (ECG) is the study of greater relevance for diagnose, treatment and pursuit of the patients who undergo some of the presentations of the Acute Coronary Syndrome. The diagnoses sensitivity it is conditional one at the moment in which it is made and by the presence of symptomatology; whereas the foretell value it is support by the type of electrocardiographic alteration, magnitude and location. The objective of the present revision is to analize on one's infirmary the importance of the valuation of the assessment of the electrocardiogram, that orient to us towards an opportune and truthful planning of the specific cares of the patient with acute coronary syndrome. With which future complications can be limited. The concepts of ischemia, injury and necrosis, as well as electrocardiographic examples of some clinical forms of the ischemic cardiopathy appear.

WITHDRAWN: Accuracy of Peak Treadmill Exercise Echocardiography to Detect Multivessel Coronary Artery Disease: Comparison with Post-exercise Echocardiography.

The publisher regrets that this was an accidental duplication of an article that has already been published in Eur. J. Echocardiogr., 4 (2003) 182-190, . The duplicate article has therefore been withdrawn.

Effect of weaning status and storage time under vacuum upon physical characteristics of meat of the Rubia Gallega breed.

Seven to nine months old calves are the typical production of Rubia Gallega, which is the most important beef breed in Spain. A study about the influence of weaning status and vacuum storage time on veal quality characteristics is needed. The muscle longissimus thoracis from 22 non-weaned (NW) and 21 weaned (W) calves at 1day post-slaughter, and vacuum packaged for 7 and 14 days were analysed. NW showed higher yellowness and hue values than W but lower pigment concentration. The differences disappeared at longer storage times. The redness, yellowness, hue and chroma increased with aging, but the pigment concentration, expressible juice and toughness decreased with aging. Principal component analysis showed that colour variables were the most determinant characteristics in quality variation. The canonical discriminant analysis separated the samples in three groups: 1 day post-slaughter W, 1day post-slaughter NW, and vacuum packaged W and NW.

Accuracy of peak treadmill exercise echocardiography to detect multivessel coronary artery disease: comparison with post-exercise echocardiography.

AIMS: Although peak exercise echocardiography has been reported for both bicycle and treadmill exercise and has shown higher sensitivity than post-exercise imaging, little is known about its utility for identifying multivessel involvement. We sought to compare feasibility and accuracy of peak treadmill exercise echocardiography vs post-exercise echocardiography for identification of multivessel coronary artery disease and to assess its incremental value when combined with clinical and exercise test variables. METHODS AND RESULTS: The study group included 335 patients (228 men; mean (+/- SD) age 60 +/- 11 years). Two hundred and seventy-nine patients were included on the basis of having had an exercise echocardiography and a coronary angiography within 4 months of the exercise test. To avoid bias to coronary angiography, a subgroup of 56 consecutive non-diabetic patients referred for exercise echocardiography with pretest probability of coronary artery disease <10% and had atypical chest pain or were asymptomatic were also included and considered as having no coronary artery disease. Multivessel coronary artery disease (> or = 50% diameter stenosis in >1 vessel) was confirmed in 170 patients, whereas 165 patients were considered to have one-vessel coronary artery disease or no coronary lesions. Positive exercise echocardiography was defined as ischaemia or necrosis in at least two coronary territories. Post-exercise images were acquired within 125 s after exercise (49 +/- 15). Mean heart rate (bpm) was 139 +/- 19 at peak vs 117 +/- 22 at post-exercise imaging (P<0.001). Interpretable peak and post-exercise images were obtained for all patients. Sensitivity for predicting multivessel disease was higher with peak than with post-exercise imaging (79 vs 55%, P<0.001), with lower specificity (79 vs 88%, P<0.05). Predictive positive value was similar (80 vs 83%). Negative predictive value was again higher with peak imaging (78 vs 66%, P<0.01). Total accuracy was not different (79 vs 72%). A stepwise logistic regression analysis identified peak exercise echocardiography positivity for multivessel coronary artery disease as the strongest independent predictor of multivessel disease (odds ratio (OR): 7.36); also significant were male gender (OR: 4.22), diabetes mellitus (OR: 4.28), previous myocardial infarction (OR: 3.12) and increment of product heart rate x blood pressure (OR: 1.00). CONCLUSIONS: Peak treadmill exercise echocardiography is technically feasible and has higher sensitivity and negative predictive value for predicting multivessel disease than post-treadmill exercise echocardiography. This method adds independent and incremental values to clinical and exercise variables for the diagnosis of multivessel coronary artery disease. Therefore, in the clinical setting, peak exercise echocardiography should be performed to diagnose multivessel coronary artery disease.

Comparison of two-dimensional echocardiography and pulsed Doppler tissue imaging during dobutamine-atropine stress testing to detect coronary artery disease.

In order to compare the diagnostic accuracy of two-dimensional (2-D) echocardiography and pulsed Doppler tissue imaging (pDTI) during dobutamine-atropine stress testing (DAST) to detect significant coronary lesions, 41 patients underwent DAST (up to 40 microg/k/min of dobutamine with additional atropine during submaximal heart rate responses) and coronary angiography. Pulsed Doppler tissue sampling of territories corresponding to the left anterior descending (LAD), left circumflex (LCx), and right coronary arteries (RCAs) were performed in the apical four-chamber plus aorta and two-chamber apical views. The measurements were repeated at rest, at low dose (10 microg/k/min), and at peak stress. Pulsed DTI measurements included peak early systolic (Vs), peak early diastolic (Ve), and peak late diastolic (Va) velocities. Harmonic 2-D echocardiography was recorded at rest, low dose, peak stress, and recovery, and compared with pDTI assessment. Positive 2-D echocardiography was considered as infarction or ischemic response. The results were evaluated for the prediction of significant coronary stenosis (50% luminal narrowing). Feasibility of pDTI was 100%, 95%, and 98% for the LAD, the LCx, and RCA territories, respectively. At rest, Vs in territories supplied by arteries with coronary artery disease (CAD) (6.3 +/- 2.0 cm/sec) was not different from those without (6.6 +/- 2.1 cm/sec). Vs increased less in territories supplied by arteries with than without CAD (75 +/- 107% vs 102 +/- 69%, P = NS). Ve was lower in territories with CAD at rest (6.0 +/- 2.1 cm/sec vs 8.2 +/- 3.4 cm/sec, P < 0.0001) and low dose (7.2 +/- 2.1 cm/sec vs 8.8 +/- 3.6 cm/sec, P < 0.01), but similar at peak stress (7.6 +/- 3.5 cm/sec vs 8.1 +/- 3.3 cm/sec). Ve increase was similar in territories with (36 +/- 74%) than without CAD (15 +/- 6 4%). Va was similar at rest and low dose in territories with and without CAD (9.2 +/- 2.7 cm/sec vs 9.1 +/- 2.3 cm/sec and 10.9 +/- 3.1 vs 10.3 +/- 3.6 cm/sec, respectively), but lower at peak stress in territories with CAD (13.3 +/- 4.6 cm/sec vs 15.3 +/- 4.5 cm/sec, P = 0.05). The Va increase was lower in territories with CAD (43 +/- 37% vs 77 +/- 72%, P < 0.05). In a territory-based analysis, a failure to achieve Vs > or =10.5 cm/sec at peak stress in the LAD and LCx, and > or =10.0 cm/sec in the RCA territory, was found to be the more accurate limit to detect CAD in the corresponding arteries: sensitivity (95% confidence intervals): 63% (55-71), P = NS vs 2-D echocardiography: 59% (51-67); specificity 76% (68-84), P < 0.01 vs. 2-D echocardiography: 95% (89-100); and accuracy 69% (63-75), P = NS vs 2-D echocardiography: 76% (70-82). Thus, pDTI is feasible during DAST but not more accurate than 2-D echocardiography for the detection of significant CAD in a territory-based study.

Sudden death in hypertrophic cardiomyopathy: identification of high risk patients.

OBJECTIVES: We sought to identify patients with hypertrophic cardiomyopathy (HCM) at high risk of sudden death (SD). BACKGROUND: Relatively low mortality rates in HCM make conventional analysis of multiple clinical risk markers for SD problematic. This study used a referral center registry to investigate a smaller number of generally accepted noninvasive risk markers. METHODS: We studied 368 patients (14 to 65 years old, 239 males) with HCM. There were five variables: nonsustained ventricular tachycardia (NSVT), syncope, exercise blood pressure response (BPR), family history of sudden death (FHSD) and left ventricular wall thickness (LVWT). RESULTS: During follow-up (3.6+/-2.5 years [range 2 days to 9.6 years]), 36 patients (9.8%) died, 22 of them suddenly. Two patients received heart transplants. The six-year SD-free survival rate was 91% (95% confidence interval [CI] 87% to 95%). In the Cox model, there was a significant pairwise interaction between FHSD and syncope (p = 0.01), and these were subsequently considered together. The multivariate SD risk ratios (with 95% CIs) were 1.8 for BPR (0.7 to 4.4) (p = 0.22); 5.3 for FHSD and syncope (1.9 to 14.9) (p = 0.002); 1.9 for NSVT (0.7 to 5.0) (p = 0.18) and 2.9 for LVWT (1.1 to 7.1) (p = 0.03). Patients with no risk factors (n = 203) had an estimated six-year SD-free survival rate of 95% (95% CI 91% to 99%). The corresponding six-year estimates (with 95% CIs) for one (n = 122), two (n = 36) and three (n = 7) risk factors were 93% (87% to 99%), 82% (67% to 96%) and 36% (0% to 75%), respectively. Patients with two or more risk factors had a lower six-year SD survival rate (95% CI) compared with patients with one or no risk factors (72% [56% to 88%] vs. 94% [91% to 98%]) (p = 0.0001). CONCLUSIONS: This study demonstrates that patients with multiple risk factors have a substantially increased risk of SD sufficient to warrant consideration for prophylactic therapy.

Accuracy of exercise echocardiography to detect coronary artery disease in left bundle branch block unassociated with either acute or healed myocardial infarction.

To search for the value of treadmill exercise echocardiography in the detection of coronary artery disease in noninfarcted patients with left bundle branch block, we studied 35 patients (17 with coronary artery disease). We found high sensitivity, specificity, and accuracy (76%, 83%, and 80%, respectively).

Cytomegalovirus colitis mimicking a colonic neoplasm or ischemic colitis 4 years after heart transplantation.

BACKGROUND: Cytomegalovirus (CMV) colitis is a polymorphous disease presenting in immunodepressed patients in a variety of clinical forms that can delay diagnosis and therapy. We report the case of a patient who presented with abdominal pain 4 years after heart transplantation; clinical and x-ray findings were suggestive of a neoplastic or ischemic stenosis, and histopathological examination likewise initially suggested an ischemic etiology. METHODS: Tissue samples were fixed in 10% formaldehyde, embedded in paraffin, cut, and stained with hematoxylin/eosin and periodic acid-Schiff-Alcian Blue. Immunohistochemistry with monoclonal antibodies was performed using an indirect immunoperoxidase method. RESULTS: CMV colitis was eventually diagnosed and resolved with surgery and specific anti-CMV therapy. CONCLUSIONS: CMV colitis should be suspected in any heart transplant patient with signs or symptoms of abdominal pathology, even without classical signs or symptoms of CMV infection. If stenotic lesions are present, surgery may be required not only to remove the obstruction but also to rule out malignancy.

[The value of exercise echocardiography in the diagnosis of coronary disease in patients with left heart branch block in the bundle of His]. / Valor de la ecocardiografía de ejercicio en el diagnóstico de enfermedad coronaria en pacientes con bloqueo de rama izquierda del haz de His.

OBJECTIVE: To assess the diagnostic value of exercise echocardiography in patients with complete left bundle branch block and clinical suspicion of coronary artery disease. MATERIAL AND METHODS: Among 1,176 exercise echocardiograms performed from May of 1994 to November of 1996, 92 showed complete left bundle branch block in the resting electrocardiogram. We retrospectively analyzed data of 23 patients who had coronary angiography performed within 6 weeks of the exercise echo (19 males and 4 females, age 62 +/- 8, resting ejection fraction 52 +/- 10%). Previous acute myocardial infarction was demonstrated in 8 of them. The development of new or worsening regional dysfunction was considered an ischaemic response on exercise echo; whereas we assumed that there was significant coronary artery disease on the coronariography whether there was > or = 1 vessel disease in patients without previous myocardial infarction or > or = 2 vessel disease in patients with previous infarction. RESULTS: Ten patients showed multivessel disease (> or = 2 vessels, 6 with previous infarction); 5 one-vessel disease; and 8 non significant coronary artery disease. Exercise echocardiography sensitivity for ischaemia detection in the entire group was 86% (95% confidence interval 67-100%); the specificity was 67% (36-98%), predictive value of a positive test was 80% and predictive value of a negative test was 75%. Sensitivity for the detection of > 50% stenosis in the left anterior descending coronary territory was 92% (76%-100%) and specificity 64% (35%-92%); for right coronary artery sensitivity was 80% (55%-100%) and specificity 77% (54%-100%); and for left circumflex artery sensitivity was 70% (42%-98%) and specificity 69% (44%-94%). CONCLUSIONS: Exercise echocardiography may be useful in the evaluation of patients with left bundle branch block and clinical suspicion of coronary artery disease; with good sensitivity and low specificity.

Prioritizing candidate reproductive/developmental toxicants for evaluation.

To provide a rational method for the timely evaluation of possible reproductive/developmental toxicants, a prioritization scheme was developed by the California Department of Health Services to select chemicals for consideration by the Proposition 65 Scientific Advisory Panel. Initially, four ascertainment methods were used to identify and construct a master list of 164 candidate agents. Using two criteria, the potential for human exposure and the perceived reproductive/developmental hazard as judged by an ad hoc committee of experts, 42 candidates from the master list were identified as priority agents. For practical purposes, the 15 priority agents with the highest rankings will be given the highest priority in the review process. Limitations in the prioritization method used and refinements to be incorporated in an annual update are described.