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Hyperhomocysteinaemia-induced atrial remodelling in hypertensive rats.

Studies from our laboratory and others indicate that, in addition to its purported atherothrombotic effects, hyperhomocysteinaemia (Hhe) is a powerful stimulus for ventricular remodelling, dysfunction and clinical heart failure. Because changes in atrial structure and function can impact on cardiac function in progressive ventricular remodelling and dysfunction, we conducted experiments to examine structural and functional remodelling of the atria in the hyperhomocysteinaemic hypertensive rat, a previously described model of ventricular diastolic dysfunction. Atrial muscle preparations were isolated from hearts of spontaneously hypertensive rats that were fed control, intermediate Hhe-inducing or severe Hhe-inducing diet for 10 weeks. Atrial developed tension, +dT/dt(max) and -dT/dt(max) were found to increase in parallel with levels of Hhe and ventricular diastolic dysfunction. Post-rest developed tension and the maximum developed tension observed in the presence of isoproterenol were also increased significantly in both Hhe groups compared with control. These results indicate that Hhe increases both basal and maximal contractile function in atrial muscle. Atrial structural remodelling was characterized by increased interstitial fibrosis in both Hhe groups. These data suggest that Hhe-associated changes in atrial structure and function may act to maintain ventricular filling in Hhe-induced diastolic dysfunction.

Animals↗

[Surgical closure of atrial septal defect before or after the age of 25 years. Comparison with the natural history of unoperated patients].

INTRODUCTION: Surgical closure of an atrial septal defect (ASD) before the age of 25 years has been demonstrated to reduce complications during adulthood. However, the outcome for patients operated after the age of 25 is still debated. METHODS: In a retrospective study we examined the outcome of early and late surgical repair of ASD in adults, as compared with the natural evolution of unoperated patients. The study population was 280 patients (mean age 40 18 years) with non-restrictive ASD: 102 patients (group 1) underwent surgery before the age of 25 years, 90 patients (group 2) underwent surgery after the age of 25 years, and 88 unoperated patients were older than 25 years at the time of study (group 3). The variables analyzed were left ventricular systolic function, left atrial dimensions, systolic pulmonary pressure, right ventricular dimensions, the degree of mitral and tricuspid regurgitation, and the prevalence of late atrial fibrillation. RESULTS: Left ventricular systolic function and the degree of mitral regurgitation were not statistically different between groups. Compared with the patients in group 2, the patients in group 1 had a significantly lower systolic pulmonary arterial pressure (p < 0.001) and less dilated right ventricle (p < 0.001) and left atrium (p < 0.001). The degree of tricuspid regurgitation (p < 0.001) and prevalence of atrial fibrillation (p < 0.001) were significantly higher in the patients of group 2. Compared with group 3, the patients in group 2 had a significantly lower systolic pulmonary arterial pressure (p < 0.001) and less dilated right ventricle (p < 0.001). However, the left atrial dimensions, degree of tricuspid regurgitation, and prevalence of atrial fibrillation did not differ in a statistically significant way between the two groups. CONCLUSIONS: Surgical repair of an atrial septal defect in patients over 25 years of age does not fully prevent hemodynamic deterioration and the development of atrial arrhythmias. Therefore it seems that the surgical closure of ASD before adulthood should be strongly recommended.

Adolescent↗

Left atrial myopathy in cardiac amyloidosis: implications of novel echocardiographic techniques.

AIMS: To assess left atrial (LA) function and determine the prevalence of LA dysfunction in AL amyloidosis (AL) using conventional and strain echocardiography. METHODS AND RESULTS: LA ejection fraction, LA filling fraction, LA ejection force, peak LA systolic strain rate (LAsSR), and LA systolic strain (LA epsilon) were determined in 95 AL patients (70 with and 25 without echocardiographic evidence of cardiac involvement, abbreviated CAL and NCAL, respectively), 30 age-matched controls (CON), and 20 patients with diastolic dysfunction and LA dilatation (DD). Peak LAsSR >2 standard deviations below mean CON value was used as the cut-off for normal LA function. LA ejection fraction was lower in CAL when compared with CON (40.4+/-13.6 vs. 67.0+/-6%, P=0.01). Left atrial septal strain rate and strain were lower in CAL (0.8+/-0.5 s(-1) and 5.5+/-4%, respectively) compared with CON (1.8+/-0.8 s(-1) and 14+/-4%, respectively, P=<0.0001), NCAL (1.6+/-0.8 s(-1) and 13+/-7%, respectively, P<0.0001) and DD (1.3+/-0.4 s(-1) and 10+/-2%, respectively, P<0.0001). Based on peak LA systolic strain rate criteria, the cut-off values for normal LA function were -1.1 s(-1) and -1.05 s(-1) for lateral and septal walls. Using these criteria, LA dysfunction was identified in 32% (lateral LA criteria) and 60% (septal LA criteria) of CAL patients. Lateral and septal LAsSR were lower in CAL patients with vs. those without symptoms of heart failure. Inter- and intra-observer agreement was high for LA strain echocardiography. CONCLUSION: LA function assessment using strain echocardiography is feasible with low intra- and inter-observer variability. LA dysfunction is observed in AL patients without other echocardiographic features of cardiac involvement and may contribute to cardiac symptoms in CAL.

Aged↗

Effect of late postoperative atrial septal defect closure on hemodynamic function in patients with a Lateral tunnel Fontan procedure.

OBJECTIVES: The aim of this study was to evaluate prospectively the effect of late atrial septal defect closure on cardiac output and oxygen delivery in patients who have undergone the Fontan procedure. BACKGROUND: An adjustable atrial septal defect is incorporated in patients undergoing the Fontan procedure who have increased pulmonary vascular resistance or poor ventricular function, or both. After the Fontan procedure, the atrial septal defect is test occluded. Patients with mean right atrial and pulmonary artery pressures > 15 mm Hg are discharged with the atrial septal defect open. METHODS: Twelve patients (20 months to 12 years old) underwent evaluation and closure of the atrial septal defect at a mean interval of 3.8 months (range 1 to 18) after the Fontan procedure. Each patient underwent full right and left heart catheterization. Cardiac output was obtained using the cine-volume method. The study included six patients with a high transpulmonary gradient or poor ventricular function preoperatively, or both (high risk group) and six who had only borderline increased pulmonary vascular resistance (low risk group). Patients in both groups had a mean right atrial pressure > 15 mm Hg when the atrial defect was test occluded in the first week after the Fontan procedure. RESULTS: All results are given as mean value +/- SD. Ventricular end-diastolic pressure was significantly lower (p = 0.03) with the atrial septal defect open in low risk patients (6 +/- 3 mm Hg) than in high risk patients (10 +/- 3 mm Hg). With the atrial septal defect open, low risk patients had a significantly higher (p = 0.04) cardiac index (4.87 +/- 0.81 liters/min per m2) than the high risk patients (3.96 +/- 0.47 liters/min per m2). There was no significant difference (p = 0.14) in cardiac index between the two groups with occlusion of the atrial septal defect. Oxygen delivery was also significantly higher (p < 0.05) with the atrial septal defect open in low risk patients (836 +/- 99 ml/min per m2) than in high risk patients (704 +/- 106 ml/min per m2). There was no significant difference (p = 0.89) in oxygen delivery between the two groups with occlusion of the atrial septal defect. With the atrial septal defect open, the interatrial gradient was not significantly different in low risk patients (4 +/- 1 mm Hg) from that in high risk patients (4 +/- 1 mm Hg). CONCLUSIONS: These data show that an interatrial communication results in increased postoperative systemic perfusion and oxygen delivery in patients with good diastolic ventricular function after the Fontan procedure.

Atrial Function↗

A genetic model defines the importance of the atrial natriuretic peptide receptor (guanylyl cyclase-A) in the regulation of kidney function.

Disruption of the atrial natriuretic peptide (ANP) receptor [guanylyl cyclase-A (GC-A)] gene yields mice with a salt-resistant form of hypertension, raising fundamental questions on the role of ANP in acute regulation of the kidney. Here, we show that water intake, food consumption, stool weight, urine volume, and sodium excretion are not significantly different between wild-type and GC-A null mice on standard rodent chow (0.7% NaCl) or a high-salt diet (8% NaCl). In conscious mice with an indwelling catheter, the infusion of a physiological saline solution containing 4% BSA resulted in a marked natriuresis/diuresis in wild-type mice but no response in GC-A null animals. When physiological saline was given by gavage, however, the kidney response of wild-type and null mice was equivalent, raising the possibility that the gastrointestinal tract can directly regulate kidney function. However, administration of 0.9% saline through an intraperitoneal route also resulted in equal kidney responses in wild-type and null mice. When 0.9% NaCl lacking protein was infused i.v., wild-type and null mice both responded at the kidney level. Thus, GC-A appears dispensable for regulation of sodium/water excretion in response to changes in dietary sodium concentration, but likely becomes critical in volume expansions where the isooncotic pressure remains constant, such as head-out immersion or the initial and correctable stages of congestive heart failure.

Animals↗

Pure anterior conduction delay: a variant "fascicular" defect.

Based upon electrocardiographic studies of conduction disturbances, the human intraventricular conduction system has been considered trifascicular: a right bundle and a bidivisional left bundle. Right bundle branch block, left anterior hemiblock, and left posterior hemiblock have been described. Microscopic and endocardial mapping studies, however, do not demonstrate a corresponding anatomical basis of this useful functional concept. Atrial premature beats in our two cases resulted in ventricular aberrancy which strongly suggests an additional form of a functional conduction delay. Such delay is manifest as a narrow QRS with anterior displacement in the horizontal plane but no axis shift in the frontal plane. This aberrancy is important to recognize because it can mimic the ECG findings of true posterior myocardial infraction. We do not postulate, however, a specific fascicle of the left bundle as the anatomic substrate for this recently recognized effect.

Adult↗

Supraventricular tachycardias: the role of surgery.

Because of its high efficacy and low morbidity radiofrequency energy catheter ablation techniques have toppled the hierarchy of choice in the electrophysiological intervention armamentum. This review assesses current role of surgery and its foreseeable future. Most accessory AV pathways can be attained by endocardial manipulation and ablated. Surgical dissection of accessory pathways on the beating heart had documented that most pathways were paraannular, although right-sided pathways may be distant to the annulus. Results of accessory pathway ablation have shown that right-sided pathways are difficult to approach and ablate. Surgical ablation may currently be considered after failed catheter ablation. AV nodal modification using catheter ablation also yields excellent results. Radiofrequency energy creates a discrete lesion associated with discrete electrophysiological alteration. Surgical dissection is associated with more diffuse and extensive anatomical and electrophysiological changes and is no longer used even after failed catheter ablation. The arrhythmogenic anatomical substrate associated with atrial flutter is not yet well delineated in the coronary sinus os region. How to extend tissue modification for uniform success here is not yet known. Further surgical approach combined with extensive intraoperative cardiac mapping may ultimately prove a valuable guide for subsequent catheter technique. Atrial fibrillation is the last surgical frontier unchallenged by catheter techniques. Arrhythmogenic anatomical substrate is diffuse spreading over the entire atrial myocardium without a discrete target. The associated pathology is diffuse, severe, and progressive and present even in the so-called lone atrial fibrillation. Progression of underlying pathology can nullify the best designed surgical rationale in terms of sinus node chronotropic function, and atrial contractility. Currently used surgical techniques, i.e., the corridor and the Maze operations, have contributed to a better selection of patients. Surgery is still associated with significant morbidity and relative efficacy, and may be improved before becoming the electrophysiological intervention of choice for atrial fibrillation. In conclusion, atrial fibrillation is a greater surgical challenge, but has to be met with the same standard used for other supraventricular tachycardias.

Atrial Fibrillation↗

Changes in left ventricular structure and function in patients with white coat hypertension: cross sectional survey.

OBJECTIVES: To assess the relation between white coat hypertension and alterations of left ventricular structure and function. DESIGN: Cross sectional survey. SETTING: Augsburg, Germany. SUBJECTS: 1677 subjects, aged 25 to 74 years, who participated in an echocardiographic substudy of the monitoring of trends and determinants in cardiovascular disease Augsburg study during 1994-5. OUTCOME MEASURES: Blood pressure measurements and M mode, two dimensional, and Doppler echocardiography. After at least 30 minutes' rest blood pressure was measured three times by a technician, and once by a physician after echocardiography. Subjects were classified as normotensive (technician <140/90 mm Hg, physician <160/95 mm Hg; n=849), white coat hypertensive (technician <140/90 mm Hg, physician >=160/95 mm Hg; n=160), mildly hypertensive (technician >=140/90 mm Hg, physician <160/95 mm Hg; n=129), and sustained hypertensive (taking antihypertensive drugs or blood pressure measured by a technician >=140/90 mm Hg, and physician >=160/95 mm Hg; n=538). RESULTS: White coat hypertension was more common in men than women (10.9% versus 8.2% respectively) and positively related to age and body mass index. After adjustment for these variables, white coat hypertension was associated with an increase in left ventricular mass and an increased prevalence of left ventricular hypertrophy (odds ratio 1.9, 95% confidence interval 1.2 to 3.2; P=0.009) compared with normotensive patients. The increase in left ventricular mass was secondary to significantly increased septal and posterior wall thicknesses whereas end diastolic diameters were similar in both groups with white coat hypertension or normotension. Additionally, the systolic white coat effect (difference between blood pressures recorded by a technician and physician) was associated with increased left ventricular mass and increased prevalence of left ventricular hypertrophy (P<0.05 each). Values for systolic left ventricular function (M mode fractional shortening) were above normal in subjects with white coat hypertension whereas diastolic filling and left atrial size were similar to those in normotension. CONCLUSION: About 10% of the general population show exaggerated inotropic and blood pressure responses when mildly stressed. This is associated with an increased risk of left ventricular hypertrophy.

Adult↗

Natriuretic activity of human and monkey atria.

Recent evidence indicates that mammalian atria contain a substance that produces a rapid onset natriuresis in anesthetized rats. In the present experiments, small portions of human right atria obtained from patients undergoing coronary bypass surgery, as well as monkey atria and ventricles obtained from the Regional Primate Center, Seattle, were boiled or acid extracted and lyophilized. These materials (30 mg/kg) were dissolved in Ringer's lactate and injected intravenously into anesthetized monkeys to determine their effects on renal function. Their effects were also compared with those of furosemide (0.1 mg/kg) and chlorothiazide (10 mg/kg). Human and monkey atrial extracts produced significant increases in sodium and calcium excretion that were independent of changes in creatinine clearance. Monkey ventricular extract had no consistent renal effects. Furosemide, but not chlorothiazide, mimicked the renal responses to human and monkey atrial extracts in terms of time of onset, duration, and pattern of electrolyte excretion. These data suggest that primate atrial tissue contains a heat- and acid-stable natriuretic factor similar to that first described in the rat, suggesting that mammalian atrial natriuretic factors are cross-reactive among species. In addition, atrial natriuretic factors may have a mechanism of action similar to that of furosemide.

Animals↗

Clinical correlates and reference intervals for pulmonary artery systolic pressure among echocardiographically normal subjects.

BACKGROUND: Data in normal human subjects on the factors affecting pulmonary artery systolic pressure (PASP) are limited. We determined the correlates of and established a reference range for PASP as determined by Doppler transthoracic echocardiography (TTE) from a clinical echocardiographic database of 102 818 patients, of whom 15 596 (15%) had a normal Doppler TTE study. METHODS AND RESULTS: A normal TTE was based on normal cardiac structure and function during complete Doppler TTE studies. The PASP was calculated by use of the modified Bernoulli equation, with right atrial pressure assumed to be 10 mm Hg. Among TTE normal subjects, 3790 subjects (2432 women, 1358 men) from 1 to 89 years old had a measured PASP. The mean PASP was 28.3+/-4.9 mm Hg (range 15 to 57 mm Hg). PASP was independently associated with age, body mass index (BMI), male sex, left ventricular posterior wall thickness, and left ventricular ejection fraction (P<0.001). The estimated upper 95% limit for PASP among lower-risk subjects was 37.2 mm Hg. A PASP >40 mm Hg was found in 6% of those >50 years old and 5% of those with a BMI >30 kg/m(2). CONCLUSIONS: Among 3790 echocardiographically normal subjects, PASP was associated with age, BMI, sex, wall thickness, and ejection fraction. Of these subjects, 28% had a PASP >30 mm Hg, and the expected upper limit of PASP may include 40 mm Hg in older or obese subjects. These findings support the use of age- and BMI-corrected values in establishing the expected normal range for PASP.

Adolescent↗

Effects of aprindine HCL on cardiac tissues.

The effects of aprindine HCL on cardiac tissues were studied in anesthetized, open-chest dogs pretreated with atropine (0.8 mg/kg) and propranolol (1.0 mg/kg). Aprindine (10(-5)-10(-3) g/ml), injected into the sinus node artery, decreased the spontaneous sinus rate; when injected into the atrioventricular nodal artery, aprindine (10(-4) g/ml) prolonged the conduction time and functional refractory period of the atrioventricular node. Intravenous administration of aprindine (1.4, 2.8 and 4.2 mg/kg cumulative dose) prolonged atrial and ventricular conduction time and prolonged the effective refractory period of both tissues. The results from this study indicate that aprindine has a negative dromotropic effect on all cardiac tissue.

Animals↗

Electrophysiological properties of butoprozine studied by multiple intracardiac recordings on the anaesthetized dog.

Electrophysiological effects of butoprozine (L 9394 Labaz) were investigated on the anaesthetized dog by programmed electrical stimulation of the heart and simultaneous recording of the His bundle electrogram and monophasic action potentials from the auricular and ventricular endocardial wall. Butoprozine injected intravenously depressed sino-atrial node function, lengthened A-V nodal conduction time and the A-V nodal refractory period, and prolonged the atrial refractory period. Thus butoprozine acted preferentially on parts of the myocardial tissue where the slow inward current seems to be particularly involved. In this respect, butoprozine was more active than amiodarone, but in contrast to this drug, butoprozine did neither prolong the ventricular monophasic action potential duration nor the ventricular refractory period. In the anaesthetized dog both drugs have practically analogous actions except at the ventricular level, which suggests that their effect on ionic currents at this level may be different.

Amiodarone↗

[Anticoagulant related hemorrhage and thromboembolism after valvular surgery].

We reviewed anticoagulant related hemorrhage (ACRH) and thromboembolism (TE) in 84 patients after valvular surgery. There were 45 females and 39 males with a mean age of 51.8 years (range 30.5-71.2 years), who underwent valvuloplasty in 14, bioprosthetic valve replacements in 17, mechanical valve replacements in 13. A mean period from the operation to the event were 2.7 years (range 0.01-12.3 years). There were 25 ACRH events after one valvuloplasty, 4 bioprosthetic valve replacements, 20 mechanical valve replacements. About half of them, the prothrombin time were less than 25%, which was considered the effect of warfarin is high, and 8% of them had infective endocarditis (IE) previously. There were 59 TE events after 13 valvuloplasties, 13 bioprosthetic valve replacements, 33 mechanical valve replacements. In the patients with atrial fibrillation, TE occurred irrespective of operative procedures. And in the patients with mechanical valve, severely impaired left ventricular function and past history of IE, thrombi of left ventricule were caused of TE. It was suggested that past history of IE was a risk factor ACRH and TE, and severely depressed left ventricular function and atrial fibrillation were for TE.

Adult↗

Measurement of ventricular function by ECG gating during atrial fibrillation.

The assumptions necessary to perform ECG-gated cardiac studies are seemingly not valid for patients in atrial fibrillation (AF). To evaluate the effect of AF on equilibrium gated scintigraphy, beat-by-beat measurements of left-ventricular function were made on seven subjects in AF (mean heart rate 64 bpm), using a high-efficiency nonimaging detector. The parameters evaluated were ejection fraction (EF), time to end-systole (TES), peak rates of ejection and filling (PER,PFR), and their times of occurrence (TPER,TPFR). By averaging together single-beat values of EF, PER, etc., it was possible to determine the true mean values of these parameters. The single-beat mean values were compared with the corresponding parameters calculated from one ECG-gated time-activity curve (TAC) obtained by superimposing all the single-beat TACs irrespective of their length. For this population with slow heart rates, we find that the values for EF, etc., produced from ECG-gated time-activity curves, are very similar to those obtained from the single-beat data. Thus use of ECG gating at low heart rates may allow reliable estimation of average cardiac function even in subjects with AF.

Atrial Fibrillation↗

Single-lead VDD pacing system.

A single pass ventricular lead with a dual chamber electrode system, designed for VDD pacing, was implanted in 17 patients (11 men, 6 women, aged 53 to 86 years, mean 74) for symptomatic bradycardia due to second-or third-degree AV block and normal sinus node function. Bipolar atrial electrodes, diagonally displaced along the lead axis and positioned within the right atrial cavity, are used to detect atrial activity that is then differentially processed within the pacemaker. P wave amplitude (amp) derived from a PSA-DAA device at implant was 1.38 +/- 0.28 mV. P wave signal amp derived from telemetered atrial electrograms was 1.29 +/- 0.22 mV at predischarge (n = 17), 1.31 +/- 0.24 mV at 3 months (n = 15), 1.30 +/- 0.24 mV at 6 months (n = 8), 1.51 +/- 0.34 mV at 9 months (n = 4), and 1.35 +/- 0.35 mV at 12 months (n = 2); and the far-field QRS signal measured at predischarge was of negligible voltage (0.17 +/- 0.07 mV). The susceptibility of the atrial sensor system to interference was noted with chest wall stimulation and only at higher sensitivities (0.1 to 0.3 mV) and not with isometric arm exercise. Intact VDD pacing function at rest and during exercise was established using Holter and periodic ECG monitoring. Postoperative complications included one lead displacement and one pocket hematoma. Three patients died postimplant of causes unrelated to pacemaker function. Advantages of the single-lead VDD pacing include: (1) elimination of second atrial sensing lead; (2) superior atrial sensing performance; (3) effective resistance to myopotential and far-field signal interference; and (4) stability of postimplant atrial signal amplitude.

Aged↗