A Mitochondrial Basis for Heart Failure Progression.

In health, the human heart is able to match ATP supply and demand perfectly. It requires 6 kg of ATP per day to satisfy demands of external work (mechanical force generation) and internal work (ion movements and basal metabolism). The heart is able to link supply with demand via direct responses to ADP and AMP concentrations but calcium concentrations within myocytes play a key role, signalling both inotropy, chronotropy and matched increases in ATP production. Calcium/calmodulin-dependent protein kinase (CaMKII) is a key adapter to increased workload, facilitating a greater and more rapid calcium concentration change. In the failing heart, this is dysfunctional and ATP supply is impaired. This review aims to examine the mechanisms and pathologies that link increased energy demand to this disrupted situation. We examine the roles of calcium loading, oxidative stress, mitochondrial structural abnormalities and damage-associated molecular patterns.

Noninvasive Pressure-Volume Loops Predict Major Adverse Cardiac Events in Heart Failure With Reduced Ejection Fraction.

Background: Heart failure with reduced ejection fraction (HFrEF) is characterized by ventricular remodeling and impaired myocardial energetics. Left ventricular pressure-volume (PV) loop analysis can be performed noninvasively using cardiovascular magnetic resonance (CMR) imaging to assess cardiac thermodynamic efficiency. Objectives: The aim of the study was to investigate whether noninvasive PV loop parameters, derived from CMR, could predict major adverse cardiac events (MACE) in HFrEF patients. Methods: PV loop parameters (stroke work, ventricular efficiency, external power, contractility, and energy per ejected volume) were computed from CMR cine images and brachial blood pressure. The primary end point was MACE (cardiovascular death, heart failure (HF) hospitalization, myocardial infarction, revascularization, ventricular tachycardia/fibrillation, heart transplantation, or left ventricular assist device implantation within 5 years). Associations between PV loop parameters and MACE were evaluated using multivariable Cox regression. Results: One hundred and sixty-four HFrEF patients (left ventricular ejection fraction ≤40%, age 63 [IQR: 55-70] years, 79% male) who underwent clinical CMR examination between 2004 and 2014 were included. Eighty-eight patients (54%) experienced at least one MACE after an average of 2.8 years. Unadjusted models demonstrated a significant association between MACE and all PV loop parameters (P < 0.05 for all), HF etiology (P < 0.001), left ventricular ejection fraction (P = 0.003), global longitudinal strain (P < 0.001), and N-terminal prohormone of brain natriuretic peptide level (P = 0.001). In the multivariable Cox regression analysis adjusted for age, sex, hypertension, diabetes, and HF etiology, ventricular efficiency was associated with MACE (HR: 1.04 (95% CI: 1.01-1.08) per-% decrease, P = 0.01). Conclusions: Ventricular efficiency, derived from noninvasive PV loop analysis from standard CMR scans, is associated with MACE in patients with HFrEF.

Non-invasive left ventricular pressure-volume loops from cardiovascular magnetic resonance imaging and brachial blood pressure: validation using pressure catheter measurements.

Aims: Left ventricular (LV) pressure-volume (PV) loops provide gold-standard physiological information but require invasive measurements of ventricular intracavity pressure, limiting clinical and research applications. A non-invasive method for the computation of PV loops from magnetic resonance imaging and brachial cuff blood pressure has recently been proposed. Here we evaluated the fidelity of the non-invasive PV algorithm against invasive LV pressures in humans. Methods and results: Four heart failure patients with EF < 35% and LV dyssynchrony underwent cardiovascular magnetic resonance (CMR) imaging and subsequent LV catheterization with sequential administration of two different intravenous metabolic substrate infusions (insulin/dextrose and lipid emulsion), producing eight datasets at different haemodynamic states. Pressure-volume loops were computed from CMR volumes combined with (i) a time-varying elastance function scaled to brachial blood pressure and temporally stretched to match volume data, or (ii) invasive pressures averaged from 19 to 30 sampled beats. Method comparison was conducted using linear regression and Bland-Altman analysis. Non-invasively derived PV loop parameters demonstrated high correlation and low bias when compared to invasive data for stroke work (R2 = 0.96, P < 0.0001, bias 4.6%), potential energy (R2 = 0.83, P = 0.001, bias 1.5%), end-systolic pressure-volume relationship (R2 = 0.89, P = 0.0004, bias 5.8%), ventricular efficiency (R2 = 0.98, P < 0.0001, bias 0.8%), arterial elastance (R2 = 0.88, P = 0.0006, bias -8.0%), mean external power (R2 = 0.92, P = 0.0002, bias 4.4%), and energy per ejected volume (R2 = 0.89, P = 0.0001, bias 3.7%). Variations in estimated end-diastolic pressure did not significantly affect results (P > 0.05 for all). Intraobserver analysis after one year demonstrated 0.9-3.4% bias for LV volumetry and 0.2-5.4% for PV loop-derived parameters. Conclusion: Pressure-volume loops can be precisely and accurately computed from CMR imaging and brachial cuff blood pressure in humans.

Hemodynamic forces from 4D flow magnetic resonance imaging predict left ventricular remodeling following cardiac resynchronization therapy.

BACKGROUND: Patients with heart failure and left bundle branch block (LBBB) may receive cardiac resynchronization therapy (CRT), but current selection criteria are imprecise, and many patients have limited treatment response. Hemodynamic forces (HDF) have been suggested as a marker for CRT response. The aim of this study was therefore to investigate left ventricular (LV) HDF as a predictive marker for LV remodeling after CRT. METHODS: Patients with heart failure, EF < 35% and LBBB (n = 22) underwent CMR with 4D flow prior to CRT. LV HDF were computed in three directions using the Navier-Stokes equations, reported in median N [interquartile range], and the ratio of transverse/longitudinal HDF was calculated for systole and diastole. Transthoracic echocardiography was performed before and 6 months after CRT. Patients with end-systolic volume reduction ≥ 15% were defined as responders. RESULTS: Non-responders had smaller HDF than responders in the inferior-anterior direction in systole (0.06 [0.03] vs. 0.07 [0.03], p = 0.04), and in the apex-base direction in diastole (0.09 [0.02] vs. 0.1 [0.05], p = 0.047). Non-responders had larger diastolic HDF ratio compared to responders (0.89 vs. 0.67, p = 0.004). ROC analysis of diastolic HDF ratio for identifying CRT non-responders had AUC of 0.88 (p = 0.005) with sensitivity 57% and specificity 100% for ratio > 0.87. Intragroup comparison found higher HDF ratio in systole compared to diastole for responders (p = 0.003), but not for non-responders (p = 0.8). CONCLUSION: Hemodynamic force ratio is a potential marker for identifying patients with heart failure and LBBB who are unlikely to benefit from CRT. Larger-scale studies are required before implementation of HDF analysis into clinical practice.

Increased biventricular hemodynamic forces in precapillary pulmonary hypertension.

Precapillary pulmonary hypertension (PHprecap) is a condition with elevated pulmonary vascular pressure and resistance. Patients have a poor prognosis and understanding the underlying pathophysiological mechanisms is crucial to guide and improve treatment. Ventricular hemodynamic forces (HDF) are a potential early marker of cardiac dysfunction, which may improve evaluation of treatment effect. Therefore, we aimed to investigate if HDF differ in patients with PHprecap compared to healthy controls. Patients with PHprecap (n = 20) and age- and sex-matched healthy controls (n = 12) underwent cardiac magnetic resonance imaging including 4D flow. Biventricular HDF were computed in three spatial directions throughout the cardiac cycle using the Navier-Stokes equations. Biventricular HDF (N) indexed to stroke volume (l) were larger in patients than controls in all three directions. Data is presented as median N/l for patients vs controls. In the RV, systolic HDF diaphragm-outflow tract were 2.1 vs 1.4 (p = 0.003), and septum-free wall 0.64 vs 0.42 (p = 0.007). Diastolic RV HDF apex-base were 1.4 vs 0.87 (p < 0.0001), diaphragm-outflow tract 0.80 vs 0.47 (p = 0.005), and septum-free wall 0.60 vs 0.38 (p = 0.003). In the LV, systolic HDF apex-base were 2.1 vs 1.5 (p = 0.005), and lateral wall-septum 1.5 vs 1.2 (p = 0.02). Diastolic LV HDF apex-base were 1.6 vs 1.2 (p = 0.008), and inferior-anterior 0.46 vs 0.24 (p = 0.02). Hemodynamic force analysis conveys information of pathological cardiac pumping mechanisms complementary to more established volumetric and functional parameters in precapillary pulmonary hypertension. The right ventricle compensates for the increased afterload in part by augmenting transverse forces, and left ventricular hemodynamic abnormalities are mainly a result of underfilling rather than intrinsic ventricular dysfunction.

Noninvasive Assessment of Left Ventricular Pressure-Volume Relations: Inter- and Intraobserver Variability and Assessment Across Heart Failure Subtypes.

A novel method to derive pressure-volume (PV) loops noninvasively from cardiac magnetic resonance images has recently been developed. The aim of this study was to evaluate inter- and intraobserver variability of hemodynamic parameters obtained from noninvasive PV loops in healthy controls, subclinical diastolic dysfunction (SDD), and patients with heart failure with preserved ejection fraction, mildly reduced ejection fraction, and reduced ejection fraction. We included 75 subjects, of whom 15 were healthy controls, 15 subjects with SDD (defined as fulfilling 1 to 2 echocardiographic criteria for diastolic dysfunction), and 15 patients with preserved ejection fraction, 15 with mildly reduced ejection fraction, and 15 with reduced ejection fraction. PV loops were computed using time-resolved left ventricular volumes from cardiac magnetic resonance images and a brachial blood pressure. Inter- and intraobserver variability and intergroup differences of PV loop-derived hemodynamic parameters were assessed. Bias was low and limits of agreement were narrow for all hemodynamic parameters in the inter- and intraobserver comparisons. Interobserver difference for stroke work was 2 ± 9%, potential energy was 4 ± 11%, and maximal ventricular elastance was -4 ± 7%. Intraobserver for stroke work was -1 ± 7%, potential energy was 3 ± 4%, and maximal ventricular elastance was 1 ± 5%. In conclusion, this study presents a fully noninvasive left ventricular PV loop analysis across healthy controls, subjects with SDD, and patients with heart failure with preserved or impaired systolic function. In conclusion, the method for PV loop computation from clinical-standard manual left ventricular segmentation was rapid and robust, bridging the gap between clinical and research settings.

Kinetic energy of left ventricular blood flow across heart failure phenotypes and in subclinical diastolic dysfunction.

Kinetic energy (KE) of intracardiac blood flow reflects myocardial work spent on accelerating blood and provides a mechanistic window into diastolic filling dynamics. Diastolic dysfunction may represent an early stage in the development of heart failure (HF). Here we evaluated the hemodynamic effects of impaired diastolic function in subjects with and without HF, testing the hypothesis that left ventricular KE differs between controls, subjects with subclinical diastolic dysfunction (SDD), and patients with HF. We studied 77 subjects [16 controls, 20 subjects with SDD, 16 heart failure with preserved ejection fraction (HFpEF), 9 heart failure with mildly reduced ejection fraction (HFmrEF), and 16 heart failure with reduced ejection fraction (HFrEF) patients, age- and sex-matched at the group level]. Cardiac magnetic resonance at 1.5 T included intracardiac four-dimensional (4-D) flow and cine imaging. Left ventricular KE was calculated as 0.5 × m × v2. Systolic KE was similar between groups (P > 0.4), also after indexing to stroke volume (P = 0.25), and was primarily driven by ventricular emptying rate (P < 0.0001, R2 = 0.52). Diastolic KE was higher in patients with heart failure than in controls (P < 0.05) but similar between SDD and HFpEF (P > 0.18), correlating with inflow conditions (E-wave velocity, P < 0.0001, R2 = 0.24) and end-diastolic volume (P = 0.0003, R2 = 0.17) but not with average e' (P = 0.07). Diastolic KE differs between controls and heart failure, suggesting more work is spent filling the failing ventricle, whereas systolic KE does not differentiate between well-matched groups with normal ejection fractions even in the presence of relaxation abnormalities and heart failure. Mechanistically, KE reflects the acceleration imparted on the blood and is driven by variations in ventricular emptying and filling rates, volumes, and heart rate, regardless of underlying pathology.NEW & NOTEWORTHY Here we present the first study of left ventricular kinetic energy in individuals with subclinical diastolic dysfunction and in heart failure patients with preserved or impaired systolic function. Kinetic energy differs between groups in diastole, and reflects altered filling and emptying processes. Kinetic energy analysis should be considered in studies seeking to characterize myocardial energetics comprehensively.

Hemodynamic force analysis is not ready for clinical trials on HFpEF.

Hemodynamic force analysis has been proposed as a novel tool for early detection of subclinical systolic dysfunction in heart failure with preserved ejection fraction (HFpEF). Here we investigated the ability of hemodynamic forces to discriminate between healthy subjects and heart failure patients with varying degrees of systolic dysfunction. We studied 34 controls, 16 HFpEF patients, and 25 heart failure patients with mid-range (HFmrEF) or reduced ejection fraction (HFrEF) using cardiac magnetic resonance with acquisition of cine images and 4D flow at 1.5 T. The Navier-Stokes equation was used to compute global left ventricular hemodynamic forces over the entire cardiac cycle. Forces were analyzed for systole, diastole, and the entire heartbeat, with and without normalization to left ventricular volume. Volume-normalized hemodynamic forces demonstrated significant positive correlation with EF (r2 = 0.47, p < 0.0001) and were found significantly lower in heart failure with reduced ejection fraction compared to controls (p < 0.0001 for systole and diastole). No difference was seen between controls and HFpEF (p > 0.34). Non-normalized forces displayed no differences between controls and HFpEF (p > 0.24 for all analyses) and did not correlate with EF (p = 0.36). Left ventricular hemodynamic force analysis, whether indexed to LV volumes or not, is not ready for clinical trials on HFpEF assessment.

Automated left atrial time-resolved segmentation in MRI long-axis cine images using active contours.

BACKGROUND: Segmentation of the left atrium (LA) is required to evaluate atrial size and function, which are important imaging biomarkers for a wide range of cardiovascular conditions, such as atrial fibrillation, stroke, and diastolic dysfunction. LA segmentations are currently being performed manually, which is time-consuming and observer-dependent. METHODS: This study presents an automated image processing algorithm for time-resolved LA segmentation in cardiac magnetic resonance imaging (MRI) long-axis cine images of the 2-chamber (2ch) and 4-chamber (4ch) views using active contours. The proposed algorithm combines mitral valve tracking, automated threshold calculation, edge detection on a radially resampled image, edge tracking based on Dijkstra's algorithm, and post-processing involving smoothing and interpolation. The algorithm was evaluated in 37 patients diagnosed mainly with paroxysmal atrial fibrillation. Segmentation accuracy was assessed using the Dice similarity coefficient (DSC) and Hausdorff distance (HD), with manual segmentations in all time frames as the reference standard. For inter-observer variability analysis, a second observer performed manual segmentations at end-diastole and end-systole on all subjects. RESULTS: The proposed automated method achieved high performance in segmenting the LA in long-axis cine sequences, with a DSC of 0.96 for 2ch and 0.95 for 4ch, and an HD of 5.5 mm for 2ch and 6.4 mm for 4ch. The manual inter-observer variability analysis had an average DSC of 0.95 and an average HD of 4.9 mm. CONCLUSION: The proposed automated method achieved performance on par with human experts analyzing MRI images for evaluation of atrial size and function. Video Abstract.

Hemodynamic forces using four-dimensional flow MRI: an independent biomarker of cardiac function in heart failure with left ventricular dyssynchrony?

Patients with heart failure with left ventricular (LV) dyssynchrony often do not respond to cardiac resynchronization therapy (CRT), indicating that the pathophysiology is insufficiently understood. Intracardiac hemodynamic forces computed from four-dimensional (4-D) flow MRI have been proposed as a new measure of cardiac function. We therefore aimed to investigate how hemodynamic forces are altered in LV dyssynchrony. Thirty-one patients with heart failure and LV dyssynchrony and 39 control subjects underwent cardiac MRI with the acquisition of 4-D flow. Hemodynamic forces were computed using Navier-Stokes equations and integrated over the manually delineated LV volume. The ratio between transverse (lateral-septal and inferior-anterior) and longitudinal (apical-basal) forces was calculated for systole and diastole separately and compared with QRS duration, aortic valve opening delay, global longitudinal strain, and ejection fraction (EF). Patients exhibited hemodynamic force patterns that were significantly altered compared with control subjects, including loss of longitudinal forces in diastole (force ratio, control subjects vs. patients: 0.32 vs. 0.90, P < 0.0001) and increased transverse force magnitudes. The systolic force ratio was correlated with global longitudinal strain and EF ( P < 0.01). The diastolic force ratio separated patients from control subjects (area under the curve: 0.98, P < 0.0001) but was not correlated to other dyssynchrony measures ( P > 0.05 for all). Hemodynamic forces by 4-D flow represent a new approach to the quantification of LV dyssynchrony. Diastolic force patterns separate healthy from diseased ventricles. Different force patterns in patients indicate the possible use of force analysis for risk stratification and CRT implantation guidance. NEW & NOTEWORTHY In this report, we demonstrate that patients with heart failure with left ventricular dyssynchrony exhibit significantly altered hemodynamic forces compared with normal. Force patterns in patients mechanistically reflect left ventricular dysfunction on the organ level, largely independent of traditional dyssynchrony measures. Force analysis may help clinical decision making and could potentially be used to improve therapy outcomes.

Hemodynamic forces in the left and right ventricles of the human heart using 4D flow magnetic resonance imaging: Phantom validation, reproducibility, sensitivity to respiratory gating and free analysis software.

PURPOSE: To investigate the accuracy, reproducibility and sensitivity to respiratory gating, field strength and ventricle segmentation of hemodynamic force quantification in the left and right ventricles of the heart (LV and RV) using 4D-flow magnetic resonance imaging (MRI), and to provide free hemodynamic force analysis software. MATERIALS AND METHODS: A pulsatile flow phantom was imaged using 4D flow MRI and laser-based particle image velocimetry (PIV). Cardiac 4D flow MRI was performed in healthy volunteers at 1.5T (n = 23). Reproducibility was investigated using MR scanners from two different vendors on the same day (n = 8). Subsets of volunteers were also imaged without respiratory gating (n = 17), at 3T on the same day (n = 6), and 1-12 days later on the same scanner (n = 9, median 6 days). Agreement was measured using the intraclass correlation coefficient (ICC). RESULTS: Phantom validation showed good accuracy for both scanners (Scanner 1: bias -14±9%, y = 0.82x+0.08, R2 = 0.96, Scanner 2: bias -12±8%, y = 0.99x-0.08, R2 = 1.00). Force reproducibility was strong in the LV (0.09±0.07 vs 0.09±0.07 N, bias 0.00±0.04 N, ICC = 0.87) and RV (0.09±0.06 vs 0.09±0.05 N, bias 0.00±0.03, ICC = 0.83). Strong to very strong agreement was found for scans with and without respiratory gating (LV/RV: ICC = 0.94/0.95), scans on different days (ICC = 0.92/0.87), and 1.5T and 3T scans (ICC = 0.93/0.94). CONCLUSION: Software for quantification of hemodynamic forces in 4D-flow MRI was developed, and results show high accuracy and strong to very strong reproducibility for both the LV and RV, supporting its use for research and clinical investigations. The software including source code is released freely for research.

On estimating intraventricular hemodynamic forces from endocardial dynamics: A comparative study with 4D flow MRI.

Intraventricular pressure gradients or hemodynamic forces, which are their global measure integrated over the left ventricular volume, have a fundamental importance in ventricular function. They may help revealing a sub-optimal cardiac function that is not evident in terms of tissue motion, which is naturally heterogeneous and variable, and can influence cardiac adaptation. However, hemodynamic forces are not utilized in clinical cardiology due to the unavailability of simple non-invasive measurement tools. Hemodynamic forces depend on the intraventricular flow; nevertheless, most of them are imputable to the dynamics of the endocardial flow boundary and to the exchange of momentum across the mitral and aortic orifices. In this study, we introduce a simplified model based on first principles of fluid dynamics that allows estimating hemodynamic forces without knowing the velocity field inside the LV. The model is validated with 3D phase-contrast MRI (known as 4D flow MRI) in 15 subjects, (5 healthy and 10 patients) using the endocardial surface reconstructed from the three standard long-axis projections. Results demonstrate that the model provides consistent estimates for the base-apex component (mean correlation coefficient r=0.77 for instantaneous values and r=0.88 for root mean square) and good estimates of the inferolateral-anteroseptal component (r=0.50 and 0.84, respectively). The present method represents a potential integration to the existing ones quantifying endocardial deformation in MRI and echocardiography to add a physics-based estimation of the corresponding hemodynamic forces. These could help the clinician to early detect sub-clinical diseases and differentiate between different cardiac dysfunctional states.

Left and right ventricular hemodynamic forces in healthy volunteers and elite athletes assessed with 4D flow magnetic resonance imaging.

Intracardiac blood flow is driven by hemodynamic forces that are exchanged between the blood and myocardium. Previous studies have been limited to 2D measurements or investigated only left ventricular (LV) forces. Right ventricular (RV) forces and their mechanistic contribution to asymmetric redirection of flow in the RV have not been measured. We therefore aimed to quantify 3D hemodynamic forces in both ventricles in a cohort of healthy subjects, using magnetic resonance imaging 4D flow measurements. Twenty five controls, 14 elite endurance athletes, and 2 patients with LV dyssynchrony were included. 4D flow data were used as input for the Navier-Stokes equations to compute hemodynamic forces over the entire cardiac cycle. Hemodynamic forces were found in a qualitatively consistent pattern in all healthy subjects, with variations in amplitude. LV forces were mainly aligned along the apical-basal longitudinal axis, with an additional component aimed toward the aortic valve during systole. Conversely, RV forces were found in both longitudinal and short-axis planes, with a systolic force component driving a slingshot-like acceleration that explains the mechanism behind the redirection of blood flow toward the pulmonary valve. No differences were found between controls and athletes when indexing forces to ventricular volumes, indicating that cardiac force expenditures are tuned to accelerate blood similarly in small and large hearts. Patients' forces differed from controls in both timing and amplitude. Normal cardiac pumping is associated with specific force patterns for both ventricles, and deviation from these forces may be a sensitive marker of ventricular dysfunction. Reference values are provided for future studies.NEW & NOTEWORTHY Biventricular hemodynamic forces were quantified for the first time in healthy controls and elite athletes (n = 39). Hemodynamic forces constitute a slingshot-like mechanism in the right ventricle, redirecting blood flow toward the pulmonary circulation. Force patterns were similar between healthy subjects and athletes, indicating potential utility as a cardiac function biomarker.

Vortex ring behavior provides the epigenetic blueprint for the human heart.

The laws of fluid dynamics govern vortex ring formation and precede cardiac development by billions of years, suggesting that diastolic vortex ring formation is instrumental in defining the shape of the heart. Using novel and validated magnetic resonance imaging measurements, we show that the healthy left ventricle moves in tandem with the expanding vortex ring, indicating that cardiac form and function is epigenetically optimized to accommodate vortex ring formation for volume pumping. Healthy hearts demonstrate a strong coupling between vortex and cardiac volumes (R(2) = 0.83), but this optimized phenotype is lost in heart failure, suggesting restoration of normal vortex ring dynamics as a new, and possibly important consideration for individualized heart failure treatment. Vortex ring volume was unrelated to early rapid filling (E-wave) velocity in patients and controls. Characteristics of vortex-wall interaction provide unique physiologic and mechanistic information about cardiac diastolic function that may be applied to guide the design and implantation of prosthetic valves, and have potential clinical utility as therapeutic targets for tailored medicine or measures of cardiac health.

Vortex-ring mixing as a measure of diastolic function of the human heart: Phantom validation and initial observations in healthy volunteers and patients with heart failure.

PURPOSE: To present and validate a new method for 4D flow quantification of vortex-ring mixing during early, rapid filling of the left ventricle (LV) as a potential index of diastolic dysfunction and heart failure. MATERIALS AND METHODS: 4D flow mixing measurements were validated using planar laser-induced fluorescence (PLIF) in a phantom setup. Controls (n = 23) and heart failure patients (n = 23) were studied using 4D flow at 1.5T (26 subjects) or 3T (20 subjects) to determine vortex volume (VV) and inflowing volume (VVinflow ). The volume mixed into the vortex-ring was quantified as VVmix-in = VV-VVinflow . The mixing ratio was defined as MXR = VVmix-in /VV. Furthermore, we quantified the fraction of the end-systolic volume (ESV) mixed into the vortex-ring (VVmix-in /ESV) and the fraction of the LV volume at diastasis (DV) occupied by the vortex-ring (VV/DV). RESULTS: PLIF validation of MXR showed fair agreement (R(2) = 0.45, mean ± SD 1 ± 6%). MXR was higher in patients compared to controls (28 ± 11% vs. 16 ± 10%, P < 0.001), while VVmix-in /ESV and VV/DV were lower in patients (10 ± 6% vs. 18 ± 12%, P < 0.01 and 25 ± 8% vs. 50 ± 6%, P < 0.0001). CONCLUSION: Vortex-ring mixing can be quantified using 4D flow. The differences in mixing parameters observed between controls and patients motivate further investigation as indices of diastolic dysfunction. J. Magn. Reson. Imaging 2016;43:1386-1397.

Left ventricular fluid kinetic energy time curves in heart failure from cardiovascular magnetic resonance 4D flow data.

BACKGROUND: Measurement of intracardiac kinetic energy (KE) provides new insights into cardiac hemodynamics and may improve assessment and understanding of heart failure. We therefore aimed to investigate left ventricular (LV) KE time curves in patients with heart failure and in controls. METHODS: Patients with heart failure (n = 29, NYHA class I-IV) and controls (n = 12) underwent cardiovascular magnetic resonance (CMR) including 4D flow. The vortex-ring boundary was computed using Lagrangian coherent structures. The LV endocardium and vortex-ring were manually delineated and KE was calculated as ½mv(2) of the blood within the whole LV and the vortex ring, respectively. RESULTS: The systolic average KE was higher in patients compared to controls (2.2 ± 1.4 mJ vs 1.6 ± 0.6 mJ, p = 0.048), but lower when indexing to EDV (6.3 ± 2.2 µJ/ml vs 8.0 ± 2.1 µJ/ml, p = 0.025). No difference was seen in diastolic average KE (3.2 ± 2.3 mJ vs 2.0 ± 0.8 mJ, p = 0.13) even when indexing to EDV (9.0 ± 4.4 µJ/ml vs 10.2 ± 3.3 µJ/ml, p = 0.41). In patients, a smaller fraction of diastolic average KE was observed inside the vortex ring compared to controls (72 ± 6% vs 54 ± 9%, p < 0.0001). Three distinctive KE time curves were seen in patients which were markedly different from findings in controls, and with a moderate agreement between KE time curve patterns and degree of diastolic dysfunction (Cohen's kappa = 0.49), but unrelated to NYHA classification (p = 0.12), or 6-minute walk test (p = 0.72). CONCLUSION: Patients with heart failure exhibit higher systolic average KE compared to controls, suggesting altered intracardiac blood flow. The different KE time curves seen in patients may represent a conceptually new approach for heart failure classification.

Moderate intensity supine exercise causes decreased cardiac volumes and increased outer volume variations: a cardiovascular magnetic resonance study.

BACKGROUND: The effects on left and right ventricular (LV, RV) volumes during physical exercise remains controversial. Furthermore, no previous study has investigated the effects of exercise on longitudinal contribution to stroke volume (SV) and the outer volume variation of the heart. The aim of this study was to determine if LV, RV and total heart volumes (THV) as well as cardiac pumping mechanisms change during physical exercise compared to rest using cardiovascular magnetic resonance (CMR). METHODS: 26 healthy volunteers (6 women) underwent CMR at rest and exercise. Exercise was performed using a custom built ergometer for one-legged exercise in the supine position during breath hold imaging. Cardiac volumes and atrio-ventricular plane displacement were determined. Heart rate (HR) was obtained from ECG. RESULTS: HR increased during exercise from 60±2 to 94±2 bpm, (p<0.001). LVEDV remained unchanged (p=0.81) and LVESV decreased with -9±18% (p<0.05) causing LVSV to increase with 8±3% (p<0.05). RVEDV and RVESV decreased by -7±10% and -24±14% respectively, (p<0.001) and RVSV increased 5±17% during exercise although not statistically significant (p=0.18). Longitudinal contribution to RVSV decreased during exercise by -6±15% (p<0.05) but was unchanged for LVSV (p=0.74). THV decreased during exercise by -4±1%, (p<0.01) and total heart volume variation (THVV) increased during exercise from 5.9±0.5% to 9.7±0.6% (p<0.001). CONCLUSIONS: Cardiac volumes and function are significantly altered during supine physical exercise. THV becomes significantly smaller due to decreases in RVEDV whilst LVEDV remains unchanged. THVV and consequently radial pumping increases during exercise which may improve diastolic suction during the rapid filling phase.

Quantification of left and right atrial kinetic energy using four-dimensional intracardiac magnetic resonance imaging flow measurements.

Kinetic energy (KE) of atrial blood has been postulated as a possible contributor to ventricular filling. Therefore, we aimed to quantify the left (LA) and right (RA) atrial blood KE using cardiac magnetic resonance (CMR). Fifteen healthy volunteers underwent CMR at 3 T, including a four-dimensional phase-contrast flow sequence. Mean LA KE was lower than RA KE (1.1 ± 0.1 vs. 1.7 ± 0.1 mJ, P < 0.01). Three KE peaks were seen in both atria: one in ventricular systole, one during early ventricular diastole, and one during atrial contraction. The systolic LA peak was significantly smaller than the RA peak (P < 0.001), and the early diastolic LA peak was larger than the RA peak (P < 0.05). Rotational flow contained 46 ± 7% of total KE and conserved energy better than nonrotational flow did. The KE increase in early diastole was higher in the LA (P < 0.001). Systolic KE correlated with the combination of atrial volume and systolic velocity of the atrioventricular plane displacement (r(2) = 0.57 for LA and r(2) = 0.64 for RA). Early diastolic KE of the LA correlated with left ventricle (LV) mass (r(2) = 0.28), however, no such correlation was found in the right heart. This suggests that LA KE increases during early ventricular diastole due to LV elastic recoil, indicating that LV filling is dependent on diastolic suction. Right ventricle (RV) relaxation does not seem to contribute to atrial KE. Instead, RA KE generated during ventricular systole may be conserved in a hydraulic "flywheel" and transferred to the RV through helical flow, which may contribute to RV filling.