Arrhythmic Mitral Valve Prolapse Phenotype: An Unsupervised Machine Learning Analysis Using a Multicenter Cardiac MRI Registry.

Purpose To use unsupervised machine learning to identify phenotypic clusters with increased risk of arrhythmic mitral valve prolapse (MVP). Materials and Methods This retrospective study included patients with MVP without hemodynamically significant mitral regurgitation or left ventricular (LV) dysfunction undergoing late gadolinium enhancement (LGE) cardiac MRI between October 2007 and June 2020 in 15 European tertiary centers. The study end point was a composite of sustained ventricular tachycardia, (aborted) sudden cardiac death, or unexplained syncope. Unsupervised data-driven hierarchical k-mean algorithm was utilized to identify phenotypic clusters. The association between clusters and the study end point was assessed by Cox proportional hazards model. Results A total of 474 patients (mean age, 47 years ± 16 [SD]; 244 female, 230 male) with two phenotypic clusters were identified. Patients in cluster 2 (199 of 474, 42%) had more severe mitral valve degeneration (ie, bileaflet MVP and leaflet displacement), left and right heart chamber remodeling, and myocardial fibrosis as assessed with LGE cardiac MRI than those in cluster 1. Demographic and clinical features (ie, symptoms, arrhythmias at Holter monitoring) had negligible contribution in differentiating the two clusters. Compared with cluster 1, the risk of developing the study end point over a median follow-up of 39 months was significantly higher in cluster 2 patients (hazard ratio: 3.79 [95% CI: 1.19, 12.12], P = .02) after adjustment for LGE extent. Conclusion Among patients with MVP without significant mitral regurgitation or LV dysfunction, unsupervised machine learning enabled the identification of two phenotypic clusters with distinct arrhythmic outcomes based primarily on cardiac MRI features. These results encourage the use of in-depth imaging-based phenotyping for implementing arrhythmic risk prediction in MVP. Keywords: MR Imaging, Cardiac, Cardiac MRI, Mitral Valve Prolapse, Cluster Analysis, Ventricular Arrhythmia, Sudden Cardiac Death, Unsupervised Machine Learning Supplemental material is available for this article. © RSNA, 2024.

Cardiac magnetic resonance patterns of left ventricular remodeling in patients with severe aortic stenosis referred to surgical aortic valve replacement.

Left ventricular (LV) hypertrophy is a common finding in patients with severe aortic stenosis (AS). Cardiac magnetic resonance (CMR) is the gold-standard technique to evaluate LV remodeling. Our aim was to assess the prevalence and describe the patterns of LV adaptation in AS patients before and after surgical aortic valve replacement (AVR). Prospective study of 130 consecutive patients (71y [IQR 68-77y], 48% men) with severe AS, referred for surgical AVR. Patterns of LV remodeling were assessed by CMR. Besides normal LV ventricular structure, four other patterns were considered: concentric remodeling, concentric hypertrophy, eccentric hypertrophy, and adverse remodeling. At baseline CMR study: mean LV indexed mass: 81.8 ± 26.7 g/m2; mean end-diastolic LV indexed volume: 85.7 ± 23.1 mL/m2 and median geometric remodeling ratio: 0.96 g/mL [IQR 0.82-1.08 g/mL]. LV hypertrophy occurred in 49% of subjects (concentric 44%; eccentric 5%). Both normal LV structure and concentric remodeling had a prevalence of 25% among the cohort; one patient had an adverse remodeling pattern. Asymmetric LV wall thickening was present in 55% of the patients, with predominant septal involvement. AVR was performed in 119 patients. At 3-6 months after AVR, LV remodeling changed to: normal ventricular geometry in 60%, concentric remodeling in 27%, concentric hypertrophy in 10%, eccentric hypertrophy in 3% and adverse remodeling (one patient). Indexes of AS severity, LV systolic and diastolic function and NT-proBNP were significantly different among the distinct patterns of remodeling. Several distinct patterns of LV remodelling beyond concentric hypertrophy occur in patients with classical severe AS. Asymmetric hypertrophy is a common finding and LV response after AVR is diverse.

Assessment of myocardial strain patterns in patients with left bundle branch block using cardiac magnetic resonance.

Recently, a classification with four types of septal longitudinal strain patterns was described using echocardiography, suggesting a pathophysiological continuum of left bundle branch block (LBBB)-induced left ventricle (LV) remodeling. The aim of this study was to assess the feasibility of classifying these strain patterns using cardiovascular magnetic resonance (CMR), and to evaluate their association with LV remodeling and myocardial scar. Single center registry included LBBB patients with septal flash (SF) referred to CMR to assess the cause of LV systolic dysfunction. Semi-automated feature-tracking cardiac resonance (FT-CMR) was used to quantify myocardial strain and detect the four strain patterns. A total of 115 patients were studied (age 66 ± 11 years, 57% men, 28% with ischemic heart disease). In longitudinal strain analysis, 23 patients (20%) were classified in stage LBBB-1, 37 (32.1%) in LBBB-2, 25 (21.7%) in LBBB-3, and 30 (26%) in LBBB-4. Patients at higher stages had more prominent septal flash, higher LV volumes, lower LV ejection fraction, and lower absolute strain values (p < 0.05 for all). Late gadolinium enhancement (LGE) was found in 55% of the patients (n = 63). No differences were found between the strain patterns regarding the presence, distribution or location of LGE. Among patients with LBBB, there was a good association between strain patterns assessed by FT-CMR analysis and the degree of LV remodeling and LV dysfunction. This association seems to be independent from the presence and distribution of LGE.

Histopathological myocardial changes in patients with severe aortic stenosis referred for surgical valve replacement: a cardiac magnetic resonance correlation study.

AIMS: Myocardial fibrosis (MF) takes part in left ventricular (LV) remodelling in patients with aortic stenosis (AS), driving the transition from hypertrophy to heart failure. The structural changes that occur in this transition are not fully enlightened. The aim of this study was to describe histopathological changes at endomyocardial biopsy (EMB) in patients with severe AS referred to surgical aortic valve replacement (AVR) and to correlate them with LV tissue characterization from pre-operative cardiac magnetic resonance (CMR). METHODS AND RESULTS: One-hundred fifty-eight patients [73 (68-77) years, 50% women] were referred for surgical AVR because of severe symptomatic AS, with pre-operative CMR (n = 143) with late gadolinium enhancement (LGE), T1, T2 mapping, and extracellular volume fraction (ECV) quantification. Intra-operative septal EMB was obtained in 129 patients. MF was assessed through Masson's Trichrome histochemistry. Immunohistochemistry was performed for both inflammatory cells and extracellular matrix (ECM) characterization (Type I Collagen, Fibronectin, Tenascin C). Non-ischaemic LGE was present in 106 patients (67.1%) [median fraction: 5.0% (2.0-9.7)]. Native T1 was above normal [1053 ms (1024-1071)] and T2 within the normal range [39.3 ms (37.3-42.0)]. Median MF was 11.9% (6.54-19.97), with predominant type I collagen perivascular distribution (95.3%). Sub-endocardial cardiomyocyte ischaemic-like changes were identified in 45% of EMB. There was no inflammation, despite ECM remodelling expression. MF quantification at EMB was correlated with LGE mass (P = 0.008) but not with global ECV (P = 0.125). CONCLUSION: Patients with severe symptomatic AS referred for surgical AVR have unspecific histological myocardial changes, including signs of cardiomyocyte ischaemic insult. ECM remodelling is ongoing, with MF heterogeneity. These features may be recognized by comprehensive CMR protocols. However, no single CMR parameter captures the burden of MF and histological myocardial changes in this setting.

Subendocardial "ischemic-like" state in patients with severe aortic stenosis: Insights from myocardial histopathology and ultrastructure.

BACKGROUND: Myocardial adaptation to severe aortic stenosis (AS) is a complex process that involves myocardial fibrosis (MF) beyond cardiomyocyte hypertrophy. Perfusion impairment is believed to be involved in myocardial remodeling in chronic pressure overload. AIM: To describe morphological and ultrastructural myocardial changes at endomyocardial tissue sampling, possibly reflecting subendocardial ischemia, in a group of patients with severe AS referred to surgical aortic valve replacement (AVR), with no previous history of ischemic cardiomyopathy. METHODS: One-hundred-fifty-eight patients (73 [68-77] years, 50% women) referred for surgical AVR because of severe symptomatic AS with preoperative clinical and imaging study and no previous history of ischemic cardiomyopathy. Intra-operative septal endomyocardial sampling was obtained in 129 patients. Tissue sections were stained with Masson´s Trichrome for MF quantification and periodic acid-Schiff (PAS) staining was performed to assess the presence of intracellular glycogen. Ultrastructure was analyzed through Transmission electron microscopy (TEM). RESULTS: MF totalized a median fraction of 11.90% (6.54-19.97%) of EMB, with highly prevalent perivascular involvement (95.3%). None of the samples had histological evidence of myocardial infarction. In 58 patients (45%) we found subendocardial groups of cardiomyocytes with cytoplasmatic enlargement, vacuolization and myofiber derangement, surrounded by extensive interstitial fibrosis. These cardiomyocytes were PAS positive, PAS-diastase resistant and Alcian Blue/PAS indicative of the presence of neutral intracellular glyco-saccharides. At TEM there were signs of cardiomyocyte degeneration with sarcomere disorganization and reduction, organelle rarefaction but no signs of intracellular specific accumulation. CONCLUSION: Almost half of the patients with severe AS referred for surgical AVR have histological and ultrastructural signs of subendocardial cardiomyocyte ischemic insult. It might be inferred that local perfusion imbalance contributes to myocardial remodeling and fibrosis in chronic pressure overload.

External validation of the unifying concept for the quantitative assessment of functional mitral regurgitation.

PURPOSE: A novel conceptual framework was introduced to enhance the quantitative assessment of functional mitral regurgitation (FMR) and improve risk stratification. However, the data was derived from a single-center cohort and lack external validation. We aimed to validate the proposed algorithm using a different patient population. METHODS: Patients with at least mild FMR and reduced left ventricular ejection fraction (< 50%) were retrospectively identified at a single-center. The cohort was stratified in low, intermediate and high-risk according to the proposed framework, on the basis of effective regurgitant orifice area (EROA) and regurgitant volume (RegVol). Patients within the intermediate-risk group were subsequently reclassified into either the low-risk category (Regurgitant Fraction, RegFrac < 50%) or the high-risk category (RegFrac ≥ 50%) based on their regurgitant fraction. The primary endpoint was all-cause mortality. RESULTS: A total of 572 patients were included. During a median follow-up of 3.8 years there were 254 deaths (44%). On multivariable analysis, the proposed thresholds for FMR severity remained independently associated with all-cause mortality (adjusted hazard ratio: 1.488; 95% confidence interval [CI]: 1.110-2.013; p-value = 0.010). This algorithm demonstrated superior discriminative ability (C-statistic: 0.664) compared to contemporary guidelines (C-statistic: 0.522; p-value for comparison < 0.001). Additionally, it resulted in a significant improvement in the net reclassification index (0.162; p-value < 0.001). CONCLUSIONS: Within our cohort, the application of the proposed concept demonstrated a significant association with a higher risk of all-cause mortality. Moreover, this conceptual framework showcased the potential to improve the accuracy of risk prediction beyond current guidelines.

Influence of Age on the Diagnostic Value of Coronary Artery Calcium Score for Ruling Out Obstructive Coronary Disease in Symptomatic Patients.

Concerns have been raised about the added diagnostic value of coronary artery calcium score (CACS) of 0 for reducing the likelihood of obstructive coronary artery disease (CAD) in younger patients. Our study aimed to assess the influence of age on the value of CAC = 0 in symptomatic patients who underwent coronary computed tomography angiography (CCTA). We conducted a 2-center retrospective study assessing symptomatic patients with suspected CAD who underwent CACS and CCTA. Pretest probability was calculated according to the Juarez-Orozco method and obstructive CAD was defined as ≥50% luminal stenosis. The diagnostic likelihood ratios and negative predictive values were used to assess the diagnostic value of a CACS of 0 to rule out obstructive CAD. A total of 2,043 patients (mean age 60 ± 11 years, 60% women, 48.5% CACS of 0) were analyzed. The pretest probability of obstructive CAD increased with age, whereas the proportion of patients with a CACS of 0 decreased with age. The added diagnostic value of a CACS of 0 was lower in younger patients (negative likelihood ratios ranging from 0.36 for <50 years to 0.10 for ≥70 years). However, the prevalence of obstructive CAD in patients with a CACS of 0 was low in all age groups. In a cohort of symptomatic patients who underwent CCTA for suspected CAD, the added diagnostic value of a CACS of 0 decreases significantly at younger ages. However, it is offset by their lower pretest probabilities, yielding high negative predictive values independently of age.

Is myocardial fibrosis appropriately assessed by calibrated and 2D strain derived integrated backscatter?

AIMS: Increased collagen content of the myocardium modifies tissue reflectivity and integrated backscatter (IBS) indexes are suggested as markers of myocardial fibrosis (MF). We sought to assess the correlation between calibrated (c) IBS and bidimensional (2D) strain derived IBS with left ventricular (LV) MF in patients with severe aortic stenosis (AS). METHODS AND RESULTS: We made a prospective observational cohort study including 157 patients with severe AS referred for surgical aortic valve replacement (AVR), with complete preoperative transthoracic echocardiography, cardiac magnetic resonance (CMR) and endomyocardial biopsy (EMB) obtained from the anterior basal septum at the time of surgery. Two groups of 30 patients were specifically evaluated, with and without late gadolinium enhancement (LGE) at CMR. IBS was obtained at QRS peak from both parasternal long axis (PLAX) and apical-three-chamber (AP3C) views and measured in decibels (dB). Whole-cardiac cycle IBS at basal anterior septum was obtained from 2D longitudinal strain. Correlation analysis of reflectivity indexes was performed with global and segmental (anterior basal septum) values of native T1 and extracellular volume (ECV), and EMB collagen volume fraction (CVF) (Masson´s Trichrome). IBS values were compared in both group of patients (LGE + vs. LGE -). 60 patients (74 [36-74] years, 45% male) with high gradient (mean gradient: 63 ± 20mmHg), normal flow (45 ± 10mL/m2) AS and preserved left ventricular ejection fraction (60 ± 9%) were included. Basal septum cIBS was - 17.45 (-31.2-10.95) and - 9.17 ± 9.45dB from PLAX and A3C views, respectively. No significant correlations were found between IBS and both non-invasive CMR tissue characterization and CVF: median MF of 9.7(2.1-79.9)%. Acoustic indexes were not significantly different according to the presence of pre-operative LGE. CONCLUSION: In this group of patients with classical severe AS, IBS reflectivity indexes are of no added value to discriminate the presence of MF.

Implications of three different testing strategies in the diagnostic approach to patients with stable chest pain and low pretest probability of obstructive coronary artery disease.

INTRODUCTION: The clinical implications of a widespread adoption of guideline recommendations for patients with stable chest pain and low pretest probability (PTP) of obstructive coronary artery disease (CAD) remain unclear. We aimed to assess the results of three different testing strategies in this subgroup of patients: A) defer testing; B) perform coronary artery calcium score (CACS), withholding further testing if CACS â€‹= â€‹0 and proceeding to coronary computed tomography angiography (CCTA) if CACS>0; C) perform CCTA in all. METHODS: Two-center cross-sectional study assessing 1328 symptomatic patients undergoing CACS and CCTA for suspected CAD. PTP was calculated based on age, sex and symptom typicality. Obstructive CAD was defined as any luminal stenosis ≥50% on CCTA. RESULTS: The prevalence of obstructive CAD was 8.6% (n â€‹= â€‹114). In the 786 patients (56.8%) with CACS â€‹= â€‹0, 8.5% (n â€‹= â€‹67) had some degree of CAD [1.9% (n â€‹= â€‹15) obstructive, and 6.6% (n â€‹= â€‹52) nonobstructive]. Among those with CACS>0 (n â€‹= â€‹542), 18.3% (n â€‹= â€‹99) had obstructive CAD. The number of patients needed to scan (NNS) to identify one patient with obstructive CAD was 13 for strategy B vs. A, and 91 for strategy C vs. B. CONCLUSIONS: Using CACS as gatekeeper would decrease CCTA use by more than 50%, at the cost of missing obstructive CAD in one in 100 patients. These findings may help inform decisions on testing, which will ultimately depend on the willingness to accept some diagnostic uncertainty.

Case report: Mutation in NPPA gene as a cause of fibrotic atrial myopathy.

Early-onset atrial fibrillation (AF) can be the manifestation of a genetic atrial myopathy. However, specific genetic identification of a mutation causing atrial fibrosis is rare. We report a case of a young patient with an asymptomatic AF, diagnosed during a routine examination. The cardiac MRI revealed extensive atrial fibrosis and the electrophysiology study showed extensive areas of low voltage. The genetic investigation identified a homozygous pathogenic variant in the NPPA gene in the index case and the presence of the variant in heterozygosity in both parents.

Quantitative assessment of myocardial fibrosis by digital image analysis: An adjunctive tool for pathologist "ground truth".

AIMS: Myocardial fibrosis (MF) is a common pathological process in a wide range of cardiovascular diseases. Its quantity has diagnostic and prognostic relevance. We aimed to assess if the complementary use of an automated artificial intelligence software might improve the precision of the pathologist´s quantification of MF on endomyocardial biopsies (EMB). METHODS AND RESULTS: Intraoperative EMB samples from 30 patients with severe aortic stenosis submitted to surgical aortic valve replacement were analysed. Tissue sections were stained with Masson´s trichrome for collagen/fibrosis and whole slide images (WSI) from the experimental glass slides were obtained at a resolution of 0.5 µm using a digital microscopic scanner. Three experienced pathologists made a first quantification of MF excluding the subendocardium. After two weeks, an algorithm for Masson´s trichrome brightfield WSI (at QuPath software) was applied and the automatic quantification was revealed to the pathologists, who were asked to reassess MF, blinded to their first evaluation. The impact of the automatic algorithm on the inter-observer agreement was evaluated using Bland-Altman type methodology. Median values of MF on EMB were 8.33% [IQR 5.00-12.08%] and 13.60% [IQR 7.32-21.2%], respectively for the first pathologist´s and automatic algorithm quantification, being highly correlated (R2: 0.79; p < 0.001). Interobserver discordance was relevant, particularly for higher percentages of MF. The knowledge of the automatic quantification significantly improved the overall pathologist´s agreement, which became unaffected by the degree of MF severity. CONCLUSIONS: The use of an automated artificial intelligence software for MF quantification on EMB samples improves the reproducibility of measurements by experienced pathologists. By improving the reliability of the quantification of myocardial tissue components, this adjunctive tool may facilitate the implementation of imaging-pathology correlation studies.

Predictive value of a positive stress single-photon emission computed tomography or stress cardiac magnetic resonance for ruling in obstructive coronary artery disease in a real-world setting.

INTRODUCTION AND OBJECTIVES: Randomized controlled trials comparing stress cardiac magnetic resonance (CMR) and single-photon emission computed tomography (SPECT) suggest similar diagnostic accuracy for detecting obstructive coronary artery disease (CAD). There are few data on whether this remains true in routine clinical practice. The aim of this study was to assess clinical and angiographic characteristics of patients undergoing invasive coronary angiography (ICA) after stress CMR or SPECT, and to compare their positive predictive value with published results from the CE-MARC trial. METHODS: In this retrospective tertiary-center analysis, we included 429 patients undergoing ICA after a positive stress CMR or positive SPECT performed within the previous 12 months. Obstructive CAD was defined as any coronary artery stenosis ≥50% in a vessel compatible with the ischemic territory on stress testing. RESULTS: Of the total 429 patients, 356 (83%) were referred after a positive SPECT, and 73 (17%) after a positive stress CMR. Patients did not differ according to age, cardiovascular risk factors, previous revascularization or left ventricular dysfunction, but patients with SPECT were more frequently male (p=0.046). The prevalence of obstructive CAD was similar in patients with positive SPECT vs. positive stress CMR (76.1% vs. 80.8%, respectively, p=0.385). The positive predictive values of both techniques were similar to those reported in the CE-MARC trial. CONCLUSION: In this tertiary center analysis, stress CMR and SPECT showed similar positive predictive values, comparable to those reported in the CE-MARC trial. This finding supports the emerging adoption of CMR in clinical practice for the diagnosis and management of CAD.

Peak left atrial longitudinal strain is associated with all-cause mortality in patients with ventricular functional mitral regurgitation.

PURPOSE: Chronic mitral regurgitation promotes left atrial (LA) remodeling. However, the significance of LA dysfunction in the setting of ventricular functional mitral regurgitation (FMR) has not been fully investigated. Our aim was to assess the prognostic impact of peak atrial longitudinal strain (PALS), a surrogate of LA function, in patients with FMR and reduced left ventricular ejection fraction (LVEF). METHODS: Patients with at least mild ventricular FMR and LVEF < 50% under optimized medical therapy who underwent transthoracic echocardiography at a single center were retrospectively identified in the laboratory database. PALS was assessed by 2D speckle tracking in the apical 4-chamber view and the study population was divided in two groups according to the best cut-off value of PALS, using receiver operating characteristics (ROC) curve analysis. The primary endpoint-point was all-cause mortality. RESULTS: A total of 307 patients (median age 70 years, 77% male) were included. Median LVEF was 35% (IQR: 27 - 40%) and median effective regurgitant orifice area (EROA) was 15mm2 (IQR: 9 - 22mm2). According to current European guidelines, 32 patients had severe FMR (10%). During a median follow-up of 3.5 years (IQR 1.4 - 6.6), 148 patients died. The unadjusted mortality incidence per 100 persons-years increased with progressively lower values of PALS. On multivariable analysis, PALS remained independently associated with all-cause mortality (adjusted hazard ratio 1.052 per % decrease; 95% CI: 1.010 - 1.095; P = 0.016), even after adjustment for several (n = 14) clinical and echocardiographic confounders. CONCLUSION: PALS is independently associated with all-cause mortality in patients with reduced LVEF and ventricular FMR.

Coronary artery calcium score as a gatekeeper for further testing in patients with low pretest probability of obstructive coronary artery disease: A cost-effectiveness analysis.

INTRODUCTION AND OBJECTIVES: Current guidelines recommend not routinely testing patients with chest pain and low pretest probability (PTP <15%) of obstructive coronary artery disease (CAD), but envisage the use of risk modifiers, such as coronary artery calcium score (CACS), to refine patient selection for testing. We aimed to assess the cost-effectiveness (CE) of three different testing strategies in this population: (A) defer testing; (B) perform CACS, withholding further testing if CACS=0, and proceeding to coronary CT angiography (CCTA) if CACS>0; (C) CCTA in all. METHODS: We developed a CE model using data from a two-center cross-sectional study of 1385 patients with non-acute chest pain and PTP <15% undergoing CACS followed by CCTA. Key input data included the prevalence of obstructive CAD on CCTA (10.3%), the proportion with CACS=0 (57%), and the negative predictive value of CACS for obstructive CAD on CCTA (98.1%). RESULTS: Not testing would correctly classify 89.7% of cases and at a cost of €121433 per 1000 patients. Using CACS as a gatekeeper for CCTA would correctly diagnose 98.9% of cases and cost €247116/1000 patients. Employing first-line CCTA would correctly classify all patients, at a cost of €271007/1000 diagnosed patients. The added cost for an additional correct diagnosis was €1366 for CACS±CCTA vs. no testing, and €2172 for CCTA vs. CACS±CCTA. CONCLUSIONS: CACS as a gatekeeper for further testing is cost-effective between a threshold of €1366 and €2172 per additional correct diagnosis. CCTA yields the most correct diagnoses and is cost-effective above a threshold of €2172.

LGE prevalence and patterns in severe aortic stenosis: When "junctional" means the same.

BACKGROUND: Left ventricular (LV) remodeling in severe aortic valve stenosis (AS) is a complex process that goes beyond hypertrophic response. Reparative/replacement fibrosis is considered irreversible and has recognized value in both risk stratification and prognosis. Currently, cardiac magnetic resonance (CMR) is the gold-standard imaging technique for fibrosis identification through late gadolinium enhancement (LGE) assessment. However, its prevalence and distribution are quite variable among series. Our goal was to assess LGE prevalence and patterns in severe AS. METHODOLOGY: Single-center prospective cohort of 140 patients with severe symptomatic high-gradient AS (mean age 72 ± 8 years; mean valvular transaortic gradient 61 ± 18 mmHg; mean LV ejection fraction by echocardiogram 58 ± 9%) undergoing surgical aortic valve replacement. Those with previous myocardial infarction and/or non-ischemic cardiomyopathy were excluded. All patients performed 1.5 T LGE-CMR prior to surgery. RESULTS: Overall, 103 patients (74%) had non-ischemic LGE (median LGE mass 2.8 g [IQR 0.0-7.8] g), many of them with combined mid-wall and junctional enhancement pattern (36%). LGE was most frequently observed in the mid-basal segments of the interventricular septum. Seventy-four patients (53%) had non-exclusively junctional LGE. Contrary to those with junctional enhancement, patients with non-exclusively junctional LGE had higher LV volumes/mass, worse LV ejection fraction and worse global longitudinal strain. CONCLUSION: Among patients with severe, symptomatic, high-gradient AS, LGE is frequent, primarily affecting the mid-basal interventricular septum. Contrary to junctional LGE, the presence of non-junctional LGE seems to correlate with adverse markers of LV remodeling.

Prevalence and significance of relative apical sparing in aortic stenosis: insights from an echo and cardiovascular magnetic resonance study of patients referred for surgical aortic valve replacement.

AIMS: This study aims to assess the prevalence of relative apical sparing pattern (RASP) in patients with severe symptomatic aortic stenosis (AS), referred for surgical aortic valve replacement (AVR), to evaluate its significance, possible relation to amyloid deposition, and persistence after surgery. METHODS AND RESULTS: Prospective study of 150 consecutive patients [age 73 (interquartile range: 68-77), 51% women], with severe symptomatic AS referred to surgical AVR. All patients underwent cardiac magnetic resonance (CMR) before surgery. RASP was defined by [average apical longitudinal strain (LS)/(average basal LS + average mid LS)] > 1 by echocardiography. AVR was performed in 119 (79.3%) patients. Both Congo red and sodium sulphate-Alcian blue (SAB) stain were used to exclude amyloid on septal myocardial biopsy. LV remodelling and tissue characterization parameters were compared in patients with and without RASP. Deformation pattern was re-assessed at 3-6 months after AVR.RASP was present in 23 patients (15.3%). There was no suspicion of amyloid at pre-operative CMR [native T1 value 1053 ms (1025-1076 ms); extracellular volume (ECV) 28% (25-30%)]. None of the patients had amyloid deposition at histopathology. Patients with RASP had significantly higher pre-operative LV mass and increased septal wall thickness. They also had higher N-terminal pro b-type natriuretic peptide (NT-proBNP) levels [1564 (766-3318) vs. 548 (221-1440) pg/mL, P = 0.010], lower LV ejection fraction (53.7 ± 10.5 vs. 60.5 ± 10.2%, P = 0.005), and higher absolute late gadolinium enhancement (LGE) mass [9.7 (5.4-14.1) vs. 4.8 (1.9-8.6) g, P = 0.016] at CMR. Follow-up evaluation after AVR revealed RASP disappearance in all except two of the patients. CONCLUSION: RASP is not specific of cardiac amyloidosis. It may also be found in severe symptomatic AS without amyloidosis, reflecting advanced LV disease, being mostly reversible after surgery.

Abiotrophia defectiva Endocarditis: A Rare Cause with Aggressive Systemic Embolisation and Need of Valve Replacement.

Infective endocarditis (IE) is a well-described infectious disease, one with increased morbidity and mortality being the third or fourth most common life-threatening infection syndrome. Abiotrophia defectiva is a non-motile, catalase negative, gram-positive coccus in a chain, which can be isolated from the oral cavity, intestinal, and genitourinary tracts. IE due to this agent is rare and associated with heart valve destruction, congestive heart failure, and high embolisation rates, these being the major mortality causes. We present a case of IE due to this agent, complicated with a stroke, and splenic and renal infarction, with the need for aortic valve replacement. This article highlights the gaps of knowledge left by the rarity of this disease, which range from its diagnosis to its treatment, and what we need to mitigate such gaps, supported with a case description of a successful treatment of this infection. LEARNING POINTS: Infective endocarditis due to Abiotrophia defectiva has usually an indolent course, but the embolisation potential is very high.The major causes of mortality with this species are congestive heart failure due to valve destruction and the presence of multiple emboli.Surgical intervention rates are high with Abiotrophia defectiva, reaching 50% of cases.

Myocardial Fibrosis at Cardiac MRI Helps Predict Adverse Clinical Outcome in Patients with Mitral Valve Prolapse.

Background Patients with mitral valve prolapse (MVP) may develop adverse outcomes even in the absence of mitral regurgitation or left ventricular (LV) dysfunction. Purpose To investigate the prognostic value of mitral annulus disjunction (MAD) and myocardial fibrosis at late gadolinium enhancement (LGE) cardiac MRI in patients with MVP without moderate-to-severe mitral regurgitation or LV dysfunction. Materials and Methods In this longitudinal retrospective study, 118 144 cardiac MRI studies were evaluated between October 2007 and June 2020 at 15 European tertiary medical centers. Follow-up was from the date of cardiac MRI examination to June 2020; the minimum and maximum follow-up intervals were 6 months and 156 months, respectively. Patients were excluded if at least one of the following conditions was present: cardiomyopathy, LV ejection fraction less than 40%, ischemic heart disease, congenital heart disease, inflammatory heart disease, moderate or worse mitral regurgitation, participation in competitive sport, or electrocardiogram suggestive of channelopathies. In the remainder, cardiac MRI studies were reanalyzed, and patients were included if they were aged 18 years or older, MVP was diagnosed at cardiac MRI, and clinical information and electrocardiogram monitoring were available within 3 months from cardiac MRI examination. The end point was a composite of adverse outcomes: sustained ventricular tachycardia (VT), sudden cardiac death (SCD), or unexplained syncope. Multivariable Cox regression analysis was performed. Results A total of 474 patients (mean age, 47 years ± 16 [SD]; 244 women) were included. Over a median follow-up of 3.3 years, 18 patients (4%) reached the study end point. LGE presence (hazard ratio, 4.2 [95% CI: 1.5, 11.9]; P = .006) and extent (hazard ratio, 1.2 per 1% increase [95% CI: 1.1, 1.4]; P = .006), but not MAD presence (P = .89), were associated with clinical outcome. LGE presence had incremental prognostic value over MVP severity and sustained VT and aborted SCD at baseline (area under the receiver operating characteristic curve, 0.70 vs 0.62; P = .03). Conclusion In contrast to mitral annulus disjunction, myocardial fibrosis determined according to late gadolinium enhancement at cardiac MRI was associated with adverse outcome in patients with mitral valve prolapse without moderate-to-severe mitral regurgitation or left ventricular dysfunction. © RSNA, 2022 Online supplemental material is available for this article. See also the editorial by Gerber in this issue.

Secondary mitral regurgitation: Maintaining coherence with the American Society of Echocardiography grading guidelines, which proportionality concept best predicts prognosis in the real world?

INTRODUCTION: Proportionality of secondary mitral regurgitation (sMR) may be a key factor in deciding whether a patient may benefit from mitral intervention. The aim of this study was to evaluate the prognostic value of two different concepts of proportionality and assess their ability to improve MR stratification proposed by the American Society of Echocardiography (ASE) guidelines. METHODS: We conducted a retrospective analysis in patients with reduced left ventricular ejection fraction (LVEF) (<50%) and at least mild sMR. Proportionality status was calculated using formulas proposed by a) Grayburn et al. - disproportionate sMR defined as EROALVEDV >0.14; b) Lopes et al. - disproportionate sMR whenever measured EROA>theoretical EROA (determined as 50%×LVEF×LVEDVMitralVTI). Primary endpoint was all-cause mortality. RESULTS: A total of 572 patients (69±12 years; 76% male) were included. Mean LVEF was 33±9%, with a median left ventricular end-diastolic volume of 174 mL [136;220] and a median effective regurgitant orifice area of 14 mm2 [8;22]. During mean follow-up of 4.1±2.7 years, there were 254 deaths. There was considerable disagreement (p<0.001) between both formulas: of 96 patients with disproportionate sMR according to Lopes' criteria, 46 (48%) were considered proportionate according to Grayburn's; and of 62 patients with disproportionate sMR according to Grayburn's, 12 (19%) were considered proportionate according to Lopes' formula. In multivariate analysis, only Lopes' definition of disproportionate sMR maintained independent prognostic value (hazard ratio 1.5; 95% confidence interval 1.07-2.1, p=0.018) and improved the risk stratification of ASE sMR classification. CONCLUSION: Of the two formulas available to define disproportionate sMR, Lopes' model emerged as the only one with independent prognostic value while improving the risk stratification proposed by the ASE guidelines.