Prognostic value of visual and quantitative CMR regional myocardial function in patients with suspected myocarditis.

According to updated Lake-Louise Criteria, impaired regional myocardial function serves as a supportive criterion in diagnosing myocarditis. This study aimed to assess visual regional wall motional abnormalities (RWMA) and novel quantitative regional longitudinal peak strain (RLS) for risk stratification in the clinical setting of myocarditis. In patients undergoing CMR and meeting clinical criteria for suspected myocarditis global longitudinal strain (GLS), late gadolinium enhancement (LGE), RWMA and RLS were assessed in the anterior, septal, inferior, and lateral regions and correlated to the occurrence of major adverse cardiac events (MACE), including heart failure hospitalization, sustained ventricular tachycardia, recurrent myocarditis, and all-cause death. In 690 consecutive patients (age: 48.0 ± 16.0 years; 37.7% female) with suspected myocarditis impaired RLS was correlated with RWMA and LV-GLS but not with the presence of LGE. At median follow up of 3.8 years, MACE occurred in 116 (16.8%) patients. Both, RWMA and RLS in anterior-, septal-, inferior-, and lateral- locations were univariately associated with outcomes (all p < 0.001), but not after adjusting for clinical characteristics and LV-GLS. In the subgroup of patients with normal LV function, RWMA were not predictive of outcomes, whereas septal RLS had incremental and independent prognostic value over clinical characteristics (HRadjusted = 1.132, 95% CI 1.020-1.256; p = 0.020). RWMA and RLS can be used to assess regional impairment of myocardial function in myocarditis but are of limited prognostic value in the overall population. However, in the subgroup of patients with normal LV function, septal RLS represents a distinctive marker of regional LV dysfunction, offering potential for risk-stratification.

Perioperative hyperoxia- impact on myocardial biomarkers, strain and outcome in high-risk patients undergoing non-cardiac surgery: Protocol for a prospective randomized controlled trial.

BACKGROUND: Supplemental oxygen is used during every general anesthesia. However, for the maintenance phase of a general anesthesia, in most cases the longest part of anesthesia, only scarce evidence of dosing supplemental oxygen exists. Oxygen is a well-known coronary vasoconstrictor and thus may contribute to cardiovascular complications especially in vulnerable high-risk patients with coronary artery disease undergoing major non-cardiac surgery. Myocardial biomarkers are early indicators of myocardial injury. Oxygen supply demand mismatches due to coronary artery disease aggravated by hyperoxia might be displayed by changes from the biomarker's baseline-values. This study is designed to detect changes in myocardial biomarkers levels associated with perioperative hyperoxia. METHODS: This prospective randomized controlled interventional trial investigates the impact of maintaining perioperative high oxygen supplementation in high-risk patients undergoing non-cardiac vascular surgery on cardiac biomarkers, myocardial strain and outcome in 110 patients. Patients are allocated to be supplemented with either 0.3 (normal) or 0.8 (high) fraction of inspired oxygen (FiO2) perioperatively. Included is a short crossover phase during which transesophageal echocardiography is used to evaluate myocardial function at FiO2 0.3 and 0.8 by strain analysis in each patient. Patients will be followed up for complications at 30 days and 1 year. CONCLUSION: The trial is designed to evaluate perioperative changes from baseline myocardial biomarkers associated with perioperative FiO2. Furthermore, exploration and correlation of changes in biomarkers, acute early changes in myocardial function and clinical outcomes induced by different FiO2 may be possible.

Introducing a free-breathing MRI method to assess peri-operative myocardial oxygenation and function: A volunteer cohort study.

BACKGROUND: Induction of general anaesthesia has many potential triggers for peri-operative myocardial ischaemia including the acute disturbance of blood gases that frequently follows alterations in breathing and ventilation patterns. Free-breathing oxygenation-sensitive cardiovascular magnetic resonance (OS-CMR) imaging may provide the opportunity to continuously quantify the impact of such triggers on myocardial oxygenation. OBJECTIVE: To investigate the impact of breathing patterns that simulate induction of general anaesthesia on myocardial oxygenation in awake healthy adults using continuous OS-CMR imaging. DESIGN: Prospective observational study. SETTING: Single-centre university hospital. Recruitment from August 2020 to January 2022. PARTICIPANTS: Thirty-two healthy volunteers younger than 45 years old were recruited. Data were analysed from n = 29 (69% male individuals). INTERVENTION: Participants performed a simulated induction breathing manoeuvre consisting of 2.5 min paced breathing with a respiration rate of 14 breaths per minute, followed by 5 deep breaths, then apnoea for up to 60s inside a magnetic resonance imaging scanner (MRI). Cardiac images were acquired with the traditional OS-CMR sequence (OSbh-cine), which requires apnoea for acquisition and with two free-breathing OS-CMR sequences: a high-resolution single-shot sequence (OSfb-ss) and a real-time cine sequence (OSfb-rtcine). MAIN OUTCOME MEASURES: Myocardial oxygenation response at the end of the paced breathing period and at the 30 s timepoint during the subsequent apnoea, reflecting the time of successful intubation in a clinical setting. RESULTS: The paced breathing followed by five deep breaths significantly reduced myocardial oxygenation, which was observed with all three techniques (OSbh-cine -6.0 ±â€Š2.6%, OSfb-ss -12.0 ±â€Š5.9%, OSfb-rtcine -5.4 ±â€Š7.0%, all P < 0.05). The subsequent vasodilating stimulus of apnoea then significantly increased myocardial oxygenation (OSbh-cine 6.8 ±â€Š3.1%, OSfb-ss 8.4 ±â€Š5.6%, OSfb-rtcine 15.7 ±â€Š10.0%, all P < 0.01). The free-breathing sequences were reproducible and were not inferior to the original sequence for any stage. CONCLUSION: Breathing manoeuvres simulating induction of general anaesthesia cause dynamic alterations of myocardial oxygenation in young volunteers, which can be quantified continuously with free-breathing OS-CMR. Introducing these new imaging techniques into peri-operative studies may throw new light into the mechanisms of peri-operative perturbations of myocardial tissue oxygenation and ischaemia. VISUALABSTRACT: http://links.lww.com/EJA/A922.

Focal and diffuse myocardial fibrosis both contribute to regional hypoperfusion assessed by post-processing quantitative-perfusion MRI techniques.

Introduction: Indications for stress-cardiovascular magnetic resonance imaging (CMR) to assess myocardial ischemia and viability are growing. First pass perfusion and late gadolinium enhancement (LGE) have limited value in balanced ischemia and diffuse fibrosis. Quantitative perfusion (QP) to assess absolute pixelwise myocardial blood flow (MBF) and extracellular volume (ECV) as a measure of diffuse fibrosis can overcome these limitations. We investigated the use of post-processing techniques for quantifying both pixelwise MBF and diffuse fibrosis in patients with clinically indicated CMR stress exams. We then assessed if focal and diffuse myocardial fibrosis and other features quantified during the CMR exam explain individual MBF findings. Methods: This prospective observational study enrolled 125 patients undergoing a clinically indicated stress-CMR scan. In addition to the clinical report, MBF during regadenoson-stress was quantified using a post-processing QP method and T1 maps were used to calculate ECV. Factors that were associated with poor MBF were investigated. Results: Of the 109 patients included (66 ± 11 years, 32% female), global and regional perfusion was quantified by QP analysis in both the presence and absence of visual first pass perfusion deficits. Similarly, ECV analysis identified diffuse fibrosis in myocardium beyond segments with LGE. Multivariable analysis showed both LGE (ß = -0.191, p = 0.001) and ECV (ß = -0.011, p < 0.001) were independent predictors of reduced MBF. In patients without clinically defined first pass perfusion deficits, the microvascular risk-factors of age and wall thickness further contributed to poor MBF (p < 0.001). Discussion: Quantitative analysis of MBF and diffuse fibrosis detected regional tissue abnormalities not identified by traditional visual assessment. Multi-parametric quantitative analysis may refine the work-up of the etiology of myocardial ischemia in patients referred for clinical CMR stress testing in the future and provide a deeper insight into ischemic heart disease.

Microvascular Dysfunction as a Possible Link Between Heart Failure and Cognitive Dysfunction.

BACKGROUND: Microvascular function in the brain and heart may play an important role in the course of patients with heart failure (HF), but its relationship with ventricular and cognitive function is not well understood. We hypothesized that microvascular function in HF is closely related to both, cardiac and cognitive function. METHODS: In healthy controls and symptomatic patients with HF (New York Heart Association functional class II or III), we used oxygenation-sensitive magnetic resonance imaging during a standardized breathing maneuver to determine the cerebral oxygenation reserve and the myocardial oxygenation reserve (MORE) as markers for microvascular function. A stepwise multivariable linear regression was performed to determine the variables that best predict changes in cerebral oxygenation reserve and MORE. We also measured cognitive function using the Montreal Cognitive Assessment test. RESULTS: Twenty patients with HF (age 64.4±8.3 years; 50% female sex), and 21 healthy controls (age 55.0±5.1 years; 62% female sex) were included in the analysis. In patients with HF, cerebral oxygenation reserve and MORE were lower than in healthy controls (MORE, -0.1±3.3 versus 5.0±4.2, cerebral oxygenation reserve: 0.43±0.47 versus 1.21±0.60, respectively) as were Montreal Cognitive Assessment score results (HF, 23.9±3.7; healthy, 27.8±1.5; P=0.002). The Montreal Cognitive Assessment score in patients was correlated with cardiac output (r=0.55, P=0.011) and MORE (r=0.46, P=0.040). In addition to the presence of HF, significant predictors of cerebral and myocardial oxygenation reserve were cardiac output and end-diastolic volume, respectively. CONCLUSIONS: Our results indicate that heart failure is an independent predictor of coronary and cerebral microvascular dysfunction as defined by a reduced response to a vasodilatory breathing maneuver. This impaired response was associated with reduced cognitive function.

Predictive value of cardiac magnetic resonance right ventricular longitudinal strain in patients with suspected myocarditis.

BACKGROUND: Recent evidence underlined the importance of right (RV) involvement in suspected myocarditis. We aim to analyze the possible incremental prognostic value from RV global longitudinal strain (GLS) by CMR. METHODS: Patients referred for CMR, meeting clinical criteria for suspected myocarditis and no other cardiomyopathy were enrolled in a dual-center register cohort study. Ejection fraction (EF), GLS and tissue characteristics were assessed in both ventricles to assess their association to first major adverse cardiovascular events (MACE) including hospitalization for heart failure (HF), ventricular tachycardia (VT), recurrent myocarditis and death. RESULTS: Among 659 patients (62.8% male; 48.1 ± 16.1 years), RV GLS was impaired (> - 15.4%) in 144 (21.9%) individuals, of whom 76 (58%), 108 (77.1%), 27 (18.8%) and 40 (32.8%) had impaired right ventricular ejection fraction (RVEF), impaired left ventricular ejection fraction (LVEF), RV late gadolinium enhancement (LGE) or RV edema, respectively. After a median observation time of 3.7 years, 45 (6.8%) patients were hospitalized for HF, 42 (6.4%) patients died, 33 (5%) developed VT and 16 (2.4%) had recurrent myocarditis. Impaired RV GLS was associated with MACE (HR = 1.07, 95% CI 1.04-1.10; p < 0.001), HF hospitalization (HR = 1.17, 95% CI 1.12-1.23; p < 0.001), and death (HR = 1.07, 95% CI 1.02-1.12; p = 0.004), but not with VT and recurrent myocarditis in univariate analysis. RV GLS lost its association with outcomes, when adjusted for RVEF, LVEF, LV GLS and LV LGE extent. CONCLUSION: RV strain is associated with MACE, HF hospitalization and death but has neither independent nor incremental prognostic value after adjustment for RV and LV function and tissue characteristics. Therefore, assessing RV GLS in the setting of myocarditis has only limited value.

Hyperoxia-induced deterioration of diastolic function in anaesthetised patients with coronary artery disease - Randomised crossover trial.

Background: There are no current recommendations for oxygen titration in patients with stable coronary artery disease. This study investigates the effect of iatrogenic hyperoxia on cardiac function in patients with coronary artery disease undergoing general anaesthesia. Methods: Patients scheduled for elective coronary artery bypass graft surgery were prospectively recruited into this randomised crossover clinical trial. All patients were exposed to inspired oxygen fractions of 0.3 (normoxaemia) and 0.8 (hyperoxia) in randomised order. A transoesophageal echocardiographic imaging protocol was performed during each exposure. Primary analysis investigated changes in 3D peak strain, whereas secondary analyses investigated other systolic and diastolic responses. Results: There was no statistical difference in systolic function between normoxaemia and hyperoxia. However, the response in systolic function to hyperoxia was dependent on ventricular function at normoxaemia. Patients with a normoxaemic left ventricular (LV) global longitudinal strain (GLS) poorer than the derived cut-off (>-15.4%) improved with hyperoxia (P<0.01), whereas in patients with normoxaemic LV-GLS <-15.4%, LV-GLS worsened with transition to hyperoxia (P<0.01). The same was seen for right ventricular GLS with a cut-off at -24.1%. Diastolic function worsened during hyperoxia indicated by a significant increase of averaged E/e' (8.6 [2.6]. vs 8.2 [2.4], P=0.01) and E/A ratio (1.4 (0.4) vs 1.3 (0.4), P=0.01). Conclusions: Although the response of biventricular systolic variables is dependent on systolic function at normoxaemia, diastolic function consistently worsens under hyperoxia. In coronary artery disease, intraoperative strain analysis may offer guidance for oxygen titration. Clinical trial registration: NCT04424433.

Analysis of bi-atrial function using CMR feature tracking and long-axis shortening approaches in patients with diastolic dysfunction and atrial fibrillation.

OBJECTIVES: Atrial function can be assessed using advancing cardiovascular magnetic resonance (CMR) post-processing methods: atrial feature tracking (FT) strain analysis or a long-axis shortening (LAS) technique. This study aimed to first compare the two FT and LAS techniques in healthy individuals and cardiovascular patients and then investigated how left (LA) and right atrial (RA) measurements are related to the severity of diastolic dysfunction or atrial fibrillation. METHODS: Sixty healthy controls and 90 cardiovascular disease patients with coronary artery disease, heart failure, or atrial fibrillation, underwent CMR. LA and RA were analyzed for standard volumetry as well as for myocardial deformation using FT and LAS for the different functional phases (reservoir, conduit, booster). Additionally, ventricular shortening and valve excursion measurements were assessed with the LAS module. RESULTS: The measurements for each of the LA and RA phases were correlated (p < 0.05) between the two approaches, with the highest correlation coefficients occurring in the reservoir phase (LA: r = 0.83, p < 0.01, RA: r = 0.66, p < 0.01). Both methods demonstrated reduced LA (FT: 26 ± 13% vs 48 ± 12%, LAS: 25 ± 11% vs 42 ± 8%, p < 0.01) and RA reservoir function (FT: 28 ± 15% vs 42 ± 15%, LAS: 27 ± 12% vs 42 ± 10%, p < 0.01) in patients compared to controls. Atrial LAS and FT decreased with diastolic dysfunction and atrial fibrillation. This mirrored ventricular dysfunction measurements. CONCLUSION: Similar results were generated for bi-atrial function measurements between two CMR post-processing approaches of FT and LAS. Moreover, these methods allowed for the assessment of incremental deterioration of LA and RA function with increasing left ventricular diastolic dysfunction and atrial fibrillation. A CMR-based analysis of bi-atrial strain or shortening discriminates patients with early-stage diastolic dysfunction prior to the presence of compromised atrial and ventricular ejection fractions that occur with late-stage diastolic dysfunction and atrial fibrillation. KEY POINTS: • Assessing right and left atrial function with CMR feature tracking or long-axis shortening techniques yields similar measurements and could potentially be used interchangeably based on the software capabilities of individual sites. • Atrial deformation and/or long-axis shortening allow for early detection of subtle atrial myopathy in diastolic dysfunction, even when atrial enlargement is not yet apparent. • Using a CMR-based analysis to understand the individual atrial-ventricular interaction in addition to tissue characteristics allows for a comprehensive interrogation of all four heart chambers. In patients, this could add clinically meaningful information and potentially allow for optimal therapies to be chosen to better target the dysfunction.

Dynamic Cardiac Magnetic Resonance Fingerprinting During Vasoactive Breathing Maneuvers: First Results.

BACKGROUND: Cardiac magnetic resonance fingerprinting (cMRF) enables simultaneous mapping of myocardial T1 and T2 with very short acquisition times. Breathing maneuvers have been utilized as a vasoactive stress test to dynamically characterize myocardial tissue in vivo. We tested the feasibility of sequential, rapid cMRF acquisitions during breathing maneuvers to quantify myocardial T1 and T2 changes. METHODS: We measured T1 and T2 values using conventional T1 and T2-mapping techniques (modified look locker inversion [MOLLI] and T2-prepared balanced-steady state free precession), and a 15 heartbeat (15-hb) and rapid 5-hb cMRF sequence in a phantom and in 9 healthy volunteers. The cMRF5-hb sequence was also used to dynamically assess T1 and T2 changes over the course of a vasoactive combined breathing maneuver. RESULTS: In healthy volunteers, the mean myocardial T1 of the different mapping methodologies were: MOLLI 1,224 ± 81 ms, cMRF15-hb 1,359 ± 97 ms, and cMRF5-hb 1,357 ± 76 ms. The mean myocardial T2 measured with the conventional mapping technique was 41.7 ± 6.7 ms, while for cMRF15-hb 29.6 ± 5.8 ms and cMRF5-hb 30.5 ± 5.8 ms. T2 was reduced with vasoconstriction (post-hyperventilation compared to a baseline resting state) (30.15 ± 1.53 ms vs. 27.99 ± 2.07 ms, p = 0.02), while T1 did not change with hyperventilation. During the vasodilatory breath-hold, no significant change of myocardial T1 and T2 was observed. CONCLUSIONS: cMRF5-hb enables simultaneous mapping of myocardial T1 and T2, and may be used to track dynamic changes of myocardial T1 and T2 during vasoactive combined breathing maneuvers.

Prognostic Value of Right Ventricular Function in Patients With Suspected Myocarditis Undergoing Cardiac Magnetic Resonance.

BACKGROUND: Risk-stratification of myocarditis is based on functional parameters and tissue characterization of the left ventricle (LV), whereas right ventricular (RV) involvement remains mostly unrecognized. OBJECTIVES: In this study, the authors sought to analyze the prognostic value of RV involvement in myocarditis by cardiac magnetic resonance (CMR). METHODS: Patients meeting the recommended clinical criteria for suspected myocarditis were enrolled at 2 centers. Exclusion criteria were the evidence of coronary artery disease, pulmonary artery hypertension or structural cardiomyopathy. Biventricular ejection fraction, edema according to T2-weighted images, and late gadolinium enhancement (LGE) were linked to a composite end point of major adverse cardiovascular events (MACE), including heart failure hospitalization, ventricular arrhythmia, recurrent myocarditis, and death. RESULTS: Among 1,125 consecutive patients, 736 (mean age: 47.8 ± 16.1 years) met the clinical diagnosis of suspected myocarditis and were followed for 3.7 years. Signs of RV involvement (abnormal right ventricular ejection fraction [RVEF], RV edema, and RV-LGE) were present in 188 (25.6%), 158 (21.5%), and 92 (12.5%) patients, respectively. MACE occurred in 122 patients (16.6%) and was univariably associated with left ventricular ejection fraction (LVEF), LV edema, LV-LGE, RV-LGE, RV edema, and RVEF. In a series of nesting multivariable Cox regression models, the addition of RVEF (HRadj: 0.974 [95% CI: 0.956-0.993]; P = 0.006) improved prognostication (chi-square test = 89.5; P = 0.001 vs model 1; P = 0.006 vs model 2) compared with model 1 including only clinical variables (chi-square test = 28.54) and model 2 based on clinical parameters, LVEF, and LV-LGE extent (chi-square test = 78.93). CONCLUSIONS: This study emphasizes the role of RV involvement in myocarditis and demonstrates the independent and incremental prognostic value of RVEF beyond clinical variables, CMR tissue characterization, and LV function. (Inflammatory Cardiomyopathy Bern Registry [FlamBER]; NCT04774549; CMR Features in Patients With Suspected Myocarditis [CMRMyo]; NCT03470571).

Feature tracking strain analysis detects the onset of regional diastolic dysfunction in territories with acute myocardial injury induced by transthoracic electrical interventions.

Electric interventions are used to terminate arrhythmia. However, myocardial injury from the electrical intervention can follow unique pathways and it is unknown how this affects regional ventricular function. This study investigated the impact of transthoracic electrical shocks on systolic and diastolic myocardial deformation. Ten healthy anaesthetized female swine received five transthoracic shocks (5 × 200 J) and six controls underwent a cardiovascular magnetic resonance exam prior to and 5 h after the intervention. Serial transthoracic shocks led to a global reduction in both left (LV, - 15.6 ± 3.3% to - 13.0 ± 3.6%, p < 0.01) and right ventricular (RV, - 16.1 ± 2.3% to - 12.8 ± 4.2%, p = 0.03) peak circumferential strain as a marker of systolic function and to a decrease in LV early diastolic strain rate (1.19 ± 0.35/s to 0.95 ± 0.37/s, p = 0.02), assessed by feature tracking analysis. The extent of myocardial edema (ΔT1) was related to an aggravation of regional LV and RV diastolic dysfunction, whereas only RV systolic function was regionally associated with an increase in T1. In conclusion, serial transthoracic shocks in a healthy swine model attenuate biventricular systolic function, but it is the acute development of regional diastolic dysfunction that is associated with the onset of colocalized myocardial edema.

Diagnostic performance of cardiac magnetic resonance segmental myocardial strain for detecting microvascular obstruction and late gadolinium enhancement in patients presenting after a ST-elevation myocardial infarction.

Background: Microvascular obstruction (MVO) and Late Gadolinium Enhancement (LGE) assessed in cardiac magnetic resonance (CMR) are associated with adverse outcome in patients with ST-elevation myocardial infarction (STEMI). Our aim was to analyze the diagnostic performance of segmental strain for the detection of MVO and LGE. Methods: Patients with anterior STEMI, who underwent additional CMR were enrolled in this sub-study of the CARE-AMI trial. Using CMR feature tracking (FT) segmental circumferential peak strain (SCS) was measured and the diagnostic performance of SCS to discriminate MVO and LGE was assessed in a derivation and validation cohort. Results: Forty-eight STEMI patients (62 ± 12 years old), 39 (81%) males, who underwent CMR (i.e., mean 3.0 ± 1.5 days) after primary percutaneous coronary intervention (PCI) were included. All patients presented with LGE and in 40 (83%) patients, MVO was additionally present. Segments in all patients were visually classified and 146 (19%) segments showed MVO (i.e., LGE+/MVO+), 308 (40%) segments showed LGE and no MVO (i.e., LGE+/MVO-), and 314 (41%) segments showed no LGE (i.e., LGE-). Diagnostic performance of SCS for detecting MVO segments (i.e., LGE+/MVO+ vs. LGE+/MVO-, and LGE-) showed an AUC = 0.764 and SCS cut-off value was -11.2%, resulting in a sensitivity of 78% and a specificity of 67% with a positive predictive value (PPV) of 30% and a negative predictive value (NPV) of 94% when tested in the validation group. For LGE segments (i.e., LGE+/MVO+ and LGE+/MVO- vs. LGE-) AUC = 0.848 and SCS with a cut-off value of -13.8% yielded to a sensitivity of 76%, specificity of 74%, PPV of 81%, and NPV of 70%. Conclusion: Segmental strain in STEMI patients was associated with good diagnostic performance for detection of MVO+ segments and very good diagnostic performance of LGE+ segments. Segmental strain may be useful as a potential contrast-free surrogate marker to improve early risk stratification in patients after primary PCI.

Combined Analysis of Myocardial Deformation and Oxygenation Detects Inducible Ischemia Unmasked by Breathing Maneuvers in Chronic Coronary Syndrome.

Introduction: In patients with chronic coronary syndromes, hyperventilation followed by apnea has been shown to unmask myocardium susceptible to inducible deoxygenation. The aim of this study was to assess whether such a provoked response is co-localized with myocardial dysfunction. Methods: A group of twenty-six CAD patients with a defined stenosis (quantitative coronary angiography > 50%) underwent a cardiovascular magnetic resonance (CMR) exam prior to revascularization. Healthy volunteers older than 50 years served as controls (n = 12). Participants hyperventilated for 60s followed by brief apnea. Oxygenation-sensitive images were analyzed for changes in myocardial oxygenation and strain. Results: In healthy subjects, hyperventilation resulted in global myocardial deoxygenation (-10.2 ± 8.2%, p < 0.001) and augmented peak circumferential systolic strain (-3.3 ± 1.6%, p < 0.001). At the end of apnea, myocardial signal intensity had increased (+9.1 ± 5.3%, p < 0.001) and strain had normalized to baseline. CAD patients had a similar global oxygenation response to hyperventilation (-5.8 ± 9.6%, p = 0.085) but showed no change in peak strain from their resting state (-1.3 ± 1.6%), which was significantly attenuated in comparison the strain response observed in controls (p = 0.008). With apnea, the CAD patients showed an attenuated global oxygenation response to apnea compared to controls (+2.7 ± 6.2%, p < 0.001). This was accompanied by a significant depression of peak strain (3.0 ± 1.7%, p < 0.001), which also differed from the control response (p = 0.025). Regional analysis demonstrated that post-stenotic myocardium was most susceptible to de-oxygenation and systolic strain abnormalities during respiratory maneuvers. CMR measures at rest were unable to discriminate post-stenotic territory (p > 0.05), yet this was significant for both myocardial oxygenation [area under the curve (AUC): 0.88, p > 0.001] and peak strain (AUC: 0.73, p = 0.023) measured with apnea. A combined analysis of myocardial oxygenation and peak strain resulted in an incrementally higher AUC of 0.91, p < 0.001 than strain alone. Conclusion: In myocardium of patients with chronic coronary syndromes and primarily intermediate coronary stenoses, cine oxygenation-sensitive CMR can identify an impaired vascular and functional response to a vasoactive breathing maneuver stimulus indicative of inducible ischemia.

Patient and physician preferences for non-invasive diagnostic cardiovascular imaging technologies: a discrete choice experiment.

PURPOSE: Diagnostic imaging techniques have to be selected for their accuracy, efficiency, cost-efficiency, and impact on outcome. But beyond that, the choice of non-invasive cardiovascular imaging tests for diagnosing coronary artery disease also has to respect patient safety and comfort. In this study, we investigated patient and physician preference in relation to the choice of cardiovascular imaging tests. RESULTS: A total of 211 subjects (148 cardiac patients and 63 physicians) were enrolled and completed a discrete choice experiment. Tests and modalities were deconstructed into 6 attributes (risks and side effects, diagnostic accuracy, patient out-of-pocket cost, type of procedure, type of scanner and test duration). A Sawtooth software choice-based conjoint analysis with hierarchical Bayes estimation was performed and showed the risks and side effects attribute was assigned the most relative importance (30%) when considering patients' preference. Patients gave notably high value to tests with milder side effects, while preferring to avoid exposure to ionizing radiation and risks associated the use of pharmacological agents inducing direct coronary arteriolar vasodilation. Physicians allocated more importance to the patient out-of-pocket cost attribute (29%). Both patients and physicians valued tests' risks and side effects, diagnostic accuracy, patient out-of-pocket cost as the three most important attributes, but in diverging order. A market simulation comparing current cardiovascular imaging tests revealed breathing maneuver-enhanced cardiac magnetic resonance had the highest shares of preference in both patients (59.6%) and physicians (32.7%). CONCLUSION: A patients' preference for a particular cardiovascular imaging test was most determined by the risks and side effects, while physicians prioritized less costly tests for their patients. In shared decision-making with patients, physicians should therefore focus on a balanced discussion of risks and side effects associated with cardiovascular imaging tests. Both, patients and physicians would prefer a cardiovascular MR imaging test using a vasoactive breathing maneuver instead of currently used alternatives that require intravenous contrast agents, pharmacological stress, or radiation.

Insights Into Myocardial Oxygenation and Cardiovascular Magnetic Resonance Tissue Biomarkers in Heart Failure With Preserved Ejection Fraction.

BACKGROUND: The pathophysiology of heart failure with preserved ejection fraction is not well understood, but evidence strongly suggests involvement of microvascular dysfunction. We studied the myocardial oxygenation reserve as a direct marker of coronary vascular function and its relation to myocardial deformation and tissue characteristics by cardiovascular magnetic resonance (CMR). METHODS: In a dual-center case-control study, patients with heart failure and preserved ejection fraction (>50%) and healthy controls older than 50 years underwent quantitative CMR for ventricular volumes and functional assessment with feature tracking, as well as tissue characterization (T1, T2, extracellular volume). Coronary vascular function was measured by oxygenation-sensitive (OS)-CMR of the myocardial oxygenation response to a vasoactive breathing maneuver. RESULTS: Twenty-nine patients completed the CMR exam. Compared with cutoffs derived from 12 control subjects, circumferential peak strain was attenuated in 97% of patients. Native T1 was elevated in 93%, extracellular volume was elevated in 83%. Sixty-six percent of patients revealed either regional or global myocardial edema, defined by an increased myocardial T2. An attenuated global myocardial oxygenation reserve (<4.4%) was observed in 96% of the patients (1.7±3.9% versus 9.1±5.3% in controls, P<0.001). This was correlated with septal wall thickness (r=-0.54, P=0.003), edema (myocardial T2; ß=-0.26% oxygenation-sensitive/ms [95% CI, -0.49 to -0.03], P=0.029), and reduced diastolic strain rate (ß=1.50% oxygenation-sensitive/s-1 [95% CI, 0.06-2.90], P=0.042). CONCLUSIONS: In patients with clinical heart failure with preserved ejection fraction, vascular dysfunction as measured by an attenuated myocardial oxygenation reserve is associated with myocardial edema, a thicker septum, and diastolic dysfunction. A quantitative comprehensive CMR exam including oxygenation-sensitive-CMR allows for comprehensive imaging-based phenotyping of heart failure with preserved ejection fraction.

Reproducibility and its confounders of CMR feature tracking myocardial strain analysis in patients with suspected myocarditis.

OBJECTIVES: Cardiovascular magnetic resonance feature tracking (CMR-FT) is an emerging technique for assessing myocardial strain with valuable diagnostic and prognostic potential. However, the reproducibility of biventricular CMR-FT analysis in a large cardiovascular population has not been assessed. Also, evidence of confounders impacting reader reproducibility for CMR-FT in patients is unknown and currently limits the clinical implementation of this technique. METHODS: From a dual-center database of patients referred to CMR for suspected myocarditis, 125 patients were randomly selected to undergo biventricular CMR-FT analysis for 2-dimensional systolic and diastolic measures, with additional 3-dimensional analysis for the left ventricle. All image analysis was replicated by a single reader and by a second reader for intra- and inter-reader analysis (Circle Cardiovascular Imaging). Reliability was tested with intraclass correlation (ICC) tests, and the impact of imaging confounders on agreement was assessed through multivariable analysis. RESULTS: Left and right ventricular ejection fractions were reduced in 34% and 37% of the patients, respectively. Good to excellent reliability was shown for 2D (all ICC > 0.85) and 3D (all ICC > 0.70) peak strain and early diastolic strain rate for both ventricles in longitudinal orientation as well as circumferential orientations for the left ventricle. An increased slice number improved agreement while the presence of pericardial effusion compromised diastolic strain rate agreement, and arrhythmia compromised right ventricular agreement. CONCLUSION: In a large clinical cohort, we could show CMR-FT yields excellent inter-reader and intra-reader reproducibility. Multi-parametric CMR-FT of the right and left ventricles appears to be a robust tool in cardiovascular patients referred to CMR. CLINICALTRIALS: gov Identifier: NCT03470571, NCT04774549. Key Points • Cardiovascular magnetic resonance feature tracking (CMR-FT) is an emerging technique to measure myocardial strain in cardiovascular patients referred for CMR; however, the evaluation of its reproducibility in a large cohort has not yet been performed. • In a large clinical cohort, CMR-FT yields excellent inter-reader and intra-reader reproducibility for both left and right ventricular systolic and diastolic parameters. • Arrhythmia and pericardial effusion compromise agreement of select FT parameters, but poor ejection fraction does not.

Assessment of Myocardial Function During Blood Pressure Manipulations Using Feature Tracking Cardiovascular Magnetic Resonance.

Background: Coronary autoregulation is a feedback system, which maintains near-constant myocardial blood flow over a range of mean arterial pressure (MAP). Yet in emergency or peri-operative situations, hypotensive or hypertensive episodes may quickly arise. It is not yet established how rapid blood pressure changes outside of the autoregulation zone (ARZ) impact left (LV) and right ventricular (RV) function. Using cardiovascular magnetic resonance (CMR) imaging, measurements of myocardial tissue oxygenation and ventricular systolic and diastolic function can comprehensively assess the heart throughout a range of changing blood pressures. Design and methods: In 10 anesthetized swine, MAP was varied in steps of 10-15 mmHg from 29 to 196 mmHg using phenylephrine and urapidil inside a 3-Tesla MRI scanner. At each MAP level, oxygenation-sensitive (OS) cine images along with arterial and coronary sinus blood gas samples were obtained and blood flow was measured from a surgically implanted flow probe on the left anterior descending coronary artery. Using CMR feature tracking-software, LV and RV circumferential systolic and diastolic strain parameters were measured from the myocardial oxygenation cines. Results: LV and RV peak strain are compromised both below the lower limit (LV: Δ1.2 ± 0.4%, RV: Δ4.4 ± 1.2%, p < 0.001) and above the upper limit (LV: Δ2.1 ± 0.4, RV: Δ5.4 ± 1.4, p < 0.001) of the ARZ in comparison to a baseline of 70 mmHg. LV strain demonstrates a non-linear relationship with invasive and non-invasive measures of oxygenation. Specifically for the LV at hypotensive levels below the ARZ, systolic dysfunction is related to myocardial deoxygenation (ß = -0.216, p = 0.036) in OS-CMR and both systolic and diastolic dysfunction are linked to reduced coronary blood flow (peak strain: ß = -0.028, p = 0.047, early diastolic strain rate: ß = 0.026, p = 0.002). These relationships were not observed at hypertensive levels. Conclusion: In an animal model, biventricular function is compromised outside the coronary autoregulatory zone. Dysfunction at pressures below the lower limit is likely caused by insufficient blood flow and tissue deoxygenation. Conversely, hypertension-induced systolic and diastolic dysfunction points to high afterload as a cause. These findings from an experimental model are translatable to the clinical peri-operative environment in which myocardial deformation may have the potential to guide blood pressure management, in particular at varying individual autoregulation thresholds.

Study design for a randomized crossover study investigating myocardial strain analysis in patients with coronary artery disease at hyperoxia and normoxemia prior to coronary artery bypass graft surgery (StrECHO-O2).

BACKGROUND: Supplemental oxygen (O2) is used routinely during anesthesia. In the treatment of acute myocardial infarction, it has been established that hyperoxia is to be avoided, whereas information on benefit and risk of hyperoxia in patients with stable coronary artery disease (CAD) remain scarce, especially in the setting of general anesthesia. This study will compare the immediate effects of normoxemia and hyperoxia on cardiac function, with a primary focus on changes in peak longitudinal left-ventricular strain, in anesthetized stable chronic CAD patients using peri-operative transesophageal echocardiography (TEE). METHODS: A single-center randomized cross-over clinical trial will be conducted, enrolling 106 patients undergoing elective coronary artery bypass graft surgery. After the induction of anesthesia and prior to the start of surgery, cardiac function will be assessed by 2D and 3D TEE. Images will be acquired at two different oxygen states for each patient in randomized order. The fraction of inspired oxygen (FIO2) will be titrated to a normoxemic state (oxygen saturation of 95-98%) and adjusted to a hyperoxic state (FIO2 = 0.8). TEE images will be analyzed in a blinded manner for standard cardiac function and strain parameters. CONCLUSION: By using myocardial strain assessed by TEE, early and subtle signs of biventricular systolic and diastolic dysfunction can be promptly measured intraoperatively prior to the onset of severe signs of ischemia. The results may help anesthesiologists to better understand the effects of FIO2 on cardiac function and potentially tailor oxygen therapy to patients with CAD undergoing general anesthesia.

Noninvasive assessment of clinically significant portal hypertension using ΔT1 of the liver and spleen and ECV of the spleen on routine Gd-EOB-DTPA liver MRI.

PURPOSE: To analyze the predictive value of ΔT1 of the liver and spleen as well as the extracellular volume fraction (ECV) of the spleen as noninvasive biomarkers for the determination of clinically significant portal hypertension (CSPH) on routine Gd-EOB-DTPA liver MRI. METHOD: 195 consecutive patients with known or suspected chronic liver disease from 9/2018 to 7/2019 with Gd-EOB-DTPA liver MRI and abdominal T1 mapping were retrospectively included. Based on the presence of splenomegaly with thrombocytopenia, ascites and portosystemic collaterals, the patients were divided into noCSPH (n = 113), compensated CSPH (cCSPH, ≥1 finding without ascites; n = 55) and decompensated CSPH (dCSPH, ascites ± other findings; n = 27). T1 times were measured in the liver, spleen and abdominal aorta in the unenhanced and contrast-enhanced T1 maps. Native T1 times and ΔT1 of the liver and spleen as well as ECV of the spleen were compared between groups using the Kruskal-Wallis test with Dunn's post hoc test. Furthermore, cutoff values for group differentiation were calculated using ROC analysis with Youden's index. RESULTS: ΔT1 of the liver was significantly lower in patients with cCSPH and dCSPH (p < 0.001) compared to patients with noCSPH. In the ROC analyses for differentiation between noCSPH and CSPH (cCSPH + dCSPH), a cutoff of < 0.67 for ΔT1 of the liver (AUC = 0.79) performed better than ΔT1 (AUC = 0.69) and ECV (AUC = 0.63) of the spleen with cutoffs of > 0.29 and > 41.9, respectively. CONCLUSION: ΔT1 of the liver and spleen in addition to ECV of the spleen allow for determination of CSPH on routine Gd-EOB-DTPA liver MRI.