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Objective: To investigate the effects of digoxin on left atrial (LA) function in patients with congestive heart failure and dilated left atria. Patients: 30 patients with enlarged left atrium (maximum LA diameter > 4 mm) caused by heart failure (New York Heart Association functional class III or IV) were studied before and after treatment with digoxin (0.25 mg orally for 12 days). Digoxin was also administered to 30 normal participants who served as controls. Main outcome measures: LA active (AEF) and passive emptying fractions (PEF), reservoir fraction (RF), kinetic energy (KE), and mean velocity of circumferential atrial fibre shortening (Vcf) were calculated from echocardiographic measurements of LA volumes and transmitral Doppler flow velocities at baseline and on the third, sixth, eighth, and 12th day after digoxin administration. Results: LA AEF, PEF, RF, KE, and Vcf were significantly lower in patients than in controls (p < 0.001). LA AEF, PEF, RF, KE, and Vcf increased significantly both in patients and controls after digoxin administration (p < 0.001). This increase was greater in patients than in controls (p < 0.001). KE was linearly correlated with LA volume at the onset of atrial systole in all participants. The slope and the intercept of this relation were significantly increased after digoxin both in patients and in controls (p < 0.001). Conclusions: LA performance is impaired in patients with heart failure. Dilated atria manifest atrial failure. Digoxin improves LA performance and LA contractility both in dilated and in normal atria. The effects of digoxin on LA contractility are augmented in the failing atria compared with the normal atria.

Diastolic fluid dynamics in the left ventricle (LV) has been examined in multiple clinical studies for understanding cardiac function in healthy humans and developing diagnostic measures in disease conditions. The question of how intraventricular filling vortex flow pattern is affected by increasing heart rate (HR) is still unanswered. Previous studies on healthy subjects have shown a correlation between increasing HR and diminished E/A ratio of transmitral peak velocities during early filling (E-wave) to atrial systole (A-wave). We hypothesize that with increasing HR under constant E/A ratio, E-wave contribution to intraventricular vortex propagation is diminished. A physiologic in vitro flow phantom consisting of a LV physical model was used for this study. HR was varied across 70, 100 and 120 beats per minute (bpm) with E/A of 1.1–1.2. Intraventricular flow patterns were characterized using 2D particle image velocimetry measured across three parallel longitudinal (apical–basal) planes in the LV. A pair of counter-rotating vortices was observed during E-wave across all HRs. With increasing HR, diminished vortex propagation occurred during E-wave and atrial systole was found to amplify secondary vorticity production. The diastolic time point where peak vortex circulation occurred was delayed with increasing HR, with peak circulation for 120bpm occurring as late as 90% into diastole near the end of A-wave. The role of atrial systole is elevated for higher HR due to the limited time available for filling. Our baseline findings and analysis approach can be applied to studies of clinical conditions where impaired exercise tolerance is observed.

Doc number: O6

The hemodynamic waveforms obtained with pulmonary capillary wedge pressure tracings in the cardiac catheterization laboratory or during monitoring in the intensive care unit are probably among the most important and practical clinical hemodynamic data. Use of the pressure half‐time method appears to be more predictive of the true valve area in patients with hemodynamic tracings of combined mitral regurgitation and stenosis. Normally, V waves on the pulmonary capillary wedge tracing reflect left atrial filling during ventricular systole and atrial emptying immediately after ventricular systole and ventricular relaxation. The compliance of the ventricle and atrium is the major determinant of changes in the atrial and ventricular pressure waves. In patients with myocardial infarction, the mean pulmonary capillary wedge pressure often correlates better with the pressure before the A wave at the beginning of atrial systole.

This chapter contains sections titled: Pathophysiology Mechanisms of MR References

Exaggerated orthostatic changes in systolic blood pressure (SBP) were associated with adverse cardiovascular events. We aim to assess the association between orthostatic SBP changes and incident atrial fibrillation (AF). We performed a post hoc analysis of SPRINT (Systolic Blood Pressure Intervention Trial). Orthostatic SBP changes were defined as standing SBP minus seated SBP. Patients were grouped into tertiles of orthostatic SBP changes. We used Cox proportional regression models to assess the association of orthostatic SBP changes with incident AF. Among 8455 participants included in this analysis, 327 incident AF cases occurred during follow‐up. After adjusting for age, female, race, smoking, alcohol use, history of cardiovascular disease, history of chronic kidney disease, and body mass index, an SBP increase ≥6 mmHg to standing was independently associated with a 43% higher risk of incident AF (HR: 1.43; 95% CI: 1.07–1.90; p = 0.014) compared to nonsignificant orthostatic SBP changes (>–4 to <6 mmHg). A SBP decrease ≥4 mmHg to standing showed a nonsignificant higher risk of developing AF compared to SBP changes of >–4 to <6 mmHg. In subgroup analysis, the results presented a similar tendency to the main result. Sensitivity analyses also generated consistent results while additionally adjusting for seated and standing blood pressure or heart rate. In this post hoc analysis of the SPRINT trial, exaggerated SBP increase on standing independently predicts incident AF. Trial Registration: ClinicalTrials.gov identifier: NCT00000620.

ObjectiveTo improve the echocardiographic assessment of heart failure in patients with atrial fibrillation (AF) by comparing conventional averaging of consecutive beats with an index-beat approach, whereby measurements are taken after two cycles with similar R-R interval.MethodsTransthoracic echocardiography was performed using a standardised and blinded protocol in patients enrolled in the RATE-AF (RAte control Therapy Evaluation in permanent Atrial Fibrillation) randomised trial. We compared reproducibility of the index-beat and conventional consecutive-beat methods to calculate left ventricular ejection fraction (LVEF), global longitudinal strain (GLS) and E/e’ (mitral E wave max/average diastolic tissue Doppler velocity), and assessed intraoperator/interoperator variability, time efficiency and validity against natriuretic peptides.Results160 patients were included, 46% of whom were women, with a median age of 75 years (IQR 69–82) and a median heart rate of 100 beats per minute (IQR 86–112). The index-beat had the lowest within-beat coefficient of variation for LVEF (32%, vs 51% for 5 consecutive beats and 53% for 10 consecutive beats), GLS (26%, vs 43% and 42%) and E/e’ (25%, vs 41% and 41%). Intraoperator (n=50) and interoperator (n=18) reproducibility were both superior for index-beats and this method was quicker to perform (p<0.001): 35.4 s to measure E/e’ (95% CI 33.1 to 37.8) compared with 44.7 s for 5-beat (95% CI 41.8 to 47.5) and 98.1 s for 10-beat (95% CI 91.7 to 104.4) analyses. Using a single index-beat did not compromise the association of LVEF, GLS or E/e’ with natriuretic peptide levels.ConclusionsCompared with averaging of multiple beats in patients with AF, the index-beat approach improves reproducibility and saves time without a negative impact on validity, potentially improving the diagnosis and classification of heart failure in patients with AF.

Background Whether elevated blood pressure (BP) is a modifiable risk factor for atrial fibrillation (AF) is not established. We tested (1) whether the association between BP and risk of AF is causal, (2) whether it varies according to individual’s genetic susceptibility for AF, and (3) the extent to which specific BP-lowering drugs are expected to reduce this risk. Methods First, causality of association was assessed through two-sample Mendelian randomization, using data from two independent genome-wide association studies that included a population of one million Europeans in total. Second, the UK Biobank data of 329,237 participants at baseline was used to study the effect of BP on AF according to genetic susceptibility of developing AF. Third, a possible treatment effect with major BP-lowering drug classes on AF risk was predicted through genetic variants in genes encode the therapeutic targets of each drug class. Estimated drug effects were compared with effects on incident coronary heart disease, for which direct trial evidence exists. Results The two-sample Mendelian randomization analysis indicated that, on average, exposure to a higher systolic BP increased the risk of AF by 19% (odds ratio per each 10-mmHg [OR] 1.19 [1.12 to 1.27]). This association was replicated in the UK biobank using individual participant data. However, in a further genetic risk-stratified analysis, there was evidence for a linear gradient in the relative effects of systolic BP on AF; while there was no conclusive evidence of an effect in those with low genetic risk, a strong effect was observed among those with high genetic susceptibility for AF. The comparison of predicted treatment effects using genetic proxies for three main drug classes (angiotensin-converting enzyme inhibitors, beta-blockers, and calcium channel blockers) suggested similar average effects for the prevention of atrial fibrillation and coronary heart disease. Conclusions The effect of elevated BP on the risk of AF is likely to be causal, suggesting that BP-lowering treatment may be effective in AF prevention. However, average effects masked clinically important variations, with a more pronounced effect in individuals with high genetic susceptibility risk for AF.

[Display omitted] •Lower left atrial (LA) strain and LA strain rate were independently associated with new-onset atrial fibrillation (AF).•Lower LA strain and LA strain rate predicted AF even in participants with normal LA volume.•Reduced reservoir function predicted AF in participants with smaller LA volume.•Reduced pump function predicted AF in participants with larger LA volume. Atrial fibrillation (AF) is frequent in older adults and associated with left atrial (LA) dysfunction. LA strain (LAε) and LA strain rate (LASR) may detect subclinical LA disease. We investigated whether reduced LAε and LASR predict new-onset AF in older adults without history of AF or stroke. LAε and LASR were assessed by speckle-tracking echocardiography in 824 participants from the community-based Cardiovascular Abnormalities and Brain Lesions study. Positive longitudinal LAε and LASR during ventricular systole, LASR during early ventricular diastole, and LASR during LA contraction were measured. Cause-specific hazards regression model evaluated the association of LAε and LASR with incident AF, adjusting for pertinent covariates. The mean age was 71.1 ± 9.2 years (313 men, 511 women). During a mean follow-up of 10.9 years, new-onset AF occurred in 105 participants (12.7%). Lower LAε and LASR at baseline were observed in patients with new-onset AF (all p <0.01). In multivariable analysis, positive longitudinal LAε (adjusted hazard ratio [HR] per SD decrease 2.05, confidence interval [CI] 1.24 to 3.36) and LASR during LA contraction (HR per SD increase 2.24, CI 1.37 to 3.65) remained associated with new-onset AF, independently of LA volumes and left ventricular function. Along with positive longitudinal LAε, reduced LASR during ventricular systole predicted AF in participants with LA volume below the median value (HR 2.54, CI 1.10 to 6.09), whereas reduced LASR during LA contraction predicted AF in participants with larger LA (HR 2.35, CI 1.31 to 4.23). In conclusion, reduced positive longitudinal LAε and LASR predict new-onset AF in older adults regardless of LA size and may improve AF risk stratification.

Restoration of sinus rhythm in atrial fibrillation (AF) by radiofrequency catheter ablation (RFCA) is associated with a transient stunning of left atrial (LA) function. However, the long-term effects of different ablation strategies on LA function remain undetermined. We performed randomized controlled trial to evaluate the effects of RFCA, cryoablation, and 3D mapping-guided cryoablation on LA function of proximal AF patients within 1 year. The 3D mapping-guided cryoablation was defined as a maximum of two cryoablation procedures for each pulmonary vein accompanied by RFCA for additional points until complete pulmonary vein isolation was achieved. Conventional and speckle tracking echocardiographic analyses were performed to evaluate LA function. Among the 210 patients (70 in each group) included, a trend of decreasing LA systolic and diastolic function was observed in all groups, as evidenced by decreases in peak A-wave velocity, the global LA peak systolic strain, the peak strain rate, the peak early diastolic strain rate, and the peak late diastolic strain rate within 7 days to 3 months after ablation followed by gradual recovery thereafter. However, the temporal changes in the above four strain parameters among the three groups did not differ significantly within 1 year after ablation (all p > 0.05). Parameters of the LA emptying fraction and LA dimensions were not significantly affected. These results suggested that stunning of LA function occurred within 7 days to 3 months after ablation, and different strategies of AF ablation did not differentially affect the temporal changes in LA function up to 1 year after ablation.