Circulating miRNA in functional tricuspid regurgitation. Unveiling novel links to heart failure: A pilot study.

AIM: Severe functional tricuspid regurgitation (FTR) is associated with high risk of cardiovascular events, particularly heart failure (HF) and mortality. MicroRNAs (miRNAs) have been recently identified as novel biomarkers in different cardiovascular conditions, but no studies have focused on FTR. We sought to (1) to identify and validate circulating miRNAs as regulators of FTR and (2) to test association of miRNA with heart failure and mortality in FTR. METHODS AND RESULTS: Consecutive patients with isolated severe FTR (n = 100) evaluated in the outpatient Heart Valve Clinic and age- and gender-matched subjects with no TR (controls, n = 50) were prospectively recruited. The experimental design included (1) a screening phase to identify candidate miRNA differentially expressed in FTR (n = 8) compared with controls (n = 8) through miRNA array profiling of 192 miRNAs using quantitative reverse transcription PCR arrays [qRT-PCR]) and (2) a validation phase in which candidate miRNAs identified in the initial screening were selected for further validation by qRT-PCR in a prospectively recruited cohort of FTR (n = 92) and controls (n = 42). Bioinformatics analysis was used to predict their potential target genes and functional pathways elicited. A combined endpoint of hospital admission due to heart failure (HF) and all-cause mortality was defined. Initial screening identified 16 differentially expressed miRNAs in FTR compared with controls, subsequently confirmed in the validation phase (n = 16 were excluded due to significant haemolysis). miR-186-5p, miR-30e-5p, and miR-152-3p identified FTR with high predictive value [AUC of 0.93 (0.88-0.97), 0.83 (0.75-0.91) and 0.84 (0.76-0.92), respectively]. During a median follow-up of 20.4 months (IQR 8-35 months), 32% of FTR patients reached the combined endpoint. Patients with low relative expression of miR-15a-5p, miR-92a-3p, miR101-3p, and miR-363-3p, miR-324-3p, and miR-22-3p showed significantly higher rates of events (log-rank test for all P < 0.01). Both miR-15a-5p [hazard ratio: 0.21 (0.06-0.649, P = 0.007) and miR-92a-3p (0.27 (0.09-0.76), P = 0.01] were associated with outcomes after adjusting for age, gender, and New York Heart Association functional class. CONCLUSIONS: Circulating miRNAs are novel diagnostic and prognostic biomarkers in severe FTR. The quantification of miR-186-5p, miR-30e-5p, and miR-152-3p held strong diagnostic value, and the quantification of miR-15a-5p and miR-92a-3p are independently associated with outcomes. The recognition of specific miRNAs offers a novel perspective for TR evaluation.

STREI: a new index of right heart function in isolated severe tricuspid regurgitation by speckle-tracking echocardiography.

AIMS: Right ventricular (RV) performance determines clinical management in severe tricuspid regurgitation (TR). Right atrial (RA) function complements RV assessment in TR. This study aimed to design a novel index by speckle-tracking echocardiography (STREI index) integrating RA and RV strain information and to evaluate the clinical utility of combining RV and RA strain for prediction of cardiovascular (CV) outcomes. METHODS AND RESULTS: Consecutive patients with at least (≥) severe TR evaluated in the Heart Valve Clinic (n = 300) were prospectively included. An additional independent TR cohort was included for external validation (n = 50). STREI index was developed with the formula: [2 ∗ RV-free wall longitudinal strain (RV-FWLS)] + reservoir RA strain (RASr). The composite endpoint included hospital admission due to heart failure and all-cause mortality. A total of 176 patients with ≥severe TR were finally included. STREI index identified a higher percentage of patients with RV dysfunction compared with conventional parameters. After a median follow-up of 2.2 years (interquartile range: 12-41 months), a total of 38% reached the composite endpoint. STREI values were predictors of outcomes independently of TR severity and RV dimensions. The combination of prognostic cut-off values of RASr (<10%) and RV-FWLS (>-20%) (STREI stratification) stratified four different groups of risk independently of TR severity, RV dimensions, and clinical status (adj HR per stratum 1.89 (1.4-2.34), P < 0.001). Pre-defined cut-off values achieved similar prognostic performance in the validation cohort (n = 50). CONCLUSION: STREI index is a novel parameter of RV performance that independently predicts CV events. The combination of RA and RV strain stratifies better patients' risk, reflecting a broader effect of TR on right heart chambers.

La clasificación 4A para pacientes con insuficiencia tricuspídea / The 4A classification for patients with tricuspid regurgitation

Introducción y objetivos: La insuficiencia tricuspídea (IT) significativa se asocia con un aumento de la morbimortalidad. La valoración clínica del paciente con IT es un reto. Nuestro objetivo es establecer una nueva clasificación clínica, específica para pacientes con IT, denominada clasificación 4A, y evaluar su impacto pronóstico. Métodos: Se incluyó a pacientes evaluados en la clínica valvular, con IT aislada al menos grave y ausencia de antecedentes de insuficiencia cardiaca (IC). Se recogieron síntomas y signos de astenia, edema en extremidades inferiores, dolor o distensión abdominal y anorexia (asthenia, ankle swelling, abdominal pain or distention and anorexia) y se realizó un seguimiento cada 6 meses. La clasificación 4A abarca desde A0 (ninguna A) a A3 (3 o 4 Aes). Se definió un resultado combinado de ingreso hospitalario debido a IC derecha o muerte de causa cardiovascular. Resultados: Se incluyó a 135 pacientes con IT significativa entre 2016 y 2021 (el 69% mujeres; media de edad, 78±7 años). Durante un seguimiento medio de 26 [intervalo intercuartílico, 10-41] meses, 53 pacientes (39%) alcanzaron el resultado combinado. Ingresaron por IC 46 (34%) y murió un 5% (n=7). Al inicio, el 94% de los pacientes se encontraban en NYHA I o II, mientras que el 24% ya presentaba A2 o A3. La presencia de A2 o A3 se asoció con una alta incidencia de eventos. El cambio en la puntuación de la clasificación 4A fue un marcador independiente de IC y muerte cardiovascular (HR ajustada por unidad de cambio de la clasificación 4A=1,95 [1,37-2,77]; p <0,001). Conclusiones: Se muestra una nueva clasificación clínica específica para pacientes con IT basada en signos y síntomas de IC derecha y predictora de eventos.

Introduction and objectives: Significant tricuspid regurgitation (TR) is associated with increased morbidity and mortality. Clinical evaluation of TR patients is challenging. Our aim was to establish a new clinical classification specific for patients with TR, the 4A classification, and evaluate its prognostic performance. Methods: We included patients with isolated TR that was at least severe and without previous episodes of heart failure (HF) who were assessed in the heart valve clinic. We registered signs and symptoms of asthenia, ankle swelling, abdominal pain or distention and/or anorexia and followed up the patients every 6 months. The 4A classification ranged from A0 (no A) to A3 (3 or 4 As present). We defined a combined endpoint consisting of hospital admission due to right HF or cardiovascular mortality. Results: We included 135 patients with significant TR between 2016 and 2021 (69% females, mean age 78±7 years). During a median follow-up of 26 [IQR, 10-41] months, 39% (n=53) patients had the combined endpoint: 34% (n=46) were admitted for HF and 5% (n=7) died. At baseline, 94% of the patients were in NYHA I or II, while 24% were in classes A2 or A3. The presence of A2 or A3 conferred a high incidence of events. The change in 4A class remained an independent marker of HF and cardiovascular mortality (adjusted HR per unit of change of 4A class, 1.95 [1.37-2.77]; P<.001). Conclusions: This study reports a novel clinical classification specifically for patients with TR that is based on signs and symptoms of right HF and has prognostic value for events.(AU)

Clinical utility and prognostic value of right atrial function in severe tricuspid regurgitation: one more piece of the puzzle.

AIMS: The optimal management of severe tricuspid regurgitation (TR) remains controversial. While right ventricular systolic function is an established prognostic marker of outcomes, the potential role of right atrial (RA) function is unknown. This study aimed to describe RA function by 2D speckle-tracking echocardiography (STE) in at least severe TR and to evaluate its potential association with cardiovascular outcomes. METHODS AND RESULTS: Consecutive patients with at least (≥) severe TR (severe, massive, or torrential TR) evaluated in the Heart Valve Clinic following a comprehensive clinical protocol were included. Consecutive control subjects and patients with permanent isolated atrial fibrillation (AF) were included for comparison (control and AF group, respectively). RA function was measured with 2D-STE and two components of RA function were calculated: reservoir (RASr) and contractile (RASct) strain (AutoStrain, Philips Medical Systems the EPIQ system). A combined endpoint of hospital admission due to heart failure (HF) or all-cause mortality was defined. Patients with ≥ severe TR (n = 140) showed lower RASr compared with controls (n = 20) and with the AF group (n = 20) (P < 0.001). Atrial TR showed lower RASr compared with other aetiologies of TR (P < 0.001). After a median follow-up of 2.2 years (IQR: 12-41 months), RASr remained an independent predictor of mortality and HF. A cut-off value of RASr of <9.4% held the best accuracy to predict outcomes. CONCLUSION: RA function by 2D-STE independently predicts mortality and HF hospitalizations in patients with ≥ severe TR.

The 4A classification for patients with tricuspid regurgitation.

INTRODUCTION AND OBJECTIVES: Significant tricuspid regurgitation (TR) is associated with increased morbidity and mortality. Clinical evaluation of TR patients is challenging. Our aim was to establish a new clinical classification specific for patients with TR, the 4A classification, and evaluate its prognostic performance. METHODS: We included patients with isolated TR that was at least severe and without previous episodes of heart failure (HF) who were assessed in the heart valve clinic. We registered signs and symptoms of asthenia, ankle swelling, abdominal pain or distention and/or anorexia and followed up the patients every 6 months. The 4A classification ranged from A0 (no A) to A3 (3 or 4 As present). We defined a combined endpoint consisting of hospital admission due to right HF or cardiovascular mortality. RESULTS: We included 135 patients with significant TR between 2016 and 2021 (69% females, mean age 78±7 years). During a median follow-up of 26 [IQR, 10-41] months, 39% (n=53) patients had the combined endpoint: 34% (n=46) were admitted for HF and 5% (n=7) died. At baseline, 94% of the patients were in NYHA I or II, while 24% were in classes A2 or A3. The presence of A2 or A3 conferred a high incidence of events. The change in 4A class remained an independent marker of HF and cardiovascular mortality (adjusted HR per unit of change of 4A class, 1.95 [1.37-2.77]; P<.001). CONCLUSIONS: This study reports a novel clinical classification specifically for patients with TR that is based on signs and symptoms of right HF and has prognostic value for events.

Prognostic Impact of Right Ventricular Strain in Isolated Severe Tricuspid Regurgitation.

BACKGROUND: Right ventricular (RV) systolic function is an established marker of outcomes in patients with severe tricuspid regurgitation (TR). Timely detection of RV dysfunction using conventional two-dimensional echocardiography is challenging. RV strain has emerged as an accurate and sensitive tool for the evaluation of RV function, with the capability to detect subclinical RV dysfunction. The aim of this study was to evaluate the prognostic value of RV strain parameters in early stages of severe TR. METHODS: Consecutive patients with at least severe TR (severe, massive, or torrential) and the absence of a formal indication for tricuspid valve intervention in secondary TR evaluated in the Heart Valve Clinic were prospectively included. RV systolic function was measured using conventional echocardiographic indices (RV fractional area change, tricuspid annular plane systolic excursion, and Doppler tissue imaging S wave [S']) and speckle-tracking echocardiography-derived automatic peak global longitudinal strain and free wall longitudinal strain (FWLS) using an automated two-dimensional strain analytic software. A combined end point of hospital admission due to heart failure or all-cause mortality was defined. RESULTS: A total of 266 patients were enrolled in the study, and 151 were ultimately included. Strain parameters detected a higher percentage of abnormal RV values compared with conventional indices. During a median follow-up period of 26 months (interquartile range, 13-42 months), 35% of the patients reached the combined end point. Cumulative event-free survival was significantly worse in patients with impaired RV global longitudinal strain and RV FWLS. Conventional indices of RV systolic function were not associated with outcomes (P > .05 for all). On multivariate analysis, RV FWLS was independently associated with mortality and heart failure (adjusted hazard ratio for abnormal RV FWLS, 5.90; 95% CI, 3.17-10.99; P < .001). CONCLUSION: In early stages of severe TR, RV FWLS is more frequently impaired compared with conventional indices of RV function. Among all parameters, RV FWLS is the strongest predictor of mortality and heart failure, independent of additional prognostic markers.

Impact of right ventricular systolic function in patients with significant tricuspid regurgitation. A cardiac magnetic resonance study.

BACKGROUND: Right ventricle (RV) dilatation and dysfunction are established criteria for intervention in severe tricuspid regurgitation (TR); however thresholds to support intervention are lacking. New measures of RV function such as RV shortening (RVS) and effective RV ejection fraction (eRVEF) may be earlier markers of RV dysfunction. PURPOSE: to compare the prognostic impact of different parameters of RV function and to describe cut-off values of RV size/function and TR severity of poor prognosis. METHODS: Consecutive patients evaluated in the Heart Valve Clinic with significant TR (severe, massive or torrential TR) undergoing a CMR study were included. In addition to parameters of biventricular volume and function, RVS and eRVEF were assessed. A combined endpoint of hospital admission due to right heart failure and cardiovascular mortality was defined. RESULTS: 75 patients were included (age 75 ± 8 years, female 75%). During a median follow-up of 3 years (IQR: 1.4-3.9 years), 39% experienced the endpoint. Cut-off values of worse prognosis were: RVS ≥ -14%, eRVEF ≤34%, RVEF ≤58%, RV-EDV ≥100 ml/m2, TR regurgitant fraction (TRF) ≥40% and TR volume ≥ 42 ml. RVS and eRVEF identified higher rates of RV dysfunction than RVEF. After adjustment for age and LVEF, both eRVEF ≤34% (HR: 5.29 [2.25-12.4]) and RVS ≥ -14% (HR: 3.46 [1.13-9.17]) were significantly associated with outcomes. Among all parameters of RV function, eRVEF was the strongest predictor of outcomes, incremental to RVEF (ΔC-statistic 0.139 [0.040-0.237], p = 0.005). Patients with eRVEF ≤34% and RV-EDV ≥100 ml/m2 or eRVEF ≤34% and TRF ≥40% had the worst prognosis (p < 0.01 for both). CONCLUSION: RVS and eRVEF identify higher rates of RV dysfunction beyond RVEF. Among all measures, eRVEF held the strongest association with outcomes, incremental to RVEF.

Feasibility and Reproducibility of Left Atrium Measurements Using Different Three-Dimensional Echocardiographic Modalities.

Left atrium (LA) volume is a biomarker of cardiovascular outcomes. Three-dimensional echocardiography (3DE) provides an accurate LA evaluation, but data regarding the optimal 3DE method is scarce. We assessed the feasibility and reproducibility of LA measurements using different 3DE methods. One hundred and ninety-four patients were prospectively analyzed. Conventional 3DE and two semi-automatic 3DE algorithms (Tomtec™ and Dynamic Heart Model (DHM)) were used in 110 patients. Intra- and interobserver reproducibility and intervendor comparison were performed in additional patients' subsets. Forty patients underwent cardiac magnetic resonance (CMR). Feasibility was 100% for Tomtec, 98.2% for DHM, and 72.8% for conventional 3DE. Tomtec volumes were higher than 3DE and DHM (p < 0.001). Reproducibility was better for DHM (intraobserver LA maximum volume (LAmax) ICC 0.99 (95% CI 1.0-0.99), LA minimum volume (LAmin) 0.98 (95% CI 0.95-0.99), LApreA 0.96 (95% CI 0.91-0.98); interobserver LAmax ICC 0.98 (95% CI 0.96-0.99), LAmin 0.99 (95% CI 0.99-1.00), and LApreA 0.97 (95% CI 0.94-0.99)). Intervendor comparison showed differences between left ventricle (LV) software adapted for LA (p < 0.001). Tomtec underestimated the least LA volumes compared to CMR. These findings emphasize that dedicated software should be used for LA assessment, for consistent clinical longitudinal follow-up and research.

Right ventricle assessment in patients with severe aortic stenosis undergoing transcatheter aortic valve implantation.

INTRODUCTION: Limited data are available regarding the evaluation of right ventricular (RV) performance in patients with aortic stenosis (AS) undergoing transcatheter aortic valve implantation (TAVI). OBJECTIVE: To evaluate the prevalence of RV dysfunction in patients with severe AS undergoing TAVI and long-term changes. METHODS: Consecutive patients with severe AS undergoing TAVI from January 2016 to July 2017 were included. RV anatomical and functional parameters were analyzed: RV diameters, fractional area change, tricuspid annular plane systolic excursion (TAPSE), S-wave tissue Doppler of the tricuspid annulus (RV-S'TDI), global longitudinal strain (RV-GLS), and free wall strain (RV-FWS). Preprocedure and 1-year echo were analyzed. RESULTS: Final population included 114 patients, mean age 83.63 ± 6.31 years, and 38.2% women. The prevalence of abnormal RV function was high, variable depending on the parameter that we analyzed, and it showed a significant reduction 1 year after TAVI implantation: 13.9% vs 6.8% (TAPSE < 17mm), P = .04; 26.3% vs 20% (fractional area change < 35%), P = .048; 41.2% vs 29.2% (RV-S'TDI < 9.5cm/s), P = .04; 48.7% vs 39.5% (RV-GLS > [20]), P = .049; and 48.7% vs 28.9% (RV-FWS > [20]), P = .03. Significant differences were noted between patients with low-flow (LF) vs normal-flow (NF) AS in RV dysfunction prevalence as well as in RV function recovery which is less evident in LF compared with NF patients. CONCLUSIONS: RV dysfunction is high among symptomatic AS patients undergoing TAVI, with variable prevalence depending on the echocardiographic parameter used.

Native T1 and T2 provide distinctive signatures in hypertrophic cardiac conditions - Comparison of uremic, hypertensive and hypertrophic cardiomyopathy.

AIMS: Profound left ventricular (LV) hypertrophy with diastolic dysfunction and heart failure is the cardinal manifestation of heart remodelling in chronic kidney disease (CKD). Previous studies related increased T1 mapping values in CKD with diffuse fibrosis. Native T1 is a non-specific readout that may also relate to increased intramyocardial fluid. We examined concomitant T1 and T2 mapping signatures and undertook comparisons with other hypertrophic conditions. METHODS: In this prospective multicentre study, consecutive CKD patients (n = 154) undergoing routine clinical cardiac magnetic resonance (CMR) imaging were compared with patients with hypertensive (HTN, n = 163) and hypertrophic cardiomyopathy (HCM, n = 158), and normotensive controls (n = 133). RESULTS: Native T1 was significantly higher in all patient groups, whereas native T2 in CKD only (p < 0.001 vs. all groups). Native T1 and T2 were interrelated in patient groups and the strength of association was condition-specific (CKD r = 0.558, HTN r = 0.324, both p < 0.001; HCM r = 0.157, p = 0.05). Native T1 and T2 were similarly correlated in all CKD stages (S3 r = 0.501, S4 0.586, S5 r = 0.424, p < 0.001 for all). Native T1 was the strongest myocardial discriminator between patients and controls (area under the curve, AUC HCM: 0.97; CKD: 0.97, HTN 0.98), native T2 between CKD vs HCM (AUC 0.90) and native T1 and T2 between CKD vs HTN (AUC: 0.83 and 0.80 respectively), p < 0.001 for all. CONCLUSIONS: Our findings reveal different CMR signatures of common hypertrophic cardiac phenotypes. Native T1 was raised in all conditions, indicating the presence of pathologic hypertrophic remodelling. Markedly raised native T2 was CKD-specific, suggesting a prominent role of intramyocardial fluid.

Mid-term outcome of severe tricuspid regurgitation: are there any differences according to mechanism and severity?

AIMS: Patients with significant tricuspid regurgitation (TR) addressed according the new classification in torrential TR may have different prognosis compared with just severe TR patients. We sought to determine distribution and mechanism of consecutive severe TR patients, in accordance with aetiology and severity by applying the new proposed classification scheme and their long-term outcomes. METHODS AND RESULTS: Between January and December 2013, 249 patients with significant TR referred to the cardiac imaging unit (mean age 79.9 ± 10.2 years; 29.8% female) were included. Patients were divided according to aetiology in six groups, and TR severity was reclassified into severe, massive, and torrential TR. The follow-up period was of 313 ± 103 days. When considering cardiovascular mortality, patients in the massive/torrential group showed the highest number of events (P < 0.007). Patients with TR due to pulmonary diseases had the worst prognosis according to different aetiology. Noteworthy, the best predictors for the combined endpoint [cardiovascular mortality and readmission admission for heart failure (HF)] were TR severity according to the new classification [hazard ratio (HR) 2.48, 95% confidence interval (CI) 1.25-4.93] and clinical scores such as New York Heart Association classification and congestive status (HR 1.78, 95% CI 1.28-2.49; HR 2.08, 95% CI 1.06-4.06, respectively). CONCLUSION: Patients with massive/torrential TR and patients with comorbidities, especially pulmonary disease, were identified as populations at higher risk of death and readmission for HF. New classification scheme and clinical assessment may establish who may benefit the most of intensive therapeutic treatments and intervention on the tricuspid valve.

Prognostic value of left atrial function by cardiovascular magnetic resonance feature tracking in hypertrophic cardiomyopathy.

Left atrium (LA) size has an important role in determining prognosis and risk stratification in hypertrophic cardiomyopathy (HCM). Cardiovascular magnetic resonance myocardial feature tracking (CMR-FT) is a novel technique for the quantification of LA function. Our aim was first to evaluate LA function by CMR-FT and volumetric analysis in patients with HCM; and secondly we sought to determine the association of LA-longitudinal strain (LA-LS) with major cardiovascular outcomes, particularly all cause mortality and heart failure. 75 patients with HCM and 75 control subjects underwent a conventional CMR study including assessment of LA function by CMR-FT (LA-LS) and volumetric analysis. A primary endpoint of all-cause mortality and secondary combined endpoint of hospital admission related to heart failure, lethal ventricular arrhythmias or cardiovascular death were defined. Compared to controls, LA-LS and all volumetric indices of LA function were significantly impaired in HCM even in patients with normal LA volume and normal LV filling pressures. LA-LS showed moderate-high correlation with LA-emptying fraction (total, active and passive LA-EF, r = 0.68, r = 0.67, r = 0.31, p < 0.001 for all) and with parameters of diastolic function (E/é, r = 0.4, p < 0.001). The age, minimum LA volume and % of LGE were independent predictors of LA-LS (p < 0.01 for all). During a mean follow-up of 3.3 ± 1.2 years LA-LS was associated with the primary (HR: 0.85 (0.73-0.98), p = 0.02) and the secondary end-point (HR: 0.88 (0.82-0.96), p = 0.003). LA-LS by CMR-FT provides accurate measurements of LA function in HCM patients. LA-LS may become a novel potential predictor of poor cardiac outcomes, particularly cardiovascular mortality and HF.

Primary cardiac natural killer/T-cell lymphoma, a very rare form of lymphoma.

Extranodal natural killer/T-cell lymphoma is a rare non-Hodgkin lymphoma that is divided into nasal, non-nasal, and aggressive/leukemia subtypes, according to anatomic origin and clinical manifestations, with each subtype carrying a different prognosis. We present a case of primary cardiac natural killer/T-cell lymphoma with extension to other organs in a 38-year-old man, to highlight the role of imaging in categorizing nasal versus non-nasal types. This distinction has relevant implications for patient care because the non-nasal type has a much lower survival rate.

Society for Cardiovascular Magnetic Resonance (SCMR) expert consensus for CMR imaging endpoints in clinical research: part I - analytical validation and clinical qualification.

Cardiovascular disease remains a leading cause of morbidity and mortality globally. Changing natural history of the disease due to improved care of acute conditions and ageing population necessitates new strategies to tackle conditions which have more chronic and indolent course. These include an increased deployment of safe screening methods, life-long surveillance, and monitoring of both disease activity and tailored-treatment, by way of increasingly personalized medical care. Cardiovascular magnetic resonance (CMR) is a non-invasive, ionising radiation-free method, which can support a significant number of clinically relevant measurements and offers new opportunities to advance the state of art of diagnosis, prognosis and treatment. The objective of the SCMR Clinical Trial Taskforce was to summarizes the evidence to emphasize where currently CMR-guided clinical care can indeed translate into meaningful use and efficient deployment of resources results in meaningful and efficient use. The objective of the present initiative was to provide an appraisal of evidence on analytical validation, including the accuracy and precision, and clinical qualification of parameters in disease context, clarifying the strengths and weaknesses of the state of art, as well as the gaps in the current evidence This paper is complementary to the existing position papers on standardized acquisition and post-processing ensuring robustness and transferability for widespread use. Themed imaging-endpoint guidance on trial design to support drug-discovery or change in clinical practice (part II), will be presented in a follow-up paper in due course. As CMR continues to undergo rapid development, regular updates of the present recommendations are foreseen.

Segunda publicación nuevos anticoagulantes orales: guía práctica para los médicos / Second publication new oral anticoagulants: a practical guide for doctors

Resumen Los nuevos anticoagulantes orales suponen una atractiva alternativa para los clásicos antagonistas de la vitamina K (AVKs) en la prevención de ictus en pacientes con fibrilación auricular no valvular. A diferencia de los AVKs, estos anticoagulantes no requieren monitorización ni ajuste de dosis y poseen propiedades farmacológicas favorables. La falta de antídoto efi caz, su coste, o dudas en cuanto a la seguridad en los pacientes con enfermedad renal avanzada pueden explicar su lento ritmo de expansión. El uso seguro y eficaz de estos nuevos medicamentos depende en gran medida de la experiencia clínica entre la comunidad médica. Esta revisión discute las peculiaridades de los nuevos anticoagulantes orales, propor cionando algoritmos prácticos y fáciles de usar para su aplicación en la práctica clínica diaria.

Abstract New oral anticoagulants suppose an attractive alternative for classical vitamin K antagonists (AVKs) in stroke prevention for patients with non-valvular atrial fibrillation. Unlike AVKs, these anticoagulants do not require monitoring or dose adjustment and have favourable pharmacological properties. The lack of an effective antidote, its cost, or doubts regarding the safety of patients with advanced kidney disease may explain its slow rate of expansion. The safe and effective use of these new medications depends largely on clinical experience among the medical community. This review discusses the peculiarities of the new oral anticoagulants, providing practical and easy-to-use algorithms for their application in daily clinical practice.

Three-dimensional full automated software in the evaluation of the left ventricle function: from theory to clinical practice.

Left ventricular systolic function evaluation is an essential part of all transthoracic echocardiographic (TTE) studies. 3D echocardiography (3DE) is superior to 2D and is recommended as the method of choice. However, since it is time consuming and requires training, it is rarely performed. Different automatic analysis software tries to overcome these limitations but they need to be accurate and reproducible before they can be used clinically. The aim of this study was to test the accuracy and reproducibility of new 3D automatic quantitative software in everyday clinical practice. 69 patients referred to our Echo Lab for a clinically indicated echocardiographic examination were included. All patients underwent a full TTE with 3D image acquisition. Left ventricular volumes and ejection fraction (LVEF) were obtained using Heart Model software, and compared with conventional 3D volumetric data. Automated analysis was performed using three different sliders setting, with or without regional editing if necessary. 20 patients underwent a cardiac magnetic resonance (CMR) study the same day of the echo and automated measurements were also compared with a CMR reference. Intra- and inter-technique comparisons including linear regression with Pearson correlation coefficients and Bland-Altman analyses were calculated. Mean age of the patients was 59 years, with 49.3% male. The automated 3DE model demonstrated excellent correlation with the conventional 3DE measurements of LVEF, using three different sliders settings (r = 0.906; r = 0.898 and r = 0.940). Correlations with CMR values were very good as well (r = 0.888; r = 0.869; r = 0.913). Similarly, no significant differences were noted between the values of EDV and ESV, measured with the automated model or CMR, with excellent correlation (EDV: r = 0.892, r = 0.842, 0.910; ESV: r = 0.925, r = 0.860, r = 0.907). Finally, volumes calculated with the automated software were significantly greater than those obtained manually, but they showed a very good correlation (EDV: r = 0.875, r = 0.856, r = 0.891; ESV: r = 0.929, r = 0.879, r = 949). 3D automatic software for LV quantification is feasible and shows excellent correlations with both CMR and 3D echocardiography, considered the gold standard. No clinically relevant differences were noted when applying different border settings. This technique holds promise to facilitate the integration of 3D TTE into clinical practice.

Native T1 and ECV of Noninfarcted Myocardium and Outcome in Patients With Coronary Artery Disease.

BACKGROUND: Coronary artery disease (CAD) remains the major cause of cardiac morbidity and mortality worldwide, despite the advances in treatment with coronary revascularization and modern antiremodeling therapy. Risk stratification in CAD patients is primarily based on left ventricular volumes, ejection fraction (LVEF), risk scores, and the presence and extent of late gadolinium enhancement (LGE). The prognostic role of T1 mapping in noninfarcted myocardium in CAD patients has not yet been determined. OBJECTIVES: This study sought to examine prognostic significance of native T1 mapping of noninfarcted myocardium in patients with CAD. METHODS: A prospective, observational, multicenter longitudinal study of consecutive patients undergoing routine cardiac magnetic resonance imaging with T1 mapping and LGE. The primary endpoint was all-cause mortality. Major adverse cardiocerebrovascular events (MACCE) (cardiac mortality, nonfatal acute coronary syndrome, stroke, and appropriate device discharge) are also reported. RESULTS: A total of 34 deaths and 71 MACCE (n = 665, males n = 424, median age [interquartile range] 57 [22] years; 64%; median follow-up period of 17 [11] months) were observed. Native T1 and extracellular volume were univariate predictors of outcome. Native T1 and LGE were stronger predictors of survival and MACCE compared with extracellular volume, LVEF, cardiac volumes, and clinical scores (p < 0.001). Native T1 of noninfarcted myocardium was the sole independent predictor of all-cause mortality (chi-square = 21.7; p < 0.001), which was accentuated in the absence of LGE or LVEF ≤35%. For MACCE, native T1 and LGE extent were joint independent predictors (chi-square = 25.6; p < 0.001). CONCLUSIONS: Characterization of noninfarcted myocardium by native T1 is an important predictor of outcome in CAD patients, over and above the traditional risk stratifiers. The current study's results provide a basis for a novel risk stratification model in CAD based on a complementary assessment of noninfarcted myocardium and post-infarction scar, by native T1 mapping and LGE, respectively.

Three-dimensional echocardiographic quantification of the left-heart chambers using an automated adaptive analytics algorithm: multicentre validation study.

Aims: Although recommended by current guidelines, adoption of three-dimensional echocardiographic (3DE) chamber quantification in clinical practice has lagged because of time-consuming analysis. We recently validated an automated algorithm that measures left atrial (LA) and left ventricular (LV) volumes and ejection fraction (EF). This study aimed to determine the accuracy and reproducibility of these measurements in a multicentre setting. Methods and results: 180 patients underwent 3DE imaging (Philips) at six sites. Images were analysed using automated HeartModel (HM) software with endocardial border correction when necessary and by manual tracing. Measurements were performed by each site and by the Core Laboratory (CL) as the reference. Inter-technique comparisons included HM measurements by the sites against manual tracing by CL, and showed strong correlations (r-values: LVEDV: 0.97, LVESV: 0.97, LVEF: 0.88, LAV: 0.96), with the automated technique slightly underestimating LV volumes (biases: LVEDV: -14 ± 20 ml, LVESV: -6 ± 20 ml), LVEF (-2 ± 7%) and LAV (-9 ± 10 ml). Intra-technique comparisons included HM measurements by the sites against CL, with and without corrections. Corrections were unnecessary or minimal in most patients, and improved the measurements only modestly. Comparisons without corrections showed perfect agreement for all parameters. With corrections, correlations were better (r-values: LVEDV: 0.99, LVESV: 0.99, LVEF: 0.94, LAV: 0.99) and biases (LVEDV: -8 ± 12 ml, LVESV: -6 ± 12 ml, LVEF: 1 ± 5%, LAV: -10 ± 6 ml) smaller than in inter-technique comparison. All automated measurements with corrections were more reproducible than manual measurements. Conclusion: Automated 3DE analysis of left-heart chambers is an accurate alternative to conventional manual methodology, which yields almost the same values across laboratories and is more reproducible. This technique may contribute towards full integration of 3DE quantification into clinical routine.

Comparison of MOLLI, shMOLLLI, and SASHA in discrimination between health and disease and relationship with histologically derived collagen volume fraction.

Aims: To determine the bioequivalence of several T1 mapping sequences in myocardial characterization of diffuse myocardial fibrosis. Methods and results: We performed an intra-individual sequence comparison of three types of T1 mapping sequences [MOdified Look-Locker Inversion recovery (MOLLI), Shortened MOdified Look-Locker Inversion recovery ((sh)MOLLI), and SAturation recovery single-SHot Acquisition (SASHA)]. We employed two model diseases of diffuse interstitial fibrosis [patients with non-ischaemic dilated cardiomyopathy (NIDCM), n = 32] and aortic stenosis [(AS), n = 25)]. Twenty-six healthy individuals served as controls. Relationship with collagen volume fraction (CVF) was assessed using endomyocardial biopsies (EMB) intraoperatively in 12 AS patients. T2 mapping (GraSE) was also performed. Myocardial native T1 with MOLLI and shMOLLI showed, firstly, an excellent discriminatory accuracy between health and disease [area under the curves (P-value): 0.94 (0.88-0.99); 0.87 (0.79-0.94); 0.61 (0.49-0.72)], secondly, relationship between histological CVF [native T1 MOLLI vs. shMOLLI vs. SASHA: r = 0.582 (P = 0.027), r = 0.524 (P = 0.046), r = 0.443 (P = 0.150)], and thirdly, with native T2 [r = 0.628(P < 0.001), r = 0.459 (P = 0.003), r = 0.211 (P = 0.083)]. The respective relationships for extracellular volume fraction with CVF [r = 0.489 (P = 0.044), r = 0.417 (0.071), r = 0.353 (P = 0.287)] were significant for MOLLI, but not other sequences. In AS patients, native T2 was significantly higher compared to controls, and associated with levels of C-reactive protein and troponin. Conclusion: T1 mapping sequences differ in their bioequivalence for discrimination between health and disease as well as associations with diffuse myocardial fibrosis.