Cardiac Work Research Articles

Role of ATP supply in limiting reserve cardiac power output

Reserve cardiac power output (CPO) is the additional rate of mechanical work done by the heart in maximal exercise compared to the work rate at resting conditions. Recruitment of cardiac work and cardiac output during exercise requires matching mitochondrial ATP synthesis to increases in ATP consumption. We hypothesize that the physiological maximal capacity of the myocardium to do mechanical work is limited by the maximal capacity of myocardial mitochondria to synthesize ATP at free energy levels necessary to drive cardiac contraction.

QT interval prolongation, torsades de pointes and psychotropic medication

QT interval reflects the duration of action potential of myocardial cells. Its prolongation in electrocardiogram is related to risk of torsades de pointes (TdP), a form of polymorphous ventricular tachycardia, and sudden cardiac death, which is one of the main causes of early mortality in psychiatric patients. The fact that only a proportion of patients with drug-induced QT prolongation manifest TdP or die shows that QT prolongation alone is not the perfect biological predictive marker of arrhythmia manifestation. Yet, it continues to be useful but needs to be combined with other known risk factors. This paper is a narrative review based on search in reference books and in PubMed and ScienceDirect databases using the terms [Torsades de pointes OR QT prolongation] AND [Psychotropic drugs OR antipsychotics OR antidepressants]. Its aim is to present basic knowledge about the pathophysiology of TdP arrhythmia and QT prolongation and their relationship with psychotropic drugs. TdP is a relatively slow-rate tachycardia and, in some cases, may stop abruptly without manifestation of clinical symptoms. The diagnosis is based on electrocardiographic findings, the symptoms are similar to those of any tachyarrhythmia and they are related to heart rate and its effects on arterial pressure and cardiac work. QT interval prolongation and TdP result from structural and functional disorders of ion channels and related proteins which are implicated in the process of ventricular repolarization. Psychotropic drugs are commonly used not only in psychiatric patients but in many patients with somatic disease as well. They can affect transmission of electrical impulses from sinus node to ventricular myocardium in various ways and most of its classes prolong QT interval in therapeutic doses or in cases of intoxication. Thus, their careful administration and monitoring of patients, especially hospitalized ones, are of vital importance. More data is available concerning the effects of antipsychotic and antidepressant medication. Among the first group, first generation, classical antipsychotics, especially the lower potency drugs, are considered to carry greater risk. Caution should be exercised when administering thioridazine, haloperidol, pimozide, sertindole and ziprasidone. Among antidepressants, caution is warranted when administering tricyclic antidepressants, citalopram and escitalopram. Among the other psychotropics, much information is available about methadone.

Characteristics of circulatory failure after out-of-hospital cardiac arrest: a prospective cohort study

BackgroundCirculatory failure after out-of-hospital cardiac arrest (OHCA) as part of the postcardiac arrest syndrome (PCAS) is believed to be caused by an initial myocardial depression that later subsides into a...

Myocardial Energy Response to Glyceryl Trinitrate: Physiology Revisited.

Objective: Although intravenous nitrates are commonly used in clinical medicine, they have been shown to increase myocardial oxygen consumption and inhibit complex IV of the electron transport chain. As such we sought to measure whether myocardial energetics were impaired during glyceryl trinitrate (GTN) infusion.Methods: 10 healthy volunteers underwent cardiac magnetic resonance imaging to assess cardiac function and 31phosphorus magnetic resonance spectroscopy to measure Phosphocreatine/ATP (PCr/ATP) ratio and creatine kinase forward rate constant (CK kf) before and during an intravenous infusion of GTN.Results: During GTN infusion, mean arterial pressure (78 ± 7 vs. 65 ± 6 mmHg, p < 0.001), left ventricular (LV) stroke work (7,708 ± 2,782 vs. 6,071 ± 2,660 ml mmHg, p < 0.001), and rate pressure product (7,214 ± 1,051 vs. 6,929 ± 976 mmHg bpm, p = 0.06) all fell. LV ejection fraction increased (61 ± 3 vs. 66 ± 4%, p < 0.001), with cardiac output remaining constant (6.2 ± 1.5 vs. 6.5 ± 1.4 l/min, p = 0.37). Myocardial PCr/ATP fell during GTN infusion (2.17 ± 0.2 vs. 1.99 ± 0.22, p = 0.03) with an increase in both CK kf (0.16 ± 0.07 vs. 0.25 ± 0.1 s−1, p = 0.006) and CK flux (1.8 ± 0.8 vs. 2.6 ± 1.1 μmol/g/s, p = 0.03).Conclusion: During GTN infusion, despite reduced LV stroke work and maintained cardiac output, there was a 44% increase in myocardial ATP delivery through CK. As PCr/ATP fell, this increase in ATP demand coincided with GTN-induced impairment of mitochondrial oxidative phosphorylation. Overall, this suggests that while GTN reduces cardiac work, it does so at the expense of increasing ATP demand beyond the capacity to increase ATP production.

A retrievable, dual-chamber stent protects against warm ischemia of donor organs in a model of donation after circulatory death

BackgroundIschemic injury during the agonal period of donation after circulatory death donors remains a significant barrier to increasing abdominal transplants. A major obstacle has been the inability to improve visceral perfusion, while at the same time respecting the ethics of the organ donor. A retrievable dual-chamber stentgraft could potentially isolate the organ perfusion from systemic hypotension and hypoxia, without increasing cardiac work or committing the donor. MethodsRetrievable dumbbell-shaped stents were laser welded from nitinol wire and covered with polytetrafluoroethylene. Yorkshire pigs were assigned to either agonal control or dumbbell-shaped dual-chamber stentgraft. A central lumen maintained aortic flow, while an outer visceral chamber was perfused with oxygenated blood. A 1-hour agonal phase of hypoxia and hypotension was simulated. Stents were removed by simple sheath advancement. Cardiac monitoring, labs, and visceral flow were recorded followed by recovery of the animal to a goal of 48 hours. ResultsCardiac stress did not increase during stent deployment. Visceral pO2 and flow were dramatically improved in stented animal relative to control animals. Five of 7 control animals were killed after renal failure complications, whereas all stent animals survived. Histology confirmed increased ischemic changes among control kidneys compared to stented animals. ConclusionA dual-chamber stent improved outcomes after a simulated agonal phase. The stent did not increase cardiac work, thus respecting a key ethical consideration. The ability of a dual-chamber stent to prevent ischemia during organ recovery may become a powerful tool to address the critical donor organ shortage.

Sympathetic regulation of coronary circulation during handgrip exercise and isolated muscle metaboreflex activation in men.

What is the central question of this study? What is the role of β- and α-adrenergic receptors in the control of the coronary circulation during handgrip exercise and isolated muscle metaboreflex activation in humans? What is the main finding and its importance? β-Adrenergic receptor, but not α-adrenergic receptor, blockade significantly blunted the increases in coronary blood velocity observed during handgrip. Coronary blood velocity was unchanged from baseline during isolated muscle metaboreflex activation. This highlights the important role of β-adrenergic receptors in the coronary circulation during handgrip in humans, and the more limited involvement of the α-adrenergic receptors. We sought to investigate the role of β- and α-adrenergic receptors in coronary circulation during static handgrip exercise and isolated muscle metaboreflex activation in humans. Seventeen healthy young men underwent two experimental sessions, consisting of 3min of static handgrip exercise at a target force of 40% maximum voluntary force (not achieved for the full 3min), and 3min of metaboreflex activation (post-exercise ischaemia) in two conditions: (1) control and β-blockade (oral propranolol), and (2) control and α-blockade (oral prazosin). In both sessions, coronary blood velocity (CBV, echocardiography) was increased during handgrip (Δ8.0±7.4cms-1 ) but unchanged with metaboreflex activation (Δ2.5±3.2cms-1 ) under control conditions. β-Blockade abolished the increase in CBV during handgrip, while CBV was unchanged from control with α-blockade. Cardiac work, estimated from rate pressure product (RPP; systolic blood pressure multiplied by heart rate), increased during handgrip and metaboreflex in control conditions in both sessions. β-Blockade reduced RPP responses to handgrip and metaboreflex, whereas α-blockade increased RPP, but the responses to handgrip and metaboreflex were unchanged. CBV and RPP were only significantly correlated during handgrip under control (r=0.71, P<0.01) and β-blockade (r=0.54, P=0.03) conditions, and the slope of this relationship was unaltered with β-blockade. Collectively, these findings indicate that β-adrenergic receptors play the primary role to the increase of coronary circulation during handgrip exercise, but CBV is unchanged with metaboreflex activation, while α-adrenergic receptor stimulation seems to exert no effect in the control of the coronary circulation during handgrip exercise and isolated muscle metaboreflex activation in humans.

Abstract 9649: Challenging The Dogma: Increasing Cardiac Fatty Acid Rather Than Glucose Utilisation Improves Cardiac Function in Severe Non-Ischaemic Heart Failure With Reduced Ejection Fraction (HFrEF)

Introduction: Based on the premise that in HFrEF the heart is metabolically inflexible and oxygen limited, current metabolic therapies aim to increase glucose oxidation. However, if the human failing heart is neither inflexible nor oxygen limited, this approach is called into question. Methods: During either insulin-glucose (GI) or Intralipid infusion (IL) (random order), 20 non-ischaemic HFrEF patients underwent cardiac magnetic resonance imaging and 31 P-spectroscopy at rest and during dobutamine infusion (mean 100 bpm). 10 patients underwent invasive arteriovenous blood sampling (left main–coronary sinus), coronary flow and left ventricular (LV) pressure-volume loop measurements, during GI and IL infusion, at rest and during rapid atrial pacing (100 bpm). Results: At rest, during IL fatty acid (FA) uptake was higher (61±53 vs 5±13 μmol/min, p=0.03) and during GI, glucose uptake was higher (97±53 vs 45±36 μmol/min, p=0.04). Compared to fasting conditions, LV ejection fraction was higher during IL (40±9 vs 35±9%, p&lt;0.001), but unchanged during GI (34±8%). Cardiac work was higher during IL (466±148 vs 549±163 mmHg.L/min, p=0.02), as was LV developed pressure (by 6mmHg, p=0.049). At rest, during IL, myocardial oxygen uptake (MVO 2 20±9 vs 15±9 ml/min, p=0.05) and phosphocreatine/ATP ratio (PCr/ATP 2.01±0.33 vs 1.86±0.25, p=0.02) were higher and lactate was consumed. Stress cardiac work was again higher during IL (by 62mmHg.L/min, p=0.009). Despite higher cardiac work and MVO 2 during IL at stress, PCr/ATP was again unchanged and lactate consumed. During GI, with atrial pacing (100 bpm) FA uptake was increased &gt;4 fold (5±14 vs 24±32 μmol/min, p=0.04), suggesting selective FA preference. Conclusions: In severe HFrEF cardiac metabolic flexibility is retained changing substrate use to match arterial supply and workload. At rest and stress, increased FA uptake, but not glucose is associated with increased contractility. Cardiac preference to FA was observed during stress. Despite increased MVO 2 , the phosphocreatine pool remains stable and lactate is consumed, showing that mitochondrial oxygen supply was not fixed or limited. This challenges existing dogma, suggesting increasing FA oxidation and not glucose should be the therapeutic target in HFrEF.

Abstract 9321: Cardiac Work and End-Organ Perfusion During Biventricular Compared to Left Ventricular Impella and Norepinephrine Support in a Porcine Model of Severe Cardiogenic Shock

Background: Vasopressors are often combined with left ventricular (LV) mechanical support in severe cardiogenic shock to increase end-organ perfusion. Biventricular mechanical support might improve end-organ perfusion at lower cardiac workload compared to LV mechanical support and vasopressor infusion in severe cardiogenic shock. Aim: To compare LV and right ventricular (RV) total cardiac work (pressure-volume area x heart rate x 10 3 ) and organ-specific venous oxygen saturations from the pulmonary artery (SvO 2 ), kidney- and cerebral- veins in pigs with cardiogenic shock treated with biventricular (Bipella) versus ImpellaCP + norepinephrine 0.10 μg/kg/min (Imp+NE). Methods: Cardiogenic shock was induced by injections of microspheres into the left main coronary artery in eight pigs (approx. 70 kg). From conductance catheters in both ventricles, cardiac workload was calculated, and oxygen saturations were attained from the pulmonary artery, internal jugular- and kidney vein. Pigs were allocated in a crossover model to Bipella for 60 minutes (n=4) or Imp+NE for 30 minutes (n=4) and after completion shifted to the opposite treatment. Results are presented as median(Q1;Q3). Results: Bipella effectively unloaded the LV with reduction in LV work compared to Imp+NE (569[410-685] vs 357[206-509] 10 3 ml x mmHg/min, p=0.0078) while RV work was comparable (p=0.74). A significant increase in SvO 2 (66[63-73] vs 49[44-58]%, p=0.01) and cerebral venous oxygen saturations (71[63-77] vs 62[48-66]%, p=0.016) was observed during Imp+NE compared to Bipella, whereas no difference in kidney oxygen saturations was demonstrated (p=0.31). Conclusion: In this porcine study of cardiogenic shock due to left main coronary ischemia, Bipella decreased LV workload, but systemic oxygen delivery was not optimal (Figure). Imp+NE provided a higher LV workload balanced by an improvement in cerebral- and mixed venous oxygen saturation.

Abstract 12881: Abnormal Retinal Perfusion Indices by Optical Coherence Tomography Angiography (OCTA) Associate With Abnormal Coronary Flow Reserve

Background: Retinal microvascular evaluation could serve as a marker for cardiovascular disease risk. OCTA is a noninvasive method to quantitatively assess the retinal microvasculature. Coronary flow reserve (CFR), an integrated measure of focal, diffuse, and small-vessel coronary artery disease, identifies patients at risk for cardiac death. We aimed to identify associations between OCTA findings and CFR in patients undergoing cardiac positron emission tomography (PET) testing. Methods: Subjects (n=60) underwent a stress myocardial perfusion PET scan to quantify CFR and OCTA of both eyes on same day. CFR is the ratio of myocardial blood flow at peak stress compared to rest and adjusted for baseline cardiac work. OCTA scans were analyzed using a custom-built software to quantify foveal avascular zone (FAZ) geometry and vessel density metrics in the retina, reflecting retinal microvasculature. We used Spearman to correlate markers of retinal microvasculature with CFR. Results: Demographics of enrolled subjects are shown in Table I. Baseline cardiac risk factors were common and 22 (37%) subjects had an abnormal stress test. Retinal perfusion as indicated by the vessel index (ρ=0.35, p=0.006) and vessel diameter index (ρ=0.27, p=0.039) in the superficial 6x6 mm slabs were positively correlated with CFR. There was a trend towards negative association between FAZ area in the retina slab and CFR (ρ= -0.17, p=0.1). Conclusions: CFR was correlated with retinal perfusion indices based on OCTA, suggesting a relationship between coronary and retinal vascular health. These data provide potential insight into systemic vascular health and could provide an additional tool to assess cardiac risk.

CONTROL OF INTRAOPERATIVE SHIVERING UNDER SPINAL ANAESTHESIA- A PROSPECTIVE RANDOMIZED COMPARATIVE STUDY OF NALBUPHINE WITH TRAMADOL

spinal anesthesia is a widely used technique for both elective and emergency surgeries. Shivering is one of the most commonly recognized complications of the central neuraxial blockade because of impairment of thermoregulatory control, reported in 40%-70% of the patients undergoing surgery under spinal anaesthesia. Post-anesthetic shivering is defined as an involuntary,spontaneous,rhythmic oscillating muscle hyperactivity that increases metabolic heat production up to 600% after anesthesia. Shivering during neuraxial anesthesia is a common issue that could have possibly adverse impacts, for example, increased oxygen consumption, carbon dioxide production, lung ventilation and cardiac work, as well as causing diminished mixed venous oxygen saturation. Spinal anesthesia impedes the thermoregulatory system by restraining tonic vasoconstriction which assumes significant role in the regulation of temperature

Myocardial efficiency in patients with different aetiologies and stages of heart failure.

Myocardial external efficiency (MEE) is the ratio of cardiac work in relation with energy expenditure. We studied MEE in patients with different aetiologies and stages of heart failure (HF) to discover the role and causes of deranged MEE. In addition, we explored the impact of patient characteristics such as sex, body mass index (BMI), and age on myocardial energetics. Cardiac energetic profiles were assessed with 11C-acetate positron emission tomography (PET) and left ventricular ejection fraction (LVEF) was acquired with echocardiography. MEE was studied in 121 participants: healthy controls (n = 20); HF patients with reduced (HFrEF; n = 25) and mildly reduced (HFmrEF; n = 23) LVEF; and patients with asymptomatic (AS-asymp; n = 38) and symptomatic (AS-symp; n = 15) aortic stenosis (AS). Reduced MEE coincided with symptoms of HF irrespective of aetiology and declined in tandem with deteriorating LVEF. Patients with AS-symp and HFmrEF had reduced MEE as compared with controls (22.2 ± 4.9%, P = 0.041 and 20.0 ± 4.2%, P < 0.001 vs. 26.1 ± 5.8% in controls) and a further decline was observed in patients with HFrEF (14.7 ± 6.3%, P < 0.001). Disproportionate left ventricular hypertrophy was a major cause of reduced MEE. Female sex (P < 0.001), a lower BMI (P = 0.001), and advanced age (P = 0.03) were associated with a lower MEE. MEE was reduced in patients with HFrEF, HFmrEF, and HF due to pressure overload and MEE may therefore constitute a treatment target in HF. Patients with LVH, advanced age, female sex, and low BMI had more pronounced reduction in MEE and personalized treatment within these patient subgroups could be relevant.

Cardiovascular Side Effects of Chimeric Antigen Receptor (CAR) T-Cell Products: A Single Center Experience in a Minority Rich, Ethnically Diverse Real-World Cohort

Introduction:Axicabtagene ciloleucel (Axi-Cel), an autologous anti-CD19 chimeric antigen receptor (CAR) T-cell therapy demonstrated efficacy in patients with refractory large B cell lymphoma when conventional treatments failed. Cardiovascular side effects of CAR-T therapy that have been noticed so far include hypotension, left ventricular dysfunction, heart failure and cardiogenic shock in settings of CRS. We aimed to assess the cardiovascular side effects in a racially/ ethnically diverse patient population who underwent CAR-T cell therapy.Methods:This study included thirty-four consecutive adult patients who underwent treatment with CAR-T cell product Axi-Cel at an academic health system between 2018-2021. We performed detailed chart reviews and collected information related to the age, gender, hematological malignancy diagnosis, other medical comorbidities, therapeutic regimens, pretreatment cardiac risk factors, development of CRS with grading , pre and post treatment electrocardiograms ( EKG), transthoracic echocardiograms( TTE) , death, cause of death, and duration between administration of CAR-T products and death of the patients . We collected data pertaining to development of hypotension, EKG changes, arrhythmias, left ventricular systolic dysfunction, heart failure (HF), acute cardiac syndrome (ACS), troponin elevation, echocardiographic changes post CAR-T cell therapy, and follow up visits after 60 days to get information pertaining to development of hypotension, tachycardia or SOB, need for further cardiac work up, and cardiology referral.Results:Mean age of our study participants was 65 years ranging between ages of 30 and 84 years with 38 % (13/34) female and 62% (21/34) male study participants. Study population was predominantly Hispanic, white and African American with percentages of 35% (12/34), 32% (11/34), 26 %(9/34) respectively followed by categories Asian 2.9% (1/34) and other at 2.9 %( 1/34). Sixty seven percent (22/37) patients had primary diffuse large B cell lymphoma (DLBCL) and 32% (11/34) had different primary malignancy with transformation into DLBCL. Thirty eight percent individuals had received autologous stem cell transplant. Sixty one percent (21/34) of our study participants developed cytokine release syndrome, with CRS grades 1-3 in 57% (12/29), 25% (08/21) and 4.7% (1/21) respectively. Thirty four percent (09/34) study participants died after cellular therapy. Septic shock and disease progression each were primary cause of death in 55 % (5/9) of patients, followed by respiratory failure in 22% (2/9) and ventricular fibrillation leading to cardiac arrest in 11% (1/9) of the patients. Mean duration of time between administration of therapy and death was 70 days. The cardiovascular effects noted immediately post CAR-T treatment and observations from follow up oncology visits are listed in Table 1. Troponin elevation was noticed in two study participants in settings of CRS, but one participant exhibited troponin elevation in absence of CRS. Seventeen percent of patients (6/34) developed left ventricular dysfunction after Axi-Cel. Most of them had concurrent CRS but one case of fatal heart failure occurred in absence of CRS. Three patients developed fatal arrhythmias post CAR-T therapy (1- Non sustained ventricular tachycardia in settings of CRS, 2- supraventricular tachycardia in settings of CRS, and 3- ventricular tachycardia needing defibrillation without CRS). Only one patient developed ACS in settings of CRS which lead to patient's demise.Conclusions: In a real world, minority rich cohort, we observed that a significant number of our patients had preexisting cardiovascular findings including abnormal EKG (30% excluding sinus tachycardia) or abnormal echocardiographic findings (46%). Hypotension (68%) and sinus tachycardia (59%) were the most commonly observed cardiovascular toxicities. Although Axi-Cel was in general safe and well tolerated, we observed cardiovascular side effects associated with and independent of CRS. Notably, six patients (17%) developed left ventricular dysfunction including one fatality which was independent of CRS. There was only one fatal coronary syndrome and two cases of troponin elevation in our series. Our study stresses the importance of a thorough cardio-oncology evaluation before proceeding with cellular therapies as well as involved follow up during and after hospitalization. [Display omitted] DisclosuresGritsman: iOnctura: Research Funding. Shastri: Kymera Therapeutics: Research Funding; Onclive: Honoraria; Guidepoint: Consultancy; GLC: Consultancy. Verma: BMS: Research Funding; GSK: Research Funding; Incyte: Research Funding; Medpacto: Research Funding; Curis: Research Funding; Eli Lilly: Research Funding; Stelexis: Consultancy, Current equity holder in publicly-traded company; Novartis: Consultancy; Acceleron: Consultancy; Celgene: Consultancy; Stelexis: Current equity holder in publicly-traded company; Throws Exception: Current equity holder in publicly-traded company.

Application of beta-blockers in burn management

Severe burn injuries cause chronic inflammation, which produces a subsequent hypermetabolic response that starts immediately and persists for at least 3 years. The hypermetabolic state, which is thought to be due to postburn elevations of endogenous catecholamines and cortisol, is associated with a number of harmful physiologic derangements including immunosuppression, impaired wound healing, muscle catabolism, and hepatic dysfunction. Beta-blockers have become first line agents for reducing these adverse effects of hypermetabolism in severe burns. This review discusses the underlying pharmacological mechanisms demonstrated by clinical studies evaluating the safety and efficacy of beta-blockers in the management of burn injuries. A literature search was performed using the PubMed database to identify articles on beta-blockers and burn management. The review yielded 33 relevant results consisting of randomized controlled trials, original research articles, and meta-analyses in pediatric and adult burn patients. Propranolol administration reduced insulin resistance, lipolysis, proteolysis, cardiac work, and bone loss resulting from burn-associated hypermetabolism. Propranolol also effectively reduced myocardial stress, resting energy expenditure, and central deposition of fat. Recent studies have begun to evaluate incorporation of anabolic agents and rehabilitative exercise therapy. However, at this time propranolol continues to be the most effective therapy for reducing the hypermetabolic response and other morbidities resulting from burn injuries.

Resident stem cells in the heart.

Cardiovascular disease is the leading cause of mobility and morality worldwide, in which the ischemic heart disease is the most common type of the diseases. During last decade, a major progress in the study of the pathogenesis of heart disease has been achieved. For example, the discovery of adult stem/progenitor cells in the heart and vessel tissues may play a role in tissue regeneration. However, the issue of 31 retractions for cardiac stem cell work has caused a "storm of trust" in the heart stem cell field, in which both founders and scientists have become cautious and conservative in stem cell research of the heart. Despite that the existence of adult cardiac stem cells has been denied, recent studies confirmed that there are many other resident stem/progenitor cells in adult heart. Although these cells cannot differentiate into cardiomyocytes, the role they played in heart repair after injury should not be ignored. The purpose of this short article is to briefly review the current research progress in resident stem/progenitor cells in the heart, to discuss how they function during cardiac repair and to point out unanswered questions in the research field.

Saphenion®: Oxygen Multi-Step Therapy in Varicose Veins: Improvement of the Microcirculation- Our Prospective Study Results in 118 Cases Over 6 Months

Oxygen multi-step therapy for Varicose Veins: Oxygen as an energy carrier, all mechanisms in the human organism during growth, its maintenance and its physical and mental activity require energy. This becomes particularly clear to the patient during cardiac work, breathing work in the lungs, skeletal muscles and intellectual work. The pathology of the microcirculation in the capillaries depends largely on the oxygen partial pressure and on the blood pressure in the supplying arteries and the high pressure in the draining veins.

Automated non-invasive pressure-volume loop analysis of cardiac aging in a large cohort of healthy community dwellers

Abstract Background/Introduction Pressure-volume loops (PVloops) provide a wealth of information on cardiac function that is not readily available from cardiac imaging alone. Methods To estimate left ventricular (LV) PVloops non-invasively have been available, but have so far not been used to interrogate ventricular function in large patient cohorts, due to the complexity of estimating PVloops. A new method was recently validated that construct PVloops non-invasively from cine cardiac magnetic resonance (CMR), based on the time-varying elastance model [1]. At the same time, we have validated a framework for automated, quality controlled analysis of cine CMR in large cohorts of patients/subjects [2]. Combining these two methods could automated PVloop estimation, enabling analysis of ventricular pressure-volume relationships in large study populations. Purpose Evaluate if CMR-based non-invasive PVloops can be used to interrogate the impact of cardiac ageing on LV function occurring in a large population of healthy community dwellers. Methods Non-invasive PVloops were calculated from a full cardiac cycle LV volume curve and brachial blood pressure data using a recently validated method based on the time-varying elastance model [1], in 7,650 healthy community dwellers from the UKBiobank population study. The LV volume curve was automatically obtained using our state-of-the-art, quality controlled deep learning (DL) based cine CMR analysis framework [2]. External Work, pressure-volume-area (PVA), end-systolic pressure (Pes), ventricular elastance (Ees, an estimate of contractility) and arterial elastance (Ea) and energy per ejected volume (EEV: PVA/ stroke volume) were calculated from the PVloops. We performed univariate regression between PVloop parameters and age. We also calculated the additional impact of cardiovascular risk-factors in a multivariate analysis. Results See results in table 1. With age, LV volumes fall (p&amp;lt;0.001) in healthy subjects, while systolic blood pressure and Pes increases (both p&amp;lt;0.001). As a result of the higher afterload, PVA (p=0.894) and EW (p=0.499) do not significantly change with age despite a lower SV. Arterial elastance (Ea) increased, and so did contractility, as measured by Ees (p&amp;lt;0.001). Due to all these changes, EEV increased with age (p&amp;lt;0.001). In multivariate analysis, cardiovascular risk factors hypercholesterolemia and hypertension negatively impacted Pes, PVA, Ees and EEV. Diabetes and smoking habits did not. Conclusion Non-invasive CMR-based PVloop analyses capture the impact of known changes occurring during cardiac ageing on cardiac work, contractility and energetic expenditure. Obtaining PVloops automatically using our AI analysis system in this large cohort of healthy subjects allows to formulate reference for assessment of cardiac disease. Funding Acknowledgement Type of funding sources: Public grant(s) – National budget only. Main funding source(s): The authors acknowledge financial support (support) the National Institute for Health Research (NIHR) Cardiovascular MedTech Co-operative (previously existing as the Cardiovascular Healthcare Technology Co-operative 2012 - 2017) award to the Guy's and St Thomas' NHS Foundation Trust, in partnership with King's College London and the NIHR comprehensive Biomedical Research Centre of the Guy's &amp; St Thomas' NHS Foundation Trust. The views expressed are those of the author(s) and not necessarily those of the NHS, the NIHR or the Department of Health Univariate regression analysisExample of estimated PV loop

Mechanoenergetic coupling in heart failure with preserved, mid-range and reduced left ventricular ejection fraction

Abstract Background Heart failure (HF) classification based on left ventricular ejection fraction (LVEF) can vary because of changes in filling pressures, afterload, and contractile function. 11C-acetate positron emission tomography (PET) provides a load-independent measure of myocardial external efficiency (MEE) by simultaneous assessment of myocardial oxygen consumption (MVO2), cardiac work, left ventricular mass (LVM), end-systolic wall stress (ESWS), and myocardial blood flow (MBF). Purpose We aimed to characterize mechanoenergetic derangements in patients with HF and to study its interrelation with age, sex and obesity. Methods MEE was measured in 121 participants with 11C-acetate PET, and LVEF was acquired with echocardiography. We investigated healthy controls (n=20) and patients with HF and reduced LVEF &amp;lt;40% (HFrEF; n=25), mid-range LVEF 40–49% (HFmrEF; n=23), as well as patients with asymptomatic aortic valve stenosis (AS) and LVEF ≥50% (AS-asymp; n=38), and symptomatic AS and LVEF ≥50% (defined as HF with preserved LVEF (HFpEF); n=15). Results MEE declined in tandem with reduced LVEF from HFpEF and HFmrEF to HFrEF (p=0.041, p&amp;lt;0.001, and p&amp;lt;0.001 versus control, respectively; Figure 1). Impaired MEE was aggravated with increasing LVM (p=0.001) due to a disproportionate increase in overall left ventricular MVO2. In a multivariate analysis, female sex (p&amp;lt;0.001), a lower body mass index (p&amp;lt;0.001), and advanced age (p=0.01) were associated with a lower MEE (Figure 2). HFpEF, HFmrEF, and HFrEF patients had distinct energetic profiles involving MEE, MVO2, MBF, ESWS, and LVM (Figure 2). Conclusions Mechanoenergetic uncoupling was evident in every clinical state within the HF syndrome and associated with left ventricular hypertrophy and progressive systolic dysfunction. Sex, age, and obesity impacted myocardial energetics. To date, the present study is the largest investigation of mechanoenergetic coupling across several categories of patients with heart failure. 11C-acetate PET extends our pathophysiological comprehension of the HF syndrome beyond LVEF. Funding Acknowledgement Type of funding sources: Foundation. Main funding source(s): The Danish Heart FoundationThe Lundbeck Foundation Relationship between LVEF and MEEMyocardial energetics in heart failure

Myocardial efficiency in severe asymptomatic primary mitral regurgitation: relation to quantitative measures of regurgitation

Abstract Objectives To study the association of myocardial external efficiency (MEE) in mitral regurgitation (MR) towards routinely used quantitative indicators of disease severity and progression. Background Quantitative assessment of LV function and regurgitation in asymptomatic severe primary MR is crucial for management. MEE is a load-independent indicator of mechano-energetic coupling and can be measured non-invasively using 11C-acetate positron emission tomography (PET). The role of MEE in this setting has not been studied. Methods 48 asymptomatic patients with severe primary mitral regurgitation underwent PET, echo, and CMR on the same day. MEE was automatically derived from PET as the ratio of cardiac work (cardiac output * mean arterial pressure) and total left ventricular (LV) oxygen consumption (mean MVO2 * LV mass). LV function and mitral regurgitant volumes (RegVol) were measured by echo and CMR. MEE in MR was compared to healthy volunteers (n=9). MEE and parameters of regurgitation severity and of LV volumes and function were studied as predictors of outcome (valve surgery or death). Results MEE was reduced in MR (21.5±4.2%) vs healthy volunteers (32.0±5.6%, p&amp;lt;0.001) and showed weak but significant correlations (r2&amp;lt;0.25) with regurgitation severity and LV volumes. There were 23 cardiac events (valve surgery: 22; cardiovascular death: 1) during follow-up (median 2.7 years, IQR 1.9–3.2). Univariate Cox models showed that MEE, echocardiographic left atrial volume as well as RegVol and LV ventricular volumes from both echo and CMR were significant outcome predictors (all p&amp;lt;0.05), while LVEF and NT-pro-BNP were not (p&amp;gt;0.05). Prediction by MEE was not affected by age, sex or BMI. When categorically divided by the median MEE was a strong predictor in Kaplan-Meier analysis (log-rank p=0.0004, figure 1) and remained independently significant, compared to all other univariate predictors in bivariate Cox models. Conclusions This study suggests an important role of energetic insufficiency in progression of asymptomatic severe primary MR. Reduced MEE was linked to outcome independently of standard functional measures of regurgitation severity or left ventricular size and function. Strategies for improvement of myocardial energetics in MR are warranted. Funding Acknowledgement Type of funding sources: Public grant(s) – National budget only. Main funding source(s): Swedish Heart-Lung Foundation Figure 1

Low myocardial mechano-energetic efficiency is an independent predictor of prognosis in advanced chronic liver disease.

We aimed at investigating if a low myocardial mechano-energetic efficiency (MEE) with energy waste could be a feature of cirrhotic cardiomyopathy and predictive of poor prognosis. We retrospectively interrogated a large data set of 115 cirrhotic patients followed up for 6 years and compared with 50 healthy controls. Echocardiographic and haemodynamic parameters were assessed at baseline according with current guidelines. MEE was estimated by echocardiographic stroke volume (z-derived)/(heart rate × 0.6). Cirrhotic patients presented low peripheral vascular resistance, a compensatory hyperdynamic syndrome with increased cardiac work, left atrial and left ventricular (LV) dimension and mass. Systolic parameters and MEE were similar between patients and controls. Patients with cirrhosis and refractory ascites showed significantly lower MEE compared with both patients with treatable ascites and patients without ascites (1.68 ± 0.47 vs. 1.98 ± 0.64 and 1.80 ± 0.37 ml/s; P < 0.05). Increased age and heart rate and reduced body weight, cardiac dimension and work significantly correlated with lower MEE, mostly when compared nonalcoholic with alcoholic cirrhosis (1.65 ± 0.42 vs. 1.95 ± 0.56 ml/s respectively; P = 0.002). Among the cardiovascular parameters left atrium enlargement and reduced MEE were independent predictors of death. In advanced chronic liver disease left ventricular performance is blunted due to an energetically inefficient cardiac mechanical work which correlates with a poor prognosis. Therefore, the simple basal assessment of MEE can identify patients with a worst prognosis which requires a close follow-up.

Stellaria media tea protects against diabetes-induced cardiac dysfunction in rats without affecting glucose tolerance

Background and aimCommon chickweed (Stellaria media) tea has traditionally been applied for treatment of various metabolic diseases including diabetes in folk medicine; however, experimental evidence to support this practice is lacking. Therefore, we aimed to assess the effect of Stellaria media tea on glucose homeostasis and cardiac performance in a rat model of diabetes. Experimental procedureHot water extract of Stellaria media herb were analyzed and used in this study, where diabetes was induced by fructose-enriched diet supplemented with a single injection of streptozotocin. Half of the animals received Stellaria media tea (100 mg/kg) by oral gavage. At the end of the 20-week experimental period, blood samples were collected and isolated working heart perfusions were performed. Results and conclusionCompared to the animals receiving standard chow, serum fasting glucose level was increased and glucose tolerance was diminished in diabetic rats. Stellaria media tea did not affect significantly fasting hyperglycemia and glucose intolerance; however, it attenuated diabetes-induced deterioration of cardiac output and cardiac work. Analysis of the chemical composition of Stellaria media tea suggested the presence of rutin and various apigenin glycosides which have been reported to alleviate diabetic cardiomyopathy. Moreover, Stellaria media prevented diabetes-induced increase in cardiac STAT3 phosphorylation. We demonstrated for the first time that Stellaria media tea may beneficially affect cardiac dysfunction induced by diabetes without improvement of glucose homeostasis. Rutin and/or apigenin glycosides as well as modulation of STAT3 signaling may be implicated in the protection of Stellaria media tea against diabetic cardiomyopathy.