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.

Right ventricular dyssynchrony predicts outcome in pulmonary arterial hypertension when assessed in multiple CMR views.

BACKGROUND: Right ventricular (RV) dyssynchrony or post systolic contraction (PSC) cause inefficient pumping and have not been investigated as prognostic markers in pulmonary arterial hypertension (PAH). OBJECTIVES: To investigate if RV dyssynchrony and PSC are prognostic markers of transplantation-free survival in PAH and if multiple RV views improve the prognostication. METHODS: Patients with PAH undergoing cardiac magnetic resonance (CMR) between 2003-2021 were included. For strain analysis, endocardial end-diastolic RV contours were delineated in RV 3-chamber (RV3ch), 4-chamber (4ch) and midventricular short axis slice (SAX). RV dyssynchrony was defined as standard deviation of time to peak strain in the walls from one (4ch), two (4ch and SAX) or three views (4ch, SAX and RV3ch). PSC was defined as peak strain occurring after pulmonary valve closure. Outcome was defined as death or lung transplantation. RESULTS: One hundred-one patients (58±19 years, 66% women) were included. Median follow-up was 37 [51] months. There were 60 events (55 deaths and 5 lung transplantations). Outcome was associated with RV dyssynchrony from three views and with RV strain in 4ch. An increase of RV dyssynchrony - from 3 views - by 1% was associated with a 10% increased risk of lung transplantation or death. There was no association between outcome and RV dyssynchrony in one or two views nor with PSC. CONCLUSION: Right ventricular dyssynchrony from three views were associated with outcome in PAH, whereas assessing dyssynchrony from one or two views and PSC were not. This implies that assessment of multiple instead of single RV views potentially could be used for prognostication in PAH.

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.

Left Ventricular Diastolic Function in Children with Atrial Septal Defects Improves After Closure by Means of Increased Hydraulic Force.

Hydraulic force aids diastolic filling of the left ventricle (LV) by facilitating basal movement of the atrioventricular plane. The short-axis atrioventricular area difference (AVAD) determines direction and magnitude of this force. Patients with atrial septal defect (ASD) have reduced LV filling due to the left-to-right shunt across the atrial septum and thus potentially altered hydraulic force. The aims were therefore to use cardiac magnetic resonance images to assess whether AVAD and thus the hydraulic force differ in children with ASD compared to healthy children, and if it improves after ASD closure. Twenty-two children with ASD underwent cardiac magnetic resonance before ASD closure. Of these 22 children, 17 of them repeated their examination also after ASD closure. Twelve controls were included. Left atrial and ventricular areas were delineated in short-axis images, and AVAD was defined as the largest ventricular area minus the largest atrial area at each time frame and normalized to body height (AVADi). At end diastole AVADi was positive in all participants, suggesting a force acting towards the atrium assisting the diastolic movement of the atrioventricular plane; however, lower in children both before (6.3 cm2/m [5.2-8.0]; p < 0.0001) and after ASD closure (8.7 cm2/m [6.6-8.5]; p = 0.0003) compared to controls (12.2 cm2/m [11.3-13.9]). Left ventricular diastolic function improves after ASD closure in children by means of improved hydraulic force assessed by AVAD. Although AVADi improved after ASD closure, it was still lower than in controls, indicating diastolic abnormality even after ASD closure. In patients where AVADi is low, ASD closure may help avoid diastolic function deterioration and improve outcome. This could likely be important also in patients with small shunt volumes, especially if they are younger, who currently do not undergo ASD closure. Changes in clinical routine may be considered pending larger outcome studies.

Atrioventricular Area Difference Aids Diastolic Filling in Patients with Repaired Tetralogy of Fallot.

A hydraulic force aids diastolic filling of the left ventricle (LV) and is proportional to the difference in short-axis area between the left ventricle and atrium; the atrioventricular area difference (AVAD). Patients with repaired Tetralogy of Fallot (rToF) and pulmonary regurgitation (PR) have reduced LV filling which could lead to a negative AVAD and a hydraulic force impeding diastolic filling. The aim was to assess AVAD and to determine whether the hydraulic force aids or impedes diastolic filling in patients with rToF and PR, compared to controls. Twelve children with rToF (11.5 [9-13] years), 12 pediatric controls (10.5 [9-13] years), 12 adults with rToF (21.5 [19-27] years) and 12 adult controls (24 [21-29] years) were retrospectively included. Cine short-axis images were acquired using cardiac magnetic resonance imaging. Atrioventricular area difference was calculated as the largest left ventricular short-axis area minus the largest left atrial short-axis area at beginning of diastole and end diastole and indexed to height (AVADi). Children and adults with rToF and PR had higher AVADi (0.3 cm2/m [- 1.3 to 0.8] and - 0.6 [- 1.5 to - 0.2]) at beginning of diastole compared to controls (- 2.7 cm2/m [- 4.9 to - 1.7], p = 0.015) and - 3.3 cm2/m [- 3.8 to - 2.8], p = 0.017). At end diastole AVADi did not differ between patients and controls. Children and adults with rToF and pulmonary regurgitation have an atrioventricular area difference that do not differ from controls and thus a net hydraulic force that contributes to left ventricular diastolic filling, despite a small underfilled left ventricle due to pulmonary regurgitation.

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.

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.

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.

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.

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.

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.

Pulmonary perfusion and NYHA classification improve after cardiac resynchronization therapy.

BACKGROUND: Evaluation of cardiac resynchronization therapy (CRT) often includes New York Heart Association (NYHA) classification, and echocardiography. However, these measures have limitations. Perfusion gradients from ventilation/perfusion single-photon emission computed tomography (V/P SPECT) are related to left-heart filling pressures and have been validated against invasive right-heart catheterization. The aim was to assess if changes in perfusion gradients are associated with improvements in heart failure (HF) symptoms after CRT, and if they correlate with currently used diagnostic methods in the follow-up of patients with HF after receiving CRT. METHODS AND RESULTS: Nineteen patients underwent V/P SPECT, echocardiography, NYHA classification, and the quality-of-life scoring system "Minnesota living with HF" (MLWHF), before and after CRT. CRT caused improvement in perfusion gradients from V/P SPECT which were associated with improvements in NYHA classification (P = .0456), whereas improvements in end-systolic volume (LVESV) from echocardiography were not. After receiving CRT, the proportion of patients who improved was lower using LVESV (n = 7/19, 37%) than perfusion gradients (n = 13/19, 68%). Neither change in perfusion gradients nor LVESV was associated with changes in MLWHF (P = 1.0, respectively). CONCLUSIONS: Measurement of perfusion gradients from V/P SPECT is a promising quantitative user-independent surrogate measure of left-sided filling pressure in the assessment of CRT response in patients with HF.

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.

Pulmonary blood volume measured by cardiovascular magnetic resonance: influence of pulmonary transit time methods and left atrial volume.

BACKGROUND: Increased pulmonary blood volume (PBV) is a measure of congestion and is associated with an increased risk of cardiovascular events. PBV can be quantified using cardiovascular magnetic resonance (CMR) imaging as the product of cardiac output and pulmonary transit time (PTT), the latter measured from the contrast time-intensity curves in the right and left side of the heart from first-pass perfusion (FPP). Several methods of estimating PTT exist, including pulmonary transit beats (PTB), peak-to-peak, and center of gravity (CoG). The aim of this study was to determine the accuracy and precision for these methods of quantifying the PBV, taking the left atrium volume (LAV) into consideration. METHODS: Fifty-eight participants (64 ± 11 years, 24 women) underwent 1.5 T CMR. PTT was quantified from (1) a basal left ventricular short-axis image (FPP), and (2) the reference method with a separate contrast administration using an image intersecting the pulmonary artery (PA) and the LA (CoG(PA-LA)). RESULTS: Compared to the reference, PBV for (a) PTB(FPP) was 14 ± 17% larger, (b) peak-peak(FPP) was 17 ± 16% larger, and (c) CoG(FPP) was 18 ± 10% larger. Subtraction of the LAV (available for n = 50) decreased overall differences to - 1 ± 19%, 2 ± 18%, and 3 ± 12% for PTB(FPP), peak-peak(FPP), and CoG(FPP), respectively. Lowest interobserver variability was seen for CoG(FPP) (- 2 ± 7%). CONCLUSIONS: CoG(PA-LA) and FPP methods measured the same PBV only when adjusting for the LAV, since FPP inherently quantifies a volume consisting of PBV + LAV. CoG(FPP) had the best precision and lowest interobserver variability among the FPP methods of measuring PBV.

MVnet: automated time-resolved tracking of the mitral valve plane in CMR long-axis cine images with residual neural networks: a multi-center, multi-vendor study.

BACKGROUND: Mitral annular plane systolic excursion (MAPSE) and left ventricular (LV) early diastolic velocity (e') are key metrics of systolic and diastolic function, but not often measured by cardiovascular magnetic resonance (CMR). Its derivation is possible with manual, precise annotation of the mitral valve (MV) insertion points along the cardiac cycle in both two and four-chamber long-axis cines, but this process is highly time-consuming, laborious, and prone to errors. A fully automated, consistent, fast, and accurate method for MV plane tracking is lacking. In this study, we propose MVnet, a deep learning approach for MV point localization and tracking capable of deriving such clinical metrics comparable to human expert-level performance, and validated it in a multi-vendor, multi-center clinical population. METHODS: The proposed pipeline first performs a coarse MV point annotation in a given cine accurately enough to apply an automated linear transformation task, which standardizes the size, cropping, resolution, and heart orientation, and second, tracks the MV points with high accuracy. The model was trained and evaluated on 38,854 cine images from 703 patients with diverse cardiovascular conditions, scanned on equipment from 3 main vendors, 16 centers, and 7 countries, and manually annotated by 10 observers. Agreement was assessed by the intra-class correlation coefficient (ICC) for both clinical metrics and by the distance error in the MV plane displacement. For inter-observer variability analysis, an additional pair of observers performed manual annotations in a randomly chosen set of 50 patients. RESULTS: MVnet achieved a fast segmentation (<1 s/cine) with excellent ICCs of 0.94 (MAPSE) and 0.93 (LV e') and a MV plane tracking error of -0.10 ± 0.97 mm. In a similar manner, the inter-observer variability analysis yielded ICCs of 0.95 and 0.89 and a tracking error of -0.15 ± 1.18 mm, respectively. CONCLUSION: A dual-stage deep learning approach for automated annotation of MV points for systolic and diastolic evaluation in CMR long-axis cine images was developed. The method is able to carefully track these points with high accuracy and in a timely manner. This will improve the feasibility of CMR methods which rely on valve tracking and increase their utility in a clinical setting.

To what extent are perfusion defects seen by myocardial perfusion SPECT in patients with left bundle branch block related to myocardial infarction, ECG characteristics, and myocardial wall motion?

INTRODUCTION: We investigated if uptake pattern on myocardial perfusion SPECT (MPS) in patients with left bundle branch block (LBBB) is related to myocardial fibrosis, myocardial wall motion, and electrocardiography (ECG) characteristics. METHODS: Twenty-three patients (9 women) with LBBB, examined with MPS and cardiac magnetic resonance (CMR), were included. Tracer uptake on MPS was classified by visual interpretation as typical LBBB pattern (Defect+, n = 13) or not (Defect-, n = 10) and quantitatively. CMR images were evaluated for wall thickness and for myocardial wall motion both by visual assessment and by regional myocardial radial strain from feature tracking, and for presence and location of myocardial fibrosis. ECGs were analyzed regarding QRS duration and the presence of strict criteria for LBBB. RESULTS: Wall thickness was slightly lower in the septum compared to the lateral wall in Defect+ patients (5.6 ± 1.1 vs 6.0 ± 1.3 mm, P = 0.03) but not in Defect- patients (5.6 ± 1.0 vs 5.6 ± 0.9 mm, P = 0.84). Defect+ patients showed a larger proportion of dyskinetic segments in the septum and hyperkinetic segments in the lateral wall compared to Defect- patients (P = 0.006 and P = 0.004, respectively). Decreased myocardial radial strain was associated with decreased tracer uptake by MPS (R = 0.37, P < 0.001). Areas of fibrosis did not match areas with uptake defect on MPS. No differences in ECG variables were seen. CONCLUSION: The heterogeneous regional tracer uptake in some patients with LBBB is related to underlying regional myocardial dyskinesia, wall thickening, and wall thickness rather than stress-induced ischemia, myocardial fibrosis, or specific ECG characteristics.

Appropriate coronary revascularization can be accomplished if myocardial perfusion is quantified by positron emission tomography prior to treatment decision.

BACKGROUND: Many patients undergo percutaneous coronary intervention (PCI) without the use of non-invasive stress testing prior to treatment. The aim of this study was to determine the potential added value of guiding revascularization by quantitative assessment of myocardial perfusion prior to intervention. METHODS AND RESULTS: Thirty-three patients (10 females) with suspected or established CAD who had been referred for a clinical coronary angiography (CA) with possibility for PCI were included. Adenosine stress and rest 13N-NH3 PET, cardiac magnetic resonance (CMR), and cardiopulmonary exercise test were performed 4 ± 3 weeks before and 5 ± 1 months after CA. The angiographer was blinded to the PET and CMR results. Myocardial flow reserve (MFR) < 2.0 by PET was considered abnormal. A PCI was performed in 19/33 patients. In 41% (11/27) of the revascularized vessel territories, a normal regional MFR was found prior to the PCI and no improvement in MFR was found at follow-up (P = 0.9). However, vessel territories with regional MFR < 2.0 at baseline improved significantly after PCI (P = 0.003). Of the 14 patients not undergoing PCI, four had MFR < 2.0 in one or more coronary territories. CONCLUSION: Assessment of quantitative myocardial perfusion prior to revascularization could lead to more appropriate use of CA when managing patients with stable CAD.

Regional contributions to left ventricular stroke volume determined by cardiac magnetic resonance imaging in cardiac resynchronization therapy.

BACKGROUND: Cardiac resynchronization therapy (CRT) restores ventricular synchrony and induces left ventricular (LV) reverse remodeling in patients with heart failure (HF) and dyssynchrony. However, 30% of treated patients are non-responders despite all efforts. Cardiac magnetic resonance imaging (CMR) can be used to quantify regional contributions to stroke volume (SV) as potential CRT predictors. The aim of this study was to determine if LV longitudinal (SVlong%), lateral (SVlat%), and septal (SVsept%) contributions to SV differ from healthy controls and investigate if these parameters can predict CRT response. METHODS: Sixty-five patients (19 women, 67 ± 9 years) with symptomatic HF (LVEF ≤ 35%) and broadened QRS (≥ 120 ms) underwent CMR. SVlong% was calculated as the volume encompassed by the atrioventricular plane displacement (AVPD) from end diastole (ED) to end systole (ES) divided by total SV. SVlat%, and SVsept% were calculated as the volume encompassed by radial contraction from ED to ES. Twenty age- and sex-matched healthy volunteers were used as controls. The regional measures were compared to outcome response defined as ≥ 15% decrease in echocardiographic LV end-systolic volume (LVESV) from pre- to 6-months post CRT (delta, Δ). RESULTS: AVPD and SVlong% were lower in patients compared to controls (8.3 ± 3.2 mm vs 15.3 ± 1.6 mm, P < 0.001; and 53 ± 18% vs 64 ± 8%, P < 0.01). SVsept% was lower (0 ± 15% vs 10 ± 4%, P < 0.01) with a higher SVlat% in the patient group (42 ± 16% vs 29 ± 7%, P < 0.01). There were no differences between responders and non-responders in neither SVlong% (P = 0.87), SVlat% (P = 0.09), nor SVsept% (P = 0.65). In patients with septal net motion towards the right ventricle (n = 28) ΔLVESV was - 18 ± 22% and with septal net motion towards the LV (n = 37) ΔLVESV was - 19 ± 23% (P = 0.96). CONCLUSIONS: Longitudinal function, expressed as AVPD and longitudinal contribution to SV, is decreased in patients with HF scheduled for CRT. A larger lateral contribution to SV compensates for the abnormal septal systolic net movement. However, LV reverse remodeling could not be predicted by these regional contributors to SV.

Changes in left and right ventricular longitudinal function after pulmonary valve replacement in patients with Tetralogy of Fallot.

Timing and indication for pulmonary valve replacement (PVR) in patients with repaired Tetralogy of Fallot (rToF) and pulmonary regurgitation (PR) are uncertain. To improve understanding of pumping mechanics, we investigated atrioventricular coupling before and after surgical PVR. Cardiovascular magnetic resonance was performed in patients (n = 12) with rToF and PR > 35% before and after PVR and in healthy controls (n = 15). Atrioventricular plane displacement (AVPD), global longitudinal peak systolic strain (GLS), atrial and ventricular volumes, and caval blood flows were analyzed. Right ventricular (RV) AVPD and RV free wall GLS were lower in patients before PVR compared with controls (P < 0.0001; P < 0.01) and decreased after PVR (P < 0.0001 for both). Left ventricular AVPD was lower in patients before PVR compared with controls (P < 0.05) and decreased after PVR (P < 0.01). Left ventricular GLS did not differ between patients and controls (P > 0.05). Right atrial reservoir volume and RV stroke volume generated by AVPD correlated in controls (r = 0.93; P < 0.0001) and patients before PVR (r = 0.88; P < 0.001) but not after PVR. In conclusion, there is a clear atrioventricular coupling in patients before PVR that is lost after PVR, possibly because of loss of pericardial integrity. Impaired atrioventricular coupling complicates assessment of ventricular function after surgery using measurements of longitudinal function. Changes in atrioventricular coupling seen in patients with rToF may be energetically unfavorable, and long-term effects of surgery on atrioventricular coupling is therefore of interest. Also, AVPD and GLS cannot be used interchangeably to assess longitudinal function in rToF.NEW & NOTEWORTHY There is a clear atrioventricular coupling in patients with Tetralogy of Fallot (ToF) and pulmonary regurgitation before surgical pulmonary valve replacement (PVR) that is lost after operation, possibly because of loss of pericardial integrity. The impaired atrioventricular coupling complicates assessment of ventricular function after surgery when using measurements of longitudinal function. Left ventricular atrioventricular plane displacement (AVPD) found differences between patients and controls and changes after PVR that longitudinal strain could not detect. This indicates that AVPD and strain cannot be used interchangeably to assess longitudinal function in repaired ToF.

Measuring extracellular volume fraction by MRI: First verification of values given by clinical sequences.

PURPOSE: To verify MR measurements of myocardial extracellular volume fraction (ECV) based on clinically applicable T1-mapping sequences against ECV measurements by radioisotope tracer in pigs and to relate the results to those obtained in volunteers. METHODS: Between May 2016 and March 2017, 8 volunteers (25 ± 4 years, 3 female) and 8 pigs (4 female) underwent ECV assessment with SASHA, MOLLI5(3b)3, MOLLI5(3s)3, and MOLLI5s(3s)3s. Myocardial ECV was measured independently in pigs using a radioisotope tracer method. RESULTS: In pigs, ECV in normal myocardium was not different between radioisotope (average ± standard deviation; 19 ± 2%) and SASHA (21 ± 2%; P = 0.086). ECV was higher by MOLLI5(3b)3 (26 ± 2%), MOLLI5(3s)3 (25 ± 2%), and MOLLI5s(3s)3s (25 ± 2%) compared with SASHA or radioisotope (P ≤ 0.001 for all). ECV in volunteers was higher by MOLLI5(3b)3 (26 ± 3%) and MOLLI5(3s)3 (26 ± 3%) than by SASHA (22 ± 3%; P = 0.022 and P = 0.033). No difference was found between MOLLI5s(3s)3s (25 ± 3%) and SASHA (P = 0.225). Native T1 of blood and myocardium as well as postcontrast T1 of myocardium was consistently lower using MOLLI compared with SASHA. ECV increased over time as measured by MOLLI5(3b)3 and MOLLI5(3s)3 for pigs (0.08% and 0.07%/min; P = 0.004 and P = 0.013) and by MOLLI5s(3s)3s for volunteers (0.07%/min; P = 0.032) but did not increase as measured by SASHA. CONCLUSION: Clinically available MOLLI and SASHA techniques can be used to accurately estimate ECV in normal myocardium where MOLLI-sequences show minor overestimation driven by underestimation of postcontrast T1 when compared with SASHA. The timing of imaging after contrast administration affected the measurement of ECV using some variants of the MOLLI sequence.