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Left ventricular noncompaction (LVNC) is a heterogeneous entity with uncertain prognosis. This study sought to develop and validate a prediction model of major adverse cardiovascular events (MACE) and to identify LVNC cases without events during long-term follow-up. This is a retrospective longitudinal multicenter cohort study of consecutive patients fulfilling LVNC criteria by echocardiography or cardiovascular magnetic resonance. MACE were defined as heart failure (HF), ventricular arrhythmias (VAs), systemic embolisms, or all-cause mortality. A total of 585 patients were included (45 ± 20 years of age, 57% male). LV ejection fraction (LVEF) was 48% ± 17%, and 18% presented late gadolinium enhancement (LGE). After a median follow-up of 5.1 years, MACE occurred in 223 (38%) patients: HF in 110 (19%), VAs in 87 (15%), systemic embolisms in 18 (3%), and 34 (6%) died. LVEF was the main variable independently associated with MACE (P < 0.05). LGE was associated with HF and VAs in patients with LVEF >35% (P < 0.05). A prediction model of MACE was developed using Cox regression, composed by age, sex, electrocardiography, cardiovascular risk factors, LVEF, and family aggregation. C-index was 0.72 (95% confidence interval: 0.67-0.75) in the derivation cohort and 0.72 (95% confidence interval: 0.71-0.73) in an external validation cohort. Patients with no electrocardiogram abnormalities, LVEF ≥50%, no LGE, and negative family screening presented no MACE at follow-up. LVNC is associated with an increased risk of heart failure and ventricular arrhythmias. LVEF is the variable most strongly associated with MACE; however, LGE confers additional risk in patients without severe systolic dysfunction. A risk prediction model is developed and validated to guide management. The project was partially funded by a grant from the Catalan Society of Cardiology (Barcelona, Spain). Hospital Universitario Virgen de la Arrixaca (Murcia, Spain) was supported by a grant from the Foundation Marató TV3 (218/C/2015) (Barcelona, Spain). Hospital Universitario y Politécnico La Fe (Valencia, Spain) was partially supported by Fondo Europeo de Desarrollo Regional (“Unión Europea, Una forma de hacer Europa”) (Madrid, Spain) and the Instituto de Salud Carlos III (La Fe Biobank PT17/0015/ 0043) (Madrid, Spain). Dr Guala was supported by funding from the Spanish Ministry of Science, Innovation and Universities (IJC2018-037349-I) (Madrid, Spain). Dr La Mura was supported by a research grant from the Cardiopath PhD program (Naples, Italy). Prof de la Pompa was supported by grants PID2019-104776RB-I00 and CB16/11/00399 (CIBER CV) from the Spanish Ministry of Science, Innovation and Universities. Dr Bayes-Genis was supported by grants from CIBER Cardiovascular (CB16/11/00403 and 16/11/00420) (Madrid, Spain) and AdvanceCat 2014-2020 (Barcelona, Spain); and has received advisory board and lecture fees from Novartis, Boehringer Ingelheim, Vifor, Roche Diagnostics, and Critical Diagnostics. Dr Pontone has received speaker honorarium and/or institutional research grants from GE Healthcare, Bracco, Boehringer Ingelheim, and HeartFlow. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose. Sí

Resumen Introduccion y objetivos El sindrome aortico agudo (SAA) tiene una alta mortalidad que obliga a un tratamiento precoz. El proposito del presente estudio es analizar los cambios en el abordaje y el tratamiento del SAA a lo largo de 20 anos. Metodos Se incluyo prospectivamente a 451 pacientes (336 varones; media de edad, 60,9 ± 12,4 anos) diagnosticados de SAA, 270 con el tipo A y 181 con el tipo B, desde 1999 hasta 2018. Se analizaron variables clinicas, diagnosticas y del tratamiento y las complicaciones hospitalarias. Resultados El uso de la tomografia computarizada (TC) como primera tecnica diagnostica se incremento del 62,8 al 94,2% (p Conclusiones El diagnostico y el tratamiento del SAA han presentado importantes cambios en las ultimas 2 decadas. La TC se ha consolidado como la tecnica diagnostica de eleccion. La mortalidad del SAA tipo A ha disminuido de manera muy importante debido a la mejora de los resultados del tratamiento quirurgico. En el SAA tipo B, el tratamiento medico solo se ha reducido debido a la aparicion del tratamiento endovascular, pero la mortalidad hospitalaria no ha disminuido de manera significativa.

Arrhythmia; Heritable thoracic aortic disease Arritmia; Enfermedad hereditaria de la aorta torácica Arrítmia; Malaltia hereditària de l'aorta toràcica Background Heritable thoracic aortic diseases (HTAD), typically entailing aortic complications, can be caused by pathogenic variants or likely pathogenic variants (PV/LPVs) in several genes, including fibrillin1 (FBN1), Actin Alpha2 (ACTA2) and genes encoding components of the transforming growth factor (TGF)-β signaling pathway. In addition to aortic complications, non-aortic cardiac disease such as impaired myocardial function and/or arrhythmia have been increasingly reported, mainly in Marfan syndrome with underlying FBN1 PV/LPVs and are acknowledged as additional causes of morbidity and mortality. The prevalence of these manifestations in the various HTAD entities is largely unknown. Methods This international multicentre retrospective study collected data on patients with HTAD presenting non-aortic cardiac disease. A total of 9 centers from 7 different countries participated. Patients 12 years or older carrying a PV/LPV in one of the following genes: FBN1, TGFBR1, TGFBR2, TGFB2, TGFB3, SMAD3 and ACTA2 were screened. Non-aortic cardiac disease included impaired myocardial function and/or arrhythmia. Impaired myocardial function was defined as (a)symptomatic reduced ejection fraction (EF

Cardiac amyloidosis (CA) is produced by amyloid fiber deposition in the myocardium. The most frequent forms are those caused by light chains (AL) and transthyretin (ATTR). Our objective was to describe the diagnosis, treatment and outcomes of CA in a specialized Spanish center.We included all patients diagnosed with CA in Hospital Universitario Puerta de Hierro Majadahonda from May 2008 to September 2018. We analyzed their clinical characteristics, outcomes, and survival.We included 180 patients with CA, of whom 64 (36%) had AL (50% men; mean age, 65±11 years) and 116 had ATTR (72% men; mean age 79±11 years; 18 with hereditary ATTR). The most common presentation was heart failure in both groups (81% in AL and 45% in ATTR, P.01). Other forms of presentation in ATTR patients were atrial arrhythmias (16%), conduction disorders (6%), and incidental finding (6%); 70 patients (40%), had a previous alternative cardiac diagnosis. Diagnosis was noninvasive in 75% of ATTR patients. Diagnostic delay was higher in ATTR (2.8±4.3 vs 0.6±0.7 years, P.001), but mortality was greater in AL patients (48% vs 32%, P=.028). Independent predictors of mortality were AL subtype (HR, 6.16; 95%CI, 1.56-24.30; P=.01), female sex (HR, 2.35; 95%CI, 1.24-4.46; P=.01), and NYHA functional class III-IV (HR, 2.07; 95%CI, 1.11-3.89; P=.02).CA is a clinical challenge, with wide variability in its presentation depending on the subtype, leading to diagnostic delay and high mortality. Improvements are needed in the early diagnosis and treatment of these patients.

Ascending aorta diameters have important clinical value in the diagnosis, follow-up, and surgical indication of many aortic diseases. However, there is no uniformity among experts regarding ascending aorta diameter quantification by echocardiography. The aim of this study was to compare maximum aortic root and ascending aorta diameters determined by the diastolic leading edge (DLE) and the systolic inner edge (SIE) conventions in adult and pediatric patients with inherited cardiovascular diseases. Transthoracic echocardiograms were performed in 328 consecutive patients (260 adults and 68 children). Aorta diameters were measured twice at the root and ascending aorta by the DLE convention following the 2015 American Society of Echocardiography (ASE) adult guidelines and the SIE convention following the 2010 ASE pediatric guidelines. Comparison of the diameters measured by the two conventions in the overall population showed a non-significant underestimation of the diameter measured by the SIE convention at root level of 0.28 mm (CI -1.36, 1.93) and at tubular ascending aorta level of 0.17 mm (CI-1.69, 2.03). Intraobserver and interobserver variability were excellent. Maximum aorta diameter measured by the leading edge convention in end-diastole and the inner edge convention in mid-systole had similar values to a mild non-significant underestimation of the inner-to-inner method that permits them to be interchangeable when used in clinical practice.

Background Marfan syndrome (MFS), Loeys-Dietz syndrome (LDS) and related heritable thoracic aortic diseases (HTAD) are well-known for their aortic complications. Myocardial dysfunction and arrhythmia are less known in this setting but have been increasingly reported as additional causes of morbidity and mortality. Related to the rarity of the disorders, data on the prevalence of these features and clinical characteristics of the patients are difficult to obtain, calling for a multicentre initiative. Purpose To study the prevalence of myocardial dysfunction and arrhythmia in patients with HTAD and describe their clinical and genetic profile. Methods Nine centres from seven countries participated in this multicentre retrospective study. Medical records of patients 12 years or older carrying a (likely) pathogenic variant in the FBN1 gene, LDS genes (TGFBR1, TGFBR2, TGFB2, TGFB3 and SMAD3) or ACTA2 gene were screened. Patients presenting myocardial dysfunction and/or arrhythmia were identified, and clinical and genetic data were collected. Myocardial dysfunction included (a)symptomatic reduced ejection fraction (EF Results In total, 3219 patients with HTAD were screened: 2761 with a variant in FBN1, 385 with a variant in one of the LDS genes (TGFBR1, TGFBR2, TGFB2, TGFB3 and SMAD3) and 73 carrying a variant in ACTA2. Myocardial dysfunction and arrhythmia were not reported in patients carrying an ACTA2 variant. Myocardial dysfunction was observed in patients with a variant in FBN1 and the LDS genes, without significant differences in prevalence (2.3% vs. 1.8%, p=0.563). Patients with a variant in the LDS genes presenting myocardial dysfunction were younger than patients carrying a variant in FBN1 (25±11 years vs. 39±17 years, p=0.034). The prevalence of VT/VF/SCD was similar in patients with a variant in one of the LDS genes compared to those with a variant in FBN1 (1.6% vs. 0.8%, p=0.132) and there was no difference in age at time of event (26±13 years vs. 33±14 years, p=0.289). Among patients with a variant in the LDS genes, the prevalence of VT/VF/SCD was highest in patients carrying a variant in the TGFBR2 gene and was significantly higher compared to patients with a variant in FBN1 (3.4% vs. 0.8%, p=0.017). In contrast, AF/AFL was significantly more often reported in patients with a variant in FBN1 compared to those with a variant in one of the LDS genes (1.7% vs. 0.3%, p=0.033). Conclusions Myocardial dysfunction and arrhythmia are rare features in patients with HTAD. They occur predominantly in patients with a variant in FBN1 and LDS genes, but were not reported in patients carrying a variant in the ACTA2 gene. Further analysis to identify other contributing factors is necessary. Funding Acknowledgement Type of funding sources: None. Figure 1

The Spanish Registry of Acute Aortic Syndrome (RESA) was launched in 2005 to identify the characteristics of acute aortic syndrome (AAS) in Spain. The aim of this study was to analyze the differences in management and mortality in the 3 RESA iterations.We analyzed data from patients with AAS prospectively included by 24 to 30 tertiary centers during the 3 iterations of the registry: RESA I (2005-2006), RESA-II (2012-2013), and RESA III (2018-2019).AAS was diagnosed in 1902 patients (74% men; age, 60.7±12.5 years): 1329 (69.9%) type A and 573 (30.1%) type B. Comparison of the 3 periods revealed that the use of computed tomography increased as the first diagnostic technique (77.1%, 77.9%, and 84.2%, respectively; P=.001). In type A, surgical management increased (79.6%, 78.7%, and 84.5%; P=.045) and overall mortality decreased (41.2%, 34.5%, and 31.2%; P=.002), due to a reduction in surgical mortality (33.4%, 25.1%, and 23.9%; P=.003). In type B, endovascular treatment increased (22.8%, 32.8%, and 38.7%; P=.006), while medical and surgical treatment decreased. Overall type B mortality also decreased (21.6%, 16.1%, and 12.0%; P=.005) in line with a reduction in mortality with medical (16.8%, 13.8%, and 8.8%, P=.030) and endovascular (27.0%, 18.0%, and 9.2%; P=.009) treatments.The iterations of RESA show a decrease in mortality from type A AAS, coinciding with an increase in surgical treatment and a reduction in surgical mortality. In type B, the use of endovascular treatment was associated with improved survival, allowing better management in patients with complications.

Objective: Cardiac amyloid infiltration can lead to systolic heart failure (HF) or to conduction disorders (CD). Patients with transthyretin (ATTR) amyloidosis are particularly exposed. We ...

Resumen Introduccion y objetivos La enfermedad de Danon (ED) es una enfermedad producida por mutaciones en el gen LAMP2. Se la considera una enfermedad multisistemica caracterizada por miocardiopatia hipertrofica con preexcitacion e hipertrofia extrema, discapacidad intelectual, miopatia, presentacion infantil y peor pronostico en varones. Hay pocas series que permitan conocer las caracteristicas clinicas y el pronostico de la ED. Metodos Se analizaron los registros clinicos de los pacientes con ED de 10 hospitales espanoles. Resultados Se incluyo a 27 pacientes (edad, 31 ± 19 anos; el 78% mujeres). Los varones mostraron una elevada prevalencia de manifestaciones extracardiacas —miopatia (80%), trastornos del aprendizaje (83%) y alteraciones visuales (60%)— que eran infrecuentes en las mujeres (el 5, el 0 y el 27% respectivamente). Aunque la miocardiopatia hipertrofica era la cardiopatia mas habitual (61%), el grosor ventricular maximo fue 15 ± 7 mm y 12 pacientes (10 mujeres) presentaron miocardiopatia dilatada. Solo 11 pacientes (49%) mostraron preexcitacion y en 16 (65%) la enfermedad se inicio despues de los 20 anos. Tras una mediana de seguimiento de 4 anos [intervalo intercuartilico, 2-9], 4 varones (67%) y 9 mujeres (43%) fallecieron o se sometieron a trasplante. El dano cardiaco y los eventos adversos ocurrieron mas tardiamente en las mujeres (37 ± 9 frente a 23 ± 16 anos y 36 ± 20 frente a 20 ± 11 anos). Conclusiones Las caracteristicas clinicas de la ED difieren sustancialmente de lo considerado tradicionalmente. La edad de presentacion de la ED es mas tardia, no se expresa como una enfermedad multisistemica en las mujeres y la preexcitacion es poco frecuente.

Funding Acknowledgements Type of funding sources: Public grant(s) – National budget only. Main funding source(s): La Marató de TV3, Instituto de Salud Carlos III through the project and Spanish Ministry of Science, Innovation and Universities. BACKGROUND Loeys-Dietz (LDS) and Marfan (MFS) syndromes are rare genetic connective tissue disorders associated with progressive aortic dilation, however, aortic dissections have been observed at lower aortic root diameters in LDS than in MFS. Recent CMR studies in MFS patients reported increased aortic stiffness (1–3) and altered rotational flow (4), but research on aortic flow dynamics and biomechanics in LDS is lacking. PURPOSE The aim of this study was to assess rotational aortic flow and aortic stiffness in LDS compared to healthy volunteers (HV) and MFS patients, using 4Dflow CMR. METHODS Twenty-one LDS and 44 MFS patients, without previous aortic dissection or surgery, and 43 HV underwent a non-contrast-enhanced 4D flow CMR. Aortic stiffness was quantified at the AAo and DAo using pulse wave velocity (PWV). In-plane rotational flow (IRF), systolic flow reversal ratio (SFRR) (5) and local aortic diameters were obtained at 20 equidistant planes from the ascending (AAo) to the proximal descending aorta (DAo). RESULTS LDS patients had lower IRF at the distal AAo and proximal DAo compared to HV (p = 0.053 and 0.004, respectively), once adjusted for age, stroke volume and local aortic diameter; but no differences were found with respect to MFS (Figure). Although SFRR at the proximal DAo was increased in LDS patients compared to both HV (p = 0.037) and MFS populations (p = 0.015), once adjusted for age and aortic diameter, the difference in magnitude was small (Figure). On the other hand, AAo and DAo PWV revealed stiffer aortas in LDS patients compared to HV but no differences versus MFS patients (Table). CONCLUSIONS Patients with Loeys-Dietz syndrome showed decreased in-plane rotational flow and abnormally-high regional aortic stiffness compared to healthy controls, and similar hemodynamics and aortic stiffness with respect to patients with Marfan syndrome.

Aortic branch aneurysms are not included in the diagnostic criteria for Marfan syndrome (MFS); however, their prevalence and eventual prognostic significance are unknown.The goal of this study was to assess the prevalence of aortic branch aneurysms in MFS and their relationship with aortic prognosis.MFS patients with a pathogenic FBN1 genetic variant and at least one magnetic resonance or computed tomography angiography study assessing aortic branches were included. Aortic events and those related to aneurysm complications were recorded during follow-up.A total of 104 aneurysms were detected in 50 (26.7%) of the 187 patients with MFS (mean age 37.9 ± 14.4 years; 54% male) included in this study, with the iliac artery being the most common location (45 aneurysms). Thirty-one patients (62%) had1 peripheral aneurysm, and surgery was performed in 5 (4.8%). Patients with aneurysms were older (41.9 ± 12.7 years vs. 36.7 ± 14.8 years; p = 0.040) and had more dilated aortic root (42.2 ± 6.4 mm vs. 38.8 ± 8.0 mm; p = 0.044) and dyslipidemia (31.0% vs. 9.7%; p = 0.001). In a subgroup of 95 patients with no previous aortic surgery or dissection followed up for 3.3 ± 2.6 years, the presence of arterial aneurysms was associated with a greater need for aortic surgery (hazard ratio: 3.4; 95% confidence interval: 1.1 to 10.3; p = 0.028) in a multivariable Cox analysis adjusted for age and aortic diameter.Aortic branch aneurysms are present in one-quarter of patients with MFS and are related to age and aortic dilation, and they independently predict the need for aortic surgery. The systematic use of whole-body vascular assessment is recommended to identify other sites of vascular involvement at risk for complications and to define the subgroup of patients with more aggressive aortic disease.

Introducción y objetivos La amiloidosis cardiaca (AC) se produce por depósito de fibras de amiloide en el miocardio. Las formas más frecuentes son la amiloidosis por cadenas ligeras (AL) y por transtiretina (ATTR). Nuestro objetivo es describir la experiencia en el diagnóstico, tratamiento y pronóstico en un centro especializado español. Métodos Se incluyeron todos los pacientes diagnosticados de AC en el XXXX1 desde mayo de 2008 a septiembre de 2018 y se analizaron sus características clínicas, evolución y supervivencia. Resultados Se incluyeron 180 pacientes con AC, de los cuales, 64 (36%) eran AL (50% varones;65±11 años) y 116 ATTR (72% varones;79±11 años, 19 con ATTR hereditaria). La forma de presentación más frecuente fue la insuficiencia cardiaca en ambos grupos (81% AL y 45% ATTR;p

Funding Acknowledgements Type of funding sources: Public Institution(s). Main funding source(s): Spanish Ministry of Science, Innovation and Universities Instituto de Salud Carlos III Background. Dilation of the aortic root is a key feature of Marfan syndrome and it is related to the occurrence of aortic events and death. On top of maximum diameter, rapid annual growth rate is suggested by guidelines for indication of aortic root replacement. Current gold-standard for aortic root diameter assessment is manual quantification on multiplanar reformatted 3D computed tomography (CT) or magnetic resonance angiogram. However, inter- and intra-observer reproducibility are limited and different measurement methods, i.e. cusp-to-cusp and cusp-to-commissure, may be used in different clinical centres, leading to difficulties in the clinical assessment of progressive dilation. Purpose. We aimed to test whether aortic root growth rate during follow-up can be reliably quantified by semi-automatic co-registration of two CT angiograms. Methods. Seven Marfan syndrome patients, free from previous aortic surgery, with a total of 11 pairs of CT were identified. Manual assessment of six aortic root diameters (right-non coronary -RN- , right-left -RL- and left-non coronary -LN- cusp-to-cusp and R, L and N cusp-to-commissure) was obtained from all CTs by an experienced researcher blind to semi-automatic results. The thoracic aorta and the outflow tract were semi-automatically segmented in the baseline CT and commissure and cusps were manually located. A 10 mm-thick region of interest containing the aortic wall was automatically generated from segmentation boundary. Co-registration was obtained with three, fully-automatic steps. Firstly, baseline and follow-up CT scans were aligned by means of a rigid registration. Then, scans were co-registered with multi-resolution affine followed by b-spline non-rigid registrations based on mutual information metric. The transformation pertaining to the location of baseline commissure and cusps points was used to locate the same points in the follow-up scan (Fig. 1 top). Results. Follow-up duration was 35 ± 22 (range 12-70.3) months. Automatic quantification of diameter growth during the follow-up was obtained in 62 out of 66 (94%) diameter comparisons. High Pearson correlation coefficients (R) and ICC were found between manual and semi-automatic assessment of growth rate, both for cusp-to-cusp and cusp-to-commissure diameters: R = 0.727 and ICC = 0.678 for RN; R = 0.822 and ICC = 0.602 for RL; R = 0.648 and ICC = 0.668 for LN; R = 0.726 and ICC = 0.711 for R; R = 0.911 and ICC = 0.895 for L and R = 0.553 and ICC = 0.482 for N. Scatter and Bland-Altman plots for all growth rates (Fig. 1) confirmed very good correlation (R = 0.810) but a slight tendency (R=-0.270) for underestimation at high growth rate. No correlation was found between follow-up duration and difference between techniques (R = 0.06). Conclusions. Semi-automatic quantification of aortic root growth rate by co-registration of pairs of CT angiograms is feasible for follow-up as short as one year. Larger studies are needed to confirm these preliminary data. Abstract Figure. CT measurements. Automatic vs manual.

Background: Thoracic endovascular aortic repair (TEVAR) is becoming the preferred treatment option to repair the proximal descending aorta after rupture following blunt traumatic injury. However, hemodynamic and mechanic implications of this intervention are poorly understood. Exploiting the possibilities of 4D flow magnetic resonance imaging, hemodynamics, stiffness and local dilation in the ascending aorta in patients following aortic repair by TEVAR are studied. Methods: Fifteen apparently healthy individuals who underwent TEVAR implantation after traumatic descending aortic injury and 44 healthy volunteers (HV) underwent 4D flow-MRI. Ascending aorta pulse wave velocity was computed [1]. Moreover, at eight planes equally distributed in the ascending aorta systolic flow reversal ratio, i.e. relative amount of backward flow during systole, and in-plane rotational flow, measuring the strength of helical flow, were computed [2,3]. Results: TEVAR patients and HV did not differ in terms of age, sex, BSA and blood pressure (Table). However, compared to HV, TEVAR patients showed reduced in-plane rotational flow in the distal ascending aorta in patients with TEVAR and increased backward systolic flow in the whole ascending aorta (Figure). Patients with TEVAR had a stiffer ascending aorta, with pulse wave velocity higher compared control (7.8 ± 4.2 vs 5.3 ± 1.9, p = 0.004). Finally, aortic root and ascending aorta diameters were larger in TEVAR patients compared to HV (Table). Healthy volunteers TEVAR patients p N 44 15 Age [years] 40 ± 12 43 ± 10 0.392 Sex [% male] 66 80 0.075 Years from intervention [years] N/A 10.3 ± 6.4 N/A Body surface area [m2] 1.87 ± 0.15 1.96 ± 0.23 0.088 Systolic blood pressure [mmHg] 127 ± 19 131 ± 15 0.389 Diastolic blood pressure [mmHg] 70 ± 11 74 ± 9 0.198 Aortic root diameter [mm] 31 ± 4 34 ± 4 0.026 Ascending aorta diameter [mm] 28 ± 4 32 ± 3 0.003 Ascending aorta PWV [m/s] 5.3 ± 1.9 7.8 ± 4.2 0.004 FigureIn-plane rotational flow (IRF, left) and systolic flow reversal ratio (SFRR, right) in healthy volunteers (black) and TEVAR patients (yellow) in the proximal (planes 1 to 4) and distal (planes 5 to 8) ascending aorta. Stars show statistically-significant differences (p < 0.05). Conclusions: The implantation of TEVAR in apparently healthy individuals after traumatic rupture of the proximal descending aorta is associated with altered hemodynamics, higher stiffness and larger aortic diameter in the region proximal to the TEVAR.

Background Connective tissue disorders, such as Loeys-Dietz (LDS) and Marfan (MFS) syndromes, are rare genetic diseases associated with progressive aortic dilation. Aortic dissections have been observed at lower aortic root diameters in LDS than in MFS, and research on aortic flow dynamics and biomechanics in LDS is lacking. Purpose To evaluate rotational aortic flow and aortic stiffness in LDS compared to healthy volunteers (HV) and MFS patients, using 4Dflow CMR. Methods Twenty-one LDS and 44 MFS patients, without previous aortic dissection or surgery, and 44 HV underwent a non-contrast-enhanced 4D flow CMR. In-plane rotational flow (IRF), systolic flow reversal ratio (SFRR) and local aortic diameters were obtained at 20 equidistant planes from the ascending (AAo) to the proximal descending aorta (DAo). Aortic stiffness was quantified at the AAo and DAo using pulse wave velocity (PWV). Results LDS patients had lower IRF at the distal AAo and proximal DAo compared to HV (p=0.053 and 0.004, respectively), once adjusted for age, stroke volume and local aortic diameter; but no differences were found with respect to MFS (Figure). Although SFRR at the proximal DAo was increased in LDS patients compared to both HV (p=0.037) and MFS populations (p=0.015), once adjusted for age and aortic diameter, the difference in magnitude was small (Figure). On the other hand, AAo and DAo PWV revealed stiffer aortas in LDS patients compared to HV but no differences versus MFS patients (Table). Conclusions LDS patients showed decreased in-plane rotational flow and abnormally-high regional aortic stiffness compared to healthy controls, and similar hemodynamics and aortic stiffness with respect to MFS patients Funding Acknowledgement Type of funding source: Public Institution(s). Main funding source(s): Instituto de Salud Carlos III, La Maratό TV3

Purpose Mutations in the PRKAG2 gene cause a syndrome characterized by hypertrophic cardiomyopathy, conduction disease and ventricular preexcitation. Only a small number of cases have been reported, and the natural history of the disease is poorly understood. The aim of this study is to describe phenotype and natural history of PRKAG2 mutation in a large multicenter international cohort. Methods We retrospectively studied clinical, electrocardiographic and echocardiographic data from 90 individuals with PRKAG2 mutations (53% males, 33±21 years) from 27 centers. Results At baseline evaluation, 93% of patients were in NYHA functional class I-II. Maximum left ventricular (LV) wall thickness was 18±8 mm and LV hypertrophy (LVH) was present in 60 (67%) subjects at baseline. LV ejection fraction was 61±12%. Seventeen pactients (19%) had a pacemaker (mean age at implantation 37±15and 16 (18%) had atrial fibrillation (AF) (mean age 41±23 years) and 33% had ventricular preexcitation or had undergone an accessory pathway ablation. After a median follow-up of 6 years (IQR:2.3–13.9), 71% of individuals had LVH, 29% had AF, 21% a de novo pacemaker (mean age at implantation 38±18 years), 14% required admission for heart failure (HF), 8% experienced sudden cardiac death or equivalent, 4% required a heart transplant and 13% died. Conclusions PRKAG2 syndrome is a severe, progressive cardiomyopathy characterized by high rates of AF, conduction disease, advanced HF and life-threatening arrhythmias. Outcome is not clearly related to the classical features of preexcitation and severe LVH, which are not always present. Natural history of PRKAG2 syndrome Funding Acknowledgement Type of funding source: Public Institution(s). Main funding source(s): Instituto de Salud Carlos III (ISCIII)

Aims To assess aortic flow and stiffness in patients with Loeys–Dietz syndrome (LDS) by 4D flow and cine cardiovascular magnetic resonance (CMR) and compare the results with those of healthy volunteers (HV) and Marfan syndrome (MFS) patients. Methods and results Twenty-one LDS and 44 MFS patients with no previous aortic dissection or surgery and 35 HV underwent non-contrast-enhanced 4D flow CMR. In-plane rotational flow (IRF), systolic flow reversal ratio (SFRR), and aortic diameters were obtained at 20 planes from the ascending (AAo) to the proximal descending aorta (DAo). IRF and SFRR were also quantified for aortic regions (proximal and distal AAo, arch and proximal DAo). Peak-systolic wall shear stress (WSS) maps were also estimated. Aortic stiffness was quantified using pulse wave velocity (PWV) and proximal AAo longitudinal strain. Compared to HV, LDS patients had lower rotational flow at the distal AAo (P = 0.002), arch (P = 0.002), and proximal DAo (P Conclusion Greater aortic stiffness as well as impaired IRF and WSS were present in LDS patients compared to HV. Conversely, similar aortic stiffness and overlapping aortic flow features were found in Loeys–Dietz and Marfan patients.

Aim To analyse the incidence, risk factors and clinical outcomes of late graft failure after heart transplantation. Methods and results We conducted an observational, single-centre study based on 547 patients who underwent cardiac transplantation from 1991 to 2014 and who survived the in-hospital postoperative period. Late graft failure was defined as the first hospitalization due to this condition after discharge. Over a mean follow-up of 8.4 ± 6 years, 178 (32.5%) patients were hospitalized due to late graft failure [incidence rate: 3.6 cases per 100 patient-years, 95% confidence interval (CI) 3.1-4.2]. Pre-transplant diabetes, higher pre-transplant transpulmonary pressure gradient and lower donor-recipient weight ratio were independently associated with higher risk of graft failure. Cardiac allograft vasculopathy, cellular rejection grade ≥1R, and antibody-mediated rejection grade ≥1 were detected in 50.6%, 44.9% and 19.2% patients, respectively, admitted due to graft failure. Left ventricular ejection fraction was ≥50% in 60.1% of these patients. Re-transplant free survival 1, 5, 10 and 15 years after the diagnosis of late graft failure was 72.2%, 38.4%, 18.4%, and 7.5%, respectively; the incidence rate of re-hospitalization due to decompensated heart failure was 40.9 episodes per 100 patient-years (95% CI 36.6-46.1). The need for inotropes, the presence of cardiac allograft vasculopathy, higher creatinine serum levels, lower ejection fraction and lower sodium serum levels were independent predictors of worse outcomes. Conclusions Late graft failure is frequent after heart transplantation, as it is associated with poor outcomes. Rejection and cardiac allograft vasculopathy are the most frequent underlying causes.

Background Due to improved surgical strategies a growing number of patients survive acute aortic dissection. Patent false lumen (FL) is common in chronic dissection and it has been associated with poor prognosis, which is mainly driven by FL expansion. Several variables indirectly related to flow characteristics have been associated with progressive aortic dilation. We aimed to evaluate whether the maximum systolic flow deceleration rate (MSDR) in the FL, quantified by 4D-flow MR, is related to FL dilation in chronic type B aortic dissection. Methods Twenty-nine patients with a patent FL after aortic dissection and a prior follow-up of at least 3 years underwent contrast-enhanced 4D-flow MR. Marfan patients were excluded. Time-resolved FL flow acceleration was calculated in a 5 cm-long volume of the descending aorta around the level of the pulmonary bifurcation. MSDR was determined as the maximum minus the minimum acceleration in systole over the corresponding time interval (Figure 1a). Aortic growth rate (GR) was measured as the difference between final and initial maximum FL diameters obtained by angio-CT divided by follow-up duration. Population was divided into tertiles based on GR. Results Demographic and clinical variables were similar among GR tertiles (Table). MSDR was lower in patients with a GR Conclusions The MSDR in the FL of chronic type B aortic dissection is linearly related to FL growth rate and discriminated between tertiles of aortic dilation. Prospective longitudinal studies are need to unveil possible prognostic value of this parameter. Table Group 1 (n = 9) Group 2 (n = 10) Group 3 (n = 10) p-value Age (years) 63.44 ±13.54 62.50 ± 13.60 64.56 ± 6.67 0.902 BSA (m2) 2.00 ± 0.18 1.77 ± 0.20 1.94 ± 0.12 0.213 Men 6 (86%) 4 (57%) 4 (100%) 0.210 Hypertension 4 (66%) 5 (71%) 4 (100%) 0.438 Atheroclerosis 1 (17%) 1 (14%) 0 (0%) 0.699 Initial Diameter (mm) 45.00 ± 7.69 36.00 ± 4.20 37.00 ± 6.48 0.078 Final Diameter (mm) 49.50 ± 6.74 44.86 ± 5.70 59.25 ± 9.84 0.049 Follow-up (year) 11.83 ± 8.79 7.82 ± 3.34 8.08 ± 4.05 0.921 GR (mm/year) 0.27 ± 0.29 1.18 ± 0.26 2.64 ± 0.97 Abstract P1600 Figure 1

Funding Acknowledgements ISCIII PI14/0106 and PI17/00381, La Marató de TV3 (20151330), Eur FP7/People 267128 and CIBERCV BACKGROUND Genetic syndromic aortic diseases are rare, with Marfan syndrome (MFS) being the most common. However, less is known of Loeys-Dietz syndrome (LDS) which has much lower prevalence and presumed worse prognosis. Increased aortic stiffness in MFS has been previously described but no studies have evaluated aortic biomechanics in LDS. Pulse wave velocity (PWV) is the gold standard measure for arterial stiffness and can be quantified by 4D flow MRI. We aim to evaluate regional aortic PWV by 4D flow MRI in LDS compared to MFS and healthy volunteers. METHODS Sixteen LDS patients with a pathogenic mutation, 76 MFS and 49 healthy volunteers were prospectively and consecutively included. No patient had previous aortic dissection or surgery. All underwent a 4D flow MRI study in a 1.5 T clinical scanner. Ascending (AAo) and descending (DAo) aorta PWV were computed using wavelet analysis of the systolic upslope for transit time calculation (Figure). Statistical comparison was made with non-parametric analysis to account for the non-normality of data and multivariate analysis was evaluated separately for AAo and DAo PWV. RESULTS Ascending and descending aortic PWV revealed stiffer aortas in LDS patients than in healthy volunteers, even after adjustment for diameter of sinus of Valsalva (SoV) and sex. Conversely, no differences in aortic stiffness were found between LDS and MFS patients (Table). CONCLUSIONS Abnormally high regional aortic stiffness was observed in LDS patients when compared with controls. The severity of increased regional aortic stiffness was found similar to the one affecting MFS patients. Table Controls (N = 49) LDS (N = 16) MFS (N = 76) LDS vs. HV LDS vs. MFN Parameter Unadjusted p-value Adjusted p-value Unadjusted p-value Adjusted p-value Age [years] 39 ± 12 39 ± 16 36 ± 12 0.903 0.599 Men 32 (65%) 6 (37%) 34 (45%) 0.079 0.782 Weight [kg] 72 ± 11 69 ± 13 74 ± 16 0.288 0.194 Height [cm] 172 ± 8 172 ±12 181 ± 11 0.834 0.008 Systolic BP [mmHg] 126 ± 18 125 ± 14 127 ± 17 0.957 0.523 Diastolic BP [mmHg] 70 ± 11 77 ± 6 75 ± 12 0.011 0.318 SoV diameter [mm] 30.6 ± 3.9 35.4 ± 4.6 38.1 ± 5.9 0.001 0.060 AAo diameter [mm] 27.7 ± 3.8 29,0 ± 5.0 29.7 ± 5.4 0.458 0.579 DAo diameter [mm] 20.0 ± 2.0 21.3 ± 3.6 22.9 ± 3.8 0.546 0.124 AAo PWV [m/s] 5.2 ± 1.9 7.6 ± 2.4 7.3 ± 2.8 0.001 0.050* 0.534 NS DAo PWV [m/s] 7.1 ± 2.2 9.4 ± 2.6 10.7 ± 4.6 0.003 0.025** 0.493 NS Abstract P372 Figure

INTRODUCTION AND OBJECTIVES Mortality is high in acute aortic syndrome (AAS), which therefore requires early treatment. This study aimed to analyze changes in the diagnosis and treatment of AAS over 20 years at our center. METHODS From 1999 to 2018, 451 patients diagnosed with AAS (336 men; mean age, 60.9±12.4 years) were prospectively included (270 type A and 181 type B). Clinical variables, diagnosis, treatment, and in-hospital complications were analyzed. RESULTS The use of computed tomography (CT) as the first-line diagnostic technique increased from 62.8% to 94.2% (P

Introduction Patent false lumen (FL) in aortic dissection has been associated with poor prognosis mainly due to aortic expansion. Although morphologic variables have been related to aortic dilatation as expression of high pressure in the FL, they do not reflect flow characteristics. We propose the maximum systolic flow deceleration rate (MSDR) in the FL, quantified by 4Dflow, assuming that flow should be strongly decelerated during systole under high pressure. Methods Twenty-nine patients with a patent FL after aortic dissection (no Marfan syndrome) and with a follow-up of at least 3 years underwent a contrast-enhanced 4D-flow MR. FL acceleration was calculated during the cardiac cycle in a sub-volume of the descending aorta (5 cm around the level of the pulmonary bifurcation). MSDR was determined as the maximum minus the minimum acceleration in systole over the corresponding time interval (Figure 1a). Aortic growth rate (GR) was defined as the difference between final and initial aortic diameters obtained by angio-CT over the period of follow-up. Population was divided into tertiles based on GR. Results Demographic, clinical variables or basal aortic diameter did not show differences among GR groups (Table 1). MSDR was statistically different in patients with a GR Table 1. Demographic and other variables Tertile 1 Tertile 2 Tertile 3 p-value Age (year) 63.4 (±13.5) 62.5 (±13.6) 64.6 (±6.7) 0.902 BSA (m2) 2.0 (±0.2) 1.8 (±0.2) 1.9 (±0.1) 0.213 Men 6 (86%) 4 (57%) 4 (100%) 0.210 Hypertension 4 (66%) 5 (71%) 4 (100%) 0.438 Atherosclerosis 1 (17%) 1 (14%) 0 (0%) 0.699 Initial diameter 45.0 (±7.69) 36.0 (±4.2) 37.0 (±6.5) 0.078 Final diameter 49.5 (±6.74) 44.9 (±5.7) 59.2 (±9.8) 0.049* Follow-up (year) 11.8 (±8.79) 7.9 (±3.3) 8.1 (±4.0) 0.921 Aortic GR (mm/year) 0.3 (±0.3) 1.2 (±0.3) 2.6 (±1.0) 0.001* MSDR (cm/s3) 1212 (±468) 2411 (±1034) 2558 (±1098) 0.005* Values are mean (±SD) or n (%). Conclusion MSDR of flow in the FL derived from 4D-flow RM is related to GR of dissected descending aorta. It is useful to discriminate mild vs. significant aorta enlargement and identify patients who may benefit from earlier therapy.

Identification of Fabry disease (FD) in cardiac patients has been restricted so far to patients with left ventricular hypertrophy. Conduction problems are frequent in FD and could precede other manifestations, offering a possible earlier diagnosis.We studied the prevalence of FD in 188 patients, This work was partially supported by grants from Genzyme-Sanofi (Investigator Initiated Research Grant 2017) and by the Instituto de Salud Carlos III (PI17/01941). Funders played no role in the design, collection, analysis, or interpretation of the data or in the decision to submit the manuscript for publication.

Objectives This study aimed to investigate the accuracy of a broad range of echocardiographic variables to develop multiparametric scores to diagnose CA in patients with proven light chain (AL) amyloidosis or those with increased heart wall thickness who had amyloid was suspected. We also aimed to further characterize the structural and functional changes associated with amyloid infiltration. Background Cardiac amyloidosis (CA) is a serious but increasingly treatable cause of heart failure. Diagnosis is challenging and frequently unclear at echocardiography, which remains the most often used imaging tool. Methods We studied 1,187 consecutive patients evaluated at 3 referral centers for CA and analyzed morphological, functional, and strain-derived echocardiogram parameters with the aim of developing a score-based diagnostic algorithm. Cardiac amyloid burden was quantified by using extracellular volume measurements at cardiac magnetic resonance. Results A total of 332 patients were diagnosed with AL amyloidosis and 339 patients with transthyretin CA. Concentric remodeling and strain-derived parameters displayed the best diagnostic performance. A multivariable logistic regression model incorporating relative wall thickness, E wave/e′ wave ratio, longitudinal strain, and tricuspid annular plane systolic excursion had the greatest diagnostic performance in AL amyloidosis (area under the curve: 0.90; 95% confidence interval: 0.87 to 0.92), whereas the addition of septal apical–to–base ratio yielded the best diagnostic accuracy in the increased heart wall thickness group (area under the curve: 0.80; 95% confidence interval: 0.85 to 0.90). Conclusions Specific functional and structural parameters characterize different burdens of CA deposition with different diagnostic performances and enable the definition of 2 scores that are sensitive and specific tools with which diagnose or exclude CA.

Introduction and objectives: Danon disease (DD) is caused by mutations in the LAMP2 gene. It is considered a multisystemic disease characterized by hypertrophic cardiomyopathy with pre-excitation and extreme hypertrophy, intellectual disability, myopathy, childhood presentation, and worse prognosis in men. There are scarce data on the clinical characteristics and prognosis of DD. Methods: We analyzed the clinical records of patients with DD from 10 Spanish hospitals. Results: Twenty-seven patients were included (mean age, 31 +/- 19 years; 78% women). Male patients showed a high prevalence of extracardiac manifestations: myopathy (80%), learning disorders (83%), and visual alterations (60%), which were uncommon findings in women (5%, 0%, and 27%, respectively). Although hypertrophic cardiomyopathy was the most common form of heart disease (61%), the mean maximum wall thickness was 15 +/- 7 mm and dilated cardiomyopathy was present in 12 patients (10 women). Pre-excitation was found in only 11 patients (49%). Age at presentation was older than 20 years in 16 patients (65%). After a median follow-up of 4 years (interquartile range, 2-9), 4 men (67%) and 9 women (43%) died or required a transplant. Cardiac disease and adverse events occurred later in women (37 +/- 9 vs 23 +/- 16 and 36 +/- 20 vs 20 +/- 11 years, respectively). Conclusions: The clinical characteristics of DD differ substantially from traditional descriptions: age at presentation of DD is older, the disease is not multisystemic in women, and pre-excitation is infrequent. (C) 2018 Sociedad Espanola de Cardiologia. Published by Elsevier Espana, S.L.U. All rights reserved.

[Background] The BAG3 (BLC2-associated athanogene 3) gene codes for an antiapoptotic protein located on the sarcomere Z-disc. Mutations in BAG3 are associated with dilated cardiomyopathy (DCM), but only a small number of cases have been reported to date, and the natural history of BAG3 cardiomyopathy is poorly understood. [Objectives] This study sought to describe the phenotype and prognosis of BAG3 mutations in a large multicenter DCM cohort. [Methods] The study cohort comprised 129 individuals with a BAG3 mutation (62% males, 35.1 ± 15.0 years of age) followed at 18 European centers. Localization of BAG3 in cardiac tissue was analyzed in patients with truncating BAG3 mutations using immunohistochemistry. [Results] At first evaluation, 57.4% of patients had DCM. After a median follow-up of 38 months (interquartile range: 7 to 95 months), 68.4% of patients had DCM and 26.1% who were initially phenotype-negative developed DCM. Disease penetrance in individuals >40 years of age was 80% at last evaluation, and there was a trend towards an earlier onset of DCM in men (age 34.6 ± 13.2 years vs. 40.7 ± 12.2 years; p = 0.053). The incidence of adverse cardiac events (death, left ventricular assist device, heart transplantation, and sustained ventricular arrhythmia) was 5.1% per year among individuals with DCM. Male sex, decreased left ventricular ejection fraction. and increased left ventricular end-diastolic diameter were associated with adverse cardiac events. Myocardial tissue from patients with a BAG3 mutation showed myofibril disarray and a relocation of BAG3 protein in the sarcomeric Z-disc. [Conclusions] DCM caused by mutations in BAG3 is characterized by high penetrance in carriers >40 years of age and a high risk of progressive heart failure. Male sex, decreased left ventricular ejection fraction, and enlarged left ventricular end-diastolic diameter are associated with adverse outcomes in patients with BAG3 mutations., This work was supported by grants from the following institutions: Instituto de Salud Carlos III (ISCIII) (PI14/ 0967, PI15/01551, AC16/0014), CIBERCV (CB16/11/00403), Progreso and Salud Foundation (Junta de Andalucia) (PI-0011/201), Ministry of Economy, Industry and Competitiveness (IJCI-2016-29393), Mutual Medical (Research Award 2017), ERA-CVD Joint Transnational Call 2016 (Genprovic), British Heart Foundation (SP/10/10/28431), Wellcome Trust (107469/Z/15/), NIHR Royal Brompton Cardiovascular Biomedical Research Unit, NIHR Imperial Biomedical Research Center, Health Innovation Challenge Fund award from the Wellcome Trust and Department of Health, U.K. (HICF-R6-373), Danish Heart Foundation (16-R107-A6617), University of Southern Denmark, the Region of Southern Denmark, Odense University Hospital, German Competence Network Heart Failure, (TP9, FKZ 01GI0205), DETECTIN-HF project (ERA-CVD framework), and PROMEX Charitable Foundation. UCL Hospitals NIHR Biomedical Research Center and Netherlands Cardiovascular Research Initiative, an initiative with support of the Dutch Heart Foundation, CVON2015-12 eDETECT and CVON2014-40 DOSIS. The CNIC is supported by the Ministry of Economy, Industry and Competitiveness and the Pro-CNIC Foundation, and is a Severo Ochoa Center of Excellence (SEV-2015-0505). Grants from ISCIII and the Spanish Ministry of Economy and Competitiveness are supported by the Plan Estatal de IþDþI 2013-2016 – European Regional Development Fund (FEDER) “A way of making Europe.” The Hospital Universitario Puerta de Hierro Majadahonda, Hôpital PitiéSalpêtrière, and Saint Bartholomews’ Hospital are members of the European Reference Network for rare, low-prevalence, and complex diseases of the heart (ERN GUARD-Heart). Drs. Ochoa, Cicerchia, and Salazar-Mendiguchia are employees of Health In Code.

Cardiac amyloidosis is an infiltrative disorder caused by extracellular protein deposition. Transthyretin is a proamyloidotic protein that produces one of the most frequent forms of cardiac amyloidosis, either through mutations or a wild-type form (previously known as senile amyloidosis). Until very recently, diagnosis of transthyretin amyloidosis (ATTR) was very uncommon and histological confirmation was mandatory, making diagnosis of ATTR a real challenge in daily clinical practice. Moreover, the specific therapeutic options to alter the clinical course of the disease were very limited. However, advances in cardiac imaging and diagnostic strategies have improved recognition of ATTR. In addition, several compounds able to modify the natural history of the disease are in the final phases of research, with promising results. Given that effective therapies are on the horizon, cardiologists should be well-versed in this disease and be familiar with its diagnosis and treatment. This review describes the broad clinical spectrum of ATTR in detail, as well as recent advances in the diagnosis and treatment of this condition.

Background: Aortic type B dissection is a life-threating condition in which blood flows between aortic wall layers. Despite a role for morphological variables, such as entry tear location and dimension, in the prediction of progressive false lumen (FL) dilation has been suggested, the role of flow characteristics has not been studied due to the unavailability of proper flow descriptions. Now that 4D phase-contrast magnetic resonance imaging (4D-flow MRI) allows for the evaluation of flow field with unprecedented detail, we tested whether flow deceleration in the FL, being a marker of occluded flow exit, is related to FL dilation. Methods: In 29 patients with a patent FL and with a retrospective CT-based follow-up >3 years underwent 4D-flow MRI. Flow acceleration in the FL was calculated in a standardized sub-volume of the descending aorta. The maximum systolic flow deceleration rate (MSDR) was quantified as maximum minus minimum acceleration during systole divided by the corresponding time interval (Figure 1a). Results: Demographic and clinical variables were similar among growth-rate (GR) tertiles. MSDR was statistically different in patients with a GR

Background: Low longitudinal strain of the ascending aorta (AAo) by cardiac magnetic resonance (CMR) predicts dilation and aortic events in Marfan syndrome (MFS) [1], possibly reflecting aortic stiffness [2]. Speckle-tracking is established for cardiac deformation, but proximal aorta applications are challenging due to wall thickness and substantial motion. We aimed to validate a purpose-specific speckle-tracking tool for root longitudinal strain analysis by comparison with CMR-derived AAo longitudinal strain and as predictor of dilation in MFS patients. Methods: CMR feature-tracking [1] and echocardiography speckle-tracking where applied to 25 MFS patients free from previous aortic surgery by a single observer blind to clinical data. For echocardiography, two regions of interests were manually created covering both walls in a parasternal long-axis view and tracked along the cardiac cycle. Longitudinal strain was computed as the average of maximum increase in relative distance of several sub-regions covering both walls. Aortic diameter was measured on CMR images. Results: Both techniques were successfully applied to all patients. Aortic root longitudinal strain by echocardiography was linearly related to CMR-derived AAo longitudinal strain (R = 0.573, p = 0.003, Figure A) and was higher (20.4 ± 8.4 vs 10.5 ± 3.8), especially at higher absolute values (Figure B). After a mean follow up of 45 ± 13 months, aortic root diameter growth rate was 0.27 ± 0.3 mm/year. In multivariable analysis corrected for root diameter and heart rate (p = 0.083 and 0.005, respectively), baseline longitudinal strain by echocardiography was independently related to progressive dilation (B = −0.017, p = 0.005). Conclusion: Aortic root longitudinal strain by echocardiography is related to CMR-derived AAo longitudinal strain and is an independent predictor of progressive dilation in MFS patients.

The presence of mitral regurgitation (MR) is associated with an impaired prognosis in patients with ischemic heart disease. However, data with regard to the impact of this condition in patients with ST-segment elevation myocardial infarction (STEMI) treated by means of primary percutaneous coronary intervention (PPCI) are lacking. Our aim was to assess the effect of MR in the long-term prognosis of patients with STEMI after PPCI. We analyzed a prospective registry of 1,868 patients (mean age 62 ± 13 years, 79.9% men) with STEMI treated by PPCI in our center from January 2006 to December 2010. Our primary outcome was the composite end point of all-cause mortality or admission due to heart failure during follow-up. After exclusions, 1,036 patients remained for the final analysis. Moderate or severe MR was detected in 119 patients (11.5%). Those with more severe MR were more frequently women (p0.001), older (p0.001), and with lower ejection fraction (p0.001). After a median follow-up of 2.8 years (1.7 to 4.3), a total of 139 patients (13.4%) experienced our primary end point. There was an association between the unfavorable combined event and the degree of MR (p0.001). After adjustment for relevant confounders, moderate or severe MR remained as an independent predictor of the combined primary end point (adjusted hazard ratio [HR] 3.14, 95% confidence interval [CI] 1.57 to 6.27) and each event separately (adjusted HR death 3.1, 95% CI 1.34 to 7.2; adjusted HR heart failure 3.3, 95% CI 1.16 to 9.4). In conclusion, moderate or severe MR detected early with echocardiography was independently associated with a worse long-term prognosis in patients with STEMI treated with PPCI.

To analyse the incidence, risk factors and clinical outcomes of late graft failure after heart transplantation.We conducted an observational, single-centre study based on 547 patients who underwent cardiac transplantation from 1991 to 2014 and who survived the in-hospital postoperative period. Late graft failure was defined as the first hospitalization due to this condition after discharge. Over a mean follow-up of 8.4 ± 6 years, 178 (32.5%) patients were hospitalized due to late graft failure [incidence rate: 3.6 cases per 100 patient-years, 95% confidence interval (CI) 3.1-4.2]. Pre-transplant diabetes, higher pre-transplant transpulmonary pressure gradient and lower donor-recipient weight ratio were independently associated with higher risk of graft failure. Cardiac allograft vasculopathy, cellular rejection grade ≥1R, and antibody-mediated rejection grade ≥1 were detected in 50.6%, 44.9% and 19.2% patients, respectively, admitted due to graft failure. Left ventricular ejection fraction was ≥50% in 60.1% of these patients. Re-transplant free survival 1, 5, 10 and 15 years after the diagnosis of late graft failure was 72.2%, 38.4%, 18.4%, and 7.5%, respectively; the incidence rate of re-hospitalization due to decompensated heart failure was 40.9 episodes per 100 patient-years (95% CI 36.6-46.1). The need for inotropes, the presence of cardiac allograft vasculopathy, higher creatinine serum levels, lower ejection fraction and lower sodium serum levels were independent predictors of worse outcomes.Late graft failure is frequent after heart transplantation, as it is associated with poor outcomes. Rejection and cardiac allograft vasculopathy are the most frequent underlying causes.

La amiloidosis cardiaca es una enfermedad infiltrativa por depósito extracelular de proteínas. De las proteínas proamiloidóticas a nivel cardiaco, la transtiretina produce una de las formas más frecuentes de amiloidosis cardiaca, bien por mutaciones o bien en su forma natural (wild-type) conocida previamente como amiloidosis senil. Hasta muy recientemente, el diagnóstico de amiloidosis por transtiretina (ATTR) se producía en reducidas ocasiones y requería confirmación histológica, por lo que establecer el diagnóstico constituía un verdadero reto en la práctica clínica habitual. Además, las opciones terapéuticas específicas para alterar el curso clínico de la enfermedad eran muy limitadas. Sin embargo, avances en el campo de la imagen cardiaca y en la estrategia diagnóstica de la enfermedad están facilitando un reconocimiento creciente de la ATTR. De forma adicional, diversos compuestos capaces de modificar la historia de la enfermedad se encuentran en fases finales de investigación, con resultados prometedores. Dado que una terapia efectiva parece estar cada vez más próxima, se hace imprescindible que los cardiólogos conozcan esta patología en profundidad y estén familiarizados con su diagnóstico y tratamiento. En esta revisión se repasará detalladamente el amplio espectro clínico de la ATTR, así como los recientes avances en el diagnóstico y tratamiento de esta entidad. pre-print 383 KB

A 44-year-old man was referred to the cardiology outpatient clinic due to dyspnea on exertion. He had undergone aortic valve replacement with a biological prosthetic valve (Carpentier-Edwards 23 mm, Edwards Lifesciences, Irvine, California) and reconstruction of the mitroaortic junction due to

Primary percutaneous coronary intervention (PPCI) is the preferred reperfusion therapy for patients presenting with ST-segment elevation myocardial infarction (STEMI) when it can be performed expeditiously and by experienced operators. In spite of excellent clinical results this technique is associated with longer delays than thrombolysis and this fact may nullify the benefit of selecting this therapeutic option. Several strategies have been proposed to decrease the temporal delays to deliver PPCI. Among them, prehospital diagnosis and direct transfer to the cath lab, by-passing the emergency department of hospitals, has emerged as an attractive way of diminishing delays. The purpose of this review is to address the effect of direct transfer on time delays and clinical events of patients with STEMI treated by PPCI.

[Abstract] Background. A high frequency of venous thromboembolism (VTE) has been observed after lung, kidney, and liver transplantation. However, data about the incidence of this complication among heart transplant (HT) recipients are lacking. Methods. We analyzed the incidence, recurrence, and predisposing factors of VTE in a single-center cohort of 635 patients who underwent HT from April 1991 to April 2013. Deep venous thrombosis (DVT) and pulmonary embolism (PE) were considered as VTE episodes. Results. During a median post-transplant follow-up of 8.4 years, 62 VTE episodes occurred in 54 patients (8.5%). Incidence rates of VTE, DVT, and PE were, respectively, 12.7 (95% confidence interval [CI], 9.7–16.3), 8.4 (95% CI, 6.0–11.4), and 7.0 (95% CI 4.8–9.7) episodes per 1,000 patient-years. Incidence rates of VTE during the first post-transplant year and beyond were, respectively, 45.1 (95% CI, 28.9–67.1) and 8.7 (95% CI 6.2–11.2) episodes per 1,000 patient-years. The incidence rate of VTE recurrence after a first VTE episode was 30.5 (95% CI, 13.2–60.2) episodes per 1,000 patient-years. By means of multivariable Cox regression, chronic renal dysfunction, older age, obesity, and the use of mammalian target of rapamycin inhibitors were identified as independent risk factors for VTE among HT recipients. Conclusions. VTE is a frequent complication after HT, mainly during the first post-operative year. In view of a high recurrence rate, long-term anti-coagulation should be considered in HT recipients who experience a first VTE episode.

Introduction Cardiac allograft vasculopathy (CAV) remains a major impediment to long-term survival after heart transplantation (HT). Limited data exist regarding the impact of coronary revascularization in these patients. Objective To evaluate the outcomes of revascularization procedures in patients with CAV compared with patients who did not undergo revascularization. Methods Retrospective analysis of 249 patients who underwent HT at our center between June 1998 and December 2009 and who were examined by coronary angiography after HT. We included patients with moderate or severe CAV according to the International Society for Heart and Lung Transplantation (ISHLT) nomenclature to evaluated outcomes after revascularization or diagnostic angiography. Major adverse cardiovascular events (MACE) comprised death, acute coronary syndrome, coronary revascularization, admission because of heart failure not due to an acute rejection episode, and cardiac retransplantation. Results Moderate or severe CAV was detected in 43 patients. Twelve (27.9%) underwent coronary revascularization: eight percutaneous interventions and four bypass surgeries. Indications for revascularization were symptomatic ischemia or noninvasive evidence of ischemia ( n = 6, 14.0%) or high-risk asymptomatic CAV ( n = 6; 14.0%), namely, lesions located in the left main or proximal anterior descending arteries or multivessel disease with left ventricular dysfunction. The remaining 31 (72.1%), who did not undergo revascularization showed an absence of ischemia during exercise echocardiography ( n = 11; 25.6%) or diffuse disease not amenable to revascularization ( n = 20; 46.5%). During a mean follow-up of 3.0 ± 2.4 years, MACE occurred in three revascularized patients (25.0%), in one with absence of stress-induced ischemia (9.1%) and in 13 with nonrevascularizable disease (65%; P = .012). Conclusions Revascularization procedures were effective in HT patients with evidence of ischemia or high-risk CAV. Patients with absence of stress-induced ischemia have a good prognosis without revascularization. On the other hand, diffuse nonrevascularizable CAV is associated with a poor prognosis.

A 65-year-old male was admitted to our institution due to atypical chest pain. His previous medical history revealed the presence of an anterior wall myocardial infarction that extended clinically silent 30 years ago. Angiographic images revealed the presence of a linear filling defect in the

Although cardiac allograft vasculopathy (CAV) is the major impediment to long-term survival after heart transplantation (HT), it is only recently that standards governing the grading of this entity have been introduced in the form of the International Society for Heart and Lung Transplantation’s recommended nomenclature (ISHLT-RN), which is based on angiographic findings and graft function. The prognostic value of this grading system remains unknown. In this study we evaluated the prevalence and prognostic significance of ISHLT-RN CAV grades assigned 1 year after HT. We retrospectively studied 169 consecutive patients who underwent HT at our center between January 2000 and December 2009, and coronary angiography 1 year after HT (median time 12.3 months, interquartile range 9.7 to 13.7 months). Patients’ baseline characteristics (Table 1) were