Left Pressure Research Articles

Randomized Crossover Trial of 2-Week Ketone Ester Treatment in Patients With Type 2 Diabetes and Heart Failure With Preserved Ejection Fraction.

Heart failure with preserved ejection fraction (HFpEF) is a major cause of morbidity and mortality in patients with type 2 diabetes (T2DM). Acute increases in circulating levels of ketone body 3-hydroxybutyrate have beneficial acute hemodynamic effects in patients without T2DM with chronic heart failure with reduced ejection fraction. However, the cardiovascular effects of prolonged oral ketone ester (KE) treatment in patients with T2DM and HFpEF remain unknown. A total of 24 patients with T2DM and HFpEF completed a 6-week randomized, double-blind crossover study. All patients received 2 weeks of KE treatment (25 g D-ß-hydroxybutyrate-(R)-1,3-butanediol × 4 daily) and isocaloric and isovolumic placebo, separated by a 2-week washout period. At the end of each treatment period, patients underwent right heart catheterization, echocardiography, and blood samples at trough levels of intervention, and then during a 4-hour resting period after a single dose. A subsequent second dose was administered, followed by an exercise test. The primary end point was cardiac output during the 4-hour rest period. During the 4-hour resting period, circulating 3-hydroxybutyrate levels were 10-fold higher after KE treatment (1010±56 µmol/L; P<0.001) compared with placebo (91±55 µmol/L). Compared with placebo, KE treatment increased cardiac output by 0.2 L/min (95% CI, 0.1 to 0.3) during the 4-hour period and decreased pulmonary capillary wedge pressure at rest by 1 mm Hg (95% CI, -2 to 0) and at peak exercise by 5 mm Hg (95% CI, -9 to -1). KE treatment decreased the pressure-flow relationship (∆ pulmonary capillary wedge pressure/∆ cardiac output) significantly during exercise (P<0.001) and increased stroke volume by 10 mL (95% CI, 0 to 20) at peak exercise. KE right-shifted the left ventricular end-diastolic pressure-volume relationship, suggestive of reduced left ventricular stiffness and improved compliance. Favorable hemodynamic responses of KE treatment were also observed in patients treated with sodium-glucose transporter-2 inhibitors and glucagon-like peptide-1 analogs. In patients with T2DM and HFpEF, a 2-week oral KE treatment increased cardiac output and reduced cardiac filling pressures and ventricular stiffness. At peak exercise, KE treatment markedly decreased pulmonary capillary wedge pressure and improved pressure-flow relationship. Modulation of circulating ketone levels is a potential new treatment modality for patients with T2DM and HFpEF. URL: https://www.clinicaltrials.gov; Unique Identifier: NCT05236335.

The Hemodynamic Effects of Bolus Dose Calcium in Patients Undergoing Pulmonary Artery Reconstruction and Unifocalization Surgery: A Pilot Study

Objectives: To determine if bolus administration of calcium increases pulmonary artery pressures after unifocalization procedures or pulmonary artery reconstruction surgery. Design: Retrospective cohort study using Stanford University's data warehouse. Setting: A large pediatric heart center within an academic quaternary care facility. Participants: All patients undergoing pulmonary artery reconstruction or unifocalization procedure identifiable within the data warehouse. Interventions: We collected data from Stanford University's data repository; we formatted it and analyzed it using RStudio (v 2023.06.1+524). Measurements and Main Results: Our primary outcome is the change in pulmonary artery systolic pressure (PASP) after a bolus administration of calcium. Secondary endpoints include changes in pulmonary arterial to systemic arterial pressure ratio, mean arterial pressure, right sided filling pressure, and left atrial pressure. We used the Friedman test to assess differences and the Durbin-Conover rank-sum for pairwise comparisons. We found a difference in PASP after a bolus dose of calcium (Friedman X2 = 13.67, p = 0.003), with a higher PASP five minutes after calcium administration when compared to two minutes before the administration (35 mmHg versus 33 mmHg, p = 0.01), and a higher PASP 10 minutes after calcium administration when compared to two minutes before the administration (35 mmHg versus 33 mmHg, p = 0.008). Conclusions: Calcium bolus administration led to an increase in pulmonary arterial pressure in patients after pulmonary artery reconstruction or unifocalization surgeries. It may be prudent to avoid bolus administration in this patient population immediately after repair or in patients with right ventricular dysfunction.

Exploring Atrial Shunt Therapy for Heart Failure: A Comprehensive Review of the Atrial Coronary Sinus Shunt.

Heart failure is a prevalent and severe medical condition characterized by the heart's inability to pump blood efficiently, leading to poor circulation and symptoms such as pulmonary congestion. Despite advancements in medical treatments, many patients continue to experience significant symptoms with reduced quality of life. This article explores the left atrial coronary sinus shunt as an innovative interventional strategy to address hemodynamic issues in heart failure. The shunt aims to decrease left atrial pressure and alleviate pulmonary congestion by creating a connection between the left atrium and the coronary sinus.

Risk factors for raised left ventricular filling pressure by cardiovascular magnetic resonance: Prognostic insights.

Cardiovascular magnetic resonance (CMR) imaging shows promise in estimating pulmonary capillary wedge pressure (PCWP) non-invasively. At the population level, the prognostic role of CMR-modelled PCWP remains unknown. Furthermore, the relationship between CMR-modelled PCWP and established risk factors for cardiovascular disease has not been well characterized. The main aim of this study was to investigate the prognostic value of CMR-modelled PCWP at the population level. Employing data from the imaging substudy of the UK Biobank, a very large prospective population-based cohort study, CMR-modelled PCWP was calculated using a model incorporating left atrial volume, left ventricular mass and sex. Logistic regression explored the relationships between typical cardiovascular risk factors and raised CMR-modelled PCWP (≥15mmHg). Cox regression was used to examine the impact of typical risk factors and CMR-modelled PCWP on heart failure (HF) and major adverse cardiovascular events (MACE). Data from 39163 participants were included in the study. Median age of all participants was 64years (inter-quartile range: 58 to 70), and 47% were males. Clinical characteristics independently associated with raised CMR-modelled PCWP included hypertension [odds ratio (OR) 1.57, 95% confidence interval (CI) 1.44-1.70, P<0.001], body mass index (BMI) [OR 1.57, 95% CI 1.52-1.62, per standard deviation (SD) increment, P<0.001], male sex (OR 1.37, 95% CI 1.26-1.47, P<0.001), age (OR 1.33, 95% CI 1.27-1.41, per decade increment, P<0.001) and regular alcohol consumption (OR 1.10, 95% CI 1.02-1.19, P=0.012). After adjusting for potential confounders, CMR-modelled PCWP was independently associated with incident HF [hazard ratio (HR) 2.91, 95% CI 2.07-4.07, P<0.001] and MACE (HR 1.48, 95% CI 1.16-1.89, P=0.002). Raised CMR-modelled PCWP is an independent risk factor for incident HF and MACE. CMR-modelled PCWP should be incorporated into routine CMR reports to guide HF diagnosis and further management.

Pleural Effusion and Invasive Hemodynamic Measurements in Advanced Heart Failure.

Pleural effusion is present in 50% to 80% of patients with acute heart failure, depending on image modality. We aim to describe the association between the presence and size of pleural effusion and central hemodynamics, including pulmonary capillary wedge pressure (PCWP) in an advanced heart failure population. An observational, cross-sectional study in a cohort of patients with advanced heart failure (left ventricular ejection fraction ≤45%) who underwent right heart catheterization at The Department of Cardiology at Copenhagen University Hospital, Rigshospitalet, Denmark, between January 1, 2002 and October 31, 2020. The presence and size of pleural effusion were determined by a semiquantitative score of chest x-rays or computed tomography scans performed within 2 days of right heart catheterization. In 346 patients (50±13 years; 78% males) with median left ventricular ejection fraction of 20% (15-25), we identified 162 (47%) with pleural effusion. The pleural effusion size was medium in 38 (24%) and large in 30 (19%). Patients with pleural effusion had a 4.3 mm Hg (2.5-6.1) higher PCWP and 2.4 mm Hg (1.2-3.6) higher central venous pressure (P<0.001 for both). Patients with a medium/large pleural effusion had statistically significantly higher filling pressures than patients with a small effusion. Higher PCWP (odds ratio [OR], 1.06 [1.03-1.10]) and central venous pressure (OR, 1.09 [1.05-1.15]) were associated with pleural effusion in multivariable logistic regression adjusted for age, sex, and heart failure medications (P<0.001 for both). In a subgroup of 204 (63%) patients with serum albumin data, PCWP (OR, 1.06 [1.01-1.11]; P=0.032), central venous pressure (OR, 1.14 [1.06-1.23]; P<0.001) and serum albumin level (OR, 0.89 [0.83-0.95]; P<0.001) were independently associated with the presence of a medium/large-sized pleural effusion. In patients with left ventricular ejection fraction ≤45% undergoing right heart catheterization as part of advanced heart failure work-up, pleural effusion was associated with higher PCWP and central venous pressure and lower serum albumin.

Dapagliflozin Enhances Arterial and Venous Compliance During Exercise in Heart Failure With Preserved Ejection Fraction: Insights From the CAMEO-DAPA Trial.

Systemic arterial compliance and venous capacitance are typically impaired in patients with heart failure with preserved ejection fraction (HFpEF), contributing to hemodynamic congestion with stress. Sodium-glucose cotransporter-2 inhibitors reduce hemodynamic congestion and improve clinical outcomes in patients with HFpEF, but the mechanisms remain unclear. This study tested the hypothesis that Dapagliflozin would improve systemic arterial compliance and venous capacitance during exercise in patients with HFpEF. In this secondary analysis from the CAMEO-DAPA trial (Cardiac and Metabolic Effects of Dapagliflozin in Heart Failure With Preserved Ejection Fraction Trial), 37 patients with HFpEF (mean age 68 ± 9 years, women 65%) underwent invasive hemodynamic exercise testing with simultaneous echocardiography at baseline and following treatment for 24 weeks with Dapagliflozin or placebo. Radial artery pressure (BP) was measured continuously using a fluid-filled catheter with transformation to aortic pressure, central hemodynamics were measured using high-fidelity micromanometers, and stressed blood volume was estimated from hemodynamic indices fit to a comprehensive cardiovascular model. There was no statistically significant effect of Dapagliflozin on resting BP, but Dapagliflozin reduced systolic BP during peak exercise (estimated treatment difference [ETD], -18.8 mm Hg [95% CI, -33.9 to -3.7] P=0.016). Reduction in BP was related to improved exertional total arterial compliance (ETD, 0.06 mL/mm Hg/m2 [95% CI, 0.003-0.11] P=0.039) and aortic root characteristic impedance (ETD, -2.6 mm Hg/mL*sec [95% CI: -5.1 to -0.03] P=0.048), with no significant effect on systemic vascular resistance. Dapagliflozin reduced estimated stressed blood volume at rest and during peak exercise (ETD, -292 mm Hg [95% CI, -530 to -53] P=0.018), and improved venous capacitance evidenced by a decline in ratio of estimated stressed blood volume to total blood volume (ETD, -7.3% [95% CI, -13.3 to -1.3] P=0.020). Each of these effects of Dapagliflozin at peak exercise were also observed during matched 20W exercise intensity. Improvements in total arterial compliance and estimated stressed blood volume were correlated with decreases in body weight, and reduction in systolic BP with treatment was correlated with the change in estimated stressed blood volume during exercise (r=0.40, P=0.019). Decreases in BP were correlated with reduction in pulmonary capillary wedge pressure during exercise (r=0.56, P<0.001). In patients with HFpEF, treatment with Dapagliflozin improved systemic arterial compliance and venous capacitance during exercise, while reducing aortic characteristic impedance, suggesting a reduction in arterial wall stiffness. These vascular effects may partially explain the clinical benefits with sodium-glucose cotransporter-2 inhibitors in HFpEF. URL: https://www.clinicaltrials.gov; Unique identifier: NCT04730947.

Abstract Mo039: Risk of Structural and Hemodynamic changes in Left Atrium in Patients with Heart Failure undergoing Percutaneous Left Atrial Appendage Occlusion: A Retrospective Analysis

Background: Exclusion of left atrial appendage (LAA) in animals reduces compliance and increases left atrial pressure. We hypothesize that percutaneous left atrial appendage occlusion (LAAO) would lead to structural and hemodynamic changes in left atrium and assess the risk using echocardiographic cut-offs used for evaluating left atrial pressure in heart failure patients. Methods: We queried TriNetx database for adult patients with heart failure undergoing percutaneous LAAO. We excluded those who underwent surgical or alternative percutaneous procedures pertaining to LAA, procedures pertaining to mitral valve (MV), mitral valvular pathologies, mechanical circulatory support placement, pacemaker placement, and those with left bundle branch block. We calculated risk of meeting echocardiographic cut-offs used in evaluation of left atrial pressure; MV maximum E-wave velocity ≥50cm/s, left atrial end systolic volume index (LAESVI) indexed to body surface area ≥34 ml/m2, Tricuspid Regurgitation systolic jet velocity ≥ 2.8 m/s, Pulmonary vein Systole/Diastole ratio ≤ 1, mitral valve lateral annulus E/e' ≥ 13 and Mitral valve E/A ratio ≥2. Those meeting the respective cut-off before LAAO were excluded. All diagnoses, procedures, and echocardiographic parameters were identified using International Classification of Diseases, Current Procedural Terminology, and Logical Observation Identifiers Names and Codes. Results: We identified 4,046 patients with heart failure undergoing percutaneous LAAO. Baseline demographics and diagnosis were; mean (SD) age 75.4 (8.1) years, 37% females, 92% hypertension, 67% ischemic heart disease, 42% diabetes mellitus, 41% chronic kidney disease, and 42% were overweight or obese. Risk of meeting echocardiographic cut-offs used in evaluating left atrial pressure was low with 0.24% (10) patients having LAESVI indexed to body surface area ≥34 ml/m2, Tricuspid Regurgitation systolic jet velocity ≥ 2.8 m/s, Pulmonary vein Systole/Diastole ratio ≤ 1, and Mitral valve E/A ratio ≥ 2. Risk of having MV maximum E-wave velocity ≥50cm/s was 0.58% and no patients had mitral valve lateral annulus E/e' ≥ 13. (Figure 1) Conclusion: Risk of meeting echocardiographic cut-offs used in evaluation of left atrial pressure in patients with heart failure undergoing percutaneous LAAO is low.

Peripheral Venous Pressure And NT-proBNP Phenotypes as Surrogates for Invasive Fontan Haemodynamics in Adults

We hypothesized that phenotyping patients using a combination of resting peripheral venous pressure (PVP) and N-terminal pro–brain natriuretic peptide (NT-proBNP) would predict invasive Fontan haemodynamics. Accordingly, 35 adults with a history of Fontan palliation were categorized into 3 groups according to PVP and NT-proBNP values: normal, ↑NT-proBNP (≥300 pg/dL) or ↑PVP (≥15 mm Hg), and ↑PVP+↑NT-proBNP. Those in the normal values group universally had normal resting pulmonary artery wedge and Fontan pressures, with a single patient having abnormal exercise values; conversely, all patients in the ↑PVP+↑NT-proBNP group had increased resting Fontan or pulmonary artery wedge pressures, with those in the ↑NT-proBNP or ↑PVP group constituting an intermediate group.

A less-invasive left atrial assist device concept for diastolic heart failure: First in vitro and in vivo assessment

ObjectiveA less-invasive left atrial assist device (LAADx) is a novel and implantable, extracardiac blood pump concept, intended for the treatment of diastolic heart failure, represented by heart failure with preserved ejection fraction. MethodsA mixed-flow pump was used as the working LAADx model. Its performance was evaluated at 3 speeds, using an in vitro pulsatile mock circulatory loop, with a pneumatic pump that can simulate diastolic heart failure conditions by adjusting the diastolic drive pressure. The LAADx model was implanted in 4 healthy calves. The pump's inflow and outflow cannulas were inserted into the left atrium (LA) and left ventricle (LV), respectively, without cardiopulmonary bypass. The LAADx was operated at 3 speeds, and diastolic heart failure-like conditions were induced by inflating a balloon, inserted into the LV. ResultsWith the in vitro study, diastolic heart failure-like conditions were successfully induced, exhibiting decreased cardiac output and aortic pressure as well as increased mean LA pressure both mitigated with the LAADx support. With regard to the in vivo study, simulated diastolic heart failure conditions showed a decrease in aortic pressure and an increase in LA pressure and LV end-diastolic pressure, which were again mitigated by the LAADx. Echocardiography showed good positioning of the outflow cannula and neither cardiac dysfunction nor mitral interference was observed. ConclusionsInitial in vitro and in vivo results confirmed that the LAADx model, a device concept driven by creating an extracardiac route from the LA to LV, has the potential to mitigate high LA pressure and improve LV filling of heart failure with preserved ejection fraction pathology.

Does Sinus Rhythm Restoration in Patients With Atrial Fibrillation Undergoing Pulmonary Vein Isolation Have Acute Hemodynamic Benefits?

Although the restoration and maintenance of sinus rhythm (SR) in patients with atrial fibrillation (AF) have long-term benefits, few studies have investigated the acute hemodynamic benefits immediately after SR restoration. Therefore, we investigated whether hemodynamic changes occurred in the first few minutes after cardioversion from AF to SR. We retrospectively enrolled 145 patients with AF and divided them into a pre-AF group comprising patients in whom SR was restored by electrical cardioversion during pulmonary vein isolation (PVI; n = 74) and a control group comprising patients who were in SR throughout the procedure (n = 71). The pre-AF group was subdivided into subgroups according to AF classification (paroxysmal AF (PAF), persistent AF (PerAF), and long-standing persistent AF (LSPAF)) and into quartiles based on the AF-heart rate (HR). The mean arterial pressure (MAP) and left atrial pressure (LAP) were measured immediately after transseptal puncture (pre-measurement) and before withdrawal from the left atrium after PVI (post-measurement). The changes in MAP and LAP between the pre- and post-measurement (ΔMAP and ΔLAP) were calculated by subtracting the pre-measurements (MAPpre and LAPpre) from the post-measurements (MAPpost and LAPpost). In the pre-AF group, the time from cardioversion to post-measurement was 19 ± 16 min. When ΔMAP and ΔLAP were compared with the control group, ΔMAP was significantly smaller (4.9 ± 17.8 vs. 11.0 ± 14.2 mm Hg, respectively; P = 0.025), and ΔLAP was not significantly different between the groups. In the subgroup analyses, although ΔLAP was not significantly different among AF types, ΔMAP was significantly increased in the PAF group compared to the PerAF and LSPAF groups (24.0 ± 18.5 vs. 3.1 ± 16.8 and 4.5 ± 18.1 mm Hg, respectively; P = 0.042). The HRpre in the quartiles with the lowest, second, third, and highest AF-HR were approximately 58, 74, 86, and 109 beats per minute (bpm), respectively. The ΔLAP and ΔMAP were not significantly different among the AF-HR quartile groups. In patients with PAF, atrial contractions may resume quickly, which leads to hemodynamic improvement immediately after SR restoration. As for AF-HR, there was no significant impairment of ventricular diastolic filling at approximately < 109 bpm.

Association of Cardiac MRI-derived Aortic Stiffness with Early Stages and Progression of Heart Failure with Preserved Ejection Fraction.

Purpose To investigate if aortic stiffening as detected with cardiac MRI is an early phenomenon in the development and progression of heart failure with preserved ejection fraction (HFpEF). Materials and Methods Both clinical and preclinical studies were performed. The clinical study was a secondary analysis of the prospective HFpEF stress trial (August 2017 through September 2019) and included 48 participants (median age, 69 years [range, 65-73 years]; 33 female, 15 male) with noncardiac dyspnea (NCD, n = 21), overt HFpEF at rest (pulmonary capillary wedge pressure [PCWP] ≥ 15 mm Hg, n = 14), and masked HFpEF at rest diagnosed during exercise stress (PCWP ≥ 25 mm Hg, n = 13) according to right heart catheterization. Additionally, all participants underwent echocardiography and cardiac MRI at rest and during exercise stress. Aortic pulse wave velocity (PWV) was calculated. The mechanistic preclinical study characterized cardiac function and structure in transgenic mice with induced arterial stiffness (Runx2-smTg mice). Statistical analyses comprised nonparametric and parametric comparisons, Spearman correlations, and logistic regression models. Results Participants with HFpEF showed increased PWV (NCD vs masked HFpEF: 7.0 m/sec [IQR: 5.0-9.5 m/sec] vs 10.0 m/sec [IQR: 8.0-13.4 m/sec], P = .005; NCD vs overt HFpEF: 7.0 m/sec [IQR: 5.0-9.5 m/sec] vs 11.0 m/sec [IQR: 7.5-12.0 m/sec], P = .01). Increased PWV correlated with higher PCWP (P = .006), left atrial and left ventricular long-axis strain (all P < .02), and N-terminal pro-brain natriuretic peptide levels (P < .001). Participants with overt HFpEF had higher levels of myocardial fibrosis, as demonstrated by increased native T1 times (1199 msec [IQR: 1169-1228 msec] vs 1234 msec [IQR: 1208-1255 msec], P = .009). Aortic stiffness was independently associated with HFpEF on multivariable analyses (odds ratio, 1.31; P = .049). Runx2-smTG mice exhibited an "HFpEF" phenotype compared with wild-type controls, with preserved left ventricular fractional shortening but an early and late diastolic mitral annulus velocity less than 1 (mean, 0.67 ± 0.39 [standard error of the mean] vs 1.45 ± 0.47; P = .004), increased myocardial collagen deposition (mean, 11% ± 1 vs 2% ± 1; P < .001), and increased brain natriuretic peptide levels (mean, 171 pg/mL ± 23 vs 101 pg/mL ± 10; P < .001). Conclusion This study provides translational evidence that increased arterial stiffness might be associated with development and progression of HFpEF and may facilitate its early detection. Keywords: MR Functional Imaging, MR Imaging, Animal Studies, Cardiac, Aorta, Heart ClinicalTrials.gov identifier NCT03260621 Supplemental material is available for this article. © RSNA, 2024.

Relationship between obesity, cardiac hemodynamics, and heart failure in adults with coarctation of aorta.

Patients with coarctation of aorta (COA) have arterial stiffening and left ventricular (LV) diastolic dysfunction similar to patients with heart failure with preserved ejection fraction (HFpEF) and obese subjects. However, the relationship between obesity, cardiac hemodynamics, and HF in adults with COA is unknown. The purpose of this study was to compare cardiac hemodynamics and prevalence of HFpEF between COA patients with vs without obesity, and to assess the relationship between obesity and HFpEF in this population. Adults with COA who underwent right heart catheterization were divided into an obese group (body mass index, BMI > 30 kg/m2) or a non-obese group (BMI ≤ 30 kg/m2). We also selected a control group of subjects without structural heart disease and with normal invasive hemodynamics at rest (n = 36). HFpEF was defined as having clinical symptoms of HF (exertional dyspnea or fatigue), LV ejection fraction of at least 50%, and pulmonary artery wedge pressure (PAWP) greater than 15 mm Hg at rest. Of 99 COA patients, 29 (29%) had obesity. The obese COA group had higher right atrial pressure and PAWP, and worse pulmonary and systemic vascular function compared with the non-obese COA group and the control group. The overall prevalence of HFpEF in adults with COA was 32%, and the prevalence was higher in COA patients with obesity (55%) compared with those without obesity (23%). Obesity was associated with HFpEF after adjustment for demographic indices, comorbidities, and vascular function. The abnormal hemodynamics and higher prevalence of HFpEF in COA patients with obesity underscores the need for intervention to address obesity in this population.

Mechanical power ratio threshold for ventilator-induced lung injury

RationaleMechanical power (MP) is a summary variable incorporating all causes of ventilator-induced-lung-injury (VILI). We expressed MP as the ratio between observed and normal expected values (MPratio).ObjectiveTo define a threshold value of MPratio leading to the development of VILI.MethodsIn a population of 82 healthy pigs, a threshold of MPratio for VILI, as assessed by histological variables and confirmed by using unsupervised cluster analysis was 4.5. The population was divided into two groups with MPratio above or below the threshold.Measurements and main resultsWe measured physiological variables every six hours. At the end of the experiment, we measured lung weight and wet-to-dry ratio to quantify edema. Histological samples were analyzed for alveolar ruptures, inflammation, alveolar edema, atelectasis. An MPratio threshold of 4.5 was associated with worse injury, lung weight, wet-to-dry ratio and fluid balance (all p < 0.001). After 48 h, in the two MPratio clusters (above or below 4.5), respiratory system elastance, mean pulmonary artery pressure and physiological dead space differed by 32%, 36% and 22%, respectively (all p < 0.001), being worse in the high MPratio group. Also, the changes in driving pressure, lung elastance, pulmonary artery occlusion pressure, central venous pressure differed by 17%, 64%, 8%, 25%, respectively (all p < 0.001).LimitationsThe main limitation of this study is its retrospective design. In addition, the computation for the expected MP in pigs is based on arbitrary criteria. Different values of expected MP may change the absolute value of MP ratio but will not change the concept of the existence of an injury threshold.ConclusionsThe concept of MPratio is a physiological and intuitive way to quantify the risk of ventilator-induced lung injury. Our results suggest that a mechanical power ratio > 4.5 MPratio in healthy lungs subjected to 48 h of mechanical ventilation appears to be a threshold for the development of ventilator-induced lung injury, as indicated by the convergence of histological, physiological, and anatomical alterations. In humans and in lungs that are already injured, this threshold is likely to be different.

Determinants of invasive left atrial pressure in patients with atrial fibrillation.

Estimation of left ventricular (LV) filling pressures in patients with atrial fibrillation (AF) is challenging due to lack of reliable parameters. This study investigates the association between cardiac structure and function and invasive mean left atrial pressure (LAP). This is a multi-center prospective study enrolling patients undergoing transcatheter ablation for AF. The invasive measurement of LAP was performed at the time of the procedure while the echocardiography within the previous 24 hours. A mean LAP ≥ 15 mmHg was considered as increased. Overall, 101 patients were included (mean age 65.8 ± 8.5 years, 68% male, mean LV ejection fraction 56.6 ± 8.0%). No significant differences regarding clinical characteristics were detected between the group of patients with normal (n=47) or increased LAP (n=54). The latter showed lower values of LV global longitudinal strain, larger left atrial volumes (LAV) and worse right ventricular (RV) function. After multivariable adjustment, higher E/e' ratio (p=0.041) and minimal LAV index (LAVI min) (p=0.031), lower peak atrial longitudinal strain (PALS) (p=0.030) and RV free wall strain (p=0.037), but not maximal LAV index (LAVI max) (p=0.137), were significantly associated with mean LAP. The associations were not modified by cardiac rhythm. Overall, LAVI min showed the best diagnostic accuracy to predict elevated LAP (AUC 0.703). LA structure and function assessment well correlates with mean LAP in patients with AF. These measures may be used in the assessment of filling pressure in these patients.

Coronary microvascular dysfunction and left heart filling pressures in patients with type 2 diabetes.

Patients with type 2 diabetes (T2D) have a high prevalence of diastolic dysfunction and heart failure with preserved ejection fraction (HFpEF), which in turn leads to an increased risk of hospitalization and death. However, the factors of risk and their relative importance in leading to higher left ventricular filling pressures are still disputed. We sought to clarify the associations of a wide range of invasive and non-invasive risk factors with cardiac filling pressures in high-risk T2D patients. Patients with T2D at high risk of cardiovascular events were prospectively enrolled in this study. Participants were thoroughly phenotyped including right heart catheterization at rest and during exercise, echocardiography, urinary excretion of albumin (UACR), and quantification of their myocardial blood flow rate (MFR) using cardiac 82Rb-PET/CT. Of the 37 patients included in the study, 22 (59%) patients met invasive criteria for HFpEF. Only 2 out of 39 variables emerged as independent factors associated with left ventricular filling pressure as assessed by pulmonary capillary wedge pressure (PCWP) at rest; history of hypertension (coefficient: 2.6mmHg [0.3; 5.0], P=0.030) and MFR (P=0.026). We found a significant inverse association between MFR and PCWP with a coefficient of -2.3mmHg (-4.3; -0.3) in PCWP per integer change of MFR. The MFR ranged from 1.18 to 3.68 in our study, which corresponds to a difference in PCWP of approximately 6mmHg between patients with the lowest compared to the highest MFR. During exercise, only 2 variables emerged as borderline independent factors associated with PCWP: myocardial flow reserve (coefficient: -4.4 [-9.6; 0.8], P=0.091) and beta-blockers use (coefficient: 6.1 [-0.1; 12.4], P=0.053). In patients with type 2 diabetes without known HFpEF but risk factors for cardiovascular disease, myocardial blood flow rate was independently associated with PCWP at rest across the range from normal to abnormal left heart filling pressures. A clinically significant difference of 6mmHg in PWCP was attributable to differences in MFR in patients with the lowest compared with the highest MFR values. This suggests that strategies than attenuate microvascular dysfunction could slow progression of increased left ventricular left heart filling pressures in patients at increased risk.

Left ventricular diastolic function assessed by speckle tracking echocardiography in patients with left ventricular aneurysm.

Speckle-tracking echocardiography (STE) parameters are an integral part of the assessment of left ventricular (LV) function. We aimed to evaluate established and novel STE parameters of LV diastolic function and their prognostic role in patients with LV anteroapical aneurysm undergoing surgical ventricular repair (SVR). We retrospectively examined the data of 137 patients with anteroapical LV aneurysm who underwent SVR. In 27 patients, the correlation of STE parameters with invasive hemodynamic parameters was evaluated. Preoperative echocardiographic parameters were assessed for their association with outcome, defined as all-cause mortality, LV assist device implantation, or heart transplantation. The late diastolic strain rate (GLSRa) showed a stronger correlation with mean pulmonary artery pressure (r = - 0.75, p < 0.001) than all other parameters. GLSRa was also significantly correlated with mean pulmonary capillary wedge pressure and LV end-diastolic pressure. In the multivariate model, GLSRa and the ratio of early diastolic filling velocity to GLSRa demonstrated incremental prognostic value in addition to clinical and echocardiographic parameters. Patients with GLSRa < 0.59s-1 had significantly shorter event-free survival than those with GLSRa > 0.59s-1 (6.7 vs. 10.9years, p < 0.001). Peak reservoir left atrial strain showed a weaker association with hemodynamic parameters and outcome compared to GLSRa. In patients with LV aneurysm, late diastolic strain rate and left atrial strain can be used for the assessment of LV diastolic function and have a predictive value for the outcome after surgical ventricular restoration.

Dapagliflozin and Right Ventricular–Pulmonary Vascular Interaction in Heart Failure With Preserved Ejection Fraction

Increases in pulmonary capillary wedge pressure (PCWP) during exercise reduce pulmonary artery (PA) compliance, increase pulsatile right ventricular (RV) afterload, and impair RV-PA coupling in patients with heart failure with preserved ejection fraction (HFpEF). The effects of the sodium-glucose cotransporter 2 (SGLT2) inhibitor dapagliflozin on pulmonary vascular properties and RV-PA coupling are unknown. To test the effect of dapagliflozin on right ventricular performance and pulmonary vascular load during exertion in HFpEF. Evaluation of the Cardiac and Metabolic Effects of Dapagliflozin in Heart Failure With Preserved Ejection Fraction (CAMEO-DAPA) randomized clinical trial demonstrated improvement in PCWP at rest and exercise over 24 weeks with dapagliflozin compared with placebo with participants recruited between February 2021 and May 2022. This secondary analysis evaluates the effects of dapagliflozin on pulsatile pulmonary vascular load and RV-PA coupling using simultaneous echocardiography and high-fidelity invasive hemodynamic testing with exercise. This was a single-center study including patients with hemodynamically confirmed HFpEF with exercise PCWP of 25 mm Hg or greater. Dapagliflozin or placebo for 24 weeks. Pulsatile pulmonary vascular load (PA compliance and elastance) and right ventricular performance (PA pulsatility index, RV systolic velocity [s']/PA mean) during rest and exercise. Among 37 randomized participants (mean [SD] age, 67.4 [8.5] years; 25 female [65%]; mean [SD] body mass index, 34.9 [6.7]; calculated as weight in kilograms divided by height in meters squared), there was no effect of dapagliflozin on PA loading or RV-PA interaction at rest. However, with exercise, dapagliflozin improved PA compliance (placebo-corrected mean difference, 0.57 mL/mm Hg; 95% CI, 0.11-1.03 mL/mm Hg; P = .02) and decreased PA elastance (stiffness; -0.17 mm Hg/mL; 95% CI, -0.28 to -0.07 mm Hg/mL; P = .001). RV function during exercise improved, with increase in PA pulsatility index (0.33; 95% CI, 0.08-0.59; P = .01) and increase in exercise RV s' indexed to PA pressure (0.09 cm·s-1/mm Hg; 95% CI, 0.02-0.16 cm·s-1/mm Hg; P = .01). Improvements in pulsatile RV load and RV-PA coupling were correlated with reduction in right atrial (RA) pressure (PA elastance Pearson r = 0.55; P =.008; RV s'/PA elastance Pearson r = -0.60; P =.002) and PCWP (PA elastance Pearson r = 0.58; P <.001; RV s'/PA elastance Pearson r = -0.47; P = .02). Dapagliflozin increased resistance-compliance time (dapagliflozin, median [IQR] change, 0.06 [0.03-0.15] seconds; placebo, median [IQR] change, 0.01 [-0.02 to 0.05] seconds; P =.046), resulting in higher PA compliance for any exercise pulmonary vascular resistance. Results of this randomized clinical trial reveal that treatment with dapagliflozin for 24 weeks reduced pulsatile pulmonary vascular load and enhanced dynamic RV-PA interaction during exercise in patients with HFpEF, findings that are related to the magnitude of PCWP reduction. Benefits on dynamic right ventricular-pulmonary vascular coupling may partially explain the benefits of SGLT2 inhibitors in HFpEF. ClinicalTrials.gov Identifier: NCT04730947.

Comprehensive non-invasive haemodynamic assessment in acute decompensated heart failure-related cardiogenic shock: a step towards echodynamics.

Haemodynamic assessment can be determinant in phenotyping cardiogenic shock (CS) and guiding patient management. Aim of this study was to evaluate the correlation between echocardiographic and invasive assessment of haemodynamics in acute decompensated heart failure-related CS (ADHF-CS). All consecutive ADHF-CS patients (SCAI shock stage ≥B) undergoing right heart catheterization (RHC) between 2020 and 2022 were prospectively enrolled. Patients underwent echocardiography 30 min before RHC. The evaluated haemodynamic parameters and their echocardiographic estimates ('e') comprised cardiac index (CI), wedge pressure (WP), pulmonary artery pressures (PAP), cardiac power output (CPO) and pulmonary artery pulsatility index (PAPi). Hundred and one ADHF-CS patients (56 ± 11 years, 64% SCAI shock stage C, left ventricular ejection fraction 29 ± 5%) were included. Good correlation was found for CI, systolic PAP, RAP, and CPO (Pearson r > 0.8 for all), moderate correlation for ePAPi (r = 0.67) and PVR (r = 0.51), while estimation of WP was weak. The sensitivity and specificity of eCI to identify low output state (CI ≤2.2 L/min/m2) were 0.97 and 0.73, respectively, those of eWP for elevated filling pressures (WP >15 mmHg) were 0.84 and 0.55, those of ePAPs for PAPs ≥35 mmHg were 0.87 and 0.63, those of eCPO for CPO <0.6 W were 0.76 and 0.85, those of ePAPi for PAPi <1.85 were 0.89 and 0.92. Echocardiographic phenotyping of CS showed a good agreement with invasive classification (K value 0.457, P < 0.001). Echocardiographic estimation of haemodynamics and subsequent phenotypization of CS is feasible with good agreement with invasive evaluation.

Clinical features, haemodynamics, and outcomes of heart failure with preserved ejection fraction in coarctation of aorta.

There are similarities in the pathogenesis of cardiac remodelling and dysfunction in heart failure with preserved ejection fraction (HFpEF) and coarctation of aorta (COA). We hypothesized that clinical HFpEF would be highly prevalent in adults with COA, and that the presence of HFpEF would increase the risk of mortality in this population. The aim of this study was to define the clinical features, haemodynamics, and prognostic implications of HFpEF in COA. Consecutive adults with repaired COA that underwent right heart catheterization were identified retrospectively. HFpEF was defined as heart failure symptoms (exertional dyspnoea or fatigue), preserved left ventricular ejection fraction ≥50%, and pulmonary artery wedge pressure at rest >15 mmHg. Of 99 COA patients, 32 (32%) had HFpEF. The correlates of HFpEF were obesity (adjusted odds ratio [OR] 4.15, 95% confidence interval [CI] 1.31-13.2), atrial fibrillation (adjusted OR 3.13, 95% CI 1.00-10.7), total arterial compliance index (adjusted OR 0.12, 95% CI 0.06-0.41 per 1 ml/mmHg*m2), and pulmonary artery compliance index (adjusted OR 0.36, 95% CI 0.15-0.56 per 1 ml/mmHg*m2). Of 99 patients, 24 (24%) died and 5 (5%) underwent heart transplant. The 10-year cumulative incidence of death/transplant was higher in COA patients with HFpEF compared with patients without HFpEF (39% vs. 12%, p = 0.001). The presence of HFpEF was associated with increased risk of death/transplant (adjusted hazard ratio 1.68, 95% CI 1.16-3.11). Heart failure with preserved ejection fraction is common in adults with COA and is associated with greater risk of death/transplant, emphasizing a pressing need for interventions to prevent and treat HFpEF in COA.

HeartMate 3 for Heart Failure with Preserved Ejection Fraction: In Vitro Hemodynamic Evaluation and Anatomical Fitting.

Heart failure with preserved ejection fraction (HFpEF) constitutes approximately 50% of heart failure (HF) cases, and encompasses different phenotypes. Among these, most patients with HFpEF exhibit structural heart changes, often with smaller left ventricular cavities, which pose challenges for utilizing ventricular assist devices (VADs). A left atrial to aortic (LA-Ao) VAD configuration could address these challenges, potentially enhancing patient quality of life by lowering elevated mean left atrial pressure (MLAP). This study assessed the anatomical compatibility and left atrial unloading capacity using a simulated VAD-supported HFpEF patient. A HeartMate3-supported HFpEF patient in an LA-Ao configuration was simulated using a cardiovascular simulator. Hemodynamic parameters were recorded during rest and exercise at seven pump flow rates. Computed tomography scans of 14 HFpEF (NYHA II-III) and six heart failure with reduced ejection fraction patients were analysed for anatomical comparisons. HFpEF models were independently assessed for virtual anatomical fit with the HM3 in the LA-Ao configuration. Baseline MLAP was reduced from 15 to 11mmHg with the addition of 1L/min HM3 support in the rest condition. In an exercise simulation, 6L/min of HM3 support was required to reduce the MLAP from 29 to 16mmHg. The HM3 successfully accommodated six HFpEF patients without causing interference with other cardiac structures, whereas it caused impingement ranging from 4 to 14mm in the remaining patients. This study demonstrated that the HM3 in an LA-Ao configuration may be suitable for unloading the left atrium and relieving pulmonary congestion in some HFpEF patients where size-related limitations can be addressed through pre-surgical anatomical fit analysis.