Comparison by real-time three-dimensional echocardiography of left ventricular geometry in hypertrophic cardiomyopathy versus secondary left ventricular hypertrophy.
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Adult↗
Biomedical subjects
J D Thomas
Publications and source records attributed to J D Thomas.
Stroke-distance measurement after acute myocardial infarction.
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Echocardiography, Doppler↗
Treatment of hypertension with perindopril reduces plasma atrial natriuretic peptide levels, left ventricular mass, and improves echocardiographic parameters of diastolic function.
BACKGROUND: Hypertension is a major independent risk factor for cardiac deaths, and diastolic dysfunction is a usual finding during the course of this disease. HYPOTHESIS: This study was designed to investigate the effects of chronic therapy with perindopril on left ventricular (LV) mass, left atrial size, diastolic function, and plasma level of atrial natriuretic peptide (ANP) in patients with hypertension. METHODS: Twenty four patients who had not been previously taking any antihypertensive medication and without prior history of angina pectoris, myocardial infarction, congestive heart failure, dysrhythmias, valvular heart disease, or systemic illnesses received 4-8 mg/day of perindopril orally. Echocardiographic studies were acquired at baseline and 6 months after the initiation of therapy. RESULTS: Systolic and diastolic blood pressure decreased from 174 +/- 19.7 and 107.5 +/- 7.8 mmHg to 134 +/- 10.6 and 82 +/- 6.7 mmHg, respectively (p < 0.001). Left ventricular mass decreased from 252.4 +/- 8.3 to 205.7 +/- 7.08 g and left atrial volume from 20.4 +/- 5.1 to 17.6 +/- 5.2 ml, respectively (p < 0.001). Transmitral Doppler early and atrial filling velocity ratio (E/A) increased from 0.69 +/- 0.06 to 0.92 +/- 0.05 m/s and plasma ANP level decreased from 71.9 +/- 11.7 to 35.3 +/- 7.8 pg/ml (p < 0.001). Reduction of LV mass correlated positively with a reduction in ANP levels (r = 0.66, p < 0.0005). CONCLUSIONS: Perindopril caused a significant reduction of LV mass, left atrial volume, and plasma ANP levels, as well as improvement in Doppler parameters of LV filling in this group of patients with hypertension.
Adult↗
Vascular mechanics of the coronary artery.
UNLABELLED: This paper describes our research into the vascular mechanics of the coronary artery and plaque. The three sections describe the determination of arterial mechanical properties using intravascular ultrasound (IVUS), a constitutive relation for the arterial wall, and finite element method (FEM) models of the arterial wall and atheroma. METHODS: Inflation testing of porcine left anterior descending coronary arteries was conducted. The changes in the vessel geometry were monitored using IVUS, and intracoronary pressure was recorded using a pressure transducer. The creep and quasistatic stress/strain responses were determined. A Standard Linear Solid (SLS) was modified to reproduce the non-linear elastic behavior of the arterial wall. This Standard Non-linear Solid (SNS) was implemented into an axisymetric thick-walled cylinder numerical model. Finite element analysis models were created for five age groups and four levels of stenosis using the Pathobiological Determinants of Atherosclerosis Youth (PDAY) database. RESULTS: The arteries exhibited non-linear elastic behavior. The total tissue creep strain was epsilon creep = 0.082 +/- 0.018 mm/mm. The numerical model could reproduce both the non-linearity of the porcine data and time dependent behavior of the arterial wall found in the literature with a correlation coefficient of 0.985. Increasing age had a strong positive correlation with the shoulder stress level, (r = 0.95). The 30% stenosis had the highest shoulder stress due to the combination of a fully formed lipid pool and a thin cap. CONCLUSIONS: Studying the solid mechanics of the arterial wall and the atheroma provide important insights into the mechanisms involved in plaque rupture.
Animals↗
Intraoperative echocardiographic detection of regurgitant jets after valve replacement.
BACKGROUND: Paravalvular jets, documented by intraoperative transesophageal echocardiography, have prompted immediate valve explantation by others, yet the significance of these jets is unknown. METHODS: Twenty-seven patients had intraoperative transesophageal two-dimensional color Doppler echocardiography, performed to assess the number and area of regurgitant jets after valve replacement, before and after protamine. Patients were grouped by first time versus redo operation, valve position and type. RESULTS: Before protamine, 55 jets were identified (2.04+/-1.4 per patient) versus 29 jets after (1.07+/-1.2 per patient, p = 0.0002). Total jet area improved from 2.0+/-2.2 cm2 to 0.86+/-1.7 cm2 with protamine (p<0.0001). In all patients jet area decreased (average decrease, 70.7%+/-27.0%). First time and redo operations had similar improvements in jet number and area (both p>0.6). Furthermore, mitral and mechanical valves each had more jets and overall greater jet area when compared to aortic and tissue valves, respectively. CONCLUSIONS: Following valve replacement, multiple jets are detected by intraoperative transesophageal echocardiography. They are more common and larger in the mitral position and with mechanical valves. Improvement occurs with reversal of anticoagulation.
Adult↗
Cosgrove-Edwards Annuloplasty System: midterm results.
BACKGROUND: The Cosgrove-Edwards Annuloplasty System includes a universally flexible band that corrects mitral annular dilatation via measured plication of the posterior annulus. The purpose of this study was to evaluate midterm clinical and functional results in the first 197 patients receiving this flexible annuloplasty band at mitral valve repair. METHODS: From February 1993 to July 1994, 197 consecutive patients with mitral regurgitation had mitral valve repair using this system. Valve disease was degenerative in 73%, rheumatic in 15%, ischemic in 5%, infectious in 2.5%, and other in 4%. RESULTS: Immediately after repair, echocardiographic mitral regurgitation was none or trivial in 92%, 1+ in 5%, and 2+ in 3%. There were no hospital deaths. Late follow-up was available in 195 patients (99%), with 661 patient-years of follow-up available for analysis. Four-year actuarial survival was 93%, freedom from thromboembolism 94%, from endocarditis 98%, and from reoperation 95%. At a mean interval of 18 months, echocardiography in 157 patients demonstrated no or trace mitral regurgitation in 56%, 1+ in 24%, 2+ in 9%, 3+ in 6%, and 4+ in 3%. At a mean of 61 +/- 5 months, reconstruction of the mitral annulus from real-time three-dimensional echocardiographic images in 10 patients confirmed preserved nonplanar shape and sphincter mechanism of the mitral annulus. Annular orifice area decreased 28% +/- 11% during the cardiac cycle from a mean of 10.1 +/- 3.9 cm2 in diastole to 7.2 +/- 2.8 cm2 in systole. CONCLUSIONS: This annuloplasty system is effective for repair of mitral regurgitation secondary to all causes and preserves mitral annular flexibility and function at 5-year follow-up.
Female↗
Neonatal nicotine exposure alters hippocampal EEG and event-related potentials (ERPs) in rats.
A consensus is forming that nicotine can damage the developing rat central nervous system. However, few studies have assessed the electrophysiological effects of neonatal nicotine exposure in rodents in brain regions known to be sensitive to the teratogenic properties of nicotine. In a previous study it was reported that 1.0 and 4.0 mg/kg/day nicotine exposure from postnatal days 4-9, a developmental period corresponding to human third-trimester exposure, significantly altered hippocampal event-related potentials (ERPs) but did not effect cortical ERPs, cortical EEG, or hippocampal EEG. Because alterations in behavior and cortical/hippocampal neurochemistry and morphology have been reported following nicotine exposure, the present study used a higher dose of nicotine during the postnatal period (6.0 mg/kg/day) determine if functional changes in the EEG of these regions might contribute to behavioral changes that have been observed. Male Sprague-Dawley rats were exposed to 6. 0 mg/kg/day nicotine via gastric infusion using an artificial rearing, "pup-in-the-cup," technique for 6 consecutive days (postnatal days 4-9). At adulthood, EEG and auditory ERPs were recorded from the cortex and hippocampus. There were no significant differences in EEG or ERPs recorded from the cortex between nicotine-treated and control subjects. Examination of the hippocampal EEG revealed significantly decreased power in the 1-2-Hz frequency band of nicotine-treated rats. In addition, there was a significantly attenuated P300 ERP response to a noise tone in the nicotine-treated rats compared to controls. These data indicate that neonatal nicotine exposure alters functional activity in the hippocampus of adult rats. These effects are likely to be the result of synaptic disorganization in the hippocampus, and indicate that neonatal nicotine exposure exerts teratogenic effects on the developing central nervous system, particularly the hippocampus, which persist into adulthood.
Animals↗
Ten-fold augmentation of endothelial uptake of vascular endothelial growth factor with ultrasound after systemic administration.
OBJECTIVES: In this study, the feasibility of delivering and enhancing the uptake of vascular endothelial growth factor (VEGF) into the intact endothelium by using ultrasound (US) facilitation was determined. BACKGROUND: A limitation of tissue-targeted drug delivery is the need for direct arterial cannulation. We postulate a mechanism by which agents injected intravenously may be targeted to a tissue using US and ultrasonic contrast agents. METHODS: We used a rat model to test the ability of US and an ultrasonic contrast agent perflurocarbon exposed sonicated dextrose albumin (PESDA) to increase uptake of VEGF in the myocardium. Continuous wave Doppler US (0.6 W/cm2 at 1 MHz for 15 min) was applied to the chest wall overlying the myocardium during intravenous injection with either VEGF (100 microg/kg) alone or a combination of VEGF and PESDA (0.1%). Control rats had VEGF infused without US or PESDA. The VEGF uptake was measured quantitatively in the heart, lung, liver and kidneys by enzyme-linked immunosorbent assay (ng/g of tissue) and morphologically by fluorescence microscopy. RESULTS: There was an eight-fold increase in VEGF uptake in the heart by US alone (16.86 +/- 1.56 vs. 2.11 +/- 0.953 ng/g of tissue, p < 0.0001) and a 13-fold increase with US + PESDA (26.78 +/- 2.88 vs. 2.11 +/- 0.953 ng/g of tissue, p < 0.0001) compared with control rats. Fluorescence microscopy revealed deposition of VEGF in the endothelium of small intramyocardial arterioles. CONCLUSIONS: These results show a marked increase in endothelial VEGF uptake with US and US + PESDA. Thus, US may be used to augment endothelial VEGF uptake 10-fold to 13-fold.
Animals↗
Elevated circulating levels of serum tumor necrosis factor-alpha in patients with hemodynamically significant pressure and volume overload.
OBJECTIVES: We sought to determine whether serum tumor necrosis factor-alpha (TNF-alpha) levels are elevated in patients with hemodynamically significant pressure and volume overload. BACKGROUND: It has been previously shown that TNF-alpha messenger ribonucleic acid (mRNA) and protein are rapidly expressed in the hearts of animal models subjected to abrupt hemodynamic overloading. The clinical significance of these experimental findings has not been tested in pathophysiologically relevant clinical models in human subjects. METHODS: We prospectively measured serum TNF-alpha levels and serum TNF receptor 1 and 2 levels in 21 patients with severe aortic stenosis (AS), in 26 patients with 3+ to 4+ mitral regurgitation (MR) and in normal age- and gender-matched control subjects. Patients with AS and MR were either in New York Heart Association (NYHA) functional class I or II and had no significant coronary disease. We compared the cytokine levels among the groups using analysis of variance. We related cytokine levels to the severity of AS using simple regression analysis. RESULTS: Serum TNF-alpha levels in patients with AS (2.1 +/- 1.6 pg/ml, n = 21) and MR (1.3 +/-0.7 pg/ml, n = 26) were significantly higher than those in the control subjects (0.7 +/-0.2 pg/ml, n = 28). Serum TNF receptor 1 and 2 levels were also higher in patients with AS and MR than in control subjects. Cytokine levels were higher in patients in NYHA class II than in those in class I. In patients with a normal ejection fraction (>50%, n = 16), there was a mild positive correlation (r = 0.56, p = 0.025) between serum TNF-alpha levels and the mean gradient across the aortic valve. CONCLUSIONS: This study demonstrates that serum TNF-alpha is elevated in patients with chronic hemodynamic overloading and early cardiac decompensation. Furthermore, these findings suggest not only that peripheral TNF-alpha levels correlate with the severity of the hemodynamic pressure overload, but also that peripheral TNF-alpha and TNF receptor levels increase in direct relation to deteriorating NYHA functional class.
Aged↗
Color M-mode Doppler flow propagation velocity is a preload insensitive index of left ventricular relaxation: animal and human validation.
OBJECTIVES: To determine the effect of preload in color M-mode Doppler flow propagation velocity (v(p)). BACKGROUND: The interpretation of Doppler filling patterns is limited by confounding effects of left ventricular (LV) relaxation and preload. Color M-mode v(p) has been proposed as a new index of LV relaxation. METHODS: We studied four dogs before and during inferior caval (IVC) occlusion at five different inotropic stages and 14 patients before and during partial cardiopulmonary bypass. Left ventricular (LV) end-diastolic volumes (LV-EDV), the time constant of isovolumic relaxation (tau), left atrial (LA) pre-A and LV end-diastolic pressures (LV-EDP) were measured. Peak velocity during early filling (E) and v(p) were extracted by digital analysis of color M-mode Doppler images. RESULTS: In both animals and humans, LV-EDV and LV-EDP decreased significantly from baseline to IVC occlusion (both p < 0.001). Peak early filling (E) velocity decreased in animals from 56 +/- 21 to 42 +/- 17 cm/s (p < 0.001) without change in v(p) (from 35 +/- 15 to 35 +/- 16, p = 0.99). Results were similar in humans (from 69 +/- 15 to 53 +/- 22 cm/s, p < 0.001, and 37 +/- 12 to 34 +/- 16, p = 0.30). In both species, there was a strong correlation between LV relaxation (tau) and v(p) (r = 0.78, p < 0.001, r = 0.86, p < 0.001). CONCLUSIONS: Our results indicate that color M-mode Doppler v(p) is not affected by preload alterations and confirms that LV relaxation is its main physiologic determinant in both animals during varying lusitropic conditions and in humans with heart disease.
Aged↗
Neonatal alcohol exposure produces more severe motor coordination deficits in high alcohol sensitive rats compared to low alcohol sensitive rats.
Prenatal exposure to alcohol can produce a number of behavioral alterations, including hyperactivity, learning deficits and motor impairments. However, the severity and nature of behavioral alterations varies markedly among children of women who drink during pregnancy. One important determinant of this variation may be genetic differences in the response to alcohol. Recently, we demonstrated that exposure to alcohol during development produced hyperactivity in rats bred for high alcohol sensitivity (HAS), but not in rats bred for low alcohol sensitivity (LAS). These lines were selectively bred for extremes in alcohol-induced "sleep time." The present study investigated the effects of ethanol exposure during development on motor coordination later in life in both HAS and LAS rats. Using an artificial rearing procedure, neonatal pups from each line were exposed to a binge-like alcohol treatment on postnatal days (PD) 4-9. Within each line, one group was exposed to ethanol (6.0 g/kg/day), one group served as an artificially reared control, and a third served as a normally reared control group. On PD 30, parallel bar motor performance was evaluated. Exposure to ethanol during development severely impaired motor performance in the HAS rats compared to their controls. In LAS rats, early ethanol exposure produced only mild and nonsignificant effects on motor performance. Thus, HAS rats were more vulnerable to ethanol-induced motor deficits compared to the LAS rats. Importantly, there were no differences in peak blood alcohol level between the lines, indicating that vulnerability to ethanol's teratogenic effects was not due to differences in metabolic rate. These results suggest that genetic differences in response to alcohol may serve as a predictor for susceptibility to ethanol's teratogenic effects.
Alcohol Drinking↗
Subendocardial motion in hypertrophic cardiomyopathy: assessment from long- and short-axis views by pulsed tissue Doppler imaging.
BACKGROUND: Tissue Doppler imaging (TDI) is a recently developed technique that allows the instantaneous measurement of intrinsic regional myocardial motion velocity. Pulsed TDI is capable of separately assessing left ventricular (LV) regional motion velocity caused by circumferential and longitudinal fiber contraction. This particular feature of function is still controversial in patients with hypertrophic cardiomyopathy (HC). METHODS: To better characterize intrinsic circumferential and longitudinal LV systolic myocardial function in HC, we used pulsed TDI to measure short- and long-axis LV motion velocities, respectively. The subendocardial motion velocity patterns at the middle of the LV posterior wall (PW) and ventricular septum (IVS) in LV parasternal and apical long-axis views were recorded by pulsed TDI in 19 patients with nonobstructive HC and in 21 normal controls (NC). RESULTS: Peak short- and long-axis systolic subendocardial velocities in both the LV PW and IVS were significantly smaller in the HC group than in the NC group, and the time to peak velocity was significantly delayed. Furthermore, peak PW systolic velocity was significantly greater along the long axis than along the short axis in the NC group (8.8 +/- 1.5 cm/s vs 8.2 +/- 1.4 cm/s, P <.05), whereas the opposite was observed in the HC group (6.1 +/- 1.2 cm/s vs 7.5 +/- 1.0 cm/s, P <.0001). No significant differences were found in either group between the long- and short-axis IVS velocities (HC: 5.9 +/- 1.4 cm/s vs 5.5 +/- 1.3 cm/s; NC: 7.8 +/- 1.3 cm/s vs 7.9 +/- 1.6 cm/s). CONCLUSIONS: By using the capability of pulsed TDI for the evaluation of intrinsic myocardial velocity instantaneously in a specific region and direction, we found impairment of LV myocardial systolic function in patients with HC not only in the hypertrophied IVS but also in the nonhypertrophied LV PW. We also found a greater decrease in LV PW velocities along the long axis than the short axis, suggesting greater impairment of long-axis contraction in patients with HC. Because our HC patients did not appear to have excessive intracavitary pressure, these results suggest that the relatively normal-appearing PW is directly affected by the HC pathologic process.
Adult↗
Efficacy of anticoagulation in resolving left atrial and left atrial appendage thrombi: A transesophageal echocardiographic study.
BACKGROUND: Transesophageal echocardiography (TEE) is the gold standard for evaluation of the left atrium and the left atrial appendage (LAA) for the presence of thrombi. Anticoagulation is conventionally used for patients with atrial fibrillation to prevent embolization of atrial thrombi. The mechanism of benefit and effectiveness of thrombi resolution with anticoagulation is not well defined. METHODS AND RESULTS: We used a TEE database of 9058 consecutive studies performed between January 1996 and November 1998 to identify all patients with thrombi reported in the left atrium and/or LAA. One hundred seventy-four patients with thrombi in the left atrial cavity (LAC) and LAA were identified (1.9% of transesophageal studies performed). The incidence of LAA thrombi was 6.6 times higher than LAC thrombi (151 vs 23, respectively). Almost all LAC thrombi were visualized on transthoracic echocardiography (90.5%). Mitral valve pathology was associated with LAC location of thrombi (P <.0001), whereas atrial fibrillation or flutter was present in most patients with LAA location of thrombi. Anticoagulation of 47 +/- 18 days was associated with thrombus resolution in 80.1% of the patients on follow-up TEE. Further anticoagulation resulted in limited additional benefit. CONCLUSIONS: LAC thrombi are rare and are usually associated with mitral valve pathology. Transthoracic echocardiography is effective in identifying these thrombi. LAA thrombi occur predominantly in patients with atrial fibrillation or flutter. Short-term anticoagulation achieves a high rate of resolution of LAA and LAC thrombi but does not obviate the need for follow-up TEE.
Adult↗
Analysis of shape and motion of the mitral annulus in subjects with and without cardiomyopathy by echocardiographic 3-dimensional reconstruction.
The shape and dynamics of the mitral annulus of 10 patients without heart disease (controls), 3 patients with dilated cardiomyopathy, and 5 patients with hypertrophic obstructive cardiomyopathy and normal systolic function were analyzed by transesophageal echocardiography and 3-dimensional reconstruction. Mitral annular orifice area, apico-basal motion of the annulus, and nonplanarity were calculated over time. Annular area was largest in end diastole and smallest in end systole. Mean areas were 11.8 +/- 2.5 cm(2) (controls), 15.2 +/- 4.2 cm(2) (dilated cardiomyopathy), and 10.2 +/- 2.4 cm(2) (hypertrophic cardiomyopathy) (P = not significant). After correction for body surface, annuli from patients with normal left ventricular function were smaller than annuli from patients with dilated cardiomyopathy (5.9 +/- 1.2 cm(2)/m(2) vs 7.7 +/- 1.0 cm(2)/m(2); P <.02). The change in area during the cardiac cycle showed significant differences: 23.8% +/- 5.1% (controls), 13.2% +/- 2.3% (dilated cardiomyopathy), and 32.4% +/- 7.6% (hypertrophic cardiomyopathy) (P <.001). Apico-basal motion was highest in controls, followed by those with hypertrophic obstructive and dilated cardiomyopathy (1.0 +/- 0.3 cm, 0.8 +/- 0.2 cm, 0.3 +/- 0.2 cm, respectively; P <.01). Visual inspection and Fourier analysis showed a consistent pattern of anteroseptal and posterolateral elevations of the annulus toward the left atrium. In conclusion, although area changes and apico-basal motion of the mitral annulus strongly depend on left ventricular systolic function, nonplanarity is a structural feature preserved throughout the cardiac cycle in all three groups.
Adult↗
Transesophageal echocardiography assessment of severe ostial left main coronary stenosis.
Doppler echocardiography is commonly used in the assessment of stenotic valvular orifices. We describe the application of transesophageal echocardiography for the detection of a critical ostial left main coronary stenosis. Because preoperative coronary angiography often is not routinely performed in young patients undergoing valve surgery, application of Doppler echocardiography can potentially prevent catastrophic complications, particularly in atypical cases.
Adult↗
New imaging technology: measurement of myocardial perfusion by contrast echocardiography.
Myocardial perfusion imaging has long been a goal for the non-invasive echocardiographic assessment of the heart. However, many factors at play in perfusion imaging have made this goal elusive. Harmonic imaging and triggered imaging with newer contrast agents have made myocardial perfusion imaging potentially practical in the very near future. The application of indicator dilution theory to the coronary circulation and bubble contrast agents is fraught with complexities and sources of error. Therefore, quantification of myocardial perfusion by non-invasive echocardiographic imaging requires further investigation in order to make this technique clinically viable.
Contrast Media↗
Individualizing the aorto-radial pressure transfer function: feasibility of a model-based approach.
We fitted a three-segment transmission line model for the radial-carotid/aorta pressure transfer function (TFF) in 31 controls and 30 patients with coronary artery disease using noninvasively measured (tonometry) radial and carotid artery pressures (P(car)). Except for the distal reflection coefficient (0.85 +/- 0.21 in patients vs. 0.71 +/- 0.25 in controls; P < 0.05), model parameters were not different between patients or controls. Parameters were not related to blood pressure, age, or heart rate. We further assessed a point-to-point averaged TFF (TFF(avg)) as well as upper (TFF(max)) and lower (TFF(min)) enveloping TFF. Pulse pressure (PP) and augmentation index (AIx) were derived on original and reconstructed P(car) (P(car,r)). TFF(avg) yielded closest morphological agreement between P(car) and P(car,r) (root mean square = 4.3 +/- 2.3 mmHg), and TTF(avg) best predicted PP (41.5 +/- 11.8 vs. 41.1 +/- 10.0 mmHg measured) and AIx (-0.02 +/- 0.19 vs. 0.01 +/- 0.19). PP and AIx, calculated from P(car) or P(car,r), were higher in patients than in controls, irrespectively of the TFF used. We conclude that 1) averaged TFF yield significant discrepancies between reconstructed and measured pressure waveforms and subsequent derived AIx; and 2) different TFFs seem to preserve the information in the pressure wave that discriminates between controls and patients.
Adult↗
Doppler echo evaluation of pulmonary venous-left atrial pressure gradients: human and numerical model studies.
The simplified Bernoulli equation relates fluid convective energy derived from flow velocities to a pressure gradient and is commonly used in clinical echocardiography to determine pressure differences across stenotic orifices. Its application to pulmonary venous flow has not been described in humans. Twelve patients undergoing cardiac surgery had simultaneous high-fidelity pulmonary venous and left atrial pressure measurements and pulmonary venous pulsed Doppler echocardiography performed. Convective gradients for the systolic (S), diastolic (D), and atrial reversal (AR) phases of pulmonary venous flow were determined using the simplified Bernoulli equation and correlated with measured actual pressure differences. A linear relationship was observed between the convective (y) and actual (x) pressure differences for the S (y = 0.23x + 0.0074, r = 0.82) and D (y = 0.22x + 0.092, r = 0.81) waves, but not for the AR wave (y = 0. 030x + 0.13, r = 0.10). Numerical modeling resulted in similar slopes for the S (y = 0.200x - 0.127, r = 0.97), D (y = 0.247x - 0. 354, r = 0.99), and AR (y = 0.087x - 0.083, r = 0.96) waves. Consistent with numerical modeling, the convective term strongly correlates with but significantly underestimates actual gradient because of large inertial forces.
Atrial Function↗