Increase In Left Atrial Pressure Research Articles

Verification of intra- and inter-atrial conduction during Bachmann's bundle pacing using longitudinal bi-atrial strain

Abstract Introduction Although atrial septal pacing has been reported to reduce atrial fibrillation (AF) burden, there is less evidence regarding its effect on the prevention of permanent AF and the improvement of long-term clinical outcomes. However, Bachmann's bundle pacing (BBp), which features P-wave morphology similar to sinus rhythm and shortened P-wave duration (PWD), was reported to significantly reduce permanent AF recurrences and occurrences compared with right atrial appendage pacing (RAAp) and non-specific right septal pacing. Purpose Possible mechanisms for AF suppression with BBp are that fast inter-atrial conduction through BB decreases global atrial activation time and the dispersion of the overall atrial refractoriness, and it prevents the decrease in left ventricular filling and increase in left atrial pressure associated with delayed left atrial contraction. Intra-and inter-atrial conduction during BBp was evaluated using longitudinal bi-atrial strain. Methods In patients with successful BBp implantation defined by electrocardiographic criteria using SelectSecure pacing lead and C315 delivery catheter (Medtronic, Inc), both left atrium (LA) and right atrium (RA) global longitudinal strain (GLS) in simultaneous phases were measured using Philips Ultrasound Workspace 2D Strain in apical 4-chamber view during atrial pacing to assess intra- and inter-atrial conduction delay. The atrial GLS were measured semi-automatically, and the strain rate was analyzed in the three segments of septal wall, lateral wall, and roof and their average. The negative peak of strain rate during atrial systole was the starting point of atrial contraction, and time to peak (TTP) was measured. The difference in TTP between septal and lateral walls in each atrium was measured as intra-atrial conduction delay and the difference in average TTP between LA and RA as inter-atrial conduction delay. Results Ten patients who underwent successful BBp were enrolled (Sick sinus syndrome: 3, advanced atrioventricular block: 2, complete atrioventricular block: 5). At implantation, bipolar atrial electrogram amplitude was 2.03±0.93 mV, atrial lead impedance was 632.7±157.6 Ω, and atrial pacing threshold was 0.7±0.2 V at 0.4 ms. The PWD during sinus rhythm on the 12-lead ECG was 132.8±10.6 ms, while during BBp it was 108.0±11.9 ms, which was significantly shorter in the BBp group (p<0.001). The intra-atrial conduction delay in RA and LA was 10.9 ± 12.1 ms and 12.1 ± 17.3 ms, respectively, and the inter-atrial conduction delay was 6.6 ± 8.6 ms. On the other hand, for the 10 RAAp and 10 sinus rhythm patients as control groups, the inter-atrial conduction delay was 29.7±13.8 ms and 8.5±9.5 ms, respectively. BBp had significantly less inter-atrial conduction delay than RAAp (p=0.005) and was comparable to sinus rhythm (p=0.719). Conclusion Longitudinal bi-atrial strain suggested that BBp significantly reduced inter-atrial delay and it might be effective in AF suppression.Longitudinal bi-atrial strain

Atrial fibrillation is perpetuated by human heart secretome in ex-vivo langendorff-perfused hearts

Abstract Introduction Atrial fibrillation (AF) confers high morbidity and mortality, yet parts of the underlying pathophysiology remain elusive. Left atrial (LA) pressure is altered by the presence of AF and vice-versa. The cardiac secretome might be influenced by LA pressure and potentially alters the susceptibility of the atria to AF. We investigated the effect of the human cardiac secretome on atrial electrophysiology in a translational ex-vivo setting. Methods We obtained venous (coronary sinus) serum samples during AF and in sinus rhythm (SR) in patients hospitalized for pulmonary vein isolation (PVI). Moreover, LA tissue was collected from patients undergoing cardiac surgery and coronary sinus serum samples were collected before (CTRL) and after intraoperative volume challenge (VC). Single cardiomyocytes were isolated from human LA tissue and Ca2+ dependent excitation-contraction coupling (ECC) was studied using confocal line-scan imaging with CTRL or VC. Moreover, a modified Langendorff-Setup with the ability to monitor and control intra-cardiac pressure was utilized to perfuse mouse hearts with AF and SR serum. A multielectrode array (MEA) was placed on the epicardial aspect of the left atrium to measure electrical signals in a spatiotemporal fashion. External bipolar burst pacing protocols were applied to test AF inducibility. Results Ca2+ dependent ECC (i.e. Ca2+ amplitude and release) in human cardiomyocytes was unaltered with exposure to VC serum. Upon introducing a modified version of the Langendorff setup with the ability of linear pressure adjustment, a burst pacing protocol to test for AF inducibility was successfully implemented in mice atria. Atria perfused with human AF serum showed significantly increased AF inducibility as compared to SR serum. Moreover, both, total AF duration as well as number of AF episodes (i.e. AF burden) were increased in AF vs. SR serum upon several different pacing protocols. Conclusion Cardiac secretome during increased LA pressure had no significant effect on Ca2+ dependent ECC in human cardiomyocytes. However, secretome during AF conferred pro-arrhythmogenic properties as compared to SR, further strengthening the concept of "AF begets AF". Ongoing experiments test the hypothesis of potential differences in the multi-level omics profile of AF serum as the underlying mechanism.

The hybrid (physical-computational) cardiovascular simulator to study valvular diseases

To better understand the impact of valvular heart disease (VHD) on the hemodynamics of the circulatory system, investigations can be carried out using a model of the cardiovascular system. In this study, a previously developed hybrid (hydro-numerical) simulator of the cardiovascular system (HCS) was adapted and used. In our HCS Björk-Shiley mechanical heart valves were used, playing the role of mitral and aortic ones. In order to simulate aortic stenosis (AS) and mitral regurgitation (MR), special mechanical devices have been developed and integrated with the HCS. The simulation results proved that the system works correctly. Namely, in the case of AS − the mean pulmonary arterial pressure was increased due to increased preload of the left ventricle and the decrease in right ventricular preload was caused by a decrease in systemic arterial pressure. The severity of AS was performed based on the transaortic pressure gradient as well as using the Gorlin and Aaslid equations. In the case of severe AS, when the mean gradient was above 40 mmHg, the aortic valve orifice area was 0.5 cm2, which is in line with ACC/AHA guidelines. For the case of MR − with increasing severity of MR, there was a decrease in the left ventricular pressure and an increase in left atrial pressure. Using mechanical heart valves to simulate VHD by the HCS can be a valuable tool for biomedical research, providing a safe and controlled environment to study and understand the pathophysiology of VHD.

Computational modeling of heart failure in microgravity transitions.

The space tourism industry is growing due to advances in rocket technology. Privatised space travel exposes non-professional astronauts with health profiles comprising underlying conditions to microgravity. Prior research has typically focused on the effects of microgravity on human physiology in healthy astronauts, and little is known how the effects of microgravity may play out in the pathophysiology of underlying medical conditions, such as heart failure. This study used an established, controlled lumped mathematical model of the cardiopulmonary system to simulate the effects of entry into microgravity in the setting of heart failure with both, reduced and preserved ejection fraction. We find that exposure to microgravity eventuates an increased cardiac output, and in patients with heart failure there is an unwanted increase in left atrial pressure, indicating an elevated risk for development of pulmonary oedema. This model gives insight into the risks of space flight for people with heart failure, and the impact this may have on mission success in space tourism.

Abstract 15989: Gore Cardioform Device Complicated by Delayed Right Atrial Disk Expansion

This is a 31-year-old male with a recently discovered secundum atrial septal defect (ASD) with significant left-to-right shunt and associated right ventricular enlargement and dysfunction underwent an uncomplicated percutaneous ASD closure device placement earlier in 2023. Five weeks later, upon repeat transthoracic echocardiogram (TTE), the patient was found to have new onset atrial flutter and what was thought to be a large device-related thrombus abutting the right atrial disc. The patient was admitted to the hospital, started on systemic anticoagulation, and AV nodal blocker therapy. X-rays and a transesophageal echocardiogram (TEE) were performed and showed a Gore Cardioform ASD occluder device that was complicated with significant expansion of the right atrial disk and loosening of fabric likely in the setting of displacement of locking pin (Figure 1A-B). No clear thrombus was visualized. The patient underwent an uncomplicated ASD closure device removal, ASD repair with pericardial patch, right sided Maze, and left atrial appendage ligation in May of 2023 (Figure 1C). We report a case of extreme expansion of the right atrial disk of the Gore Cardioform septal occlusion device. Very few cases of right or left atrial disk expansion have been reported but only in the immediate post-implantation period. This is thought to be secondary to immediate post-operative increase in left atrial pressures. In our patient, intra-procedural TEE and immediate post-procedural TTE the day after showed a well-apposed device across the ASD with no residual shunt. Furthermore, the wedge pressure measured during the procedure was within normal limits. Extreme expansion of the right atrial disk five weeks after the implantation has not been reported. While we know that the pin unlocking caused the expansion of the atrial disk, it is currently unclear as to what initiated this series of events.

Abstract 14837: Increase in Left Atrial Pressure After Cryoballoon Ablation Indicates Worse Atrial Function: Evidence From APPEARANCE-AF Trial

Introduction: Left atrial pressure (LAP) is a direct reflection of left atrial function, while LAP could fluctuate following left atrial procedure. The pattern of LAP change in response to pulmonary vein isolation (PVI) and its significance remain to be explored. Hypothesis: The change of LAP before and after PVI could indicate atrial function and predict adverse events. Methods: 28 patients from APPEARANCE-AF trial underwent PVI using cryoballoon ablation were included. Pre-ablation and post-ablation LAP were directly measured via catheter. The correlation of LAP change with demographics, biochemical measurements, and speckle traced echocardiographic indexes of left atrium (LA) were investigated. Results: The included cohort has a mean age of 73.8±8.4 years old, with 12 male (42.9%). Instant PVI was achieved in all patients without complications. The average mean LAP (mLAP) measured before and after PVI was 8.2±4.5 mmHg (pre mLAP) and 14.0±6.5 mmHg (post mLAP), with a significant increment (ΔmLAP: 5.8±4.5 mmHg, P<0.001). In the evaluation of the association of LAP with LA function, the change in LAP significantly correlated with LA strain rate in reservoir (LASr, r=-0.58, P=0.001) and conduit phase (LAScd, r=0.63, P<0.001) and LA ejection fraction (r=-0.48, P=0.014). Furthermore, we divided the cohort into group with significant increment of LAP (inc-mLAP, increment of mLAP > 5 mmHg, n=14) and group with non-significant increment of LAP (ninc-mLAP, mLAP ≤ 5 mmHg, n=14). Correspondingly, patients with larger LAP increment presented significant worse atrial function indicated by LASr (17.3%±5.6% ninc-mLAP vs 11.5%±7.3% inc-mLAP, P=0.030), LAScd (-9.6%±2.2% ninc-mLAP vs -5.7%±3.6% inc-mLAP, P=0.003). Conclusions: PVI could significantly increase LAP, and a higher change of LAP could indicate worse atrial function. Measuring the change of LAP might be valuable in predicting the prognosis of PVI.

Pulmonary Hypertension Associated with Left Heart Disease.

Pulmonary hypertension (PH) is a common complication of diseases affecting the left heart, mostly found in patients suffering from heart failure, with or without preserved left ventricular ejection fraction. Initially driven by a passive increase in left atrial pressure (postcapillary PH), several mechanisms may lead in a subset of patient to significant structural changes of the pulmonary vessels or a precapillary component. In addition, the right ventricle may be independently affected, which results in right ventricular to pulmonary artery uncoupling and right ventricular failure, all being associated with a worse outcome. The differential diagnosis of PH associated with left heart disease versus pulmonary arterial hypertension (PAH) is especially challenging in patients with cardiovascular comorbidities and/or heart failure with preserved ejection fraction (HFpEF). A stepwise approach to diagnosis is proposed, starting with a proper clinical multidimensional phenotyping to identify patients in whom hemodynamic confirmation is deemed necessary. Provocative testing (exercise testing, fluid loading, or simple leg raising) is useful in the cath laboratory to identify patients with abnormal response who are more likely to suffer from HFpEF. In contrast with group 1 PH, management of PH associated with left heart disease must focus on the treatment of the underlying condition. Some PAH-approved targets have been unsuccessfully tried in clinical studies in a heterogeneous group of patients, some even leading to an increase in adverse events. There is currently no approved therapy for PH associated with left heart disease.

Acute Hemodynamics in the Fontan Circulation: Open-Label Study of Vasopressin.

To describe the acute hemodynamic effect of vasopressin on the Fontan circulation, including systemic and pulmonary pressures and resistances, left atrial pressure, and cardiac index. Prospective, open-label, nonrandomized study (NCT04463394). Cardiac catheterization laboratory at Lucile Packard Children's Hospital, Stanford. Patients 3-50 years old with a Fontan circulation who were referred to the cardiac catheterization laboratory for hemodynamic assessment and/or intervention. A 0.03 U/kg IV (maximum dose 1 unit) bolus of vasopressin was administered over 5 minutes, followed by a maintenance infusion of 0.3 mU/kg/min (maximum dose 0.03 U/min). Comprehensive cardiac catheterization measurements before and after vasopressin administration. Measurements included pulmonary artery, atrial, and systemic arterial pressures, oxygen saturations, and systemic and pulmonary flows and resistances. There were 28 patients studied. Median age was 13.5 (9.1, 17) years, and 16 (57%) patients had a single or dominant right ventricle. Following vasopressin administration, systolic blood pressure and systemic vascular resistance (SVR) increased by 17.5 (13.0, 22.8) mm Hg ( Z value -4.6, p < 0.001) and 3.8 (1.8, 7.5) Wood Units ( Z value -4.6, p < 0.001), respectively. The pulmonary vascular resistance (PVR) decreased by 0.4 ± 0.4 WU ( t statistic 6.2, p < 0.001), and the left atrial pressure increased by 1.0 (0.0, 2.0) mm Hg ( Z value -3.5, p < 0.001). The PVR:SVR decreased by 0.04 ± 0.03 ( t statistic 8.1, p < 0.001). Neither the pulmonary artery pressure (median difference 0.0 [-1.0, 1.0], Z value -0.4, p = 0.69) nor cardiac index (0.1 ± 0.3, t statistic -1.4, p = 0.18) changed significantly. There were no adverse events. In Fontan patients undergoing cardiac catheterization, vasopressin administration resulted in a significant increase in systolic blood pressure, SVR, and left atrial pressure, decrease in PVR, and no change in cardiac index or pulmonary artery pressure. These findings suggest that in Fontan patients vasopressin may be an option for treating systemic hypotension during sedation or general anesthesia.

Transient Increase in the Terminal Negative Deflection of the P Wave in Lead V1 during Treadmill Testing Identifies Exercise Induced Aggravated Left Ventricular Dysfunction

Terminal negative deflection of the P wave in lead V1 is produced by posteriorly directed depolarization of the left atrium. A value of more than 0.04 mm sec suggests increase in left atrial pressure. Transient new appearance of this finding during treadmill testing suggests transient exercise induced increase in left atrial pressure. Indirectly it suggests transient exercise induced/aggravated increase in left ventricular end diastolic pressure. In presence of clinical and/or electrocardiographic findings of myocardial ischemia, this finding suggest ischemia induced left ventricular dysfunction. Earlier this finding appears during exercise and longer it lasts during recovery, more severe is the left ventricular dysfunction.

Abstract 12468: Hemodynamic Validation of Echocardiographic Left Ventricular to Left Atrial Volumes Ratio Indices in Heart Failure With Preserved Ejection Fraction

Introduction: The assessment of mean left atrial (LA) pressure rather than Left Ventricular (LV) end-diastolic pressure reflects more accurately filling pressure which is pathophysiological landmark of Heart Failure with preserved Ejection Fraction (HFpEF). Hypothesis: We sought to test whether the measurement of LV to LA volume ratio at the specific cardiac phases can estimate resting LA pressure in patients with HFpEF. Methods: Fifty-three HFpEF patients (mean age 71+-10 years) who underwent cardiac catheterization including direct, at rest, retrograde LA pressure, were analysed. Echocardiographic data was obtained 1.5+-1.0 hours off cardiac catheterization. Patients were divided into: Group 1 (normal filling pressure) and Group 2 (elevated filling pressure, mean LA pressure &gt;12mmHg and/or pulmonary capillary wedge pressure 14mmHg). The ratio of LV/LA volume was measured in end-systole (LV ES /LA max ), end-diastole (LV ED /LA min ), diastasis (LV dias /LA dias ), and as both maximum (LV ED /LA max ), and minimum (LV ES /LA min ). Results: All measured LV/LA ratios were lower in Group 2 as compared to Group 1 and correlated inversely with an increased LA pressure (LV ED /LA min , r=-0.54, p&lt;0.001; LV ES /LA min , r=-0.53, p&lt;0.001; LV ED /LA max , r=-0.52, p&lt;0.001; LV dias /LA dias , r=-0.50, p&lt;0.001; LV ES /LA max , r=-0.37, p=0.013. The following ratios, LV dias /LA dias , LV ED /LA max , LV ED /LA min , and LV ES /LA min , were the most accurate echocardiographic indices to differentiate HFpEF patients between Group 2 and Group 1 (independently off the presence atrial fibrillation), with the area under the curve &gt;0.75 and statistically noninferior to the following a new LA function parameters such as: LA reservoir strain, index LA reservoir strain, LA total emptying fraction and LA active emptying fraction. The cut-off values for LV ES /LA min &lt;1.45 and LV dias /LA dias &lt;1.30 had the sensitivity 78%, 74% and specificity 71%, 71%, respectively, to differentiate patients between Group 2 and Group 1. Conclusions: Among all studied echocardiographic indices the LV ES /LA min and LV dias /LA dias were the most accurate parameters to assess the level of LA pressure in HFpEF.

Exercise and hypoxia unmask pulmonary vascular disease and right ventricular dysfunction in a 10- to 12-week-old swine model of neonatal oxidative injury.

Prematurely born young adults who experienced neonatal oxidative injury (NOI) of the lungs have increased incidence of cardiovascular disease. Here, we investigated the long‐term effects of NOI on cardiopulmonary function in piglets at the age of 10–12 weeks. To induce NOI, term‐born piglets (1.81 ± 0.06 kg) were exposed to hypoxia (10–12% FiO2), within 2 days after birth, and maintained for 4 weeks or until symptoms of heart failure developed (range 16–28 days), while SHAM piglets were normoxia raised. Following recovery (>5 weeks), NOI piglets were surgically instrumented to measure haemodynamics during hypoxic challenge testing (HCT) and exercise with modulation of the nitric‐oxide system. During exercise, NOI piglets showed a normal increase in cardiac index, but an exaggerated increase in pulmonary artery pressure and a blunted increase in left atrial pressure – suggesting left atrial under‐filling – consistent with an elevated pulmonary vascular resistance (PVR), which correlated with the duration of hypoxia exposure. Moreover, hypoxia duration correlated inversely with stroke volume (SV) during exercise. Nitric oxide synthase inhibition and HCT resulted in an exaggerated increase in PVR, while the PVR reduction by phosphodiesterase‐5 inhibition was enhanced in NOI compared to SHAM piglets. Finally, within the NOI piglet group, prolonged duration of hypoxia was associated with a better maintenance of SV during HCT, likely due to the increase in RV mass. In conclusion, duration of neonatal hypoxia appears an important determinant of alterations in cardiopulmonary function that persist further into life. These changes encompass both pulmonary vascular and cardiac responses to hypoxia and exercise. Key points Children who suffered from neonatal oxidative injury, such as very preterm born infants, have increased risk of cardiopulmonary disease later in life.Risk stratification requires knowledge of the mechanistic underpinning and the time course of progression into cardiopulmonary disease.Exercise and hypoxic challenge testing showed that 10‐ to 12‐week‐old swine that previously experienced neonatal oxidative injury had increased pulmonary vascular resistance and nitric oxide dependency.Duration of neonatal oxidative injury was a determinant of structural and functional cardiopulmonary remodelling later in life.Remodelling of the right ventricle, as a result of prolonged neonatal oxidative injury, resulted in worse performance during exercise, but enabled better performance during the hypoxic challenge test.Increased nitric oxide dependency together with age‐ or comorbidity‐related endothelial dysfunction may contribute to predisposition to pulmonary hypertension later in life.

GCW-UNet segmentation of cardiac magnetic resonance images for evaluation of left atrial enlargement

Background and objectiveLeft atrial enlargement (LAE) is an anatomical variation of the left atrium and the result of the long-term increase of left atrial pressure. Most of the increase in stress or volume is due to potential cardiovascular disease. Studies have shown that LAE can independently predict the development of clinically significant cardiovascular disease and heart failure. If the left atrial volume is accurately measured, it will be an essential indicator of human health and an essential means for doctors to find patients' potential diseases. We can analyze the dynamic changes in the left atrial structure and analyze left atrial dilation. However, manual segmentation was inefficient and error-prone before the 3D reconstruction of the left atrium. In order to solve this problem, a convolution neural network (CNN) method based on cardiac magnetic resonance image (MRI) is proposed to automatically segment the left atrial region. MethodologyIn this paper, we have proposed and developed a novel U-Net with Gaussian blur and channel weight neural network (GCW-UNet) to automatically segment the left atrial region in the MRI of a patient with LAE. After Gaussian blur, different resolutions of the MRI are obtained. High-resolution MRI clearly shows the detailed features of the left atrium, while low-resolution MRI clearly shows the overall outline of the left atrium, which can solve the problem of more minor MRI features. Adaptive channel weights can enhance the atrial segmentation capability of the network. ResultsCompared with the state-of-the-art left atrial segmentation methods, our CNN-based technique results in the segmentation of the left atrium being closer to the manual segmentation by an experienced radiologist. On the test datasets, the mean Dice similarity coefficient reaches 93.57%. ConclusionFirstly, MRI has a small number of imaging artifacts, which results in low segmentation accuracy. Our method successfully solves the problem. Secondly, due to the high similarity between the background (the area outside the left atrium) and the foreground (the left atrium) in MRI, traditional neural networks misclassify the background as the foreground. Our GCW-Unit can address the imbalanced number of pixels between the foreground and background. Finally, after segmenting the left atrium in the MRI by GCW-Unit, we reconstructed the left atrium to model a three-dimensional heart of a patient suffering from LAE. Based on the different time frames of one heartbeat, we could present the dynamics of the left atrial structure during a cardiac cycle. This can better assist in the evaluation of LAE in heart patients.

PO-657-07 SPONTANEOUS RESTORATION OF SINUS RHYTHM AFTER INTER ATRIAL SHUNT PLACEMENT IN A PATIENT WITH LONGSTANDING PERSISTENT ATRIAL FIBRILLATION

Left atrial (LA) pressure overload is an important mediator of atrial remodeling and stretch-induced atrial fibrillation (AF). Mechanoelectrical alterations promote atrial myocyte hypertrophy, fibrosis, and potassium gene expression with resultant proarrhythmic spatiotemporal changes in atrial action potential. Increased LA pressure is known to predict incidence and recurrence of AF. An Inter Atrial Shunt Device (IASD) is an experimental treatment for heart failure with preserved ejection fraction (HFpEF), used to reduce LA pressure and improve HF symptoms.

Numerical predictions of shear stress and cyclic stretch in pulmonary hypertension due to left heart failure.

Isolated post-capillary pulmonary hypertension (Ipc-PH) occurs due to left heart failure, which contributes to 1 out of every 9 deaths in the United States. In some patients, through unknown mechanisms, Ipc-PH transitions to combined pre-/post-capillary PH (Cpc-PH) and is associated with a dramatic increase in mortality. Altered mechanical forces and subsequent biological signaling in the pulmonary vascular bed likely contribute to the transition from Ipc-PH to Cpc-PH. However, even in a healthy pulmonary circulation, the mechanical forces in the smallest vessels (the arterioles, capillary bed, and venules) have not been quantitatively defined. This study is the first to examine this question via a computational fluid dynamics model of the human pulmonary arteries, arterioles, venules, and veins. Using this model, we predict temporal and spatial dynamics of cyclic stretch and wall shear stress with healthy and diseased hemodynamics. In the normotensive case for large vessels, numerical simulations show that large arteries have higher pressure and flow than large veins, as well as more pronounced changes in area throughout the cardiac cycle. In the microvasculature, shear stress increases and cyclic stretch decreases as vessel radius decreases. When we impose an increase in left atrial pressure to simulate Ipc-PH, shear stress decreases and cyclic stretch increases as compared to the healthy case. Overall, this model predicts pressure, flow, shear stress, and cyclic stretch that providing a way to analyze and investigate hypotheses related to disease progression in the pulmonary circulation.

Transcatheter interatrial shunt device for the treatment of heart failure with preserved ejection fraction

Abstract Background: Nearly half of patients with heart failure (HF) have preserved ejection fraction and the mortality and morbidity of patients with HF with preserved ejection fraction (HFpEF) are high. However, there is no established therapy to improve survival in these patients. HFpEF patients are often elderly and their primary chronic symptom is severe exercise intolerance. Thus, improvement of exercise capacity presents another important clinical outcome in HFpEF patients. A steep increase in left atrial pressure during exercise is an important cause of exertional dyspnea in HFpEF patients. The creation of a left-to-right interatrial shunt to decompress the left atrium may improve symptoms in patients with HFpEF. A novel transcatheter interatrial shunt device (IASD) has been developed and evaluated in patients with HFpEF in several clinical trials. However, there is insufficient evidence regarding the benefit of transcatheter IASD in these patients. Methods: This meta-analysis will include randomized controlled trials and single-arm trials on the effects of transcatheter IASD on exercise capacity, HF symptoms, and health-related quality of life in HFpEF patients. Information of studies will be collected from PubMed, Web of Science, Cochrane Library, and ClinicalTrials.gov. The primary outcome will be exercise capacity (6-minute walking distance). The secondary outcomes will be HF symptoms, health-related quality of life, and mortality and hospitalization rates. Discussion: This meta-analysis will evaluate the effect of transcatheter IASD in HFpEF patients, providing evidence to the clinical use of transcatheter IASD in these patients. Systematic review registration: INPLASY202120025

Localized Pulmonary Vein Scar Promotes Atrial Fibrillation in High Left Atrial Pressure.

BackgroundPulmonary vein (PV) ablation is unsuccessful in atrial fibrillation (AF) patients with high left atrial (LA) pressure. Increased atrial stretch by increased pressure is proarrhythmic for AF, and myocardial scar alters wall deformation. We hypothesized that localized PV scar is proarrhythmic for AF in high LA pressure.MethodsRadiofrequency energy was delivered locally in the right PV of healthy sheep. The sheep recovered for 4 months. Explanted hearts (n = 9 PV scar, n = 9 controls) were perfused with 1:4 blood:Tyrode’s solution in a four-chamber working heart setup. Programmed PV stimulation was performed during low (∼12 mmHg) and high (∼25 mmHg) LA pressure. An AF inducibility index was calculated based on the number of induction attempts and the number of attempts causing AF (run of ≥ 20 premature atrial complexes).ResultsIn high LA pressure, the presence of PV scar increased the AF inducibility index compared with control hearts (0.83 ± 0.20 vs. 0.38 ± 0.40 arb. unit, respectively, p = 0.014). The diastolic stimulation threshold in high LA pressure was higher (108 ± 23 vs. 77 ± 16 mA, respectively, p = 0.006), and its heterogeneity was increased in hearts with PV scar compared with controls. In high LA pressure, the refractory period was shorter in PV scar than in control hearts (178 ± 39 vs. 235 ± 48 ms, p = 0.011).ConclusionLocalized PV scar only in combination with increased LA pressure facilitated the inducibility of AF. This was associated with changes in tissue excitability remote from the PV scar. Localized PV ablation is potentially proarrhythmic in patients with increased LA pressure.

Ballistocardiography to identify high left atrial pressure in patients with heart failure.

Due to a high prevalence and morbidity rate, heart failure (HF) constitutes an immense economic burden on the global health care system. An increase in left atrial pressure (LAP) precedes the occurrence of any HF symptoms. In this study, we applied a novel non-invasive method of ballistocardiography (BCG) to extract early diastolic ventricular vibration waves [the BCG-B3 index, which corresponds to the third heart sound (S3) at the end of the rapid filling phase of diastole]. This study evaluated the predictive value of the BCG-B3 index for LAP in HF patients. A total of 83 HF patients and 20 patients with underlying diseases were prospectively enrolled, and their cross-sectional BCG and echocardiography (ECHO) data were collected. BCG obtains a signal through a high-precision fiber-optic sensor placed on the patient's back. LAP or pulmonary capillary wedge pressure (PCWP) was estimated by the ratio of mitral inflow peak early diastolic velocity to the early diastolic velocity of the mitral annulus (E/e') or the Nagueh equation (LAP = 1.24 × E/e' + 1.9). To evaluate the diagnostic efficacy of the BCG-B3 index, a receiver operating characteristic (ROC) curve was plotted, and the area under the ROC curve (AUC) was calculated. The best cutoff value for the BCG-B3 index was determined by the maximum Youden index. The correlation coefficient between the BCG-B3 index and E/e' ratio was 0.51 (P<0.01). Under an optimal cutoff value of 55.13, the BCG-B3 index showed a positive consistency value of 0.93, a negative consistency value of 0.53, and an overall consistency value of 0.82 for identification of significantly elevated LAP. The BCG-B3 index derived by noninvasive BCG using a built-in fiber-optic sensor has important diagnostic value for identifying significantly elevated LAP in HF patients with high accuracy. BCG examination is not limited by place or the doctor's experience. Therefore, BCG can provide timely assessments for HF patients, enabling early diagnosis and treatment.

Ablation scar in a single pulmonary vein causes proarrhythmic mechanical destabilization in healthy sheep atria

Abstract Funding Acknowledgements Type of funding sources: Public hospital(s). Main funding source(s): Catharina Hospital, Eindhoven Medtronic (unrestricted research grant) Background Ablative pulmonary vein isolation (PVI) prevents AF in 60% of AF patients. The absence of an antiarrhythmic effect of PVI is poorly understood. Atrial and PV stretch is proarrhythmic but the mechanical effect of PV ablation scar on AF arrhythmogenesis is unknown. We hypothesize that single ablation scars are potentially proarrhythmic because they create heterogeneous stretch. Purpose To evaluate the mechanical effect of a purposely incomplete PVI ablation scar on left atrial (LA) electrophysiology. Methods Functional cardiac MRIs in vivo in sheep (n = 11) before and 3-months after incomplete PVI by radiofrequency in the right PV (RPV) were analyzed with a feature-tracking algorithm to obtain local strain in the LA. The ablated hearts were explanted and perfused with 1:5 blood:Krebs solution in a dual-chamber working-heart set-up. Diagnostic multi-electrode endocardial catheters were positioned in the RPV and left PV (LPV). Premature stimulation was performed in each PV in low (∼12mmHg) and high (∼25mmHg) LA pressure. Twelve control hearts without ablation scar underwent similar ex vivo investigation. Results The maximum longitudinal strain of the myocardial wall between the RPV and LPV increased from 20.2 ± 6.2% to 33.5 ± 16.0% (before vs. after ablation, respectively; p = 0.032), whereas the maximum radial strain of the LA septum close to the RPV decreased from 45.6 ± 9.7% to 35.8 ± 7.3% (before vs. after ablation, respectively; p = 0.035). Sustained AF (&amp;gt;30s) was more often induced during stimulation in hearts with ablation scar than in control (25.0% and 11.5% of induction attempts (n = 76 and n = 87) in ablated and control hearts, respectively; p = 0.025). In ablated hearts, an increase in LA pressure augmented AF inducibility (12.8% vs. 37.8% of induction attempts (n = 39 vs. n = 37), low vs. high LA pressure, respectively; p = 0.023), whereas this was not the case in control hearts (4.4% vs. 19.0% of induction attempts (n = 45 vs. n = 42), low vs. high LA pressure; p = 0.289). The number of spontaneous premature atrial complexes (PACs) not leading to AF were similar in ablated and control hearts (0 ± 0 vs. 0 ± 2 total PACs within 20ms of refractory period during premature stimulation protocol, respectively; p = 0.411). The diastolic stimulation threshold of RPV was higher in the ablated than in control hearts (90 ± 63 vs. 79 ± 31mA, respectively; p = 0.049). The refractory period was similar in the ablated and control hearts (237 ± 62 vs. 235 ± 55ms, respectively; p = 0.873). Conclusion Local ablation scar caused regionally disparate bio-mechanical changes in proximity to ablative energy delivery and increased inducibility of sustained AF especially during increased LA stretch. This was associated with decreased tissue excitability without changes in refractoriness. A single incomplete PVI ablation scar therefore is proarrhythmic. Development of ablation lesion sets that homogenize atrial mechanics and electrophysiology may improve AF ablation success.

Effect of obesity and epicardial fat/fatty infiltration on electrical and structural remodeling associated with atrial fibrillation in a novel canine model of obesity and atrial fibrillation: A comparative study.

How obesity and epicardial fat influence atrial fibrillation (AF) is unknown. To investigate the effect of obesity/epicardial fat on the AF substrate, we divided 20 beagle dogs of normal weight into four groups (n = 5 each): one of the four groups (Obese-rapid atrial pacing [RAP] group) served as a novel canine model of obesity and AF. The other three groups comprised dogs fed a standard diet without RAP (Control group), dogs fed a high-fat diet without RAP (Obese group), or dogs fed a standard diet with RAP (RAP group). All underwent electrophysiology study, and hearts were excised for histopathologic and fibrosis-related gene expression analyses. Left atrial (LA) pressure was significantly higher in the Obese group than in the Control, RAP, and Obese-RAP groups (23.4 ± 6.9 vs. 11.4 ± 2.1, 11.9 ± 6.4, and 13.5 ± 2.9 mmHg; p = .005). The effective refractory period of the inferior PV was significantly shorter in the RAP and Obese-RAP groups than in the Control group (p = .043). Short-duration AF was induced at greatest frequency in the Obese-RAP and Obese groups (p < .05). Epicardial fat/Fatty infiltration was greatest in the Obese-RAP group, and greater in the Obese and RAP groups than in the Control group. %interstitial fibrosis/fibrosis-related gene expression was significantly greater in the Obese-RAP and RAP groups (p < .05). Vulnerability to AF was associated with increased LA pressure and increased epicardial fat/fatty infiltration in our Obese group, and with increased epicardial fat/fibrofatty infiltration in the RAP and Obese-RAP groups. These may explain the role of obesity/epicardial fat in the pathogenesis of AF.

Changes in left ventricular size, geometry, pump function and left heart pressures during healthy aging.

There are cross-sectional and longitudinal imaging studies using echocardiography and cardiac magnetic resonance in healthy adult subjects which have demonstrated associations of left ventricular (LV) structure and pump function with age. There are also cross-sectional data regarding the relationships of age with invasively measured left heart chamber pressures. Increasing age is associated with decreases in LV end-diastolic volume (LVEDV), end-systolic volume (LVESV), end-diastolic length (LVEDL), stroke volume (SV) and cardiac output (CO), and increases in relative wall thickness (RWT), LV mass/LVEDV ratio (LVMVR) and ejection fraction (LVEF). Older age is not accompanied by a change in mean left atrial (LA) pressure, but there is both direct and indirect evidence which suggests that LV end-diastolic pressure (LVEDP) increases with age. LVEDV remains lower in older than younger subjects during fluid infusion and the resulting increases in LA pressure. The combination of an increase in LVEF with reductions of both SV and CO demonstrates an age-related increase in divergence between LVEF and LV pump function. A lower LVEDV in older compared to younger subjects can be characterized as an aging-related decrease in LV capacity, with the higher LVEDP in older subjects also indicating a reduction of preload reserve.