The detrimental role of galectin-3 and endoplasmic reticulum stress in the cardiac consequences of myocardial ischemia in the context of obesity.

The association between cardiac fibrosis and galectin-3 was evaluated in patients with acute myocardial infarction (MI). The role of galectin-3 and its association with endoplasmic reticulum (ER) stress activation in the progression of cardiovascular fibrosis was also evaluated in obese-infarcted rats. The inhibitor of galectin-3 activity, modified citrus pectin (MCP; 100 mg/kg/day), and the inhibitor of the ER stress activation, 4-phenylbutyric acid (4-PBA; 500 mg/kg/day), were administered for 4 weeks after MI in obese rats. Overweight-obese patients who suffered a first MI showed higher circulating galectin-3 levels, higher extracellular volume, and LV infarcted size, as well as lower E/e'ratio and LVEF compared with normal-weight patients. A correlation was observed between galectin-3 levels and extracellular volume. Obese-infarcted animals presented cardiac hypertrophy and reduction in LVEF, and E/A ratio as compared with control animals. They also showed an increase in galectin-3 gene expression, as well as cardiac fibrosis and reduced autophagic flux. These alterations were associated with ER stress activation characterized by enhanced cardiac levels of binding immunoglobulin protein, which were correlated with those of galectin-3. Both MCP and 4-PBA not only reduced cardiac fibrosis, oxidative stress, galectin-3 levels, and ER stress activation, but also prevented cardiac functional alterations and ameliorated autophagic flux. These results show the relevant role of galectin-3 in the development of diffuse fibrosis associated with MI in the context of obesity in both the animal model and patients. Galectin-3 in tandem with ER stress activation could modulate different downstream mechanisms, including inflammation, oxidative stress, and autophagy.

Echocardiographic and clinical features of patients developing prosthesis-patient mismatch after transcatheter aortic valve replacement: Insights from the Recovery-TAVR registry.

BACKGROUND: The impact of prosthesis-patient mismatch (PPM) on major endpoints after transcatheter aortic valve replacement (TAVR) is controversial and the effects on progression of heart damage are poorly investigated. Therefore, our study aims to evaluate the prevalence and predictors of PPM in a "real world" cohort of patients at intermediate and low surgical risk, its impact on mortality and the clinical-echocardiographic progression of heart damage. METHODS: 963 patients who underwent TAVR procedure between 2017 and 2021, from the RECOVERY-TAVR international multicenter observational registry, were included in this analysis. Multiparametric echocardiographic data of these patients were analyzed at 1-year follow-up (FU). Clinical and echocardiographic features were stratified by presence of PPM and PPM severity, as per the most current international recommendations, using VARC-3 criteria. RESULTS: 18% of patients developed post-TAVR. PPM, and 7.7% of the whole cohort had severe PPM. At baseline, 50.3% of patients with PPM were male (vs 46.2% in the cohort without PPM, P = .33), aged 82 (IQR 79-85y) years vs 82 (IQR 78-86 P = .46), and 55.6% had Balloon-Expandable valves implanted (vs 46.8% of patients without PPM, P = .04); they had smaller left ventricular outflow tract (LVOT) diameter (20 mm, IQR 19-21 vs 20 mm, IQR 20-22, P = .02), reduced SVi (34.2 vs 38 mL/m2, P < .01) and transaortic flow rate (190.6 vs 211 mL/s, P < .01). At predischarge FU patients with PPM had more paravalvular aortic regurgitation (moderate-severe AR 15.8% vs 9.2%, P < .01). At 1-year FU, maladaptive alterations of left ventricular parameters were found in patients with PPM, with a significant increase in end-systolic diameter (33 mm vs 28 mm, P = .03) and a significant increase in left ventricle end systolic indexed volume in those with moderate and severe PPM (52 IQR 42-64 and 52, IQR 41-64 vs 44 IQR 35-59 in those without, P = .02)). No evidence of a significant impact of PPM on overall (P = .71) and CV (P = .70) mortality was observed. Patients with moderate/severe PPM had worse NYHA functional class at 1 year (NYHA III-IV 13% vs 7.8%, P = .03). Prosthesis size≤23 mm (OR 11.6, 1.68-80.1) was an independent predictor of PPM, while SVi (OR 0.87, 0.83-0.91, P < .001) and LVOT diameter (OR 0.79, 0.65-0.95, P = .01) had protective effect. CONCLUSIONS: PPM was observed in 18% of patients undergoing TAVR. Echocardiographic evaluations demonstrated a PPM-related pattern of early ventricular maladaptive alterations, possibly precursor to a reduction in cardiac function, associated with a significant deterioration in NYHA class at 1 year. These findings emphasize the importance of prevention of PPM of any grade in patients undergoing TAVR procedure, especially in populations at risk.

Diabetes mellitus is associated to high-risk late gadolinium enhancement and worse outcomes in patients with nonischemic dilated cardiomyopathy.

BACKGROUND: Diabetes mellitus (DM) is associated with a worse prognosis in patients with heart failure. Our aim was to analyze the clinical and imaging features of patients with DM and their association with outcomes in comparison to nondiabetic patients in a cohort of patients with nonischemic dilated cardiomyopathy (DCM). METHODS: This is a prospective cohort study of patients with DCM evaluated in a tertiary care center from 2018 to 2021. Transthoracic echocardiography and cardiac magnetic resonance findings were assessed. A high-risk late gadolinium enhancement (LGE) pattern was defined as epicardial, transmural, or septal plus free-wall. The primary outcome was a composite of heart failure hospitalizations and all-cause mortality. Multivariable analyses were performed to evaluate the impact of DM on outcomes. RESULTS: We studied 192 patients, of which 51 (26.6%) had DM. The median left ventricular ejection fraction was 30%, and 106 (55.2%) had LGE. No significant differences were found in systolic function parameters between patients with and without DM. E/e values were higher (15 vs. 11.9, p = 0.025), and both LGE (68.6% vs. 50.4%; p = 0.025) and a high-risk LGE pattern (31.4% vs. 18.5%; p = 0.047) were more frequently found in patients with DM. The primary outcome occurred more frequently in diabetic patients (41.2% vs. 23.6%, p = 0.017). DM was an independent predictor of outcomes (OR 2.01; p = 0.049) and of LGE presence (OR 2.15; p = 0.048) in the multivariable analysis. Patients with both DM and LGE had the highest risk of events (HR 3.1; p = 0.003). CONCLUSION: DM is related to a higher presence of LGE in DCM patients and is an independent predictor of outcomes. Patients with DM and LGE had a threefold risk of events. A multimodality imaging approach allows better risk stratification of these patients and may influence therapeutic options.

Methodology for the induction of myocardial infarction and cardiac function evaluation.

Cardiovascular disease (CVD) is the main cause of death worldwide, with myocardial infarction (MI) being the most prevalent pathology involved in CVD. MI is characterized by a deficiency in oxygen supply to the myocardium, thereby promoting ventricular remodeling of the ischemic and remote zone of the heart. Cardiac remodeling associated with MI could promote the development of heart failure and finally death. For these reasons, it is important to develop animal models that mimic human cardiac disease which could help to identify new mechanisms involved in the pathology and, consequently, develop new therapeutic strategies. We herein describe in detail a protocol for MI induction with low mortality rate (<15%) in rats by ligation of the left anterior descending artery. In addition, we also describe two imaging techniques which allow to evaluate cardiac structure and function-including deformation parameters in rats such as transthoracic echocardiography and cardiac magnetic resonance. This animal model could be useful for acute and chronic studies and for evaluating the potential usefulness of different treatments.

Aortic Stenosis and the Evolution of Cardiac Damage after Transcatheter Aortic Valve Replacement.

Background/Objectives: Severe aortic stenosis (AS) is the most frequent valvular heart disease. Models for stratifying cardiac damage associated with aortic stenosis have been developed to predict outcomes following valve replacement. However, evidence regarding morphological and functional evolution, as well as potential changes in the degree of cardiac damage, is limited. We aim to provide information on the evolution of cardiac morphology and the function of patients undergoing transcatheter aortic valve replacement (TAVR) who have been classified using a cardiac damage staging system. Methods: In total, 496 patients were included in the analysis, and were classified into four stages based on the extent of cardiac damage as follows: Stage 0, no cardiac damage: left ventricle global longitudinal strain (LV-GLS) < -17%; right ventricular-arterial coupling (RVAc) ≥ 0.35), and absence of significant mitral regurgitation (MR). Stage 1, left-sided subclinical damage: LV-GLS ≥ -17%. Stage 2, left-sided damage: significant MR. Stage 3, right-sided damage: RVAc < 0.35. Results: The mean age was 82.1 ± 5.9 years, and 53.0% were female. In total, 24.5% of patients met the criteria for Stage 0, and Stage 1 included 42.8% of patients, Stage 2 included 16.5%, and Stage 3 comprised 16.2% of patients. Mortality was 8.4% for stage 0, 17.4% for stage 1, 25.6% for stage 2, and 28.6% for stage 3 patients (p = 0.004). Diabetes mellitus (DM) (p = 0.047) and chronic kidney disease (CKD) (p = 0.024) were the only clinical predictors of no change or worsening in the stage of cardiac damage. Regarding echocardiographic variables, concomitant tricuspid, and mitral regurgitation, ≥ 2 were both significantly associated with no change or worsening, also (p < 0.001). Conclusions: Cardiac damage that is secondary to severe aortic stenosis has morphological and functional repercussions that, even after valve replacement, persist and might worsen the prognosis.

Valvulitis: a new echocardiographic criterion for the diagnosis of bioprosthetic aortic valve infective endocarditis.

INTRODUCTION AND OBJECTIVES: Diffuse homogeneous hypoechoic leaflet thickening, with a wavy leaflet motion documented by transesophageal echocardiography (TEE), has been described in some cases of prosthetic valve endocarditis (PVE) involving aortic bioprosthesis (AoBio-PVE). This echocardiographic finding has been termed valvulitis. We aimed to estimate the prevalence of valvulitis, precisely describe its echocardiographic characteristics, and determine their clinical significance in patients with AoBio-PVE. METHODS: From 2011 to 2022, 388 consecutive patients with infective endocarditis (IE) admitted to a tertiary care hospital were prospectively included in a multipurpose database. For this study, all patients with AoBio-PVE (n=86) were selected, and their TEE images were thoroughly evaluated by 3 independent cardiologists to identify all cases of valvulitis. RESULTS: The prevalence of isolated valvulitis was 12.8%, and 20.9% of patients had valvulitis accompanied by other classic echocardiographic findings of IE. A total of 9 out of 11 patients with isolated valvulitis had significant valve stenosis, whereas significant aortic valve regurgitation was documented in only 1 patient. Compared with the other patients with AoBio-PVE, cardiac surgery was less frequently performed in patients with isolated valvulitis (27.3% vs 62.7%, P=.017). In 4 out of 5 patients with valve stenosis who did not undergo surgery but underwent follow-up TEE, valve gradients significantly improved with appropriate antibiotic therapy. CONCLUSIONS: Valvulitis can be the only echocardiographic finding in infected AoBio and needs to be identified by imaging specialists for early diagnosis. However, this entity is a diagnostic challenge and additional imaging techniques might be required to confirm the diagnosis. Larger series are needed.

Deformación miocárdica en miocardiopatía dilatada no isquémica mediante feature tracking. Factibilidad e implicaciones pronósticas / Myocardial strain in nonischemic dilated cardiomyopathy with feature tracking. Feasibility and prognostic implications

Introducción y objetivos El análisis de la deformación miocárdica puede aportar información adicional a la fracción de eyección del ventrículo izquierdo (FEVI) en la miocardiopatía dilatada no isquémica (MDNI). El objetivo es analizar la factibilidad del estudio del strain del ventrículo izquierdo mediante feature tracking (FT) de cardiorresonancia magnética en la MDNI y determinar su relevancia clínica y pronóstica. Métodos Se incluyó retrospectivamente a los pacientes consecutivos con MDNI sometidos a cardiorresonancia magnética. Se obtuvieron el strain global longitudinal, circunferencial y radial del ventrículo izquierdo de secuencias convencionales de cine mediante un software de análisis de FT. Se evaluó su asociación con el evento combinado (insuficiencia cardiaca, implante de desfibrilador en prevención secundaria y muerte). Resultados Se pudo realizar el FT en los 98 pacientes evaluados (edad, 68± 13 años; el 72% varones). La concordancia intraobservador e interobservadores fue buena para el strain global longitudinal y circunferencial, y más limitada para el radial. El strain global circunferencial se asoció de manera independiente (OR=1,16; p=0,045) con la normalización de la FEVI en el seguimiento y fue el único parámetro morfológico con asociación independiente (OR=1,15; p=0,038) con el evento combinado. Un valor <–8,2% fue capaz de predecir la aparición de este evento en el seguimiento (Log-ranktest, 4,6; p=0,032) Conclusiones El análisis del strain del ventrículo izquierdo mediante FT es factible y reproducible en MDNI. El strain global circunferencial fue capaz de predecir la recuperación de la FEVI y la aparición de eventos cardiovasculares mayores en el seguimiento. (AU)

Introduction and objectives Myocardial strain analysis could provide additional information to left ventricular ejection fraction (LVEF) in nonischemic dilated cardiomyopathy (NIDC). Our aim was to analyze the feasibility of left ventricular strain evaluation using cardiac magnetic resonance feature tracking (FT) in NIDC, and to determine its clinical and prognostic impact. Methods We retrospectively included consecutive patients with NIDC who underwent cardiac magnetic resonance. Left ventricular global longitudinal, circumferential and radial strain were obtained from standard cine sequences using FT analysis software. We evaluated their association with a composite endpoint (heart failure, implantable cardioverter-defibrillator in secondary prevention, or death). Results FT analysis could be performed in all of the 98 patients (mean age 68±13 years, 72% men). Intra- and interobserver concordance was good for global longitudinal and circumferential strain but was worse for radial strain. Global circumferential strain was independently associated (OR, 1.16; P=.045) with LVEF normalization during follow-up and was the only morphological parameter independently associated with the composite endpoint (OR, 1.15; P=.038). A cutoff value <−8.2% was able to predict the incidence of this event during follow-up (log-rank 4.6; P=.032). Conclusions Left ventricular strain analysis with FT is feasible and reproducible in NIDC. Global circumferential strain was able to predict LVEF recovery and the appearance of major cardiovascular events during follow-up. (AU)

Medida tridimensional del área del anillo tricúspide. Un nuevo criterio en la selección de candidatos a anuloplastia / Three-dimensional tricuspid area. A new criterion to improve patient selection for annuloplasty in tricuspid regurgitation

Introducción y objetivos: El desarrollo tardío de insuficiencia tricúspide funcional tras cirugía valvular izquierda de origen reumático es un importante predictor de mal pronóstico. Este estudio investiga la utilidad y precisión diagnóstica del área tricúspide evaluada por ecocardiografía transtorácica tridimensional en comparación con el diámetro bidimensional (D2D) convencional para evaluar la dilatación significativa del anillo tricúspide, proporcionando puntos de corte que podrían utilizarse en la práctica clínica para mejorar la selección de pacientes para cirugía. Métodos: Se incluyeron prospectivamente 109 pacientes con valvulopatía reumática en ausencia de reemplazo valvular previo. La insuficiencia tricúspide se dividió en tres grupos: leve, moderado y grave. Se obtuvieron los puntos de corte óptimos del área tridimensional (A3D) y del D2D para la identificación de la dilatación significativa del anillo tricúspide y se compararon con los umbrales de las guías actuales. También se evaluaron los factores predictivos de la dilatación del A3D. Resultados: Se identificaron los puntos de corte óptimos, absolutos y ajustados por el área de superficie corporal (ASC), de ambos parámetros (A3D: 10,4 cm2, 6,5 cm2/m2, D2D: 35 mm, 21 mm/m2) siendo el parámetro A3D/ASC el que obtuvo el mejor rendimiento diagnóstico (ABC=0,83). El área tricúspide por ecocardiografía transtorácica tridimensional ayudó a reclasificar la indicación quirúrgica en el 14% de pacientes con insuficiencia tricúspide leve (IC95%, 1-15%; p=0,03) y en el 37% con insuficiencia tricúspide moderada (IC95%, 22-37%; p<0,0001), mientras que el A3D/ASC cambió los criterios de cirugía en los casos de insuficiencia tricúspide leve (17%, IC95%, 3-17%; p=0,01) en comparación con el D2D/ASC. En el análisis multivariable, los volúmenes de la aurícula derecha e izquierda y el diámetro del ventrículo derecho basal se correlacionaron independientemente con el A3D. Conclusiones: El umbral del D2D actual propuesto de 40 mm infraestima la dilatación del anillo tricúspide. Aunque 21 mm/m2 podría ser un criterio de selección razonable, la combinación con la evaluación del A3D mejora la selección de pacientes candidatos para cirugía

Introduction and objectives: Late functional tricuspid regurgitation after rheumatic left-sided valve surgery is an important predictor of poor prognosis. This study investigated the usefulness and accuracy of 3-dimensional transthoracic echocardiography tricuspid area compared with conventional 2-dimensional diameter (2DD) for assessing significant tricuspid annulus dilatation, providing cutoff values that could be used in clinical practice to improve patient selection for surgery. Methods: We prospectively included 109 patients with rheumatic heart disease in the absence of previous valve replacement. Tricuspid regurgitation was divided into 3 groups: mild, moderate, and severe. Optimal 3-dimensional area (3DA) and 2DD cutoff points for identification of significant tricuspid annulus dilatation were obtained and compared with current guideline thresholds. Predictive factors for 3DA dilatation were also assessed. Results: Optimal cutoff points for both absolute and adjusted to body surface area (BSA) tricuspid annulus dilatation were identified (3DA: 10.4 cm2, 6.5 cm2/m2; 2DD: 35 mm, 21 mm/m2); 3DA/BSA had the best diagnostic performance (AUC=0.83). Three-dimensional transthoracic echocardiography tricuspid area helped to reclassify surgical indication in 14% of patients with mild tricuspid regurgitation (95%CI, 1%-15%; P=.03) and 37% with moderate tricuspid regurgitation (95%CI, 22%-37%; P<.0001), whereas 3DA/BSA changed surgery criteria in cases of mild tricuspid regurgitation (17%; 95%CI, 3%-17%; P=.01) compared with 2DD/BSA. On multivariable analysis, right and left atrial volumes and basal right ventricle diameter were independently correlated with 3DA. Conclusions: The current 40 mm threshold underestimates tricuspid annulus dilatation. Although 21 mm/m2 seems to be a reasonable criterion, the combination with 3DA assessment improves patient selection for surgery