Myocardial Oxygen Consumption Research Articles

Recent advances in mesenchymal stem cell therapy for myocardial infarction.

Myocardial infarction refers to the ischemic necrosis of myocardium, characterized by a sharp reduction or interruption of blood flow in the coronary arteries due to the coronary artery occlusion, resulting in severe and prolonged ischemia in the corresponding myocardium and ultimately leading to ischemic necrosis of the myocardium. Given its high risk, it is considered as one of the most serious health threats today. In current clinical practice, multiple approaches have been explored to diminish myocardial oxygen consumption and alleviate symptoms, but notable success remains elusive. Accumulated clinical evidence has showed that the implantation of mesenchymal stem cell for treating myocardial infarction is both effective and safe. Nevertheless, there persists controversy and variability regarding the standardizing MSC transplantation protocols, optimizing dosage, and determining the most effective routes of administration. Addressing these remaining issues will pave the way of integration of MSCs as a feasible mainstream cardiac treatment.

Impact of Hemoglobin Level in Ex Vivo Heart Perfusion on Donation After Circulatory Death Hearts: A Juvenile Porcine Experimental Model.

Ex vivo heart perfusion (EVHP) of donation after circulatory death (DCD) hearts has become an effective strategy in adults; however, the small circulating volume in pediatrics poses the challenge of a low-hemoglobin (Hb) perfusate. We aimed to determine the impact of perfusate Hb levels during EVHP on DCD hearts using a juvenile porcine model. Sixteen DCD piglet hearts (11-14 kg) were reperfused for 4 h in unloaded mode followed by working mode. Metabolism, cardiac function, and cell damage were compared between the low-Hb (Hb, 5.0-5.9 g/dL; n = 8) and control (Hb, 7.5-8.4 g/dL; n = 8) groups. Between-group differences were evaluated using 2-sample t-tests or Fisher's Exact tests. During unloaded mode, the low-Hb group showed lower myocardial oxygen consumption (P < 0.001), a higher arterial lactate level (P = 0.001), and worse systolic ventricular function (P < 0.001). During working mode, the low-Hb group had a lower cardiac output (mean, 71% versus 106% of normal cardiac output, P = 0.010) and a higher arterial lactate level (P = 0.031). Adjusted cardiac troponin-I (P = 0.112) did not differ between the groups. Morphological myocyte injury in the left ventricle was more severe in the low-Hb group (P = 0.028). Low-Hb perfusate with inadequate oxygen delivery induced anaerobic metabolism, resulting in suboptimal DCD heart recovery and declined cardiac function. Arranging an optimal perfusate is crucial to organ protection, and further endeavors to refine the priming volume of EVHP or the transfusion strategy are required.

Changes in rate-pressure product associated with pregnancy

In nonpregnant individuals, the rate-pressure product, the product of heart rate and systolic blood pressure, is used as a noninvasive surrogate of myocardial O2 consumption during cardiac stress testing. Pregnancy is considered a physiological cardiovascular stress test. Evidence describing the impact of pregnancy on myocardial O2 demand, as assessed by the rate-pressure product, is limited. This study aimed to describe changes in the rate-pressure product for each pregnancy trimester, during labor and delivery, and the postpartum period among low-risk pregnancies. This was a retrospective cohort study that assessed uncomplicated pregnancies delivered vaginally at term. We collected rate-pressure product (heart rate × systolic blood pressure) values preconception, during pregnancy for each trimester (at ≤13 weeks + 6/7 days, at 14 weeks + 0/7 days through 27 weeks + 6/7 days, and at ≥28 weeks + 0/7 days), during the labor and delivery encounter (hospital admission until complete cervical dilation, complete cervical dilation until placental delivery, and after placental delivery until hospital discharge), and during the outpatient postpartum visit at 2 to 6 weeks after delivery. We calculated the percentage change at each time point from the preconception rate-pressure product (delta rate-pressure product). We used a mixed-linear model to analyze differences in the mean delta rate-pressure product over time and the influence of prepregnancy age, prepregnancy body mass index, and neuraxial anesthesia status during labor and delivery on these estimates. Our cohort comprised 316 patients. The mean rate-pressure product increased significantly from preconception starting at the third trimester of pregnancy and during labor and delivery (P≤.05). The mean delta rate-pressure product peaked at 12% and 38% in the third trimester and during labor and delivery, respectively. Prepregnancy body mass index was inversely correlated with the mean delta rate-pressure product changes (estimate, -0.308; 95% confidence interval, -0.536 to -0.80; P=.008). In contrast, neither the prepregnancy age, nor neuraxial anesthesia status during labor had a significant influence on this parameter. This study validates the transient but significant increase in the rate-pressure product, a clinical estimate of myocardial O2 demand, during uncomplicated pregnancies delivered vaginally at term. Pregnant individuals with lower prepregnancy body mass index experienced a sharper increase in this parameter. Patients who receive neuraxial anesthesia during labor and delivery experience similar changes in the rate-pressure product as those who did not.

Rate-Pressure Product is a Novel Predictor for Short- and Long-Term Mortality in Patients with Acute Coronary Syndrome Undergoing Primary PCI/Immediate Invasive Strategy.

Rate-pressure product (RPP) calculated by multiplying heart rate by systolic blood pressure, is a convenient indicator closely associated with cardiac work or myocardial oxygen consumption. It has been reported to relate strongly to important indices of cardiovascular risk in patients with myocardial ischemia. However, its relationship with short- and long-term mortality in patients with acute coronary syndrome (ACS) undergoing primary PCI/immediate invasive strategy has not been defined. This study analyzed 1301 consecutive ACS patients who had undergone primary PCI, between January 2018 and September 2021. Patients with systolic BP < 90 mmHg were excluded to avoid the confounding effect of cardiogenic shock. RPP values were collected on admission and were divided into four groups: RPP ≤ 7.4, 7.4 ≤ 8.8, 8.8 <8.8 < RPP8, and RPP > 10.8. Clinical endpoints were in-hospital cardiac and long-term all-cause mortality. The predictive performance was assessed by C-statistic, multivariate analysis and survival analysis. Multivariate analysis showed that these in the highest vs lowest category of RPP (>10.8 vs ≤7.4) had OR of 4.33 (95% CI=1.10 -17.01; P = 0.036) in in-hospital cardiac mortality and 3.15 (95% CI=1.24 -8.00; P = 0.016) in long-term all-cause mortality. In C-statistic analyses, RPP was a strong predictor in ACS, STEMI or UA/NSTEMI group for in-hospital cardiac mortality (AUC = 0.746, 95% CI = 0.722-0.770, p < 0.001) and long-term all-cause mortality (AUC = 0.701, 95% CI = 0.675-0.725, p < 0.001). The Kaplan-Meier event rate for long-term survival of RPP > 10.8 was significantly lower than that of RPP ≤ 10.8. RPP showed a positive association with in-hospital cardiac or long-term all-cause mortality in ACS patients undergoing primary PCI/immediate invasive strategy, and RPP > 10.8 can be as an independent predictor.

Coronary vasospasm testing: escape from the cath lab!

Coronary vasospasm stands as a widely acknowledged and frequent culprit behind chest pain, acute coronary syndrome, and sudden cardiac death, yet it remains a challenging diagnosis. Current guidelines recommend invasive coronary function testing to assess pathophysiology and mechanisms and to define treatment. In reality, this protocol is rarely applied, because it necessitates extended occupation of the cath lab, repetitive administration of nephrotoxic iodine contrast agents, the need for repeated testing on both coronary arteries leading to considerable radiation exposure, and significant direct expenses. The promising perspective for vasospasm testing is a noninvasive approach with advanced echocardiographic techniques, such as transthoracic Doppler echocardiography, with more sensitive indicators of ischemia. Hyperventilation and exercise tests are used for vasospasm directed testing, with assessment of the new parameters: coronary flow velocities and reserve, allowing to see deeper into macro and microvascular pathophysiology. Association between coronary flow, global longitudinal strain and microvascular dysfunction (MVD) and impaired values at hyperemia was previously demonstrated. Reduction in coronary flow velocity (CFV) despite heightened myocardial oxygen consumption and double product during hyperventilation are indicative of coronary vasospasm. Normal coronary angiography finding in patients with documented evidence of ischemia should initiate additional diagnostic testing in order to increase the yield of specific diagnosis in patients with suspected vasospasm, which could help to personalize treatment and prognosis. In order to achieve this, non-invasive provocative stress echocardiography tests should be included in the diagnostic workup. This approach, characterized by its simplicity, feasibility, safety, and efficacy, is currently undergoing extensive testing on a large scale.

A ketogenic diet lowers myocardial fatty acid oxidation but does not affect oxygen consumption: a study in overweight humans.

A ketogenic diet (KD) characterized by very low carbohydrate intake and high fat consumption may simultaneously induce weight loss and be cardioprotective. The "thrifty substrate hypothesis" posits that ketone bodies are more energy efficient compared with other cardiac oxidative substrates such as fatty acids. This work aimed to study whether a KD with presumed increased myocardial ketone body utilization reduces cardiac fatty acid uptake and oxidation, resulting in decreased myocardial oxygen consumption (MVO2 ). This randomized controlled crossover trial examined 11 individuals with overweight or obesity on two occasions: (1) after a KD and (2) after a standard diet. Myocardial free fatty acid (FFA) oxidation, uptake, and esterification rate were measured using dynamic [11 C]palmitate positron emission tomography (PET)/computed tomography, whereas MVO2 and myocardial external efficiency (MEE) were measured using dynamic [11 C]acetate PET. The KD increased plasma β-hydroxybutyrate, reduced myocardial FFA oxidation (p < 0.01) and uptake (p = 0.03), and increased FFA esterification (p = 0.03). No changes were observed in MVO2 (p = 0.2) or MEE (p = 0.87). A KD significantly reduced myocardial FFA uptake and oxidation, presumably by increasing ketone body oxidation. However, this change in cardiac substrate utilization did not improve MVO2 , speaking against the thrifty substrate hypothesis.

Lidocaine, Esmolol, and Beyond: A Comprehensive Analysis of Hemodynamic Stress during Laryngoscopy and Intubation

Aim: To evaluate the haemodynamic stress response in combination of lidocaine and esmolol versus lidocaine or esmolol alone during laryngoscopy and intubation Methods: This research comprised 60 patients who provided written permission and met the inclusion and exclusion criteria. Selected patients were randomly assigned to one of three groups based on a computer-generated random number: lignocaine 1.5 mg/kg (n=40), esmolol 2mg/kg (n=40), or lignocaine 1mg/kg and esmolol 1mg/kg (n=40). This research comprised patients aged 20 to 42 who had elective procedures under general anaesthetic and had ASA I and II. Patients with contraindications to beta blockers, such as bronchial asthma, COPD, a basal heart rate of 60 beats per minute, respiratory impairment, and documented reactions to local anaesthetics. Results: There were no significant variations in age, preoperative heart rate, or blood pressure between the groups. Males and females were approximately equally dispersed throughout all groupings. Following the delivery of the test medicines, all three groups saw a substantial drop in heart rate (Group E 61.23±3.64, Group L 73.25±5.36, Group LE 72.23±5.36) (p&lt;0.001). Four Group E patients developed bradycardia. (HR &lt;60). Although both Group LE and Group L showed near baseline values, Group L showed near baseline values until the third minute, whereas Group LE showed a continuous reduction in heart rate rates. After 30 minutes, all three groups' heart rates were statistically insignificant. Following induction and administration of the test medicines, systolic, diastolic, and hence mean arterial blood pressure lowers gradually in all three groups (p&lt;0.001). (This is for systolic blood pressure.). Group E 97.36±5.69, Group L 125.39±6.36, Group LE 116.78±4.78) Group E 60.034.69, Group L 82.935.36, Group LE 72.034.78) (Group E 72.10±3.69, Group L 96.90±3.85, Group LE 86.44±2.87) Before intubation, patients in Group E experienced substantial decreases in systolic, diastolic, and mean arterial blood pressure (less than 20% of baseline). Following intubation, blood pressure levels in Group LE were near baseline until the 30th minute (p&lt;0.001). Group E had a consistent fall in all three blood pressure readings following intubation until the fifth minute. Group E's blood pressures were likewise around baseline at the 15th and 30th minutes. Until the 15th minute, Group L had a considerable rise in all three blood pressures. Conclusion: As a result, esmolol and lidocaine together are a safe and effective strategy to minimise laryngoscopy responses to intubation and extubation, lowering myocardial oxygen consumption and the risk of myocardial ischemia under general anaesthesia.

Myocardial work indices in bileaflet mitral valve prolapse patients.

Mechanisms underlying left ventricular dysfunction and arrhythmogenesis in bileaflet mitral valve prolapse (BMVP) patients are not well defined. Myocardial work index (MWI) is a non-invasive assessment that correlates with myocardial oxygen consumption. We aimed to compare global and regional MWI in BMVP patients with normal controls. In this retrospective study, we calculated MWI in BMVP patients and controls using GE EchoPAC (GE Healthcare, Chicago, IL, USA) software. Of 147 BMVP patients (59% women, mean age 54 ± 15 years), 16 had a flail mitral leaflet. There was regional heterogeneity in MWIs, with increased posterolateral trident myocardial work (2099 ± 271 vs. 1895 ± 321 mm Hg%, P = 0.039), constructive work (2831 ± 366 vs. 2257 ± 338 mm Hg%, P < 0.001), wasted work [87 (52-194) vs. 71 (42-103) mm Hg%, P = 0.015], peak systolic strain (-23.0 ± 2.4 vs. -19 ± 3%, P < 0.001), and reduction in myocardial work efficiency [95.00 (93.50-97.75) vs. 96.75 (95.00-97.75) %, P = 0.020] in 100 BMVP patients compared with age- and sex-matched controls. BMVP patients' basal septal wall MWIs were lower than those of controls. The higher work indices in patients with BMVP were reduced in those who developed flail leaflets. No significant differences in work indices were seen between ventricular arrhythmia and non-arrhythmia BMVP patients. Regional differences in MWIs were noted in the BMVP patients compared with controls, with overall reduced myocardial efficiency in the posterolateral trident and basal septal regions. In cross-sectional analysis, MWIs were not different in patients with ventricular tachyarrhythmias. Impact of MWI on long-term prognosis needs to be determined.

Biologically derived epicardial patch induces macrophage mediated pathophysiologic repair in chronically infarcted swine hearts

There are nearly 65 million people with chronic heart failure (CHF) globally, with no treatment directed at the pathologic cause of the disease, the loss of functioning cardiomyocytes. We have an allogeneic cardiac patch comprised of cardiomyocytes and human fibroblasts on a bioresorbable matrix. This patch increases blood flow to the damaged heart and improves left ventricular (LV) function in an immune competent rat model of ischemic CHF. After 6 months of treatment in an immune competent Yucatan mini swine ischemic CHF model, this patch restores LV contractility without constrictive physiology, partially reversing maladaptive LV and right ventricular remodeling, increases exercise tolerance, without inducing any cardiac arrhythmias or a change in myocardial oxygen consumption. Digital spatial profiling in mice with patch placement 3 weeks after a myocardial infarction shows that the patch induces a CD45pos immune cell response that results in an infiltration of dendritic cells and macrophages with high expression of macrophages polarization to the anti-inflammatory reparative M2 phenotype. Leveraging the host native immune system allows for the potential use of immunomodulatory therapies for treatment of chronic inflammatory diseases not limited to ischemic CHF.

Short-term effects of sacubitril/valsartan therapy on myocardial oxygen consumption and energetic efficiency of cardiac work in heart failure with reduced ejection fraction: A randomized controlled study.

We sought to evaluate the mechanism of angiotensin receptor-neprilysin inhibitor (ARNI) sacubitril/valsartan therapy and compare it with a valsartan-only control group in patients with heart failure with reduced ejection fraction (HFrEF). The study was a phase IV, prospective, randomized, double-blind, parallel-group study in patients with New York Heart Association class II-III heart failure and left ventricular ejection fraction (LVEF) ≤35%. During a 6-week run-in period, all patients received valsartan therapy, which was up-titrated to the highest tolerated dose level (80 mg bid or 160 mg bid) and then randomized to either valsartan or sacubitril/valsartan. Myocardial oxygen consumption, energetic efficiency of cardiac work, cardiac and systemic haemodynamics were quantified using echocardiography and 11 C-acetate positron emission tomography before and after 6 weeks of therapy (on stable dose) in 55 patients (ARNI group: n = 27, mean age 63 ± 10 years, LVEF 29.2 ± 10.4%; and valsartan-only control group: n = 28, mean age 64 ± 8 years, LVEF 29.0 ± 7.3%; all p = NS). The energetic efficiency of cardiac work remained unchanged in both treatment arms. However, both diastolic (-4.5 mmHg; p = 0.026) and systolic blood pressure (-9.8 mmHg; p = 0.0007), myocardial perfusion (-0.054 ml/g/min; p = 0.045), and left ventricular mechanical work (-296; p = 0.038) decreased significantly in the ARNI group compared to the control group. Although myocardial oxygen consumption decreased in the ARNI group (-5.4%) compared with the run-in period and remained unchanged in the control group (+0.5%), the between-treatment group difference was not significant (p = 0.088). We found no differences in the energetic efficiency of cardiac work between ARNI and valsartan-only groups in HFrEF patients. However, ARNI appears to have haemodynamic and cardiac mechanical effects over valsartan in heart failure patients.

Increased cardiac output and left ventricular contractility in pigs paced with vs. without restored respiratory sinus arrhythmia - proof of principle of a newly developed pacing device

Abstract Background Heart rate variability (HRV) correlates with the severity and mortality of heart failure. Respiratory sinus arrhythmia (RSA) is defined by the dynamic increase and decrease in heart rate between breaths. Restoration of RSA might be beneficial in patients with heart failure and/or patients in need of permanent pacing. Purpose The aim of this translational, proof-of-principle study was to investigate the effect of pacing with or without RSA using a newly designed pacing device on the left ventricular contractility and cardiac output. Methods The project was initiated with the aim of designing a new pacing device capable of restoring RSA in paced hearts with the help of lung inflation sensors. Neuronal networks were designed to reconstruct the human brain using ultra-low energy-consuming technology. The lung inflation sensor fed the detected inspiration data back to the pacing device, which paced the heart via pacing leads (DDD) in the right atrium and ventricle. In total, 5 intubated but spontaneously breathing landrace pigs were paced without RSA (fixed-rate pacing) and with restored RSA. Stroke volume and cardiac output were measured by echocardiography (diameter of left ventricular outflow tract and velocity time integral measured by pulsed wave doppler averaged over three heart beats). Preload-independent cardiac contractility was measured via a pressure-volume loop catheter in the left ventricle during occlusion of the inferior vena cava. Fig. 1 indicates the setup of the trial. The trials were conducted according to the relevant rules (NIH Publication no. 85-23 revised 1985) and in accordance with national law. Results Echocardiography (n=5) showed a mean left ventricular outflow tract diameter of 21 ± 0.1 mm. The mean intrinsic heart rate was 87 ± 14 bpm, and the mean paced heart rate was 104 ± 5 bpm in the pigs (65 ± 3 kg). The main outcomes are displayed in Fig. 2: The left ventricular stroke volume increased by 11ml (+21%, p=0.036) with 100% RSA compared to pacing without RSA, while cardiac output increased by 1.14 l/min (+21%, p=0.037). The pressure volume area is proportional to the total myocardial oxygen consumption and decreased by 6234 mmHg*ml (-39%, p=0.004). Cardiac efficiency represents the relative amount of blood being pumped consuming one unit energy and increased by 0.163 (+72%, p=0.033). End-systolic pressure volume relationship demonstrated a non-significant increase by 0.183 mmHg/ml (+45%, p=0.25). Parameters of diastolic function (Tau) did not differ between the groups. Conclusion Restoration of RSA by our newly developed pacing device significantly improved the cardiac contractility/output in our proof-of-principle large animal translational model. Chronic trials will be required to definitively confirm the positive effects of RSA on cardiac remodeling.Fig. 1: Set-up of the animal trials.Fig. 2: Main results (mean/std error)

Impact of beta blockers on perioperative complications in patients undergoing major noncardiac surgery

Abstract Introduction Beta blockers (BB) are broadly used in patients with cardiovascular disease because they are known to decrease myocardial oxygen consumption by decreasing heart rate and myocardial contractility. Pilot studies have shown conflicting results. Therefore, we aimed to evaluate the impact of preoperative BB therapy on (1) the incidence of cardiac perioperative myocardial injury/infarction (PMI) within 48 hours after surgery and (2) long-term MACE within 365 days in patients after major noncardiac surgery. Methods We prospectively included consecutive high-risk patients undergoing inpatient major noncardiac surgery at a university hospital and a hospital, both in Switzerland, who were eligible for the institutional active PMI surveillance and response program. The primary endpoint was PMI due to cardiac causes (type 1 myocardial infarction (MI), tachyarrhythmia, acute heart failure, or type 2 MI) within 3 days after surgery, centrally adjudicated by two independent experts. The secondary endpoint was the occurrence of MACE, defined as a composite of acute myocardial infarction, acute heart failure, life-threatening arrhythmia, and cardiovascular death, within 365 days. We used inverse probability of treatment weighting to account for differences between BB and non-BB users and then performed a univariable logistic regression with cardiac PMI and a univariable Cox proportional hazard model with MACE as a dependent variable. Results Between October 2014 and February 2018, we included 7751 high-risk patients undergoing major inpatient noncardiac surgery. The median age was 74 years and 45% were female. 2856 of 7751 patients (36.8%) received preoperative BB therapy. Patients receiving BB therapy had more cardiovascular comorbidities like known coronary artery disease, atrial fibrillation, or hypertension. After IPTW, we achieved a good balance between patients receiving BB therapy and those who did not. 812 patients (10.5%) had a cardiac PMI within 3 days after surgery. When comparing the patients receiving BB to those that did not, we did not see any difference in the occurrence of cardiac PMI, resulting in a weighted odds ratio of 0.99 (95% Confidence interval [CI] 0.89-1.10). The composite secondary endpoint MACE within 365 days occurred in 9% of all patients. In multivariable analysis, there was no difference between patients receiving BB and those that did not, with a weighted hazard ratio of 1.07 (95% CI 0.86-1.33). Conclusion In our patient cohort, we could not see any difference in cardiac PMI between patients receiving BB therapy and those who did not, suggesting that continuing BB perioperatively is safe but not associated with any benefit. Also after 1 year, we saw no difference in MACE between patients receiving BB therapy versus those who did not.MACE within 365 days

Heterogeneity of patients phenotyped as heart failure with mildly reduced ejection fraction

Abstract Background Current phenotyping of heart failure (HF) is based on the ejection fraction (EF) criterion, resulting into three types including the mildly reduced (mr) category. Little is known about the heterogeneity of the volumetric (ie left ventricular [LV] size) and clinical characteristics (including myocardial oxygen consumption, MVO2) of patients who are assigned to the HFmrEF class. Method The metric EF combines details on end-systolic volume index (ESVi) and end-diastolic volume index (EDVi). Both volumetric measures can be presented in the volume regulation graph (VRG), allowing the graphical inspection of the behavior of EF under a variety of conditions, with stratification options based on age, sex or other clinically relevant determinants. To overcome the limitations intrinsic to ratio-based metrics such as EF, we introduced a logical EF-companion (EFCi), defined as the square root of (ESVi² + EDVi²). In other studies the EFCi has been shown to offer incremental value beyond the single use of EF. Patients LV volumes were determined by biplane angiocardiography in 190 HF patients (69 women), and retrospectively analyzed. Results Average ESVi values for mrEF are 57.9 and 60.2 mL/m² for men (n = 22) and women (n = 10), respectively. The distribution of {EDVi, ESVi} data pairs in the VRG is shown in Figure 1, stratified for women and men. Patients categorized as HFmrEF are indicated by separate markers, and located in the region between the lines that indicate the 40 and 50% limits for EF. The double arrowed yellow bar refers to the wide ESVi range (27 to 118 mL/m²) for the patients within this narrow EF bandwidth. As ESVi refers to the extent of (reverse) remodeling and is associated with MVO2, there is a clear need the consider ESVi or EFCi for patients, in addition to their nearly similar EF values. Figure 2 shows the distribution of EFCi (range 59.5 to 231.8 mL/m2) for all HFmrEF patients, and clearly illustrates the supplementary value of the companion to the ratio-based metric EF. Conclusions As the bandwidth for EF narrows, the specificity of EF decreases and the higher the need to rely on EFCi. Thus, in contrast to the current view indicating that HFmrEF patients form a well-defined rather homogeneous phenotype exhibiting comparable clinically relevant characteristics, we found a relatively pronounced heterogeneity within the HFmrEF phenotype group. Distinguishing individual patients within the HFmrEF phenotype can be realized by considering the newly introduced parameter EFCi. This approach resolves most of the criticism thus far expressed regarding limitations of EF. The proposed additional dimension beyond EF offers a more comprehensive description of these patients, and will allow a personalized analysis based on a more careful characterization. Further investigations are warranted to explore implications for patient management.Figure 1.VRG for HF patients (n = 190)Figure 2.HFmrEF vs EFCi (n = 32)

Impaired cardiac BCAA catabolism associated with impaired myocardial efficiency during exercise in a porcine model with multiple risk factors

Abstract Background Diabetes mellitus (DM), chronic kidney disease (CKD) and consumption of a high-fat diet (HFD), are well known risk factors for diastolic heart failure. We recently developed a multiple comorbidity swine model (MCS), with DM (streptozotocin), HFD and CKD (kidney embolization), and showed that 6 months of sustained hyperglycemia, hypercholesterolemia and kidney dysfunction resulted in inflammation and oxidative stress associated with coronary microvascular dysfunction and left ventricular diastolic dysfunction. Additionally, MCS animals showed impaired myocardial efficiency during exercise as demonstrated by increased myocardial oxygen consumption (Fig. A), suggesting an impairment in myocardial mitochondrial function. Purpose Here we used a combined omics (single nuclei RNA sequencing and proteomics) approach to study the molecular pathways involved in mitochondrial dysfunction. Methods 15 MCS and 10 healthy control female swine were included in the study. Proteome analysis and single nuclei RNA sequencing, was performed on frozen left ventricle myocardial samples. Results Proteome analysis of MCS hearts showed reduced expression of branched-chain amino acid (BCAA) catabolism proteins (Fig. B), most notably BCAT2, MCCC1 and MCCC2. Single nuclei RNA sequencing of a subgroup of the same animals demonstrated a downregulation of these genes specifically in cardiomyocyte subpopulations. Besides being a source of ATP, via oxidative phosphorylation in mitochondria, BCAAs, encompassing essential amino acids (leucine, valine and isoleucine), act as signaling molecules. Thus, increased BCAA levels reduce insulin sensitivity, modulate mitochondrial substrate utilization and impair mitochondrial function, resulting in increased mitochondrial production of reactive oxygen species (ROS). These findings are consistent with our data in the MCS swine indicating that impaired BCAA metabolism was found in the myocardium of animals with comorbidities and were associated with increased ROS levels (8-isoprostane 12.9±0.8 pg/mg protein in MCS vs 10.3±0.5 in healthy animals, P=0.02 by T-test) and impaired myocardial efficiency during exercise (Fig. A). Conclusion Taken together, these findings suggest an essential role of altered BCAA cardiomyocyte metabolism resulting in mitochondrial dysfunction, increased oxidative stress and subsequent alterations in the myocardial function.Fig.

Abstract 14318: Right Ventriculo- Arterial Coupling Assessment by High-Fidelity Hemodynamic Measurements in Patients Undergoing Left Ventricular Assist Device Implantation

Background: The changes in RV function after LVAD placement are not fully understood. RV- PA coupling, defined as the ratio of RV end-systolic to arterial elastances (E ES /E A ), offers unique insight into the cardiopulmonary unit and opportunity to address these knowledge gaps. We present early results from our study investigating RV adaptive changes after LVAD implantation by intraoperative placement of RV conductance catheters. Methods: Conductance catheter, echocardiographic, and hemodynamic data were gathered starting on the day of surgery. We used a 7Fr high-fidelity RV conductance catheter delivered through a 9Fr central venous sheath. P-V loop parameters were obtained before skin incision and after chest closure. Single- beat methods were used for E ES /E A determination. Early RVF was defined according to INTERMACS criteria. Intraoperative pre- and post-implantation echocardiographic and hemodynamic parameters were compared. Results: We present data on the first 14 patients who underwent successful placement of the RV conductance catheter. Moderate or severe RVF occurred in 3 patients (21.4%). Data are presented in the table. While overall E Es (1.2 vs 1.3, p=0.785), E A (1.1 vs 1.3, p=0.154), and RV-PA coupling (E ES /E A ratio 1.1 vs 1.0, p=0.129 ) remained unchanged, several patients underwent dramatic changes, either increase or decrease, in E ES and E A (Figure). Measures of energetic expense, such as stroke work ( SW, correlate of myocardial energy transferred) and pressure-volume area (PVA, correlate of myocardial oxygen consumption) significantly decreased after LVAD implantation. Conclusions: We have shown that RV function assessment using conductance catheters and 3D echocardiography is feasible and able to identify individual responses in RV-PA coupling after LVAD implantation. Continued accrual of data will help identify different phenotypes of RV adaptation and establish a cut-off level of RV-PA uncoupling at which RVF occurs.

Abstract 15111: The Combination of Vagal Nerve Stimulation and Intra-Aortic Balloon Pumping Rapidly Modulates Heart Rate and Cardiac Load While Maintaining Hemodynamics in a Dog Model of Acute Heart Failure

Background: In acute heart failure (AHF) condition, excessive tachycardia increases myocardial oxygen consumption (MVO 2 ). Recently, we have developed an intravenous vagal nerve stimulation (iVNS) catheter which can stimulate right vagal nerve and induce HR reduction (Fig. 1). Since inappropriate bradycardia in AHF condition leads to hemodynamic instability, the use of intra-aortic balloon pumping (IABP) may serve as a beneficial adjunctive therapy for iVNS. Methods: We induced AHF by the direct ethanol injection (0.5-2 ml/kg) to myocardium. The specialized basket catheter was inserted through the right femoral vein and placed in the superior vena cava. The IABP with 20-cc balloon was inserted through left femoral artery. We also calculated MVO 2 by the product of coronary flow and the difference of oxygen saturation between coronary artery and coronary sinus. We compared HR, MVO 2 , and hemodynamics between baseline and 3-min after iVNS (n=11). In addition, we examined the impact of IABP on hemodynamics during iVNS in AHF condition (n=8). Results: The direct ethanol injection increased LAP (+3.6±7.2 mmHg) and decreased left ventricular ejection fraction (-28±9.8%). The iVNS (20Hz, 10-22 V) rapidly reduced HR (-13±6.9%, P&lt;0.01) and MVO2 (-11±8.1%, P&lt;0.05), while slightly decreased CO (-10±7.3%) and increased LAP (+2.0±3.5 mmHg) (Fig. 2). An adding of IABP during iVNS increased CO (1.2±0.24 vs. 1.3±0.30 l/min, P&lt;0.05) and decreased LAP (14±8.6 vs. 13±8.2 mmHg, P&lt;0.05) . Conclusion: The combination of iVNS and IABP shows clinical potential as a novel therapy for effectively modulating excessive cardiac load in cases of unstable hemodynamics.

The mechanism and kinetics of antianginal effect formation after laser therapy course in patients with angina pectoris

Purpose: To assess some mechanisms of antianginal effect formation under low-level infrared laser irradiation in patients with angina pectoris, as well as to clarify the kinetics of this clinical effect after laser therapy course. Materials and methods. 88 male patients, aged 54.2 ± 3.7, with angina pectoris of functional class II–III were examined. 63 patients of the main group had a ten-day course of laser therapy. 25 patients were included in the control group in which laser irradiation was only simulated. At the initial stage and one month after laser therapy or its imitation, and in the main group additionally after 3 and 6 months, bicycle ergometric tests were performed to determine exercise tolerance and evaluate the double product indicator at the level of initial (P1) and maximum (P2) threshold load, if its threshold power exceeded the initial one. Results and discussion. The increase of exercise tolerance was observed in 79.5 % of patients from the main group one month later and in 81.7 % three months later after finishing laser therapy course, with the increase in exercise tolerance by 19.1 W (+ 30.4 %; p = 0.023) and by 22.7 W (36.2 %; p = 0.009), respectively. The antianginal effect lasted for about 6 months of follow-up in 62.0 % of treated patients. The double product indicator reflecting myocardial oxygen consumption at P1 level after laser irradiation had a pronounced downward trend. This indicator increased at maximum load (P2) by 19.1 % (p = 0.04) and by 24.1 % (p = 0.006) during repeated examinations in 1 and 3 months, respectively. By the sixth month of observation, studied parameters returned to the initial levels. There were no statistically significant changes in the studied parameters in patients from the control group. Conclusion. The data obtained indicate that a ten-day course of laser therapy triggers high and long-lasting antianginal effect in patients with angina pectoris. The mechanism of its action is caused with the economization factor of cardiac activity and with the increase of coronary blood flow productivity.

Anesthetic considerations in supravalvular aortic stenosis: A case series

Supravalvular aortic stenosis (SVAS), characterized by elastin arteriopathy, presents either as a localized narrowing at the sinotubular junction or as a diffuse form with additional involvement of the ascending aorta, aortic arch, and its branches. Associated lesions of the aortic valve, coronary artery narrowing, and pulmonary artery stenosis can further complicate the disease process. These patients are inherently at risk for developing myocardial ischemia, particularly in the setting of anesthesia or sedation. The left ventricular hypertrophy, secondary to the obstruction, results in increased left ventricular wall tension and myocardial oxygen consumption. Associated anatomic factors in the coronary arteries can further impair coronary blood flow. Any anesthetic drug that further increases oxygen consumption or decreases the coronary blood flow will result in an imbalance and increase the risk of cardiac arrest. We present a series of three patients with SVAS who were operated at our institute and subsequently discharged with good outcomes. The hemodynamic goal during the perioperative should aim to balance the myocardial oxygen supply-demand ratio. Extreme vigilance and aggressive resuscitative measures are needed to prevent any adverse myocardial event that can happen immediately after anesthetic induction or during periods of intense sympathetic stimulation such as laryngoscopy, sternotomy, aortic cannulation, or during emergence from anesthesia.

Guide to Temporary Mechanical Support in Cardiogenic Shock: Choosing Wisely.

Cardiogenic shock is a multisystem pathology that carries a high mortality rate, and initial pharmacotherapies include the use of vasopressors and inotropes. These agents can increase myocardial oxygen consumption and decrease tissue perfusion that can oftentimes result in a state of refractory cardiogenic shock for which temporary mechanical circulatory support can be considered. Numerous support devices are available, each with its own hemodynamic blueprint. Defining a patient's hemodynamic profile and understanding the phenotype of cardiogenic shock is important in device selection. Careful patient selection incorporating a multidisciplinary team approach should be utilized.

Peculiarities of Systemic Hemodynamics and Autonomic Status in Medical Personnel of PCR-Laboratories with Different Emotional Intelligence

INTRODUCTION: The ongoing pandemic of a new coronavirus infection COVID-19 (COronaVIrus Disease 2019) places high demands on the activity of PCR-laboratories (laboratories performing polymerase chain reaction). The medical personnel experience overloads due to stay in the red zone wearing the individual protection means, and also in association with a high personal responsibility for the result of their work. One of the criteria that is proposed for professional selection with the aim of increasing the effectiveness of the work of personnel of PCR-laboratories, is the emotional quotient (EQ).&#x0D; AIM: To analyze the state of systemic hemodynamics and heart rate variability in medical workers of PCR-laboratories with different emotional intelligence working in condition of COVID-19 pandemic using means of individual protection against the biological factor.&#x0D; MATERIALS AND METHODS: The extent of health risk and tension of adaptation mechanisms during the work were evaluated by parameters of systemic hemodynamics (tonometry, pulse oximetry) and heart rate variability (cardiorhythmography). Thirty three individuals with the working period in a PCR-laboratory from 1 to 33 months were examined. The average age of the participants at the time of inclusion in the study was 32.4 1.44 years. In 33.7%, EQ corresponded to the medium level (81120 points), and in 66.7% to the high level (121168 points).&#x0D; RESULTS: Before the start of the work shift, increased blood supply to tissues in personnel with high EQ was achieved by increased heart activity: cardiac output (CO) 3938.9 ml/min, interquartile range (IQR) = 3404.24230.2 ml/min with the underlying reduction of vessel tone: total peripheral vascular resistance (TPVR) 1922.8 dyn s/cm5, IQR = 1636.52085.8 dyn s/cm5. After the end of the shift, to these compensatory mechanisms (CO 4284.7 ml/min, IQR = 3935.44688.8 ml/min; TPVR 1692.4 dyn s/cm5, IQR = 1584.61903.1 dyn s/cm5), increased myocardial oxygen consumption (MOC; 7917.5 RU, IQR = 7430.28811.0 RU) added as a reaction to the muscular component of labor activity. In individuals with average EQ, these mechanisms were less pronounced in considerable mental stress: before the shift CO 3722.0 ml/min, IQR = 3163.13739.0 ml/min, p = 0.013; TPVR 2303.1 dyn s/cm5, IQR = 2058.12402.1 dyn s/cm5, p = 0.016; after the shift CO 3375.0 ml/min, IQR = 3372.04402.0 ml/min, p = 0.010; TPVR 2010.5 dyn s/cm5, IQR = 1972.62351.9 dyn s/cm5, p = 0.017; MOC 7450.0 RU, IQR = 6653.37867.3 RU, p = 0.023.&#x0D; CONCLUSION: The extent of tension of mechanisms of self-regulation of systemic circulation, apart from characteristics of used technical means and the working regime, significantly depends on the level of emotional intelligence. With this, personnel with high emotional intellect are preferable for the work in the red zone because of lower tension of regulatory mechanisms.