Intracardiac echocardiography during radiofrequency catheter ablation of cardiac arrhythmias in humans.

OBJECTIVES: The purpose of this study was to describe our preliminary experience using catheter-based intracardiac echocardiography as an adjunct to biplane fluoroscopy for guiding radiofrequency catheter ablation of atrial arrhythmias in the right side of the heart. BACKGROUND: Catheter ablation requires precise positioning and stable ablation electrode-endocardial contact. This procedure is currently guided by an analysis of intracardiac electrograms and fluoroscopy. However, the use of fluoroscopy does not allow the endocardium and certain anatomic landmarks to be identified and is associated with the hazards of radiation exposure. METHODS: Seventeen symptomatic patients were studied. A 10F 10-MHz intracardiac imaging catheter was used to visualize specific anatomic landmarks in the right atrium for directing the ablation electrode in 15 patients undergoing radiofrequency ablation of 19 arrhythmias and to assist with interatrial septal puncture in 3 patients. RESULTS: Continuous intracardiac imaging was performed for a mean +/- SD of 63.6 +/- 39.2 min and demonstrated distal electrode-endocardial tissue contact in 81 (60%) of 134 radiofrequency applications. Movement of the catheter was demonstrated during 36 (44%), microcavitations during 39 (48%) and thrombus during 15 (19%) of the 81 imaged applications. In 7 of 10 procedures for atrial flutter, successful ablation was directed at anatomic corridors in the right atrium visualized with intracardiac echocardiography. During ablation of atrial tachycardia, imaging identified abnormal atrial anatomy related to previous surgery and guided successful ablation of a reentrant tachycardia circulating around these anatomic obstacles. In two procedures for slow pathway modification of atrioventricular node reentrant tachycardia, intracardiac echocardiography confirmed catheter stability at the tricuspid annulus anterior to the coronary sinus. CONCLUSIONS: During catheter ablation, intracardiac echocardiography augments fluoroscopy by visualizing anatomic landmarks, ensuring stable endocardial contact and assisting in transseptal puncture. Ablation of typical atrial flutter can be successfully directed at anatomic corridors identified using intracardiac imaging.

Radiofrequency catheter ablation of atriofascicular and nodoventricular Mahaim tracts.

BACKGROUND: Several mechanisms have been proposed to explain the pathogenesis of tachycardia in patients with Mahaim tracts. The tachycardia may involve antegrade conduction over an atriofascicular pathway with decremental properties or a nodofascicular pathway. METHODS AND RESULTS: We report six patients with recurrent episodes of preexcited tachycardia with findings consistent with "Mahaim tract" conduction. All patients exhibited decremental antegrade preexcited conduction with atrial pacing and a preexcited tachycardia with initial activation of the proximal right bundle branch. In four patients (group 1), atrial premature complexes (APCs) induced at the tricuspid annulus just after the inscription of the septal atrial electrogram and during left bundle branch block preexcited tachycardia advanced the next preexcited ventricular complex. In these patients, discrete Mahaim potentials were inscribed over the right anterolateral or lateral tricuspid annulus. Two patients (group 2) had evidence of dual atrioventricular nodal conduction. APCs during left bundle branch block tachycardia just after inscription of the septal atrial electrogram failed to advance the next ventricular complex with similar preexcited morphology, and no Mahaim potentials could be recorded from the tricuspid annulus. In group 1 patients, application of radiofrequency energy to sites recording the Mahaim potentials resulted in tachycardia cure. For patients in group 2, selective slow atrioventricular nodal pathway ablation in the midseptal region resulted in complete ablation of both the slow atrioventricular nodal pathway and Mahaim conduction in two patients. CONCLUSIONS: Mahaim tachycardia can be due to atriofascicular pathways, which may be ablated over the right tricuspid annulus, or to septal pathways, which may arise from the slow atrioventricular nodal pathway in patients with dual atrioventricular nodal physiology. In the latter circumstance, successful ablation is achieved by placing the lesion in the midseptal region.

Improved hemodynamic function and mechanical efficiency in congestive heart failure with sodium dichloroacetate.

OBJECTIVES: The purpose of this study was to determine whether sodium dichloroacetate improves hemodynamic performance and mechanical efficiency in congestive heart failure. BACKGROUND: Congestive heart failure is associated with impaired hemodynamic performance and reduced mechanical efficiency. Dichloroacetate stimulates pyruvate dehydrogenase activity by inhibition of pyruvate dehydrogenase kinase, which results in inhibition of free fatty acid metabolism and stimulation of high respiratory quotient glucose and lactate consumption by the heart. Facilitation of glucose and lactate consumption with dichloroacetate should improve mechanical efficiency of the failing ventricle. METHODS: Ten patients with New York Heart Association functional class III to IV congestive heart failure were studied. Dichloroacetate (50 mg/kg body weight) was administered intravenously for 30 min, with measurements of hemodynamic variables, coronary sinus blood flow and blood gas, glucose and lactate levels for 2 h. The same patients were also given dobutamine (5 to 12.5 micrograms/kg per min) for comparison. RESULTS: Therapeutic levels of dichloroacetate were achieved (100 to 160 micrograms/liter of plasma). Myocardial consumption of lactate was stimulated from 29% to 37.4%. Forward stroke volumes increased (+5.3 ml/beat, p < 0.02), as did left ventricular stroke work (+1.8 g-m/m2 per beat, p < 0.02) and left ventricular minute work (from 1.38 to 1.55 kg-m/m2 per min, p < 0.01). Myocardial oxygen consumption decreased (from 19.3 to 16.5 ml/min, p = 0.06) as left ventricular minute work increased. Left ventricular mechanical efficiency thus improved from 15.2% to 20.6% (p = 0.03). Dobutamine administration resulted in the opposite trend with respect to myocardial lactate extraction (from 34% to 15.3%, p < 0.02). Stroke volume increased (+7.4 ml/beat, p = NS vs. dichloroacetate), as did left ventricular minute work (from 1.29 to 1.59 g-m/m2 per min, p < 0.01 vs. dichloroacetate) and myocardial oxygen consumption (from 18.6 to 21.0 ml/min, p = 0.06 vs. dichloroacetate). Left ventricular mechanical efficiency did not change with dobutamine administration (from 16.4% to 15.8%, p = NS). CONCLUSIONS: Dichloroacetate administration stimulates myocardial lactate consumption and improves left ventricular mechanical efficiency. Forward stroke volume and left ventricular minute work increase significantly, with a simultaneous reduction in myocardial oxygen consumption. Dobutamine administration results in similar hemodynamic improvements but with no change in left ventricular mechanical efficiency and with opposite effects on lactate metabolism. The opposing metabolic actions, yet similar hemodynamic responses, of dichloroacetate and dobutamine suggest that these agents may be complementary in the treatment of congestive heart failure.

Radiofrequency catheter ablation of atrial arrhythmias. Results and mechanisms.

BACKGROUND: Radio frequency catheter ablation is accepted therapy for patients with paroxysmal supraventricular tachycardia and has a low rate of complications. For patients with atrial arrhythmias, catheter ablation of the His bundle has been an option when drugs fail or produce untoward side effects. Although preventing rapid ventricular response, this procedure requires a permanent pacemaker and does not restore the atrium to normal rhythm. Therefore, we evaluated the safety and efficacy of radiofrequency ablation directed at the atrial substrate. METHODS AND RESULTS: Thirty-seven patients with 42 atrial arrhythmias (mean +/- SD age, 41 +/- 24 years) who had failed a median of three drugs were enrolled. Diagnoses were automatic atrial tachycardia in 12, atypical atrial flutter in 1, typical atrial flutter in 18, reentrant atrial tachycardia in 8, and sinus node reentry in 3 patients. Sites for atrial flutter ablation were based on anatomic barriers in the floor of the right atrium. For automatic atrial tachycardia, the site of earliest activation before the P wave was sought. All with reentrant atrial tachycardia had previous surgery for congenital heart disease and reentry around a surgical scar, anatomic defect, or atriotomy incision and our goal was to identify a site of early activation in a zone of slow conduction. At target sites, 20 to 50 W of radiofrequency energy was delivered during tachycardia between the 4- or 5-mm catheter tip and a skin patch, except in 4 patients with atrial flutter, in whom a catheter with a 10-mm thermistor-embedded tip was used. Procedure end point was inability to reinduce tachycardia. Acute success was achieved in 11 of 12 (92%) with automatic atrial tachycardia, 17 of 18 (94%) with typical atrial flutter, 7 of 8 (88%) with reentrant atrial tachycardia, and 3 of 3 (100%) with sinus node reentry but not in the patient with atypical atrial flutter. For tachycardia involving reentry (reentrant atrial tachycardia and atrial flutter), successful ablation required severing an isthmus of slow conduction. For those with atrial flutter, this was between the tricuspid annulus and the coronary sinus os (10) or posterior (4) or posterolateral (3) between the inferior vena cava (2) or an atriotomy scar (1) and the tricuspid annulus. Deep venous thrombosis occurred in 1 patient. At mean follow-up of 290 +/- 40 days, the ablated arrhythmia recurred in 1 (9%) with automatic atrial tachycardia, 5 (29%) with atrial flutter, and 1 (14%) with reentrant atrial tachycardia, all of whom had successful repeat ablation. Previously undetected arrhythmias occurred in 2 patients who are either asymptomatic or controlled with medication. CONCLUSIONS: Ablation of automatic and reentrant atrial tachycardia and atrial flutter had a high success rate and caused no complications from energy application. Repeat procedures may be required for long-term success, especially in patients with atrial flutter. The mechanism by which ablation is successful is similar for atrial flutter and other forms of atrial reentry and involves severing a critical isthmus of slow conduction bounded by anatomic or structural obstacles. Automatic arrhythmias are abolished by directing lesions at the focus of abnormal impulse formation.

Importance of oxygen-haemoglobin binding to oxygen transport in congestive heart failure.

OBJECTIVE: To assess the importance of 2,3-diphosphoglycerate (2,3-DPG) and oxygen-haemoglobin binding to oxygen transport in patients with congestive heart failure. METHODS: In 30 patients with severe congestive heart failure, arterial, mixed venous, and coronary sinus venous blood concentrations of 2,3-DPG were measured and systemic output and coronary sinus blood flow were measured by a thermodilution technique. Oxygen-haemoglobin affinity was expressed as the oxygen tension in mm Hg at which blood is 50% saturated with oxygen (P50). RESULTS: Compared with normal values, 2,3-DPG was high in arterial blood (2.58 mumol/ml, p = 0.01; 20.8 mumol/g haemoglobin, p < 0.0001). Significant gradients between arterial, mixed venous, and coronary sinus blood 2,3-DPG concentrations were also found (mixed venous = 2.40 mumol/ml, p = 0.05 v arterial blood; coronary sinus venous blood = 2.23 mumol/ml, p < 0.04 v arterial blood). P50 was correspondingly high compared with the accepted normal value (mean 29.7 mm Hg, normal 26.6 mm Hg, p < 0.001). Systemic oxygen transport (351 ml O2/min/m2) varied directly with the forward cardiac index (r = 0.89, p < 0.0001). There was no relation between systemic oxygen transport and arterial oxygen content. Similarly, myocardial oxygen transport was found to vary directly with coronary sinus blood flow. Calculations of changes in cardiac index and coronary sinus blood flow at normal oxygen-haemoglobin binding indicate that a considerable increase in cardiac index and coronary blood flow would be required to maintain similar systemic and myocardial oxygen transport. CONCLUSIONS: In patients with severe heart failure increased 2,3-DPG and reduced oxygen-haemoglobin binding may be compensatory mechanisms that maintain adequate systemic and delivery of oxygen to myocardial tissue.

Flosequinan, a new vasodilator: systemic and coronary hemodynamics and neuroendocrine effects in congestive heart failure.

OBJECTIVES: The aim of this study was to evaluate the immediate and long-term systemic and coronary hemodynamic, metabolic and neurohormonal effects of flosequinan in patients with congestive heart failure. BACKGROUND: Preliminary studies have shown that this new long-acting oral systemic vasodilator may have beneficial effects in patients with heart failure. METHODS: Thirteen patients with congestive heart failure were studied. Systemic and coronary hemodynamic, metabolic and neurohormonal effects of flosequinan were assessed acutely with repeat systemic hemodynamic studies after 6 weeks of treatment. RESULTS: The administration of flosequinan acutely and after long-term treatment, resulted in a significant increase in cardiac index, stroke work index and stroke volume index with a reduction in systemic and pulmonary vascular resistances. The improvement in ventricular function was associated with an improvement in left ventricular efficiency without a change in myocardial oxygen consumption or coronary sinus blood flow. Myocardial oxygen extraction and net myocardial lactate extraction also did not change significantly with flosequinan therapy. Systemic catecholamine levels and myocardial catecholamine balance did not change. Plasma arterial and coronary sinus atrial natriuretic factor concentrations were elevated at baseline; the latter concentrations at the level of the great cardiac vein were significantly higher than those of arterial concentrations, indicating increased left ventricular release of atrial natriuretic factor in congestive heart failure. Both arterial and coronary sinus atrial natriuretic factor levels were significantly reduced with the administration of flosequinan at peak effect in association with an improvement in systemic hemodynamics. CONCLUSIONS: Flosequinan therapy in patients with congestive heart failure results in a sustained beneficial hemodynamic action and improved cardiac performance without an increase in metabolic demand or activation of the sympathetic nervous system.

Dopexamine hydrochloride in chronic congestive heart failure with improved cardiac performance without increased metabolic cost.

Dopexamine hydrochloride is a new intravenous, short-acting agent with agonist activity at beta 2-adrenergic and DA1-dopaminergic receptors. The effects of dopexamine hydrochloride infusion on systemic and coronary hemodynamics, myocardial metabolism and the neuroendocrine system were evaluated in 10 patients with chronic severe congestive heart failure at baseline, at rates of 1, 2, 4 and 6 micrograms/kg/min at 15-minute intervals, and after a 1-hour infusion of the "optimal" dose. Right atrial pressure was reduced by 25% (p less than 0.01), pulmonary capillary wedge pressure by 26% (p less than 0.05), systemic vascular resistance by 44% (p less than 0.001) and pulmonary vascular resistance by 34% (p less than 0.01) after the optimal dose. Heart rate increased by 17% (p less than 0.01), rate-pressure product by 17% (p less than 0.01) and stroke volume index by 31% (p less than 0.001). There was no change in mean arterial pressure, myocardial oxygen consumption, coronary sinus blood flow, myocardial oxygen extraction or norepinephrine balance. None of the patients demonstrated net myocardial lactate production. These findings suggest that dopexamine hydrochloride improves systemic hemodynamics and cardiac performance without adversely affecting myocardial energetics or norepinephrine balance. Thus, dopexamine hydrochloride may be a useful agent for the short-term treatment of congestive heart failure.

Exercise-induced reversal of age-related declines of oxidative reactions, mitochondrial yield, and flavins in skeletal muscle of the rat.

The ability of gastrocnemius muscle homogenates to catalyze the oxidation of succinate, glutamate + malate, pyruvate + malate, palmitoyl-coenzyme A, decanoylcarnitine and palmitoylcarnitine in the presence of ADP decreased by approximately 32% in sedentary male Sprague-Dawley rats between the ages of 9 and 25 months. Following 21 weeks of treadmill training (running), such homogenates from 25-month-old animals catalyzed oxidations 55% more rapidly than those from 25-month-old sedentary rats, and 17% faster than those from 9-month-old sedentary rats. Total and peptide-bound flavin of gastrocnemius muscles also declined between 9 and 25 months of age and were elevated in the 25-month-old endurance trained rats to levels greater than both 9- and 25-month-old sedentary animals. The yield of protein in the mitochondrial fraction from the quadriceps femoris muscle decreased between 9 and 25 months and was restored to the 9-month level by endurance training. The kinetic characteristics of the isolated mitochondria were not influenced by age or exercise. These data indicate that 2-year-old rats retain the capacity to increase skeletal muscle oxidative capacity and mitochondrial population density in response to endurance training.