Hemodynamic Profile Research Articles

Two Different Hemodynamic Responses in ME/CFS Patients with Postural Orthostatic Tachycardia Syndrome During Head-Up Tilt Testing

Introduction: While the diagnosis of postural orthostatic tachycardia syndrome (POTS) is based on heart rate (HR) and blood pressure (BP) criteria, the pathophysiology of POTS is not fully understood as multiple pathophysiological mechanisms have been recognized. Also, cardiac function, being dependent on preload, afterload, contractility, and HR, has not been properly studied. Preload and contractility changes can be inferred from stroke volume index (SVI) changes during a tilt test. Afterload plays a minor role in POTS as a normal BP response is a prerequisite for POTS. Therefore, we analyzed the HR-SVI relation during a tilt test in myalgic encephalomyelitis (ME/CFS) patients with POTS and compared the data with ME/CFS patients with a normal HR-BP response and with that of healthy controls (HC). Material and Methods: In ME/CFS patients with either POTS (n = 233) or a normal HR-BP response (n = 507) and healthy controls (n = 48), we measured SVI (by suprasternal echo), HR, and BP during the tilt. Results: In all ME/CFS patients, the decrease in SVI was larger compared to HC. In patients with a normal HR-BP response and in POTS patients with a HR increase between 30–39 bpm, there was an inverse relationship between the HR increase and SVI decrease during the tilt, compatible with increased venous pooling. In POTS patients with a HR increase ≥40 bpm, this inverse relation was lost, and SVI changes were significantly less compared to POTS patients with a HR increase between 30–39 bpm, suggestive of a hyperadrenergic response. Conclusions: In ME/CFS patients with POTS, two different hemodynamic profiles can be observed: in patients with a limited HR increase, mainly increased venous pooling is observed, while in patients with a large (≥ 40 bpm) HR increase the data are suggestive of a hyperadrenergic response. These two different profiles may have different therapeutic implications.

A Retrospective Study to Investigate the Relationship Between Body Mass Index and Hemodynamic Characteristics in Hypertensive Patients.

The relationship between hemodynamic parameters and body mass index (BMI) in the context of blood pressure regulation in hypertension is unclear. Here, we analyzed data from 1368 uncontrolled hypertensive patients, including key hemodynamic indicators such as heart rate (HR), cardiac index (CI), arterial stiffness (AS), systemic vascular resistance index (SVRI), and thoracic blood ratio (TBR). In this cohort, the average BMI across all hypertension patients was 26.859±3.897 (kg/m2), with obese patients (BMI≥28kg/m2) averaging 31.01±2.87kg/m2 and non-obese (BMI<28kg/m2) averaging 24.70±2.28kg/m2. Younger obese patients exhibited higher diastolic pressures than non-obese peers (p<0.01). Hemodynamic analysis showed obese patients had increased HR and SVRI but lower CI and AS (p<0.01). Hypertensive males aged under 60 with obesity displayed a more prominent peripheral vascular phenotype (p<0.05) and volemic phenotype (p<0.01) than non-obese males. Obese females aged under 60 showed a higher incidence of cardiac phenotype (p<0.01). Across genders, obese hypertensive patients aged over 60 had a greater prevalence of volemic phenotype than non-obese patients (p<0.05, p<0.01, respectively). BMI inversely correlated with CI and positively with SVRI across age and gender categories (p<0.01). Taken together, we find that patients with hypertension exhibit diverse hemodynamic profiles, and BMI significantly correlates with hemodynamic parameters such as SVRI and CI. Our research identifies BMI as a valuable target for personalized hypertension treatment.

To compare the efficacy of hyperbaric levobupivacaine (0.5%) versus hyperbaric bupivacaine (0.5%) in the subarachnoid block for infraumbilical surgeries

Background: Spinal anesthesia is the neuraxial regional anesthesia technique used in infraumbilical surgeries such as inguinal hernia, hydrocele, hysterectomy, and lower limb surgeries. Levobupivacaine and bupivacaine are local anesthetic agents used for spinal anesthesia. Aims and Objectives: The aim of the study was to compare the efficacy of hyperbaric levobupivacaine (0.5%) versus hyperbaric bupivacaine (0.5%) in subarachnoid blocks for infraumbilical surgeries. Materials and Methods: A total of 112 patients with American Society of Anesthesiologists grades 1 and 2 scheduled for infraumbilical surgeries were randomly divided into two groups. Group L received 3 mL of hyperbaric levobupivacaine, and group B received 3 mL of hyperbaric bupivacaine intrathecally. The onset of sensory block, onset, and duration of motor block, duration of analgesia and time of first rescue analgesia, hemodynamic parameters, and post-operative side effects, if any, were recorded. Results: The time of onset of sensory block at T10 for group L was 03.16±00.29 min and for group B was 02.16±00.27 min and the time of onset of motor block was higher in group L (03.29±00.32 min) compared to group B (02.45±00.32 min). Duration of motor block was significantly shorter in group L (209.80±6.44 min) compared to group B (252.41±11.49 min). All these findings were statistically significant. Conclusion: Levobupivacaine had a delayed onset of sensory and motor block as compared to bupivacaine, but due to its short duration of motor block and better hemodynamic profile, it seems to be a better alternative to bupivacaine.

Comparative evaluation of Bailey manoeuvre of deep extubation with conventional awake extubation technique - A randomized clinical study

Background: Extubation is a critical procedure in anesthesia and critical care, often accompanied by complications, such as bucking, coughing, and hemodynamic instability, particularly after major surgeries. The Bailey manoeuvre, involving deep extubation with the i-gel laryngeal mask airway (LMA), may mitigate these issues. The study was planned to compare the hemodynamic effects and side effect profiles of conventional awake endotracheal extubation and exchange extubation with the i-gel LMA. Aims and Objectives: The study was designed to compare hemodynamic stress response and respiratory complication between the conventional extubation group and the following exchange extubation group. Materials and Methods: In a prospective, randomized, single-blinded controlled study, 60 patients undergoing surgery under general anesthesia were divided into two groups: Group T (awake extubation) and Group L (exchange extubation with the i-gel LMA). Hemodynamic parameters and side effects were recorded and analyzed. Results: Group L exhibited significantly lower heart rates, systolic and diastolic blood pressures, and mean arterial pressures at various time points post-extubation compared to Group T. The incidence of hypertension was significantly higher in Group T (90%) versus Group L (50%). Bucking and coughing less in the i-gel LMA exchange group compared to the standard endotracheal tube extubation group. Conclusion: Exchange extubation with the i-gel LMA offers better hemodynamic stability and a lower incidence of hypertension compared to conventional awake extubation. This technique may be particularly beneficial for high-risk patients and those undergoing complex surgeries.

A prospective comparative study of levobupivacaine hydrochloride 0.5% with ropivacaine hydrochloride 0.75% for peri-operative epidural anesthesia in infra- umbilical surgeries

Background: Epidural anesthesia is a neuraxial regional anesthesia used to provide surgical anesthesia, to supplement general anesthesia, and to provide intra and post-operative analgesia. Levobupivacaine and ropivacaine are local anesthetic agents used in an epidural. Aims and Objectives: The aim of this study is to evaluate the onset and duration of sensory and motor block, duration of analgesia, hemodynamics, and adverse effects of levobupivacaine and ropivacaine given epidurally for infra-umbilical surgeries. Materials and Methods: This prospective randomized study was conducted in a total of 142 patients undergoing an infra-umbilical surgery, divided into two groups of 71 patients each. Group L received 15 mL of 0.5% levobupivacaine and Group R received 15 mL of 0.75% of ropivacaine. The onset and duration of sensory and motor blockade, duration of analgesia, hemodynamics, and side effects were assessed. Results: The mean time of onset of sensory and motor block is faster with ropivacaine (P&lt;0.05). The duration of sensory and motor block and analgesia was longer with ropivacaine (P&lt;0.05), whereas the incidence of side effects such as hypotension was more with ropivacaine. Conclusion: Our study concluded that ropivacaine produced a superior quality of epidural block but levobupivacaine had a more stable hemodynamic profile.

In Vitro Analysis of Left Ventricular Assist Device Outflow Graft Orientations and Their Effect on Aortic Hemodynamics.

Continuous-flow left ventricular assist devices have become an important treatment option for patients with advanced heart failure. However, adverse hemodynamic effects as consequence of an altered blood flow within the aorta and the aortic root remain a topic of concern. In this work, we investigated the influence of the outflow graft orientation on the hemodynamic profile and flow parameters within the thoracic aorta. Aortic models with different outflow graft orientations were designed and three-dimensional (3D) printed to mimic common implantation configurations and were integrated into a pulsatile mock circulatory flow loop. Assist device function was achieved using a rotary pump, replicating nonpulsatile, continuous support flows of 1-5 L/min. Flow velocity, wall shear stress, and pressure gradients were investigated for each configuration using sonography and four-dimensional (4D) flow magnetic resonance imaging. Mean wall shear stresses measured in 4D flow software were lowest for a graft inclination angle of 45°. Streamline visualization revealed areas of nonuniform, retrograde, and vortex flow in all models but most prominent for the aortic model with an outflow graft inclination of 60°. The insights gained from this research may aid in understanding clinical outcomes following assist device implantation and long-term mechanical circulatory support.

The effects of Dapagliflozin in a real-world population of HFrEF patients with different hemodynamic profiles: worse is better

BackgroundSodium-Glucose Cotransporter-2 inhibitors (SGLT2i) represent a deep revolution of the therapeutic approach to heart failure (HF), preventing its insurgence but also improving the management of the disease and slowing its natural progression. To date, few studies have explored the effectiveness of SGLT2i and, in particular, Dapagliflozin in a real-world population. Therefore, in this observational prospective study, we evaluated Dapagliflozin's effectiveness in a real-world HF population categorized in the different hemodynamic profiles.MethodsFrom January 2022 to June 2023, we enrolled 240 patients with chronic HF and reduced ejection fraction (HFrEF) on optimal medical therapy, according to 2021 ESC guidelines, that added treatment with Dapagliflozin from the HF Clinics of 6 Italian University Hospitals. Clinical, biochemical, and echocardiographic parameters were collected before and after 6 months of Dapagliflozin introduction. Moreover, the HFrEF population was classified according to hemodynamic profiles (A: SV ≥ 35 ml/m2; E/e′ < 15; B: SV ≥ 35 ml/m2; E/e′ ≥ 15; C: SV < 35 ml/m2; E/e′ < 15; D: SV < 35 ml/m2; E/e′ ≥ 15). Then, we compared the Dapagliflozin population with two retrospective HF cohorts, hereinafter referred to as Guide Line 2012 (GL 2012) group and Guide Line 2016 (GL 2016) group, in accordance with the HF ESC guidelines in force at the time of patients enrolment. Precisely, we evaluated the changes to baseline in clinical, functional, biochemical, and echocardiographic parameters and compared them to the GL 2012 and GL 2016 groups.ResultsDapagliflozin population (67.18 ± 11.11 years) showed a significant improvement in the echocardiographic and functional parameters (left ventricular ejection fraction [LVEF], LV end-diastolic volume [LVEDV], LVEDV index, stroke volume index [SVi], left atrium volume index [LAVi], filling pressure [E/e′ ratio], tricuspid annular plane systolic excursion [TAPSE], tricuspid annular S′ velocity [RVs’], fractional area change [FAC], inferior vena cava [IVC diameter], pulmonary artery systolic pressure [sPAP], NYHA class, and quality of life) compared to baseline. In particular, TAPSE and right ventricle diameter (RVD1) ameliorate in congestive profiles (B and D); accordingly, the furosemide dose significantly decreased in these profiles. Comparing the three populations, the analysis of echocardiographic parameters (baseline vs follow-up) highlighted a significant decrease of sPAP in the Dapagliflozin population (p < 0.05), while no changes were recorded in the GL 2012 and GL 2016 population. Moreover, at the baseline evaluation, the GL 2012 and 2016 groups needed a higher significant dose of furosemide compared to Dapagliflozin group. Finally, Dapagliflozin patients had significantly fewer rehospitalizations (1.25%) compared with the other two groups (GL 2012 18.89%, p 0.0097; GL 2016 15.32%, p 0.0497).ConclusionsWe demonstrate that Dapagliflozin is rapidly effective in an HFrEF real-world population; furthermore, the more significant effect is recorded in HFrEF patients with a congestive profile (B and D), supporting the introduction of Dapagliflozin in patients with a congestive profile and a worse prognosis. In conclusion, our data suggest evaluating the patient's hemodynamic state beyond LVEF in HFrEF.

Effect of remimazolam besylate versus propofol on haemodynamic profiles in patients undergoing thyroid surgery with recurrent laryngeal nerve monitoring: a protocol for a randomised controlled trial

IntroductionThyroid surgery with intraoperative nerve monitoring under total intravenous anaesthesia often requires deeper sedation due to limitations or lack of neuromuscular blocking agents, usually resulting in haemodynamic instability. Remimazolam, a...

Pharmacologic Treatment of Pulmonary Hypertension Due to Heart Failure with Preserved Ejection Fraction: Are There More Arrows on Our Bow?

Pulmonary hypertension (PH) associated with heart failure with preserved ejection fraction (PH-HFpEF) represents a frequent form of PH related to left ventricular dysfunction. The pathophysiology of PH-HFpEF is intricate, and varied and includes vascular, cardiac, and pulmonary factors that contribute synergistically to developing this clinical syndrome. Improved knowledge of the pathophysiology of PH-HFpEF has paved the way for the use of new drugs such as angiotensin receptor neprilysin inhibitors (ARNIs), non-steroidal mineral corticoid receptor antagonist (nsMRA), sodium-glucose cotransporter inhibitors (SGLT2is), levosimendan, and glucagon-like peptide 1 (GLP-1) agonists. ARNIs are a widely used drug for the treatment of PH associated with heart failure with reduced ejection fraction. They have also recently been used in PH-HFpEF patients with hemodynamic benefits that need to be confirmed in future research. Finerenone is an innovative non-steroidal mineralocorticoid receptor antagonist that exhibits notable cardioprotective and renoprotective properties in individuals suffering from chronic diabetic kidney disease. It also enhances outcomes for patients with heart failure, whether they have mildly reduced or preserved ejection fraction. Moreover, in experimental studies, finerenone has been found to lower pulmonary artery pressure, reduce muscularization, and decrease the wall thickness of pulmonary arteries. SGLT2i have revolutionized the treatment of patients with heart failure irrespective of left ventricular ejection fraction, and their treatment is also associated with an improvement in the hemodynamics profile in patients with PH-HFpEF. Levosimendan is a widely used inodilator in the treatment of acute and advanced heart failure. In addition, its use in patients with PH-HFpEF (supported by the positive effects on pulmonary hemodynamics that levosimendan exerts) has recently demonstrated hemodynamic benefit in a small phase 2 study that paved the way for phase 3 studies and the creation of an oral formulation of levosimendan. Finally, GLP1 agonists are a class of drugs that, in preliminary evidence, have shown a positive effect on cardiac hemodynamics, mainly by facilitating left ventricular unloading. These effects, along with the reduction in insulin resistance and weight loss, likely lead to beneficial outcomes for PH-HFpEF patients, especially those with obesity as a comorbidity.

Improvements in Hemodynamics and Right Heart Remodeling Following Balloon Pulmonary Angioplasty Treatment in Patients With Chronic Thromboembolic Pulmonary Hypertension: A Retrospective Study.

This study aimed to evaluate the hemodynamic alterations and right heart remodeling dynamics in patients with inoperable chronic thromboembolic pulmonary hypertension (CTEPH) undergoing treatment with balloon pulmonary angioplasty (BPA). This retrospective cohort study involved a cohort of 31 patients with a confirmed diagnosis of CTEPH. Comprehensive clinical evaluations were systematically performed before BPA, and at 3 and 6 months following the procedure. Significant clinical progress was evidenced by the uplift in the percentage of patients achieving WHO-FC II, escalating from 19.35% at baseline to 51.61% at 6 months after BPA (p = 0.003). NT-proBNP levels significantly dropped from a median of 614.6 to 69.9 pg/mL(p < 0.001). Hemodynamic assessments showed significant decreases in mean PAP from 45.53 ± 11.19 to 22.56 ± 5.81 mmHg (p < 0.001) and PVR from 8.33 to 2.86 WU (p < 0.001). Echocardiographic analysis revealed substantial reductions in the right atrial area (RAA, from 20.29 ± 7.55 to 16.79 ± 4.82 cm2, p < 0.001) and right ventricular internal diameter (RVID, from 4.13 ± 0.79 to 3.68 ± 0.59 cm, p = 0.001) at the 3-month interval post-BPA. These improvements were sustained or even enhanced by the 6-month mark, with RAA and RVID further diminishing (to 14.46 ± 3.78 cm2 and 3.29 ± 0.54 cm, respectively; both p < 0.01). The TAPSE/PASP ratios showed progressive improvement from baseline (0.32 ± 0.13) to 3 months (0.42 ± 0.13) and continued to improve at 6 months following BPA (0.50 ± 0.11, p = 0.04 compared to 3 months post-BPA). BPA has significantly ameliorated clinical conditions, hemodynamic profiles, and initiated a continued reversal in right heart remodeling in patients with CTEPH.

Right Ventricular-Pulmonary Arterial Uncoupling as a Predictor of Invasive Hemodynamics and Normotensive Shock in Acute Pulmonary Embolism

Right ventricular-pulmonary arterial (RV-PA) coupling describes the relationship between RV contractility and its afterload and is estimated as the ratio of the tricuspid annular plane systolic excursion (TAPSE) to pulmonary arterial systolic pressure (PASP) via echocardiography. Whether TAPSE/PASP is reflective of invasive hemodynamics or occult shock in acute pulmonary embolism (PE) is unknown. This was a single-center retrospective study over a 3-year period of consecutive patients with PE undergoing mechanical thrombectomy and simultaneous pulmonary artery catheterization with echocardiograms performed within 24 hours prior to the procedure.Seventy patients (81% intermediate-risk) had complete invasive hemodynamic profiles and echocardiograms with TAPSE/PASP calculated. The optimal cutoff for TAPSE/PASP as a predictor of a reduced cardiac index (CI≤ 2.2 L/min/m2) was 0.34 mm/mmHg with an AUC of 0.97 and sensitivity, specificity, positive predictive value, and negative predictive value of 97.3%, 90.9%, 92.3% and 96.8%, respectively. Every 0.1 mm/mmHg decrease in TAPSE/PASP was associated with a 0.24 L/min/m2 decrease in the CI. This relationship was similar when restricted to intermediate-risk PE. The TAPSE/PASP ratio was predictive of normotensive shock with an OR 2.63 (95% CI: 1.42, 4.76, p=0.002) per unit decrease in the ratio.In conclusion, patients with acute PE undergoing mechanical thrombectomy, TAPSE/PASP was a strong predictor of a reduced CI and normotensive shock. This means of non-invasive point-of-care assessment of hemodynamics may have added value in PE risk stratification.

Hemodynamic profiles and survival in chronic advanced heart failure patients evaluated for heart replacement therapy

Abstract Background Advanced heart failure (HF) is associated with dismal prognosis despite optimal medical therapy. Invasive assessment with right heart catheterization (RHC) is a valuable tool to assess transplant candidates and hemodynamic profiling is crucial to stratify prognosis and select patients for advanced therapies. Purpose This study aims to examine the relationship between hemodynamic profiles based on cardiac index (CI) and filling pressures and survival in ambulatory patients with advanced HF evaluated for heart replacement therapy (HRT) such as heart transplantation (HT) and left ventricular assist device (LVAD) implant. Methods We analyzed adult ambulatory advanced HF patients evaluated for HRT with an available baseline RHC from 2003 to 2022. Hemodynamic data were classified using a CI &amp;lt; 2.2 l/min/m2 as marker of reduced cardiac output ("cold" profile opposed to the "warm" profile) and increased filling pressure, defined as right atrial pressure ≥ 10 mmHg and/or pulmonary capillary wedge pressure (PCWP) ≥ 15 mmHg as a marker for congestion ("wet" profile opposed to the "dry" profile). Study endpoint was death or urgent HT or LVAD implant at 5 years. Results Study population included 610 patients (mean age 53±10 years, 79% males). According to hemodynamic criteria, 332 patients (55%) exhibited a "wet cold" hemodynamic profile, 117 (19%) a "cold dry", 91 (15%) a "warm wet" and 66 (11%) a "warm dry" phenotype. The "wet" patients showed a significantly higher prevalence of pulmonary hypertension (96% wet cold, 94% wet warm vs 21% dry warm, 19% dry cold; p&amp;lt;0,001), a lower pulmonary artery pulsatility index (4,0 wet cold, 4,1 wet warm vs 7,4 dry warm, 6,9 dry cold; p&amp;lt;0,001). No differences were found in etiology of HF. Both reduced CI [OR 1,6 (1-2,4), p=0.003] and increased filling pressures [OR 1,9, (1,2-2,8) p=0.007] were associated with worse outcomes. Survival differed significantly among hemodynamic profiles, with a survival rate of 48% in the "cold wet" profile compared to 68% in the "cold dry" [OR 1,9 (1,2-3,1) p=0,007] and 65% in the "warm dry" [OR 2,2 (1,1-4,2), p=0.01]. The difference between "cold wet" and "warm wet" was borderline significant (p=0.07). Further stratification between right and left ventricular filling pressures showed that isolated right ventricular congestion was rare and associated with low event rate, while in patients with preserved CI, biventricular congestion was associated with borderline worse survival as compared to isolated left ventricular increased filling pressures (p=0.06). Conclusions Hemodynamic profiles assessed with RHC stratify prognosis in ambulatory patients with advanced HF referred for HRT. Evaluation of hemodynamic phenotype may help identify subgroups of patients at high risk and guide therapeutic decisions. Further studies are needed to confirm these findings and develop personalized management strategies to improve clinical outcomes in this population.Survival-hemodynamic phenotypeSurvival-filling pressures

Pharmacologic treatment of hypertension guided by non-invasive haemodynamics in primary care improves blood pressure control

Abstract Background Current guidelines on hypertension (HTN) provide blood pressure (BP) targets and therapeutic algorithms but ignore the potential to treat individual patients according to their haemodynamic profile. We have shown that use of non-invasive haemodynamic information obtained by impedance cardiography (ICG) can improve BP control in the primary care setting. Purpose To investigate whether improved rates of BP control by matching patients’ non-invasive haemodynamics to specific pharmacologic treatments and increasing patient engagement translates into improved clinical outcome measures. Methods Electronic medical records (EMR) were obtained for 14,698 patients from two US primary care groups between 2014 and 2023. ICG was done when BP exceeded 140/90 mmHg. Haemodynamic measurements included mean arterial pressure (MAP), cardiac index (CI), cardiac power index (CPI), total peripheral resistance index (TPRI), stroke index (SI) and heart rate (HR) (Figure 1). Haemodynamic ICG profiles were classified as: Vasoconstriction, Hyperdynamic, or Mixed pattern. Printed clinical decision support (CDS) tools and later an EMR integrated CDS application were used to communicate recommendations to physicians. Printed reports were shared with patients to increase their engagement. Pharmacological therapy was tailored based on haemodynamic information. Rates of successful BP treatment and the occurrence of myocardial infarction (MI) or stroke were tracked through the EMR. Results Of 14,698 patients, 50% were women, 17% were Black and 17% were aged 18-49 years, 45% aged 50-69 years, and 38% age ≥ 70 years. A total of 21,246 ICGs were performed classifying patients as Vasoconstriction 47%, Hyperdynamic with high heart rate (HR) or high stroke index (SI) 24%, and Mixed Haemodynamic (combination of Vasoconstriction and Hyperdynamic) 29% (Figure 1). Demographic features were not strongly associated with haemodynamic classification. Within 2-3 years of inclusion, &amp;gt;85% of patient achieved BP control (&amp;lt;140/90 mmHg), which was sustained during follow-up. Over a median (IQR) follow-up of 8 (2016-2023) years, there were 14 (5) MI and 34 (16) strokes. These event rates appear to be lower than those reported in other large cohorts of patients with HTN. Conclusions Treating patients with HTN according to their individual haemodynamic profile is associated with high rates of BP control. Further analysis will determine whether the rates of MI, stroke and death are lower than expected based on the patients baseline risk profile.Haemodynamic Status (ICG Test Results)

Artificial intelligence-enabled electrocardiogram for left ventricular diastolic dysfunction and long-term risk of new-onset atrial fibrillation

Abstract Background Heart failure (HF) and atrial fibrillation (AF) are intertwined, sharing common risk factors and influencing each other in a reciprocal manner. While left ventricular diastolic dysfunction (LVDD) stands as a hallmark of HF's hemodynamic profile, its direct correlation with heightened AF risk remains uncertain. Our recent validation of an artificial intelligence-enabled electrocardiogram (AI-ECG) algorithm for LVDD detection has opened new avenues. Yet, whether AI-ECG-detected LVDD correlates with long-term AF risk remains unexplored. Methods We performed a retrospective study among all patients with a comprehensive LVDD assessment from the test population of the AI-ECG LVDD study between September 2001 and June 2022. Patients with prior documented AF according to health records or previous ECG were excluded. Patients were classified by AI-ECG as normal diastolic function (DF), grade 1 (G1), grade 2 (G2), or grade 3 (G3) LVDD. We assessed the risk of AF across AI-ECG LVDD grade, with normal DF as reference, with competing risk models. Results Of 97,023 patients free of AF at baseline, 63,533 (65.4%), 10,776 (11.1%), 18,940 (19.5%), and 3,774 (3.9%) were classified as normal DF, G1-LVDD, G2-LVDD, and G3-LVDD, respectively. Worse AI-ECG LVDD was associated with older age, lower left ventricular ejection fraction (LVEF), and higher rates of HF, diabetes, hypertension, chronic pulmonary disease, renal failure, and cardiovascular disease (p-of-trend&amp;lt;0.001 for all). Over a median follow-up of 4.8 years (interquartile range 1.8-9.2 years), new-onset AF occurred in 6,795 (7.0%) patients. In multivariable survival analysis, adjusted to multiple risk factors including LVEF and clinical HF, G2 and G3 LVDD, representing patients with high filling pressures, were independently associated with a higher AF-risk [G2-LVDD: adjusted hazard ratio (aHR) 1.64 (95% confidence interval (95%CI) 1.52-1.73), G3-LVDD: aHR 2.24 (95%CI 2.02-2.48)]. Conclusion The AI-ECG LVDD algorithm independently predicts long-term AF risk, regardless of LVEF and clinical HF status, highlighting its potential for identifying high-risk populations and guiding proactive monitoring and management.

The cardioprotective potential of soluble urokinase Plasminogen Activator Receptor (suPAR) in myocardial ischemia

Abstract Background and aims: Increased circulating soluble urokinase plasminogen activator receptor (suPAR) levels are associated with adverse cardiovascular outcomes, however, any cardiovascular-related functions remain unknown. This study aimed to (i) document haemodynamic profiles in isolated rat hearts under the influence of suPAR, and to (ii) explore any mechanisms triggered by suPAR following myocardial ischaemia-reperfusion. Methods We undertook a 4-pronged approach (Figure 1). A Langendorff isolated rat heart model was used to perfuse all hearts with Krebs-Henseleit solution flowing retrogradely through the aorta at 37°C. A balloon inserted into the left ventricle allowed measurements of ventricular pressure, and a pressure transducer placed above the aorta recorded perfusion pressure for coronary flow rates. The experimental protocol consisted an initial 30-minute stabilisation period, followed by 40 minutes of ischemia via buffer flow cessation. Hearts were subsequently recovered during 90 minutes of reperfusion, receiving either suPAR treatment or perfusion buffer as controls. An inhibitor arm comprising co-infusion of suPAR and a monoclonal antibody capable of binding to suPAR was also assessed. Troponin T was measured in outflow perfusates collected at specific intervals. Proteins from hearts in treatment groups were separated using gel electrophoresis, with Western blotting to visualise the phosphorylation status of kinases (Akt, STAT). High-flow respirometry and fluorometry were investigated in cardiac mitochondria to determine respiration rates and ATP production in ischaemia reperfusion under the influence of suPAR. Statistical analysis was conducted with ANOVA using SPSS. Results Hearts receiving suPAR infusion at reperfusion (n = 16) showed a significant increase in developed pressure (p = .017) and lower perfusion pressure (p = .02) compared to controls (n = 16), revealing that suPAR-treated hearts recovered with better contractility and vasodilatory properties post-ischaemia. suPAR’s haemodynamic profiles in the antibody group were similar to controls, attenuating suPAR-induced effects (n = 8). Outflow effluents in suPAR-treated hearts obtained &amp;gt;3 fold lower serial Troponin T values than controls (p &amp;lt; .001). Heart tissues receiving suPAR treatment revealed a 1.7-fold increase in Akt (p = .001) and a 3.8-fold increase in STAT3 phosphorylation compared to controls (p &amp;lt; .001) and the inhibitor group (p = .04). Finally, suPAR increased mitochondrial ATP production by 28% (p = .013) compared to controls after ischaemia. Conclusion This is a world-first demonstration of suPAR’s cardioprotective influences in isolated rat hearts recovering from ischaemia. suPAR’s ability to promote cardiac contractility and vasodilation was associated with lesser injury as shown by Troponin T reduction. Mechanistically, suPAR infusion upregulated two key cardioprotective pathways, which may also function to protect cardiac mitochondria.Figure 1 - Schematic of Methods

Idiopathic pulmonary arterial hypertension, associated with connective tissue disease and comorbidities: prognostic differences? Results the Spanish Registry of pulmonary hypertension (REHAP Registry)

Abstract Introduction Idiopathic pulmonary arterial hypertension (iPAH) and associated with connective tissue disease (PAH-SSc) are the most frequent groups of pulmonary arterial hypertension (PAH) but their long-term survival is usually unequal. Comorbidities, increasing in frequency in these patients, show prognostic influences but it is not known whether these differ in both groups of patients. Methods We collected patients diagnosed with iPAH, heritable, associated with drug or toxine exposure and PAH-SSc between 2014 and 2023 from the Spanish Registry of Pulmonary Hypertension. Patients are classifies into iPAH and PAH-SSc. We analyzed baseline characteristics and the distribution of the different comorbidities in the two groups. Survival analyses estimated by Kaplan-Meier analysis using the log-rank test were done according to PAH etiology and comorbidities and Cox proportional hazard analyses were performed to determine the effects of baseline characteristics on survival. Results Seven hundred and fifty-seven patients were selected for this study. The characteristics of the patients are shown in Table 1. Patients with PAH-SSc compared to iPAH were older (62 vs 56 years), more female (81.8% vs 62.4%), had a more favorable hemodynamic profile, TAPSE/sPAP ratio and lower NT-proBNP levels. No differences were found in functional class or 6MWT. We found a higher proportion of patients in a low and intermediate risk profile, according to ESC, in patients with PAH-SSC as opposed to PAHi (46.8/50.9% vs. 29.3/64.5%; p&amp;lt;0.001). Regarding comorbidities, history of smoking (27.1 vs 54%; p&amp;lt;0-001), obesity (17.1 vs 20.7%; p&amp;lt;0.001) and diabetes (9.4 vs 22.1%; p&amp;lt;0.001) are less frequent in PAH-SSc than in iPAH. There are no differences in the rest of the comorbidities studied in the two groups of patients. In a survival analysis, we found no differences between patients with iPAH and PAH-SSc at 7-year follow-up. Patients with ≥ 3 comorbidities had statistically significantly higher mortality (p&amp;lt;0.001) compared to those with 0 or 1-2 comorbidities in both etiologies. There were no differences between 0 and 1-2 comorbidities. (Figure 1). Variables associated with mortality were male sex (HR 1.9, 95% CI 1,28 – 2.8), age (HR 1.04, 95% CI 1.02 – 1.06), the intermediate risk profile (HR 2.64, 95% CI 1.62 – 4.32) and high risk profile (HR 9.97, 95% CI 4.36 – 18.47), but not etiology. The presence of connective tissue diseases, were not associated with increased mortality. Conclusions Patients with PAH-SSc show lower comorbidities, better hemodynamic profile, RV-PA coupling and risk profile than those with iPAH. Comorbidity has a great relevance in survival but without differences according to etiology. The presence of male sex, age, the intermediate and high risk profile is associated with worse survival, but not the connective tissue diseases.

VExUS score improvement is associated with better outcomes in acute decompensated heart failure

Abstract Background Venous Excess Ultrasound Score (VExUS) has recently emerged as a non-invasive tool for venous congestion assessment in acute decompensated heart failure (ADHF). Although VExUS is associated with cardiorenal syndrome, the prognostic role regarding hard outcomes in ADHF is still unknown. Purpose To evaluate whether dynamic changes in VExUS within 72 hours after Cardiovascular Intensive Care Unit (CICU) admission is associated with in-hospital mortality in ADHF patients. Methods Prospective cohort study enrolling consecutive patients with ADHF admitted to CICU of a tertiary public hospital. VExUS evaluations ranging from 0 (no congestion) and 3 (severe congestion) and assessing the inferior vena cava, hepatic, and portal veins flow, were initially performed within 24 hours of admission and re-evaluated at 72 hours (third day) after treatment initiation. Changes in VExUS scores were compared between these two time points. Mann-Whitney test and logistic regression was performed to evaluate VExUS improvement association with mortality. Results Between October 2022 and January 2024, 81 patients were admitted to the CICU due to ADHF. Following the exclusion of 10 patients who were not assessed within the first 24 hours, 71 patients were included in the final analysis. Mean age was 65 ± 13.3 years, with 66.7% being male. Ischemic etiology was identified in 40.7%, and atrial fibrillation was present in 34.6%. Mean left ventricular ejection fraction was 27.4% ± 12.2, and 64.2% had right ventricular dysfunction. Upon admission, 73.2% were classified as B and 23.9% as C hemodynamic profiles. Overall in-hospital mortality was 25.9%. In-hospital mortality across VExUS categories assessed in the third day was 16.7%, 12.5%, 28.6% e 40%, for VExUS 0-3, respectively. The median VExUS variation between the two time points was greater in patients who survived [-1 vs. 0; p=0.030] and VExUS improvement at 72 hours was associated with a 46% decrease in hospital mortality for each class reduction (OR=0.536; 95% CI 0.29-0-81; p=0.043 - Figure 1). Conclusion Improvement in VExUS score between admission and 72 hours is associated with reduced in-hospital mortality. This finding highlights the potential role of dynamic VExUS monitoring for identifying delayed treatment response patients. Thus, changes in VExUS emerged as a prognostic tool offering a pathway to potentially intensify treatment strategies for high-risk patients with ADHF.VExUS score changes within 72 hours

The importance of comorbidities in idiopathic and associated with connective tissue disease pulmonary arterial hypertension: from the Spanish Registry of Pulmonary Hypertension (REHAP Registry)

Abstract Introduction Comorbidities play a major role in the prognosis of patients with pulmonary arterial hypertension (PAH). These comorbidities are present in more than 80% of patients diagnosed in the last years with idiopathic PAH (iPAH) and their presence is associated with increased morbidity and mortality although its influence on PAH associated with connective tissue disease (PAH-SSc) is unknown. We studied the impact of comorbidities on iPAH and PAH-SSc in the Spanish population. Methods We collected patients diagnosed with iPAH, heritable, associated with drug or toxine exposure and PAH-SSc between 2014 and 2023 from the Spanish Registry of Pulmonary Hypertension. Patients are classified into: no comorbidities, 1-2 comorbidities and ≥3 comorbidities. We analyzed the impact of comorbidities in baseline characteristics, exercise capacity and hemodynamic profile, as well as in the risk profile and initial treatment. Survival analyses estimated by Kaplan-Meier analysis using the log-rank test and Cox proportional hazard analyses were performed to determine the effects of baseline characteristics on survival. Results 757 patients were selected for this study. The characteristics of the patients are shown in Table 1. As the number of comorbidities increases (0/1-2/≥3) we found higher age (49/59/67 years; p&amp;lt;0.001), higher percentage of male sex (12.9/29.9/43.4%; p&amp;lt;0.001) and higher FC III at diagnosis (42.7/46.9/59.6%; p=0.013). We observed a shorter distance in 6MWD, higher NT-proBNP levels, lower DLCO and a less unfavorable hemodynamic profile (PAPm, PAWP, CI and PVR). The most frequent comorbidities were a history of smoking (46.4%), followed by arterial hypertension (41.5%), obesity (24.6%) and chronic kidney disease (19.2%). Diabetes mellitus, although less frequent, reached more than 55% in patients with ≥3 comorbidities (p&amp;lt;0.001). The presence of ≥ 3 comorbidities was more frequent in iPAH than PAH-SSc (p&amp;lt;0,001). Intermediate risk profile was the most common (58.4%) and this reached 68.7% in those with ≥3 comorbidities due to a lower number of patients in a low-risk profile (p&amp;lt;0.001). A statistically significant lower survival (p&amp;lt;0.001) was observed in patients with ≥ 3 comorbidities; however, we found no differences between 0 and 1-2 comorbidities at 7-year follow-up (Figure 1). Variables associated with mortality were male sex (HR 1.88, 95% CI 1,26 – 2.8), age (HR 1.04, 95% CI 1.02 – 1.06) and the presence of ≥3 comorbidities (HR 1.49, 95% CI 0.98 – 2.27), not the presence of connective tissue diseases, which were not associated with increased mortality in our study. Conclusions The presence of comorbidities in iPAH and PAH-SSc is very frequent in the Spanish population. They are associated with a worse clinical profile, risk profile, lower use of oral double theraphy and prostacyclins. The presence of ≥3 comorbidities is associated with worse survival, not the presence of 1-2 comorbidities or connective tissue disease.

Safety and mid-term outcomes of impella compared to intra-aortic balloon pumping in patients who required mechanical cardiac support

Abstract Background Impella (Abiomed USA) is a promising alternative to improve prognosis in patients with cardiogenic shock requiring mechanical cardiac support (MCS). Despite of its advanced hemodynamic profile, its superiority regarding prognosis has not been established yet. Aims The aims of this study were to investigate safety and mid-term outcomes of Impella compared to IABP in patients who required MCS. Methods In this single-center study, consecutive 205 patients who required IABP or Impella from January 2017 to June 2023 were evaluated retrospectively. The primary outcome was 180-day mortality. Secondary outcomes were the rate of complications including hemolysis, thrombocytopenia, bleeding, limb ischemia, acute kidney impairment and stroke. Major complication was defined as major bleeding (BARC 3-5), limb ischemia and stroke. Results Of all patients, 62 (30.2%) received Impella and 143 (69.8%) IABP. The rate of patients required extracorporeal membrane oxygenation (ECMO) support was not significantly different between two groups (31.4 % vs 38.7%; p=0.34. There were no significant differences in 180-day mortality between two groups (36.2% vs 31.1%; p=0.55). Further investigation according to SCAI classification demonstrated that the mortality rate in SCAI C group was significantly lower in Impella than IABP group (34.1% vs 6.7%; p=0.02), whereas there were not significant differences in mortality between two groups in SCAI D and E groups (54.8% vs 61.4%; p=0.71). The rate of major complications was significantly higher in Impella group (54.4% vs 72.1%; p=0.02). The rate of hemolysis (19.6% vs. 58.1%, p&amp;lt;0.01), thrombocytopenia (19.6% vs. 58.1%, p&amp;lt;0.01), limb ischemia (4.3% vs. 17.7%, p&amp;lt;0.01), acute kidney impairment (37.7% vs 64.5%, p&amp;lt;0.01) and initiation of renal replacement therapy (13.8% vs 29%, p=0.02) were significantly higher in Impella group. Multivariate analysis adjusting for Impella use, out of hospital cardiopulmonary arrest (OHCPA), initial lactate ≥60 md/dL and major complication, revealed that age ≥70 (hazard ratio (HR): 3.1, 95%CI: 1.73-5.61) and use of ECMO (HR: 4.3, 95%CI: 2.54-7.31) were independent predictor of mortality. The mortality rate arose up to 83.3% in patients with age ≥70, OHCPA and use of ECMO (HR: 9.7, 95%CI: 4.07-23.02). Conclusion The mortality rate did not differ between Impella and IABP, however Impella was associated with improved mortality in patients with SCAI C group. The complications were high likely seen in patients with Impella compared to IABP. Our findings indicate that Impella results in better outcomes with careful selection of patients, defining its indication and appropriate care. A further investigation would be of value to elucidate whether Impella improve prognosis.

A randomized, double-blind, placebo-controlled, mechanistic trial on the safety, tolerability and pharmacodynamics of ninerafaxstat in patients with angina and chronic coronary syndrome

Abstract Background/Introduction Symptoms of angina resulting from reversible myocardial ischemia in chronic coronary syndromes have a negative impact on quality of life. Metabolic alterations are a key feature of ischemia, including reduced ATP generation by mitochondrial oxidative phosphorylation, NAD+ depletion, anaerobic glycolysis, proton &amp; lactate accumulation leading to contractile dysfunction. Ninerafaxstat is a novel cardiac mitotrope that shifts metabolism from fatty acids towards glucose utilization, optimizing myocardial energy production during ischemia. Purpose We aimed to investigate the safety, tolerability, impact on myocardial glucose utilization and preliminary anti-ischemic efficacy of ninerafaxstat administered for 8 weeks to patients with symptomatic chronic stable angina who were on anti-anginal therapy and had evidence of myocardial stress hypoperfusion using 15O-H2O PET imaging. Methods IMPROVE-Ischemia was an international, randomized, double-blind, placebo-controlled mechanistic trial comparing ninerafaxstat vs. placebo in patients with symptomatic chronic coronary syndrome. The primary endpoint was the safety and tolerability of ninerafaxstat. Key efficacy evaluations were undertaken at baseline and end-of-treatment (Week 8) including imaging core laboratory assessments of 15O-H2O PET perfusion rest and stress imaging to quantify absolute myocardial blood flow (MBF), dobutamine stress echo with contrast for evaluation of LV contractile response during demand stress using the wall motion score index (WMSI) and, in a subgroup of subjects, 18F-FDG-PET imaging of myocardial glucose metabolism. Results The study randomized 58 subjects (mean age 68.6±7.1 years) with symptomatic stable angina and inducible hypoperfusion from 4 sites across 3 countries (Denmark, Finland, Sweden). 22% had type 2 diabetes and 50% had undergone percutaneous and/or surgical coronary revascularization. The majority (68%) were on ≥2 (up to 4) regular anti-anginals. Ninerafaxstat was well tolerated without impact on systemic hemodynamics. At Week 8, ninerafaxstat significantly increased myocardial glucose utilization and, in those with dobutamine-induced deterioration in wall motion at baseline assessment (n=25, pre-specified subgroup), resulted in a ~50% improvement in mean and peak stress WMSI, without altering rest or hyperemic stress MBF (Table 1). Conclusion(s) Treatment with ninerafaxstat was well-tolerated and showed a neutral hemodynamic profile. Ninerafaxstat significantly increased myocardial glucose utilization consistent with its mechanism of action and improved myocardial contractile response to dobutamine stress in subjects with baseline stress inducible deterioration of wall motion. These findings support a direct, metabolically-mediated, anti-ischemic effect of ninerafaxstat on top of existing anti-anginal agents, supporting its further development in cardiac pathologies characterised by ischemia.