Effect of Cardiac Resynchronization Therapy on Inflammation in Congestive Heart Failure: A Review.

Congestive heart failure is associated with increased levels of several inflammatory mediators, and animal studies have shown that infusion of a number of cytokines can induce heart failure. However, several drugs with proven efficacy in heart failure have failed to affect inflammatory mediators, and anti-inflammatory therapy in heart failure patients has thus far been disappointing. Hence, to what extent heart failure is caused by or responsible for the increased inflammatory burden in the patient is still unclear. Over the past couple of decades, resynchronization therapy with a biventricular pacemaker has emerged as an effective treatment in a subset of heart failure patients, reducing both morbidity and mortality. Such treatment has also been shown to affect the inflammation associated with heart failure. In this study, we review recent data on the association between heart failure and inflammation, and in particular how resynchronization therapy can affect the inflammatory process.

Importance of characteristics and modalities of physical activity and exercise in the management of cardiovascular health in individuals with cardiovascular risk factors: recommendations from the EACPR. Part II.

In a previous paper, as the first of a series of three on the importance of characteristics and modalities of physical activity (PA) and exercise in the management of cardiovascular health within the general population, we concluded that, in the population at large, PA and aerobic exercise capacity clearly are inversely associated with increased cardiovascular disease risk and all-cause and cardiovascular mortality and that a dose­response curve on cardiovascular outcome has been demonstrated in most studies. More and more evidence is accumulated that engaging in regular PA and exercise interventions are essential components for reducing the severity of cardiovascular risk factors, such as obesity and abdominal fat, high BP, metabolic risk factors, and systemic inflammation. However, it is less clear whether and which type of PA and exercise intervention (aerobic exercise, dynamic resistive exercise, or both) or characteristic of exercise (frequency, intensity, time or duration, and volume) would yield more benefit for each separate risk factor. The present paper, therefore, will review and make recommendations for PA and exercise training in the management of cardiovascular health in individuals with cardiovascular risk factors. The guidance offered in this series of papers is aimed at medical doctors, health practitioners, kinesiologists, physiotherapists and exercise physiologists, politicians, public health policy makers, and individual members of the public. Based on previous and the current literature overviews, recommendations from the European Association on Cardiovascular Prevention and Rehabilitation are formulated regarding type, volume, and intensity of PA and regarding appropriate risk evaluation during exercise in individuals with cardiovascular risk factors.

A young man with acute dilated cardiomyopathy associated with methylphenidate.

An 18-year-old obese man with a body mass index of 40, diagnosed with attention-deficit hyperactivity disorder and treated with methylphenidate (Concerta) was acutely admitted to hospital with hypoxia and dyspnoea. On investigation signs of liver-, renal-, and heart-failure were found. Noradrenalin infusion was started. Echocardiography showed dilated left ventricle and an ejection fraction (EF) of 25%. Liver function improved, noradrenalin and dobutamine were tapered, but three days after admission a new echocardiography showed an EF of 10%. The patient was transferred to the National Hospital (Rikshospitalet, Oslo), where intensified treatment including intra aortic balloon pump (IABP) was instituted. Cardiac function improved, and 3 weeks later the IABP was disconnected. EF at this point was 15%. The patient was denied heart transplantation due to various cofactors. The investigation concluded with a probable relationship between his cardiomyopathy and the use of methylphenidate (Concerta).

Massive pulmonary embolism with cardiac arrest treated with continuous thrombolysis and concomitant hypothermia.

This case report describes the clinical course in a 49-year-old man with repeated cardiac arrests due to massive pulmonary embolism. He was successfully treated with intravenous tenecteplase followed by catheter-based alteplase infusion during external cooling. The case illustrates that vitally important bolus thrombolytic therapy may be continued as catheter-based treatment along with hypothermia without significant bleeding complications.

Physical activity for primary and secondary prevention. Position paper of the Working Group on Cardiac Rehabilitation and Exercise Physiology of the European Society of Cardiology.

There is now clear scientific evidence linking regular aerobic physical activity to a significant cardiovascular risk reduction, and a sedentary lifestyle is currently considered one of the five major risk factors for cardiovascular disease. In the European Union, available data seem to indicate that less than 50% of the citizens are involved in regular aerobic leisure-time and/or occupational physical activity, and that the observed increasing prevalence of obesity is associated with a sedentary lifestyle. It seems reasonable therefore to provide institutions, health services, and individuals with information able to implement effective strategies for the adoption of a physically active lifestyle and for helping people to effectively incorporate physical activity into their daily life both in the primary and the secondary prevention settings. This paper summarizes the available scientific evidence dealing with the relationship between physical activity and cardiovascular health in primary and secondary prevention, and focuses on the preventive effects of aerobic physical activity, whose health benefits have been extensively documented.

Secondary prevention through cardiac rehabilitation: position paper of the Working Group on Cardiac Rehabilitation and Exercise Physiology of the European Society of Cardiology.

The purpose of this statement is to provide specific recommendations in regard to evaluation and intervention in each of the core components of cardiac rehabilitation (CR) to assist CR staff in the design and development of their programmes; the statement should also assist health care providers, insurers, policy makers and consumers in the recognition of the comprehensive nature of such programmes. Those charged with responsibility for secondary prevention of cardiovascular disease, whether at European, at national or at individual centre level, need to consider where and how structured programmes of CR can be delivered to the large constituency of patients now considered eligible for CR.

Aquatic mosses as a monitoring tool for 137Cs contamination in streams and rivers-a field study from central southern Norway.

Mosses are frequently used as biomonitors for trace element pollution in the aquatic environment. The purpose of this study was to assess their usefulness as a tool in monitoring and in regional surveys of radioactive contamination. Specimens of the aquatic mosses, Fontinalis antipyretica and F. dalecarlica, were transplanted from non-contaminated areas to streams and rivers in the Norwegian Jotunheimen Mountains and neighbouring lowland areas that had received radioactive fallout after the Chernobyl accident. Equilibrium concentrations of 137Cs in the exposed mosses were reached after a few weeks. Two series from 20 streams in 1994 and 1996 show linear correlations between activities in water and moss samples and biomagnification ratios of 10(4) - 10(5). We conclude that mosses are better suited for monitoring purposes than water samples, because they provide values integrated over weeks while the radioactivity in surface waters can be subject to rapid variations according to hydrological events. The activity concentrations in aquatic mosses can be easily measured with good precision even when aqueous concentrations are below the limit of detection. Use of aquatic mosses also reduces the logistic problems of transporting large volumes of water, especially in areas inaccessible by road.

Gender differences in systolic left ventricular function in hypertensive patients with electrocardiographic left ventricular hypertrophy (the LIFE study).

Echocardiography was performed in 944 untreated hypertensive patients (391 women and 553 men, mean age 66 years) who had electrocardiographic left ventricular (LV) hypertrophy at baseline in the Losartan Intervention For End point reduction in hypertension (LIFE) study to evaluate gender-associated differences in systolic LV function. Women had significantly lower diastolic blood pressure (175/97 vs 173/99 mm Hg) and body surface area and a higher body mass index (all p < 0.01). Women also had higher LV ejection fraction (EF), endocardial and midwall fractional shortening (63% vs 60%, 35% and 33%, and 16% vs 15%, respectively, all p < 0.01), higher stress-corrected midwall fractional shortening (98% vs 96%, p < 0.05), and lower circumferential end-systolic wall stress (178 vs 187 kdynes/cm(2), p < 0.01). There was no difference in age or LV mass indexed for height(2.7), but relative wall thickness was higher in women (0.42 vs 0.41, p < 0.05). In multiple regression analyses: (1) EF and endocardial fractional shortening were 2% to 3% higher in women than men, independent of the effects of LV stress, body mass index, and height (multiple r = 0.77 and 0.75, respectively, gender p < 0.02 in both models); (2) midwall fractional shortening was 0.5% higher in women, independent of the effects of age, body mass index, circumferential end-systolic stress, and absence of diabetes (multiple r = 0.36, p = 0.014 for gender); and (3) stress-corrected LV midwall fractional shortening was 2% higher (p = 0.004) in women, independent of the effects of age, height, heart rate, body mass index, and diabetes (multiple r = 0.33). Thus, female gender is an independent predictor of higher systolic LV function in hypertensive patients with electrocardiographic LV hypertrophy.

Diltiazem does not increase ventricular fibrillation threshold during hypothermia.

This study was designed to investigate whether the calcium channel blocker diltiazem affects the threshold for ventricular fibrillation during hypothermia in dogs. Ten dogs were cooled from 37 to 25 degrees C and rewarmed to 37 degrees C. The threshold for ventricular fibrillation was determined at body temperatures 37, 34, 31, 28 and 25 degrees C by programmed electrical stimulation using a stimulation protocol which involved application of maximal five extrastimuli. At 25 degrees C, six dogs were given an i.v. bolus dose of 100 micrograms.kg-1 followed by a continuous infusion of 100 micrograms.kg-1.h-1 of diltiazem hydrochloride. The other four dogs, were given no drugs at 25 degrees C and served as a control group. The dogs were rewarmed, and the stimulus protocol was performed at the same temperatures as during cooling. Cooling from 37 to 25 degrees C reduced the threshold for ventricular fibrillation in both groups. Heart rate were reduced, monophasic action potential duration at the apex and base of the heart increased from 167 +/- 5 ms to 469 +/- 17 ms and from 164 +/- 5 ms to 466 +/- 17 ms, respectively, when the temperature was reduced. The ventricular effective refractory period increased from 176 +/- 9 ms at 37 degrees C to 472 +/- 15 ms at 25 degrees C. Cooling increased QRS time on the ECG from 55 +/- 4 ms to 138 +/- 13 ms. Addition of diltiazem at 25 degrees C did not affect the threshold for ventricular fibrillation during rewarming. Further, diltiazem at 25 degrees C did not affect the heart rate or refractoriness.(ABSTRACT TRUNCATED AT 250 WORDS)

Effect of bretylium tosylate on ventricular fibrillation threshold during hypothermia in dogs.

How bretylium tosylate affected the ventricular fibrillation threshold, electrophysiological parameters, and plasma catecholamine levels during hypothermia in dogs was studied. Threshold for ventricular fibrillation was determined by programmed electrical stimulation using a stimulation protocol that involved applying a maximum of five extrastimuli at body temperatures 37, 34, 31, 28, and 25 degrees C, and at the same temperatures during rewarming. Electrocardiogram, epicardial monophasic action potentials (MAP), and electrograms were recorded, and ventricular effective refractory period (VERP) was determined at each of the above temperatures. In one group (n = 7), a bolus dosage of bretylium tosylate (BT), 6 mg/kg body wt, was administered at 25 degrees C before rewarming. Another group (n = 4) was exposed to cooling and rewarming without addition of BT. Cooling to 25 degrees C reduced ventricular fibrillation threshold linearly, reduced heart rate, increased VERP and MAP, and slowed myocardial conduction velocity in both groups. There was no overall increase in plasma catecholamine levels during cooling. Addition of BT at 25 degrees C increased ventricular fibrillation threshold during rewarming compared with cooling. Addition of BT at 25 degrees C increased VERP by +/- 32 milliseconds and the corrected JT time by 0.06 +/- 0.02 seconds. VERP and JTc increased during rewarming with BT compared with cooling with no drug. BT had no effect on conduction velocity, and plasma catecholamine levels were not reduced. The antiarrhythmic effect of BT during hypothermia was attributed to an increased wavelength of refractoriness by its increase in the refractory period. This increased wavelength of refractoriness may prevent excitable gaps or increase circuit pathway in the setting of reentry arrhythmias.

Prevention of some hypothermia induced electromechanical changes by calcium channel blockade.

OBJECTIVE: Cooling induces electromechanical changes in the heart. The aim of the study was to examine how the calcium channel blocker, nisoldipine (NIS), altered these changes compared to those induced by other drugs that shorten action potential duration such as tetrodotoxin and nicorandil. METHODS: Guinea pig papillary muscle action potentials and developed force were recorded using the conventional microelectrode technique and a force transducer. Restitution of action potential duration was determined by introducing extrastimuli at progressively longer diastolic intervals from 40 to 9000 ms. Preparations were divided into four groups: (1) no drug (control); (2) 1 microM tetrodotoxin, a sodium channel blocker; (3) 1 mM nicorandil, an ATP sensitive potassium channel activator; and (4) 1 microM nisoldipine (n = 6 in each group). Action potential duration and developed force were recorded after addition of drug at 37 degrees C, and at each 1 degree C change in temperature during cooling to 27 degrees C. The restitution protocol was performed at 37 degrees C and 27 degrees C. RESULTS: Tetrodotoxin had no effect on action potential duration at 90% of repolarisation (APD90) while nisoldipine and nicorandil greatly shortened APD90. Cooling from 37 degrees to 27 degrees C with nisoldipine produced less hypothermia induced lengthening in APD90 than in the other group. Developed force did not increase with reduction in temperature in the presence of nisoldipine. The range of premature action potential durations was defined as the difference in APD90 at diastolic interval of 40 and 100 ms. This range decreased with nisoldipine in contrast to the marked increases that occurred in the other groups during cooling. CONCLUSIONS: Increased intracellular Ca2+ might be responsible for the hypothermia induced increase in APD90, developed force, and range of premature action potential durations, since calcium channel blockade, which prevents an increase in intracellular Ca2+, greatly reduced these changes. The reduced range of premature action potential durations may reduce dispersion of ventricular refractoriness, and hence be expected to decrease hypothermia induced arrhythmias.

Ambulatory electrocardiographic findings in top athletes, athletic students and control subjects.

Aim of the present study was to evaluate 24 h electrocardiographic recording in 30 top athletes, 30 athletic students and 30 sedentary control subjects. Each group consisted of 15 males and 15 females and were matched for age (about 24 years). Training was not allowed during the recording. Top athletes had the lowest diurnal and nocturnal heart rate, but the difference between top athletes and athletic students was far less pronounced than between athletic students and controls. This may indicate that bradycardia reaches a lower limit with moderate degrees of training. Atrioventricular (AV) block II was found in 3 top athletes and 4 athletic students and in none of the subjects, the longest pause being 2.4 s in both athletic groups. Most episodes occurred during night and nearly all were Mobitz type I. In all cases of AV block II the QRS complexes were narrow and AV block III did not occur. SA block was found in 3 top athletes, 1 athletic student and 1 control subject, the longest pause being 3.1, 2.9 and 1.9 s, respectively. Ventricular premature beats were rare in all groups and complex ventricular arrhythmias were not found. Half of the subjects were in Lown class 0, the other half in Lown class 1. Supraventricular premature beats were also scarce and most frequent in top athletes, followed by athletic students and sedentary controls (2.0, 1.0, 0.7 beats/h, respectively).

Electrocardiographic findings of repolarization in athletic students and control subjects.

We have investigated resting electrocardiograms in 1,299 athletic students and 151 sedentary control subjects. ST elevations were more frequent and pronounced in athletes compared to controls, whereas there was no difference in ST depressions. Athletes with ST elevation above 2 mm were characterized by lower heart rate, increased PQ duration, increased indices of left, right and septal hypertrophy and T wave amplitude. Negative T waves in 3 of 6 precordial leads, V3-6, were found in 1.5% of athletes and 0.7% of controls, and in V5-6 in 0.4% of athletes and none of controls, the differences not being significant. Athletes had significantly more often a T wave axis between +30 and -180 degrees and less often a frontal T wave axis between +30 and +180 degrees. The mean QRS-T angle was significantly greater in athletes, and U waves were more prominent. Analyzing athletes with QTc below and above 0.430 s, we found an increased heart rate, QRS duration, ST depression and a more pronounced left QRS axis in the group with QTc above 0.430 s. There was a positive correlation between QTc and heart rate which indicates that the use of Bazett's formula leads to an underestimation of QTc at lower heart rates and to an overestimation at higher heart rates. Bazett's formula does not provide an adequate correction for heart rate and should be used with caution. Our finding of a prolonged QTc in athletes compared to control subjects in spite of lower heart rate in the athletic group demonstrates that a real QTc prolongation exists in athletes.

Left ventricular mass and cardiovascular reactivity in young men.

The relation between left ventricular wall thickness and mass, arterial plasma catecholamines, and blood pressure at rest and during a mental arithmetic challenge and a cold pressor test was examined in 69 healthy men 19 years of age. The subjects were recruited from the 1st (n = 21), 50th (n = 26), and 99th (n = 22) percentiles in mean blood pressure. All underwent echocardiography to determine mean wall thickness and left ventricular mass. Continuous intra-arterial blood pressure, electrocardiogram, and arterial sampling of plasma catecholamines were performed after 30 minutes of supine rest, during a 5-minute mental arithmetic challenge, and during a 1-minute cold pressor test. Stepwise multiple-regression analyses considering mean wall thickness and left ventricular mass as the dependent variables were applied. Intra-arterial systolic blood pressure (r = .54, P < .0001) and arterial plasma epinephrine (r = .31, P = .009) after 30 minutes of supine rest were the only independent explanatory variables of mean wall thickness (multiple R2 = .33, P < .0001). Blood pressure at screening and during mental stress and cold pressor tests were not independent explanatory variables. The present study suggests that resting arterial blood pressure and plasma epinephrine may be of importance for development of left ventricular hypertrophy.

Mechanisms for hypothermia-induced increase in contractile force studied by mechanical restitution and post-rest contractions in guinea-pig papillary muscle.

Lowering myocardial temperature increases contractile force, presumably by increasing intracellular calcium content. To study the mechanisms behind this, we compared the effects of some known inotropic interventions with hypothermia on mechanical restitution and post-rest contractile force in isolated guinea-pig papillary muscles. In four groups (n = 6 per group), the effects of: (1) reducing the ability for Na/Ca exchange to extrude Ca2+ (a) by increasing [Na+]i with ouabain or (b) by increasing [Ca2+]o; and (2) activation of calcium channels with Bay-K 8644, were compared with lowering temperature from 37 to 27 degrees C. Normally (at 37 degrees C and 2 mM CaCl2), mechanical restitution could be described by a rapid recovery phase with a time constant between 180 and 220 ms, followed by a slowly decaying phase with a time constant between 5000 and 8000 ms and post-rest contractions (1-10 min rest) were markedly depressed compared to steady-state contractions. Steady-state developed force was markedly increased at 27 degrees C, after 1 microM ouabain, 6 mM CaCl2 or 0.1 microM Bay-K 8644. At 27 degrees C the rapid recovery phase of restitution was delayed while the slowly decaying phase was not affected. Ouabain and increased [Ca2+]o caused elevation of the slowly decaying phase of restitution and markedly attenuated the post-rest depression of developed force, which may be attributed to a reduced diastolic extrusion of Ca2+ via the Na/Ca exchanger. Hypothermia and Bay-K 8644 on the other hand, augmented this post-rest depression. Hence, this study suggests that increased Ca2+ influx due to delayed inactivation of calcium channels may account for the increased developed force during hypothermia rather than reduced diastolic extrusion of Ca2+ via the Na/Ca exchanger.

Effects of temperature on cycle length dependent changes and restitution of action potential duration in guinea pig ventricular muscle.

OBJECTIVE: The aim was to investigate the effects of temperature on cycle length dependent changes of action potential duration and on restitution of action potential duration. METHODS: Guinea pig papillary muscle action potentials were recorded using conventional microelectrode techniques. Action potential duration was measured at cycle lengths ranging from 500 to 2000 ms at both 27 degrees C and 37 degrees C. Restitution of action potential duration was determined by introducing an extra stimulus at progressively longer diastolic intervals from 40 to 9000 ms at pacing cycle lengths of 500, 1000, and 2000 ms. RESULTS: At 37 degrees C, action potential duration measured at 90% of repolarisation (APD90) during continuous pacing and the maximum value of APD90 achieved during restitution (APD90pl) decreased by 18(SEM 6) ms (n = 7) and 24(7) ms (n = 6), respectively, when pacing cycle length was reduced from 2000 to 500 ms. At 27 degrees C, the magnitude of the shortening of APD90 and APD90pl observed when pacing cycle length was similarly reduced was greater than at 37 degrees C, ie, 143(21) ms (n = 6) and 115(11) ms (n = 6), respectively. Thus the relation for restitution of action potential duration shifted downwards with reduction in pacing cycle length, and the magnitude of this shift was greater at 27 degrees C than at 37 degrees C. The difference between APD90 at the shortest diastolic interval (40 ms) and at diastolic interval of 100 ms (range of premature action potential durations) was much greater at 27 degrees C than at 37 degrees C at all three pacing cycle lengths. CONCLUSIONS: Reduction in temperature magnifies the cycle length dependent changes in action potential duration both during abrupt changes in cycle length, as with an extra stimulus, and during changes of steady state cycle length. This may indicate a greater dispersion of premature action potential durations during hypothermia, and hence predispose to hypothermia induced arrhythmias.

Electrocardiographic findings of left, right and septal hypertrophy in athletic students and sedentary controls.

We have previously demonstrated increased voltage of septal, right and left ventricular depolarization in 1,299 athletic students compared to 151 sedentary controls. In the present investigation we have studied the prevalence of hypertrophy and the correlation between hypertrophy and other ECG findings. An increase of Q waves of more than 0.2 mV was associated with increased indices of right and left ventricular hypertrophy. Right ventricular hypertrophy was associated with an increased prevalence of incomplete right bundle branch block and increased parameters of septal and left ventricular hypertrophy. Left ventricular hypertrophy was associated with increased indices of septal and right ventricular hypertrophy and with bradycardia. Furthermore, left ventricular hypertrophy was characterized by ST elevation and increased T wave amplitudes, but not by repolarization abnormalities. Thus, our data point to a harmonious hypertrophy. Based on our findings we suggest the following normal limits in young people (20-30 years) according to the 97.5 percentile regarding the Sokolow index: for athletic students 5.3 (males) and 3.6 mV (females), for sedentary controls 4.0 (males) and 3.6 mV (females). It remains to be clarified whether these values are also valid in top athletes.

Electrocardiographic and echocardiographic findings in top athletes, athletic students and sedentary controls.

Thirty top level athletes, 30 athletic students and 30 sedentary controls underwent electrocardiographic and echocardiographic investigation. Resting ECG in athletes showed increased indices of hypertrophy compared to controls. The echocardiographic examination demonstrated an increase in left ventricular mass (LVM) of 47% in top athletes and 23% in athletic students compared to controls. The relationship between wall thickness and diameter was similar in all groups, as were parameters of systolic and diastolic left ventricular function at rest. There was no correlation between LVM assessed by echocardiography and ventricular ectopic activity assessed by Holter monitoring in this normotensive population. Highly significant correlations between ECG and echocardiographic parameters of hypertrophy were demonstrated.

Electrocardiographic findings of heart rate and conduction times in athletic students and sedentary control subjects.

We have investigated resting electrocardiograms in 1,299 athletic students and 151 sedentary control subjects. Bradycardia was significantly more common in athletes. The athletic group was divided according to a heart rate < 50, 50-100, and above 100 beats/min. Atrioventricular conduction time, prevalence of ectopic beats and other rhythms, parameters of right and left ventricular hypertrophy, ST elevation, and T wave amplitude were increased in the sinus bradycardia group. A significant negative correlation was found between heart rate and PQ duration in athletes. In the sinus tachycardia group, the PQ duration was shorter and the ST depression more prominent than in the other groups. The subjects were also divided according to PQ > or = 0.22, 0.21-0.12, and < 0.12 s. Parameters of left ventricular hypertrophy were markedly increased in athletes with PQ > or = 0.22 s, while the heart rate was only slightly decreased, suggesting an association between prolonged atrioventricular conduction time and left ventricular hypertrophy. Incomplete right bundle branch block was associated with a lower heart rate, increased duration of QRS and QTC, voltage of precordial Q waves, indices of right ventricular hypertrophy, and negative T waves. These findings are typical of right ventricular hypertrophy, indicating a close relation of incomplete right bundle branch block to right ventricular hypertrophy.

Electrocardiographic findings according to level of fitness and sport activity.

We have investigated 52 ECG parameters in 1,299 athletes and 151 control subjects. Data on fitness were available in 840 athletes. They were split in three groups according to level of fitness and compared with each other and the control group with regard to the ECG findings. The most marked findings with increasing fitness were lower heart rate, increased prevalence of bradycardia, increased precordial ST segment elevation, and increased T wave amplitudes. Only slightly increased parameters of right and left ventricular hypertrophy were found. A highly significant correlation was found between fitness and heart rate, while no such correlation was found between fitness and the Sokolow index. The athletes were subdivided according to sports activity, and ECG parameters were compared in endurance athletes, ball players, strength athletes, gymnasts, and controls. Apart from a lower heart rate in endurance athletes and ball players as compared with strength athletes and gymnasts, few differences were found between the athletic groups. The heart rate is the most important parameter reflecting level of fitness and sports activity. The differences in ECG findings are relatively minor and do not distinguish type of sport activity.