Is atrial fibrillation in HFpEF a distinct phenotype? Insights from multiparametric MRI and circulating biomarkers.

BACKGROUND: Heart failure with preserved ejection fraction (HFpEF) and atrial fibrillation (AF) frequently co-exist. There is a limited understanding on whether this coexistence is associated with distinct alterations in myocardial remodelling and mechanics. We aimed to determine if patients with atrial fibrillation (AF) and heart failure with preserved ejection fraction (HFpEF) represent a distinct phenotype. METHODS: In this secondary analysis of adults with HFpEF (NCT03050593), participants were comprehensively phenotyped with stress cardiac MRI, echocardiography and plasma fibroinflammatory biomarkers, and were followed for the composite endpoint (HF hospitalisation or death) at a median of 8.5 years. Those with AF were compared to sinus rhythm (SR) and unsupervised cluster analysis was performed to explore possible phenotypes. RESULTS: 136 subjects were included (SR = 75, AF = 61). The AF group was older (76 ± 8 vs. 70 ± 10 years) with less diabetes (36% vs. 61%) compared to the SR group and had higher left atrial (LA) volumes (61 ± 30 vs. 39 ± 15 mL/m2, p < 0.001), lower LA ejection fraction (EF) (31 ± 15 vs. 51 ± 12%, p < 0.001), worse left ventricular (LV) systolic function (LVEF 63 ± 8 vs. 68 ± 8%, p = 0.002; global longitudinal strain 13.6 ± 2.9 vs. 14.7 ± 2.4%, p = 0.003) but higher LV peak early diastolic strain rates (0.73 ± 0.28 vs. 0.53 ± 0.17 1/s, p < 0.001). The AF group had higher levels of syndecan-1, matrix metalloproteinase-2, proBNP, angiopoietin-2 and pentraxin-3, but lower level of interleukin-8. No difference in clinical outcomes was observed between the groups. Three distinct clusters were identified with the poorest outcomes (Log-rank p = 0.029) in cluster 2 (hypertensive and fibroinflammatory) which had equal representation of SR and AF. CONCLUSIONS: Presence of AF in HFpEF is associated with cardiac structural and functional changes together with altered expression of several fibro-inflammatory biomarkers. Distinct phenotypes exist in HFpEF which may have differing clinical outcomes.

Randomized Placebo-Controlled Trial to Evaluate Effects of Eplerenone on Myocardial Perfusion and Function Among Persons With Human Immunodeficiency Virus (HIV)-Results From the MIRACLE HIV Study.

BACKGROUND: Increased renin angiotensin aldosterone system (RAAS) activity may contribute to excess cardiovascular disease in people with HIV (PWH). We investigated how RAAS blockade may improve myocardial perfusion, injury, and function among well-treated PWH. METHODS: Forty PWH, on stable ART, without known heart disease were randomized to eplerenone 50 mg PO BID (n = 20) or identical placebo (n = 20) for 12 months. The primary endpoints were (1) myocardial perfusion assessed by coronary flow reserve (CFR) on cardiac PET or stress myocardial blood flow (sMBF) on cardiac MRI or (2) myocardial inflammation by extracellular mass index (ECMi) on cardiac MRI. RESULTS: Beneficial effects on myocardial perfusion were seen for sMBF by cardiac MRI (mean [SD]: 0.09 [0.56] vs -0.53 [0.68] mL/min/g; P = .03) but not CFR by cardiac PET (0.01 [0.64] vs -0.07 [0.48]; P = .72, eplerenone vs placebo). Eplerenone improved parameters of myocardial function on cardiac MRI including left ventricular end diastolic volume (-13 [28] vs 10 [26] mL; P = .03) and global circumferential strain (GCS; median [interquartile range 25th-75th]: -1.3% [-2.9%-1.0%] vs 2.3% [-0.4%-4.1%]; P = .03), eplerenone versus placebo respectively. On cardiac MRI, improvement in sMBF related to improvement in global circumferential strain (ρ = -0.65, P = .057) among those treated with eplerenone. Selecting for those with impaired myocardial perfusion (CFR <2.5 and/or sMBF <1.8), there was a treatment effect of eplerenone versus placebo to improve CFR (0.28 [0.27] vs -0.05 [0.36]; P = .04). Eplerenone prevented a small increase in troponin (0.00 [-0.13-0.00] vs 0.00 [0.00-0.74] ng/L; P = .03) without effects on ECMi (0.9 [-2.3-4.3] vs -0.7 [-2.2--0.1] g/m2; P = .38). CD4+ T-cell count (127 [-38-286] vs -6 [-168-53] cells/µL; P = .02) increased in the eplerenone- versus placebo-treated groups. CONCLUSIONS: RAAS blockade with eplerenone benefitted key indices and prevented worsening of myocardial perfusion, injury, and function among PWH with subclinical cardiac disease when compared with placebo. CLINICAL TRIALS REGISTRATION: NCT02740179 (https://clinicaltrials.gov/ct2/show/NCT02740179?term=NCT02740179&draw=2&rank=1).

Atorvastatin for Anthracycline-Associated Cardiac Dysfunction: The STOP-CA Randomized Clinical Trial.

Importance: Anthracyclines treat a broad range of cancers. Basic and retrospective clinical data have suggested that use of atorvastatin may be associated with a reduction in cardiac dysfunction due to anthracycline use. Objective: To test whether atorvastatin is associated with a reduction in the proportion of patients with lymphoma receiving anthracyclines who develop cardiac dysfunction. Design, Setting, and Participants: Double-blind randomized clinical trial conducted at 9 academic medical centers in the US and Canada among 300 patients with lymphoma who were scheduled to receive anthracycline-based chemotherapy. Enrollment occurred between January 25, 2017, and September 10, 2021, with final follow-up on October 10, 2022. Interventions: Participants were randomized to receive atorvastatin, 40 mg/d (n = 150), or placebo (n = 150) for 12 months. Main Outcomes and Measures: The primary outcome was the proportion of participants with an absolute decline in left ventricular ejection fraction (LVEF) of ≥10% from prior to chemotherapy to a final value of <55% over 12 months. A secondary outcome was the proportion of participants with an absolute decline in LVEF of ≥5% from prior to chemotherapy to a final value of <55% over 12 months. Results: Of the 300 participants randomized (mean age, 50 [SD, 17] years; 142 women [47%]), 286 (95%) completed the trial. Among the entire cohort, the baseline mean LVEF was 63% (SD, 4.6%) and the follow-up LVEF was 58% (SD, 5.7%). Study drug adherence was noted in 91% of participants. At 12-month follow-up, 46 (15%) had a decline in LVEF of 10% or greater from prior to chemotherapy to a final value of less than 55%. The incidence of the primary end point was 9% (13/150) in the atorvastatin group and 22% (33/150) in the placebo group (P = .002). The odds of a 10% or greater decline in LVEF to a final value of less than 55% after anthracycline treatment was almost 3 times greater for participants randomized to placebo compared with those randomized to atorvastatin (odds ratio, 2.9; 95% CI, 1.4-6.4). Compared with placebo, atorvastatin also reduced the incidence of the secondary end point (13% vs 29%; P = .001). There were 13 adjudicated heart failure events (4%) over 24 months of follow-up. There was no difference in the rates of incident heart failure between study groups (3% with atorvastatin, 6% with placebo; P = .26). The number of serious related adverse events was low and similar between groups. Conclusions and Relevance: Among patients with lymphoma treated with anthracycline-based chemotherapy, atorvastatin reduced the incidence of cardiac dysfunction. This finding may support the use of atorvastatin in patients with lymphoma at high risk of cardiac dysfunction due to anthracycline use. Trial Registration: ClinicalTrials.gov Identifier: NCT02943590.

Toward Replacing Late Gadolinium Enhancement With Artificial Intelligence Virtual Native Enhancement for Gadolinium-Free Cardiovascular Magnetic Resonance Tissue Characterization in Hypertrophic Cardiomyopathy.

BACKGROUND: Late gadolinium enhancement (LGE) cardiovascular magnetic resonance (CMR) imaging is the gold standard for noninvasive myocardial tissue characterization but requires intravenous contrast agent administration. It is highly desired to develop a contrast agent-free technology to replace LGE for faster and cheaper CMR scans. METHODS: A CMR virtual native enhancement (VNE) imaging technology was developed using artificial intelligence. The deep learning model for generating VNE uses multiple streams of convolutional neural networks to exploit and enhance the existing signals in native T1 maps (pixel-wise maps of tissue T1 relaxation times) and cine imaging of cardiac structure and function, presenting them as LGE-equivalent images. The VNE generator was trained using generative adversarial networks. This technology was first developed on CMR datasets from the multicenter Hypertrophic Cardiomyopathy Registry, using hypertrophic cardiomyopathy as an exemplar. The datasets were randomized into 2 independent groups for deep learning training and testing. The test data of VNE and LGE were scored and contoured by experienced human operators to assess image quality, visuospatial agreement, and myocardial lesion burden quantification. Image quality was compared using a nonparametric Wilcoxon test. Intra- and interobserver agreement was analyzed using intraclass correlation coefficients (ICC). Lesion quantification by VNE and LGE were compared using linear regression and ICC. RESULTS: A total of 1348 hypertrophic cardiomyopathy patients provided 4093 triplets of matched T1 maps, cines, and LGE datasets. After randomization and data quality control, 2695 datasets were used for VNE method development and 345 were used for independent testing. VNE had significantly better image quality than LGE, as assessed by 4 operators (n=345 datasets; P<0.001 [Wilcoxon test]). VNE revealed lesions characteristic of hypertrophic cardiomyopathy in high visuospatial agreement with LGE. In 121 patients (n=326 datasets), VNE correlated with LGE in detecting and quantifying both hyperintensity myocardial lesions (r=0.77-0.79; ICC=0.77-0.87; P<0.001) and intermediate-intensity lesions (r=0.70-0.76; ICC=0.82-0.85; P<0.001). The native CMR images (cine plus T1 map) required for VNE can be acquired within 15 minutes and producing a VNE image takes less than 1 second. CONCLUSIONS: VNE is a new CMR technology that resembles conventional LGE but without the need for contrast administration. VNE achieved high agreement with LGE in the distribution and quantification of lesions, with significantly better image quality.

A relaxometry method that emphasizes practicality and availability.

PURPOSE: Although many methods have been proposed to quantitatively map the main MRI parameters (e.g., T1 , T2 , C × M0 ), these methods often involve special sequences not readily available on clinical scanners and/or may require long scan times. In contrast, the proposed method can readily run on most scanners, offer flexible tradeoffs between scan time and image quality, and map MRI parameters jointly to ensure spatial alignment. METHODS: The approach is based on the multi-shot spin-echo (SE) EPI sequence. The corresponding signal equation was derived and strategies for solving it were developed. As usual with multi-shot EPI, scan time can readily be traded-off against image quality by adjusting the echo train length. Validation was performed against reference relaxometry methods, in gel phantoms with varying concentrations of gadobutrol and gadoterate meglumine contrast agents. In vivo examples are further presented, from 3 neuroradiology patients. RESULTS: Bland-Altman analysis was performed: for T2 , as compared to 2D SE, bias was 0.29 ms and the 95% limits of agreement ranged from -1.15 to +1.73 ms. For T1 , compared to inversion-recovery SE (and MOLLI), bias was -20.2 ms (and -14.5 ms) and the limits of agreement ranged from -62.4 to +22.0 ms (and -53.8 to +24.9 ms). The mean relative T1 error between the proposed method and each of the 2 reference methods was similar to that of the reference methods among themselves. CONCLUSION: In the constellation of existing relaxometry methods, the proposed method is meant to stand out in terms of its practicality and availability.

Emerging Techniques in Cardiac Magnetic Resonance Imaging.

Cardiovascular disease is the leading cause of death and a significant contributor of health care costs. Noninvasive imaging plays an essential role in the management of patients with cardiovascular disease. Cardiac magnetic resonance (MR) can noninvasively assess heart and vascular abnormalities, including biventricular structure/function, blood hemodynamics, myocardial tissue composition, microstructure, perfusion, metabolism, coronary microvascular function, and aortic distensibility/stiffness. Its ability to characterize myocardial tissue composition is unique among alternative imaging modalities in cardiovascular disease. Significant growth in cardiac MR utilization, particularly in Europe in the last decade, has laid the necessary clinical groundwork to position cardiac MR as an important imaging modality in the workup of patients with cardiovascular disease. Although lack of availability, limited training, physician hesitation, and reimbursement issues have hampered widespread clinical adoption of cardiac MR in the United States, growing clinical evidence will ultimately overcome these challenges. Advances in cardiac MR techniques, particularly faster image acquisition, quantitative myocardial tissue characterization, and image analysis have been critical to its growth. In this review article, we discuss recent advances in established and emerging cardiac MR techniques that are expected to strengthen its capability in managing patients with cardiovascular disease. LEVEL OF EVIDENCE: 5 TECHNICAL EFFICACY: Stage 1.

Utilization of cardiovascular magnetic resonance (CMR) imaging for resumption of athletic activities following COVID-19 infection: an expert consensus document on behalf of the American Heart Association Council on Cardiovascular Radiology and Intervention (CVRI) Leadership and endorsed by the Society for Cardiovascular Magnetic Resonance (SCMR).

The global pandemic of coronavirus disease 2019 (COVID-19) caused by infection with severe acute respiratory suyndrome coronavirus 2 (SARS-CoV-2) is now entering its 4th year with little evidence of abatement. As of December 2022, the World Health Organization Coronavirus (COVID-19) Dashboard reported 643 million cumulative confirmed cases of COVID-19 worldwide and 98 million in the United States alone as the country with the highest number of cases. While pneumonia with lung injury has been the manifestation of COVID-19 principally responsible for morbidity and mortality, myocardial inflammation and systolic dysfunction though uncommon are well-recognized features that also associate with adverse prognosis. Given the broad swath of the population infected with COVID-19, the large number of affected professional, collegiate, and amateur athletes raises concern regarding the safe resumption of athletic activity (return to play, RTP) following resolution of infection. A variety of different testing combinations that leverage the electrocardiogram, echocardiography, circulating cardiac biomarkers, and cardiovascular magnetic resonance (CMR) imaging have been proposed and implemented to mitigate risk. CMR in particular affords high sensitivity for myocarditis but has been employed and interpreted non-uniformly in the context of COVID-19 thereby raising uncertainty as to the generalizability and clinical relevance of findings with respect to RTP. This consensus document synthesizes available evidence to contextualize the appropriate utilization of CMR in the RTP assessment of athletes with prior COVID-19 infection to facilitate informed, evidence-based decisions, while identifying knowledge gaps that merit further investigation.

Short-term adverse remodeling progression in asymptomatic aortic stenosis.

OBJECTIVES: Aortic stenosis (AS) is characterised by a long and variable asymptomatic course. Our objective was to use cardiovascular magnetic resonance imaging (MRI) to assess progression of adverse remodeling in asymptomatic AS. METHODS: Participants from the PRIMID-AS study, a prospective, multi-centre observational study of asymptomatic patients with moderate to severe AS, who remained asymptomatic at 12 months, were invited to undergo a repeat cardiac MRI. RESULTS: Forty-three participants with moderate-severe AS (mean age 64.4 ± 14.8 years, 83.4% male, aortic valve area index 0.54 ± 0.15 cm2/m2) were included. There was small but significant increase in indexed left ventricular (LV) (90.7 ± 22.0 to 94.5 ± 23.1 ml/m2, p = 0.007) and left atrial volumes (52.9 ± 11.3 to 58.6 ± 13.6 ml/m2, p < 0.001), with a decrease in systolic (LV ejection fraction 57.9 ± 4.6 to 55.6 ± 4.1%, p = 0.001) and diastolic (longitudinal diastolic strain rate 1.06 ± 0.2 to 0.99 ± 0.2 1/s, p = 0.026) function, but no overall change in LV mass or mass/volume. Late gadolinium enhancement increased (2.02 to 4.26 g, p < 0.001) but markers of diffuse interstitial fibrosis did not change significantly (extracellular volume index 12.9 [11.4, 17.0] ml/m2 to 13.3 [11.1, 15.1] ml/m2, p = 0.689). There was also a significant increase in the levels of NT-proBNP (43.6 [13.45, 137.08] pg/ml to 53.4 [19.14, 202.20] pg/ml, p = 0.001). CONCLUSIONS: There is progression in cardiac remodeling with increasing scar burden even in asymptomatic AS. Given the lack of reversibility of LGE post-AVR and its association with long-term mortality post-AVR, this suggests the potential need for earlier intervention, before the accumulation of LGE, to improve the long-term outcomes in AS. KEY POINTS: • Current guidelines recommend waiting until symptom onset before valve replacement in severe AS. • MRI showed clear progression in cardiac remodeling over 12 months in asymptomatic patients with AS, with near doubling in LGE. • This highlights the need for potentially earlier intervention or better risk stratification in AS.

Immune Correlates of Diffuse Myocardial Fibrosis and Diastolic Dysfunction Among Aging Women With Human Immunodeficiency Virus.

Human immunodeficiency virus (HIV) imparts increased heart failure risk to women. Among women with HIV (WHIV), immune pathways relating to heart failure precursors may intimate targets for heart failure prevention strategies. Twenty asymptomatic, antiretroviral-treated WHIV and 14 non-HIV-infected women matched on age and body mass index underwent cardiac magnetic resonance imaging and immune phenotyping. WHIV (vs non-HIV-infected women) exhibited increased myocardial fibrosis (extracellular volume fraction, 0.34 ± 0.06 vs 0.29 ± 0.04; P = .002), reduced diastolic function (diastolic strain rate, 1.10 ± 0.23 s-1 vs 1.39 ± 0.27 s-1; P = .003), and heightened systemic monocyte activation. Among WHIV, soluble CD163 levels correlated with myocardial fibrosis (r = 0.53; P = .02), while circulating inflammatory CD14+CD16+ monocyte CCR2 expression related directly to myocardial fibrosis (r = 0.48; P = .04) and inversely to diastolic function (r = -0.49; P = .03). Clinical Trials Registration. NCT02874703.

Reference ranges ("normal values") for cardiovascular magnetic resonance (CMR) in adults and children: 2020 update.

Cardiovascular magnetic resonance (CMR) enables assessment and quantification of morphological and functional parameters of the heart, including chamber size and function, diameters of the aorta and pulmonary arteries, flow and myocardial relaxation times. Knowledge of reference ranges ("normal values") for quantitative CMR is crucial to interpretation of results and to distinguish normal from disease. Compared to the previous version of this review published in 2015, we present updated and expanded reference values for morphological and functional CMR parameters of the cardiovascular system based on the peer-reviewed literature and current CMR techniques. Further, databases and references for deep learning methods are included.

Comparison of myocardial fibrosis quantification methods by cardiovascular magnetic resonance imaging for risk stratification of patients with suspected myocarditis.

BACKGROUND: Although the presence of late gadolinium enhancement (LGE) using cardiovascular magnetic resonance imaging (CMR) is a significant discriminator of events in patients with suspected myocarditis, no data are available on the optimal LGE quantification method. METHODS: Six hundred seventy consecutive patients (48 ± 16 years, 59% male) with suspected myocarditis were enrolled between 2002 and 2015. We performed LGE quantitation using seven different signal intensity thresholding methods based either on 2, 3, 4, 5, 6, 7 standard deviations (SD) above remote myocardium or full width at half maximum (FWHM). In addition, a LGE visual presence score (LGE-VPS) (LGE present/absent in each segment) was assessed. For each of these methods, the strength of association of LGE results with major adverse cardiac events (MACE) was determined. Inter-and intra-rater variability using intraclass-correlation coefficient (ICC) was performed for all methods. RESULTS: Ninety-eight (15%) patients experienced a MACE at a medium follow-up of 4.7 years. LGE quantification by FWHM, 2- and 3-SD demonstrated univariable association with MACE (hazard ratio [HR] 1.05, 95% confidence interval [CI]:1.02-1.08, p = 0.001; HR 1.02, 95%CI:1.00-1.04; p = 0.001; HR 1.02, 95%CI: 1.00-1.05, p = 0.035, respectively), whereas 4-SD through 7-SD methods did not reach significant association. LGE-VPS also demonstrated association with MACE (HR 1.09, 95%CI: 1.04-1.15, p < 0.001). In the multivariable model, FWHM, 2-SD methods, and LGE-VPS each demonstrated significant association with MACE adjusted to age, sex, BMI and LVEF (adjusted HR of 1.04, 1.02, and 1.07; p = 0.009, p = 0.035; and p = 0.005, respectively). In these, FWHM and LGE-VPS had the highest degrees of inter and intra-rater reproducibility based on their high ICC values. CONCLUSIONS: FWHM is the optimal semi-automated quantification method in risk-stratifying patients with suspected myocarditis, demonstrating the strongest association with MACE and the highest technical consistency. Visual LGE scoring is a reliable alternative method and is associated with a comparable association with MACE and reproducibility in these patients. TRIAL REGISTRATION NUMBER: NCT03470571 . Registered 13th March 2018. Retrospectively registered.

Comparison of exercise testing and CMR measured myocardial perfusion reserve for predicting outcome in asymptomatic aortic stenosis: the PRognostic Importance of MIcrovascular Dysfunction in Aortic Stenosis (PRIMID AS) Study.

AIMS: To assess cardiovascular magnetic resonance (CMR) measured myocardial perfusion reserve (MPR) and exercise testing in asymptomatic patients with moderate-severe AS. METHODS AND RESULTS: Multi-centre, prospective, observational study, with blinded analysis of CMR data. Patients underwent adenosine stress CMR, symptom-limited exercise testing (ETT) and echocardiography and were followed up for 12-30 months. The primary outcome was a composite of: typical AS symptoms necessitating referral for AVR, cardiovascular death and major adverse cardiovascular events. 174 patients were recruited: mean age 66.2 ± 13.34 years, 76% male, peak velocity 3.86 ± 0.56 m/s and aortic valve area index 0.57 ± 0.14 cm2/m2. A primary outcome occurred in 47 (27%) patients over a median follow-up of 374 (IQR 351-498) days. The mean MPR in those with and without a primary outcome was 2.06 ± 0.65 and 2.34 ± 0.70 (P = 0.022), while the incidence of a symptom-limited ETT was 45.7% and 27.0% (P = 0.020), respectively. MPR showed moderate association with outcome area under curve (AUC) = 0.61 (0.52-0.71, P = 0.020), as did exercise testing (AUC = 0.59 (0.51-0.68, P = 0.027), with no significant difference between the two. CONCLUSIONS: MPR was associated with symptom-onset in initially asymptomatic patients with AS, but with moderate accuracy and was not superior to symptom-limited exercise testing. ClinicalTrials.gov (NCT01658345).

Effect of Omega-3 Acid Ethyl Esters on Left Ventricular Remodeling After Acute Myocardial Infarction: The OMEGA-REMODEL Randomized Clinical Trial.

BACKGROUND: Omega-3 fatty acids from fish oil have been associated with beneficial cardiovascular effects, but their role in modifying cardiac structures and tissue characteristics in patients who have had an acute myocardial infarction while receiving current guideline-based therapy remains unknown. METHODS: In a multicenter, double-blind, placebo-controlled trial, participants presenting with an acute myocardial infarction were randomly assigned 1:1 to 6 months of high-dose omega-3 fatty acids (n=180) or placebo (n=178). Cardiac magnetic resonance imaging was used to assess cardiac structure and tissue characteristics at baseline and after study therapy. The primary study endpoint was change in left ventricular systolic volume index. Secondary endpoints included change in noninfarct myocardial fibrosis, left ventricular ejection fraction, and infarct size. RESULTS: By intention-to-treat analysis, patients randomly assigned to omega-3 fatty acids experienced a significant reduction of left ventricular systolic volume index (-5.8%, P=0.017), and noninfarct myocardial fibrosis (-5.6%, P=0.026) in comparison with placebo. Per-protocol analysis revealed that those patients who achieved the highest quartile increase in red blood cell omega-3 index experienced a 13% reduction in left ventricular systolic volume index in comparison with the lowest quartile. In addition, patients in the omega-3 fatty acid arm underwent significant reductions in serum biomarkers of systemic and vascular inflammation and myocardial fibrosis. There were no adverse events associated with high-dose omega-3 fatty acid therapy. CONCLUSIONS: Treatment of patients with acute myocardial infarction with high-dose omega-3 fatty acids was associated with reduction of adverse left ventricular remodeling, noninfarct myocardial fibrosis, and serum biomarkers of systemic inflammation beyond current guideline-based standard of care. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifier: NCT00729430.

Left Atrial structure and function in hypertrophic cardiomyopathy sarcomere mutation carriers with and without left ventricular hypertrophy.

BACKGROUND: Impaired left atrial (LA) function is an early marker of cardiac dysfunction and predictor of adverse cardiac events. Herein, we assess LA structure and function in hypertrophy in hypertrophic cardiomyopathy (HCM) sarcomere mutation carriers with and without left ventricular hypertrophy (LVH). METHOD: Seventy-three participants of the HCMNet study who underwent cardiovascular magnetic resonance (CMR) imaging were studied, including mutation carriers with overt HCM (n = 34), preclinical mutation carriers without HCM (n = 24) and healthy, familial controls (n = 15). RESULTS: LA volumes were similar between preclinical, control and overt HCM cohorts after covariate adjustment. However, there was evidence of impaired LA function with decreased LA total emptying function in both preclinical (64 ± 8%) and overt HCM (59 ± 10%), compared with controls (70 ± 7%; p = 0.002 and p = 0.005, respectively). LA passive emptying function was also decreased in overt HCM (35 ± 11%) compared with controls (47 ± 10%; p = 0.006). Both LAtotal emptying function and LA passive emptying function were inversely correlated with the extent of late gadolinium enhancement (LGE; p = 0.005 and p < 0.05, respectively), LV mass (p = 0.02 and p < 0.001) and interventricular septal thickness (p < 0.001 for both) and serum NT-proBNP levels (p < 0.001 for both). CONCLUSION: LA dysfunction is detectable by CMR in preclinical HCM mutation carriers despite non-distinguishable LV wall thickness and LA volume. LA function appears most impaired in subjects with overt HCM and a greater extent of LV fibrosis.

Aortic stiffening and its impact on left atrial volumes and function in patients after successful coarctation repair: a multiparametric cardiovascular magnetic resonance study.

BACKGROUND: The increased cardiovascular morbidity of adults with late repair of aortic coarctation (CoA) has been well documented. In contrast, successful CoA repair in early childhood has a generally good prognosis, though adverse vascular and ventricular characteristics may be abnormal, which could increase long-term risk. This study sought to perform a comprehensive analysis of aortic elasticity and left ventricular (LV) function in patients with aortic coarctation (CoA) using cardiovascular magnetic resonance (CMR). In a subgroup of patients, we assessed structure and function of the common carotid arteries to probe for signs of systemic vascular remodeling. METHODS: Fifty-one patients (median age 17.3 years), 13.9 ± 7.5 years after CoA repair, and 54 controls (median age 19.8 years) underwent CMR. We determined distensibility and pulse wave velocity (PWV) at different aortic locations. In a subgroup, common carotid artery distensibility, PWV, wall thickness and wall area were measured. LV ejection fraction (EF), volumes, and mass were measured from short axis views. Left atrial (LA) volumes and functional parameters (LAEFPassive, LAEFContractile, LAEFReservoir) were assessed from axial cine images. RESULTS: In patients distensibility of the whole thoracic aorta was reduced (p < 0.05) while PWV was only significantly higher in the aortic arch (p < 0.01). Distensibility of the descending aorta at the level of the pulmonary arteries and PWV in the descending aorta, both correlated negatively with age at CoA repair. LA volume before atrial contraction and minimal LA volume were higher in patients (p < 0.05). LAEFPassive and LAEFReservoir were reduced (p < 0.05), and LAEFReservoir correlated negatively with aortic arch PWV (p < 0.05). LVEF, volumes and mass were not different from controls. Carotid wall thickness and PWV were higher in patients compared to controls (p < 0.05). CONCLUSIONS: Patients after CoA repair have impaired bioelastic properties of the thoracic aorta with impact on LV diastolic function. Reduced descending aortic elasticity is associated with older age at time of CoA repair. The remodeling of the common carotid artery in our sub-study suggests systemic vessel wall changes.