Atrial Pressure Research Articles

The role of atrial pacing site in reducing filling pressures by accelerated pacing in virtual HFpEF patients

Abstract Background Patients with heart failure with preserved ejection fraction (HFpEF) and pacemakers have been shown to benefit from moderately accelerated pacing rates compared to the standard 60bpm. HFpEF patients often present with prolonged P-wave duration (PWD) and atrial fibrillation. Right atrial appendage pacing (RAAP) lengthens PWD, RA septal (RASP) has a neutral effect, while Bachmann’s bundle pacing (BBP) normalizes or shortens PWD compared to sinus rhythm. The mechanical and hemodynamic effects of atrial pacing site selection remain unknown. Aim To investigate the impact of RAAP, RASP and BBP on cardiac mechanics and hemodynamics in an established cohort of virtual HFpEF patients undergoing accelerated pacing. Method HFpEF with prolonged PWD was simulated using the validated CircAdapt computational model of the human cardiovascular system. First, left ventricular (LV) diastolic dysfunction was simulated by decreasing LV myocardial relaxation rate and compliance, such that mean left atrial (LA) pressure (mLAP) was 15mmHg. Second, PWD was prolonged by prescribing a gradual electrical activation delay from RA to LA of 140ms. We then simulated atrial pacing with three different lead positions (Fig.1, left) and gradually increased pacing rate with a constant 120-ms paced atrioventricular (AV) delay. The CircAdapt model computed regional LA strain and mLAP with RAAP, RASP, and BBP. Cardiac output (5L/min) and mean arterial pressure (92mmHg) were kept constant in all simulations. Results Simulated BBP demonstrated the most synchronous LA mechanical activation and function, characterized by uniform segmental LA strain patterns and highest LA reservoir strain (LASR) (Fig.1, middle, with colored arrows highlighting the mechanical dyssynchrony). Hemodynamically (Fig.1, right), BBP acutely decreased mLAP (-1.0mmHg) at the initial heart rate of 60bpm, while RAAP increased it (+0.3mmHg). As pacing rate accelerated, BBP reduces filling pressure (mLAP: -2.8mmHg), more than RASP (-1.8mmHg) or RAAP (-1.2mmHg) at 80bpm. At high pacing rates, RASP and RAAP adversely increase mLAP, due to the prolonged atrial contraction duration and shorter LV filling time. Conclusion Our simulations of different atrial pacing sites in virtual HFpEF patients suggest that BBP yields the most synchronous LA activation pattern and a more substantial reduction in filling pressures with accelerated atrial pacing compared to RASP. Reduction in mLAP with accelerated pacing was attenuated with RAAP. While our study concentrated on a specific paced AV interval, the favorable outcomes observed with BBP could be further improved by including different, rate-adaptive, AV protocols.Fig 1.

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.

Impact of myocardial phenotype on atrioventricular delay optimization at rest and during exercise: insights from a virtual patient study

Abstract Background The usefulness of atrioventricular delay (AVD) optimization in cardiac resynchronization therapy (CRT) for heart failure (HF) patients with left bundle branch block (LBBB) and reduced left ventricular ejection fraction (LVEF) is still debated. Yet, studies have not explored the role of non-electrical myocardial disease substrates in determining optimal AVD settings among patients. Purpose We first hypothesized that acute response to AVD optimization might be modulated by various myocardial disease substrates. Furthermore, we hypothesized that cardiac function is more sensitive to changes in AV coupling during exercise and that this sensitivity is also modulated by underlying myocardial disease substrates. Methods We used the CircAdapt model of the human heart and circulation to simulate different types of LV remodeling that can be found in CRT candidates. First, an LBBB-like pattern of mechanical activation was imposed by delaying LV free wall (LVFW) and interventricular septal (IVS) activation relative to right ventricular free wall activation. Then, two types of LV remodeling were simulated by LV dilation with preserved or impaired myocardial contractility, resulting in LVEF <35%. To investigate the effect of diastolic dysfunction, we increased passive myocardial stiffness of the IVS and LVFW on both substrates with LV remodeling until a mean left atrial pressure (mLAP) of 14 mmHg was reached. CRT was simulated by resynchronizing IVS and LVFW. AVD optimization was conducted by gradually reducing the paced AVD from 220 ms to 40 ms in steps of 20 ms. In each simulation, the optimal paced AVD at rest (cardiac output (CO) and heart rate (HR) of 4.2 L/min and 80 bpm, respectively) was assessed using stroke volume (SV) and mLAP which is used as a measure of LV filling pressure. To investigate the relative effect of these myocardial phenotypes during AVD optimization under exercise, CO and HR were increased step-wise. Results The gain in SV by AVD optimization was larger in the simulations with healthy myocardium than in those with hypo-contractile and stiff myocardium (Figure 1: top-row). However, mLAP was comparably decreased by AVD optimization in healthy and diseased myocardium (Figure 1: bottom row). During exercise, the optimum AVD shifted to shorter values (Figure 2: top-row), and mLAP was much more sensitive to AVD, particularly in the presence of hypo-contractile and stiff myocardium (Figure 2: bottom row). Conclusion Virtual patient simulations show that both myocardial hypocontractility and stiffness dampen the effect of AVD optimization on SV. Furthermore, simulations suggest that patients benefit more from AVD optimization during exercise than during resting conditions. These mechanistic insights may help to gain more benefit from AVD optimization for patients undergoing CRT.AVD optimization at restAVD optimization during exercise

Accelerated pacing reduces left heart filling pressures: a novel therapy for heart failure with preserved ejection fraction?

Abstract Background The recent MyPACE trial demonstrated significant improvement of quality-of-life, physical activity, and atrial fibrillation (AF) burden with accelerated pacing as compared to the standard 60bpm back-up rate setting in patients with heart failure with preserved ejection fraction (HFpEF) and indication for pacemaker therapy. We hypothesized that a potential working mechanism underlying these improved outcomes lies in the reduction of left heart filling pressures during accelerated pacing, reducing congestion and atrial stretch. Aim To assess the acute effects of accelerated atrial pacing on left heart filling pressures in consecutive AF patients undergoing catheter ablation. Methods Fifty AF patients undergoing catheter ablation were prospectively enrolled for accelerated atrial pacing. As illustrated in Figure 1, pacing was performed proximally in coronary sinus (CS). Pacing rate was increased incrementally from resting heart rate by 10-bpm increments up to Wenckebach rhythm, with 30-sec intervals of pacing on and off for hemodynamic stabilization. Left atrial pressure (LAP) was continuously monitored via a fluid-filled transseptal sheath (SL0 sheath, Abbott). Acute pacing-induced changes in mean LAP and PR-interval were evaluated at each pacing rate and compared between resting heart rate, the patient-specific optimal heart rate (i.e., the rate resulting in the lowest mean LAP), and the maximum pacing rate. Results Atrial pacing acutely decreased mean LAP from 14.8[9.8; 18.4] to 12.8[8.5; 15.8]mmHg (median[IQR], p<0.001) as heart rate increased from 51[47; 61] to 90[70; 100]bpm (p<0.001) (Figure 2, resting versus optimal category). Among the 50 patients included, only 4 did not exhibit a decrease in LAP. Further increasing pacing rate to a maximum of 130[100; 140]bpm resulted in an acute LAP increase to 16.2[12.7; 19.9]mmHg (p<0.001) to values above resting mean LAP. Accelerated pacing induced negative AV dromotropy, i.e., lengthening of the PR-interval from 169[150; 185] to 186[164; 209]ms (p=0.003) and 270[217; 310]ms (p<0.001). Conclusion Our study demonstrated that moderately accelerated atrial pacing reduced mean LAP in AF patients undergoing catheter ablation. While our primary focus was on acute response in AF patients, the reduction in mean LAP during moderate pacing rates may suggest a promising therapeutic approach for managing HFpEF patients. However, caution is warranted as pacing rates beyond the optimal range led to a marked increase in LAP. Additionally, increasing pacing rates were observed to induce varying degrees of AV-node dromotropy, which potentially modulates therapy response.Fig 1. Overview of clinical protocolFig 2. Response to accelerated pacing

Agreement of left atrial pressure with clinical risk scores and echocardiographic features in patients with atrial fibrillation referred for catheter ablation

Abstract Background Heart failure with preserved ejection fraction (HFpEF) frequently coexists with atrial fibrillation (AF). The diagnosis of HFpEF in AF is difficult because some diagnostic criteria for HFpEF may be associated with AF instead of HFpEF per se. Left atrial pressure (LAP) ≥15 mmHg has been used to confirm the diagnosis of HFpEF. Purpose We aimed to 1) determine LAP measurements in patients with AF undergoing catheter ablation; 2) assess the agreement between LAP measurement HFpEF risk scores and 3) determine the association between LAP measurement and clinical and echocardiographic features. Methods Consecutive patients with paroxysmal or persistent AF scheduled for catheter ablation were included. Participants were considered to have HFpEF if the mean LAP was ≥15 mm Hg. The LAP was measured only in sedated patients with spontaneous breathing. Participants had high probability of HFpEF if scored >5points in H2FPEF and/or ≥5 points in HFA-PEFF score. Results Of 107 participants, 29 (27%) had HFpEF according to mean LAP and 32 (30%) had high probability of HFpEF according to HFpEF scores. The highest agreement of HFpEF risk scores relative to elevated LAP was observed for H2FPEF score; among patients with mean LAP ≥15 mm Hg, 38% [n=11/29] of them had also high risk of HFpEF based on H2FPEF score, whereas only 10% [n=3/29] had high risk of HFpEF based on HFA-PEFF score. In multivariable analysis, the independent predictors of HFpEF were left ventricular ejection fraction (LVEF; OR 0.77, 95%CI 0,.64-0.91), intraventricular septum diameter (IVSd; OR 1.75, 95%CI 1.11-2.74), global longitudinal strain (GLS; OR 1.24, 9%CI 1.05-1.48). Conclusions More than one-fourth of patients scheduled for catheter ablation had HFpEF according to elevated LAP. The highest agreement to elevated LAP was observed for the H2FPEF score. Predictors of HFpEF diagnosis were lower LVEF, higher IVSd and GLS.

Increased left atrial pressure is associated with fibrosis, elevated mechanical load and ventricular diastolic dysfunction in patients undergoing AF catheter ablation

Abstract Background Increased left atrial filling pressures might be a hallmark feature of atrial cardiomyopathy which has been associated with an increased incidence of atrial fibrillation (AF) recurrence even after successful pulmonary vein isolation (PVI). The interplay between left atrial pressure, measured during the ablation procedure, and other parameters characterising atrial and ventricular remodelling in patients with AF remains elusive. Methods and Results Between 2018 and 2022, 182 patients undergoing PVI for paroxysmal or persistent AF were included in the study. Mean left atrial pressure (mLAP) was measured invasively during the ablation procedure after transseptal puncture. A mLAP higher than 15 mmHg was considered the cut-off value for LA hypertension. Bipolar high-density 3D electro-anatomical maps (Carto) obtained during the procedure were used to manually quantify low-voltage (<0.5 mV) and normal voltage areas of the LA surface and a global low-voltage/normal voltage ratio index was derived. Contemporary transthoracic echocardiography data were included to evaluate LV systolic and diastolic function and blood samples were obtained post-procedurally from all patients. In bivariate linear regression analysis, mLAP reached only modest correlation with E/e’ as an imaging marker of diastolic dysfunction (R=0.31, p=0.005) (Figure 1A), with particular differences in mLAP values between patients with marked diastolic impairment (E/e’ > 15) vs. subgroups with mild dysfunction ( 8 < E/e’ ≤ 15) or normal diastolic function (E/e’ ≤ 8 ) (Figure 1B), log NT proBNP (R=0.34, p<0.001) (Figure 1C) and low-voltage/normal voltage ratio index (R=0.21, p=0.014) (Figure 1D). For a total of 158 patients, data about 1 year recurrence of AF were available, of these 22 (13.9%) had a recurrence after two procedures using cryo-energy for the index PVI and radiofrequency ablation for the re-PVI (second procedure). A Kaplan-Meier analysis and log-rank test showed a trend but no statistical significance regarding an increased AF recurrence rate between patients with and without LA hypertension (χ2 = 2.63, p= 0.09) (Figure 2). Conclusion Direct intra-procedural invasive measurement of LA pressures can offer an important and convenient novel piece of information for patients undergoing catheter ablation procedures for AF, with potential implication for post-procedural recurrence risk stratification. Atrial hypertension is only partially related to LV diastolic impairment, atrial fibrosis and myocardial mechanical load burden.

#2058 IVC diameter and collapsibility via point-of-care ultrasound among clinically euvolemic Filipinos in Victoriano Luna Medical Center, Philippines

Abstract Background and Aims History, physical findings, and laboratory tests have limited sensitivity and specificity to assess relative intravascular volume or volume responsiveness. Inferior vena cava (IVC) ultrasound provides a direct assessment of relative intravascular volume status. The Journal of the American Society of Echocardiography (2010), recommended that an IVC diameter of <2.1 cm and collapsibility of >50% with a sniff indicates normal right atrial pressure of 3 mmHg (0-5 mmHg), while an IVC diameter of >2.1 cm with <50% inspiratory collapse indicates high right atrial pressure of 15 mmHg (10-20 mmHg). However, there have been occasions in the hospital setting wherein clinically hypervolemic Filipino patients were observed to have inferior vena cava diameters of less than 2.0 cm. This study aims to determine the average IVC diameter among clinically euvolemic Filipinos and to evaluate the applicability of standardized ultrasonographic IVC measurements in the Filipino population. Method This is a prospective observational study that included 45 clinically euvolemic patients and staff of Victoriano Luna Medical Center from 01 September 2023 to 01 November 2023. The demographic profile and anthropometric measurements of the volunteers were obtained. Ultrasound assessment was performed bedside and the IVC diameter was measured during passive respiration without sniff test 1 to 2 cm distal to the hepatic vein or 3 to 4 cm distal to the junction of the right atrium and inferior vena cava. The maximum and minimum diameters of the inferior vena cava was also measured using M-mode, and its collapsibility index was computed using the following formula: collapsibility index (CI) = (IVC max – IVC min) / IVC max. Categorical variables such as sex and comorbidities will be presented as frequencies and percentages while continuous variables such as age, body mass index, and inferior vena cava diameter and collapsibility will be presented as mean and standard deviation or median and interquartile range. Results The study group mainly consisted of males aged 65 years and below with normal body mass index for Asians. Cut-off values for the maximum inferior vena cava diameter were based on the venous excess ultrasound grading system, or VEXUS score, by Beaubien-Souligny et al. (2020) wherein congestion was considered at IVC diameters more than or equal to 2.0 cm. Of the 45 participants, 33 had maximum inferior vena cava diameter of less than 2.0 cm. Twenty-eight (28) out of 45 participants had a collapsibility index of more than 50%, which is indicative of normal right atrial pressure. Of the 33 with a maximum inferior vena cava diameter of less than 2.0 cm, 11 of which had a collapsibility index between 20 and 50%, and 22 with more than 50%. The remaining 12 participants had a maximum IVC diameter of more than or equal to 2.0 cm, with five having a collapsibility index between 20 and 50% and six with more than 50%. The mean maximum IVC diameter in the 45 volunteers on quiet respiration was 1.79 cm (+0.47), with an average computed collapsibility index of 54.43% (+19.78). Conclusion Thirty-three participants (73.33%) had a maximum inferior vena cava diameter of less than 2.0 cm, 22 of which have a collapsibility index of more than 50%. Among the 45 volunteers, the mean IVC maximum diameter on quiet respiration was 1.79 cm (+0.47), with an average computed collapsibility index of 54.43% (+19.78). Based on the results, standardized ultrasonographic IVC measurements can be applied on the Filipino population. Considering the Filipinos’ petite stature, the average IVC diameter among Filipinos is smaller and further investigation is warranted to establish clear cut-off values to identify plethoric IVCs in the Filipino setting.

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.

Optimizing Resuscitation of the Donation after Circulatory Death Heart by Mitochondrial Protection in a Female Porcine Model.

Due to the shortage of donor organs, an increasing number of transplant organs are harvested after circulatory arrest (donation after circulatory death [DCD]). Using a translational porcine model of DCD, this study developed and evaluated a protocol based on cardioprotection by multidrug postconditioning to optimize resuscitation of DCD hearts during ex situ heart perfusion (ESHP). Hearts of female pigs (45.0 ± 4.5 kg) were procured following a clinically identical DCD protocol, consisting of the termination of ventilator support and confirmation of circulatory arrest, followed by a 15-min standoff period. DCD hearts were randomly allocated to ESHP (38.4°C) in the absence (untreated, N = 5) or presence (treated, N = 5) of a postconditioning treatment added to the perfusate, consisting of Intralipid (1%), sevoflurane (2% v/v), and remifentanil (3 nM). All hearts were perfused with blood and Krebs-Henseleit solution (1:1) for 60 min in Langendorff mode and for an additional 300 min in working mode for a total perfusion time of 6 h. Oxidative capacity and detailed left ventricular mechanical function under an increasing workload (left atrial pressure, 6 to 12 mmHg) were assessed hourly. Left ventricular tissue was snap-frozen at the end of ESHP and used for molecular analyses. Left ventricular inotropy (LVdP/dtmax) did not decline over time in treated DCD hearts and was significantly higher at the end of the protocol as compared with untreated DCD hearts (ΔLVdP/dtmax = 440 mmHg/s; P = 0.009). Treated DCD hearts exhibited persistently higher left ventricular stroke work index during the 6-h period of ESHP, whereas untreated DCD hearts displayed a significant decline (change in left ventricular stroke work index = -3.10 ml · mmHg/g; P(time within untreated group) < 0.001). Treated DCD hearts displayed higher metabolic activity as measured by oxygen consumption (ΔO2 = 3.11 ml O2 · min-1 · 100 g-1; P = 0.004) and released lower amounts of cell-free mitochondrial DNA into the perfusate, a marker of potential graft dysfunction. Treated hearts also used fatty acids from Intralipid as an energy source, whereas untreated DCD hearts showed glyceroneogenesis with triglyceride accumulation and depletion of tricarboxylic acid cycle intermediates; reduced mitochondrial complex I, II, and III activities with accumulation of mitochondrial NADH, and signs of ultrastructural damage. A translationally relevant protective ESHP protocol consisting of treatment with Intralipid, sevoflurane, and remifentanil markedly accelerated functional recovery and improved viability of DCD hearts.

UNLOADING STRATEGIES IN ADVANCED HEART FAILURE: THE ROLE OF POINT–OF–CARE ULTRASOUND

Abstract Patients with advanced heart failure (HF) exhibit repeated episodes of fluid retention (pulmonary and/or systemic congestion) and/or of reduced cardiac output at rest (peripheral hypoperfusion) requiring hospitalization along with diuretics/inotropic infusion. Pulmonary artery catheter (PAC) provides haemodynamic information to guide the therapy, however PAC is invasive and time consuming. Point of care ultrasonography (POCUS) represents a promising diagnostic tool at the bedside, performed by the physician to assess non invasively volume status, cardiac output and monitor decongestive therapy. Recently, abnormal Doppler flow patterns due to increased right atrial pressure have been described in the hepatic, portal, and intrarenal veins. Thus, the recent venous excess ultrasound score (VExUS) has been used to describe fluid status along with the diameter and collapsibility of the inferior vena cava. Furthermore HF patients show high filling pressures, therefore they often require mechanical or medical unloading. In this regard, point of care ultrasound represents a valid tool to monitor non invasively the filling pressures and the responsiveness to those treatments. Here, we illustrate with several clinical cases where VExUS/POCUS were pivotal in clinical management.

Atrial Arrhythmias Following Pulmonary Thromboendarterectomy: A Comprehensive Review Of Current Literature.

Chronic thromboembolic pulmonary hypertension (CTEPH) presents as a progressive vascular condition arising from previous episodes of acute pulmonary embolism, contributing to the development of pulmonary hypertension (PH). Pulmonary thromboendarterectomy (PTE) is the gold-standard surgical treatment for CTEPH; however, it may be associated with postoperative sequelae, including atrial arrhythmias (AAs). This comprehensive literature review explores the potential mechanisms for PTE-induced AAs with emphasis on the role of PH-related atrial remodelling and the predisposing factors. The identified preoperative predictors for AAs include advanced age, male gender, elevated resting heart rate, previous AAs, and baseline elevated right atrial pressure. Furthermore, we explore the available data on the association between post-PTE pericardial effusions and the development of AAs. Lastly, we briefly discuss the emerging role of radiomic analysis of epicardial adipose tissue as an imaging biomarker for predicting AAs.

The impact of cardiovascular and lung comorbidities in patients with pulmonary arterial hypertension: A systematic review and meta-analysis

BackgroundContemporary patients with pulmonary arterial hypertension (PAH) are older and exhibit cardiovascular and/or lung comorbidities. Such patients have typically been excluded from major PAH drug trials. This systematic review compares baseline characteristics, hemodynamic parameters, and mortality rate between PAH patients with significant number of comorbidities compared to those with fewer or no comorbidities. ΜethodsA systematic literature search in PubMed and Cochrane databases was conducted searching for studies comparing PAH patients with more than two cardiovascular comorbidities and/or at least a lung comorbidity against those with fewer comorbidities. ResultsSeven observational studies were included. PAH patients with comorbidities were older, with an almost equal female-to-male ratio, shorter 6-minute walk distance, higher NT-proBNP levels, and lower lung diffusion for carbon monoxide. In terms of hemodynamics, they had higher mean right atrial pressure and pulmonary artery wedge pressure, lower mean pulmonary arterial pressure, pulmonary vascular resistance and mixed venous oxygen saturation. Pooled analysis of six studies demonstrated a higher mortality risk for PAH patients with comorbidities compared to those without (HR 1.86, 95% CI 1.20 to 2.89, p<0.001, I²=92%), with the subgroup of PAH patients with lung comorbidities having an even higher mortality risk (test for subgroup differences: p<0.001). Combination drug therapy for PAH was less frequently used in patients with comorbidities. ConclusionsCardiovascular and lung comorbidities impact the clinical characteristics and outcomes of PAH patients, highlighting the need for optimal phenotyping and tailored management for this high-risk population.

Evaluation of thyroid congestion in patients with heart failure using shear wave elastography: An observational study.

Shear wave elastography (SWE) is a noninvasive method for measuring organ stiffness. Liver stiffness measured using SWE reflects hepatic congestion in patients with heart failure (HF). However, little is known about the use of SWE to assess other organ congestions. This study aimed to evaluate the utility of SWE for assessing not only the liver but also thyroid congestion in patients with HF. This prospective study included 21 patients with HF who have normal thyroid lobes (age: 77.0 ± 11.0, men: 14). Thyroid and liver stiffness were measured by SWE using the ARIETTA 850 ultrasonography system (Fujifilm Ltd., Tokyo, Japan). SWE of the thyroid was performed on B-mode ultrasonography; a target region was identified within a region of interest. SWE was performed in each lobe of the thyroid gland. Five measurements were taken at the same location and the averages were recorded for comparison. We investigated the relationship between SWE for evaluating thyroid stiffness and the clinical characteristics of patients with HF. SWE of the thyroid was significantly correlated with SWE of the liver (R = 0.768, P < .001), thyroid stimulation hormone (R = 0.570, P = .011), free thyroxine (R = 0.493, P = .032), estimated right atrial pressure (RAP; R = 0.468, P = .033), and composite congestion score (R = 0.441, P = .045). SWE may be useful for evaluating thyroid stiffness and assessing the degree of thyroid congestion. Thyroid congestion may reflect the elevation of RAP and cause thyroid dysfunction through organ congestion.

PEEP trial and effect on hemodynamic in cardiogenic shock

Abstract Funding Acknowledgements None. Introduction Congestion is a paramount pathophysiological driver in patients with cardiogenic shock. Almost half of patients admitted due to cardiogenic shock undertake mechanical ventilation although ventilatory parameter, and their potential hemodynamic effect on the hemodynamic and congestion profile are often neglected. Purpose We sought to evaluate the hemodynamic effect of positive end-expiratory pressure (PEEP) titration on patients admitted to intensive care unit for CS. Methods We perform PEEP titration trial on patients undertaking mechanical ventilation for respiratory failure related to CS. The trial consisted in 3 steps of PEEP increase from 5 to 15 cmH2O. For each step arterial saturation, right atrial -RAP- and systemic blood pressure along with heart rate and respiratory mechanics (tidal volume-TV-, dynamic lung compliance- CLdyn, driving- Δ- and plateau pressure- Ppl) were measured. All the measures were taken at end-expiration; RAP trace was analyzed and systolic, mean and diastolic component collected. The final PEEP was decided based on the best matching between saturation, CLdyn and TV. Descriptive and repeated measures with Bonferroni correction were applied as statistical analysis (IBM SPSS 29). Results Twelve patients were included (10 male, 66 ± 7 years old; 8 acute myocardial infarction and 4 acute heart failure). At baseline the mean RAP was 8.44 (± 2.32) ; SBP 106 (IQR 92-112), HR 94 (IQR 88 - 102) Δ and Ppl pressures respectively 7.42 (± 0.79) and 12.08 (± 0.79, ),VT 427(± 65.42) and CLdyn 58.3 (± 7.1). The right atrial pressure (RAP) differed between AMI and AHDF (8.25 ± 2.25 vs 20.25 ± 1.5; p &amp;lt; 0.001), so HR did (113 ± 3.4 versus 96 ± 3.2 betas per minutes; p 0.015). RAP varied consistently during the PEEP trial (either sRAP, dRAP and mRAP- Table and Figure 1). The TV changed signficnatly between the 1st and 3rd step (p 0.004) and the CLdyn varied consistently throughout the 3 steps of the PEEP trial (p &amp;lt;0.001). A significant difference were observed according to aetiology in RAP (AMI Vs ADHF, eman difference 2.4 versus 4.3 mmHg) and in CLdyn (AMI Vs ADHF mean difference 12.31 vs 8 .65, p &amp;lt; 0.01) but not in the other parameters evaluated (p &amp;gt; 0.05). Conclusion This is the first, small, study evaluating the effect of positive pressure ventilation in CS patients according to etiologies. As previously demonstrated PEEP influences the right side hemodynamic by increasing the RAP, although resulting in better CLdyn. The extent of the effect of PEEP increased may be dependent on the underlying aetiology of CS. Considering that the sample size is extremely limited, these results advocate a wider validation. However, the positive pressures induced by the ventilation in patient with CS should be taken in consideration when the comprehensive evaluation of hemodynamic to define congestion profile and phenotype are performed.Table 1.Hemodynamic parametersGraph PEEP vs RAP

The long-term effects of the fenestration in patients with extracardiac Fontan circulation-a multicenter Korean cohort study based on national Fontan registry.

The long-term effects of fenestration in patients with Fontan circulation remain unclear. We aim to evaluate the fenestration impact on early and late outcomes in patients with extracardiac Fontan (ECF) using a propensity score matching analysis. We performed an extensive retrospective multicenter clinical data review of the Korean Fontan registry and included 1,233 patients with surgical ECF (779 fenestrated, 454 non-fenestrated). Demographics, baseline, and follow-up data were collected and comprehensively analyzed. Patients were divided into two groups according to the baseline presence or absence of surgical fenestration. Subsequently, patients were sub-divided according to the fenestration status at the last follow-up. Propensity-score matching was performed to account for collected data between the 2 groups using a multistep approach. The primary outcomes were survival and freedom from Fontan failure (FFF). We also looked at postoperative hemodynamics, cardiopulmonary exercise test results, oxygen saturations, and functional status. After propensity-score matching (454 matched pairs), there was no difference in survival or FFF between the 2 groups. However, ECF patients with baseline fenestration had significantly lower oxygen saturation (p = 0.001) and lower functional status (p < 0.001). Patients with fenestration had significantly longer bypass times, higher postoperative central venous pressure, higher postoperative left atrial pressure, and less prolonged pleural effusion in the early postoperative period. The propensity score matching according to the fenestration status at the last follow-up (148 matched pairs) showed that patients with a persistent fenestration had significantly lower oxygen saturation levels (p < 0.001). However there were no intergroup differences in the functional status, survival and FFF. Our results showed no long-term benefits of the Fenestration in terms of survival and FFF. Patients with persistent fenestration showed oxygen desaturation but no difference in exercise intolerance was shown between the 2 groups.

Role of Vascular Function in the Prognosis of Heart Failure Patients.

Background: Blood vessels have the Windkessel effect and are involved in blood circulation. The breakdown of this mechanism is also involved in the pathogenesis of heart failure (HF); however, the relationship between vascular dysfunction and HF prognosis is not fully understood. Methods: We evaluated 214 patients hospitalized for HF at our institution who underwent a cardio-ankle vascular index (CAVI), which evaluates vascular function, between January 2012 and July 2018. To investigate factors (including CAVI) associated with major adverse cardiac events (MACE) during 1 year after patients with HF were discharged, we evaluated clinical profiles, blood tests, chest X-P, 12-lead electrocardiography, and transthoracic echocardiographic findings. MACE was defined as cardiovascular death or readmission for HF. Results: The severity of HF between the MACE and non-MACE was not significantly different. Previous HF and chronic kidney disease were significantly more common in the MACE group. CAVI and % mean atrial pressure in the MACE group were statistically higher than those in the non-MACE group. The cardiac shadow as shown by chest X-P and left ventricular size in the MACE group were significantly bigger, and HF preserved ejection fraction (EF) (EF > 50%) was significantly more common in the MACE group. In multivariate analysis, CAVI was an independent predictive factor for the occurrence of MACE (model 1; hazard ratio (HR): 1.33, 95% confidence interval (CI): 1.05-1.68, p = 0.018; model 2; HR: 1.31, 95% CI: 1.07-1.60, p = 0.009). Conclusions: Because high CAVI is associated with poor prognosis of HF, these patients require more careful treatment.

Sex-Related Differences in Patients With Hypertrophic Cardiomyopathy Undergoing Alcohol Septal Ablation.

Previous studies have shown that women with hypertrophic obstructive cardiomyopathy (HCM) have worse long-term outcomes irrespective of intervention. However, the outcomes of patients undergoing alcohol septal ablation (ASA) based on sex have not been described. Hence, this study aimed to evaluate pressure changes and long-term mortality in patients with HCM undergoing ASA based on sex. This is a single-center retrospective study evaluating hemodynamic changes and long-term mortality in patients with HCM treated with ASA according to sex. A total of 259 patients were included (aged 68.4±11.9 years, 62.2% women). Women had higher age and baseline pressures at the time of ASA, with a greater percent reduction in mean left atrial pressure (men versus women: 2.2% versus 15.9%, respectively; P=0.02). Women had better survival (median survival rate of men versus women: 8.6 versus 12.5 years, respectively; P=0.011). On Cox multivariable regression, predictors of mortality were age (per group change <60 years, 61-70 years, 71-80 years, and >80 years; hazard ratio [HR], 1.45 [95% CI, 1.10-1.91], P=0.008), female sex (HR, 0.59 [95% CI, 0.35-0.99], P=0.048), chronic kidney disease (HR, 1.88 [95% CI, 1.06-3.33], P=0.031), and left ventricular outflow tract gradient reduction ≤86% (HR, 1.91 [95% CI, 1.14-3.19], P=0.014). Women with HCM undergoing ASA are older and have higher left-sided baseline pressures compared with men yet have better survival. Further studies exploring the mechanisms of differential outcomes according to sex in patients with HCM undergoing ASA are needed.

Time-Dependent Association Between Agonal Respirations and Cardiopulmonary Resuscitation Hemodynamics in a Porcine Model of Cardiac Arrest

Objective: Agonal respirations (AR) are common in patients with cardiac arrest (CA) and are associated with a higher likelihood of successful return of spontaneous circulation (ROSC). Prior preclinical studies suggest that the favorable effects of AR may be mediated by improved coronary perfusion pressure (CPP) during subsequent cardiopulmonary resuscitation (CPR) efforts, but whether this relationship is influenced by the duration of CA has yet to be studied. Accordingly, we measured CPR hemodynamics in swine following 7 minutes or 10 minutes of untreated ventricular fibrillation (VF) to determine if the frequency of AR is associated with CPP after prolonged CA. Methods: Swine (n=71) were subjected to either 7 minutes (n=50) or 10 minutes (n=21) of electrically-induced VF CA, during which the frequency of AR was recorded before the initiation of CPR with chest compressions (100/minute) and mechanical ventilation (16-20 breaths/minute). CPP was assessed during CPR by calculating the difference between aortic pressure and right atrial pressure during decompression. Animals were retrospectively stratified into two groups (high and low frequency of AR) based on the median number of AR in each cohort (7-minute CA median = 6 AR; 10-minute CA median = 9 AR).&gt;Results: In the 7-minute CA cohort, the high AR group (9.7±2.9 AR; n=28) had a significantly longer time from first to last AR (102±6 vs. 34±6 seconds; p&lt;0.001), shorter time from final AR to CPR initiation (208±8 vs. 280±15 seconds; p&lt;0.001), and higher CPP during CPR (14.4±1.0 vs. 9.3±0.6 mmHg; p&lt;0.001) than the low AR group (2.9±0.4 AR; n=22). In contrast, following 10 minutes of CA, the high AR group (12.0±0.4 AR; n=11) did not have a significantly different CPP during CPR (8.7±1.8 vs. 10.4±1.5 mmHg; p=0.48) when compared to the low AR group (6.2±0.5 AR; n=10). A greater number of defibrillation attempts were required to terminate VF after 10 minutes of CA (3.0±0.6) vs. 7 minutes of CA (1.2±0.1; p&lt;0.001), but this was not impacted by the frequency of AR in either cohort. Conclusion: Consistent with prior studies in swine subjected to 5 minutes of untreated CA, a high frequency of AR during a 7-minute episode of CA was associated with higher CPP upon initiation of CPR. However, the favorable effects of AR frequency on CPP during CPR were no longer apparent when the duration of untreated CA was extended to 10 minutes. These results demonstrate that the beneficial effects of AR on CPR hemodynamics are time-dependent and highlight the importance of early initiation of CPR following CA. Supported by funding from the NIH and US Department of Veteran's Affairs. This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

Allometric scaling of the parameters characterizing venous return surface in the generalized framework of circulatory equilibrium

Study objective: In the generalized framework of circulatory equilibrium (GCE), the integrated cardiac output (CO) curve characterizes the pumping abilities of the left and right hearts, whereas the venous return (VR) surface characterizes the preloading properties of the systemic and pulmonary circuits. Equilibrium CO (= VR), left (PLA) and right (PRA) atrial pressures are predicted from the intersection between the CO curve and VR surface. In VR surface, VR is theoretically related with stressed blood volume (V), PLA and PRA as: VR =V/W − Gs × PRA − Gp × PLA, where Gs and Gp is a ratio of systemic (Cs) and pulmonary (Cp) vascular compliance to W (time constant of the systemic and pulmonary circuits), respectively. However, there was a concern whether the standard parameters can be applicable to animals with different body size including human. The objective of this study is to experimentally investigate whether an allometric scaling of the parameters (Gs, Gp, W, Cs, Cp) of the VR surface is feasible. Hypothesis: Kleiber’s law indicates that an animal's metabolic rate scales to the 3⁄4 power of the animal's body weight (BW). Based on this, we hypothesize that Cs and Cp may be proportionate to BW, W may be proportionate to BW1/4. Hence, Gs and Gp may be proportionate to BW3/4. Methodology: Seven mongrel dogs (BW 26±2.8 kg) and 4 beagles (BW 9±0.5 kg) were anesthetized, and their left and right hearts were replaced by dual mechanical pumps. While V was kept constant, by controlling the speed of the fluid pumps, VR (ml/min), PLA and PRA (mmHg) were changed variably over a wide range to obtain six sets of VR, PLA and PRA. After the change of a known amount of V (4 mL/kg), six sets of VR, PLA and PRA were obtained in a similar manner. Using 12 sets of VR, PLA and PRA, we obtained Gs, Gp, W, Cs, and Cp using regression analysis in each animal. Finally, we analyzed relations between BW and all these parameters using regression analysis over the 11 animals. Data: Gs (r2=0.73, p value for independent variable piv&lt;0.01; p value for intercept, pi=0.57) and Gp (r2=0.81, piv&lt;0.01, pi=0.64) were proportionate to BW3/4. Cs (r2=0.37, piv=0.027, pi=0.40) and Cp (r2=0.61, piv&lt;0.01, pi=0.48) were proportionate to BW. However, W (r2=-0.11, piv=0.90, pi=0.17) was not associated with BW1/4. Summary of results: All parameters characterizing VR surface except for W were significantly associated with BW. W did not show a significant association with BW, potentially due to the low variations of BW. Conclusions: Allometric scaling of VR surface may be feasible and effective in future clinical application of GCE. NTT Research, Inc. This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

Clinical usefulness of endothelial progenitor cells in predicting the efficacy of riociguat in chronic thromboembolic pulmonary hypertension.

Endothelial dysfunction is important in the pathology of pulmonary hypertension, and circulating endothelial progenitor cells (EPCs) have been studied to evaluate endothelial dysfunction. In patients with chronic thromboembolic pulmonary hypertension (CTEPH), riociguat reportedly increases the number of circulating EPCs. However, the relationship between EPC numbers at baseline and changes in clinical parameters after riociguat administration has not been fully elucidated. Here, we evaluated 27 treatment-naïve patients with CTEPH and analyzed the relationships between EPC number at diagnosis and clinical variables (age, hemodynamics, atrial blood gas parameters, brain natriuretic peptide, and exercise tolerance) before and after riociguat initiation. EPCs were defined as CD45dim CD34+ CD133+ cells and measured by flow cytometry. A low number of circulating EPCs at diagnosis was significantly correlated with increased reductions in mean pulmonary arterial pressure (mPAP) (correlation coefficient = 0.535, P = 0.004) and right atrial pressure (correlation coefficient = 0.618, P = 0.001) upon riociguat treatment. We then divided the study population into two groups according to the mPAP change: a weak-response group (a decrease in mPAP of 4 mmHg or less) and a strong-response group (a decrease in mPAP of more than 4 mmHg). The number of EPCs at diagnosis was significantly lower in the strong-response group than in the weak-response group (P = 0.022), but there were no significant differences in other clinical variables or in medication profiles. In conclusion, circulating EPC numbers could be a potential predictor of the therapeutic effect of riociguat in CTEPH patients.