Invasive Hemodynamic Measurements Research Articles

Right ventricular to pulmonary artery coupling in chronic thromboembolic pulmonary hypertension

BackgroundChronic thromboembolic pulmonary hypertension (CTEPH) is characterized by increased pulmonary vascular resistance (PVR) and pressure and right ventricular (RV) dysfunction. We aimed to evaluate the correlation of RV to pulmonary artery coupling, measured as the tricuspid annular plane systolic excursion/pulmonary arterial systolic pressure (TAPSE/PASP) ratio, and invasive hemodynamic measurements, and to assess the changes in this ratio following CTEPH treatment. MethodsWe conducted a retrospective cohort study of CTEPH patients treated at Aarhus University Hospital with pulmonary angioplasty (BPA), pulmonary endarterectomy (PEA), and or medical therapy only. Patients underwent transthoracic echocardiography and right heart catheterization at baseline and follow-up. The primary endpoint was the association between TAPSE/PASP and PVR. Secondary endpoints included other hemodynamic and functional parameters. ResultsThe study included 139 patients. Mean TAPSE/PASP at baseline was 0.22 [0.16, 0.29] mm/mmHg. An exponential decay correlation was found between TAPSE/PASP and PVR (correlation coefficient − 0.67, p < 0.001). The TAPSE/PASP ratio improved from 0.23 [0.18; 0.29] to 0.33 [0.26; 0.46] mm/mmHg, p < 0.0001, following BPA, and from 0.20 [0.15;0.27] to 0.35 [0.21;0.41] mm/mmHg, p = 0.0007 following PEA, indicating enhanced RV to pulmonary artery coupling. ConclusionIn patients with CTEPH, the echocardiographic TAPSE/PASP ratio as a measure of RV-PA coupling correlates well with invasively measured pulmonary vascular resistance. The TAPSE/PASP ratio improved after BPA or PEA treatments suggesting a potential use for monitoring patient outcomes. Further prospective studies are warranted to establish the prognostic value of the TAPSE/PASP ratio and ability to guide treatment decisions.

Intracoronary ECG ST-segment shift remission time during reactive myocardial hyperemia: a new method to assess hemodynamic coronary stenosis severity.

Fractional flow reserve (FFR) measurements are recommended for assessing hemodynamic coronary stenosis severity. Intracoronary ECG (icECG) is easily obtainable and highly sensitive in detecting myocardial ischemia due to its close vicinity to the myocardium. We hypothesized that the remission time of myocardial ischemia on icECG after a controlled coronary occlusion accurately detects hemodynamically relevant coronary stenosis. This retrospective, observational study included patients with chronic coronary syndrome undergoing hemodynamic coronary stenosis assessment immediately following a strictly 1-min proximal coronary artery balloon occlusion with simultaneous icECG recording. icECG was used for a beat-to-beat analysis of the ST-segment shift during reactive hyperemia immediately following balloon deflation. The time from coronary balloon deflation until the ST-segment shift reached 37% of its maximum level, i.e., icECG ST-segment shift remission time (τ-icECG in seconds), was obtained by an automatic algorithm. τ-icECG was tested against the simultaneously obtained reactive hyperemia FFR at a threshold of 0.80 as a reference parameter. From 120 patients, 139 icECGs (age, 68 ± 10 yr old) were analyzed. Receiver operating characteristic (ROC) analysis of τ-icECG for the detection of hemodynamically relevant coronary stenosis at an FFR of ≤0.80 was performed. The area under the ROC curve was equal to 0.621 (P = 0.0363) at an optimal τ-icECG threshold of 8 s (sensitivity, 61%; specificity, 67%). τ-icECG correlated inversely and linearly with FFR (P = 0.0327). This first proof-of-concept study demonstrates that τ-icECG, a measure of icECG ST segment-shift remission after a 1-min coronary artery balloon occlusion accurately detects hemodynamically relevant coronary artery stenosis according to FFR at a threshold of ≥8 s.NEW & NOTEWORTHY Invasive hemodynamic measurements are recommended by the current cardiology guidelines to guide percutaneous coronary interventions in the setting of chronic coronary syndrome. However, those pressure-derived indices demonstrate several theoretical and practical limitations. Thus, this study demonstrates the accuracy of a novel, pathophysiology-driven approach using intracoronary ECG for the identification of hemodynamically relevant coronary lesions by quantitatively assessing myocardial ischemia remission.

Interactions between the gut microbiome, associated metabolites and the manifestation and progression of heart failure with preserved ejection fraction in ZSF1 rats

BackgroundHeart failure with preserved ejection fraction (HFpEF) is associated with systemic inflammation, obesity, metabolic syndrome, and gut microbiome changes. Increased trimethylamine-N-oxide (TMAO) levels are predictive for mortality in HFpEF. The TMAO precursor trimethylamine (TMA) is synthesized by the intestinal microbiome, crosses the intestinal barrier and is metabolized to TMAO by hepatic flavin-containing monooxygenases (FMO). The intricate interactions of microbiome alterations and TMAO in relation to HFpEF manifestation and progression are analyzed here.MethodsHealthy lean (L-ZSF1, n = 12) and obese ZSF1 rats with HFpEF (O-ZSF1, n = 12) were studied. HFpEF was confirmed by transthoracic echocardiography, invasive hemodynamic measurements, and detection of N-terminal pro-brain natriuretic peptide (NT-proBNP). TMAO, carnitine, symmetric dimethylarginine (SDMA), and amino acids were measured using mass-spectrometry. The intestinal epithelial barrier was analyzed by immunohistochemistry, in-vitro impedance measurements and determination of plasma lipopolysaccharide via ELISA. Hepatic FMO3 quantity was determined by Western blot. The fecal microbiome at the age of 8, 13 and 20 weeks was assessed using 16s rRNA amplicon sequencing.ResultsIncreased levels of TMAO (+ 54%), carnitine (+ 46%) and the cardiac stress marker NT-proBNP (+ 25%) as well as a pronounced amino acid imbalance were observed in obese rats with HFpEF. SDMA levels in O-ZSF1 were comparable to L-ZSF1, indicating stable kidney function. Anatomy and zonula occludens protein density in the intestinal epithelium remained unchanged, but both impedance measurements and increased levels of LPS indicated an impaired epithelial barrier function. FMO3 was decreased (− 20%) in the enlarged, but histologically normal livers of O-ZSF1. Alpha diversity, as indicated by the Shannon diversity index, was comparable at 8 weeks of age, but decreased by 13 weeks of age, when HFpEF manifests in O-ZSF1. Bray–Curtis dissimilarity (Beta-Diversity) was shown to be effective in differentiating L-ZSF1 from O-ZSF1 at 20 weeks of age. Members of the microbial families Lactobacillaceae, Ruminococcaceae, Erysipelotrichaceae and Lachnospiraceae were significantly differentially abundant in O-ZSF1 and L-ZSF1 rats.ConclusionsIn the ZSF1 HFpEF rat model, increased dietary intake is associated with alterations in gut microbiome composition and bacterial metabolites, an impaired intestinal barrier, and changes in pro-inflammatory and health-predictive metabolic profiles. HFpEF as well as its most common comorbidities obesity and metabolic syndrome and the alterations described here evolve in parallel and are likely to be interrelated and mutually reinforcing. Dietary adaption may have a positive impact on all entities.Graphical abstract

Plasma catecholamines in patients undergoing invasive cardiopulmonary exercise test for exercise intolerance

BackgroundInvasive cardiopulmonary exercise testing (iCPET) combines traditional cardiopulmonary exercise testing with invasive hemodynamic measurements to assess exercise intolerance, which can be caused by preload insufficiency (PI), characterized by low ventricular filling pressures and reduced cardiac output during exertion. We hypothesize that plasma catecholamine levels at rest and during exercise correlate with hemodynamic parameters in PI. MethodsWe included adult patients who underwent iCPET for exercise intolerance and had plasma catecholamines measured at rest and peak exercise. ResultsAmong 84 patients, PI was identified in 57 (67.8 %). Compared to patients without PI, those with PI were younger [median (IQR) 37 (28, 46) vs 47 (39,55) years, p = 0.005] and had lower workload at peak exercise [81 (66, 96) vs 95 (83.5, 110.50) Watts, p = 0.006]. Patients with PI had higher heart rates at rest and peak exercise [87 (78, 97) vs 79 (74, 87) bpm, p = 0.04; and 167 (154, 183) vs 156 (136, 168) bpm, p = 0.01, respectively]. In all patients, epinephrine and norepinephrine at peak exercise directly correlated with peak workload (r:0.41, p < 0.001 and r:0.47, p < 0.001, respectively). Resting epinephrine was higher in patients with PI [136 (60, 210) vs 77 (41, 110) pg/mL, p = 0.02]. There was no significant difference in the change in catecholamines from rest to peak exercise between patients with or without PI. ConclusionPI patients exhibited elevated heart rate and epinephrine at rest, indicating increased sympathetic activity. We did not find strong associations between catecholamines and cardiac filling pressures, suggesting that catecholamine levels are predominantly influenced by peak workload.

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.

Abstract Mo103: Aberrant Trans- and De- Nitrosylation Underpins Nitrosative Stress in Cardiometabolic HFpEF

Background: Heart failure with preserved ejection fraction (HFpEF) is among the leading causes of cardiovascular mortality and morbidity. Recent reports suggest excessive myocardial protein S-nitrosylation (-SNO), a hallmark of nitrosative stress, contributes to HFpEF pathophysiology. However, the role of transnitrosylases, enzymes that induce protein-SNO, or denitrosylases, enzymes that eliminate protein-SNO, have not been investigated in the context of HFpEF. Research Questions and Goals: We sought to investigate the regulation of protein nitrosylation dynamics in a rat model of cardiometabolic HFpEF. Methods: Echocardiographic assessment, invasive hemodynamic measurements, and exercise testing were conducted in WKY or ZSF1 obese (Ob) rats to evaluate HFpEF severity. Nitric oxide (NO) bioavailability and protein-SNO levels were determined in the heart tissue. Endothelial-dependent vascular reactivity was assayed to further evaluate NO signaling. In parallel, single-cell (sc) RNA sequencing was performed to determine the transcriptional changes in trans- and denitrosylases, as well as NO synthases. Results: We observed progressive deterioration in LV diastolic function (significantly elevated E/e’ and LV end-diastolic pressure) and exercise performance in ZSF1 Ob when compared to WKY controls. Notably, ZSF1 Ob rats exhibited an age-dependent elevation in protein-SNO levels, despite significant reduction in NO bioavailability and signaling. Targeted sc transcriptomic analysis revealed significantly elevated expression of transnitrosylases such as hemoglobin subunit α and β in cardiomyocytes, endothelial cells, and cardiac fibroblasts from ZSF1 Ob hearts. In contrast, significantly reduced expression of denitrosylases such as thioredoxin 2 was found in the ZSF1 Ob cardiomyocytes. No change was observed in expression of NO synthases (nNOS, iNOS, eNOS). Conclusion: Herein, we demonstrate a profound disconnect between insufficient NO bioavailability and nitrosative stress in ZSF1 Ob rat model of HFpEF. Our data suggests the pathological accumulation of nitroso - proteins, may be attributed in part to the derangement of transnitrosylases and denitrosylases expression. Restoration of physiological protein nitrosylation dynamics may represent a novel therapeutic approach for HFpEF, and warrants further investigation.

Comparison of myocardial perfusion study and invasive hemodynamic measurement of the significance of non-infarct-related residual stenoses in ST elevation myocardial infarction patients.

Nearly 50% of ST elevation myocardial infarction (STEMI) patients have multivessel coronary artery disease. The optimal selection of non-culprit lesions for complete revascularization is a matter of current debate. Little is known about the predictive value of myocardial perfusion study (MPS) in this scenario. We enrolled 49 STEMI patients (61.5 ± 10.3 years) with at least one major non-culprit lesion (50-90%) other than left main coronary artery lesions. Overall 63 non-infarct- related artery (IRA) stenoses (65.2 ± 11.9%) were recommended for further evaluation using Fractional Flow Reserve (FFR) measurement as is standard in our institution. Prior to FFR, all patients were scheduled for non-invasive MPS using single-photon emission computed tomography (SPECT). Both FFR and MPS were performed 4-8 weeks after STEMI with MPS preceding FFR within no more than 48 hours. An FFR value of ≤0.80 was considered significant and guided the final revascularization strategy. The results of MPS were correlated to FFR as well as to the clinical and angiographic characteristics of both culprit and non-infarct-related lesions. Based on FFR, 30 out of 63 stenoses (47.6%) in 27 patients were considered hemodynamically significant (FFR 0.69 ± 0.08, range 0.51-0.79) compared to residual 33 stenoses considered negative (FFR 0.87 ± 0.04, range 0.81-0.96). The MPS revealed abnormal myocardium (23.6% average, range 5-56%) in 21 patients (42.8%). Among those patients, only 9 showed the evidence of ischemic myocardium (average 10.8%, range 4-18%) with low sensitivity of MPS in predicting positive FFR. Besides that, higher proportion of patients (71.4% vs. 42.9%, P=0.047) with overall lower FFR values (0.73 vs. 0.80, P=0.014, resp.) in non-IRAs as well as higher proportion of patients with more severely compromised flow in IRAs (P=0.048) during STEMI had MPS-detected abnormal myocardium. In STEMI patients with multivessel coronary artery disease, we observed rather weak correlation between MPS using SPECT and invasive hemodynamic measurement using FFR in ischemia detection.

Acute haemodynamic changes during left atrial appendage closure

Abstract Purpose Left atrial appendage closure (LAAC) presents an alternative treatment for stroke prevention in atrial fibrillation (AF) in patients with contraindication for long-term anticoagulation. However, even in patients in AF, left atrial appendage plays an important role in reservoir function of left atrium. The purpose of this study was to assess acute hemodynamic effects during LAAC. Methods Consecutive patients indicated for LAAC from January 2022 to October 2023 were enrolled. The invasive hemodynamic measurements were done at the beginning of the procedure after transseptal puncture, and at the end from the procedure after device deployment. Following parameters were measured: systolic, and diastolic blood pressure, and pressure in left atrium (LA), all measurements were done at rest and after 3 minute isometric exercise (handgrip). Results Thirty-two patients were included (age 76,2+7,1 yrs, 22 (69%) males, 23 (72%) permanent AF, left ventricular ejection fraction 52+11,8%). No patients experienced moderate/severe mitral insufficiency, the saline intake during procedure was 738 ml. Isometric exercise significantly increased the LA pressure: the LA pressures (rest/exercise) were 13.7+6.7 mmHg/16.7+8.8 mmHg (p=0.003) at the beginning of the procedure, and 17.0+7.3mmHg/20.0+7.3 mmHg (p=0.005) after device deployment. The LA pressure obtained after device deployment (both rest/exercise) were significantly higher compared to values obtained at the beginning of the procedure. (p=0.003). Conclusions LAAC is associated acute increase of both rest and exercise LA pressure. Whether its acute negative effect remains over time needs further investigation.

Quantitative and qualitative assessment of left atrial cardiomyopathy as well as prediction of atrial fibrillation recurrences upon PVI using machine learning

Abstract Introduction Atrial fibrillation (AF) is one of the most common heart pathologies in daily clinical practice and confers significant mortality and morbidity. However, AF ablation often proves ineffective - even after successful pulmonary vein isolation (PVI). The prediction of PVI failure for the long-term treatment of AF as well as the improved assessment of the underlying substrate appears pivotal. We hypothesize, that ML can be applied to better characterize the substrate and recurrence in AF patients upon PVI. Methods &amp; Results We retrospectively evaluated data from 205 patients that underwent AF ablation between 2019 and 2023, including high-density 3D electroanatomic maps (sinus rhythm), LA rotational angiography, invasive LA hemodynamic measurements (after transseptal passage), echocardiography, 12-lead ECG and laboratory testing. A neuronal net was trained on selected features extracted from those datasets using supervised learning and employed to predict measures of atrial cardiomyopathy and AF recurrence. Patients were 66±1 years old and received first or second pulmonary vein isolation (PVI) for paroxysmal atrial fibrillation with 18% documented recurrences upon a mean follow-up of 23±1months. First, we extensively refined or developed tools for automated P-wave analysis from 12-lead ECGs as well as local LA voltage and volume quantification. Next, LA hemodynamics and volumes were assessed: Mean LA volume as derived from rotational angiography significantly correlated with LA volume index as obtained using echocardiography. Interestingly, LA size showed no correlation with NT-proBNP, LA low voltage or LA hemodynamics. In addition, global (25±2% of total LA area) and local (i.e. anterior, posterior, roof) LA voltage was determined and shown to be an independent predictor of AF recurrence. In our first unselected subset of 136 patients with 2nd PVI for atrial fibrillation, our ML models predicted LA fibrosis (i.e. low voltage regions; Utah stage) from 12-lead ECGs with an accuracy of 90%. Accuracy was 87% for the prediction of AF recurrences from LA pressure and low-voltage regions. In addition, the algorithm predicted AF recurrences from 12-lead SR ECGs obtained before PVI with an accuracy of 91%. Conclusion Artificial neural networks allow to quantitatively and qualitatively predict measures of atrial cardiomyopathy and atrial fibrillation recurrence probability upon complete PVI with high accuracy.Figures

Acute hemodynamic effects of the Marshall-Plan ablation on left and right atrial pressure: does 'respecting atrial physiology' prevent stiff left atria? A retrospective single- center analysis

Abstract Introduction Stiff left atrium (STILA)-syndrome is a relevant concern after extensive ablation in the left atrium (LA) e.g. in persistent atrial fibrillation (AF). STILA often causes disabling heart failure symptoms worse than the initial arrhythmia symptoms. Therefore preventing adverse ablation-induced hemodynamic effects is of utmost concern. Methods This single-center study retrospectively analyzed data from 89 consecutive patients who underwent biatrial ablation for AF following the Marshall-Plan between February 2022 and November 2023. The procedures included ablation of the CTI and PVI where necessary followed by ablation of a LA roof line and ablation of the lateral mitral isthmus after previously performed ethanol ablation of the vein of Marshall. This lesion set is considered to maintain physiological activation of the LA. This study evaluates acute hemodynamic changes following the Marshall-Plan. Invasive hemodynamic measurements of mean left and right atrial pressure, as well as A- and V-waves were performed in all patients before and after the ablation. We assessed the acute changes of atrial hemodynamics in these procedures. Continuous data are given as mean ± standard deviation, categorical data are expressed as number and percentages. Differences between groups were determined by Student’s t-test, chisquare-test, and Fisher’s exact test using SPSS software. A p-value of &amp;lt;0.05 was deemed significant. Results The patients' mean age was 70.1 ± 7.5 years and 39.0% were female. Mean BMI was 28.9 ± 5.2 kg/m². Procedures were performed under general anesthesia (with a PEEP of 5.5cmH2O (2-10 cmH2O)) and took 181 minutes on average. Left atrial mean pressure averaged at 15.7mmHg before the procedure. The overall average change of left atrial mean pressure was +1,8mmHg. The average change in left atrial A- and V-Wave amounted to -1.9mmHg and -0.9mmHg respectively. The pre-procedural average right atrial mean pressure was 12.1mmHg. Right atrial mean pressure inclined by +1.6mmHg. The average change in right atrial A- and V-Wave was +0.6mmHg and +1.1mmHg respectively. The i.v. administered volume averaged 1900 ± 285ml. 3.3% of patients showed an increase of mean LA-pressure &amp;gt;9mmHg. Those patients tended to be older (74.3years), were all male (100%) and had a higher BMI (31.5 kg/m²) as well as higher amount of i.v. administered volume (2333ml) and a longer procedure (213min). Discussion Complex and extensive biatrial ablation following the Marshall-Plan does not lead to acute significant increases in left or right atrial pressures. The administered i.v. volume might explain the slight increases observed. In our observation, the rate of significant increases in LA-pressure is low. This suggests that disrupting the (left) atrial activation pattern might play a role in the development of diastolic dysfunction and thereby STILA-syndrome. Respecting atrial physiology may be beneficial for preventing adverse hemodyamic changes after ablation.

Application of homocysteine as a non-invasive and effort-free measurements for risk assessment of patients with pulmonary hypertension.

Current guideline-recommended multiparameters used to assess the risk levels of pulmonary arterial hypertension (PAH) are invasive hemodynamic measurements or effort-dependent exercise tests. Serum natriuretic peptide is only one kind of effort-free biomarker that has been adopted for risk assessment. This study aimed to investigate the application of homocysteine as a non-invasive and effort-free measurement for the risk assessment of patients with PAH. Samples of 50 patients diagnosed with PAH via right heart catheterization were obtained, and the patients were divided into low-, intermediate- and high-risk groups for further analysis. Additionally, serum N-terminal prohormone of B-type natriuretic peptide (NT-proBNP) and homocysteine levels of monocrotaline (MCT)-induced PAH rats were analyzed at each week with progressed severity of PAH, and they were sacrificed on day 28 with pathology being assessed. Hyperhomocysteinemia was an independent predictor (odds ratio [OR]: 1.256; 95% confidence interval [CI]: 1.002-1.574) and showed a linear correlation with NT-proBNP. Hyperhomocysteinemia could discriminate between low/intermediate and high-risk levels in PAH with a cut-off value in 12 μmol/L. Moreover, the elevated homocysteine levels by weeks in MCT rats also demonstrated the association between homocysteine and the severity of PAH. Homocysteine can be a non-invasive and effort-free risk assessment for patients with pulmonary hypertension. Homocysteine level had a linear correlation with NT-proBNP level, and patients with hyperhomocysteinemia had a higher risk level, higher NT-proBNP level, and decreased lower diffusing capacity for carbon monoxide. The correlation between homocysteine level and PAH severity was also demonstrated in MCT rats.

Impact of pulmonary hypertension on outcomes after TEER in patients suffering from mitral regurgitation.

Data on associations of invasively determined hemodynamic parameters with procedural success and outcomes in patients suffering from mitral regurgitation (MR) undergoing transcatheter edge-to-edge repair of the mitral valve (M-TEER) is limited. We enrolled 239 patients with symptomatic MR of grade 2 + , who received M-TEER. All patients underwent extensive pre-interventional invasive hemodynamic measurements via right heart catheterization (mean pulmonary arterial pressure (mPAP), systolic- (PAPsys) and diastolic pulmonary arterial pressure (PAPdia), pulmonary arterial wedge pressure (PAWP), a-wave, v-wave, pulmonary vascular resistance (PVR), transpulmonary pressure gradient (TPG), cardiac index (CI), stroke volume index (SVI)). mPAP and PAWP at baseline were neither associated with procedural success, immediate reduction of MR, nor residual MR after 6months of follow-up. The composite outcome (All-cause mortality (ACM) and/or heart failure induced rehospitalization (HFH)) and HFH differed significantly after M-TEER when stratified according to mPAP, PAWP, PAPdia, a-wave and v-wave. ACM was not associated with the afore mentioned parameters. Neither PVR, TPG, CI nor SVI were associated with the composite outcome and HFH, respectively. In multivariable analyses, PAWP was independently associated with the composite outcome and HFH. PVR and SVI were not associated with outcomes. PAWP at baseline was significantly and independently associated with HFH and might serve as a valuable parameter for identifying patients at high risk for HFH after M-TEER. ACM and procedural success were not affected by pulmonary arterial pressure before M-TEER. We suggest that the post-capillary component of PH serves as the driving force behind the risk of HFH.

Early postnatal moderate catch‑up growth in rats with nutritional intrauterine growth restriction preserves pulmonary vascular and cognitive function in adulthood.

Intrauterine growth restriction (IUGR) with rapid postnatal catch-up growth is strongly associated with pulmonary vascular dysfunction in adulthood, whereas IUGR with delayed growth in early postnatal life results in long-term brain deficits. In the present study, it was hypothesized that IUGR with early moderate catch-up growth may alleviate pulmonary vascular remodeling in adulthood without affecting memory function. An IUGR model was established by restricting maternal nutrition during pregnancy. Different growth patterns were achieved by adjusting the litter size in each group during lactation. Rats meeting the weight requirement at weaning were selected for subsequent studies at three time points (3, 9 and 13 weeks). Cognitive function was evaluated using a Y-maze. Invasive hemodynamic measurements were conducted to measure the mean pulmonary arterial pressure (mPAP). In addition, primary pulmonary artery smooth muscle cells (PASMCs) and pulmonary vascular endothelial cells (PVECs) were cultured to investigate their role in the increase in mPAP following rapid catch-up growth. The results showed that memory function deficits in the rats in the delayed growth group were associated with reduced proliferation of neural stem cells in the subgranular zone of the hippocampus. Furthermore, moderate catch-up growth at the three time points improved memory function while maintaining a normal mPAP. In adult IUGR rats experiencing rapid catch-up growth, although memory function improved, elevated mPAP and medial thickening of pulmonary arterioles were observed. Additionally, PASMCs exhibited excessive proliferation, migration and anti-apoptotic activity in the rapid catch-up group, and PVECs also displayed excessive proliferation. These results suggested that moderate catch-up growth after IUGR is a better strategy for optimal cognition and cardiovascular health in adulthood compared with rapid catch-up growth or delayed growth.

Age-specific determinants of reduced exercise capacity in youth after heart transplant: A longitudinal cohort study

BackgroundAlthough prior studies show that children have impaired exercise capacity after heart transplant, the age-specific determinants of this phenomenon are not well understood. We examine exercise capacity and its associations in school-age and adolescent youth post-heart transplant. MethodsThis retrospective cohort study of heart transplant patients who completed a cardiopulmonary exercise test between 1999-2018 includes 332 tests on 104 patients younger than 18 years. Tests were stratified into those by school-aged children (5 to 11 years old) and adolescents (12-17). The primary outcome was peak oxygen consumption; secondary outcomes were anaerobic threshold and peak power production. Potential determinants included age at transplant, diagnosis, and laboratory and invasive hemodynamic measurements. ResultsAll exercise capacity outcomes for patients post-transplant regardless of age were significantly reduced compared to the predicted performance of age and sex-matched controls. Percent predicted median peak oxygen consumption (62.63, 95% confidence interval 59.18, 66.07), anaerobic threshold (66.52, 95%CI 62.24, 70.81), and peak power production (54.00, 95%CI 50.56, 57.44) were reduced. Younger age at transplant and a higher peak heart rate were independently associated with increased peak oxygen consumption across age groups. Elevated wedge pressure and BNP predict decreased exercise capacity in adolescents. ConclusionsYouth after heart transplant have significantly reduced exercise capacity. Younger age at transplant and higher peak heart rate predict increased exercise capacity throughout childhood. Indicators of congestion predict decreased exercise capacity in adolescents. These findings should encourage deeper attention to the relationship between exercise physiology and the social context of children after transplant.

Characterization and Prognostic Implications of Respirophasic Variation in Invasive Hemodynamic Measurements at Rest and With Exercise

Characterization and Prognostic Implications of Respirophasic Variation in Invasive Hemodynamic Measurements at Rest and With Exercise

Comparison of angiographic estimation and invasive hemodynamic measurement of the significance of non-infarct-related residual stenoses in ST-elevation myocardial infarction patients.

Up to 50% of patients with ST elevation myocardial infarction (STEMI) have ≥ 50% stenosis in a major non-infarct-related artery. Several studies have evaluated the prognostic value of the completion of revascularization with overall inconclusive results. Selection of the stenoses was based on the angiographic evaluation, invasive hemodynamic measurement or the combined approach. It is unknown whether such a selection provides correlation of comparable patient groups. We enrolled 51 patients (62.7 ±10.2 years) with acute STEMI and at least one residual (50-90%) stenosis in a non-infarct-related major coronary artery (excluding left main coronary artery). Overall 65 stenoses (67.9 ±10.7%) were evaluated angiographically following primary percutaneous coronary intervention and the hemodynamic significance was estimated with respect to the stenosis severity, caliber of the arterial segment, localization of the stenosis (proximity) as well as the estimated size of the supplied vascular territory. During subsequent hospitalization, invasive measurement of the hemodynamic significance using fractional flow reserve (FFR) was performed to guide the final revascularization strategy (FFR value of ≤ 0.80 considered significant). Based on angiographic evaluation, a total of 44 stenoses would be recommended for treatment, whereas only 31 stenoses were revascularized based on FFR measurement. Moreover, visual evaluation and hemodynamic measurement were discrepant in 27 of 65 (41.5%) stenoses. We observed a weak correlation between visual angiographic evaluation and invasive hemodynamic measurement. More stents would be implanted based on angiographic evaluation compared to FFR measurement.

The FXYD1 protein plays a protective role against pulmonary hypertension and arterial remodeling via redox and inflammatory mechanisms.

Pulmonary hypertension (PH) consists of a heterogenous group of diseases that culminate in increased pulmonary arterial pressure and right ventricular (RV) dysfunction. We sought to investigate the role of FXYD1, a small membrane protein that modulates Na+-K+-ATPase function, in the pathophysiology of PH. We mined online transcriptome databases to assess FXYD1 expression in PH. We characterized the effects of FXYD1 knockout (KO) in mice on right and left ventricular (RV and LV) function using echocardiography and measured invasive hemodynamic measurements under normal conditions and after treatment with bleomycin sulfate or chronic hypoxia to induce PH. Using immunohistochemistry, immunoblotting, and functional assays, we examined the effects of FXYD1 KO on pulmonary microvasculature and RV and LV structure and assessed signaling via endothelial nitric oxide synthase (eNOS) and inflammatory pathways. FXYD1 lung expression tended to be lower in samples from patients with idiopathic pulmonary arterial hypertension (IPAH) compared with controls, supporting a potential pathophysiological role. FXYD1 KO mice displayed characteristics of PH including significant increases in pulmonary arterial pressure, increased muscularization of small pulmonary arterioles, and impaired RV systolic function, in addition to LV systolic dysfunction. However, when PH was stimulated with standard models of lung injury-induced PH, there was no exacerbation of disease in FXYD1 KO mice. Both the lungs and left ventricles exhibited elevated nitrosative stress and inflammatory milieu. The absence of FXYD1 in mice results in LV inflammation and cardiopulmonary redox signaling changes that predispose to pathophysiological features of PH, suggesting FXYD1 may be protective.NEW & NOTEWORTHY This is the first study to show that deficiency of the FXYD1 protein is associated with pulmonary hypertension. FXYD1 expression is lower in the lungs of people with idiopathic pulmonary artery hypertension. FXYD1 deficiency results in both left and right ventricular functional impairment. Finally, FXYD1 may endogenously protect the heart from oxidative and inflammatory injury.

Association between invasively measured central aortic pulse pressure and diameter of ascending aorta

Data on the relationship between arterial pulsatile hemodynamics and aortic root geometry, using invasive hemodynamic measurement, has been scarce. Thus, this study aimed to assess the relationship between invasively measured aortic pulse pressure (aPP) and the diameter of ascending aorta (AoD). We analyzed 665 subjects (64.3 ± 11.0 years; 34.6% female) who underwent elective invasive coronary angiography (ICA) for the evaluation of coronary artery disease. Transthoracic echocardiography was performed on the same day, and AoD was measured at the level of 1 cm above the sinotubular junction at the end-diastole. Body surface area (BSA)-adjusted AoD (AoD/BSA) was used for the analysis. A pig-tail catheter was used to measure aortic pressures at a level approximately 3 cm above the aortic valve just before ICA. aPP was calculated as the difference between systolic and diastolic pressures of the aorta. In multiple linear regression analyses, aPP (β = 0.259; P < 0.001) was found to be significantly correlated with AoD/BSA even after controlling for potential confounders. This correlation power was stronger than aortic systolic pressure (β = 0.189; P < 0.001) and brachial pulse pressure (β = 0.091; P = 0.018) at the same multivariable analyses. In conclusion, our study demonstrated a significant association between invasively measured aPP and AoD/BSA, providing stronger evidence for the link between central aortic pulsatile hemodynamics and aortic root geometry.

Atrial fibrosis heterogeneity is a risk for atrial fibrillation in pigs with ischaemic heart failure.

Atrial fibrillation (AF) is the most common arrhythmia and is associated with considerable morbidity and mortality. Ischaemic heart failure (IHF) remains one of the most common causes of AF in clinical practice. However, ischaemia-mediated mechanisms leading to AF are still incompletely understood, and thus, current treatment approaches are limited. To improve our understanding of the pathophysiology, we studied a porcine IHF model. In pigs, IHF was induced by balloon occlusion of the left anterior descending artery for 90 min. After 30 days of reperfusion, invasive haemodynamic measurements and electrophysiological studies were performed. Masson trichrome and immunofluorescence staining were conducted to assess interstitial fibrosis and myofibroblast activation in different heart regions. After 30 days of reperfusion, heart failure with significantly reduced ejection fraction (left anterior obique 30°, 34.78 ± 3.29% [IHF] vs. 62.03 ± 2.36% [control], p < .001; anterior-posterior 0°, 29.16 ± 3.61% vs. 59.54 ± 1.09%, p < .01) was observed. These pigs showed a significantly higher susceptibility to AF (33.90% [IHF] vs. 12.98% [control], p < .05). Histological assessment revealed aggravated fibrosis in atrial appendages but not in atrial free walls in IHF pigs (11.13 ± 1.44% vs. 5.99 ± .86%, p < .01 [LAA], 8.28 ± .56% vs. 6.01 ± .35%, p < .01 [RAA]), which was paralleled by enhanced myofibroblast activation (12.09 ± .65% vs. 9.00 ± .94%, p < .05 [LAA], 14.37 ± .60% vs. 10.30 ± 1.41%, p < .05 [RAA]). Correlation analysis indicated that not fibrosis per se but its cross-regional heterogeneous distribution across the left atrium was associated with AF susceptibility (r = .6344, p < .01). Our results suggest that left atrial cross-regional fibrosis difference rather than overall fibrosis level is associated with IHF-related AF susceptibility, presumably by establishing local conduction disturbances and heterogeneity.

Abstract 11774: Right Ventricular Function and Myocardial Blood Volume Analyses by Convolutional Neural Network in Experimental Pulmonary Hypertension

Introduction: Survival of patients with pulmonary hypertension (PH) is highly dependent on the right ventricular (RV) function. Despite the association of various factors with adaptive or maladaptive RV phenotypes, the contribution of microvascular density to RV adaptation to pressure overload remains unclear. Hypothesis: This study aimed to evaluate the RV myocardial blood volume and its role in the RV adaptation to pressure overload. Methods: Both the University Animal Care Committee and the federal authorities for animal research of the Regierungsprasidium Giessen (Hessen, Germany) approved the study protocol. The study used adult Wistar-Kyoto rats and Sprague-Dawley rats to induce PH using SuHx and monocrotaline (MCT), respectively. Echocardiography, in vivo contrast-μCT, and invasive hemodynamic measurements were performed. The researchers used an artificial intelligence (AI)-based convolutional neural network (CNN) approach to reconstruct, segment, and analyze the cardiac μCT images. The RV functional reserve was evaluated during mCT acquisition and dobutamine stress test, and metabolomics analysis was performed. Results: The data showed that SuHx rats developed maladaptive cardiac function and RV-PA uncoupling. MCT rats exhibited adaptive RV function at days 14 and 21, but maladaptive function at day 35, which was associated with RV-PA uncoupling and reduced RV functional reserve. Impaired PKA-CREB signaling pathway was also found to be associated with the reduced RV functional reserve in the MCT rats. In both PH models, the absolute RV blood volume significantly increased with the development of RV hypertrophy, but the relative blood volume decreased, which was associated with maladaptive RV function Conclusions: This study is the first to demonstrate the use of AI CNN in post-processing of μCT-derived cardiac images from experimental PH models. Additionally, a single-beat PV loop was established for the first time in a rat model of PH by combining non-invasive and invasive techniques. The findings suggest that RV maladaptive function in rat models of PH is characterized by capillary rarefaction, impaired RV reserve in response to dobutamine infusion, which is associated with impaired PKA-CREB signaling pathway in the RV.