Heart rhythm characterisation during unexplained transient loss of consciousness in dogs.

The identification of the heart rhythm during an episode of transient loss of consciousness (TLOC) is considered the reference standard method to elucidate the underlying aetiology. This study aimed to characterise heart rhythm in dogs during TLOC using Holter and external loop recorder monitoring. We retrospectively reviewed 24-h Holter monitoring and external loop recorder tracings from 8084 dogs. Heart rhythms from dogs that experienced TLOC during the recording was analysed to identify rhythm disturbances that occurred during episodes of TLOC. Electrocardiograms (ECGs) were subsequently categorised into Type 1 (ventricular arrest), Type 2 (sinus bradycardia), Type 3 (no/slight rhythm variations), and Type 4 (tachycardia). Transient LOC was documented in 92 dogs over 230 episodes of TLOC. Percentage of cases with ECGs compatible with each classification were as follows: 72.1%, Type 1; 6.1%, Type 2; 20.9%, Type 3; and 0.9%, Type 4. Cardiac rhythm during the TLOC could have been a consequence of a neurocardiogenic mechanism in 46.7% cases, while intrinsic rhythm disturbances of the sinus node or of the atrioventricular node were diagnosed in 31.5% cases. In two cases, tachycardia was the possible cause of the TLOC. ECG patterns in dogs presenting with multiple TLOC episodes were completely reproducible during each episode. TLOC in dogs was primarily caused by ventricular arrest. Most dogs with TLOC had electrocardiographic finding suggestive of a reflex or neurally-mediated syncope, but one third had an ECG more suggestive of a conduction disorder. Distinguishing these two entities could help inform diagnostic, therapeutic, and prognostic plans.

Effects of immune system status on long-term results of cardiac resynchronization therapy.

AIM: Cardiac resynchronization therapy (CRT) is an effective therapy for patients with reduced systolic function and enlarged QRS. Recently, some Authors have demonstrated that the presence of positive antinuclear antibodies (ANAs) may play a role in the development of heart failure in a population of patients implanted with PM. METHODS: We investigated the effect of positive ANAs in 90 patients (mean age 71±8 years) implanted with a CRT device in our Centre between May 2010 and June 2013. To assess for immunologic contribution to CRT outcome, patients were divided into positive and negative ANAs (ANA +, ANA -), considering as positive patients with an ANAs dilution > 1:80. The primary endpoint was constituted by a combined endpoint of death or first hospitalization for heart failure; secondary endpoints were constituted by: 1) incidence of first hospitalization for heart failure; and 2) total cause mortality. RESULTS: After a mean follow-up of 1200 days, primary endpoint occurred in 11 patients (30%) of ANA+ group and in 8 patients (15.1%) of ANA-group. The significant difference is due to difference in heart failure events (27% vs. 11.3%, P<0.05), whilst difference in total mortality did not reach statistical significance (10.8% vs. 3.8%). CONCLUSION: Immune status seems to play a role in patients with congestive heart failure. If this immunological alteration is a determinant or a consequence of heart failure remains unclear.

Efficacy of ranolazine in a patient with idiopathic dilated cardiomyopathy and electrical storm.

A case of idiopathic dilated cardiomyopathy with an arrhythmic storm refractory to the usual antiarrhythmic therapy will be reported. The idiopathic structural heart disease of the patient is a vulnerable anatomic substrate in itself, for electrical instability and reentry mechanism, because of heterogeneous areas of scarred myocardium and low left ventricle ejection fraction. In this case, the ranolazine administration was safe and effective for the prevention of further electrical storms.

The importance of reducing heart rate in cardiovascular diseases: effects of Ivabradine.

Heart rate is a major determinant of cardiac output, myocardial oxygen consumption and coronary blood flow under physiological and pathological conditions. Experimental and clinical data have demonstrated that heart rate reduction is the main mechanism for reducing ischemia, improving left ventricular function, decreasing the risk of plaque rupture and post myocardial infarction mortality. Nowadays betablockers are the best class of drugs that can lower heart rate in patients with cardiovascular diseases, but sometimes their use is limited by some contraindications. Ivabradine is a new drug that reduces the firing rate of pacemaker cells in the sinoatrial node through a different mechanism with respect to betablockers. The purpose of this review is to investigate the main trials that support Ivabradine adoption in clinical practice.

Ventricular tachycardia in English bulldogs with localised right ventricular outflow tract enlargement.

OBJECTIVES: To describe the electrocardiographic characteristics of ventricular tachycardia arising from the right ventricular outflow tract and the particular association between this arrhythmia and the presence of localised right ventricular outflow tract enlargement in English bulldogs. METHODS: Five English bulldogs were referred with a history of syncope or cardiogenic shock. In all dogs, 12-lead surface ECG, thoracic radiograph and echocardiography were collected. In all but one dog 24-hours Holter monitoring and signal-averaged ECGs was examined and in one dog electrophysiological study and radiofrequency catheter ablation of the VT substrate was performed. RESULTS: Documented arrhythmias included a single sustained monomorphic wide QRS tachycardia in four dogs, and an alternans of two different monomorphic forms in one dog. Mean QRS duration during tachy-cardia was 91·6 ±9·83 milliseconds. QRS complexes manifested a left bundle branch block morphology and an inferior axis (81 ±13·73°). R wave notching was present in the caudal (inferior) leads in three tachy-cardias. Lead I was negative in 3 of 6, positive in 1 of 6 and isodiphasic in 2 of 6. Lead aVL was negative in 5 of 6 and positive in 1 of 6. Signal-averaged electrocardiograms revealed late potentials in three dogs. Echocardiography showed a localised right ventricular outflow tract enlargement in all dogs. Cardiac map-ping established two sites of origin of ventricular tachycardia within the right ventricular outflow tract in one dog: caudal free-wall and cranial-septal. CLINICAL SIGNIFICANCE: The presence of a localised right ventricular outflow tract enlargement and ventricular tachycardia with left bundle branch block morphology could suggest segmental arrhythmogenic right ven-tricular cardiomyopathy in the English bulldog.

[Role of inflammation mediators in the pathogenesis of heart failure]. / Ruolo dei mediatori dell'infiammazione nella patogenesi dello scompenso cardiaco.

A number of factors are involved in congestive heart failure pathogenesis. Among these, inflammatory mediators could have a crucial role. Patients with congestive heart failure show increased plasma levels of "proinflammatory cytokines", in particular tumor necrosis factor-alpha and interleukin-6. Clinical and experimental models have demonstrated that these cytokines induce left ventricular dysfunction, pulmonary edema, ventricular remodeling, skeletal muscle abnormalities, myocyte apoptosis and endothelial dysfunction, suggesting the possibility that increased plasma concentration of cytokines could not be just an epiphenomenon, but an effective pathogenetic mechanism of disease progression. Additional inflammatory proteins involved in the acute phase response could play a part in the pathogenesis of heart failure. Pentraxin 3 is a prototypical long pentraxin, structurally related, although with different functions, to C-reactive protein, is produced by immune system cells, fibroblasts and particularly by cardiac endothelial cells and myocytes, as demonstrated in murine and human models. Its synthesis is rapidly induced after exposition to bacterial lipopolysaccharide and proinflammatory cytokines, as interleukin-1beta and tumor necrosis factor-alpha. In heart diseases, pentraxin 3 could be involved in the acute local inflammatory response to myocardial injury (e.g. necrosis) and in heart failure pathogenetic mechanisms, but its exact role is not yet settled. Defining the specific part played by these molecules in the pathogenesis of heart failure could lead to new therapeutic approaches in the treatment of cardiac insufficiency.

A rationale for the use of beta-blockers as standard treatment for heart failure.

BACKGROUND: Cardiac sympathetic activation is one of the major and earlier changes observed in patients with heart failure. Its relation to the severity of the disease and its independent prognostic value show that it may directly contribute to the progression of heart failure. beta-Blockers are the most effective tool to counteract the untoward effects of sympathetic activation on the cardiovascular system. METHODS AND RESULTS: We reviewed the results of the placebo-controlled, double-blind studies about the effects of beta-blockers in patients with heart failure. These studies have involved almost 10,000 patients to date and have consistently shown that the long-term administration of beta-blockers is associated with a highly significant improvement in both left ventricular function and prognosis of the patients with heart failure. The evidence supporting the use of beta-blockers now equals or even surpasses that of angiotensin-converting enzyme inhibitors; therefore beta-blockers should be considered part of standard therapy. Issues that remain unclarified include the mechanisms through which beta-blockers may improve cardiac function and their tolerability and efficacy in specific groups of patients (such as those with asymptomatic left ventricular dysfunction, severe heart failure, the elderly, or those with left ventricular diastolic dysfunction). It is not currently clear whether the pharmacologic differences between individual beta-blockers are clinically relevant. If they are, the potential for even greater benefit with certain agents exists. It is hoped that these issues will be clarified by the results of ongoing multicenter trials.

Maximal and submaximal exercise testing in heart failure.

Although reduced exercise capacity is the main complaint of patients with congestive heart failure (CHF), the best method to measure it remains controversial. Peak VO2, obtained using maximal exercise testing, is the most accurate measure of maximal functional capacity. It is related to peak exercise cardiac output and is one of the most important independent variables for the prognostic assessment of patients with CHF. It has, however, a low sensitivity for measurement of changes induced by therapy and is poorly related to everyday physical activity, patient symptoms, and quality of life. The anerobic threshold may also be regarded as a parameter of maximal functional capacity. Its value is mainly indirect, because it shows that the patient is performing a maximal effort limited by the cardiovascular system. The VO2 kinetics at the start and at the end of exercise are probably more related to patient symptoms, but it is unresolved which protocols and parameters might best be used to study this aspect of exercise performance. Duration of a submaximal exercise at a constant work rate and the distance walked during a 6-min walking test are gaining wide popularity as parameters of submaximal performance. However, when these exams are carried out up to exhaustion in patients with severe functional limitation, they may involve attainment of the anerobic threshold and therefore their clinical meaning may be similar to the one of a maximal exercise test. Moreover, tests based on the assessment of submaximal exercise capacity have been useful for assessment of therapy in single-center trials but have been often inadequate in multicenter trials.

Effects of neurohormonal antagonism on symptoms and quality-of-life in heart failure.

Increased mortality and reduced functional capacity are the two main characteristics of chronic heart failure. Activation of the renin-angiotensin and sympathetic systems has a primary role in the progressive worsening of heart failure and increased mortality of patients. In addition, both systems may be important in the pathogenesis of exercise intolerance, although there is only a weak relationship between neurohormonal activation and exercise capacity. While neurohormonal antagonists, such as angiotensin-converting enzyme (ACE) inhibitors and beta-blockers, consistently improve the prognosis of patients with heart failure, their effects on exercise tolerance have often been less significant. This problem has been emphasized by the introduction of beta-blockers for the therapy of heart failure. Beta blockade results in a significant improvement in left ventricular function during rest and exercise. However, the reduction in chronotropic response to exercise as well as the metabolic changes caused by these agents in skeletal muscle may result in an apparent lack of change in maximal functional capacity. This effect is particularly important with the new third generation non-selective beta-blockers. The pronounced anti-adrenergic activity of these compounds accounts for their greater negative chronotropic effect and relates to the lack of improvement in peak oxygen consumption (VO2). Submaximal exercise testing can be used to assess changes induced by these agents. However, even the six-minute walk test may act as an almost maximal test in patients with advanced heart failure: moreover, the measurement of submaximal exercise duration may be sensitive enough to detect changes in single-centre trials, but not in multicentre trials. To date, direct assessment of symptoms by both patient and physician is still the most sensitive tool to monitor changes in functional status with non-selective beta-blockers. Thus, an accurate method of measuring patients' symptoms, in addition to the clinical examination, is still necessary when neurohormonal antagonists are used in patients with chronic heart failure.

Ion retention by immobilized pH matrices.

The effect of the interaction between polyacrylamide matrices containing covalently bound acidic and basic residues and free ions was indirectly evaluated from the width of the residual salt fronts after electrophoresis under standard conditions. Around neutrality the front width is larger than at alkaline, and much larger than at acidic pH, and in all instances much higher for anions than for cations. The width decreases faster with the buffering power of the matrix than with its ionic strength. After about 5000 V x h, the migration of the salt front is very slow, and becomes negligible when diffusion is prevented. When inadequately buffered by the matrix, H+ and OH(-)--comigrating with anions and cations--increase the conductivity within the salt front and drastically lower the electrical field strength.

Immunoblotting from immobilized pH gradients. The case of alpha 2-macroglobulin.

Guidelines for effective blotting of proteins from immobilized pH gradients with a soft polyacrylamide matrix (e.g. T% = 3) include: thick (1 mm) IPG slabs, electrotransfer in a buffer tank in the presence of 0.1% SDS, nitrocellulose of the sturdiest type, thorough removal of all IPG fragments before further processing of the membrane. For alpha 2-M, IPG on a 4-6.5 gradient followed by enzyme-linked immunodetection allows the recognition of a complex pattern with several bands centered around pI 5.1. The procedure may also reveal the desialylated forms of alpha 2-M (microheterogeneity reduced to 2-3 bands), the native subunits (after reduction with thiols) and the denatured half molecules (in the presence of 8 M urea).

Properties of thin-rod immobilized pH gradients.

Immobilized pH gradient gel rods, 1.5 mm in diameter, were cast with a manifold connected to high-precision burettes. The reproducibility of gel length was ca. 1.7 mm. The average standard deviation sigma x for spot position was 2 mm after one-dimensional and 5.8 mm after two-dimensional runs. In order to bring to completion the elution of the salt fronts into the electrode compartments, carrier ampholytes had to be included in the gel formulation at concentrations of at least 0.5-1%, depending on the pH range. The presence of carrier ampholytes, however, was troublesome in two respects: the gel tended to shrink and the cathodic bands drifted with time. Ionic components in the sample were tolerated up to the following concentrations: NaCl 8 mumoles, sodium dodecyl sulfate 10 micrograms per tube. In presence of non-ionic detergents, the gels moved as a whole towards the cathode.