Adverse myocardial and vascular side effects of immune checkpoint inhibitors: a prospective multimodal cardiovascular assessment.

BACKGROUND: Immune checkpoint inhibitors (ICIs) can induce cardiovascular toxicities. OBJECTIVES: To prospectively assess the incidence of major cardiovascular events (MACE) on ICIs in solid cancer patients: myocarditis, pericarditis, acute coronary syndrome, heart failure, high-degree conduction abnormalities or sustained ventricular arrhythmias, or cardiovascular death at 6 weeks (early MACE), including asymptomatic clinical changes by an independent adjudication committee using current recommended diagnostic criteria. The secondary objective was the incidence of the above-mentioned events adding atrial fibrillation (AF) at 6 months (late MACE). RESULTS: Participants underwent pre-ICIs and repeated multimodality cardiac imaging (echocardiogram, cardiac magnetic resonance (CMR)), serum biomarkers (ultrasensitive troponin I), and rhythm surveillance (ambulatory ECG monitoring) at 6 weeks and 6 months. Forty-nine patients (38 (77.6%) male; mean age 64.3 (SD 11.0) years old) were included (June 2020-December 2021). Early MACE were observed in 9 (18.4%) patients at mean 40.1 (SD 5.9) days, with heart failure (HF) in 5 (10.2%), ventricular arrhythmias, or new conduction disorders in 4 (8.2%) patients. History of AF (HR 4.49 (CI 1.11-18.14), P = 0.035) predicted early MACE. At 6 months follow-up, 18 MACE were observed in 15/49 (31%) patients, with 6 (12.2%) HF events, 5 (10.2%) significant ventricular arrhythmias, or conduction disorders, and 4 (8.2%) AF. There was a significant decline in LVEF (P < 0.001) in patients with no MACE (P = 0.003) or HF (P = 0.0028). Higher creatinine at inclusion (HR 0.99 [0.98-1.00], P = 0.006) predicted HF on multivariate analysis. There were no significant T1 or T2 mapping changes in our study cohort on repeated CMR. CONCLUSIONS: Cardiotoxicity on ICIs is more frequent than previously described when using a thorough detection strategy, consisting mainly in HF and asymptomatic rhythm disorders.

Discordance between 2D and 4D flow in the assessment of pulmonary regurgitation severity: a right ventricular remodeling follow-up study.

OBJECTIVES: Pulmonary regurgitation (PR) is common in adult congenital heart disease (ACHD). 2D phase contrast MRI is the reference method for the quantification of PR and helps in the decision of pulmonary valve replacement (PVR). 4D flow MRI can be an alternative method to estimate PR but more validation is still needed. Our purpose was to compare 2D and 4D flow in PR quantification using the degree of right ventricular remodeling after PVR as the reference standard. METHODS: In 30 adult patients with a pulmonary valve disease recruited between 2015 and 2018, PR was assessed using both 2D and 4D flow. Based on the clinical standard of care, 22 underwent PVR. The pre PVR estimate of PR was compared using the post-operative decrease in right ventricle end-diastolic volume on follow-up exam as reference. RESULTS: In the overall cohort, regurgitant volume (Rvol) and regurgitant fraction (RF) of PR measured by 2D and 4D flow were well correlated but with moderate agreement in the overall cohort (r = 0.90, mean diff. -14 ± 12.5 mL; and r = 0.72, mean diff. -15 ± 13%; all p < 0.0001). Correlations between Rvol estimates and right ventricle end-diastolic volume decrease after PVR was higher with 4D flow (r = 0.80, p < 0.0001) than with 2D flow (r = 0.72, p < 0.0001). CONCLUSIONS: In ACHD, PR quantification from 4D flow better predicts post-PVR right ventricle remodeling than that from 2D flow. Further studies are needed to evaluate the added value of this 4D flow quantification for guiding replacement decision. KEY POINTS: • Using 4D flow MRI allows a better quantification of pulmonary regurgitation in adult congenital heart disease than 2D flow when taking right ventricle remodeling after pulmonary valve replacement as a reference. • A plane positioned perpendicular to the ejected flow volume as allowed by 4D flow provides better results to estimate pulmonary regurgitation.

Diastolic Function Assessment of Left and Right Ventricles by MRI in Systemic Sclerosis Patients.

BACKGROUND: Heart involvement is frequent although often clinically silent in systemic sclerosis (SSc) patients. Early identification of cardiac involvement can be improved by noninvasive methods such as MRI, in addition to transthoracic echocardiography (TTE). PURPOSE: To assess the ability of phase-contrast (PC)-MRI to detect subclinical left (LV) and right (RV) ventricular diastolic dysfunction in SSc patients. STUDY TYPE: Prospective. POPULATION: Thirty-five consecutive SSc patients (49 ± 14 years) and 35 sex- and age-matched healthy controls (48.6 ± 13.5 years) who underwent TTE and MRI in the same week. FIELD STRENGTH/SEQUENCE: 5 T/PC-MRI using a breath-hold velocity-encoded gradient echo sequence. ASSESSMENT: LV TTE (E/E') and LV and RV PC-MRI indices of diastolic function (LV early and late transmitral [EM , EfM , AM , AfM ] and RV transtricuspid [ET , EfT , AT , AfT ] peak filling flow velocities and flow rates, as well as LV [ E M ' ] and RV [ E T ' ] peak longitudinal myocardial velocities during diastole) were measured. STATISTICAL TESTS: Two-tailed t-test, Wilcoxon test, or Fischer test for comparison of variables between SSc and healthy control groups; sensitivity, specificity, receiver-operating-characteristic (ROC) area under the curve (AUC) to assess discriminative ability of variables. A P-value <0.05 was considered statistically significant. RESULTS: TTE LV E/E' and MRI EM / E M ' and ET / E T ' were significantly higher in SSc patients than in controls (8.27 ± 1.25 vs. 6.70 ± 1.66; 9.43 ± 2.7 vs. 6.51 ± 1.50; 6.51 [4.70-10.40] vs. 4.13 [3.22-5.75], respectively) and separated SSc patients and healthy controls with good sensitivity (68%, 71%, and 80%), specificity (85%, 94%, and 62%), and AUC (0.787, 0.807, and 0.765). LV EfM was significantly higher in SSc patients than in controls (347.1 ± 113.7 vs. 284.7 ± 94.6) as RVAfT (277 [231-355] vs. 220 [154-253] mL/sec) with impaired relaxation pattern (EfT /AfT , 0.95 [0.87-1.21] vs. 1.12 [0.93-1.47]). DATA CONCLUSION: MRI was able to detect LV and RV diastolic dysfunction in SSc patients with good accuracy in the absence of LV systolic dysfunction at echocardiography. Use of MRI can allow to better assess the early impact of myocardial fibrosis related to SSc. LEVEL OF EVIDENCE: 1 TECHNICAL EFFICACY STAGE: 2.

Comprehensive assessment of local and regional aortic stiffness in patients with tricuspid or bicuspid aortic valve aortopathy using magnetic resonance imaging.

BACKGROUND: We aimed to provide a comprehensive aortic stiffness description using magnetic resonance imaging (MRI) in patients with ascending thoracic aorta aneurysm and tricuspid (TAV-ATAA) or bicuspid (BAV) aortic valve. METHODS: This case-control study included 18 TAV-ATAA and 19 BAV patients, with no aortic valve stenosis/severe regurgitation, who were 1:1 age-, gender- and central blood pressures (BP)-matched to healthy volunteers. Each underwent simultaneous aortic MRI and BP measurements. 3D anatomical MRI provided aortic diameters. Stiffness indices included: regional ascending (AA) and descending (DA) aorta pulse wave velocity (PWV) from 4D flow MRI; local AA and DA strain, distensibility and theoretical Bramwell-Hill (BH) model-based PWV, as well as regional arch PWV from 2D flow MRI. RESULTS: Patient groups had significantly higher maximal AA diameter (median[interquartile range], TAV-ATAA: 47.5[42.0-51.3]mm, BAV: 45.0[41.0-47.0]mm) than their respective controls (29.1[26.8-31.8] and 28.1[26.0-32.0]mm, p < 0.0001), while BP were similar (p ≥ 0.25). Stiffness indices were significantly associated with age (ρ ≥ 0.33), mean BP (arch PWV: ρ = 0.25, p = 0.05; DA distensibility: ρ = -0.30, p = 0.02) or AA diameter (arch PWV: ρ = 0.28, p = 0.03; DA PWV: ρ = 0.32, p = 0.009). None of them, however, was significantly different between TAV-ATAA or BAV patients and their matched controls. Finally, while direct PWV measures were significantly correlated to BH-PWV estimates in controls (ρ ≥ 0.40), associations were non-significant in TAV-ATAA and BAV groups (p ≥ 0.18). CONCLUSIONS: The overlap of MRI-derived aortic stiffness indices between patients with TAV or BAV aortopathy and matched controls highlights another heterogeneous feature of aortopathy, and suggests the urgent need for more sensitive indices which might help better discriminate such diseases.

Neopulmonary Outflow Tract Obstruction Assessment by 4D Flow MRI in Adults With Transposition of the Great Arteries After Arterial Switch Operation.

BACKGROUND: The main complication in adult patients with transposition of the great arteries (TGA) treated by an arterial switch operation (ASO) is neopulmonary outflow tract stenosis (NPOTS). However, pulmonary flow velocity measurements cannot always be performed with transthoracic echocardiography (TTE) due to complex anatomical features. 4D flow MRI allows detection, quantification, and location of the obstruction site along the NPOTS. PURPOSE AND HYPOTHESIS: To investigate the accuracy of 4D flow for the diagnosis of NPOTS in adults with TGA corrected by ASO. STUDY TYPE: Prospective. POPULATION: Thirty-three adult patients with TGA treated by ASO (19 men, mean age 25.5 years old). FIELD STRENGTH/SEQUENCE: Accelerated 4D flow research sequence at 3T. ASSESSMENT: Maximum NPOTS velocities on TTE and 4D flow MRI done the same day. STATISTICAL TESTS: Pearson correlation coefficient, paired t-test, and Bland-Altman analysis were used to investigate the relationship between TTE and MRI data. RESULTS: In 16 patients (48.5%), evaluation of NPOTS anatomy was not obtained by TTE, while it was always possible by 4D flow. Peak flow velocity (PV) measurements in Doppler and 4D flow were highly correlated (r = 0.78; P < 0.001). PV >350 cm.s-1 was detected in only one patient (3%) by TTE vs. five patients (15%) by 4D flow. Moreover, a high correlation was found between PV and the right ventricle (RV) mass index to body surface area when using 4D flow (r = 0.63; P < 0.001). The location of NPOTS was determined in all patients using 4D flow and concerned the main pulmonary artery in 42%. DATA CONCLUSION: Compared to TTE, 4D flow MRI provides better sensitivity to detect and locate NPOTS in patients with TGA treated by ASO. 4D flow PV measurements in NPOTS were well correlated with TTE PV and RV mass. LEVEL OF EVIDENCE: 1 Technical Efficacy: Stage 2 J. Magn. Reson. Imaging 2020;51:1699-1705.

Numerical assessment and comparison of pulse wave velocity methods aiming at measuring aortic stiffness.

Pulse waveform analyses have become established components of cardiovascular research. Recently several methods have been proposed as tools to measure aortic pulse wave velocity (aPWV). The carotid-femoral pulse wave velocity (cf-PWV), the current clinical gold standard method for the noninvasive assessment of aPWV, uses the carotid-to-femoral pulse transit time difference (cf-PTT) and an estimated path length to derive cf-PWV. OBJECTIVE: The heart-ankle PWV (ha-PWV), brachial-ankle PWV (ba-PWV) and finger-toe (ft-PWV) are also methods presuming to approximate aPWV based on time delays between physiological cardiovascular signals at two locations (~heart-ankle PTT, ha-PTT; ~brachial-ankle PTT, ba-PTT; ~finger-toe PTT, ft-PTT) and a path length typically derived from the subject's height. To test the validity of these methods, we used a detailed 1D arterial network model (143 arterial segments) including the foot and hand circulation. APPROACH: The arterial tree dimensions and properties were taken from the literature and completed with data from patient scans. We calculated PTTs with all the methods mentioned above. The calculated PTTs were compared with the aortic PTT (aPTT), which is considered as the absolute reference method in this study. MAIN RESULTS: The correlation between methods and aPTT was good and significant, cf-PTT (R 2 = 0.97; P < 0.001; mean difference 5 ± 2 ms), ha-PTT (R 2 = 0.96; P < 0.001; 150 ± 23 ms), ba-PTT (R 2 = 0.96; P < 0.001; 70 ± 13 ms) and ft-PTT (R 2 = 0.95; P < 0.001; 14 ± 10 ms). Consequently, good correlation was also observed for the PWV values derived with the tested methods, but absolute values differed because of the different path lengths used. SIGNIFICANCE: In conclusion, our computer model-based analyses demonstrate that for PWV methods based on peripheral signals, pulse transit time differences closely correlate with the aortic transit time, supporting the use of these methods in clinical practice.

Assessment of left atrial function by MRI myocardial feature tracking.

BACKGROUND: Left atrium (LA) volumes and function are predictors of cardiovascular events. Because LA function cannot be assessed from cardiovascular magnetic resonance imaging (MRI) using the well-established left ventricular tagging techniques, we hypothesized that adequate feature tracking (FT) applied to conventional cine MRI data could characterize LA function accurately. METHODS: We studied 10 young (28 ± 7 years) and 10 elderly (64 ± 6 years) healthy subjects, as well as 20 patients with moderate to severe aortic valve stenosis (AVS; 73 ± 15 years, effective aortic valve area: 0.67 ± 0.36 cm(2) ). MRI cine two-, three-, and four-chamber views were analyzed using a newly proposed FT method based on spatial correlation and endocardial detection resulting in: regional and global longitudinal strain and strain rate, radial motion fraction and relative velocity for the three LA motion phases including reservoir, conduit, and LA contraction. RESULTS: FT reliability was indicated by a good overlap between tracking results and manual LA endocardial borders, the low error for comparison against theoretical strains introduced in a synthetic phantom and the good inter-observer reproducibility (coefficient of variation < 15%). While all LA functional parameters were significantly impaired in AVS patients (p < 0.04), subclinical age-related variations induced a decreasing trend on all LA parameters but were significant only for radial conduit function parameters (p < 0.03). Finally, LA functional parameters characterized LA alteration in AVS with higher sensitivity than conventional LA volumetric parameters. CONCLUSIONS: Left atrial FT is feasible on MRI cine images and its addition to conventional analysis tools might enhance the diagnosis value of MRI in many heart diseases.