Insights into the effects of Friedreich ataxia on the left ventricle using T1 mapping and late gadolinium enhancement.

Background: The left ventricular (LV) changes which occur in Friedreich ataxia (FRDA) are incompletely understood.

Methods: Cardiac magnetic resonance (CMR) imaging was performed using a 1.5T scanner in subjects with FRDA who are homozygous for an expansion of an intron 1 GAA repeat in the FXN gene.

The reduction of the left ventricular long-axis early diastolic peak velocity (e') evident by early-middle age occurs in the absence of aging-related slowing of active relaxation.

Purpose: A decrease in the left ventricular (LV) long-axis early diastolic peak velocity (e') is evident by early-middle age, but it is unknown to what extent this decrease is due to slowing of the speed of active relaxation versus a reduction in LV long-axis excursion during early diastole (EDExc).

Methods: Pulsed-wave tissue Doppler imaging (TDI) signals were acquired from the septal and lateral borders of the mitral annulus in 62 healthy adult subjects of age 18-45 years. EDExc and LV systolic excursion (SExc) were measured as the integrals of the respective TDI signals.

Dobutamine effects on systolic and diastolic left ventricular long-axis excursion and timing - significance for the interpretation of s' and e'.

Background: Dobutamine effects on the relationships of the peak velocity of left ventricular (LV) long-axis systolic motion (s') with systolic excursion (SExc), systolic duration (SDur) and heart rate, of LV long-axis early diastolic excursion (EDExc) with SExc, and of the peak velocity of LV long-axis early diastolic motion (e') with EDExc, early diastolic duration (EDDur) and isovolumic relaxation time (IVRT') are unknown.

Methods: Two groups of adult subjects, one young and healthy ( = 10), and one with impaired LV long-axis function ( = 10), were studied, with the aim of identifying consistent findings for the two groups and for the septal and lateral walls. Dobutamine was infused at doses of 5 and 10 µg/kg/min.

Determinants of left ventricular structure, filling and long axis function in systemic sclerosis.

Background: Abnormalities of left ventricular (LV) structure, filling and long-axis function have all been reported in subjects with systemic sclerosis (SSc) and a normal LV ejection fraction (EF), but previous study findings have not been consistent. The aim of this study was to identify factors which could have confounded the analyses in previous studies of SSc, and in particular to consider the variables of body surface area (BSA), sex, age, heart rate, blood pressure (BP), disease duration (DD), disease type (limited versus diffuse) and interstitial lung disease (ILD).

Methods: Echocardiography was performed on 100 subjects with SSc (79 women; age 56±15 years) with a LVEF ≥50% and free of pulmonary arterial hypertension, coronary artery disease, more than mild valvular heart disease and atrial fibrillation.

Changes in left ventricular size, geometry, pump function and left heart pressures during healthy aging.

There are cross-sectional and longitudinal imaging studies using echocardiography and cardiac magnetic resonance in healthy adult subjects which have demonstrated associations of left ventricular (LV) structure and pump function with age. There are also cross-sectional data regarding the relationships of age with invasively measured left heart chamber pressures. Increasing age is associated with decreases in LV end-diastolic volume (LVEDV), end-systolic volume (LVESV), end-diastolic length (LVEDL), stroke volume (SV) and cardiac output (CO), and increases in relative wall thickness (RWT), LV mass/LVEDV ratio (LVMVR) and ejection fraction (LVEF).

Left ventricular long-axis function in hypertrophic cardiomyopathy - Relationships between e`, early diastolic excursion and duration, and systolic excursion.

Background: The peak velocity of early diastolic mitral annular motion (e`) is believed to provide sensitive detection of left ventricular (LV) diastolic dysfunction in hypertrophic cardiomyopathy (HCM), but other aspects of LV long-axis function in HCM have received less attention. Systolic mitral annular excursion (SExc) is also reduced in HCM and must be an intrinsic limitation to the extent of the subsequent motion during diastole. However, the effects of HCM on excursion during early diastole (EDExc) and atrial contraction (AExc), the duration of early diastolic motion (EDDur), and the relationships of EDExc with SExc, and of e`with EDExc and EDDur, are all unknown.

Relationships of global longitudinal strain with s`, long-axis systolic excursion, left ventricular length and heart rate.

Background: Longitudinal left ventricular (LV) contraction can be impaired in the presence of a normal LV ejection fraction (LVEF), and abnormalities have been reported in global longitudinal strain (GLS), long-axis systolic excursion (SExc), and the peak systolic velocity (s`) of mitral annular motion using tissue Doppler imaging (TDI). However, the relationships of GLS with s` and SExc have not been systematically evaluated in subjects with a normal LVEF, and whether these relationships might be affected by variations in LV end-diastolic length (LVEDL) and heart rate is unknown.

Methods: We investigated the univariate and multivariate correlations of GLS with TDI measurements of s` and SExc (both using averages of the septal and lateral walls), LVEDL and heart rate in subjects with a normal LVEF (>50%) but a low peak early diastolic mitral annular velocity (septal e`≤ 7.

Understanding preload and preload reserve within the conceptual framework of a limited range of possible left ventricular end-diastolic volumes.

Preload has been variously defined, but if there is to be a direct relationship with activity of the Frank-Starling mechanism in its action to increase the force and extent of contraction, preload must directly reflect myocardial stretch. The Frank-Starling mechanism is activated during any stretch of a cardiac chamber beyond its resting size, which is present immediately before contraction. Every left ventricle has an intrinsic and limited range of possible volumes at end diastole.

Left ventricular structural and functional changes in Friedreich ataxia - Relationship with body size, sex, age and genetic severity.

Introduction: Although a concentric pattern of left ventricular (LV) geometry appears to be common in Friedreich ataxia (FRDA), there is no accepted method for diagnosing LV abnormalities in FRDA, sex and body size have often not been taken into consideration, and it has not been clear whether children and adults should be classified using the same criteria. The aim of this study was to better define the LV geometric changes in FRDA with respect to sex, body size and subject age, and to investigate the relationship of LV changes with genetic severity, as assessed by GAA repeat length within the shorter allele of the FXN gene (GAA1).

Methods: Echocardiography was performed in 216 subjects (68 children, 148 adults), measurements were made at end-diastole of LV internal diameter (LVEDID), septal wall thickness (SWT), LV length (LVEDL) and LV volume (LVEDV), and calculations were made of relative wall thickness (RWT), LV mass and LV ejection fraction (LVEF).

Correction: Aging and the relationships between long-axis systolic and early diastolic excursion, isovolumic relaxation time and left ventricular length-Implications for the interpretation of aging effects on e`.

[This corrects the article DOI: 10.1371/journal.pone.

Aging and the relationships between long-axis systolic and early diastolic excursion, isovolumic relaxation time and left ventricular length-Implications for the interpretation of aging effects on e`.

Background: Both the left ventricular (LV) long-axis peak early diastolic lengthening velocity (e`) and long-axis early diastolic excursion (EDExc) decrease with age, but the mechanisms underlying these decreases are not fully understood. The aim of this study was to investigate the relative contributions to aging-related decreases in e`and EDExc from LV long-axis systolic excursion (SExc), isovolumic relaxation time (IVRT, as a measure of the speed of relaxation) and LV end-diastolic length (LVEDL).

Methods: The study group was 50 healthy adult subjects of ages 17-75 years with a normal LV ejection fraction.

Differences in the determinants of right ventricular and regional left ventricular long-axis dysfunction in Friedreich ataxia.

Background: Friedreich ataxia (FRDA) is an autosomal recessive neurodegenerative condition which also has effects on the heart. In 96% of affected individuals FRDA is due to homozygosity of a GAA repeat expansion in intron 1 of the frataxin (FXN) gene. The number of GAA repeats have been shown to relate to disease severity in FRDA, this thought to be via an inverse relationship of GAA repeat number and cellular frataxin levels.

Left ventricular long axis tissue Doppler systolic velocity is independently related to heart rate and body size.

Background: The physiological factors which affect left ventricular (LV) long-axis function are not fully defined. We investigated the relationships of resting heart rate and body size with the peak velocities and amplitudes of LV systolic and early diastolic long axis motion, and also with long-axis contraction duration.

Methods: Two groups of adults free of cardiac disease underwent pulsed-wave tissue Doppler imaging at the septal and lateral mitral annular borders.

Possible Mechanisms Underlying Aging-Related Changes in Early Diastolic Filling and Long Axis Motion-Left Ventricular Length and Blood Pressure.

Background: The transmitral E wave and the peak velocity of early diastolic mitral annular motion (e`) both decrease with age, but the mechanisms underlying these age-related changes are incompletely understood. This study investigated the possible contributions of blood pressure (BP) and left ventricular end-diastolic length (LVEDL) to age-related reductions in E and e`.

Methods: The study group were 82 healthy adult subjects <55 years of age who were not obese or hypertensive.

Benign Cardiac Effects of Hemoglobin H Disease.

Background/aims: Hemoglobin H (HbH) disease is associated with iron overload, but whether this results in serious cardiac or vascular sequelae is unresolved.

Methods: We identified 39 adult subjects (age 42 ± 12 years, 13 men) with HbH disease who had undergone echocardiography, 27 of whom had also undergone cardiac and liver magnetic resonance assessment of iron loading using T2*-weighted imaging.

Results: None of the subjects had a history of heart failure or arrhythmias.

"Left ventricular filling pressure(s)" - Ambiguous and misleading terminology, best abandoned.

The use of the terms "left ventricular filling pressure" and "left ventricular filling pressures" is widespread in the cardiology literature, but the meanings ascribed to these terms have not been consistent. Left ventricular end-diastolic pressure (LVEDP) and mean left atrial pressure (LAP) cannot be used interchangeably as they will often differ in magnitude in the presence of cardiac disease and they also have different clinical significance. LVEDP is the best pressure to use when considering left ventricular function, whereas mean LAP is the most relevant pressure when considering the tendency to pulmonary congestion.

An open-label trial in Friedreich ataxia suggests clinical benefit with high-dose resveratrol, without effect on frataxin levels.

Friedreich ataxia (FRDA) is due to a triplet repeat expansion in FXN, resulting in deficiency of the mitochondrial protein frataxin. Resveratrol is a naturally occurring polyphenol, identified to increase frataxin expression in cellular and mouse models of FRDA and has anti-oxidant properties. This open-label, non-randomized trial evaluated the effect of two different doses of resveratrol on peripheral blood mononuclear cell (PBMC) frataxin levels over a 12-week period in individuals with FRDA.