Guidelines of the Spanish Society of Cardiology for clinical practice in exercise testing

Most exercise testing is performed in adults with known or suspected ischemic heart disease. In the last few years cardiac imaging techniques have been applied in this field, improving the information obtained with the procedure. However, the exceptions to this rule are emerging rapidly not only in healthy people (asymptomatic individuals, athletes, handicapped people) but also in cardiac patients (advanced congestive heart failure, hypertension, rhythm disorders, congenital heart disease, etc.). All the-se issues justify the need for a multidisciplinary consensus document in Spain.This paper reviews and updates the methodological aspects of the stress test, including those related to oxygen consumption measurements. The main aim of this review was to determine the role of exercise testing in the evaluation of ischemic heart disease as well as the applications of imaging stress testing. The usefulness of this test in other non-ischemic cardiac disorders and in selected subsets of healthy people is also reviewed.     

Giardia infections in Cuban children: the genotypes circulating in a rural population

Stool samples containing Giardia duodenalis cysts were collected from 95 primary-school children in central Cuba, and preserved by storing at -20 degrees C in 70% ethanol. Clinical data were collected for each child. Although 57% of the children were asymptomatic, the remaining 43% each reported between one and three symptoms. Following cyst quantification and isolation, molecular analyses were attempted on all cyst isolates, with the focus on the parasite's beta-giardin and glutamate-dehydrogenase (gdh) genes. Unfortunately, the cyst-preservation procedure appeared to have a deleterious effect on the cysts, since genotyping data could only be obtained for 20 of the 95 isolates. These data indicated, however, an approximately equal distribution between assemblage A (nine isolates) and assemblage B (11 isolates). Children found to be excreting relatively large numbers of cysts were more likely to be symptomatic than children who were excreting fewer cysts, and children with Giardia isolates from assemblage B were more likely to have symptomatic infections than children with isolates from assemblage A. Although considerable sequence variability was seen in the assemblage-B isolates, the assemblage-A isolates were relatively genetically homogeneous. This is the first publication from the Caribbean in which the Giardia genotypes circulating within the population have been identified, the first from the Americas providing information on associations between clinical presentation and the assemblage of the infecting Giardia, and the first to indicate that levels of cyst excretion may have clinical significance.     

Reduced myocardial perfusion reserve and transmural perfusion gradient in heart transplant arteriopathy assessed by magnetic resonance imaging

OBJECTIVES: The goal of this study was to detect transplant arteriopathy (Tx-CHD) by a reduced myocardial perfusion reserve (MPR) and resting endomyocardial/epimyocardial perfusion ratio (Endo/Epi ratio). BACKGROUND: Transplant arteriopathy often lacks clinical symptoms and is the reason for frequent surveillance angiography in heart transplant (Tx) recipients. Magnetic resonance perfusion imaging (MRPI) allows noninvasive assessment of transmural and selective endomyocardial and epimyocardial perfusion. METHODS: Fifteen healthy volunteers (controls) and three groups (A, B, C) of Tx recipients were included. In controls and patients, MPR (hyperemic/resting perfusion) and Endo/Epi ratio were determined with MRPI after injection of gadolinium-diethylenetriamine pentaacetic acid at rest and during hyperemia (intravenous adenosine). Group A (n = 10) had no left ventricular (LV) hypertrophy and/or prior rejection, while patients in group B (n = 10) had at least one of these characteristics. Patients in group A and B had a normal coronary angiogram and a coronary flow reserve (CFR) of > or =2.5 (CFR = hyperemic/resting blood flow). Group C (n = 7) had Tx-CHD diagnosed by angiography and a reduced CFR (<2.5). RESULTS: In group C, MPR (1.7 +/- 0.5) and Endo/Epi ratio (1.1 +/- 0.2) were significantly reduced compared with controls (4.2 +/- 0.7 and 1.6 +/- 0.3; both p < 0.0001), group A (3.6 +/- 0.7 and 1.6 +/- 0.2; both p < 0.0001) and B (2.7 +/- 0.9, p < 0.01 and 1.4 +/- 0.1, p < 0.04). Transplant arteriopathy can be excluded by an MPR of >2.3 with sensitivity and specificity of 100% and 85%. If LV hypertrophy and prior rejection are excluded, Tx-CHD can be excluded by an Endo/Epi ratio of >1.3 with 100% and 80%. CONCLUSIONS: Magnetic resonance perfusion imaging detects Tx-CHD by a decreased MPR. After exclusion of LV hypertrophy and prior rejection, resting Endo/Epi ratio alone might be sufficient to indicate Tx-CHD.     

Plasma levels of plasminogen activator inhibitor type 1, beta- thromboglobulin, and fibrinopeptide A before, during, and after treatment of acute myocardial infarction with alteplase

Plasma levels of plasminogen activator inhibitor type-1 (PAI-1), beta- thromboglobulin (beta TG), and fibrinopeptide A (FPA) were followed over 24 hours in 30 patients treated with alteplase for acute myocardial infarction. Samples were taken at baseline (T Oh), after 90 minutes (under alteplase, no heparin, T 1.5h), after 120 minutes (under alteplase and heparin, T 2h), 30 minutes after thrombolytic therapy (T 3.5h), as well as 12 hours (T 12h) and 24 hours (T 24h) after baseline. PAI-1 antigen levels (55 +/- 9 ng/mL at T Oh, mean +/- SEM) decreased to 35 +/- 5 (T 1.5h) and 40 +/- 6 (T 2h) ng/mL under alteplase, before increasing to 84 +/- 22 (T 3.5h), 130 +/- 30 (T 12h), and 64 +/- 7 (T 24h) ng/mL after therapy, P less than .001. A high baseline PAI-1 activity (18 +/- 3 ng/mL) decreased to 2.0 +/- 0.4 (T 1.5h) and 1.7 +/- 0.2 (T 2h) under alteplase and increased to 32 +/- 5 (T 12h) and 19 +/- 3 (T 24h) ng/mL after therapy (P less than .0001). beta TG levels (339 +/- 105 ng/mL at T Oh) decreased to 203 +/- 48 (T 2h), 154 +/- 51 (T 3.5h), 187 +/- 40 (T 12h), and 142 +/- 32 (T 24h) ng/mL under heparin (P less than .01). FPA levels (34 +/- 9 ng/mL at T Oh) increased to 85 +/- 15 ng/mL under alteplase alone (T 1.5h) and normalized under heparin (11 +/- 4, 6 +/- 2, 4 +/- 2, and 3 +/- 1 ng/mL at T 2h, T 3.5h, T 12h, and T 24h, respectively). A high level of FPA at T 3.5h correlated with reocclusion (33 +/- 12 ng/mL, n = 4 v 2.9 +/- 0.5 ng/mL, n = 21, P less than .005). We conclude that plasma levels of PAI- 1 antigen as well as activity markedly increase after alteplase therapy of acute myocardial infarction. The high activity of PAI-1 and decreasing beta TG levels suggest that platelets do not contribute significantly to this phenomenon. The marked increase of FPA levels under recombinant tissue-type plasminogen activator alone and its normalization under heparin emphasize the important role of concomitant anticoagulation in controlling further intravasal fibrin generation under alteplase.     

Pulse wave analysis of the aortic pressure waveform in patients with vasovagal syncope

Vascular reflex mechanisms contribute to vasovagal syncope. However, the alterations in central haemodynamics in patients with vasovagal syncope are unknown. 30 consecutive patients (36.5 ± 15 years, 14 females) with recurrent vasovagal syncope (VVS) and a positive tilt table test were compared to 39 age- and sex-matched controls (36.9 ± 16 years, 15 females) with a negative tilt table result and no history of syncope. Central aortic pressure parameters including augmentation index and central pulse pressure as markers of aortic stiffness were generated non-invasively by applanation tonometry of the radial artery and use of a validated mathematical transfer function. No difference in aortic augmentation index was observed between groups. (VVS 9 ± 2.6 vs. Control 11 ± 2.4, p = 0.8). However, in patients with vasovagal syncope the aortic pressure waveform significantly differed from healthy controls. A prolonged time to the peak of aortic pressure wave (aortic T2) was observed in patients with vasovagal syncope (226 ± 24 vs. 208 ± 21 ms, p = 0.001). Furthermore time to the first shoulder of the aortic pressure wave (aortic T1) was slightly shorter compared to healthy controls, but did not reach statistical significance (106 ± 22 vs. 110 ± 12 ms, p = 0.33). Patients with vasovagal syncope have an altered aortic pressure waveform at rest, but no signs of elevated aortic stiffness. The underlying mechanisms for these findings may potentially result from a complex imbalance of the autonomic nervous system with a continuous deregulation of the sympathetic and parasympathetic reflex arcs.     

Pituitary and adrenal hormones in patients after myocardial infarction under ergometer load

The levels of human growth hormone (HGH), ACTH and cortisol in the plasma of 100 middle-aged men were measured by means of radioimmunoassay (12 patients in the phase of hospitalization after myocardial infarction, 47 patients in convalescence, 31 patients in post-convalescence, 10 healthy men). Twenty patients in the phase of convalescence and all patients in post-convalescence did exercises on bicycle ergometer with submaximal loading. Patients after myocardial infarction showed significantly lower basic levels of HGH than healthy persons, and the increase in the HGH level induced by exercise was significantly lower. The hormones ACTH and cortisol showed only slight differences. The secretion of the pituitary hormones, mainly HGH, seems to be altered in patients after myocardial infarction.     

DLA-identical bone marrow grafts after low-dose total body irradiation: the effect of canine recombinant hematopoietic growth factors

Previous studies found that bone marrow (BM) allografts from DLA- identical littermates resulted in survival of two thirds of recipient dogs after otherwise lethal doses of 450 to 600 cGy of total body irradiation (TBI) because of successful allografts or autologous recovery after rejection of the allografts. The current study asked whether survival could be further improved by treating allograft recipients with recombinant canine granulocyte colony-stimulating factor (G-CSF), stem cell factor (SCF), or G-CSF/SCF. Of 21 dogs, 14 (67%) receiving allografts but no growth factors survived, 10 with successful allografts (including 5 mixed chimeras) and 4 with autologous recovery; whereas 7 animals died, 5 from infections during BM aplasia and 2 from acute graft-versus-host disease. By comparison, 30 of 34 dogs (88%) receiving hematopoietic growth factors in addition to the BM graft survived, 17 with successful allografts (including 10 mixed chimeras) and 13 with autologous recovery; whereas 4 died, all with infection related to BM aplasia after rejection of the allograft. Survival was similar for recipients of G-CSF, SCF, or the combination of G-CSF and SCF. Logistic regression analyses, which accounted for possible effects of TBI dose, showed a trend for improved survival in dogs receiving growth factors (P = .09), no change in allogeneic engraftment (P = .74), and a slight increase in autologous recovery (P = .22). In agreement with previous data, we found that grafts of BM from DLA-identical littermates improved survival of recipient dogs exposed to low but otherwise lethal doses of TBI. A further improvement in survival could be achieved by additional treatment with G-CSF, SCF, or G-CSF/SCF. Results suggest that treatment by hematopoietic growth factors along with BM grafts should be considered for victims of radiation accidents.     

Platelet adhesion and thrombus formation on subendothelium in platelets deficient in glycoproteins IIb-IIIa, Ib, and storage granules

Patients whose platelets are deficient in glycoprotein (GP) Ib, IIb- IIIa (thrombasthenia), or granule substances (storage pool deficiency, SPD) were studied to define further the properties of platelets that mediate platelet adhesion and thrombus formation on subendothelium. Both nonanticoagulated and citrated blood were exposed to everted, de- endothelialized rabbit vessel segments under controlled flow conditions and shear rates varying from 650 to 3,300 sec-1. Morphometry was used to measure platelet thrombus dimensions and the percentage of the subendothelial surface covered with contact (C) or spread (S) platelets. Adhesion was defined as C + S. The results in SPD demonstrated (1) reduced thrombus dimensions in delta-SPD (pure dense granule deficiency) in proportion to the magnitude of the dense granule defect; (2) an even greater reduction in thrombus dimensions in patients with combined deficiencies of alpha and dense granules (alpha delta-SPD); and (3) impaired platelet adhesion at several conditions in alpha delta-SPD and, in delta-SPD, a hematocrit-dependent impairment of adhesion in citrated blood at 2,600 sec-1. In thrombasthenia, platelets were present as a monolayer on the subendothelial surface in both nonanticoagulated and citrated blood, indicating an absolute requirement for GPIIb-IIIa in promoting platelet-platelet interaction at all shear rates and perfusion times. Two types of abnormalities in platelet-vessel wall interactions were observed. In nonanticoagulated blood, the percentage of platelets in the C phase was consistently increased at all shear rates, but C + S values were normal. These observations indicate that platelets deficient in GPIIb-IIIa do not spread normally on the subendothelial surface exposed to nonanticoagulated blood. With citrated blood, the C + S value in thrombasthenia was reduced at both 800 and 2,600 sec-1, as in von Willebrand's disease, and a similar degree of reduction (about 50%) was observed in normal blood treated with a monoclonal antibody to GPIIb- IIIa. The findings, together with theoretical considerations, are consistent with an hypothesis that GPIIb-IIIa mediates the spreading of platelets on subendothelium following the initial attachment through GPIb and that GPIIb-IIIa may be considered an adhesion site on the platelet membrane. Abnormalities of GPIIb-IIIa may, depending on the conditions of study, result in either increased values of C platelets or decreased values of C + S. The results of the study further suggest that a complex interaction of platelet granule factors and membrane GP mediate platelet adhesion and thrombus formation.