Tricuspid valve flow measurement using a deep learning framework for automated valve-tracking 2D phase contrast.

PURPOSE: Tricuspid valve flow velocities are challenging to measure with cardiovascular MR, as the rapidly moving valvular plane prohibits direct flow evaluation, but they are vitally important to diastolic function evaluation. We developed an automated valve-tracking 2D method for measuring flow through the dynamic tricuspid valve. METHODS: Nine healthy subjects and 2 patients were imaged. The approach uses a previously trained deep learning network, TVnet, to automatically track the tricuspid valve plane from long-axis cine images. Subsequently, the tracking information is used to acquire 2D phase contrast (PC) with a dynamic (moving) acquisition plane that tracks the valve. Direct diastolic net flows evaluated from the dynamic PC sequence were compared with flows from 2D-PC scans acquired in a static slice localized at the end-systolic valve position, and also ventricular stroke volumes (SVs) using both planimetry and 2D PC of the great vessels. RESULTS: The mean tricuspid valve systolic excursion was 17.8 ± 2.5 mm. The 2D valve-tracking PC net diastolic flow showed excellent correlation with SV by right-ventricle planimetry (bias ± 1.96 SD = -0.2 ± 10.4 mL, intraclass correlation coefficient [ICC] = 0.92) and aortic PC (-1.0 ± 13.8 mL, ICC = 0.87). In comparison, static tricuspid valve 2D PC also showed a strong correlation but had greater bias (p = 0.01) versus the right-ventricle SV (10.6 ± 16.1 mL, ICC = 0.61). In most (8 of 9) healthy subjects, trace regurgitation was measured at begin-systole. In one patient, valve-tracking PC displayed a high-velocity jet (380 cm/s) with maximal velocity agreeing with echocardiography. CONCLUSION: Automated valve-tracking 2D PC is a feasible route toward evaluation of tricuspid regurgitant velocities, potentially solving a major clinical challenge.

Non-invasive pressure-volume loops using the elastance model and CMR: a porcine validation at transient pre-loads.

Aims: Pressure-volume (PV) loops have utility in the evaluation of cardiac pathophysiology but require invasive measurements. Recently, a time-varying elastance model to derive PV loops non-invasively was proposed, using left ventricular (LV) volume by cardiovascular magnetic resonance (CMR) and brachial cuff pressure as inputs. Validation was performed using CMR and pressure measurements acquired on the same day, but not simultaneously, and without varying pre-loads. This study validates the non-invasive elastance model used to estimate PV loops at varying pre-loads, compared with simultaneous measurements of invasive pressure and volume from real-time CMR, acquired concurrent to an inferior vena cava (IVC) occlusion. Methods and results: We performed dynamic PV loop experiments under CMR guidance in 15 pigs (n = 7 naïve, n = 8 with ischaemic cardiomyopathy). Pre-load was altered by IVC occlusion, while simultaneously acquiring invasive LV pressures and volumes from real-time CMR. Pairing pressure and volume signals yielded invasive PV loops, and model-based PV loops were derived using real-time LV volumes. Haemodynamic parameters derived from invasive and model-based PV loops were compared. Across 15 pigs, 297 PV loops were recorded. Intra-class correlation coefficient (ICC) agreement was excellent between model-based and invasive parameters: stroke work (bias = 0.007 ± 0.03 J, ICC = 0.98), potential energy (bias = 0.02 ± 0.03 J, ICC = 0.99), ventricular energy efficiency (bias = -0.7 ± 2.7%, ICC = 0.98), contractility (bias = 0.04 ± 0.1 mmHg/mL, ICC = 0.97), and ventriculoarterial coupling (bias = 0.07 ± 0.15, ICC = 0.99). All haemodynamic parameters differed between naïve and cardiomyopathy animals (P < 0.05). The invasive vs. model-based PV loop dice similarity coefficient was 0.88 ± 0.04. Conclusion: An elastance model-based estimation of PV loops and associated haemodynamic parameters provided accurate measurements at transient loading conditions compared with invasive PV loops.

Patients with volume-loaded right ventricle - quantification of left ventricular hemodynamic response to intervention measured by noninvasive pressure-volume loops.

Volume loading of the right ventricle (RV) in patients with atrial septal defect (ASD) and patients with repaired Tetralogy of Fallot (rToF) affects the pumping mechanics of the left ventricle (LV). Intervention of the lesion will relieve the RV volume load however quantifiable impact on exercise capacity, arrhytmias or death are limited. A possible explanation could be remaining effects on the function of the LV. The aim of this study was therefore to investigate if hemodynamics of the LV differs between patients with RV volume load due to ASD or rToF and healthy controls and if they change after intervention. Eighteen patients with ASD, 17 patients with rToF and 16 healthy controls underwent cardiac magnetic resonance imaging (CMR) and maximal exercise test with continuous gas analysis. Reexamination was performed 13 ± 2 months after closure of the ASD in 13 of the patients and 10 ± 4 months after pulmonary valve replacement (PVR) in 9 of the patients with rToF. Non-invasive PV-loops from CMR and brachial pressures were analyzed. Stroke work (SW) and potential energy (PE) increased after ASD closure but not in ToF patients after valve repair. Patients with ASD or rToF had higher contractility and arterial elastance than controls. No major effects were seen in LV energetics or in peak VO2 after ASD closure or PVR. Peak VO2 correlated positively with SW and PE in patients with ASD (r = 0.54, p < 0.05; r = 0.61, p < 0.01) and controls (r = 0.72, p < 0.01; r = 0.53, p < 0.05) to approximately the same degree as peak VO2 and end-diastolic volume (EDV) or end-systolic volume (ESV). In ToF patients there was no correlation between PV loop parameters and peak VO2 even if correlation was found between peak VO2 and EDV or ESV. In conclusion, the LV seems to adapt its pumping according to anatomic circumstances without losing efficiency, however there are indications of persistent vascular dysfunction, expressed as high arterial elastance, which might have impact on exercise performance and prognosis. Future studies might elucidate if the duration of RV volume load and decreased LV filling have any impact on the ability of the vascular function to normalize after ASD closure or PVR.

Prognostic utility and characterization of left ventricular hypertrophy using global thickness.

Cardiovascular magnetic resonance (CMR) can accurately measure left ventricular (LV) mass, and several measures related to LV wall thickness exist. We hypothesized that prognosis can be used to select an optimal measure of wall thickness for characterizing LV hypertrophy. Subjects having undergone CMR were studied (cardiac patients, n = 2543; healthy volunteers, n = 100). A new measure, global wall thickness (GT, GTI if indexed to body surface area) was accurately calculated from LV mass and end-diastolic volume. Among patients with follow-up (n = 1575, median follow-up 5.4 years), the most predictive measure of death or hospitalization for heart failure was LV mass index (LVMI) (hazard ratio (HR)[95% confidence interval] 1.16[1.12-1.20], p < 0.001), followed by GTI (HR 1.14[1.09-1.19], p < 0.001). Among patients with normal findings (n = 326, median follow-up 5.8 years), the most predictive measure was GT (HR 1.62[1.35-1.94], p < 0.001). GT and LVMI could characterize patients as having a normal LV mass and wall thickness, concentric remodeling, concentric hypertrophy, or eccentric hypertrophy, and the three abnormal groups had worse prognosis than the normal group (p < 0.05 for all). LV mass is highly prognostic when mass is elevated, but GT is easily and accurately calculated, and adds value and discrimination amongst those with normal LV mass (early disease).

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.

Early-Onset Fetal Growth Restriction Increases Left Ventricular Sphericity in Adolescents Born Very Preterm.

Left ventricular shape alterations predict cardiovascular outcomes and have been observed in children born preterm and after fetal growth restriction (FGR). The aim was to investigate whether left ventricular shape is altered in adolescents born very preterm and if FGR has an additive effect. Adolescents born very preterm due to verified early-onset FGR and two control groups with birthweight appropriate for gestational age (AGA), born at similar gestational age and at term, respectively, underwent cardiac MRI. Principal component analysis was applied to find the modes of variation best explaining shape variability for end-diastole, end-systole, and for the combination of both, the latter indicative of function. Seventy adolescents were included (13-16 years; 49% males). Sphericity was increased for preterm FGR versus term AGA for end-diastole (36[0-60] vs - 42[- 82-8]; p = 0.01) and the combined analysis (27[- 23-94] vs - 51[- 119-11]; p = 0.01), as well as for preterm AGA versus term AGA for end-diastole (30[- 56-115] vs - 42[- 82-8]; p = 0.04), for end-systole (57[- 29-89] vs - 30[- 79-34]; p = 0.03), and the combined analysis (44[- 50-145] vs - 51[- 119-11]; p = 0.02). No group differences were observed for left ventricular mass or ejection fraction (all p ≥ 0.33). Sphericity was increased after very preterm birth and exacerbated by early-onset FGR, indicating an additive effect to that of very preterm birth on left ventricular remodeling. Increased sphericity may be a prognostic biomarker of future cardiovascular disease in this cohort that as of yet shows no signs of cardiac dysfunction using standard clinical measurements.

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 34.9±9.1) underwent separate infusions of insulin+glucose infusion (I+G) or Intralipid infusion. We used cardiovascular magnetic resonance to assess cardiac function and measured energetics using phosphorus-31 magnetic resonance spectroscopy. To investigate the effects of these infusions on cardiac substrate use, function, and myocardial oxygen uptake (MVo2), invasive arteriovenous sampling and pressure-volume loops were performed (n=9). RESULTS: At rest, we found that the heart had considerable metabolic flexibility. During I+G, cardiac glucose uptake and oxidation were predominant (70±14% total energy substrate for adenosine triphosphate production versus 17±16% for Intralipid; P=0.002); however, no change in cardiac function was seen relative to basal conditions. In contrast, during Intralipid infusion, cardiac long-chain fatty acid (LCFA) delivery, uptake, LCFA acylcarnitine production, and fatty acid oxidation were all increased (LCFA 73±17% of total substrate versus 19±26% total during I+G; P=0.009). Myocardial energetics were better with Intralipid compared with I+G (phosphocreatine/adenosine triphosphate 1.86±0.25 versus 2.01±0.33; P=0.02), and systolic and diastolic function were improved (LVEF 34.9±9.1 baseline, 33.7±8.2 I+G, 39.9±9.3 Intralipid; P<0.001). During increased cardiac workload, LCFA uptake and oxidation were again increased during both infusions. There was no evidence of systolic dysfunction or lactate efflux at 65% maximal heart rate, suggesting that a metabolic switch to fat did not cause clinically meaningful ischemic metabolism. CONCLUSIONS: Our findings show that even in nonischemic heart failure with reduced ejection fraction with severely impaired systolic function, significant cardiac metabolic flexibility is retained, including the ability to alter substrate use to match both arterial supply and changes in workload. Increasing LCFA uptake and oxidation is associated with improved myocardial energetics and contractility. Together, these findings challenge aspects of the rationale underlying existing metabolic therapies for heart failure and suggest that strategies promoting fatty acid oxidation may form the basis for future therapies.

Endurance-trained subjects and sedentary controls increase ventricular contractility and efficiency during exercise: Feasibility of hemodynamics assessed by non-invasive pressure-volume loops.

INTRODUCTION: Pressure-volume (PV) loops can be used to assess both load-dependent and load-independent measures of cardiac hemodynamics. However, analysis of PV loops during exercise is challenging as it requires invasive measures. Using a novel method, it has been shown that left ventricular (LV) PV loops at rest can be obtained non-invasively from cardiac magnetic resonance imaging (CMR) and brachial pressures. Therefore, the aim of this study was to assess if LV PV loops can be obtained non-invasively from CMR during exercise to assess cardiac hemodynamics. METHODS: Thirteen endurance trained (ET; median 48 years [IQR 34-60]) and ten age and sex matched sedentary controls (SC; 43 years [27-57]) were included. CMR images were acquired at rest and during moderate intensity supine exercise defined as 60% of expected maximal heart rate. Brachial pressures were obtained in conjunction with image acquisition. RESULTS: Contractility measured as maximal ventricular elastance (Emax) increased in both groups during exercise (ET: 1.0 mmHg/ml [0.9-1.1] to 1.1 mmHg/ml [0.9-1.2], p<0.01; SC: 1.1 mmHg/ml [0.9-1.2] to 1.2 mmHg/ml [1.0-1.3], p<0.01). Ventricular efficiency (VE) increased in ET from 70% [66-73] at rest to 78% [75-80] (p<0.01) during exercise and in SC from 68% [63-72] to 75% [73-78] (p<0.01). Arterial elastance (EA) decreased in both groups (ET: 0.8 mmHg/ml [0.7-0.9] to 0.7 mmHg/ml [0.7-0.9], p<0.05; SC: 1.0 mmHg/ml [0.9-1.2] to 0.9 mmHg/ml [0.8-1.0], p<0.05). Ventricular-arterial coupling (EA/Emax) also decreased in both groups (ET: 0.9 [0.8-1.0] to 0.7 [0.6-0.8], p<0.01; SC: 1.0 [0.9-1.1] to 0.7 [0.7-0.8], p<0.01). CONCLUSIONS: This study demonstrates for the first time that LV PV loops can be generated non-invasively during exercise using CMR. ET and SC increase ventricular efficiency and contractility and decrease afterload and ventricular-arterial coupling during moderate supine exercise. These results confirm known physiology. Therefore, this novel method is applicable to be used during exercise in different cardiac disease states, which has not been possible non-invasively before.

Mild hypothermia attenuates ischaemia/reperfusion injury: insights from serial non-invasive pressure-volume loops.

AIMS: Mild hypothermia, 32-35°C, reduces infarct size in experimental studies, potentially mediating reperfusion injuries, but human trials have been ambiguous. To elucidate the cardioprotective mechanisms of mild hypothermia, we analysed cardiac performance in a porcine model of ischaemia/reperfusion, with serial cardiovascular magnetic resonance (CMR) imaging throughout 1 week using non-invasive pressure-volume (PV) loops. METHODS AND RESULTS: Normothermia and Hypothermia group sessions (n = 7 + 7 pigs, non-random allocation) were imaged with Cardiovascular magnetic resonance (CMR) at baseline and subjected to 40 min of normothermic ischaemia by catheter intervention. Thereafter, the Hypothermia group was rapidly cooled (mean 34.5°C) for 5 min before reperfusion. Additional CMR sessions at 2 h, 24 h, and 7 days acquired ventricular volumes and ischaemic injuries (unblinded analysis). Stroke volume (SV: -24%; P = 0.029; Friedmans test) and ejection fraction (EF: -20%; P = 0.068) were notably reduced at 24 h in the Normothermia group compared with baseline. In contrast, the decreases were ameliorated in the Hypothermia group (SV: -6%; P = 0.77; EF: -6%; P = 0.13). Mean arterial pressure remained stable in Normothermic animals (-3%, P = 0.77) but dropped 2 h post-reperfusion in hypothermic animals (-18%, P = 0.007). Both groups experienced a decrease and partial recovery pattern for PV loop-derived variables over 1 week, but the adverse effects tended to attenuate in the Hypothermia group. Infarct sizes were 10 ± 8% in Hypothermic and 15 ± 8% in Normothermic animals (P = 0.32). Analysis of covariance at 24 h indicated that hypothermia has cardioprotective properties incremental to reducing infarct size, such as higher external power (P = 0.061) and lower arterial elastance (P = 0.015). CONCLUSION: Using non-invasive PV loops by CMR, we observed that mild hypothermia at reperfusion alleviates the heart's work after ischaemia/reperfusion injuries during the first week and preserves short-term cardiac performance. This hypothesis-generating study suggests hypothermia to have cardioprotective properties, incremental to reducing infarct size. The primary cardioprotective mechanism was likely an afterload reduction acutely unloading the left ventricle.

Deep learning can yield clinically useful right ventricular segmentations faster than fully manual analysis.

Right ventricular (RV) volumes are commonly obtained through time-consuming manual delineations of cardiac magnetic resonance (CMR) images. Deep learning-based methods can generate RV delineations, but few studies have assessed their ability to accelerate clinical practice. Therefore, we aimed to develop a clinical pipeline for deep learning-based RV delineations and validate its ability to reduce the manual delineation time. Quality-controlled delineations in short-axis CMR scans from 1114 subjects were used for development. Time reduction was assessed by two observers using 50 additional clinical scans. Automated delineations were subjectively rated as (A) sufficient for clinical use, or as needing (B) minor or (C) major corrections. Times were measured for manual corrections of delineations rated as B or C, and for fully manual delineations on all 50 scans. Fifty-eight % of automated delineations were rated as A, 42% as B, and none as C. The average time was 6 min for a fully manual delineation, 2 s for an automated delineation, and 2 min for a minor correction, yielding a time reduction of 87%. The deep learning-based pipeline could substantially reduce the time needed to manually obtain clinically applicable delineations, indicating ability to yield right ventricular assessments faster than fully manual analysis in clinical practice. However, these results may not generalize to clinics using other RV delineation guidelines.

Automatic Segmentation of the Fetus in 3D Magnetic Resonance Images Using Deep Learning: Accurate and Fast Fetal Volume Quantification for Clinical Use.

Magnetic resonance imaging (MRI) provides images for estimating fetal volume and weight, but manual delineations are time consuming. The aims were to (1) validate an algorithm to automatically quantify fetal volume by MRI; (2) compare fetal weight by Hadlock's formulas to that of MRI; and (3) quantify fetal blood flow and index flow to fetal weight by MRI. Forty-two fetuses at 36 (29-39) weeks gestation underwent MRI. A neural network was trained to segment the fetus, with 20 datasets for training and validation, and 22 for testing. Hadlock's formulas 1-4 with biometric parameters from MRI were compared with weight by MRI. Blood flow was measured using phase-contrast MRI and indexed to fetal weight. Bland-Altman analysis assessed the agreement between automatic and manual fetal segmentation and the agreement between Hadlock's formulas and fetal segmentation for fetal weight. Bias and 95% limits of agreement were for automatic versus manual measurements 4.5 ± 351 ml (0.01% ± 11%), and for Hadlock 1-4 vs MRI 108 ± 435 g (3% ± 14%), 211 ± 468 g (7% ± 15%), 106 ± 425 g (4% ± 14%), and 179 ± 472 g (6% ± 15%), respectively. Umbilical venous flow was 406 (range 151-650) ml/min (indexed 162 (range 52-220) ml/min/kg), and descending aortic flow was 763 (range 481-1160) ml/min (indexed 276 (range 189-386) ml/min/kg). The automatic method showed good agreement with manual measurements and saves considerable analysis time. Hadlock 1-4 generally agree with MRI. This study also illustrates the confounding effects of fetal weight on absolute blood flow, and emphasizes the benefit of indexed measurements for physiological assessment.

Infarct quantification with cardiovascular magnetic resonance using "standard deviation from remote" is unreliable: validation in multi-centre multi-vendor data.

BACKGROUND: The objective of the study was to investigate variability and agreement of the commonly used image processing method "n-SD from remote" and in particular for quantifying myocardial infarction by late gadolinium enhancement (LGE) cardiovascular magnetic resonance (CMR). LGE-CMR in tandem with the analysis method "n-SD from remote" represents the current reference standard for infarct quantification. This analytic method utilizes regions of interest (ROIs) and defines infarct as the tissue with a set number of standard deviations (SD) above the signal intensity of remote nulled myocardium. There is no consensus on what the set number of SD is supposed to be. Little is known about how size and location of ROIs and underlying signal properties in the LGE images affect results. Furthermore, the method is frequently used elsewhere in medical imaging often without careful validation. Therefore, the usage of the "n-SD" method warrants a thorough validation. METHODS: Data from 214 patients from two multi-center cardioprotection trials were included. Infarct size from different remote ROI positions, ROI size, and number of standard deviations ("n-SD") were compared with reference core lab delineations. RESULTS: Variability in infarct size caused by varying ROI position, ROI size, and "n-SD" was 47%, 48%, and 40%, respectively. The agreement between the "n-SD from remote" method and the reference infarct size by core lab delineations was low. Optimal "n-SD" threshold computed on a slice-by-slice basis showed high variability, n = 5.3 ± 2.2. CONCLUSION: The "n-SD from remote" method is unreliable for infarct quantification due to high variability which depends on different placement and size of remote ROI, number "n-SD", and image signal properties related to the CMR-scanner and sequence used. Therefore, the "n-SD from remote" method should not be used, instead methods validated against an independent standard are recommended.

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.

Haemodynamic left-ventricular changes during dobutamine stress in patients with atrial septal defect assessed with magnetic resonance imaging-based pressure-volume loops.

BACKGROUND: Atrial septal defect (ASD) results in a left-to-right shunt causing right-ventricular (RV) volume overload and decreased cardiac output from the left ventricle. Pressure-volume (PV) loops enable comprehensive assessment of ventricular function and might increase understanding of the pathophysiology of ASD. The aim of this study was to investigate if left-ventricular (LV) haemodynamic response to stress in patients with ASD differs from controls. MATERIAL AND METHODS: Patients with ASD (n = 18, age 51 ± 18) and healthy controls (n = 16, age 35 ± 13) underwent cardiac magnetic resonance (CMR) and brachial cuff pressure measurements at rest and during dobutamine stress. An in-house, validated method was used to compute PV loops. RESULTS: Patients had lower stroke work, potential energy and external power at rest than controls (p < 0.001; p < 0.05; p < 0.05). Stroke work and external power increased and potential energy decreased during stress in patients (p < 0.05; p < 0.0001; p < 0.01) and controls (p < 0.0001; p < 0.001; p < 0.01). Contractility and arterial elastance at rest were higher in patients than controls (p < 0.01; p < 0.01). Contractility increased during stress in both groups (p < 0.0001; p < 0.001). There was no difference between patients and controls in arterio-ventricular coupling. CONCLUSION: LV haemodynamic response to stress can be assessed using noninvasive PV loops derived from CMR and brachial blood pressure. Patients with ASD had normal LV energy efficiency, in contrast to other patient groups with decreased cardiac output. Data suggest that patients with ASD had an increased inotropic level at rest with high contractility and heart rate but were able to respond with a further increase during stress, albeit to not as high a cardiac output as controls.

Non-invasive quantification of pressure-volume loops in patients with Fontan circulation.

BACKGROUND: Pressure-volume (PV) loops provide comprehensive information of cardiac function, but commonly implies an invasive procedure under general anesthesia. A novel technique has made it possible to non-invasively estimate PV loops with cardiac magnetic resonance (CMR) and brachial pressure which would enable good volume estimation of often anatomically complex ventricles without the need of anesthesia in most cases. In this study we aimed to compare how hemodynamic parameters derived from PV loops in patients with Fontan circulation differ to controls. METHODS: Patients with Fontan circulation (n = 17, median age 12 years, IQR 6-15) and healthy controls (n = 17, 14 years, IQR 13-22) were examined with CMR. Short axis balanced steady-state free-precession cine images covering the entire heart were acquired. PV loops were derived from left ventricular volumes in all timeframes and brachial blood pressure from cuff sphygmomanometry. RESULTS: Fontan patients had lower stroke work, ventricular mechanical efficiency and external power compared to controls. Fontan patients with dominant right ventricle had higher potential energy indexed to body surface area but lower contractility (Ees) compared to controls. Fontan patients had higher arterial elastance (Ea) and Ea/Ees ratio than controls. Contractility showed no correlation with ejection fraction (EF) in Fontan patients irrespective of ventricular morphology. No difference was seen in energy per ejected volume between Fontan patients and controls. CONCLUSIONS: This non-invasive PV-loop method could be used in future studies to show the potential prognostic value of these measures and if changes in ventricular function over time can be detected earlier by this method compared to changes in ventricular volumes and EF. In contrast to patients with acquired heart failure, Fontan patients had similar energy per ejected volume as controls which suggests similar ventricular oxygen consumption to deliver the same volume in Fontan patients as in controls.

Ventricular longitudinal function by cardiovascular magnetic resonance predicts cardiovascular morbidity in HFrEF patients.

AIMS: Ventricular longitudinal function measured as basal-apical atrioventricular plane displacement (AVPD) or global longitudinal strain (GLS) is a potent predictor of mortality and could potentially be a predictor of heart failure-associated morbidity. We hypothesized that low AVPD and GLS are associated with the combined endpoint of cardiovascular mortality and heart failure-associated morbidity. METHODS AND RESULTS: Two hundred eighty-seven patients (age 62 ± 12 years, 78% male) with heart failure with reduced (≤40%) ejection fraction (HFrEF) referred to a cardiovascular magnetic resonance exam were included. Ventricular longitudinal function, ventricular volume, and myocardial fibrosis or infarction were analysed from cine and late gadolinium enhancement images. National registries provided data on causes of cardiovascular hospitalizations and cardiovascular mortality for the combined endpoint. Time-to-event analysis capable of including reoccurring events was employed with a 5-year follow-up. HFrEF patients had EF 26.5 ± 8.0%, AVPD 7.8 ± 2.4 mm, and GLS -7.5 ± 3.0%. In contrast, ventricular longitudinal function was approximately twice as large in an age-matched control group (AVPD 15.3 ± 1.6 mm; GLS -20.6 ± 2.0%; P < 0.001 for both). There were 578 events in total, and the majority were HF hospitalizations (n = 418). Other major events were revascularizations (n = 64), cardiovascular deaths (n = 40), and myocardial infarctions (n = 21). One hundred fifty-five (54%) patients experienced at least one event (mean 2.0, range 0-64). Of these patients, 119 (71%) had three events or fewer, and the first three events comprised 51% of all events (295 events). Patients in the bottom AVPD or GLS tertile (<6.8 mm or >-6.1%) overall experienced more than 3 times as many events as the top tertile (>8.8 mm or <-8.4%; P < 0.001). Patients in this tertile also faced more cardiovascular deaths (P < 0.05), HF hospitalizations (P = 0.001), myocardial infarctions (only GLS: P = 0.032), and accumulated longer in-hospital length-of-stay overall (AVPD 20.9 vs. 9.1 days; GLS 22.4 vs. 6.5 days; P = 0.001 for both), and from HF hospitalizations (AVPD 19.3 vs. 8.3 days; GLS 19.3 vs. 5.4 days; P = 0.001 for both). In multivariate analysis adjusted for significant covariates, AVPD and GLS remained independent predictors of events (hazard ratio 1.12 per-mm-decrease and 1.13 per-%-increase) alongside hyponatremia (<135 mmol/L), aetiology of HF, and LV end-diastolic volume index. CONCLUSIONS: Low ventricular longitudinal function is associated with an increase in number of events as well as longer in-hospital stay from cardiovascular causes. In addition, AVPD and GLS have independent prognostic value for cardiovascular mortality and morbidity in HFrEF patients.

Validation and quantification of left ventricular function during exercise and free breathing from real-time cardiac magnetic resonance images.

Exercise cardiovascular magnetic resonance (CMR) can unmask cardiac pathology not evident at rest. Real-time CMR in free breathing can be used, but respiratory motion may compromise quantification of left ventricular (LV) function. We aimed to develop and validate a post-processing algorithm that semi-automatically sorts real-time CMR images according to breathing to facilitate quantification of LV function in free breathing exercise. A semi-automatic algorithm utilizing manifold learning (Laplacian Eigenmaps) was developed for respiratory sorting. Feasibility was tested in eight healthy volunteers and eight patients who underwent ECG-gated and real-time CMR at rest. Additionally, volunteers performed exercise CMR at 60% of maximum heart rate. The algorithm was validated for exercise by comparing LV mass during exercise to rest. Respiratory sorting to end expiration and end inspiration (processing time 20 to 40 min) succeeded in all research participants. Bias ± SD for LV mass was 0 ± 5 g when comparing real-time CMR at rest, and 0 ± 7 g when comparing real-time CMR during exercise to ECG-gated at rest. This study presents a semi-automatic algorithm to retrospectively perform respiratory sorting in free breathing real-time CMR. This can facilitate implementation of exercise CMR with non-ECG-gated free breathing real-time imaging, without any additional physiological input.

Pulse Wave Velocity Measurements by Magnetic Resonance Imaging in Neonates and Adolescents: Methodological Aspects and Their Clinical Implications.

Pulse wave velocity (PWV) by cardiovascular magnetic resonance (CMR) lacks standardization. The aim of this study was to investigate methodological aspects of PWV measurements by CMR in neonates and adolescents. A computer phantom was created to validate the temporal resolution required for accurate PWV. Fifteen neonates and 71 adolescents underwent CMR with reference standard 3D angiography and phase-contrast flow acquisitions, and in a subset coronal overview images. Velocity and flow curves, transit time methods (time-to-foot (TTF), maximum upslope, and time-to-peak (TTP)), and baseline correction methods (no correction, automatic and manual) were investigated. In neonates, required timeframes per cardiac cycle for accurate PWV was 42 for the aortic arch and 41 for the thoracic aorta. In adolescents, corresponding values were 39 and 32. Aortic length differences by overview images and 3D angiography in adolescents were - 16-18 mm (aortic arch) and - 25-30 mm (thoracic aorta). Agreement in PWV between automatic and manual baseline correction was - 0.2 ± 0.3 m/s in neonates and 0.0 ± 0.1 m/s in adolescents. Velocity and flow-derived PWV measurements did not differ in either group (all p > 0.08). In neonates, transit time methods did not differ (all p > 0.19) but in adolescents PWV was higher for TTF (3.8 ± 0.5 m/s) and maximum upslope (3.7 ± 0.6 m/s) compared to TTP (2.7 ± 1.0 m/s; p < 0.0001). This study is a step toward standardization of PWV in neonates and adolescents using CMR. It provides required temporal resolution for phase-contrast flow acquisitions for typical heartrates in neonates and adolescents, and supports 3D angiography and time-to-foot with automatic baseline correction for accurate PWV measurements.

Super-Resolution Cine Image Enhancement for Fetal Cardiac Magnetic Resonance Imaging.

BACKGROUND: Fetal cardiac magnetic resonance imaging (MRI) improves the diagnosis of congenital heart defects, but is sensitive to fetal motion due to long image acquisition time. This may be overcome with faster image acquisition with low resolution, followed by image enhancement to provide clinically useful images. PURPOSE: To combine phase-encoding undersampling with super-resolution neural networks to achieve high-resolution fetal cine cardiac MR images with short acquisition time. STUDY TYPE: Prospective. SUBJECTS: Twenty-eight fetuses (gestational week 36 [interquartile range 33-38 weeks]). FIELD STRENGTH/SEQUENCE: 1.5 T, balanced steady-state free precession (bSSFP) cine sequence. ASSESSMENT: Images were acquired using fully sampled Doppler ultrasound-gated clinical bSSFP cine as reference, with equivalent cine sequences with decreased phase-encoding resolution (25%, 33%, and 50% of clinical standard). Two super-resolution methods based on convolutional neural networks were proposed and evaluated (phasrGAN and phasrresnet). Data were partitioned into training (36 cine slices), validation (3 cine slices), and test sets (67 cine slices) without overlap. Conventional reconstruction methods using bicubic interpolation and k-space zeropadding were used for comparison. Three blinded observers scored image quality between 1 and 10. STATISTICAL TESTS: Image scores are reported as median [interquartile range] and were compared using Mann-Whitney's nonparametric test with P < 0.05 showing statistically significant differences. RESULTS: Both proposed methods showed no significant difference in image quality compared to clinical images (8 [7-8.5]) down to 33% (phasrGAN 8 [6.5-8]; phasrresnet 8 [7-8], all P ≥ 0.19) phase-encoding resolution, i.e., up to three times faster image acquisition, whereas bicubic interpolation and k-space zeropadding showed significantly lower quality for 33% phase-encoding resolution (both 7 [6-8]). DATA CONCLUSION: Super-resolution enhancement can be used for fetal cine cardiac MRI to reduce image acquisition time while maintaining image quality. This may lead to an improved success rate for fetal cine MR imaging, as the impact of fetal motion is lessened by shortened acquisitions. LEVEL OF EVIDENCE: 1 TECHNICAL EFFICACY: Stage 2.