How frequently should a patient taking amiodarone be screened for thyroid dysfunction?

Amiodarone-induced thyroid dysfunction (AITD) is a common complication of amiodarone therapy and its prevalence varies according to iodine intake, subclinical thyroid disorders and the definition of AITD. There is no consensus about the frequency of screening for this condition. We evaluated 121 patients on chronic regular intake of amiodarone (mean intake = 248.5 ± 89 mg; duration of treatment = 5.3 ± 3.9 years, range = 0.57-17 years) and with stable baseline cardiac condition. Those with noAITD were followed up for a median period of 3.2 years (range: 0.6-6.7) and the incidence rate of AITD, defined by clinical and laboratorial findings as proposed by international guidelines, was obtained (62.8 per 1000 patients/year). We applied the Coxproportional hazard model to adjust for potential confounding factors and used sensitivity analysis to identify the best screening time for follow-up. We detected thyroid dysfunction in 59 (48.7%) of the 121 patients, amiodarone-induced hypothyroidism in50 (41.3%) and hyperthyroidism in 9 (7.5%). Compared with patients without AITD, there was no difference regarding dosage or duration of therapy, heart rhythm disorder or baseline cardiac condition. During the follow-up of the 62 patients without AITD at baseline evaluation, 11 developed AITD (interquartile range, IR: 62.8 (95%CI: 31.3-112.3) cases per 1000 patients/year), 9 of them with hypothyroidism - IR: 11.4 (95%CI: 1.38-41.2), and 2 hyperthyroidism - IR: 51.3 (95%CI: 23.4-97.5). Age, gender,dose, and duration of treatment were not significant after adjustment. During the first 6 months of follow-up the incidence rate for AITD was 39.3 (9.2-61.9) cases per 1000 patients/year. These data show that AITD is quite common, and support the need for screening at 6-month intervals, unless clinical follow-up dictates otherwise or further information regarding the prognosis of untreated subclinical AITD is available.

Minor segmental wall motion abnormalities detected in patients with Chagas' disease have adverse prognostic implications

Recent data from our laboratory have shown that patients with the indeterminate form of Chagas' disease can have impairment of left ventricular contractility, as evaluated by the slope of the left ventricle end-systolic pressure-dimension relationship. We also showed that Chagas' disease patients with minimal baseline wall motion abnormalities detected by two-dimensional echocardiography have more intense contractility impairment when compared to patients with the indeterminate form of the disease without this abnormality. The prognostic implications of these findings have not been established. We evaluated 59 patients (37-76 years, mean = 55 years) with different clinical forms of Chagas' disease, who had normal left ventricular global systolic function at baseline (57.6 ± 6.9 percent) and who had at least one additional echo during clinical follow-up (0.4-17.6; mean 4.6 years). Group 1 consisted of 14 patients with minor baseline left ventricle wall motion abnormalities and group 2 consisted of 45 patients without these abnormalities. During follow-up, global left ventricle systolic function deterioration was observed in 10 group 1 patients (71.4 percent) and in only 10 group 2 patients (22.2 percent; P < 0.005). Age and duration of follow-up were not independent determinants of left ventricular function deterioration in these patients. The present data indicate that mild segmental left ventricular wall motion abnormalities are associated with worsening of systolic function in Chagas' disease patients who have normal baseline global systolic performance.

Automated grading of left ventricular segmental wall motion by an artificial neural network using color kinesis images

The present study describes an auxiliary tool in the diagnosis of left ventricular (LV) segmental wall motion (WM) abnormalities based on color-coded echocardiographic WM images. An artificial neural network (ANN) was developed and validated for grading LV segmental WM using data from color kinesis (CK) images, a technique developed to display the timing and magnitude of global and regional WM in real time. We evaluated 21 normal subjects and 20 patients with LVWM abnormalities revealed by two-dimensional echocardiography. CK images were obtained in two sets of viewing planes. A method was developed to analyze CK images, providing quantitation of fractional area change in each of the 16 LV segments. Two experienced observers analyzed LVWM from two-dimensional images and scored them as: 1) normal, 2) mild hypokinesia, 3) moderate hypokinesia, 4) severe hypokinesia, 5) akinesia, and 6) dyskinesia. Based on expert analysis of 10 normal subjects and 10 patients, we trained a multilayer perceptron ANN using a back-propagation algorithm to provide automated grading of LVWM, and this ANN was then tested in the remaining subjects. Excellent concordance between expert and ANN analysis was shown by ROC curve analysis, with measured area under the curve of 0.975. An excellent correlation was also obtained for global LV segmental WM index by expert and ANN analysis (R² = 0.99). In conclusion, ANN showed high accuracy for automated semi-quantitative grading of WM based on CK images. This technique can be an important aid, improving diagnostic accuracy and reducing inter-observer variability in scoring segmental LVWM.

Effects of aerobic exercise training on heart rate variability during wakefulness and sleep and cardiorespiratory responses of young and middle-aged healthy men

The purpose of the present study was to evaluate the effects of aerobic physical training (APT) on heart rate variability (HRV) and cardiorespiratory responses at peak condition and ventilatory anaerobic threshold. Ten young (Y: median = 21 years) and seven middle-aged (MA = 53 years) healthy sedentary men were studied. Dynamic exercise tests were performed on a cycloergometer using a continuous ramp protocol (12 to 20 W/min) until exhaustion. A dynamic 24-h electrocardiogram was analyzed by time (TD) (standard deviation of mean R-R intervals) and frequency domain (FD) methods. The power spectral components were expressed as absolute (a) and normalized units (nu) at low (LF) and high (HF) frequencies and as the LF/HF ratio. Control (C) condition: HRV in TD (Y: 108, MA: 96 ms; P<0.05) and FD - LFa, HFa - was significantly higher in young (1030; 2589 ms²/Hz) than in middle-aged men (357; 342 ms²/Hz) only during sleep (P<0.05); post-training effects: resting bradycardia (P<0.05) in the awake condition in both groups; VO2 increased for both groups at anaerobic threshold (P<0.05), and at peak condition only in young men; HRV in TD and FD (a and nu) was not significantly changed by training in either groups. The vagal predominance during sleep is reduced with aging. The resting bradycardia induced by short-term APT in both age groups suggests that this adaptation is much more related to intrinsic alterations in sinus node than in efferent vagal-sympathetic modulation. Furthermore, the greater alterations in VO2 than in HRV may be related to short-term APT

Head-to-head comparison of dipyridamole, dobutamine and pacing stress echocardiography for the detection of myocardial ischemia in an animal model of coronary artery stenosis

To compare the sensitivity of dipyridamole, dobutamine and pacing stress echocardiography for the detection of myocardial ischemia we produced a physiologically significant stenosis in the left circumflex artery of 14 open-chest dogs (range: 50 to 89 percent reduction in luminal diameter). In each study, dobutamine (5 to 40 æg kg-1 min-1 in 3-min stages) and pacing (20 bpm increments, each 2 min, up to 260 bpm) were performed randomly, and then followed by dipyridamole (up to 0.84 mg/kg over 10 min). The positivity of stress echocardiography tests was quantitatively determined by a significant (P<0.05) reduction of or failure to increase absolute and percent systolic wall thickening in the stenotic artery supplied wall, as compared to the opposite wall (areas related to the left anterior descending artery). Systolic and diastolic frozen images were analyzed off-line by two blinded observers in the control and stress conditions. The results showed that 1) the sensitivity of dobutamine, dipyridamole and pacing stress tests was 57, 57 and 36 percent, respectively; 2) in animals with positive tests, the mean percent change of wall thickening in left ventricular ischemic segments was larger in the pacing (-19 Ý 11 percent) and dipyridamole (-18 Ý 16 percent) tests as compared to dobutamine (-9 Ý 6 percent) (P = 0.05), but a similar mean reduction of wall thickening was observed when this variable was normalized to a control left ventricular segment (area related to the left anterior descending artery) (pacing: -16 Ý 7 percent; dipyridamole: -25 Ý 16 percent; dobutamine: -26 Ý 10 percent; not significant), and 3) a significant correlation was observed between magnitude of coronary stenosis and left ventricular segmental dysfunction induced by ischemia in dogs submitted to positive stress tests. We conclude that the dobutamine and dipyridamole stress tests showed identical sensitivities for the detection of myocardial ischemia in this one-vessel disease animal model with a wide range of left circumflex artery stenosis. The pacing stress test was less sensitive, but the difference was not statistically significant. The magnitude of segmental left ventricular dysfunction induced by ischemia was similar in all stress tests evaluated

A pulsatile flow model for in vitro quantitative evaluation of prosthetic valve regurgitation

A pulsatile pressure-flow model was developed for in vitro quantitative color Doppler flow mapping studies of valvular regurgitation. The flow through the system was generated by a piston which was driven by stepper motors controlled by a computer. The piston was connected to acrylic chambers designed to simulate "ventricular" and "atrial" heart chambers. Inside the "ventricular" chamber, a prosthetic heart valve was placed at the inflow connection with the "atrial" chamber while another prosthetic valve was positioned at the outflow connection with flexible tubes, elastic balloons and a reservoir arranged to mimic the peripheral circulation. The flow model was filled with a 0.25 per cent corn starch/water suspension to improve Doppler imaging. A continuous flow pump transferred the liquid from the peripheral reservoir to another one connected to the "atrial" chamber. The dimensions of the flow model were designed to permit adequate imaging by Doppler echocardiography. Acoustic windows allowed placement of transducers distal and perpendicular to the valves, so that the ultrasound beam could be positioned parallel to the valvular flow. Strain-gauge and electromagnetic transducers were used for measurements of pressure and flow in different segments of the system. The flow model was also designed to fit different sizes and types of prosthetic valves. This pulsatile flow model was able to generate pressure and flow in the physiological human range, with independent adjustment of pulse duration and rate as well as of stroke volume. This model mimics flow profiles observed in patients with regurgitant prosthetic valves.

Cardiorespiratory adaptations induced by aerobic training in middle-aged men: the importance of a decrease in sympathetic stimulation for the contribution of dynamic exercise tachycardia

We investigated the effects of aerobic training on the efferent autonomic control of heart rate (HR) during dynamic exercise in middle-aged men, eight of whom underwent exercise training (T) while the other seven continued their sedentary (S) life style. The training was conducted over 10 months (three 1-h/sessions/week on a field track at 70-85 percent of the peak HR). The contribution of sympathetic and parasympathetic exercise tachycardia was determined in terms of differences in the time constant effects on the HR response obtained using a discontinuous protocol (4-min tests at 25,50,100 and 125 watts on a cycle ergometer), and a continuous protocol (25 watts/min until exhaustion allowed the quantification of the parameters (anaerobic threshold, VO2,AT; peak O2 uptake, VO2 peak; power peak) that reflect oxygen transport. The results obtained for the S and the T groups were: 1) a smaller resting HR in T (66 beats/min) when compared to S (84 beats/min); 2) during exercise, a small increase in the fast tachycardia (delta0-10 s) related to vagal withdrawal (P<0.05, only at 25 watts) was observed in T at all powers; at middle and higher powers a significant decrease (P<0.05 at 50, 100 and 125 watts) in the slow tachycardia (delta1-4 min) related to a sympathetic-dependent mechanism was observed in T; 3) VO2AT (S=1.06 and T=1.33 l/min) and VO2 peak (S=1.97 and T=2.37 l/min) were higher in T (P<0.05). These results demonstrate that aerobic training can induce significant physiological adaptations in middle-aged men, mainly expressed as a decrease in the sympathetic effects on heart rate associated with an increase in oxygen transport during dynamic exercise.

Cardiomiopatia hipertrófica tratada por técnica intervencionista de reduçäo septal / Cardiomyopaty hipertrophic treatment through technique interval the reduction septal

Mulher de 75 anos com cardiomiopatia hipertrófica obstrutiva, com dispnéia classe IV, refratária ao tratamento clínico, apresentava contra-indicaçöes relativas para abordagens cirúrgica e de implante de marcapasso. Realizou-se procedimento intervencionista para injeçäo seletiva de álcool absoluto no 1§ ramo septal da artéria interventricular anterior. O infarto septal provocado acompanhou-se de liberaçäo enzimática, elevaçäo de ST e bloqueio de ramo direito do feixe de His. Näo houve complicaçöes inesperadas, e o gradiente da via ejetiva de ventrículo esquerdo, de 66mmHg, foi imediatamente abolido. Controle ecocardiográfico evidencia manutençäo desse resultado, até o momento, dois meses após o procedimento, em correspodência a marcante alívio sintomático.

Control of heart rate during exercise in health and disease

The authors present a review of their contributions over the last decade to the study of the autonomic control of heart rate during dynamic exercise under physiological and pathological conditions. These studies included the development of new methods for the evaluation of autonomic control of heart rate during dynamic exercise in man. Pharmacological blockade of sympathetic (propranolol) and parasympathetic (atropine) efferent nerves was used to demonstrate differences in time constants and power-dependent relative participation of each division of the autonomic nervous system, as predominant mechanisms responsible for the tachycardia occurring during dynamic exercise. These findings have permitted the use of properly standardized dynamic exercise (discontinuous protocol: step powers, seated position on a bicycle ergometer, 4-min duration), as a simple and noninvasive test for the evaluation of autonomic control of the sinus node. This test has proved to be useful for detecting physiological autonomic adaptations induced by aerobic training, as well as dysfunctions occurring in pathologic conditions such as Chagas' disease and hyperthyroidism.

Detecção de isquemia miocárdica em chagásicos crônicos com precordialgia atípica pelos testes de esforço e Holter / Detection of Myocardial Ischemia in Chagas' Disease Patients with Angina-Like Symptoms by the Effort Test and Holter Monitoring

Objetivo - Investigar a freqüência e as características de alteraçöes isquêmicas miocárdicas detectadas pela eletrocardiografia de esforço e monitorizaçäo eletrocardiográfica contínua (Holter) em pacientes chagásicos com dor precordial. Métodos - Trinta e um pacientes com diagnósticos clínicos e sorológico de doença de Chagas (54,4 ñ 9,6 anos, 51// homens) foram investigados para esclarecimento causal de angina de peito intensa e preocupante a ponto de afetar o padräo de vida e exigir exploraçäo agressiva. A detecçäo de isquemia miocárdica consistiu de 1 teste de esforço máximo e 2) Holter de 24h. Todos os pacientes foram submetidos a cinecoronariografia, ocasiäo em que se executava manobra de hiperventilaçäo controlada para constataçäo de espasmo arterial coronário. Os resultados obtidos com os dois testes (esforço e Holter) foram correlacionados e confrontados com os obtidos durante a cinecoronariografia. Resultados - alteraçöes basais do eletrocardiograma (ECG) impediram a análise do segmento ST em 11 pacientes. Dos restantes, 7(35//) apresentaram angina no teste de esforço. Dois deles (10//) tiveram isquemia miocárdica concomitante, detectando-se coronariopatia orgânica/funcional em ambos (associaçäo positiva, p=0,03): lesöes de 90// na artéria circunflexa e de 50// no trajeto intramiocárdico da descendente anterior esquerda. Nesta última, após hiperventilaçäo, ocorreu espasmo que reduziu em mais de 30// o diâmetro luminal do segmento estenótico, com dor precordial e elevaçäo de ST, que reverteram com nitrato. Durante o Holter (16 pacientes com traçados aproveitáveis), 25// dos indivíduos apresentaram angina do peito, sem qualquer distúrbio arrítmico ou isquêmico concomitante. Isquemia silente ocorreu em 1 paciente (5//) durante o esforço e, em outros (18//), durante o Holter. Sua presença näo foi preditiva de alteraçöes coronárias orgânicas ou funcionais. Näo foram documentadas lesöes significativas nos 11 pacientes cujo ECG näo era passível de análise. Conclusäo - Observou-se importante limitaçäo da aplicabilidade geral dos métodos eletrocardiográficos para detecçäo de isquemia miocárdica nos pacientes chagásicos em decorrência das alteraçöes basais do ECG. Contudo, quando o ECG basal é adequado, o teste de esforço positivo (ST isquêmico, acompanhado de dor precordial) apresentou 100// de valor preditivo para doença arterial coronária orgânica/funcional. Isto ocorreu em pequena, porém näo desprezivel proporçäo desta populaçäo chagásica específica (10//). O teste de Holter näo contribuiu para elucidaçäo da origem da angina do peito em qualquer um dos doentes estudados. Ante a inconsistência dos resultados, o significado o significado clínico e fisiopatológico da isquemia silente na cardiopatia chágasica demanda investigaçäo ulterior

Purpose - To determine the incidence and characteristics of myocardial ischemia, as detected by stress electrocardiography and Holter monitoring in Chagus' patients whose main complaint was precordial pain. Methods - Thirty-one consecutive patients with Chagas' disease diagnosed on the basis of clinical and serological tests, and precordial pain severe enough to warrant cardiac catheterization were studied. Mean age was 54.4 ± 9.6 years, and 51% were males. EKG changes indicative of myocardial ischemia were sought during maximul exercise and also during 24-hour Holter monitoring. The detection of myocardial ischemia by each one of these tests was compared by Fischer exact test, and also correlated to anatomical and functional results of coronary angiography at rest and after standardized hyperventilation for detecting coronary vasospasm. Results - Baseline EKG changes mainly associated with ventricular conduction defects precluded the analysis of the ST segment in 11 patients. Among the other 20 patients, 7(35%) had angina during the exercice test, of whom only 2(10%) showed concomitant ischemic ST changes: one had 90% stenosis in the circumflex branch and the other 50% reduction of luminal diameter in a intramyocardial segment of the leit anterior descending coronary artery, undergoing further 30% constriction after hyperventilation, with pain and ST-elevation that responded to nitrate administration. Thus, a positive correlation between a positive EKG exercise test with accompanying symptoms, and organic/functional coronary artery disease was found (p = 0.03). Holter tracings of good quality were obtained in 16 patients. Angina-like symptoms occurred in 25% of these patients, without concomitant ischemic or dysrhythmic EKG changes. Conversely, silent ischemia was detected in 1 (5%) patient during exercice and in 3 (18%) patients during the Holter monitoring None of these patients had any evidence of organic or functional alterations in the coronary arteries. The absence of significant (> 50%) narrowing of the coronary arteries, t baseline and after hyperventilation, was also documented in the 11 patients in whom no valid EKG tracings were obtained for analysis. Conclusion - EKG-based methods for detecting myocardial eschemia are of limited value in the general population with Chagas' disease presenting with precordial pain, due to the high prevalence of baseline ST changes. The overall incidence of significant coronary artery disease, as detected by angiography, was low but not negligible in this population of Chagas' patients with precordial pain (4%). Nevertheless, a positive EKG test based on ST changes and accompanying pain has a 100% positive predictive accuracy for the presence of organic or functional coronary abnormalities. No additional yield was obtained with Holter monitoring, for the elucidution of the pathophysiology of the precordial pain in Chagas' patients with atypical angina. The significance of episodes of silent ischemia in some of these patients, with angiographically normal coronary arteries, remains to be determined

Depressed respiratory sinus arrhythmia: additional evidence for impairment of vagal activity in human hyperthyroidism

The efferent activity of the parasympathetic component of the autonomic nervous system was evaluated by measuring the magnitude of the respiratory sinus arrhythmia in 3 female patients with hyperthyroidism (Basedow-Graves' disease) before and after treatment. The heart rate variations induced by the test increased in all patients after treatment of thyrotoxicosis (from 15 + or - 2.9 to 28.3 + or - 6.6 beats/min; mean + or - SEM) with propylthiouracil (600 mg/day). This result confirms our previous observations indicating an important and reversible impairment of the efferent vagal activity in human hyperthyroidism

Leg endurance training has no effect on the autonomic control of hearth rate during isometric exercise

1. Heart rate (HR) response to isometric exercise (handgrp) was investigated in 7 normal males of sedentary habits befrore and after endurance training involving the muscles of the lower limbs. Thirteen additional sedentary individuals and 7 middle-distance renners were also studied. Isometric exercise was performed at 100, 75 and 50% of maximum voluntary contraction (MVC) during 10, 20 and 30 s, respectively. Training produced a 15.6 ñ 1.4% (mean ñ SEM) increase in VO2max and a reduction in resting HR from 69 ñ 1.9 to 58 ñ 1.7 bpm. HR was monitored throughout each period of isometric exercise. 2. The pattern of HR response to static effort performed by untrained muscles was comparable before and after training as well as in athletes and sedentary individuals during the first 10 s of contraction, a period during which tachycardia is aminly mediated by vagal release. after the first 10 s, when the sympathetic influence on tachycardia becomes evident, athlets and trained individuals showed a sligh but nonsignificant tendency toward lower HR increases. 3. These results do not demonstrate any appreciable alteration in the efferent activity of autonomic components induced by aerobic training of the leg muscles when isometric exercise is performed with untrained muscles

Use of isometric exercise to demonstrate cardiac parasympathetic impairment in the digestive form of Chagas' disease

Standardized handgrip at 100% of maximal voluntary capacity was used to study heart rate responses to ismetric exercise in patients with the digestive form of Chagas" disease. The chronotropic responses of the group were significantly lower (P < 0.001) than tyhose exhibited by control subjects, and comparable to those observed in a group of cardiac chagasic patient. these results show that severe impairment of autonomic control of the heart may occur in chagasic patients apparently having only digestive tract involvement