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Analysis of left ventricular contractile behaviour during atrial fibrillation.

OBJECTIVES: The purpose of this study was to explore the physiology underlying the beat-to-beat variations of ventricular function during atrial fibrillation (AF). METHODS: Left ventricular pressure, and its first derivative (LVdP/dtmax, an index of contractility, and aortic blood velocity (and its integral AVI, an ejection index), were recorded using cathetermounted transducers in 15 patients with AF during cardiac catheterisation. Transfer function modelling was used to examine the influence of preceding intervals on LVdP/dtmax, and of LVdP/dtmax on AVI. The technique also allowed simulation of the behaviour of LVdP/dtmax in response to specific manipulations of interval. RESULTS: The variations in LVdP/dtmax recorded from the AF patients were shown to be dependent on up to six preceding intervals; a maximum of 91% of the variation was explicable in this way. The influences of mechanical restitution (MR, the relationship between preceding interval and contractility), postextrasystolic potentiation (PESP, the inverse relationship between pre-preceding interval and contractility) and the decay of that potentiation were all demonstrated. These influences collectively appeared to be powerful determinants of AVI. Simulations of LVdP/dtmax, following single interval perturbations, were entirely consistent with these interval force effects. CONCLUSIONS: The cardiac interval force relationship in man is an important determinant of the beat-to-beat variations of contractile and ejection function during AF: the beat-to-beat variations in contractile (or inotropic) function are independent of changes in ventricular filling or fibre-length.

Aged↗

Utility of B-natriuretic peptide in detecting diastolic dysfunction: comparison with Doppler velocity recordings.

BACKGROUND: Although Doppler echocardiography has been used to identify abnormal left ventricular (LV) diastolic filling dynamics, inherent limitations suggest the need for additional measures of diastolic dysfunction. Because data suggest that B-natriuretic peptide (BNP) partially reflects ventricular pressure, we hypothesized that BNP levels could predict diastolic abnormalities in patients with normal systolic function. METHODS AND RESULTS: We studied 294 patients referred for echocardiography to evaluate ventricular function. Patients with abnormal systolic function were excluded. Cardiologists making the assessment of LV function were blinded to BNP levels. Patients were classified as normal, impaired relaxation, pseudonormal, and restrictivelike filling patterns. Patients diagnosed with evidence of abnormal LV diastolic function (n=119) had a mean BNP concentration of 286 +/- 31 pg/mL; those in the normal LV group (n=175) had a mean BNP concentration of 33 +/- 3 pg/mL. Patients with restrictive like filling patterns on echocardiography had the highest BNP levels (408 +/- 66 pg/mL), and patients with symptoms had higher BNP levels in all diastolic filling patterns. The area under the receiver-operating characteristic curve for BNP to detect any diastolic dysfunction was 0.92 (95% CI, 0.87 to 0.95; P<0.001). A BNP value of 62 pg/mL had a sensitivity of 85%, a specificity of 83%, and an accuracy of 84% for detecting diastolic dysfunction. CONCLUSIONS: A rapid assay for BNP can reliably detect the presence of diastolic abnormalities on echocardiography. In patients with normal systolic function, elevated BNP levels and diastolic filling abnormalities might help to reinforce the diagnosis diastolic dysfunction.

Aged↗

Conduction left-to-right and right-to-left across the crista terminalis.

A line of block between the vena cava and the crista terminalis (CT) region is important for atrial flutter (AFL), but whether it is fixed or functional is controversial. To test the hypothesis that conduction across the CT normally occurs, but when block occurs in this region it is functional, we analyzed atrial activation during right and left atrial pacing (cycle lengths of 500--130 ms), AFL, and atrial fibrillation in 15 dogs with sterile pericarditis and 7 normal dogs. Electrograms from 396 right, left, and septal atrial sites were simultaneously recorded. Activation across the CT occurred during atrial pacing, AFL, and atrial fibrillation. Activation wave fronts from the right to the left atrium and vice versa traveled over several routes, including Bachmann's bundle and inferior to the inferior vena cava, as well as across the CT. In these models, there is no fixed conduction block across the CT, and when block in the CT region occurs, as during AFL, it is functional.

Animals↗

Peripheral factors in the management of congestive heart failure.

Maladaptive changes in the periphery largely account for the symptomatology of patients with congestive heart failure (CHF). A decline in the systolic function of the left ventricle precipitates activation of neural and humoral systems to provide circulatory support. These include sympathetic release of norepinephrine, increases in angiotensin II, elevated levels of circulating arginine vasopressin, and impairment of the counterregulatory function of atrial natriuretic peptide. The resultant circulatory changes are ultimately responsible for the declining function of the peripheral vasculature and skeletal muscles of patients with CHF. In the peripheral vasculature, impaired vasodilatory capacity results from excess vessel wall stiffness, endothelial dysfunction, and structural abnormalities. The skeletal muscles develop poor aerobic capacity as a result of a change in predominant fiber type and excess reliance on glycolytic metabolic pathways. Physical deconditioning induced by symptoms tends to further promote these peripheral changes. Therapeutic interventions with symptomatic and prognostic benefits have essentially been targeted at the periphery. Angiotensin converting enzyme inhibitors may act by normalizing electrolyte and water balance, improving vascular endothelial function, and reversing structural changes in peripheral vessels. Exercise training appears to exert its benefit at the level of the vascular endothelium. Advances in the therapy of CHF depend on a greater understanding of changes in the periphery.

Angiotensin-Converting Enzyme Inhibitors↗

Atrial natriuretic peptide, blood volume, aldosterone, and sodium excretion during twin pregnancy.

BACKGROUND: The reports on plasma concentrations and physiological function of atrial natriuretic peptide (ANP) during pregnancy are conflicting. In a recent prospective study, including 40 healthy primigravidae, we found a highly significant decrease in the plasma concentration of ANP (p-ANP) during the third trimester and the results indicated that ANP takes part in regulation of blood volume and renal function during pregnancy as in the nonpregnant state. In order to test these results, a study was performed in primigravidae with twin pregnancy to test if the accentuated physiological changes here were followed by a corresponding greater decrease in p-ANP. METHODS: Ten healthy primigravidae with twin pregnancy were examined four times during pregnancy plus 12 weeks after delivery. Each time the following were measured: p-ANP, aldosterone, renin, blood volume (carbon monoxide), cardiac output (Doppler), blood pressure and sodium excretion. Interdependence of the changes in ANP and in the other parameters was tested using Spearman's rank correlation test on the delta (delta)-values (the differences in measurements between investigations). The results were compared to the results obtained during singleton pregnancy using the Mann-Whitney rank sum test. RESULTS: All pregnant values of p-ANP during twin pregnancy were lower than 12 weeks after delivery, p < 0.01. In the 20th, 28th, and 32nd week p-ANP was lower in twin pregnancy than in singleton pregnancy, p < 0.05. There was a negative correlation between changes in p-ANP and changes in: a) blood volume, R = -0.8, p < 0.0001, b) aldosterone, R = -0.66, p < 0.0001, c) renin, R = -0.52, p < 0.01, d) cardiac output, R = -0.68, p < 0.0001. There was a positive correlation between changes in p-ANP and changes in: a) fractional excretion of sodium, R = 0.73, p < 0.0001, and b) total peripheral resistance, R = 0.61, p < 0.0001. CONCLUSION: The results suggest that the competitive relationship between ANP and the renin-aldosterone system in regulating sodium balance and fluid volume is preserved during pregnancy. The vasodilation during pregnancy is not mediated by ANP.

Aldosterone↗

Global right atrial mapping of human atrial flutter: the presence of posteromedial (sinus venosa region) functional block and double potentials : a study in biplane fluoroscopy and intracardiac echocardiography.

BACKGROUND: Previous studies of atrial flutter have found linear block at the crista terminalis; this was thought to predispose the patient to the arrhythmia. More recent observations, however, have demonstrated crista conduction. We sought to characterize the posterior boundary of atrial flutter. METHODS AND RESULTS: Patients with counterclockwise flutter (n=20), clockwise flutter (n=3), or both (n=5) were studied using two 20-pole catheters. Biplane fluoroscopy determined catheter positions. During counterclockwise flutter, craniocaudal activation occurred along the entire lateral and posterior right atrial walls. Septal activation proceeded caudocranially. In all patients, a line of block was seen in the posteromedial (sinus venosa) right atrium; this was manifested by the presence of double potentials where the upward and downward activations collided. Anatomic location was confirmed by intracardiac echocardiography in 9 patients. In patients with clockwise flutter, the line of block and double potentials were seen in the same location during counterclockwise flutter, but the activation sequence around the line of block was reversed. Pacing near the site of double potentials during sinus rhythm excluded a fixed line of block, and premature atrial complexes demonstrated functional block with manifest double potentials. In 2 patients, posterior ectopy organized to subsequently initiate isthmus-dependent atrial flutter. CONCLUSIONS: (1) A functional line of block is seen at the posteromedial (sinus venosa region) right atrium during counterclockwise and clockwise atrial flutter. (2) All lateral wall right atrial activation can be uniform during flutter, without linear block or double potentials in the region of the crista terminalis. (3) Activation at the site of posteromedial right atrial functional block can organize to subsequently initiate isthmus-dependent atrial flutter.

Adult↗

Effectiveness of atrial pacing in Macaca mulatta as a function of pacing pulse intensity: modification by atropine and propranolol.

The functional relationship between heart rate, under atrial pacing, and the intensity of pacing pulses, was determined for intensities ranging from well below the complete heart rate capture threshold to suprathreshold intensities. A separate capture-intensity function was determined for each of the pacing frequencies 180, 240, 300 and 360 pulses per min, and then used to evaluate the effects of propranolol hydrochloride and atropine sulfate on atrial pacing. Propranolol resulted in an increase in the amount of current (mA) required to achieve a given degree of cardiac capture, whereas atropine resulted in a decrease. These shifts in the capture-intensity functions along the intensity axis were possibly caused by drug antagonism of beta-adrenergic and cholinergic receptors, respectively, although the effects might also have been due to modifications of the electrical responsivity of the cardiac muscle, independently of the neural blockade.

Animals↗

Impact of cardioversion strategy on functional capacity in patients with atrial fibrillation: the Assessment of Cardioversion Using Transesophageal Echocardiography (ACUTE) study.

BACKGROUND: The ACUTE Trial studied a transesophageal echocardiography (TEE)-guided strategy compared with a conventional strategy for management of patients with atrial fibrillation undergoing direct current cardioversion. The primary aim was to determine if patient functional capacity, measured by the Duke Activity Status Index (DASI), would differ between treatment strategies. METHODS: The DASI was self-administered at study enrollment and at 8-week follow-up in 1074 (88%) of 1222 total patients. Clinical outcomes associated with enrollment DASI scores and change in follow-up DASI scores were reviewed. RESULTS: There was no difference between the TEE-guided (n = 544) and conventional treatment (n = 530) groups for mean baseline and 8-week DASI scores, adjusting for baseline; however, patients who improved their DASI score were more likely to be in the TEE-guided group (P = .03). Pooled group data showed that the higher the enrollment DASI score, the more it tended to be positively related to maintenance of sinus rhythm (P = .06) at 8 weeks. The lower the enrollment DASI score, the more it was predictive of death (P = .03) and bleeding (P = .01) within 8 weeks. Patients with congestive heart failure (CHF) at enrollment showed greater improvement in DASI scores at 8 weeks compared with patients without CHF (DASI Delta 45.9% vs 31.6%, P < .001). CONCLUSIONS: There was no difference in DASI scores between treatment groups. However, TEE-guided treatment was a predictor of improved DASI at follow-up, and subgroup analysis showed that patients with CHF did show improvement in functional capacity with cardioversion.

Activities of Daily Living↗

The effect of successful electrical cardioversion on left ventricular diastolic function in patients with persistent atrial fibrillation: a tissue Doppler study.

BACKGROUND: Changes in mitral inflow and pulmonary venous flow after electrical cardioversion (ECV) in patients with persistent atrial fibrillation (AF) were showed in many former studies. In our study we investigated the effects of ECV on diastolic parameters by using tissue Doppler imaging (TDI) in patients with persistent AF. METHODS: Forty-one (24 women) consecutive patients underwent successful elective ECV for nonvalvular persistent AF, and maintained sinus rhythm for 1 month were enrolled to the study. Transthoracic echocardiography was applied to all patients before, 24 hours after and 1 month after ECV. Mitral annular TDI parameters were also measured with mitral inflow, pulmonary venous flow, and other standard echocardiographic measurements. RESULTS: No differences in peak myocardial early velocity (Em), deceleration time of Em, and myocardial isovolumic relaxation time measured from mitral lateral annulus before, 24 hours after, and one month after ECV were found. Peak myocardial late velocity measured 24 hours after ECV increased significantly at the end of 1 month. CONCLUSION: There were not any changes in LV diastolic function except restoration of atrial mechanical contraction following ECV in patients with persistent AF.

Aged↗

Local atrial natriuretic peptide signaling prevents hypertensive cardiac hypertrophy in endothelial nitric-oxide synthase-deficient mice.

The crucial functions of atrial natriuretic peptide (ANP) and endothelial nitric oxide/NO in the regulation of arterial blood pressure have been emphasized by the hypertensive phenotype of mice with systemic inactivation of either the guanylyl cyclase-A receptor for ANP (GC-A-/-) or endothelial nitric-oxide synthase (eNOS-/-). Intriguingly, similar levels of arterial hypertension are accompanied by marked cardiac hypertrophy in GC-A-/-, but not in eNOS-/-, mice, suggesting that changes in local pathways regulating cardiac growth accelerate cardiac hypertrophy in the former and protect the heart of the latter. Our recent observations in mice with conditional, cardiomyocyte-restricted GC-A deletion demonstrated that ANP locally inhibits cardiomyocyte growth. Abolition of these local, protective effects may enhance the cardiac hypertrophic response of GC-A-/- mice to persistent increases in hemodynamic load. Notably, eNOS-/- mice exhibit markedly increased cardiac ANP levels, suggesting that increased activation of cardiac GC-A can prevent hypertensive heart disease. To test this hypothesis, we generated mice with systemic inactivation of eNOS and cardiomyocyte-restricted deletion of GC-A by crossing eNOS-/- and cardiomyocyte-restricted GC-A-deficient mice. Cardiac deletion of GC-A did not affect arterial hypertension but significantly exacerbated cardiac hypertrophy and fibrosis in eNOS-/- mice. This was accompanied by marked cardiac activation of both the mitogen-activated protein kinase (MAPK) ERK 1/2 and the phosphatase calcineurin. Our observations suggest that local ANP/GC-A/cyclic GMP signaling counter-regulates MAPK/ERK- and calcineurin/nuclear factor of activated T cells-dependent pathways of cardiac myocyte growth in hypertensive eNOS-/- mice.

Animals↗

[Role of the atrium in the functional organization of the sinoatrial node].

The automatic activity of the venous sinus was studied in respect to the atrial bioelectrical activity in frogs. Each of the two parts of the divided venous sinus had different rhythms. Extra-cellular recording revealed that the APs of both parts of the sinus were closely synchronized if the parts were connected with the atrium. The data obtained suggests that this synchronization was due to atrial bioelectrical activity.

Action Potentials↗