A New Coding System for the Identification of Left Ventricular Rotation Patterns and Their Relevance to Myocardial Function.

Rotational mechanics is a fundamental determinant of left ventricular ejection fraction (LVEF). The coding system currently employed in clinical practice does not distinguish between rotational patterns. We propose an alternative coding system that makes possible to identify the rotational pattern of the LV and relate it to myocardial function. Echocardiographic images were used to generate speckle tracking-derived transmural global longitudinal strain (tGLS) and rotational parameters. The existence of twist (basal and apical rotations in opposite directions) is expressed as a rotational gradient with a positive value that is the sum of the basal and apical rotation angles. Conversely, when there is rigid rotation (basal and apical rotations in the same direction) the resulting gradient is assigned a negative value that is the subtraction between the two rotation angles. The rotational patterns were evaluated in 87 healthy subjects and 248 patients with LV hypertrophy (LVH) and contrasted with their myocardial function. Our approach allowed us to distinguish between the different rotational patterns. Twist pattern was present in healthy controls and 104 patients with LVH and normal myocardial function (tGLS ≥ 17%, both). Among 144 patients with LVH and myocardial dysfunction (tGLS < 17%), twist was detected in 83.3% and rigid rotation in 16.7%. LVEF was < 50% in 34.7%, and all patients with rigid rotation had a LVEF < 50%. The gradient rotational values showed a close relationship with LVEF (r = 0.73; p < 0.001). The proposed coding system allows us to identify the rotational patterns of the LV and to relate their values with LVEF.

Myocardial Wringing and Rigid Rotation in Cardiac Amyloidosis.

Background: The motion of the heart is a result of the helicoidal arrangement of the myofibers in the organ's wall. We aimed to study the relationship between the wringing motion state and the degree of ventricular function in patients with cardiac amyloidosis (CA). Methods: Fifty patients with CA and decreased global longitudinal strain (LS) were evaluated using 2-dimensional speckle-tracking echocardiography. We have expressed LS as positive values to facilitate understanding. Normal twist, which occurs when basal and apical rotations occur in opposite directions, was coded as positive. When the apex and base rotate in the same direction (rigid rotation), twist was coded as negative. Left ventricular (LV) wringing (calculated as twist/LS, which takes into account actions that occur simultaneously during LV systole [ie, longitudinal shortening and twist]) was evaluated according to LV ejection fraction (LVEF). Results: Most of the patients (66%) who participated in the study were diagnosed with transthyretin amyloidosis. A positive relationship was observed between wringing and LVEF (r = 0.75, P < 0.0001). In advanced stages of ventricular dysfunction, rigid rotation appeared in 66.6% of patients with LVEF ≤ 40%, in whom negative values of twist and wringing were observed. LV wringing proved to be a good discriminator of LVEF (area under the curve 0.90, P < 0.001, 95% confidence interval 0.79-0.97); for example, wringing < 1.30°/% detected LVEF < 50% with 85.7% sensibility and 89.7% specificity. Conclusions: Wringing, which integrates twist and simultaneous LV longitudinal shortening, is a conditioning rotational parameter of the degree of ventricular function in patients with CA.

Contexte: Les mouvements du cœur sont le résultat de l'orientation hélicoïdale des fibres des parois du cœur. L'objectif de notre étude était d'étudier le lien entre le mouvement « d'essorage ¼ et la fonction ventriculaire chez les patients atteints d'amylose cardiaque (AC). Méthodologie: Cinquante patients atteints d'AC et présentant une déformation longitudinale (DL) globale réduite ont fait l'objet d'une évaluation à l'aide de l'échocardiographie bidimensionnelle de suivi des marqueurs acoustiques. Nous avons choisi d'exprimer la DL en valeurs positives pour faciliter la compréhension des données. Une torsion normale, caractérisée par les mouvements de rotation opposés entre la base et l'apex du cœur, a été codée comme positive. Lorsque l'apex et la base opéraient une rotation dans la même direction (rotation rigide), la torsion était codée comme négative. Le mouvement « d'essorage ¼ du ventricule gauche (VG) (calculé comme le rapport torsion/DL, qui tient compte des actions survenant simultanément durant la systole du VG [c.-à-d., raccourcissement longitudinal et torsion]) a été évalué en fonction de la fraction d'éjection du VG (FEVG). Résultats: La plupart des patients (66 %) ayant participé à l'étude avaient reçu un diagnostic d'amylose à transthyrétine. Un lien positif a été établi entre le mouvement d'essorage et la FEVG (coefficient de corrélation [r] = 0,75, p < 0,0001). Aux stades avancés de la dysfonction ventriculaire, une rotation rigide a été observée chez 66,6 % des patients ayant une FEVG ≤ 40 % et chez qui les valeurs de torsion et d'essorage étaient négatives. L'essorage du VG s'est révélé être un facteur fiable de détermination de la FEVG (aire sous la courbe : 0,90; p < 0,001, intervalle de confiance [IC] à 95 % : 0,79-0,97); par exemple, un mouvement d'essorage < 1,30 °/% a permis de détecter une FEVG < 50 % avec une sensibilité de 85,7 % et une spécificité de 89,7 %. Conclusions: Le mouvement d'essorage, qui intègre simultanément la torsion et le raccourcissement longitudinal du VG, est un paramètre rotationnel qui influence le degré de fonction ventriculaire chez les patients atteints d'AC.

The Role of Mitochondrial Dynamic Dysfunction in Age-Associated Type 2 Diabetes.

Mitochondrial dynamics, such as fusion and fission, play a critical role in maintaining cellular metabolic homeostasis. The molecular mechanisms underlying these processes include fusion proteins (Mitofusin 1 [MFN1], Mitofusin 2 [MFN2], and optic atrophy 1 [OPA1]) and fission mediators (mitochondrial fission 1 [FIS1] and dynamin-related protein 1 [DRP1]), which interact with each other to ensure mitochondrial quality control. Interestingly, defects in these proteins can lead to the loss of mitochondrial DNA (mtDNA) integrity, impairment of mitochondrial function, a severe alteration of mitochondrial morphology, and eventually cell death. Emerging evidence has revealed a causal relationship between dysregulation of mitochondria dynamics and age-associated type 2 diabetes, a metabolic disease whose rates have reached an alarming epidemic-like level with the majority of cases (59%) recorded in men aged 65 and over. In this sense, fragmentation of mitochondrial networks is often associated with defects in cellular energy production and increased apoptosis, leading, in turn, to excessive reactive oxygen species release, mitochondrial dysfunction, and metabolic alterations, which can ultimately contribute to ß-cell dysfunction and insulin resistance. The present review discusses the processes of mitochondrial fusion and fission and their dysfunction in type 2 diabetes, with special attention given to the therapeutic potential of targeting mitochondrial dynamics in this complex metabolic disorder.

Influence of Ventricular Wringing on the Preservation of Left Ventricular Ejection Fraction in Cardiac Amyloidosis.

BACKGROUND: The purpose of this work was to determine the influence of myocardial wringing on ventricular function in patients with cardiac amyloidosis (CA). METHODS: Fifteen healthy volunteers (group 1) and 34 patients with CA (17 with left ventricular ejection fractions [LVEFs] ≥ 53% [group 2] and 17 with LVEFs < 53% [group 3]) were evaluated using two-dimensional speckle-tracking echocardiography. A control group of mass-matched patients (n = 20) with left ventricular (LV) hypertrophy and LVEFs ≥ 53% was also included. Longitudinal strain (LS), circumferential strain, and LV twist and torsion were calculated. Deformation index (DefI), a new parameter of wringing, calculated as twist/LS, that takes into account actions that occur simultaneously during LV systole (i.e., longitudinal shortening and twist), was evaluated. Torsional and wringing parameters were calculated according to LVEF. RESULTS: Lower global values of LS and circumferential strain were observed among patients with CA (LS: group 1, -20.6 ± 2.5%; group 2, -11.6 ± 4.1%; group 3, -9.0 ± 3.1%; circumferential strain: group 1, -22.7 ± 4.9%; group 2, -14.4 ± 8.0%; group 3, -13.6 ± 3.8%; P < .001 for both). Torsion did not vary between group 2 and group 1 (2.5 ± 1.1°/cm vs 2.7 ± 0.8°/cm, P = NS). In contrast, DefI was greater in group 2 than in group 1 (-1.8 ± 0.8°/% vs -1.0 ± 0.3°/%, P < .01). Torsion and DefI were lower in group 3 (1.2 ± 0.7°/cm and -1.1 ± 0.6°/%, respectively, P < .001 for both) than in group 2. DefI was similar in patients with LV hypertrophy (-1.7 ± 0.6°/%, P = NS) and group 2. CONCLUSIONS: In patients with CA, preservation of LVEF depends on greater ventricular wringing. DefI, a parameter that integrates the twist and the simultaneous longitudinal shortening of the left ventricle, is a more accurate indicator of the efficacy of this mechanism.

Relationship Between Oxidative Stress, ER Stress, and Inflammation in Type 2 Diabetes: The Battle Continues.

Type 2 diabetes (T2D) is a metabolic disorder characterized by hyperglycemia and insulin resistance in which oxidative stress is thought to be a primary cause. Considering that mitochondria are the main source of ROS, we have set out to provide a general overview on how oxidative stress is generated and related to T2D. Enhanced generation of reactive oxygen species (ROS) and oxidative stress occurs in mitochondria as a consequence of an overload of glucose and oxidative phosphorylation. Endoplasmic reticulum (ER) stress plays an important role in oxidative stress, as it is also a source of ROS. The tight interconnection between both organelles through mitochondrial-associated membranes (MAMs) means that the ROS generated in mitochondria promote ER stress. Therefore, a state of stress and mitochondrial dysfunction are consequences of this vicious cycle. The implication of mitochondria in insulin release and the exposure of pancreatic ß-cells to hyperglycemia make them especially susceptible to oxidative stress and mitochondrial dysfunction. In fact, crosstalk between both mechanisms is related with alterations in glucose homeostasis and can lead to the diabetes-associated insulin-resistance status. In the present review, we discuss the current knowledge of the relationship between oxidative stress, mitochondria, ER stress, inflammation, and lipotoxicity in T2D.

Comprehensive assessment of left ventricular myocardial function by two-dimensional speckle-tracking echocardiography.

BACKGROUND: Left ventricular ejection fraction (LVEF) results from the combined action of longitudinal and circumferential contraction, radial thickening, and basal and apical rotation. The study of these parameters together may lead to an accurate assessment of the cardiac function. METHODS: Ninety healthy volunteers, categorized by gender and age (≤ 55 and >  55 years), were evaluated using two-dimensional speckle tracking echocardiography. Transversal views of the left ventricle (LV) were obtained to calculate circumferential strain and left ventricular twist, while three apical views were obtained to determine longitudinal strain (LS) and mitral annular plane systolic excursion (MAPSE). We established the integral myocardial function of the LV according to: 1. The Combined Deformation Parameter (CDP), which includes Deformation Product (DP) - Twist x LS (° x %) - and Deformation Index (DefI) -Twist / LS (° / %)-; and 2. the Torsion Index (TorI): Twist / MAPSE (° / cm). RESULTS: The mean age of our patients was 50.3 ± 11.1 years. CDP did not vary with gender or age. The average DP was - 432 ± 172 ° x %, and the average DefI was - 0.96 ± 0.36 ° / %. DP provides information about myocardial function (normal, pseudonormal, depressed), and the DefI quotient indicates which component (s) is/are affected in cases of abnormality. TorI was higher in volunteers over 55 years (16.5 ± 15.2 vs 13.1 ± 5.0 °/cm, p = 0.003), but did not vary with gender. CONCLUSIONS: The proposed parameters integrate values of twisting and longitudinal shortening. They allow a complete physiological assessment of cardiac systolic function, and could be used for the early detection and characterization of its alteration.

Myocardial Contraction during the Diastolic Isovolumetric Period: Analysis of Longitudinal Strain by Means of Speckle Tracking Echocardiography.

BACKGROUND: According to the ventricular myocardial band model, the diastolic isovolumetric period is a contraction phenomenon. Our objective was to employ speckle-tracking echocardiography (STE) to analyze myocardial deformation of the left ventricle (LV) and to confirm if it supports the myocardial band model. METHODS: This was a prospective observational study in which 90 healthy volunteers were recruited. We evaluated different types of postsystolic shortening (PSS) from an LV longitudinal strain study. Duration of latest deformation (LD) was calculated as the time from the start of the QRS complex of the ECG to the latest longitudinal deformation peak in the 18 segments of the LV. RESULTS: The mean age of our subjects was 50.3 ± 11.1 years. PSS was observed in 48.4% of the 1620 LV segments studied (19.8%, 13.5%, and 15.1% in the basal, medial, and apical regions, respectively). PSS was more frequent in the basal, medial septal, and apical anteroseptal segments (>50%). LD peaked in the interventricular septum and in the basal segments of the LV. CONCLUSIONS: The pattern of PSS and LD revealed by STE suggests there is contraction in the postsystolic phase of the cardiac cycle. The anatomical location of the segments in which this contraction is most frequently observed corresponds to the main path of the ascending component of the myocardial band. This contraction can be attributed to the protodiastolic untwisting of the LV.

Role of Oxidative Stress and Mitochondrial Dysfunction in Skeletal Muscle in Type 2 Diabetic Patients.

Type 2 diabetes can increase the risk of skeletal muscle dysfunction and, consequently, that of cardiovascular diseases, including coronary artery disease and stroke. It is also related to a reduced capacity for exercise, but the underlying mechanism is only partially understood. There are several factors that contribute to the development of skeletal muscle dysfunction, of which oxidative stress and mitochondrial dysfunction are among the most important. This review discusses the role of oxidative stress in the development and progression of skeletal and cardiac dysfunction associated with diabetes. It also provides an overview of the potential actions of antioxidants in general and mitochondria-targeted antioxidants in particular in the treatment of muscle dysfunction in type 2 diabetes.

[Predictive value of differential pulse pressure in the diagnosis of silent myocardial ischemia in patients with type-2 diabetes]. / Valor predictivo de la presión diferencial del pulso en el diagnóstico de isquemia miocárdica silente en pacientes con diabetes tipo 2.

Silent myocardial ischemia occurs more frequently in diabetics. Differential arterial pulse pressure is a valuable predictor of cardiovascular disease. We studied 48 consecutive male patients with type-2 diabetes and no known history of ischemic heart disease. Ambulatory monitoring of arterial pressure was carried out and the presence of silent myocardial ischemia was studied using a protocol that involved: resting ECG, echocardiography, 24-hour Holter ECG, conventional exercise stress testing, and exercise testing with nuclear scanning. Nine patients (19%) had silent myocardial ischemia. Differential pulse pressure had good discriminative ability in identifying the presence of silent ischemia: the area under the receiver operating characteristic (ROC) curve was 0.83 (95% confidence interval [CI], 0.71-0.96; P=.002). This predictive ability was also observed on adjusted logistic regression modeling (odds ratio [OR], 1.24, 95% CI = 1.02-1.49). We found that the OR for the risk of silent ischemia for every 10-mmHg increase in differential pulse pressure was 8.5 (95% CI 1.7-31.2). Age and differential pulse pressure were the only independent predictors of silent myocardial ischemia found in this study.

Valor predictivo de la presión diferencial del pulso en el diagnóstico de isquemia miocárdica silente en pacientes con diabetes tipo 2 / Predictive value of differential pulse pressure in the diagnosis of silent myocardial ischemia in patients with type-2 diabetes

La isquemia miocárdica silente es más frecuente en diabéticos. La presión arterial diferencial del pulso tiene valor como predictora de riesgo de enfermedad cardiovascular. Estudiamos a 48 varones diabéticos tipo 2 consecutivos sin antecedentes de cardiopatía isquémica. Realizamos medición ambulatoria de la presión arterial y un protocolo de estudio de isquemia miocárdica silente que incluyó: ECG en reposo, ecocardiograma, Holter-ECG-24 h y ergometría convencional y con isótopos radiactivos. Nueve pacientes (19%) presentaron isquemia miocárdica silente. La presión diferencial del pulso mostró buena capacidad discriminadora para determinar la presencia de isquemia silente (área bajo la curva [COR] = 0,83; intervalo de confianza [IC] del 95%, 0,71-0,96; p = 0,002). El efecto predictor se mantuvo en el modelo de regresión logística ajustado (odds ratio [OR] = 1,24; IC del 95%, 1,02-1,49). Estimamos una OR de 8,5 (IC del 95%, 1,7-31,2) por cada incremento de 10 mmHg de la presión diferencial del pulso para el riesgo de presentar isquemia silente. La edad y la presión diferencial del pulso fueron los únicos predictores independientes de isquemia miocárdica silente encontrados en este estudio (AU)

Silent myocardial ischemia occurs more frequently in diabetics. Differential arterial pulse pressure is a valuable predictor of cardiovascular disease. We studied 48 consecutive male patients with type-2 diabetes and no known history of ischemic heart disease. Ambulatory monitoring of arterial pressure was carried out and the presence of silent myocardial ischemia was studied using a protocol that involved: resting ECG, echocardiography, 24-hour Holter ECG, conventional exercise stress testing, and exercise testing with nuclear scanning. Nine patients (19%) had silent myocardial ischemia. Differential pulse pressure had good discriminative ability in identifying the presence of silent ischemia: the area under the receiver operating characteristic (ROC) curve was 0.83 (95% confidence interval [CI], 0.71-0.96; P=.002). This predictive ability was also observed on adjusted logistic regression modeling (odds ratio [OR], 1.24, 95% CI = 1.02-1.49). We found that the OR for the risk of silent ischemia for every 10-mmHg increase in differential pulse pressure was 8.5 (95% CI 1.7-31.2). Age and differential pulse pressure were the only independent predictors of silent myocardial ischemia found in this study (AU)

Quantification of proinflammatory cytokines in the urine of congestive heart failure patients. Its relationship with plasma levels.

AIMS: Proinflammatory cytokines are important mediators for the development of heart failure and increased plasma levels of these cytokines have been reported in patients with this condition. The purpose of the study was to investigate whether urine, a non-invasively obtained biological sample, was an appropriate medium in which to measure the concentration of tumor necrosis factor-alpha (TNF-alpha) and interleukin-6 (IL-6) in patients in the advanced stages of the disease. METHODS AND RESULTS: Thirty consecutive patients who had severe congestive heart failure (NYHA classes III and IV) and 30 matched healthy control subjects were enrolled. Plasma and the first urine of the day were collected and TNF-alpha and IL-6 were quantitatively analyzed by enzyme-linked immunosorbent assays. For every subject there were no differences in the amount of cytokine determined in plasma and urine. Both urine and plasma levels of IL-6 and TNF-alpha were greater in heart failure patients than in controls. CONCLUSION: Our results show that plasmatic and urinary levels of proinflammatory cytokines did not differ significantly. Thus, urine may be a good milieu in which to study these cytokines and may have diagnostic, prognostic and therapeutic implications.

Cortocircuito izquierda-derecha por fístulas coronarias congénitas / Left to right shunt for congenital coronary arterio-venous fistulas

Las fístulas coronarias congénitas son una cardiopatía poco frecuente que, dejada a su evolución, puede producir clínica de hipertensión pulmonar e insuficiencia cardíaca e isquemia miocárdica, aunque en un porcentaje no despreciable pueden cerrarse espontáneamente. Además, son posibles las complicaciones por endocarditis, rotura, aneurisma o trombosis. Los pacientes afectados están en su gran mayoría asintomáticos y los métodos usualmente empleados para su detección son la ecocardiografía-Doppler y la angiografía. Presentamos el caso de un varón de 10 años, asintomático, remitido para estudio de soplo cardíaco, con tres fístulas, dos de ellas originadas en la arteria coronaria izquierda que drenaban al ventrículo derecho, y otra con origen en coronaria derecha y drenaje en la arteria pulmonar (AU)

Síndrome antifosfolípido con infarto de miocardio y afectación valvular aórtica / Antiphospholipid syndrome with myocardial infarction and aortic valve involvement

El síndrome antifosfolípido primario se caracteriza por trombosis arteriales y/o venosas, trombocitopenia, abortos de repetición o muerte fetal y anticuerpos antifosfolípido elevados. La afectación valvular provoca con mayor frecuencia regurgitación y se asocia a trombosis arterial. Se presenta el caso de un varón joven con diagnóstico de síndrome antifosfolípido primario y antecendentes de trombosis cerebrovascular, que ingresó por infarto subagudo de miocardio. La coronariografía demostró estenosis en las arterias coronaria derecha y descendente anterior, practicándose con éxito angioplastia transluminal percutánea sobre esta última. El ecocardiograma transtorácico demostró afectación valvular aórtica con regurgitación predominante, y el transesofágico la presencia de excrecencias sobre los velos aórticos. El estudio de laboratorio puso de manifiesto trombocitopenia, alargamiento del tiempo parcial de tromboplastina activada y anticuerpos anticardiolipina elevados. Se inició tratamiento anticoagulación oral. Tras tres meses de seguimiento, no se ha observado recurrencia alguna de los fenómenos trombóticos (AU)