Factores que inciden en la separación familiar

Left ventricular hypertrophy is defined as an increase in left ventricular mass which can be secondary to an increase in wall thickness, an increase in cavity size or both. It may be concentric, eccentric or appear as a disproportionate septal hypertrophy. It may also be physiologic. When the heart faces a hemodynamic burden, it can compensate by using the Frank-Starling mechanism to increase crossbridge formation; augment muscle mass to bear the entire load; recruit neurohormonal mechanisms to increase contractility. This increase in mass is due to the hypertrophy of existing myocytes rather than hyperplasia because cardio-myocytes become terminally differentiated soon after birth. According to LaPlace’s law, the load on any region of the myocardium is given as:

(pressure x radius) / 2 x wall thickness

Thus an increase in pressure can be offset by an increase in wall thickness. Cardiac myosins undergo an adult-to-fetal isoform transition in various models of hypertrophy. In the adult myocardium, the mRNAs encoding the fetal isoforms of alpha-actin and sarcomeric tropomyosin are re-expressed within two days in response to pressure overload. The c-fos and c-myc proto-oncogenes and a major heat shock protein gene (hsp70) are induced in the ventricular myocardium within one hour after imposition of pressure overload.⁸² It is generally believed that a mechanical signal initiates a cascade of biological events leading to coordinated cardiac growth. Within hours after a pressure overload occurs in the heart in vivo, myosin heavy chain synthesis increases by approximately 35%. This increase is initially mediated by an increase in translational efficiency.^83,84 In contradistinctionin severe pure volume overload, much of the increase

degradation rate.⁸⁵ Although the initial dilatation may be compensatory to maintain stroke volume, adverse remodeling often develops whereby the ventricle becomes progressively more spherical and wall stress increases perpetuating the dilation.

Concentric hypertrophy (increase in ratio of wall thickness/chamber dimension) and eccentric hypertrophy (cavity dilatation with a decrease in ratio of wall thickness/chamber dimension) are usually accompanied by complex changes in gene reprogramming.⁸⁶ These changes include the re-expression of immature fetal cardiac genes, such as genes that modify motor unit composition and regulation, genes that modify energy metabolism, genes that encode components of hormonal pathways e.g.

atrial natriuretic peptide, angiotensin converting enzyme. In addition, variable or later blunted expression occurs in other genes that modify intracellular ion homeostasis (e.g.

downregulation of sarcoplasmic reticulum calcium ATPase [SERCA-2], with variable upregulation of the Na⁺/Ca⁺ exchanger), and key parasympathetic and sympathetic receptors are downregulated e.g. (downregulation of beta1-adrenergic receptors and M2 muscarinic receptors and increase in ratio of angiotensin II AT2 to AT1 receptor subtypes). Some of these switches, such as the increased expression of the slow myosin ATPase isoform beta-myosin heavy chain relative to the fast myosin ATPase isoform alpha-myosin heavy chain, are adaptive and promote a more favorable myoenergetic economy. However, the long term functional implications of many of the changes in gene expression are still unclear in the context of integrated cardiovascular function in vivo.

The essence of hypertrophy is an increase in the number of force-generating units (sarcomeres) in the myocyte). Multiple tyrosine-phosphorylated kinases and serine-threonine kinases that are implicated in the signaling of hypertrophy can be found in the extracellular matrix (ECM).⁸⁷ Although critical proximal steps in mechanosignal transduction are not yet well understood, there is now evidence that the disruption of cell-cell and cell-cell-ECM contact is sufficient in itself to modulate both cell-cell growth and apoptosis.⁸⁸ In chronic hypertrophy, there are changes in intergrin expression⁸⁹ and possible intergrin shedding into adjacent ECM,⁹⁰ which raises the potential for disordered biochemical signal transduction for growth and suboptimal myocyte-ECM coupling for force generation. For myocyte growth to support an increased biomechanical load, it must be accompanied by coordinated increases in the surrounding architecture of connective tissue and ground substance, as well as the capillary and nerve networks. The connective tissue itself is primarily composed of collagen with smaller amounts of elastin, laminin and fibronectin. Although collagen types I, III and V are found in the myocardium, type I comprises approximately 85% of the total collagen in the area. The complex collagen weave provides a mechanism for translating individual myocyte force

generation into ventricular contraction, it restrains the development of interstitial edema and it is responsible for much of the ventricle’s passive diastolic stiffness.⁹¹

In pressure-overload hypertrophy, the increase in collagen production that occurs as an adaptation to overload, must be distinguished from pathological collagen deposition which is characterized by both perivascular and interstitial fibrosis.^91-94 ECM remodeling

seems to be very different in volume-overload hypertrophy in which cavity dilatation occurs in part due to both myocyte elongation and changes in collagen cross-linking and the collagen weave.^95-98 Dissolution of the collagen weave leads to increased elasticity, muscle fiber slippage and an increase in chamber size.⁹⁹ Such dissolution is predominantly related to the activation of matrix metalloproteinases (MMPs), a family of zinc-containing proteins that include stromalysins, collagenases, gelatinases and membrane type MMPs.^100-101

2.9.1.1 DIAGNOSIS OF LVH

The following have been used to diagnose left ventricular hypertrophy:

Chest x-ray: The cardiothoracic ratio is used for the assessment of cardiomegaly. A ratio

>0.5 is defined as cardiomegaly. A left ventricular preponderance may be observed on inspection.

Electrocardiography: Various criteria exist for the diagnosis of LVH.¹³¹ These include:

Sokolo-Lyon, Araoye, Cornell, Romhilt-Estes, Novacode criteria amongst others. The Sokolo-Lyon criterion (SV1+RV 5/6) detects LVH with a sensitivity of 22% and a specificity of 79%¹⁰². Another study done in blacks showed a sensitivity of 65.7% and specificity of 76.8%.⁸³ In the same study Araoye’s criterion: SV2 + RV6 > 35mm (females) & > 40mm (males) showed a sensitivity of 71.4% and specificity of 74.4%.⁸³ This did not differ significantly from Sokolo-Lyon criterion.

Echocardiography: Pathological hypertrophy may be associated with an absence of symptoms for several years before the development of heart failure or in unexpected

sudden death. In contemporary clinical practice and population studies therefore, the diagnosis of LVH depends predominantly on echocardiographic measurements or other noninvasive imaging techniques. Methods for 2D targeted M-mode echocardiographic measurements of left ventricular dimensions and the calculation of LV mass with the anatomically validated formula are described above. The detection of pathological LVH requires adjustments for sex, height and body surface area. Adjustment for body surface area however, tends to give lower values in obesity. LVM indexed to height^2.7 in the obese subject has been found to be more accurate.

Magnetic Resonance imaging: This is a highly accurate and validated method for the assessment of LVH and LV geometry.¹⁰³ Its use is however limited by its exorbitant cost.

A validation of this method showed a close correlation with echocardiographically derived LVM.¹⁰⁴

Ultra fast computed tomography: This is another imaging modality that is accurate and reproducible. It employs the use of radiation and is also expensive.

Angiography: LV mass can be determined from angiography with formulae which have been validated.¹⁰⁵ LV mass by angiography correlates modestly with echocardiographically derived values. Its use is however limited by its invasive nature.¹⁰⁵

Post Mortem: LVH may also be diagnosed post mortem. Devereux et al¹⁵⁰ from post mortem studies determined the mean total left ventricular weight. This gives an absolute value for LVM. However, it is known that LVM is affected by gender and anthropometric indices.

2.9.1.2 PROGNOSTIC IMPLICATION OF LVH

The Framingham Heart study has unequivocally demonstrated the prognostic value of echocardiographically detected LVH.¹⁰⁶ Subjects with LVH are older, more obese, have higher blood pressures and are more likely to have pre-existing coronary disease. LVH predicts an increased risk of cardiovascular morbidity and death, even after adjustment for other major risk factors (age, blood pressure, obesity, pulse pressure, diabetes, cholesterol profile, hypertension treatment, cigarette smoking). A limitation of these data is that the Framingham Heart Study is composed predominantly of white adults. The prevalence of echocardiographic LVH is reported to be higher in black adults and LVH is associated with a doubling of mortality in both black and white cohorts.¹⁰⁶

2.10 MEASURES OF BODY FAT