Increase In Cardiac Workload Research Articles

Cardiovascular effects of long-duration space flight.

Early studies exploring the physiological effects of space travel have indicated the body's capacity for reversible adaptation. However, the impact of long-duration spaceflight, exceeding 6 months, presents more intricate challenges. Extended exposure to microgravity and radiation profoundly affects the CV system. Notable phenomena include fluid shifts toward the head and modified arterial pressure. These changes disrupt blood pressure regulation and elevate cardiac output. Additionally, the loss of venous compression leads to a reduction in central venous pressure. The displacement of fluid from the vascular system to the interstitium, driven by baroreceptor stimulation, results in a 10%-15% decline in plasma volume. Intriguingly, despite potential increases in cardiac workload, cardiac muscle atrophy and perplexing variations in hematocrit levels have been observed. The mechanism underlying atrophy appears to involve a shift in protein synthesis from the endoplasmic reticulum to the mitochondria via mortalin-mediated mechanisms. Instances of arrhythmias have been recurrently documented, although generally nonlethal, in both Russian and American space missions. Long-duration spaceflight has been associated with the prolongation of the QT interval, particularly in extended missions. Exposure of the heart to the proton and heavy ion radiation pervasive in deep space contributes to coronary artery degeneration, augmented aortic stiffness, and carotid intima thickening through collagen-mediated processes. Moreover, it accelerates the onset of atherosclerosis and triggers proinflammatory responses. Upon reentry, astronauts frequently experience orthostatic intolerance and altered sympathetic responses, which bear potential hazards in scenarios requiring rapid mobilization or evacuation. Consequently, careful monitoring of these cardiac risks is imperative for forthcoming missions. While early studies illuminate the adaptability of the body to space travel's challenges, the intricacies of long-duration missions and their effects on the CV system necessitate continued investigation and vigilance to ensure astronaut health and mission success.

IGF-1 boosts mitochondrial function by a Ca2+ uptake-dependent mechanism in cultured human and rat cardiomyocytes.

A physiological increase in cardiac workload results in adaptive cardiac remodeling, characterized by increased oxidative metabolism and improvements in cardiac performance. Insulin-like growth factor-1 (IGF-1) has been identified as a critical regulator of physiological cardiac growth, but its precise role in cardiometabolic adaptations to physiological stress remains unresolved. Mitochondrial calcium (Ca2+) handling has been proposed to be required for sustaining key mitochondrial dehydrogenase activity and energy production during increased workload conditions, thus ensuring the adaptive cardiac response. We hypothesized that IGF-1 enhances mitochondrial energy production through a Ca2+-dependent mechanism to ensure adaptive cardiomyocyte growth. We found that stimulation with IGF-1 resulted in increased mitochondrial Ca2+ uptake in neonatal rat ventricular myocytes and human embryonic stem cell-derived cardiomyocytes, estimated by fluorescence microscopy and indirectly by a reduction in the pyruvate dehydrogenase phosphorylation. We showed that IGF-1 modulated the expression of mitochondrial Ca2+ uniporter (MCU) complex subunits and increased the mitochondrial membrane potential; consistent with higher MCU-mediated Ca2+ transport. Finally, we showed that IGF-1 improved mitochondrial respiration through a mechanism dependent on MCU-mediated Ca2+ transport. In conclusion, IGF-1-induced mitochondrial Ca2+ uptake is required to boost oxidative metabolism during cardiomyocyte adaptive growth.

Manipulation of cardiomyocyte MCU expression reveals distinct consequences of mitochondrial calcium uptake in early versus late adaptation to sustained stress

Rapid mitochondrial calcium (mCa2+) uptake through the mitochondrial calcium uniporter channel (mtCU) matches ATP production to acute increases in cardiac workload and energy demand, but excessive Ca2+ uptake during stress such as ischemia-reperfusion injury initiates permeability transition and cell death.

The music therapy effectiveness in hypertensive patients with acute myocardial infarction after previous coronary artery bypass surgery; 18-year experience of the MUSIC study

Abstract Patients who have clinical evidence of hypertension (HT) after coronary artery bypass surgery (CABS) have a poor prognosis in expression of acute myocardial infarction (AMI), as one of the MACE. Unrelieved anxiety can produce an increase in sympathetic nervous system activity leading to an increase in cardiac workload. The purpose of this study was to evaluate the effectiveness of music therapy on prognosis of patients with HT and AMI, after CABS. Methods 314 patients (males 78.4%, mean age 59.8±1.2 yrs) with AMI after previous CABS have been selected from the patients consecutively submitted from January 2003 to January 2019. HT was registered in 166 (53.0%) pts with AMI after previous CABS. All patients with HT were randomized and divided in 2 groups: Study group of 83 patients treated with music therapy and Control group of 83 patients with no music therapy. Each patient in study group underwent two sessions of medical therapy (12 minutes) in a day. Both groups were similar in baselines, post-AMI characteristics and post-AMI medical therapy. The plasma cytokine and catecholamine were measured in both groups. Results In the Study group, heart rate was significantly decreased by music therapy (p=0.0196). In the Control group, there were no significant changes in heart rate. Among cytokines (p=0.0160), plasma interleukin-6 (IL-6) (p=0.0179) in the Study group was significantly lower than those in the Control group, as well as plasma adrenaline (p=0.0162) and noradrenalin (p=0.0218) levels. Conclusion This study provides support for the use of musical therapy in patients with HT and AMI after previous CABS. The positive effects of music therapy, in these patients, are probably because of enhanced of parasympathetic activities and reduction of plasma cytokine and catecholamine levels. Funding Acknowledgement Type of funding sources: None.

Abstract P3053: Mitochondrial Calcium Accumulation Drives The Progression Of Non-ischemic Heart Failure: Integrated Lessons From Genetic Mouse Models

Acute mitochondrial calcium ( m Ca 2+ ) uptake stimulates bioenergetics to meet increased ATP demand, but when excessive predisposes to necrotic cell death. A major unresolved controversy is whether chronic alterations in cardiomyocyte m Ca 2+ homeostasis contribute to maladaptive remodeling and contractile dysfunction in non-ischemic heart disease. We hypothesized that cardiomyocyte m Ca 2+ accumulation drives cardiac maladaptation in response to stressors that chronically increase workload and cytosolic Ca 2+ cycling. We subjected mice with adult, cardiomyocyte-specific manipulation of m Ca 2+ uptake through the mitochondrial calcium uniporter ( Mcu deletion, Mcu -cKO; MCU overexpression, MCU-Tg) or m Ca 2+ efflux through the mitochondrial sodium-calcium exchanger, NCLX (NCLX overexpression, NCLX-OE), to chronic pressure or neurohormonal overload. Fractional shortening failed to increase in Mcu -cKO mice over the first days of isoproterenol (Iso) infusion. Mortality was increased in Mcu -cKO mice over this period, and this effect was recapitulated in NCLX-OE mice infused with angiotensin II + phenylephrine (PE), although contractility did not decline in either case. Hypertrophic responses to chronic stress were attenuated in NCLX-OE but not Mcu -cKO hearts, and adenoviral NCLX expression limited mitochondrial metabolism, protein synthesis, and cell growth in neonatal rat cardiomyocytes treated with PE. These data indicate that m Ca 2+ accumulation is required for cardiac hypertrophy, but MCU is not. MCU-Tg hearts decompensated towards failure with 1-2 weeks of Iso. Although these hearts exhibited increased cardiomyocyte necrosis, deletion of the mPTP regulator cyclophilin D failed to rescue contractility, suggesting that m Ca 2+ overload causes cardiac failure, even independent of permeability transition. Fitting with this view, NCLX-OE attenuated the decline in contractile function that occurred with 12-week pressure overload. We conclude that despite initial adaptive effects, sustained m Ca 2+ elevation drives the progression of non-ischemic heart disease triggered by a chronic increase in cardiac workload. Our findings raise concern over proposed therapeutic strategies aiming to augment m Ca 2+ accumulation in heart failure.

Computational fluid dynamics investigation on aortic hemodynamics in double aortic arch before and after ligation surgery

Double aortic arch (DAA) malformation is one of the reasons for symptomatic vascular rings, the hemodynamics of which is still poorly understood. This study aims to investigate the blood flow characteristics in patient-specific double aortic arches using computational fluid dynamics (CFD). Seven cases of infantile patients with DAA were collected and their computed tomography images were used to reconstruct 3D computational models. A modified Carreau model was used to consider the non-Newtonian effect of blood and a three-element Windkessel model taking the effect of the age of patients into account was applied to reproduce physiological pressure waveforms. Numerical results show that blood flow distribution and energy loss of DAA depends on relative sizes of the two aortic arches and their angles with the ascending aorta. Ligation of either aortic arch increases the energy loss of blood in the DAA, leading to the increase in cardiac workload. Generally, the rising rate of energy loss before and after the surgery is almost linear with the area ratio between the aortic arch without ligation and the ascending aorta.

Enhanced NCLX-dependent mitochondrial Ca2+ efflux attenuates pathological remodeling in heart failure

Mitochondrial calcium (mCa2+) uptake couples changes in cardiomyocyte energetic demand to mitochondrial ATP production. However, excessive mCa2+ uptake triggers permeability transition and necrosis. Despite these established roles during acute stress, the involvement of mCa2+ signaling in cardiac adaptations to chronic stress remains poorly defined. Changes in NCLX expression are reported in heart failure (HF) patients and models of cardiac hypertrophy. Therefore, we hypothesized that altered mCa2+ homeostasis contributes to the hypertrophic remodeling of the myocardium that occurs upon a sustained increase in cardiac workload. The impact of mCa2+ flux on cardiac function and remodeling was examined by subjecting mice with cardiomyocyte-specific overexpression (OE) of the mitochondrial Na+/Ca2+ exchanger (NCLX), the primary mediator of mCa2+ efflux, to several well-established models of hypertrophic and non-ischemic HF. Cardiomyocyte NCLX-OE preserved contractile function, prevented hypertrophy and fibrosis, and attenuated maladaptive gene programs in mice subjected to chronic pressure overload. Hypertrophy was attenuated in NCLX-OE mice, prior to any decline in cardiac contractility. NCLX-OE similarly attenuated deleterious cardiac remodeling in mice subjected to chronic neurohormonal stimulation. However, cardiomyocyte NCLX-OE unexpectedly reduced overall survival in mice subjected to severe neurohormonal stress with angiotensin II + phenylephrine. Adenoviral NCLX expression limited mCa2+ accumulation, oxidative metabolism, and de novo protein synthesis during hypertrophic stimulation of cardiomyocytes in vitro. Our findings provide genetic evidence for the contribution of mCa2+ to early pathological remodeling in non-ischemic heart disease, but also highlight a deleterious consequence of increasing mCa2+ efflux when the heart is subjected to extreme, sustained neurohormonal stress.

Sex differences in the coronary vascular response to combined chemoreflex and metaboreflex stimulation in healthy humans.

What is the central question of this study? Coronary blood flow in healthy humans is controlled by both local metabolic signalling and adrenergic activity: does the integration of these signals during acute hypoxia and adrenergic activation differ between sexes? What are the main findings and its importance? Both males and females exhibit an increase in coronary blood velocity in response to acute hypoxia, a response that is constrained by adrenergic stimulation in males but not females. These findings suggest that coronary blood flow control differs between males and females. Coronary hyperaemia is mediated through multiple signalling pathways, including local metabolic messengers and adrenergic stimulation. This study aimed to determine whether the coronary vascular response to adrenergic stressors is different between sexes in normoxia and hypoxia. Young, healthy participants (n=32; 16F) underwent three randomized trials of isometric handgrip exercise followed by post-exercise circulatory occlusion (PECO) to activate the muscle metaboreflex. End-tidal was controlled at (1) normoxic levels throughout the trial, (2) 50mmHg for the duration of the trial (hypoxia trial), or (3) 50mmHg only during PECO (mixed trial). Mean left anterior descending coronary artery velocity (LADVmean ; transthoracic Doppler echocardiography), heart rate and blood pressure were assessed at baseline and during PECO. In normoxia, there was no change in LADVmean or cardiac workload induced by PECO in males and females. Acute hypoxia increased baseline LADVmean to a greater extent in males compared with females (P<0.05), despite a similar increase in cardiac workload. The change in LADVmean induced by PECO was similar between sexes in normoxia (P=0.31), greater in males during the mixed trial (male: 12.8 (7.7) cm/s vs. female: 8.1 (6.3) cm/s; P=0.02) and reduced in males but not females in acute hypoxia (male: -4.8 (4.5) cm/s vs. female: 0.8 (6.2) cm/s; P=0.006). In summary, sex differences in the coronary vasodilatory response to hypoxia were observed, and metaboreflex activation during hypoxia caused a paradoxical reduction in coronary blood velocity in males but not females.

Abstract 10484: Cardiac Adaptation to Acute Haemodynamic Stress in Patients with Type 2 Diabetes

Background: Due to varying cardiac workloads, efficient demand-supply matching is crucial for maintaining normal cardiac function. Cardiac metabolism is profoundly affected by changes in cardiac workload. There is scarcity of non-invasive studies evaluating how the heart adapts to hemodynamic stress in type 2 diabetes (T2D) patients. Objectives: Using cardiovascular magnetic resonance (CMR) and 31 Phosphorus MR spectroscopy ( 31 P-MRS) we assessed changes in cardiac energetics, perfusion, strain, systolic and diastolic function in response to increases in cardiac workload with dobutamine stress in T2D patients and healthy volunteers (HV). Methods: 24 T2D patients and 18 matched HV were recruited. Participants with ischemic heart disease were excluded. Results: Table-1 shows clinical and CMR/ 31 P-MRS data. Compared to HV, T2D patients showed reductions in left ventricular ejection fraction (LVEF) and global longitudinal strain (GLS) at rest, and a blunted increase in LVEF and GLS during stress. Diastolic function was impaired in T2D with lower mitral in-flow E/A ratio compared to HV at rest, which was further reduced during stress in both groups. Stress myocardial blood flow was lower in T2D patients.Compared to HV, rest phosphocreatinine (PCr)/ATP ratio was 17% lower in T2D patients, with a further 8% reduction during stress. However, there was a more pronounced reduction in the PCr/ATP with stress in HV (33% relative reduction), although stress PCr/ATP remained numerically higher in HV compared to T2D patients. Conclusions: T2D is associated with blunted ability of the myocardium to significantly increase contractile function from rest to stress. Moreover, T2D patients show exacerbated reductions in myocardial energetics and diastolic function during stress. Although reductions in myocardial energetics and diastolic function in response to acute stress were also detected in HV, these assessments remained higher in HV at stress compared to T2D patients.

The Cardiovascular Side Effects of Electroconvulsive Therapy and Their Management.

Electroconvulsive therapy (ECT) remains stigmatized in the broader medical community because of misunderstandings about treatment procedures, mortality rates, and cardiovascular complications. Electroconvulsive therapy causes periprocedural hemodynamic variability because of the surges in parasympathetic and sympathetic nervous systems after the administration of the electrical charge. Patients experience an increase in cardiac workload, which is potentially dangerous for patients with preexisting heart disease. Several findings suggest that cardiac complications occur most frequently in patients with underlying cardiovascular disease. We describe the cardiovascular complications that may result from ECT treatment and offer insight on how to mitigate these concerns if they occur. PubMed was queried using terms "electroconvulsive therapy" and "cardiovascular adverse effects." A table is provided with the common cardiovascular side effects of ECT and the most recent evidence-based treatment strategies to manage them. Generally, ECT is a safe procedure in which complications are minor and manageable. Most major complications caused by ECT are related to the cardiovascular system; however, with an appropriate pre-ECT evaluation and a comprehensive multidisciplinary team approach, the cardiovascular complications can be well managed and minimized. Providing proper cardiac clearance can prevent cardiac complications and provide timely care to treatment-resistant populations who are at risk for excessive morbidity and suicide.

Cardiac rest and stress metabolism in type 2 diabetes (T2D): can the diabetic heart flex under stress?

Abstract Background Efficient matching of energy supply to demand is essential for maintaining normal cardiac function. Altered cardiac metabolism may contribute to the development of cardiac dysfunction by impairing metabolic flexibility in type 2 diabetes (T2D). Purpose We aimed to evaluate the effect of T2D on myocardial substrate preferences in response to acute increases in cardiac workload and the effects on contractile function utilising simultaneous coronary sinus (CS) and aorta blood sampling and cardiac magnetic resonance (CMR) imaging Methods Eligible participants without obstructive coronary artery disease (&amp;gt;50% luminal coronary artery stenosis on coronary angiography) underwent transmyocardial arteriovenous blood sampling. Metabolites in paired coronary sinus and arterial samples were quantified to determine myocardial fuel selection at rest and during a stress protocol with intravenous dobutamine. Free fatty acid (FFA), glucose, 3-hydroxybutyric acid (3HBA) and lactate utilisation at rest and haemodynamic stress was calculated as an extraction fraction % (EF). Participants underwent dobutamine stress multiparametric CMR imaging at 3.0 Tesla (Skyra, Siemens, Germany) on a separate visit within 21 days to quantify cardiac volumes, function and perfusion. Results Two thousand and sixty-one participants were screened and due to stringent inclusion and exclusion criteria for this mechanistic study, three T2D patients and five matching controls were enrolled. Baseline demographics and metabolic and CMR results are documented in Table 1. At peak stress levels there was a significant increase in FFA use from rest to stress in controls only (p=0.002). There were no significant differences in FA or glucose uptake between T2D patients and controls at rest or stress. 3HBA EF was significantly increased in T2D during stress (25.04% vs 5.31%, p=0.007). Mean FFA and 3-HBA changes calculated as extraction fraction at stress and rest are illustrated in Figure 1. Conclusions We demonstrate for the first time in vivo that the diabetic heart switches to ketone bodies during increased workloads as a significant fuel source. At present, it is unknown whether enhanced ketone body metabolism in T2D is beneficial, maladaptive, or a bystander. As the energetic properties of ketones are favourable, increased myocardial ketone oxidation could be an adaptive change designed to compensate for defects in myocardial energy metabolism in diabetes. Further, larger studies are warranted. Funding Acknowledgement Type of funding sources: Foundation. Main funding source(s): British Heart Foundation - Clinical Research Training FellowshipWellcome Trust Seed Grant Table 1Figure 1

Abstract 17038: Influence of Cardiac Workload on Vascular Pyridine Nucleotide Redox State

Introduction: Myocardial perfusion is enhanced during periods of elevated cardiomyocyte oxygen consumption. The coupling between blood flow and myocardial oxygen demand is mediated by redox-dependent signals, yet the influence of cardiac workload on arterial myocyte pyridine nucleotide redox status is unknown. Hypothesis: Increased cardiac workload acutely alters intramyocardial arterial myocyte [NADH] i :[NAD + ] i . Methods and Results: The genetically-encoded fluorescent biosensor Peredox-mCherry was used to monitor real-time changes in intracellular [NADH] i :[NAD] i in isolated arterial myocytes. Treatment of cells expressing Peredox-mCherry with a range of [lactate] o :[pyruvate] o resulted in significant changes in green (Ex,Em: 400, 510 nm): red (Ex,Em: 585,615 nm) fluorescence ratio (1.903 ± 0.010, 10 mM lactate, 1.072 ± 0.073, 10 mM pyruvate), affording accurate quantification of arterial myocyte [NADH] i :[NAD] i . Increased arterial myocyte [NADH] i :[NAD] i was observed in response to reductions in oxygen tension from 5% (0.0021 ± 0.0001) to 1% (0.0050 ± 0.0001; P&lt;0.05). [NADH] i :[NAD] i was not altered by direct stimulation of arterial myocytes with the beta-adrenergic agonist isoproterenol (1 μM; P = .0630). Furthermore, biosensor-expressing arterial myocytes in co-culture with human induced pluripotent stem cell-derived cardiomyocytes (iPSC-CMs) recapitulated the effects of elevated [lactate] o :[pyruvate] o and reduced oxygen tension, exhibiting frequency-dependent increases in [NADH] i :[NAD] I following electrical pacing (e.g., ~3.3 fold increase in 3 Hz vs. unpaced; P&lt;0.05). Consistent with these results, intramyocardial coronary arteries in mice acutely treated with dobutamine (10 mg/kg, i.p.) to drive high cardiac work exhibited significantly greater lactate:pyruvate ratio, used as a surrogate for [NADH] i :[NAD] i , compared with those in hearts treated with vehicle (3.17 ± 0.23 vs. 2.21 ± 0.11; P&lt;0.05). Conclusions: Our results indicate that acute increases in cardiac workload promote the elevation of [NADH] i :[NAD] i in intramyocardial arterial myocytes.

Long-term spaceflight and the cardiovascular system.

While early investigations into the physiological effects of spaceflight suggest the body's ability to reversibly adapt, the corresponding effects of long-term spaceflight (>6 months) are much less conclusive. Prolonged exposure to microgravity and radiation yields profound effects on the cardiovascular system, including a massive cephalad fluid translocation and altered arterial pressure, which attenuate blood pressure regulatory mechanisms and increase cardiac output. Also, central venous pressure decreases as a result of the loss of venous compression. The stimulation of baroreceptors by the cephalad shift results in an approximately 10%–15% reduction in plasma volume, with fluid translocating from the vascular lumen to the interstitium. Despite possible increases in cardiac workload, myocyte atrophy and notable, yet unexplained, alterations in hematocrit have been observed. Atrophy is postulated to result from shunting of protein synthesis from the endoplasmic reticulum to the mitochondria via mortalin-mediated action. While data are scarce regarding their causative agents, arrhythmias have been frequently reported, albeit sublethal, during both Russian and American expeditions, with QT interval prolongation observed in long, but not short duration, spaceflight. Exposure of the heart to the proton and heavy ion radiation of deep space has also been shown to result in coronary artery degeneration, aortic stiffness, carotid intima thickening via collagen-mediated action, accelerated atherosclerosis, and induction of a pro-inflammatory state. Upon return, long-term spaceflight frequently results in orthostatic intolerance and altered sympathetic responses, which can prove hazardous should any rapid mobilization or evacuation be required, and indicates that these cardiac risks should be especially monitored for future missions.

A CASE OF BIGEMINY AND SUCCESSFUL COMPLETION OF ACUTE ELECTROCONVULSIVE THERAPY COURSE

Introduction Electroconvulsive therapy (ECT) remains stigmatized in the broader medical community due to misunderstandings about treatment procedures, mortality rates, and cardiovascular complications. Several concerns have risen regarding the safety of ECT on the cardiovascular system. ECT causes periprocedural hemodynamic variability due to the surges in parasympathetic and sympathetic nervous systems following the administration of the electric current.1 Patients experience an increase in cardiac workload and oxygen demand, which is potentially dangerous for patients with preexisting heart disease. Several findings suggest the incidence of cardiac complications is relatively rare and occurs most frequently in patients with underlying cardiovascular disease. Methods We describe a case report of a 53 year old female with history of bipolar I disorder current episode depressed, hyperlipidemia undergoing ECT who developed cardiovascular complications after her seventh brief pulse right unilateral (BRUL) treatment. Electrocardiogram (EKG) monitoring revealed bigeminy for two to three minutes (heart rate in 80s) during post-anesthesia care. Results The cardiovascular system undergoes various changes during ECT including events secondary to the parasympathetic release such as asystole, hypotension, bradycardia, and events secondary to sympathetic release such as hypertension and tachycardia. Other complications include arrhythmias, ST elevation, and Takotsubo Cardiomyopathy. The patient was seen by cardiology for further work-up. EKG, 2-D cardiac echocardiogram, 48-hour Holter monitoring, and coronary CT calcium scan were performed. She was found to have rare premature atrial contractions (PACs) (8 in 48 hours). Her bigeminy resolved spontaneously. The patient was able to complete the acute course of BRUL ECT and continued onto maintenance ECT with good effect. We also present a table with the common cardiovascular side effects from ECT and the most recent evidence-based treatment strategies to manage them. Conclusions Generally, ECT is a safe procedure; complications are minor and manageable. Most major complications caused by ECT are related to the cardiovascular system; however, with an appropriate pre-ECT evaluation and a comprehensive multidisciplinary-team approach the cardiovascular complications can be well managed and minimized. Our case highlights the benefits of a multidisciplinary care model between psychiatry, anesthesia, and cardiology. Providing proper cardiac clearance can prevent cardiac complications and provide timely care to treatment-resistant populations who are at risk for excessive morbidity and suicide. This research was funded by None.

Handrail support produces a higher rate pressure product in apparently healthy non-treadmill users during maximal exercise testing

Objective: Exercise treadmill testing (ETT) is a well-established procedure for the diagnosis, prognosis and functional assessment of patients with suspected cardiovascular disease. The use of handrail support during ETT is often discouraged as this has been demonstrated to overestimate functional capacity. It is unknown if this increase in functional capacity translates to an increase in cardiac workload. The aim of this study was to investigate if the use of handrail support during maximal ETT produces an increase in cardiac workload when compared to no handrail support. Approach: Fifty-two consenting volunteers performed two maximal ETTs, one with handrail support and the other without, approximately one week apart. Participants were identified as either experienced treadmill users (treadmill use ⩾ once per fortnight) (n = 24) or inexperienced users (n = 28). Cardiac workload was quantified using rate pressure product (RPP) (systolic blood pressure (SBP) × heart rate (HR)) Main results: The average age of participants was 38.4 ± 11.4 years (44% male). Overall exercise duration was significantly prolonged by 44.4% with handrail support (with support 15:01 ± 2:54 min; without support 10:24 ± 2:09 min). Overall HR, SBP and maximum RPP were not significantly different between conditions. For the 28 inexperienced treadmill users maximum RPP was significantly higher during handrail support (7.5% increase) (with support 34 417 ± 4906; without support 31 821 ± 4565). Significance: Handrail support overestimates functional capacity, however produces greater maximal RPP in inexperienced treadmill users. If accurate aerobic data is required during ETT, or subjects performing ETT are experienced treadmill users, handrail support should be discouraged. Non-treadmill users or subjects fearful of falling may benefit from handrail support, particularly when maximal cardiac workload is desired.

Maturation of Cardiac Energy Metabolism During Perinatal Development.

As one of the highest energy consumer organ in mammals, the heart has to be provided with a high amount of energy as soon as its first beats in utero. During the development of this organ, energy is produced within the cardiac muscle cell depending on substrate availability, oxygen pressure and cardiac workload that drastically change at birth. Thus, energy metabolism relying essentially on carbohydrates in fetal heart is very different from the adult one and birth is the trigger of a profound maturation which ensures the transition to a highly oxidative metabolism depending on lipid utilization. To face the substantial increase in cardiac workload resulting from the growth of the organism during the postnatal period, the heart not only develops its capacity for energy production but also undergoes a hypertrophic growth to adapt its contractile capacity to its new function. This leads to a profound cytoarchitectural remodeling of the cardiomyocyte which becomes a highly compartmentalized structure. As a consequence, within the mature cardiac muscle, energy transfer between energy producing and consuming compartments requires organized energy transfer systems that are established in the early postnatal life. This review aims at describing the major rearrangements of energy metabolism during the perinatal development.

Handrail Support Produces a Higher Rate Pressure Product in Apparently Healthy Non-Treadmill Users During Maximal Exercise Testing

Objective: Exercise treadmill testing (ETT) is a well-established procedure for the diagnosis, prognosis and functional assessment of patients with suspected cardiovascular disease. The use of handrail support during ETT is often discouraged as this has been demonstrated to overestimate functional capacity. It is unknown if this increase in functional capacity translates to an increase in cardiac workload. The aim of this study was to investigate if the use of handrail support during maximal ETT produces an increase in cardiac workload when compared to no handrail support. Approach: Fifty-two consenting volunteers performed two maximal ETTs, one with handrail support and the other without, approximately one week apart. Participants were identified as either experienced treadmill users (treadmill use >= once per fortnight) (n = 24) or inexperienced users (n = 28). Cardiac workload was quantified using rate pressure product (RPP) (systolic blood pressure (SBP) x heart rate (HR)) Main results: The average age of participants was 38.4 +/- 11.4 years (44% male). Overall exercise duration was significantly prolonged by 44.4% with handrail support (with support 15:01 +/- 2:54 min; without support 10:24 +/- 2:09 min). Overall HR, SBP and maximum RPP were not significantly different between conditions. For the 28 inexperienced treadmill users maximum RPP was significantly higher during handrail support (7.5% increase) (with support 34 417 +/- 4906; without support 31 821 +/- 4565). Significance: Handrail support overestimates functional capacity, however produces greater maximal RPP in inexperienced treadmill users. If accurate aerobic data is required during ETT, or subjects performing ETT are experienced treadmill users, handrail support should be discouraged. Non-treadmill users or subjects fearful of falling may benefit from handrail support, particularly when maximal cardiac workload is desired.

Science Signaling Podcast for 28 February 2017: Balancing autophagy in the stressed heart.

This Podcast features an interview with Saumya Das, senior author of a Research Article that appears in the 28 February 2017 issue of Science Signaling, about a protein that inhibits pathological cardiac hypertrophy in mice. Temporary increases in cardiac workload, such as those caused by exercise or pregnancy, induce physiological cardiac hypertrophy, a beneficial type of heart enlargement that is adaptive. However, a sustained increase in workload due to metabolic stress or uncontrolled high blood pressure induces pathological cardiac hypertrophy, which can contribute to heart failure. Simonson et al found that expression of DNA-damage-inducible transcript 4-like (DDiT4L) increased during pathological hypertrophy, but not during physiological hypertrophy, in mice. DDiT4L promoted stress-induced autophagy in cardiomyocytes by inhibiting signaling through the mechanistic target of rapamycin complex 1 (mTORC1) and stimulating signaling through mTORC2. These findings suggest that targeting autophagy, which is important for cellular homeostasis but can be detrimental in excess, may be useful for treating some cardiovascular diseases.Listen to Podcast.

Hypoglycemia and Cardiovascular Risk: Is There a Major Link?

Severe hypoglycemia is recognized to be one of the strongest predictors of macrovascular events, adverse clinical outcomes, and mortality in patients with type 2 diabetes. However, it is uncertain whether a direct pathophysiological link exists or whether hypoglycemia is primarily a marker of vulnerability to these events. Large clinical trials have reported an increased hazard ratio for all-cause mortality and cardiovascular events in patients with type 2 diabetes and severe hypoglycemia, but such an association has not been demonstrated in prospective trials of people with type 1 diabetes. Several cardiovascular effects occur during hypoglycemia either as a result of low blood glucose levels per se or through activation of the sympathoadrenal response: hemodynamic changes with an increase in cardiac work load and potential attenuation of myocardial perfusion, electrophysiological changes that may be arrhythmogenic, induction of a prothrombotic state, and release of inflammatory markers. Although the potential for a causal relationship has been demonstrated in mechanistic studies, the evidence from large prospective studies that hypoglycemia is a major causal contributor to cardiovascular events is limited to date. Other preexisting cardiovascular risk factors in addition to hypoglycemia may be the major link to the final cardiovascular event, but a low blood glucose level can trigger these events in patients with a high cardiovascular risk.

Accuracy of the Electrocardiograph in Detecting Cardiac Left Ventricular Hypertrophy in Pediatric Patients with Aortic Valve Disease

Background: Left ventricular hypertrophy (LVH) is a pathological remodeling of myocardial tissue occurring in response to an increase in cardiac workload. The most significant cause of LVH in the pediatric population is aortic valve disease, which includes aortic valve stenosis and insufficiency. Though LVH can arise naturally in response to strenuous exercise, it has clinical utility as a marker of hypertension and heart disease. LVH can be detected using certain voltage criteria via electrocardiogram (ECG), though this approach typically exhibits poor sensitivity. The current gold standard for LVH identification is echocardiogram – however, waiting times and operator skill are significant variables in echocardiographic diagnosis of LVH. This study evaluates the sensitivity and specificity of various voltage criteria for LVH in this population, and whether amalgamating criteria can boost their accuracy. Methods: A retrospective chart review was conducted to look at the echocardiograms and electrocardiograms (ECGs) of 62 pediatric patients with aortic valve disease seen at McMaster University Medical Centre. Patient ECGs were analyzed for LVH using a number of voltage criteria: those established by the Journal of American College of Cardiology’s (JACC) standards for pediatric LVH, criteria utilized for adult LVH, and Cornell adult voltage criteria. To determine the suitability of these indices in identifying LVH via ECG, we analyzed sensitivity, specificity and negative predictive value (NPV) of each set of criteria using echocardiograms carried out within 2 months as a gold standard. Results: Our results identify Cornell Female voltage criteria as bearing the highest sensitivity (81.94%) in identifying LVH in this population, while JACC pediatric criteria demonstrated the highest specificity (77.29%). Using Cornell Female voltage criteria as a sensitive screening tool, we then applied JACC pediatric criteria (chosen for its high specificity). The combined criteria (JACCCF) demonstrated higher sensitivity and specificity (88.64% and 83.33%, respectively) than either criteria used in isolation. Conclusion: Cornell Female voltage criteria demonstrated the highest sensitivity in this population, though it is typically not utilized in a pediatric setting. Utilizing Cornell Female criteria as a screening tool in tandem with JACC criteria for its specificity yielded a set of highly specific and sensitive criteria. This approach bears promise in pediatric patients with aortic valve disease, and should be explored in other populations with LVH.