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.

Unravelling the mechanisms of CE-SSFP in imaging myocardium at risk: The effect of relaxation times on myocardial contrast.

PURPOSE: The aim of this study was to investigate the contrast mechanisms of Contrast-enhanced steady-state free-precession (CE-SSFP) through the utilization of Bloch simulations in an experimental porcine model and in patients with acute myocardial infarction. METHODS: Six pigs and ten patients with myocardial infarction underwent CMR and tissue characterization at 1.5 T whereas a Bloch simulation framework was utilized to simulate the CE-SSFP signal formation and compare it against the actual CE-SSFP signal acquired from the experimental porcine model and the patient population. The relaxation times of remote, salvaged, and infarcted myocardium were calculated after the injection of gadolinium, at the time of CE-SSFP acquisition. Simulations were performed using the same CE-SSFP pulse sequence as used on the scanner on a set of spins with the calculated relaxation times from the CMR scans. RESULTS: The normalized signal intensities of salvaged and infarcted myocardium obtained with simulations were lower than the corresponding normalized signal intensities obtained in vivo in pigs (p < 0.05, 134% vs 153%) and in patients (p < 0.05, 126% vs 145%). The results from simulations showed a linear relationship to the results obtained in the experimental porcine model (r2 = 0.61) and in patients (r2 = 0.69). CONCLUSION: The T1 and T2 values of remote, salvaged, and infarcted myocardium only partly explain the signal intensities in CE-SSFP images. Bloch simulations suggest that there may be more elements that contribute to the CE-SSFP contrast. Integration of other aspects of the MR experiment into the simulation model could further help to fully unravel the mechanisms of CE-SSFP.

Diagnostic confidence with quantitative cardiovascular magnetic resonance perfusion mapping increases with increased coverage of the left ventricle.

BACKGROUND: Quantitative cardiovascular magnetic resonance (CMR) first pass perfusion maps are conventionally acquired with 3 short-axis (SAX) views (basal, mid, and apical) in every heartbeat (3SAX/1RR). Thus, a significant part of the left ventricle (LV) myocardium, including the apex, is not covered. The aims of this study were 1) to investigate if perfusion maps acquired with 3 short-axis views sampled every other RR-interval (2RR) yield comparable quantitative measures of myocardial perfusion (MP) as 1RR and 2) to assess if acquiring 3 additional perfusion views (i.e., total of 6) every other RR-interval (2RR) increases diagnostic confidence. METHODS: In 287 patients with suspected ischemic heart disease stress and rest MP were performed on clinical indication on a 1.5T MR scanner. Eighty-three patients were examined by acquiring 3 short-axis perfusion maps with 1RR sampling (3SAX/1RR); for which also 2RR maps were reconstructed. Additionally, in 103 patients 3 short-axis and 3 long-axis (LAX; 2-, 3, and 4-chamber view) perfusion maps were acquired using 2RR sampling (3SAX + 3LAX/2RR) and in 101 patients 6 short-axis perfusion maps using 2RR sampling (6SAX/2RR) were acquired. The diagnostic confidence for ruling in or out stress-induced ischemia was scored according to a Likert scale (certain ischemia [2 points], probably ischemia [1 point], uncertain [0 points], probably no ischemia [1 point], certain no ischemia [2 points]). RESULTS: There was a strong correlation (R = 0.99) between 3SAX/1RR and 3SAX/2RR for global MP (mL/min/g). The diagnostic confidence score increased significantly when the number of perfusion views was increased from 3 to 6 (1.24 ± 0.68 vs 1.54 ± 0.64, p < 0.001 with similar increase for 3SAX+3LAX/2RR (1.29 ± 0.68 vs 1.55 ± 0.65, p < 0.001) and for 6SAX/2RR (1.19 ± 0.69 vs 1.53 ± 0.63, p < 0.001). CONCLUSION: Quantitative perfusion mapping with 2RR sampling of data yields comparable perfusion values as 1RR sampling, allowing for the acquisition of additional views within the same perfusion scan. The diagnostic confidence for stress-induced ischemia increases when adding 3 additional views, short- or long axes, to the conventional 3 short-axis views. Thus, future development and clinical implementation of quantitative CMR perfusion should aim at increasing the LV coverage from the current standard using 3 short-axis views.

Contractility, ventriculoarterial coupling, and stroke work after acute myocardial infarction using CMR-derived pressure-volume loop data.

BACKGROUND: Noninvasive left ventricular (LV) pressure-volume (PV) loops derived by cardiac magnetic resonance (CMR) have recently been shown to enable characterization of cardiac hemodynamics. Thus, such PV loops could potentially provide additional diagnostic information such as contractility, arterial elastance (Ea ) and stroke work (SW) currently not available in clinical routine. This study sought to investigate to what extent PV-loop variables derived with a novel noninvasive method can provide incremental physiological information over cardiac dimensions and blood pressure in patients with acute myocardial infarction (MI). METHODS: A total of 100 patients with acute MI and 75 controls were included in the study. All patients underwent CMR 2-6 days after MI including assessment of myocardium at risk (MaR) and infarct size (IS). Noninvasive PV loops were generated from CMR derived LV volumes and brachial blood pressure measurements. The following variables were quantified: Maximal elastance (Emax ) reflecting contractility, Ea , ventriculoarterial coupling (Ea /Emax ), SW, potential energy, external power, energy per ejected volume, and efficiency. RESULTS: All PV-loop variables were significantly different in MI patients compared to healthy volunteers, including contractility (Emax : 1.34 ± 0.48 versus 1.50 ± 0.41 mmHg/mL, p = .024), ventriculoarterial coupling (Ea /Emax : 1.27 ± 0.61 versus 0.73 ± 0.17, p < .001) and SW (0.96 ± 0.32 versus 1.38 ± 0.32 J, p < .001). These variables correlated to both MaR and IS (Emax : r2 = 0.25 and r2 = 0.29; Ea /Emax : r2 = 0.36 and r2 = 0.41; SW: r2 = 0.21 and r2 = 0.25). CONCLUSIONS: Noninvasive PV-loops provide physiological information beyond conventional diagnostic variables, such as ejection fraction, early after MI, including measures of contractility, ventriculoarterial coupling, and SW.

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).

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.

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.

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.

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.

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.

Incremental Value of Exercise ECG to Myocardial Perfusion Single-Photon Emission Computed Tomography for Prediction of Cardiac Events.

Background Both myocardial perfusion single-photon emission computed tomography (MPS) and exercise ECG (Ex-ECG) carry prognostic information in patients with stable chest pain. However, it is not fully understood if combining the findings of MPS and Ex-ECG improves risk prediction. Current guidelines no longer recommend Ex-ECG for diagnostic evaluation of chronic coronary syndrome, but Ex-ECG could still be of incremental prognostic importance. Methods and Results This study comprised 908 consecutive patients (age 63.3±9.4 years, 49% male) who performed MPS with Ex-ECG. Subjects were followed for 5 years. The end point was a composite of cardiovascular death, acute myocardial infarction, unstable angina, and unplanned percutaneous coronary intervention. National registry data and medical charts were used for end point allocation. Combining the findings of MPS and Ex-ECG resulted in concordant evidence of ischemia in 72 patients or absence of ischemia in 634 patients. Discordant results were found in 202 patients (MPS-/Ex-ECG+, n=126 and MPS+/Ex-ECG-, n=76). During follow-up, 95 events occurred. Annualized event rates significantly increased across groups (MPS-/Ex-ECG- =1.3%, MPS-/Ex-ECG+ =3.0%, MPS+/Ex-ECG- =5.1% and MPS+/Ex-ECG+ =8.0%). In multivariable analyses MPS was the strongest predictor regardless of Ex-ECG findings (MPS+/Ex-ECG-, hazard ratio [HR], 3.0, P=0.001 or MPS+/Ex-ECG+, HR,4.0, P<0.001). However, an abnormal Ex-ECG almost doubled the risk in subjects with normal MPS (MPS-/Ex-ECG+, HR, 1.9, P=0.04). Conclusions In patients with chronic coronary syndrome, combining the results from MPS and Ex-ECG led to improved risk prediction. Even though MPS is the stronger predictor, there is an incremental value of adding data from Ex-ECG to MPS, especially in patients with normal MPS.

Diagnostic accuracy for CZT gamma camera compared to conventional gamma camera technique with myocardial perfusion single-photon emission computed tomography: Assessment of myocardial infarction and function.

BACKGROUND: The solid-state cadmium-zinc-telluride (CZT) gamma camera for myocardial perfusion single-photon emission computed tomography (MPS) has theoretical advantages compared to the conventional gamma camera technique. This includes more sensitive detectors and better energy resolution. We aimed to explore the diagnostic performance of gated MPS with a CZT gamma camera compared to a conventional gamma camera for detection of myocardial infarct (MI) and assessment of left ventricular (LV) volumes and ejection fraction (LVEF), using cardiac magnetic resonance (CMR) as the reference method. METHODS: Seventy-three patients (26% female) with known or suspected chronic coronary syndrome were examined with gated MPS using both a CZT gamma camera and a conventional gamma camera as well as with CMR. Presence and extent of MI on MPS and late gadolinium enhancement (LGE) CMR was evaluated. For LV volumes, LVEF and LV mass, gated MPS images and cine CMR images were evaluated. RESULTS: MI was found in 42 patients on CMR. The overall sensitivity, specificity, positive and negative predictive values for the CZT and the conventional gamma camera were the same (67%, 100%, 100% and 69%). For infarct size > 3% on CMR, the sensitivity was 82% for the CZT and 73% for the conventional gamma camera, respectively. LV volumes were significantly underestimated by MPS compared to CMR (P ≤ .002 for all measures). The underestimation was slightly less pronounced for the CZT compared to the conventional gamma camera (2-10 mL, P ≤ .03 for all measures). For LVEF, however, accuracy was high for both gamma cameras. CONCLUSION: Differences between a CZT and a conventional gamma camera for detection of MI and assessment of LV volumes and LVEF are small and do not appear to be clinically significant.

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.

Fetal growth restriction followed by very preterm birth is associated with smaller kidneys but preserved kidney function in adolescence.

BACKGROUND: Preterm birth and fetal growth restriction (FGR) are associated with structural and functional kidney changes, increasing long-term risk for chronic kidney disease and hypertension. However, recent studies in preterm children are conflicting, indicating structural changes but normal kidney function. This study therefore assessed kidney structure and function in a cohort of adolescents born very preterm with and without verified FGR. METHODS: Adolescents born very preterm with FGR and two groups with appropriate birthweight (AGA) were included; one matched for gestational week at birth and one born at term. Cortical and medullary kidney volumes and T1 and T2* mapping values were assessed by magnetic resonance imaging. Biochemical markers of kidney function and renin-angiotensin-aldosterone system (RAAS) activation were analyzed. RESULTS: Sixty-four adolescents were included (13-16 years; 48% girls). Very preterm birth with FGR showed smaller total (66 vs. 75 ml/m2; p = 0.01) and medullary volume (19 vs. 24 ml/m2; p < 0.0001) compared to term AGA. Corticomedullary volume ratio decreased from preterm FGR (2.4) to preterm AGA (2.2) to term AGA (1.9; p = 0.004). There were no differences in T1 or T2* values (all p ≥ 0.34) or in biochemical markers (all p ≥ 0.12) between groups. CONCLUSIONS: FGR with abnormal fetal blood flow followed by very preterm birth is associated with smaller total kidney and medullary kidney volumes, but not with markers of kidney dysfunction or RAAS activation in adolescence. Decreased total kidney and medullary volumes may still precede a long-term decrease in kidney function, and potentially be used as a prognostic marker. A higher resolution version of the Graphical abstract is available as Supplementary information.

Higher blood pressure in adolescent boys after very preterm birth and fetal growth restriction.

BACKGROUND: Although preterm birth predisposes for cardiovascular disease, recent studies in children indicate normal blood pressure and arterial stiffness. This prospective cohort study therefore assessed blood pressure and arterial stiffness in adolescents born very preterm due to verified fetal growth restriction (FGR). METHODS: Adolescents (14 (13-17) years; 52% girls) born very preterm with FGR (preterm FGR; n = 24) and two control groups born with appropriate birth weight (AGA), one in similar gestation (preterm AGA; n = 27) and one at term (term AGA; n = 28) were included. 24-hour ambulatory blood pressure and aortic pulse wave velocity (PWV) and distensibility by magnetic resonance imaging were acquired. RESULTS: There were no group differences in prevalence of hypertension or in arterial stiffness (all p ≥ 0.1). In boys, diastolic and mean arterial blood pressures increased from term AGA to preterm AGA to preterm FGR with higher daytime and 24-hour mean arterial blood pressures in the preterm FGR as compared to the term AGA group. In girls, no group differences were observed (all p ≥ 0.1). CONCLUSIONS: Very preterm birth due to FGR is associated with higher, yet normal blood pressure in adolescent boys, suggesting an existing but limited impact of very preterm birth on cardiovascular risk in adolescence, enhanced by male sex and FGR. IMPACT: Very preterm birth due to fetal growth restriction was associated with higher, yet normal blood pressure in adolescent boys. In adolescence, very preterm birth due to fetal growth restriction was not associated with increased thoracic aortic stiffness. In adolescence, very preterm birth in itself showed an existing but limited effect on blood pressure and thoracic aortic stiffness. Male sex and fetal growth restriction enhanced the effect of preterm birth on blood pressure in adolescence. Male sex and fetal growth restriction should be considered as additional risk factors to that of preterm birth in cardiovascular risk stratification.

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.

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.