H and P MR Spectroscopy to Assess Muscle Mitochondrial Dysfunction in Long COVID.

Background Emerging evidence suggests mitochondrial dysfunction may play a role in the fatigue experienced by individuals with post-COVID-19 condition (PCC), commonly called long COVID, which can be assessed using MR spectroscopy. Purpose To compare mitochondrial function between participants with fatigue-predominant PCC and healthy control participants using MR spectroscopy, and to investigate the relationship between MR spectroscopic parameters and fatigue using the 11-item Chalder fatigue questionnaire. Materials and Methods This prospective, observational, single-center study (June 2021 to January 2024) included participants with PCC who reported moderate to severe fatigue, with normal blood test and echocardiographic results, alongside control participants without fatigue symptoms.

Cardiac structural, functional and energetic assessments during and after pregnancy in women with gestational diabetes mellitus, preeclampsia and healthy pregnancy.

Background: GDM and preeclampsia are common complications of pregnancy, for which overweight/obesity is a common risk factor. Both conditions are associated with a two-to-four-fold increase in future incident heart failure, which may be linked to early maladaptive myocardial changes.

Objectives: To determine maternal myocardial structural, functional, and energetic responses to pregnancies complicated by gestational diabetes mellitus (GDM) or preeclampsia compared to healthy pregnancies (HP) at third-trimester of pregnancy and twelve-months postpartum.

Myocardial Strain Imaging: Theory, Current Practice, and the Future.

Myocardial strain imaging by echocardiography or cardiac magnetic resonance (CMR) is a powerful method to diagnose cardiac disease. Strain imaging provides measures of myocardial shortening, thickening, and lengthening and can be applied to any cardiac chamber. Left ventricular (LV) global longitudinal strain by speckle-tracking echocardiography is the most widely used clinical strain parameter.

Accelerated 3D multi-channel mapping at 7 T for the brain and heart.

Purpose: To acquire accurate volumetric multi-channel maps in under 14 s whole-brain or 23 heartbeats whole-heart for parallel transmit (pTx) applications at 7 T.

Theory And Methods: We evaluate the combination of three recently proposed techniques. The acquisition of multi-channel transmit array maps is accelerated using transmit low rank (TxLR) with absolute mapping (Sandwich) acquired in a time-interleaved acquisition of modes (B1TIAMO) fashion.

Compartment-based reconstruction of acquisition-weighted P cardiac MRSI reduces sensitivity to cardiac motion and scan planning.

P magnetic resonance spectroscopic imaging (P MRSI) is a powerful technique for investigating the metabolic effects of treatments for heart failure , allowing a better understanding of their mechanism of action in patient cohorts. Unfortunately, cardiac P MRSI is fundamentally limited by low SNR, which leads to compromises in acquisition, such as no cardiac or respiratory gating or low spatial resolution, in order to achieve reasonable scan times. Spectroscopy with linear algebra modeling (SLAM) reconstruction may be able to address these challenges and therefore improve repeatability by incorporating a segmented localizer into the reconstruction.

Role of Cardiac Energetics in Aortic Stenosis Disease Progression: Identifying the High-risk Metabolic Phenotype.

Background: Severe aortic stenosis (AS) is associated with left ventricular (LV) hypertrophy and cardiac metabolic alterations with evidence of steatosis and impaired myocardial energetics. Despite this common phenotype, there is an unexplained and wide individual heterogeneity in the degree of hypertrophy and progression to myocardial fibrosis and heart failure. We sought to determine whether the cardiac metabolic state may underpin this variability.

Efficacy and tolerability of an endogenous metabolic modulator (AXA1125) in fatigue-predominant long COVID: a single-centre, double-blind, randomised controlled phase 2a pilot study.

Background: 'Long COVID' describes persistent symptoms, commonly fatigue, lasting beyond 12 weeks following SARS-CoV-2 infection. Potential causes include reduced mitochondrial function and cellular bioenergetics. AXA1125 has previously increased β-oxidation and improved bioenergetics in preclinical models along with certain clinical conditions, and therefore may reduce fatigue associated with Long COVID.

Retained Metabolic Flexibility of the Failing Human Heart.

Background: The failing heart is traditionally described as metabolically inflexible and oxygen starved, causing energetic deficit and contractile dysfunction. Current metabolic modulator therapies aim to increase glucose oxidation to increase oxygen efficiency of adenosine triphosphate production, with mixed results.

Methods: To investigate metabolic flexibility and oxygen delivery in the failing heart, 20 patients with nonischemic heart failure with reduced ejection fraction (left ventricular ejection fraction 34.

Rationale and design of a randomised trial of trientine in patients with hypertrophic cardiomyopathy.

Aims: Hypertrophic cardiomyopathy (HCM) is characterised by left ventricular hypertrophy (LVH), myocardial fibrosis, enhanced oxidative stress and energy depletion. Unbound/loosely bound tissue copper II ions are powerful catalysts of oxidative stress and inhibitors of antioxidants. Trientine is a highly selective copper II chelator.

Assessment of Cardiac Energy Metabolism, Function, and Physiology in Patients With Heart Failure Taking Empagliflozin: The Randomized, Controlled EMPA-VISION Trial.

Background: Sodium-glucose co-transporter 2 inhibitors (SGLT2i) have emerged as a paramount treatment for patients with heart failure (HF), irrespective of underlying reduced or preserved ejection fraction. However, a definite cardiac mechanism of action remains elusive. Derangements in myocardial energy metabolism are detectable in all HF phenotypes, and it was proposed that SGLT2i may improve energy production.

Compartment-based reconstruction of 3D acquisition-weighted P cardiac magnetic resonance spectroscopic imaging at 7 T: A reproducibility study.

Even at 7 T, cardiac P magnetic resonance spectroscopic imaging (MRSI) is fundamentally limited by low signal-to-noise ratio (SNR), leading to long scan times and poor temporal and spatial resolutions. Compartment-based reconstruction algorithms such as magnetic resonance spectroscopy with linear algebraic modeling (SLAM) and spectral localization by imaging (SLIM) may improve SNR or reduce scan time without changes to acquisition. Here, we compare the repeatability and SNR performance of these compartment-based methods, applied to three different acquisition schemes at 7 T.

Supplementation-induced change in muscle carnosine is paralleled by changes in muscle metabolism, protein glycation and reactive carbonyl species sequestering.

Carnosine is a performance-enhancing food supplement with a potential to modulate muscle energy metabolism and toxic metabolites disposal. In this study we explored interrelations between carnosine supplementation (2 g/day, 12 weeks) induced effects on carnosine muscle loading and parallel changes in (i) muscle energy metabolism, (ii) serum albumin glycation and (iii) reactive carbonyl species sequestering in twelve (M/F=10/2) sedentary, overweight-to-obese (BMI: 30.0+/-2.

Insights Into the Metabolic Aspects of Aortic Stenosis With the Use of Magnetic Resonance Imaging.

Pressure overload in aortic stenosis (AS) encompasses both structural and metabolic remodeling and increases the risk of decompensation into heart failure. A major component of metabolic derangement in AS is abnormal cardiac substrate use, with down-regulation of fatty acid oxidation, increased reliance on glucose metabolism, and subsequent myocardial lipid accumulation. These changes are associated with energetic and functional cardiac impairment in AS and can be assessed with the use of cardiac magnetic resonance spectroscopy (MRS).

Rapid 3D absolute B mapping using a sandwiched train presaturated TurboFLASH sequence at 7 T for the brain and heart.

Purpose: To shorten the acquisition time of magnetization-prepared absolute transmit field (B ) mapping known as presaturation TurboFLASH, or satTFL, to enable single breath-hold whole-heart 3D B mapping.

Methods: SatTFL is modified to remove the delay between the reference and prepared images (typically 5 T ), with matching transmit configurations for excitation and preparation RF pulses. The new method, called Sandwich, is evaluated as a 3D sequence, measuring whole-brain and gated whole-heart B maps in a single breath-hold.

Maternal Cardiac Changes in Women With Obesity and Gestational Diabetes Mellitus.

Objective: We investigated if women with gestational diabetes mellitus (GDM) in the third trimester of pregnancy exhibit adverse cardiac alterations in myocardial energetics, function, or tissue characteristics.

Research Design And Methods: Thirty-eight healthy, pregnant women and 30 women with GDM were recruited. Participants underwent phosphorus MRS and cardiovascular magnetic resonance for assessment of myocardial energetics (phosphocreatine [PCr] to ATP ratio), tissue characteristics, biventricular volumes and ejection fractions, left ventricular (LV) mass, global longitudinal shortening (GLS), and mitral in-flow E-wave to A-wave ratio.

Three-dimensional, 2.5-minute, 7T phosphorus magnetic resonance spectroscopic imaging of the human heart using concentric rings.

A three-dimensional (3D), density-weighted, concentric rings trajectory (CRT) magnetic resonance spectroscopic imaging (MRSI) sequence is implemented for cardiac phosphorus ( P)-MRS at 7 T. The point-by-point k-space sampling of traditional phase-encoded chemical shift imaging (CSI) sequences severely restricts the minimum scan time at higher spatial resolutions. Our proposed CRT sequence implements a stack of concentric rings, with a variable number of rings and planes spaced to optimise the density of k-space weighting.

Increased cardiac Pi/PCr in the diabetic heart observed using phosphorus magnetic resonance spectroscopy at 7T.

Phosphorus magnetic resonance spectroscopy (31P-MRS) has previously demonstrated decreased energy reserves in the form of phosphocreatine to adenosine-tri-phosphate ratio (PCr/ATP) in the hearts of patients with type 2 diabetes (T2DM). Recent 31P-MRS techniques using 7T systems, e.g.

Evaluation of Acute Supplementation With the Ketone Ester ()-3-Hydroxybutyl-(R)-3-Hydroxybutyrate (deltaG) in Healthy Volunteers by Cardiac and Skeletal Muscle P Magnetic Resonance Spectroscopy.

In this acute intervention study, we investigated the potential benefit of ketone supplementation in humans by studying cardiac phosphocreatine to adenosine-triphosphate ratios (PCr/ATP) and skeletal muscle PCr recovery using phosphorus magnetic resonance spectroscopy (P-MRS) before and after ingestion of a ketone ester drink. We recruited 28 healthy individuals: 12 aged 23-70 years for cardiac P-MRS, and 16 aged 60-75 years for skeletal muscle P-MRS. Baseline and post-intervention resting cardiac and dynamic skeletal muscle P-MRS scans were performed in one visit, where 25 g of the ketone monoester, deltaG, was administered after the baseline scan.

Myocardial Energy Response to Glyceryl Trinitrate: Physiology Revisited.

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. 10 healthy volunteers underwent cardiac magnetic resonance imaging to assess cardiac function and phosphorus magnetic resonance spectroscopy to measure Phosphocreatine/ATP (PCr/ATP) ratio and creatine kinase forward rate constant (CK ) before and during an intravenous infusion of GTN.

Energetic Basis for Exercise-Induced Pulmonary Congestion in Heart Failure With Preserved Ejection Fraction.

Background: Transient pulmonary congestion during exercise is emerging as an important determinant of reduced exercise capacity in heart failure with preserved ejection fraction (HFpEF). We sought to determine whether an abnormal cardiac energetic state underpins this process.

Methods: We recruited patients across the spectrum of diastolic dysfunction and HFpEF (controls, n=11; type 2 diabetes, n=9; HFpEF, n=14; and severe diastolic dysfunction attributable to cardiac amyloidosis, n=9).