Prioritization of Candidate Biomarkers for Degenerative Aortic Stenosis through a Systems Biology-Based In-Silico Approach.

Degenerative aortic stenosis is the most common valve disease in the elderly and is usually confirmed at an advanced stage when the only treatment is surgery. This work is focused on the study of previously defined biomarkers through systems biology and artificial neuronal networks to understand their potential role within aortic stenosis. The goal was generating a molecular panel of biomarkers to ensure an accurate diagnosis, risk stratification, and follow-up of aortic stenosis patients. We used in silico studies to combine and re-analyze the results of our previous studies and, with information from multiple databases, established a mathematical model. After this, we prioritized two proteins related to endoplasmic reticulum stress, thrombospondin-1 and endoplasmin, which have not been previously validated as markers for aortic stenosis, and analyzed them in a cell model and in plasma from human subjects. Large-scale bioinformatics tools allow us to extract the most significant results after using high throughput analytical techniques. Our results could help to prevent the development of aortic stenosis and open the possibility of a future strategy based on more specific therapies.

Validation of the usefulness of 2-dimensional strain parameters to exclude acute rejection after heart transplantation: a multicenter study.

INTRODUCTION AND OBJECTIVES: Two-dimensional speckle-tracking echocardiography has emerged as a promising alternative to endomyocardial biopsy to rule out acute cellular rejection after orthotopic heart transplantation (OHT) in single center studies. In an original cohort, 15.5% and 17% of cutoff points for left ventricular global longitudinal strain (LVGLS) and free-wall right ventricular longitudinal strain, respectively, achieved 100% negative predictive value to exclude moderate or severe acute cellular rejection (ACR ≥ 2R). Our objective was to demonstrate the usefulness of speckle-tracking and validate these cutoff points in an external cohort. METHODS: A prospective, multicenter study that included patients who were monitored during their first year after OHT was conducted. Echocardiographic studies analyzed by local investigators were compared with simultaneous paired endomyocardial biopsies samples. RESULTS: A total of 501 endomyocardial biopsy-echocardiographic studies were included in 99 patients. ACR≥2R was present in 7.4% of samples. LVGLS and free-wall right ventricular longitudinal strain were significantly reduced during ACR≥2R on univariate analysis. On multivariate analysis, LVGLS was independently associated with the presence of ACR≥2R. The original cutoff points demonstrated a negative predictive value of 94.3% to exclude ACR≥2R. CONCLUSIONS: This study maintained a strong negative predictive value to exclude ACR≥2R after OHT and LVGLS was independently associated with the presence of ACR≥2R. We propose the use of speckle-tracking, especially LVGLS, as part of the noninvasive diagnosis and management of ACR.

Huge tricuspid valve abscess.

A 60-year-old woman with colorectal adenocarcinoma underwent surgical mass resection in 2003; hepatic segmentectomy due to hepatic metastasis was performed in 2005. A port-a-cath for the administration of chemotherapy was cannulated. In April 2007, the patient developed fever and shivering, and the catheter was removed. Catheter and blood cultures were positive for methicillin-sensitive Staphylococcus aureus. TEE showed a very mobile mass (3 x 2 cm) at the junction of the posterior and anterior leaflets of the tricuspid valve. The mass had large echolucent areas inside, exhibiting an appearance like a 'ball of wool' (Panel B). Cardiac MRI confirmed the presence of a mass attached to the tricuspid valve, as shown in the delayed enhancement sequence. At surgery, a ruptured tendinous cord as well as a large abscess within the septal leaflet of the tricuspid valve was found.

Effect of primary mitral regurgitation on left ventricular synchrony.

Mitral regurgitation (MR) promotes left ventricular (LV) dilatation and eccentric remodeling. In the presence of LV dyssynchrony and heart failure, cardiac resynchronization therapy decreases the severity of MR. Whether primary MR can cause LV dyssynchrony is unknown. We investigated whether moderate to severe primary MR causes LV dyssynchrony in the presence of LV dilation and an ejection fraction (EF) >55%. We studied 37 normal subjects and 22 patients with moderate to severe MR and no coronary artery disease. Electrocardiographically gated cine and tagged cardiac magnetic resonance imaging was performed. Two-dimensional, maximum-circumferential shortening strain and time-to-peak strain (TTPS) were computed using harmonic-phase analysis of tagged magnetic resonance imaging. LV dyssynchrony was assessed by comparing TTPS delay of various LV quadrants and TTPS dispersion among the contralateral quadrants in patients with MR and normal subjects. Statistical comparison was done using a generalized linear model for repeated measurements. LV end-diastolic and LV end-systolic volumes were significantly larger in patients with MR versus normal subjects (207 +/- 11 vs 130 +/- 4 and 73 +/- 5 vs 47 +/- 2 ml, p <0.001). LVEF did not differ in patients with MR and normal subjects. The difference in the TTPS among various quadrants and the dispersion among the contralateral quadrants of the LV myocardium was similar between patients with MR and normal subjects. In conclusion, moderate to severe MR does not cause LV dyssynchrony in patients with LV dilatation and normal LVEF. Thus, cardiac resynchronization therapy in the absence of LV dyssynchrony may not decrease the severity of MR.

Double pseudoaneurysm, recurrent subvalvular aortic membrane and small left ventricular outflow tract in the same patient: who dares?

Patients with pseudoaneurysm in the left ventricular outflow tract (LVOT) commonly present vague and nonspecific symptoms making the diagnosis difficult. We present the case of a 37-year-old patient with two subvalvular pseudoaneurysms in whom a combined resection surgery, enlargement of the LVOT, aortic valve replacement (AVR) and aortic root replacement were performed using the technique of Cabrol.

Validación de la utilidad de los parámetros de deformación miocárdica para excluir el rechazo agudo tras el trasplante cardiaco: un estudio multicéntrico / Validation of the usefulness of 2-dimensional strain parameters to exclude acute rejection after heart transplantation: a multicenter study

Introducción y objetivos Algunos estudios indican que los parámetros de strain por speckle-tracking pueden ser una alternativa no invasiva a la biopsia endomiocárdica para excluir el rechazo celular agudo (RCA) moderado o grave (≥ 2R) tras el trasplante cardiaco (TxC). En una cohorte inicial, unos puntos de corte del 15,5% para el strain longitudinal global del ventrículo izquierdo (SLGVI) y el 17% para el strain de pared libre del ventrículo derecho mostraron un valor predictivo negativo del 100% para excluir RCA ≥ 2R. Nuestro objetivo es analizar la utilidad del strain y validar estos puntos de corte en una cohorte multicéntrica prospectiva externa.MétodosEstudio multicéntrico y prospectivo que incluyó a pacientes con seguimiento el primer año tras el TC. Se compararon los resultados de biopsias electivas con ecocardiogramas realizados el mismo día.ResultadosSe incluyó a 99 pacientes y 501 pares de biopsias-ecocardiogramas. El RCA ≥ 2R en las biopsias fue del 7,4%. El SLGVI y el strain longitudinal de pared libre del ventrículo derecho fueron menores durante los RCA ≥ 2R en el análisis univariante. En el análisis multivariante, el SLGVI se asoció de manera independiente con el RCA ≥ 2R. Los puntos de corte originales mostraron un valor predictivo negativo del 94,3% el RCA ≥ 2R.ConclusionesEste estudio mantiene un alto valor predictivo negativo para excluir RCA ≥ 2R tras el TxC y el SLGVI se asoció de manera independiente con el RCA ≥ 2R. El strain y, principalmente, el SLGVI pueden ser de utilidad en el diagnóstico y el tratamiento no invasivo del RCA. (AU)

Introduction and objectives Two-dimensional speckle-tracking echocardiography has emerged as a promising alternative to endomyocardial biopsy to rule out acute cellular rejection after orthotopic heart transplantation (OHT) in single center studies. In an original cohort, 15.5% and 17% of cutoff points for left ventricular global longitudinal strain (LVGLS) and free-wall right ventricular longitudinal strain, respectively, achieved 100% negative predictive value to exclude moderate or severe acute cellular rejection (ACR ≥ 2R). Our objective was to demonstrate the usefulness of speckle-tracking and validate these cutoff points in an external cohort.MethodsA prospective, multicenter study that included patients who were monitored during their first year after OHT was conducted. Echocardiographic studies analyzed by local investigators were compared with simultaneous paired endomyocardial biopsies samples.ResultsA total of 501 endomyocardial biopsy-echocardiographic studies were included in 99 patients. ACR≥2R was present in 7.4% of samples. LVGLS and free-wall right ventricular longitudinal strain were significantly reduced during ACR≥2R on univariate analysis. On multivariate analysis, LVGLS was independently associated with the presence of ACR≥2R. The original cutoff points demonstrated a negative predictive value of 94.3% to exclude ACR≥2R.ConclusionsThis study maintained a strong negative predictive value to exclude ACR≥2R after OHT and LVGLS was independently associated with the presence of ACR≥2R. We propose the use of speckle-tracking, especially LVGLS, as part of the noninvasive diagnosis and management of ACR. (AU)

Prognostic significance of ischemic mitral regurgitation after non-Q-wave acute myocardial infarction.

BACKGROUND AND AIM OF THE STUDY: The development of mitral regurgitation (MR) soon after acute myocardial infarction (AMI) is a recognized and frequent complication. Its negative impact on survival has been observed after Q-wave AMI, even when of a mild degree, and independently of left ventricular systolic function. Few data exist regarding MR after non-Q-wave AMI (nQ AMI), however. Hence, the study aim was to investigate the incidence, clinical predictors and prognostic implications of MR in the setting of nQ AMI. METHODS AND RESULTS: A total of 99 consecutive patients (37 men, 62 women; mean age 72 +/- 13 years) who suffered a nQ AMI was studied. All patients underwent echocardiography during the first week after the nQ AMI. MR was detected in 34 patients (17 men, 17 women; mean age 76 +/- 10 years). Events during follow up were coded as death, AMI, unstable angina, or heart failure. The in-hospital outcome was not significantly different between patients with and without MR. The mean follow up period was 663 +/- 574 days. In the univariate analysis, freedom from hospital survival was significantly greater in patients without MR. However, multivariate analysis showed that MR was not an independent predictor of cardiovascular hospitalization or death. CONCLUSION: The incidence of MR is high among patients with nQ AMI but, unlike results found with Q-wave AMI, its presence does not add any prognostic significance to other known negative factors in the setting of nQ AMI.

[Cardiac computed tomography: new applications of an evolving technique]. / Tomografía computarizada cardiaca: Nuevas aplicaciones de una técnica en evolución.

During the last years we have witnessed an increasing development of imaging techniques applied in Cardiology. Among them, cardiac computed tomography is an emerging and evolving technique. With the current possibility of very low radiation studies, the applications have expanded and go further coronariography In the present article we review the technical developments of cardiac computed tomography and its new applications.

[Hand-held echocardiographic devices: what do they add to the initial cardiovascular evaluation?]. / Ecocardiograma portátil: ¿qué añade a la valoración cardiovascular inicial?

INTRODUCTION AND OBJECTIVES: Hand-held echocardiographic devices have recently become available. Our objective was to determine, on the basis of clinical data and basic diagnostic techniques, whether hand-held devices offer additional information useful not provided by the initial cardiovascular diagnosis. PATIENTS AND METHOD: We prospectively studied the presence and severity (absent, mild, significative) of 7 frequent heart diseases (aortic or mitral stenosis-regurgitation, tricuspid regurgitation, and left ventricular systolic dysfunction-hypertrophy) in 36 consecutive patients (50% men; mean age 68 12 years) with 3 different methods: clinical examination and basic complementary exams, hand-held echocardiography with 2D and color Doppler imaging (OptiGo, Philips Medical Systems, The Netherlands) and a standard, last-generation transthoracic echocardiogram (Sonos 550, Philips Medical Systems, The Netherlands). We compared the results obtained with the first two methods, and combined the results of both to compare these findings against the results obtained with standard electrocardiography. Percentage agreement and Somer's D, a measure of association between ordinal variables, were calculated. RESULTS: The hand-held device obtained better results than clinical examination (agreement 87 vs. 65%; D = 0.79 0.04 vs. 0.19 0.53) and identified severe lesions that were classified incorrectly by clinical examination in 39% (14/36) patients. However, in 8 patients (10 evaluations) it misclassified severe lesions. CONCLUSIONS: In experienced hands, a hand-held echocardiographic device offers additional information not obtained from an initial cardiovascular diagnosis for common cardiovascular disorders, but it is no substitute for complete echocardiographic examination.

[Predictors of mortality following rescue percutaneous intervention]. / Factores predictores de mortalidad en la angioplastia de rescate.

INTRODUCTION AND OBJECTIVE: Rescue percutaneous transluminal coronary angioplasty (PTCA) is a mechanical reperfusion strategy aimed at achieving patency of the infarct-related artery after failed thrombolysis. However, in randomized studies the indication for rescue PTCA was per protocol rather than based on clinical criteria. The aim of this study was to determine predictors of mortality at 30 days following rescue percutaneous intervention. PATIENTS AND METHODS: Seventy-one consecutive patients who underwent rescue PTCA were included. Mean age was 61 (11) years, 80% were men and 9.8% had diabetes. RESULTS: The infarct-related artery was the left anterior descending artery in the 46.5%, and the mean percentage of stenoses was 91.0 (11.6)%. A stent was implanted in 97.2% and TIMI II-III flow was obtained in the 97.2% of the patients. Overall mortality was 9.8% at 30 days follow-up and 11.3% at 1 year follow-up. In the multivariate analysis, the independent predictors of mortality at 30 days were age (OR=1.2, 95% CI: 1.03-1.5, P=.001), Killip class III-IV (OR=20.1; 95% CI: 1.7-500; P=.003), PTCA failure (OR=indeterminate; P=.04) and left anterior descending artery involvement (OR=12.6; 95% CI: 0.7-214.9; P=.04). CONCLUSIONS: Rescue PTCA is effective in restoring blood flow in the infarct-related artery in the majority of patients in whom thrombolysis failed. The independent predictors of mortality were similar to those previously reported in acute myocardial infarction.

Infective endocarditis and caseous calcification of the mitral annulus: the odd couple.

Caseous calcification of the mitral annulus is an infrequent echocardiographic finding. The differential diagnosis includes other entities like tumors, abscess or thrombus. Both cardiac CT and cardiac MRI may be useful for its definitive diagnosis.

[Isolated left ventricular non-compaction associated with Ebstein's anomaly. Multimodality non-invasive imaging for the assessment of congenital heart disease]. / Miocardiopatía no compactada asociada a anomalía de Ebstein. Importancia de la imagen cardiaca multimodal en las cardiopatías congénitas.

To establish the etiology of heart failure in patients with congenital heart disease can be challenging. Multiple concomitant anomalies that can be missed after an initial diagnosis could be seen in these patients. In patients with congenital heart disease, a more accurate evaluation of cardiac morphology and left ventricular systolic function could be evaluated by recent non-invasive cardiac imaging techniques. We present a rare case where multimodal cardiac imaging was useful to establish the final diagnosis of left ventricular non-compaction associated with Ebstein's anomaly.

3D color-Doppler echocardiography and chronic aortic regurgitation: a novel approach for severity assessment.

BACKGROUND: 3D echocardiography provides a complete evaluation of the aortic valve and adjacent structures and it improves the assessment of this cardiac region. Three-dimensional color-Doppler echocardiography (3DCDE) evaluation might improve the measurements of the functional regurgitant orifice in patients with Chronic Aortic Regurgitation (CAR). OBJECTIVES: Our aim was to compare the accuracy of current echo-Doppler methods and 3DCDE for the assessment of CAR severity. The reference method used in this work was the CAR severity determined by means of cardiac magnetic resonance (CMR) METHODS: Thirty-two consecutive patients with an established diagnosis of CAR recruited in our institution comprised our study group. CAR severity was determined by conventional Echo-Doppler methods and by 3DCDE and their results were compared with those obtained by means of CMR. RESULTS: Mean age was 63.0 ± 13.5 years. Twenty-two patients (68.8%) were men. Compared with the traditional echo-Doppler methods, 3DCDE evaluation had the best linear association with CMR results (3D vena contracta cross sectional area method: r = 0.88; r square = 0.77; p < 0.001. 3D vena contracta cross sectional area/left ventricular outflow tract cross sectional area method: r = 0.87; r square = 0.75; p < 0.001). The ROC analysis showed an excellent area under curve for detection of severe CAR (3D vena contracta cross sectional area method = 0.97; 3D vena contracta cross sectional area/left ventricular outflow tract cross sectional area method = 0.98). Inter- and intra-observer variability for the 3DCDE evaluation was good (ICC = 0.89 and ICC = 0.91 for inter and intra observer variability respectively). CONCLUSIONS: 3DCDE is an accurate and highly reproducible diagnostic tool for estimating CAR severity. Compared with the traditional echo-Doppler methods, 3DCDE has the best agreement with the CMR determined CAR severity. Thus, 3DCDE is a diagnostic method that may improve the therapeutic management of patients with CAR.