Utilidade do Doppler Tecidular na Predição de Eventos Arrítmicos em Adultos com Tetralogia de Fallot Corrigida

INTRODUCTION: Adults with repaired tetralogy of Fallot (TOF) may be at risk for progressive right ventricular (RV) dilatation and dysfunction, which is commonly associated with arrhythmic events. In frequently volume-overloaded patients with congenital heart disease, tissue Doppler imaging (TDI) is particularly useful for assessing RV function. However, it is not known whether RV TDI can predict outcome in this population. OBJECTIVE: To evaluate whether RV TDI parameters are associated with supraventricular arrhythmic events in adults with repaired TOF. METHODS: We studied 40 consecutive patients with repaired TOF (mean age 35 +/- 11 years, 62% male) referred for routine echocardiographic exam between 2007 and 2008. The following echocardiographic measurements were obtained: left ventricular (LV) ejection fraction, LV end-systolic volume, LV end-diastolic volume, RV fractional area change, RV end-systolic area, RV end-diastolic area, left and right atrial volumes, mitral E and A velocities, RV myocardial performance index (Tei index), tricuspid annular plane systolic excursion (TAPSE), myocardial isovolumic acceleration (IVA), pulmonary regurgitation color flow area, TDI basal lateral, septal and RV lateral peak diastolic and systolic annular velocities (E' 1, A' 1, S' 1, E' s, A' s, S' s, E' rv, A' rv, S' rv), strain, strain rate and tissue tracking of the same segments. QRS duration on resting ECG, total duration of Bruce treadmill exercise stress test and presence of exercise-induced arrhythmias were also analyzed. The patients were subsequently divided into two groups: Group 1--12 patients with previous documented supraventricular arrhythmias (atrial tachycardia, fibrillation or flutter) and Group 2 (control group)--28 patients with no previous arrhythmic events. Univariate and multivariate analysis was used to assess the statistical association between the studied parameters and arrhythmic events. RESULTS: Patients with previous events were older (41 +/- 14 vs. 31 +/- 6 years, p = 0.005), had wider QRS (173 +/- 20 vs. 140 +/- 32 ms, p = 0.01) and lower maximum heart rate on treadmill stress testing (69 +/- 35 vs. 92 +/- 9%, p = 0.03). All patients were in NYHA class I or II. Clinical characteristics including age at corrective surgery, previous palliative surgery and residual defects did not differ significantly between the two groups. Left and right cardiac chamber dimensions and ventricular and valvular function as evaluated by conventional Doppler parameters were also not significantly different. Right ventricular strain and strain rate were similar between the groups. However, right ventricular myocardial TDI systolic (Sa: 5.4+2 vs. 8.5 +/- 3, p = 0.004) and diastolic indices and velocities (Ea, Aa, septal E/Ea, and RV free wall tissue tracking) were significantly reduced in patients with arrhythmias compared to the control group. Multivariate linear regression analysis identified RV early diastolic velocity as the sole variable independently associated with arrhythmic history (RV Ea: 4.5 +/- 1 vs. 6.7 +/- 2 cm/s, p = 0.01). A cut-off for RV Ea of < 6.1 cm/s identified patients in the arrhythmic group with 86% sensitivity and 59% specificity (AUC = 0.8). CONCLUSIONS: Our results suggest that TDI may detect RV dysfunction in patients with apparently normal function as assessed by conventional echocardiographic parameters. Reduction in RV early diastolic velocity appears to be an early abnormality and is associated with occurrence of arrhythmic events. TDI may be useful in risk stratification of patients with repaired tetralogy of Fallot.

Utilidade de Ecocardiografia da Sobrecarga Farmacológica com Dobutamina nas Cardiomiopatias Dilatadas não Isquémicas

INTRODUCTION: Low-dose dobutamine stress echocardiography is a common and useful technique to assess myocardial viability in patients with ischemic cardiomyopathy. OBJECTIVE: To evaluate the use of low-dose dobutamine stress echocardiography in determining the functional status of patients with idiopathic dilated cardiomyopathy (IDCM). METHODS: Prospective study of 28 patients with IDCM by transthoracic echocardiography (2D), low-dose dobutamine stress echocardiography, cardiopulmonary exercise testing (CPET) and measurement of pro-BNP. RESULTS: The mean age of the population was 50.3 +/- 11.5 years, 9 female and 19 male. Mean ejection fraction was 32.1 +/- 9.8%. All were in sinus rhythm. The following parameters were analyzed in 2D echocardiography and after dobutamine: dimensions of left atrium (LA) and of left ventricle in diastole and systole, shortening fraction (%), left ventricular end-diastolic (EDV) and end-systolic volumes (ESV), ejection fraction (EF), and mitral inflow (E, A, E/A ratio and deceleration time). In CPET, we considered the following parameters: peak VO2 and % maximal peak VO2 attained. We compared echo results with CPET. There was a correlation between age and peak VO2 (r = -0.38 with p = 0.049). In 2D echo, there was a correlation between baseline EF and LA dimensions and peak VO2 (r = 0.45 / p = 0.004 and r = -0.49 / p = 0.014, respectively). After dobutamine echo, there was a correlation between some echo parameters and peak VO2: EF - r = 0.59 / p = 0.001, LA dimensions - r = 0.56 / p = 0.007, and ESV - r = -0.45 / p = 0.026. Percentage maximal peak VO2 attained correlated with LA dimensions measured in 2D echo and after dobutamine (r = -0.398 / p = 0.036 and r = -0.674 / p = 0.02 respectively) and EF after dobutamine (r = -0.389 / p = 0.04). The value of pro-BNP correlated with LA dimensions and baseline EF (r = 0.44 / p = 0.02 and r = -0.57 / p = 0.002, respectively), and the correlation was maintained after inotropic stimulation with dobutamine (r = 0.57 / p = 0.001 and r = -0.55 / p = 0.0039). CONCLUSION: Low-dose dobutamine stress echocardiography showed stronger correlations with cardiopulmonary exercise testing than the parameters evaluated by conventional echocardiography and could be used to determine the functional status of patients with dilated cardiomyopathy; patients with greater ejection fraction after inotropic stimulation had better cardiopulmonary tests.

Incidência de "Falsos-Positivos" em Idosos com Fibrilhação Auricular Paroxística Submetidos a Teste de Inclinação

The autonomic nervous system (ANS) plays a role as a modulator in the pathogenesis of paroxysmal atrial fibrillation (PAF). The clinical pattern of vagally mediated PAF has been observed mainly in young patients. Neurocardiogenic responses during orthostatic stress are related to autonomic reflexes in which the vagal influence predominates. AIM: To evaluate the susceptibility of elderly patients with PAF to activation of vasovagal syncope mechanisms. METHODS: We performed passive head-up tilt testing (HUT) in 34 patients (62% women, aged 72 +/- 7 years), with > or = 1 year of clinical history of PAF--19 without structural heart disease, 11 with hypertensive heart disease and 4 with coronary artery disease (who had no previous myocardial infarction, had undergone myocardial revascularization, and had no documented ischemia) (PAF group), and compared the results with those obtained in a group of 34 age-matched patients (53% women, aged 74 +/- 6 years), who underwent HUT due to recurrent syncope (Sc group). In this group, 21 had no documented heart disease and none had a clinical history of AF. There was no diabetes, congestive heart failure or syncope in the PAF group. After a supine resting period, the subjects were tilted at 70 degrees for 20 minutes while in sinus rhythm. No provocative agents were used to complement the HUT. ECG and blood pressure were continuously monitored (Task Force Monitor, CNSystems). The test was considered positive when syncope or presyncope occurred with bradycardia and/or arterial hypotension. Abnormal responses were classified as cardioinhibitory, vasodepressor or mixed. RESULTS: HUT was positive in seven patients of the PAF group--vasodepressor response in five and mixed in two (20.5% of the total; 26.3% of those without heart disease)--and in eight patients (vasodepressor in six and mixed in two) of the Sc group (p=NS). During HUT, three patients of the PAF group had short periods of self-limited PAF (in one, after vasodepressor syncope). There were no differences in gender distribution, age or heart disease. No cardioinhibitory responses or orthostatic hypotension were observed. CONCLUSION: In elderly patients with PAF, a significant number of false positive results during passive HUT may be expected, suggesting increased vasovagal reactions despite aging. This suggests that ANS imbalances may be observed in this population.

Head-Up Tilt Testing with Different Nitroglycerin Dosages: Experience in Elderly Patients with Unexplained Syncope

AIMS: Protocols using sublingual nitrates have been increasingly used to improve diagnostic accuracy of head-up tilt testing (HUT). Nevertheless, exaggerated responses to nitrates have been frequently described, particularly in elderly patients. The aim of this article is to evaluate, in an elderly population with unexplained syncope, whether the impact of sublingual nitroglycerin (NTG) used as a provocative agent is dose-dependent. METHODS AND RESULTS: One hundred and twenty consecutive elderly patients submitted to HUT using NTG after an asymptomatic drug-free phase were studied. Patients were divided into three groups according to the NTG dosage: 500, 375 and 250 microg. The test was considered positive when there was reproduction of symptoms with bradycardia and/or arterial hypotension. A gradual decrease in the blood pressure after NTG was considered an exaggerated response to nitrates. There were no differences in the clinical characteristics of the different subgroups. A positive test was obtained in 50% of the patients in each group. The rate of exaggerated responses was identical in all groups and ranged between 15 and 17%. CONCLUSION: In an elderly population with syncope of unknown origin submitted to HUT, the response to NTG is not dose-dependent, and no difference was found in the rate of exaggerated responses to nitrates with different NTG dosages.

Prognostic Value of a New Cardiopulmonary Exercise Testing Parameter in Chronic Heart Failure: Oxygen Uptake Efficiency at Peak Exercise - Comparison with Oxygen Uptake Efficiency Slope

INTRODUCTION: A growing body of evidence shows the prognostic value of oxygen uptake efficiency slope (OUES), a cardiopulmonary exercise test (CPET) parameter derived from the logarithmic relationship between O(2) consumption (VO(2)) and minute ventilation (VE) in patients with chronic heart failure (CHF). OBJECTIVE: To evaluate the prognostic value of a new CPET parameter - peak oxygen uptake efficiency (POUE) - and to compare it with OUES in patients with CHF. METHODS: We prospectively studied 206 consecutive patients with stable CHF due to dilated cardiomyopathy - 153 male, aged 53.3±13.0 years, 35.4% of ischemic etiology, left ventricular ejection fraction 27.7±8.0%, 81.1% in sinus rhythm, 97.1% receiving ACE-Is or ARBs, 78.2% beta-blockers and 60.2% spironolactone - who performed a first maximal symptom-limited treadmill CPET, using the modified Bruce protocol. In 33% of patients an cardioverter-defibrillator (ICD) or cardiac resynchronization therapy device (CRT-D) was implanted during follow-up. Peak VO(2), percentage of predicted peak VO(2), VE/VCO(2) slope, OUES and POUE were analyzed. OUES was calculated using the formula VO(2) (l/min) = OUES (log(10)VE) + b. POUE was calculated as pVO(2) (l/min) / log(10)peakVE (l/min). Correlation coefficients between the studied parameters were obtained. The prognosis of each variable adjusted for age was evaluated through Cox proportional hazard models and R2 percent (R2%) and V index (V6) were used as measures of the predictive accuracy of events of each of these variables. Receiver operating characteristic (ROC) curves from logistic regression models were used to determine the cut-offs for OUES and POUE. RESULTS: pVO(2): 20.5±5.9; percentage of predicted peak VO(2): 68.6±18.2; VE/VCO(2) slope: 30.6±8.3; OUES: 1.85±0.61; POUE: 0.88±0.27. During a mean follow-up of 33.1±14.8 months, 45 (21.8%) patients died, 10 (4.9%) underwent urgent heart transplantation and in three patients (1.5%) a left ventricular assist device was implanted. All variables proved to be independent predictors of this combined event; however, VE/VCO2 slope was most strongly associated with events (HR 11.14). In this population, POUE was associated with a higher risk of events than OUES (HR 9.61 vs. 7.01), and was also a better predictor of events (R2: 28.91 vs. 22.37). CONCLUSION: POUE was more strongly associated with death, urgent heart transplantation and implantation of a left ventricular assist device and proved to be a better predictor of events than OUES. These results suggest that this new parameter can increase the prognostic value of CPET in patients with CHF.

Stress-Related Mucosal Disease: Incidence of Bleeding and the Role of Omeprazole in its Prophylaxis

BACKGROUND: Upper gastrointestinal bleeding is the severe complication of stress-related mucosal disease in hospitalized patients. In intensive care units (ICU), risk factors are well defined and only mechanical ventilation and coagulopathy proved to be relevant for significant bleeding. On the contrary, in non-ICU settings there is no consensus about this issue. Nevertheless, omeprazole is still widely used in prophylaxis of bleeding. The objective of our study was to evaluate the relevance of stress-related mucosal disease bleeding in patients admitted to an internal medicine ward, and the role of omeprazole in its prophylaxis. METHODS: We conducted a retrospective study in which we analysed consecutive patients who were admitted to our ward over a year. We recorded demographic characteristics of the patients, potential risk factors for stress-related mucosal disease (clinical data, laboratory, and medication), administration of prophylactic omeprazole, and total cost of this prophylaxis. Patients with active gastrointestinal bleeding on the admission were excluded. We recorded every upper gastrointestinal bleeding event with clinical relevance. RESULTS: Five hundred and thirty-five patients, mean age 70 years, mean length of stay 9.6+/-7.7 days; 140 (26.2%) patients were treated with 40 mg of omeprazole intravenously, 193 (36.1%) with 20mg of omeprazole orally, and 202 (37.8%) patients had no prophylaxis. There was only one episode (0.2%) of clinically relevant bleeding. CONCLUSION: In patients admitted to an internal medicine ward, incidence of upper gastrointestinal bleeding as a complication of stress-related mucosal disease is low. We found that there is no advantage in prophylaxis with omeprazole.

Development Process and Cognitive Testing of CARATkids - Control of Allergic Rhinitis and Asthma Test for Children

Background: Allergic rhinitis and asthma (ARA) are chronic inflammatory diseases of the airways that often coexist in children. The only tool to assess the ARA control, the Control of Allergic Rhinitis and Asthma Test (CARAT) is to be used by adults. We aimed to develop the Pediatric version of Control of Allergic Rhinitis and Asthma Test (CARATkids) and to test its comprehensibility in children with 4 to 12 years of age. Methods: The questionnaire development included a literature review of pediatric questionnaires on asthma and/or rhinitis control and two consensus meetings of a multidisciplinary group. Cognitive testing was carried out in a cross-sectional qualitative study using cognitive interviews. Results: Four questionnaires to assess asthma and none to assess rhinitis control in children were identified. The multidisciplinary group produced a questionnaire version for children with 17 questions with illustrations and dichotomous (yes/no) response format. The version for caregivers had 4-points and dichotomous scales. Twenty-nine children, 4 to 12 years old, and their caregivers were interviewed. Only children over 6 years old could adequately answer the questionnaire. A few words/expressions were not fully understood by children of 6 to 8 years old. The drawings illustrating the questions were considered helpful by children and caregivers. Caregivers considered the questionnaire complete and clear and preferred dichotomous over the 4-points scales. The proportion of agreement between children and their caregivers was 61%. The words/expressions that were difficult to understand were amended. Conclusion: CARATkids, the first questionnaire to assess a child’s asthma and rhinitis control was developed and its content validity was assured. Cognitive testing showed that CARATKids is well-understood by children 6 to 12 years old. The questionnaire’s measurement properties can now be assessed in a validation study.

Impact of Syncope on Quality of Life: Validation of a Measure in Patients Undergoing Tilt Testing

INTRODUCTION AND OBJECTIVES: Recurrent syncope has a significant impact on quality of life. The development of measurement scales to assess this impact that are easy to use in clinical settings is crucial. The objective of the present study is a preliminary validation of the Impact of Syncope on Quality of Life questionnaire for the Portuguese population. METHODS: The instrument underwent a process of translation, validation, analysis of cultural appropriateness and cognitive debriefing. A population of 39 patients with a history of recurrent syncope (>1 year) who underwent tilt testing, aged 52.1 ± 16.4 years (21-83), 43.5% male, most in active employment (n=18) or retired (n=13), constituted a convenience sample. The resulting Portuguese version is similar to the original, with 12 items in a single aggregate score, and underwent statistical validation, with assessment of reliability, validity and stability over time. RESULTS: With regard to reliability, the internal consistency of the scale is 0.9. Assessment of convergent and discriminant validity showed statistically significant results (p<0.01). Regarding stability over time, a test-retest of this instrument at six months after tilt testing with 22 patients of the sample who had not undergone any clinical intervention found no statistically significant changes in quality of life. CONCLUSIONS: The results indicate that this instrument is of value for assessing quality of life in patients with recurrent syncope in Portugal.

Iron Overload in a Murine Model of Hereditary Hemochromatosis Is Associated with Accelerated Progression of Osteoarthritis Under Mechanical Stress

OBJECTIVE: Hereditary hemochromatosis (HH) is a disease caused by mutations in the Hfe gene characterised by systemic iron overload and associated with an increased prevalence of osteoarthritis (OA) but the role of iron overload in the development of OA is still undefined. To further understand the molecular mechanisms involved we have used a murine model of HH and studied the progression of experimental OA under mechanical stress. DESIGN: OA was surgically induced in the knee joints of 10-week-old C57BL6 (wild-type) mice and Hfe-KO mice. OA progression was assessed using histology, micro CT, gene expression and immunohistochemistry at 8 weeks after surgery. RESULTS: Hfe-KO mice showed a systemic iron overload and an increased iron accumulation in the knee synovial membrane following surgery. The histological OA score was significantly higher in the Hfe-KO mice at 8 weeks after surgery. Micro CT study of the proximal tibia revealed increased subchondral bone volume and increased trabecular thickness. Gene expression and immunohistochemical analysis showed a significant increase in the expression of matrix metallopeptidase 3 (MMP-3) in the joints of Hfe-KO mice compared with control mice at 8 weeks after surgery. CONCLUSIONS: HH was associated with an accelerated development of OA in mice. Our findings suggest that synovial iron overload has a definite role in the progression of HH-related OA