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.

Correlação da Variação dos Níveis de NT-ProBNP com a Modificação da Capacidade Funcional em Doentes com Insuficiência Cardíaca Crónica

OBJECTIVE: We set out to evaluate whether changes in N-terminal pro-brain natriuretic peptide (proBNP) can predict changes in functional capacity, as determined by cardiopulmonary exercise testing (CPET), in patients with chronic heart failure (CHF) due to dilated cardiomyopathy (DCM). METHODS: We studied 37 patients with CHF due to DCM, 81% non-ischemic, 28 male, who performed symptom-limited treadmill CPET, with the modified Bruce protocol, in two consecutive evaluations, with determination of proBNP after 10 minutes rest prior to CPET. The time between evaluations was 9.6+/-5.5 months, and age at first evaluation was 41.1+/-13.9 years (21 to 67). RESULTS IN THE FIRST AND SECOND EVALUATIONS RESPECTIVELY WERE: NYHA functional class >II 51% and 16% (p<0.001), sinus rhythm 89% and 86.5% (NS), left ventricular ejection fraction 24.9+/-8.9% and 26.6+/-8.6% (NS), creatinine 1.03+/-0.25 and 1.09+/-0.42 mg/dl (NS), taking ACE inhibitors or ARBs 94.5% and 100% (NS), beta-blockers 73% and 97.3% (p<0.001), and spironolactone 89% and 89% (NS). We analyzed the absolute and percentage variation (AV and PV) in peak oxygen uptake (pVO2--ml/kg/min) and proBNP (pg/ml) between the two evaluations. RESULTS: (1) pVO2 AV: -17.4 to 15.2 (1.9+/-5.7); pVO2 PV: -56.1 to 84% (11.0+/-25.2); proBNP AV: -12850 to 5983 (-778.4+/-3332.5); proBNP PV: -99.0 to 379.5% (-8.8+/-86.3); (2) The correlations obtained--r value and p value [r (p)]--are shown in the table below; (3) We considered that a coefficient of variation of pVO2 PV of >10% represented a significant change in functional capacity. On ROC curve analysis, a proBNP PV value of 28% showed 80% sensitivity and 79% specificity for pVO2 PV of >10% (AUC=0.876, p=0.01, 95% CI 0.75 to 0.99). CONCLUSIONS: In patients with CHF due to DCM, changes in proBNP values correlate with variations in pVO2, as assessed by CPET. However, our results suggest that only a proBNP PV of >28% predicts a significant change in functional capacity.

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.

Valor Prognóstico da Normalização da Resposta Ventilatória ao Exercício para o Consumo Máximo de Oxigénio na Insuficiência Cardíaca

Cardiopulmonary exercise testing (CPET) is an objective method for assessment of functional capacity and for prognostic stratification of patients with chronic heart failure (CHF). In this study, we analyzed the prognostic value of a recently described CPET-derived parameter, the minute ventilation to carbon dioxide production slope normalized for peak oxygen consumption (VE/VCO2 slope/pVO2). METHODS: We prospectively studied 157 patients with stable CHF and dilated cardiomyopathy who performed maximal CPET using the modified Bruce protocol. The prognostic value of VE/VCO2 slope/pVO2 was determined and compared with traditional CPET parameters. RESULTS: During follow-up 37 patients died and 12 were transplanted. Mean follow-up in surviving patients was 29.7 months (12-36). Cox multivariate analysis revealed that VE/VCO2 slope/pVO2 had the greatest prognostic power of all the parameters studied. A VE/VCO2 slope/pVO2 of > or = 2.2 signaled cases at higher risk. CONCLUSION: Normalization of the ventilatory response to exercise for peak oxygen consumption appears to increase the prognostic value of CPET in patients with CHF.

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.

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.

Exercise-Induced Intraventricular Obstruction in a Child with Near Syncope and Chest Pain During Exercise

We report the case of a 10-year-old girl with two episodes of light-headedness and chest pain during exercise. She had an unremarkable clinical record, physical examination, ECG, and echocardiogram. Noninvasive ischemia tests were positive, but coronary angiography was normal. Exercise stress echocardiogram revealed an exercise-induced intra-left-ventricular obstruction with a peak gradient of 78 mmHg and replicated her symptoms. After starting beta-blocker therapy her clinical status improved and no residual obstruction was detected. The authors review this unsuspected clinical condition, seldom reported in the adult population and, to our knowledge, never before in a child.

Predicting Outcome after Cardiopulmonary Arrest in Therapeutic Hypothermia Patients: Clinical, Electrophysiological and Imaging Prognosticators

INTRODUCTION: Predicting outcome in comatose survivors of cardiac arrest is based on data validated by guidelines that were established before the era of therapeutic hypothermia. We sought to evaluate the predictive value of clinical, electrophysiological and imaging data on patients submitted to therapeutic hypothermia. MATERIALS AND METHODS: A retrospective analysis of consecutive patients receiving therapeutic hypothermia during years 2010 and 2011 was made. Neurological examination, somatosensory evoked potentials, auditory evoked potentials, electroencephalography and brain magnetic resonance imaging were obtained during the first 72 hours. Glasgow Outcome Scale at 6 months, dichotomized into bad outcome (grades 1 and 2) and good outcome (grades 3, 4 and 5), was defined as the primary outcome. RESULTS: A total of 26 patients were studied. Absent pupillary light reflex, absent corneal and oculocephalic reflexes, absent N20 responses on evoked potentials and myoclonic status epilepticus showed no false-positives in predicting bad outcome. A malignant electroencephalographic pattern was also associated with a bad outcome (p = 0.05), with no false-positives. Two patients with a good outcome showed motor responses no better than extension (false-positive rate of 25%, p = 0.008) within 72 hours, both of them requiring prolonged sedation. Imaging findings of brain ischemia did not correlate with outcome. DISCUSSION: Absent pupillary, corneal and oculocephalic reflexes, absent N20 responses and a malignant electroencephalographic pattern all remain accurate predictors of poor outcome in cardiac arrest patients submitted to therapeutic hypothermia. CONCLUSION: Prolonged sedation beyond the hypothermia period may confound prediction strength of motor responses.

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.

Epilepsy and Physical Exercise

Epilepsy is one of the commonest neurologic diseases and has always been associated with stigma. In the interest of safety, the activities of persons with epilepsy (PWE) are often restricted. In keeping with this, physical exercise has often been discouraged. The precise nature of a person’s seizures (or whether seizures were provoked or unprovoked) may not have been considered. Although there has been a change in attitude over the last few decades, the exact role of exercise in inducing seizures or aggravating epilepsy still remains a matter of discussion among experts in the field. Based mainly on retrospective, but also on prospective, population and animal-based research, the hypothesis that physical exercise is prejudicial has been slowly replaced by the realization that physical exercise might actually be beneficial for PWE. The benefits are related to improvement of physical and mental health parameters and social integration and reduction in markers of stress, epileptiform activity and the number of seizures. Nowadays, the general consensus is that there should be no restrictions to the practice of physical exercise in people with controlled epilepsy, except for scuba diving, skydiving and other sports at heights. Whilst broader restrictions apply for patients with uncontrolled epilepsy, individual risk assessments taking into account the seizure types, frequency, patterns or triggers may allow PWE to enjoy a wide range of physical activities.

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.