Cardiac Hemodynamics Research Articles

Introduction/Background: Vascular tone dysregulation is central to cardiovascular pathophysiology. KCNQ (Kv7) potassium channels, primarily heteromeric KCNQ4/5 channels, regulate smooth muscle membrane potential and contractility, yet the specific role of the KCNQ5 subunit in vascular reactivity remains underexplored. The absence of KCNQ5-specific tools has limited mechanistic understanding, particularly regarding receptor-mediated signaling in distinct vascular beds. Research Questions/Hypothesis: We hypothesized that KCNQ5 plays a critical, region-specific role in vascular contractility and receptor-mediated relaxation, particularly to adrenergic stimuli. We aimed to determine whether genetic deletion of KCNQ5 disrupts vasoreactivity and arterial signaling dynamics. Methods/Approach: We generated a CRISPR-based germline KCNQ5 knockout ( Kcnq5 -/- ) rat line. Using in vivo multimodal monitoring (cardiac and brain hemodynamics), ex vivo myography of mesenteric and cerebral arteries, and in vitro electrophysiology of Xenopus oocytes expressing KCNQ4/5/KCNE4 complexes, we analyzed vascular responses to pharmacologic and physiologic stimuli including adrenergic agonists, KCNQ modulators, and the botanical KCNQ5 isoform-selective vasorelaxant aloperine. Results/Data: Kcnq5 -/- rats displayed blunted heart rate, cerebral blood flow, and vasoregulatory responses to hypercapnia and isoflurane, and impaired cerebral vasodilation to aloperine. In contrast, cerebral artery segments mounted in a wire myograph displayed preserved function. In mesenteric artery segments studied using wire myography, deletion of KCNQ5 did not affect basal tone or luminal diameter but impaired relaxation responses to the Kv7 channel opener ML213, aloperine, and the β-adrenergic agonist isoprenaline. Constriction to the α 1 -adrenergic agonist methoxamine was enhanced and showed reduced sensitivity to linopirdine, highlighting KCNQ5’s key role in regulating adrenergic vasoconstriction. Cellular electrophysiology studies delineated PKA/PKC sensitivity of KCNQ5-containing channels. Conclusions: KCNQ5 is essential for receptor-mediated signaling in specific vascular beds. Its deletion enhances α 1 -adrenergic constriction and impairs β-adrenergic and botanical-induced vasorelaxation, highlighting its important functional role. These findings identify KCNQ5 as a key component of Kv7 channel architecture and vasoregulation, which likely varies across vascular beds.

Background: To prevent secondary necrosis and prolonged inflammation following cardiac ischemia, efficient clearance of dying cardiomyocytes must occur. CD47 is a “don’t eat me” signal that negatively modulates phagocyte-mediated clearance of dying cells through binding and activation of its cognate receptor SIRPα (signal-regulatory protein alpha). CD47 is upregulated in ischemic heart disease. As such, increased CD47 expression on the surface of dying cardiomyocytes may impair their efficient removal by phagocytes. Hypothesis: Blocking CD47 with a recombinant, high affinity SIRPα-Fc fusion protein, will promote the efficient removal of dying cardiomyocytes and prevent the decrease in cardiac function typically observed following an ischemic event. Methods: Myocardial infarction (MI) was induced in Sprague Dawley rats by temporary ligation of their left coronary artery for 45 minutes. Rats received the SIRPα-Fc fusion protein (n=27) or IgG placebo (n=27) by intravenous infusion (3 mg/kg) 2 hours before MI. Three additional weekly subcutaneous injections (3 mg/kg) of SIRPα-Fc fusion protein or IgG were administered. Cardiac function was assessed by left ventricular pressure-volume loops 28 days after MI. At that time, the heart was harvested and sectioned at six levels to quantify the scar area by histology with Masson trichrome staining. Results: Treatment with SIRPα-Fc fusion protein improved cardiac contractility and hemodynamics 28 days after MI compared to IgG. Specifically, statistically significant increases in ejection fraction by 29% (p<0.001), end-systolic elastance by 35% (p<0.05), preload recruitable stroke work by 25% (p<0.05), stroke volume by 24% (p<0.01) and a decrease in end-systolic volume by 28% (p<0.001) were observed following treatment with SIRPα-Fc fusion protein vs. IgG. Moreover, scar area was also decreased by 22% in rats treated with SIRPα-Fc fusion protein compared to IgG-treated animals. Conclusion: These results suggest that CD47 blockade has potential as a novel therapy for ischemic heart diseases.

Repeated sprint training in hypoxia (RSH) performed with voluntary hypoventilation at low lung volumes (RSH-VHL) has been proposed as an alternative to RSH. Recently, repeated sprint training combined with end-expiratory breath hold until the breaking point (RSH-UBP) has been suggested as a more effective stimulus. The aim of this study was to compare the physiological responses of repeated sprint training in normoxia (RSN), RSH-VHL and RSH-UBP. We hypothesized that RSH-UBP would induce greater hypercapnic and hypoxemic stress compared to the other conditions and therefore greater physiological responses. Ten healthy active men participated in three repeated sprint exercise sessions on ergocycle. Pulse oxygen saturation (SpO2), end-tidal CO2 pressure (PETCO2), muscle oxygenation, cardiac hemodynamics, and total work were continuously monitored throughout the protocol. Time spent below 96% SpO2 was higher in both RSH-VHL and RSH-UBP than in RSN (82 ± 66s and 74 ± 57s vs. 11 ± 14s, P = 0.039). Contradictory, PETCO2 was higher in RSH-VHL and RSH-UBP than in RSN (33.6 ± 4.2 and 32.9 ± 3.5 vs. 27.8 ± 4.2 mmHg, p < 0.001). Total work was lower in RSH-UBP than in RSH-VHL and RSN (33.1 ± 5.8 vs. 46.5 ± 5.7 and 47.4 ± 6.0kJ, p < 0.001) despite a higher mean power in RSH-UBP. Amplitude in the muscle deoxygenation-reoxygenation cycle was lower during RSH-UBP (p < 0.045). There was no difference in stroke volume or cardiac output between the three conditions. Overall, RSH-VHL emerged as the most effective condition for inducing large hypercapnic and hypoxemic stimuli while maintaining the training load during repeated sprint training,whereas RSH-UBP succeeded in inducing similar hypercapnic and hypoxic stress with shorter sprint durations.

Background: Heart failure (HF) with pulmonary hypertension due to left-sided heart disease (PH-LHD) is associated with poor prognosis. Dapagliflozin showed benefits in terms of ejection fraction (EF); meanwhile, sildenafil improved pulmonary pressures and right ventricular function in PH -LHD in recent clinical studies. This study assesses the potential additive effects of dapagliflozin and sildenafil on cardiac function and pulmonary hemodynamics in this population. Methods: In this prospective, randomized, controlled trial, 93 participating patients with HF and PH-LHD were randomly assigned to receive dapagliflozin (control group, n = 48) or dapagliflozin plus sildenafil 25 mg/day (test group, n = 45) in addition to conventional therapy for HF for 12 weeks. The primary outcomes were assessing changes in echocardiographic hemodynamic parameters. Secondary outcomes included outcomes, changes in cardiac enzyme (troponin), kidney function (serum creatinine), and lipid profile. Results: The average baseline median left ventricular ejection fraction (LVEF) for both groups was 30%, and the Pulmonary Artery Systolic Pressure (PASP) median was 50 mmHg. At follow-up, PASP had declined, and EF had improved compared to baseline. However, there were no statistically noticeable variations between the groups (p = 0.458, 0.331, respectively). No notable changes were observed in secondary and safety outcomes, including hospitalization rate, number of deaths, kidney function, and cardiac enzymes (p = 0.524, 1, 0.923, and 0.574, respectively). Conclusions: Addition of sildenafil to dapagliflozin did not demonstrate any significant clinical or hemodynamic benefit over dapagliflozin monotherapy in HF patients and PH-LHD. Further studies are warranted to evaluate the effects over the long term.

Virtual populations offer a promising approach for modeling cardiovascular variability in health and disease, with the potential to support or even replace clinical trials. Although most studies focus on age-related changes in the cardiovascular system, sex remains underrepresented despite its significant influence on cardiovascular physiology. This study aims to generate a healthy virtual population that canvases the full range of cardiac hemodynamics and arterial pressure variability due to age and sex. A zero-dimensional (0-D) elastance model of the left ventricle was coupled with a 0-D and 1-D model of 55 large arteries. Model parameters (cardiac properties, vessel geometry, and vascular bed) were derived from literature and systematically varied using a uniform distribution. This process yielded 972 virtual subjects, representing both sexes and spanning ages from 25 to 75 yr. Six acceptance criteria, based on vascular hemodynamics and cardiac characteristics, were applied to retain only plausible virtual subjects, resulting in 147 males and 180 females. Validation against in vivo literature data showed that the model captures the propagation of pressure waveform from the aorta to its main branches. The virtual population was also compared against a prospective observational study of 63 healthy subjects ranging from 21 to 77 yr. The simulated blood pressure profiles encompassed the physiological range observed in vivo across age and sex, demonstrating the model ability to replicate real-world measurements. This model provides a foundation for generating realistic, demographically diverse cardiovascular populations and can be extended to simulate pathological conditions and support the development of diagnostic and monitoring tools.NEW & NOTEWORTHY This study introduces a 01-1D cardiovascular model and a parameter assignment methodology to reproduce age- and sex-related physiological changes in arterial pressure and cardiac hemodynamics. Uniform sampling of input parameters was conducted to generate a virtual population, encompassing the variability of healthy individuals. A systematic analysis was performed to identify parameter combinations that led to exclusion of implausible virtual subjects. The virtual population was compared with a clinical dataset, demonstrating its potential for realistic physiological simulations.

Intramyocardial dissecting hematoma (IDH) is a rare and catastrophic complication of myocardial infarction (MI) associated with high mortality and poor prognosis. Caused by hemorrhagic dissection between spiral myocardial fibers, IDH forms a blood-filled cavity that differs from complete cardiac rupture in that it preserves the integrity of the myocardial wall and is classified as a subtype of subacute cardiac rupture. Clinical manifestations vary according to the degree of impact on cardiac structure and hemodynamics. Echocardiography and cardiac magnetic resonance are essential in the diagnosis and assessment of IDH. Optimal management strategies for this rare complication of MI have not been established, and the ongoing debate about pharmacological versus surgical interventions requires multidisciplinary discussion to determine personalized treatment plans. Given the diagnostic and therapeutic challenges of IDH, there is an urgent need for clinicians to increase their understanding in order to improve diagnostic and therapeutic capabilities. This review aims to discuss the pathophysiological mechanisms, symptoms, diagnosis, treatment and prognosis strategies of IDH after MI.

Epigallocatechin gallate-mediated inhibition of mitochondrial DNA sensing regulated by TBK1/cGAS/STING and NLRP3 alleviates cardiovascular toxicity in atherosclerosis.

ABSTRACTAimsImpaired cardiac function, reduced nitric oxide (NO) bioavailability, and inflammation are key contributors to the pathogenesis and progression of heart failure with reduced ejection fraction (HFrEF). This study aimed to investigate whether dietary inorganic nitrate supplementation can attenuate cardiac dysfunction and adverse remodeling in HFrEF by enhancing NO signaling.MethodsTwo mouse models of HFrEF, induced by myocardial infarction (MI) or transverse aortic constriction (TAC), were treated with dietary nitrate or a control diet for 4–6 weeks, initiating the treatment on day 3 after myocardial injury. Echocardiography and pressure volume (PV) loop analysis were employed to assess cardiac function and hemodynamics. Histology staining was performed to assess the degree of cardiac fibrosis. Myograph experiments were conducted to assess aortic vasorelaxation. Biomarkers related to hypertrophy, fibrosis, and inflammation were analyzed in cardiac tissues through Q‐PCR analysis and immunofluorescence staining.ResultsIn HFrEF mice, long‐term inorganic nitrate treatment increased systolic and diastolic function, enhanced vascular relaxation, and reduced both replacement and reactive fibrosis. In the nitrate group, cardiac gene expression showed downregulation of hypertrophy‐, fibrosis‐, and inflammation‐related markers, alongside upregulation of anti‐inflammatory markers associated with M1‐to‐M2 macrophage polarization. Immunofluorescence confirmed reduced fibrosis and increased anti‐inflammatory protein biomarkers associated with increased serum nitrate and cardiac cGMP levels.ConclusionsEarly initiation of dietary nitrate supplementation after myocardial injury enhances cardiac and vascular function, reduces fibrosis and inflammation, and holds promise as a cardioprotective strategy to reduce the progression of HFrEF through NO‐signaling.

One of the main methods currently used is the transthoracic echocardiographic evaluation by HyperDopler intracardiac &amp;#64258; ow dynamics. It is based on color Doppler mapping of the blood &amp;#64258; ow by CDMF/Color Doppler &amp;#64258; ow mapping/technology. In addition to conventional transthoracic echocardiography, this technique enables visualization and quantitative assessment of intracardiac blood &amp;#64258; ow. HyperDoppler methodology represents a new paradigm in the analysis of cardiac function with the potential for sensitive risk identi&amp;#64257; cation and prediction of impending cardiac damage.It has been shown that a comprehensive assessment of intracardiac structures as well as their intracavitary vortex &amp;#64258; ow can enable the detection of pathologically altered &amp;#64258; ow characteristics. Which in turn identi&amp;#64257; es new pathophysiological mechanisms in the development of cardiovascular diseases. Our methods provide additional information on hemodynamics, with the potential for early detection of cardiac dysfunction and assistance in disease treatment and prevention. Convection echocardiographic measurements of cardiac mechanics usually do not reveal signi&amp;#64257; cant changes until there is signi&amp;#64257; cant dysfunction, making them less effective for early diagnosis and treatment of cardiovascular disease. Blood &amp;#64258; ow dynamics are immediately affected when cardiac hemodynamics change, therefore analyzing it opens new perspectives for the prediction and early diagnosis of diseases. Intracardiac &amp;#64258; ow analysis is a different and modern approach to assess cardiac function, providing important and complementary information to conventional approaches based on cardiac mechanics.

An optimal valve replacement prosthesis demands durable leaflet technology, superior hemodynamic performance, and ease of use. Preclinical evaluation of polymer leaflets has historically demonstrated mechanical failure related to biodegradation. We present the preclinical evaluation of the novel TRIA™ polymer valve (Foldax, Salt Lake City, UT, USA) and a case report of TRIA mitral valve replacement. A uniquely formulated, biostable, and biocompatible polymer (LifePolymer™ [LP], Foldax) has been designed to meet the functional demands of cardiac hemodynamics. Preclinical in vitro evaluation included biocompatibility testing, thrombogenicity testing, and toxicologic assessment followed by evaluation in the arteriovenous shunt of nonhuman primates and in the aortic position in sheep. Clinical evaluation of early human aortic and mitral implantation included computed tomography imaging and echocardiographic examination. In vitro studies of LP demonstrated no evidence of toxicity or tissue injury, no cytological injury in cell culture, and no intracutaneous sensitization. LP proved to be nonhemolytic by direct and extract methods, and complement activation was insignificant. Genotoxicity analysis proved LP to be nonmutagenic. All standard toxicologic assessments were within the margin of safety. Biostability was confirmed without polymer degradation or excessive comparative thrombogenicity. Ovine 6-month aortic valve explantation showed no leaflet calcification and minimal fibrinous depositions. An early human case example shows no evidence of leaflet thrombus formation at 6 months and a mean mitral gradient of 3 mm Hg at 12 months. LP has met the requirements for a prosthetic polymer human heart valve. The surgical TRIA Mitral Valve has demonstrated promising early human clinical success, potentially facilitating a lifetime valve replacement strategy.

Atrial fibrillation (AF) is a prevalent heart arrhythmia, characterized by an irregularly irregular rhythm and the absence of identifiable P waves on ECG. Given the loss of effective atrial contraction, AF carries a risk of serious complications. If untreated, AF can promote thrombogenesis, leading to stroke, systemic embolism (e.g., limb or organ ischemia), and myocardial infarction. These serious complications highlight the importance of understanding AF and assessing stroke risk to guide optimal management of this chronic arrhythmia. Congruent with recent technological developments, advanced imaging has emerged as a modality to better understand AF. This review highlights advanced imaging techniques and their advantages, with a focus on 4D flow MRI, a novel modality that enables visualization of blood flow patterns in three dimensions and provides unique insights into cardiac hemodynamics. It also synthesizes the current literature on key hemodynamic markers identified by 4D flow MRI, including blood flow stasis, wall shear stress, and vorticity. Quantifying these markers has improved predictive accuracy of future stroke risk in AF patients, allowing clinicians to risk stratifying their patients and optimize management. Finally, the review discusses potential future markers that may further refine our understanding of AF and inform patient care.

Tricuspid Regurgitation Across the Spectrum of Heart Failure With Preserved Ejection Fraction.

SIRT3 mediates Tubeimoside I's inhibition on pulmonary artery smooth muscle cell proliferation and oxidative stress in pulmonary arterial hypertension.

A transcatheter mitral valve clip with a central filler for mitral valve regurgitation.

Background: Dibutyl phthalate (DBP) is a prevalent environmental pollutant that can accumulate in organisms, becoming amplified after the food cycle and ultimately affecting human health. Recent studies have provided evidence suggesting a potential association between exposure to DBP and cardiovascular diseases (CVDs). Objectives: This study’s objective is to investigate the toxic cardiovascular effects of long-term exposure to DBP, particularly its impact on the heart and blood vessels. To be specific, we hypothesized and verified the potential mechanisms underlying DBP-induced cardiac and vascular injuries, focusing on oxidative stress, pyroptosis, inflammatory responses, and metabolic pathways. Methods: The rats were divided into 5 groups: Control group, DBP-Low group, DBP-Medium group, DBP-High group, and DBP-High + Vitamin E group. The entire experimental period lasted 12 weeks. We conducted examinations on echocardiography, histopathology, oxidative stress biomarkers, pyroptosis-related biomarkers, and inflammatory cytokine biomarkers. Additionally, we carried out serum metabolomics analysis. Result: Our research findings indicate that long-term exposure to DBP can cause significant toxic effects on the cardiovascular system. Specifically, DBP leads to changes in oxidative stress indicators (ROS and an increase in MDA levels, alongside a decrease in GSH levels) and protein levels related to pyroptosis (NLRP3, Caspase-1 and GSDMD levels increase) in cardiac and vascular tissues, triggering oxidative inflammatory responses (IL-1β and IL-18 levels increase), damaging the heart and blood vessels (organizational structure deformation and collagen fiber infiltration) and ultimately affecting their functions (abnormalities in cardiac function and hemodynamics). Additionally, the results of metabolomics studies suggest that metabolic pathways (Biotin metabolism, TCA cycle, Vitamin B6 metabolism, Pantothenate and CoA biosynthesis, and Riboflavin metabolism) and metabolites may also be of great significance. Conclusion: Long-term exposure to DBP can induce cardiovascular toxicity in rats, manifesting as cardiac and vascular damage, as well as alterations in organ function. This process is characterized by oxidative stress, activation of the pyroptosis pathway, inflammatory responses, and modifications to metabolic pathways.

Glycoursodeoxycholic acid 3 sulfate sodium links hemodynamics and bile acid metabolism in aortic stenosis.

Severe aortic stenosis (AS) is a recognized risk factor for sudden cardiac death (SCD). Although ventricular tachyarrhythmias are the most common immediate cause of SCD, the majority of cases of SCD in patients with severe AS exhibited bradyarrhythmia as the primary rhythm. Enhanced activation of left ventricular baroreceptors (Bezold-Jarisch reflex) has been implicated in the pathogenesis of syncope in patients with AS. However, the precise mechanism by which an otherwise benign circulatory syncope can progress to cardiac arrest in severe AS remains unclear. This study proposes a haemodynamic-energetic mechanism to explain this progression, and demonstrates its plausibility using a mathematical model of cardiac haemodynamics and energetics. The model identifies states of cardiac energy imbalance, in which the energy expenditure of the heart exceeds the energy delivered to it. In individuals with a normal aortic valve, compensatory mechanisms can restore energy balance following syncope. By contrast, in severe AS, all conditions involving low peripheral vascular resistance are energetically unstable, regardless of compensatory response. Because energy imbalance is incompatible with sustained cardiac function, such states inevitably result in cardiac arrest. Importantly, the proposed mechanism does not require an exaggerated Bezold-Jarisch reflex, although the reflex probably acts as a trigger of syncope by initiating peripheral vasodilatation. Additionally, the limited coronary vasodilatory reserve commonly observed in severe AS significantly contributes to the development of myocardial energy imbalance. KEY POINTS: The precise mechanism of sudden cardiac death in patients with severe aortic stenosis remains uncertain. In the present study, we propose a novel haemodynamic-energetic mechanism of sudden cardiac death explaining how otherwise benign circulatory syncope can progress to cardiac arrest in patients with severe aortic stenosis. The plausibility of the mechanism is verified using a mathematical model. The model identifies states of cardiac energy imbalance in patients with severe aortic stenosis, where the energy expenditure of the heart exceeds the energy delivered to it, which inevitably leads to cardiac arrest. Mathematical simulation of a circulatory syncope reveals significant differences in the effects of compensatory response in patients with and without severe aortic stenosis. The results provide a comprehensive understanding of the mechanism of sudden cardiac death in patients with severe aortic stenosis.

This study aimed to determine species-specific echocardiographic parameters in rehabilitated and clinically healthy white storks (Ciconia ciconia) using transcoelomic echocardiography, providing essential reference values for avian cardiovascular assessment. Thirty-seven white storks admitted to the Istanbul University-Cerrahpasa Veterinary Faculty Rehabilitation Center were evaluated after a 3-month observation period. Only clinically healthy individuals were included. Echocardiographic measurements were performed using a transcoelomic approach without anesthesia. Cardiac parameters, including interventricular septal thickness (IVSd, IVSs), left ventricular dimensions (LVIDd, LVIDs, LVPWd, LVPWs), functional indices (fractional shortening, ejection fraction), and Doppler-derived hemodynamic values, were recorded and analyzed statistically. All individuals exhibited normal cardiac morphology and hemodynamics. No significant differences were observed between male and female storks (p>0.05). The ejection fraction ranged from 23% to 97%, and interventricular septal thickness in diastole (IVSd) was between 0.27 and 0.86 cm. Fractional shortening varied from 14% to 75%. Hemodynamic measurements, including mitral valve inflow velocities and aortic flow parameters, were comparable to values reported in other large avian species. No pathological jet flow or valvular regurgitation was detected via color Doppler imaging. This study establishes the first echocardiographic reference ranges for white storks, offering valuable insights into avian cardiac physiology. The findings contribute to wildlife rehabilitation, providing a diagnostic baseline for assessing cardiovascular health in migratory birds. Future studies incorporating larger sample sizes and age-based comparisons will enhance our understanding of species-specific cardiac adaptations.

ABSTRACTCardiac myxomas are rare and mostly benign. Their thrombogenic surface can lead to embolization, and their size can impair cardiac hemodynamics. Here, we present a unique case of large biatrial myxomas despite mild symptomatology. A female patient (62 years, Caucasian) presented with aggravation of dyspnea and palpitations, with the first occurrence only four months prior to the current clinical presentation. Only moderate changes in standard laboratory markers, including inflammation markers, were observed. Clinical symptomatology and standard transthoracic echocardiography were sufficient for the diagnosis of multiple myxomas (68 × 52 mm in the left atrium and 56 × 53 mm in the right atrium) causing mitral and tricuspid valve inflow obstructions, which were confirmed by subsequent histopathology following surgical resection. The case emphasizes the need for standardized echocardiography at the initial presentation of every patient with dyspnea to exclude cardiac myxoma as a rare cause for the symptoms. The atypical presentation underlines the necessity for serial echocardiographic assessment during follow‐up due to possible recurrence.

The combination of reduced models of cardiac valve dynamics with a one-way kinematic uncoupling of blood flow and electromechanics is a widespread approach for reducing the complexity of cardiac hemodynamics simulations. This comes, however, with a number of shortcomings: artificial pressure oscillations, missing isovolumetric phases, and valve laws without precise continuous formulation. This paper is aimed at overcoming these three difficulties while still mitigating computational cost. A novel reduced model of valve dynamics is proposed in which unidirectional flow is enforced in a mathematically sound fashion. Artificial pressure oscillations are overcome by considering a fluid-structure interaction model, which couples bi-ventricular electromechanics and blood flow in the left cavities. The interface coupling is solved in a partitioned fashion via an unconditionally stable loosely coupled scheme. A priori energy estimates are derived for both the continuous coupled problem and its numerical approximation. The benefits and limitations of the proposed approaches are illustrated in a comprehensive numerical study.