Normal Left Ventricular Mass Research Articles

Cardiovascular Status of Childhood Cancer Survivors Exposed and Unexposed to Cardiotoxic Therapy

To determine whether cardiovascular abnormalities in childhood cancer survivors are restricted to patients exposed to cardiotoxic anthracyclines and cardiac irradiation and how risk factors for atherosclerotic disease and systemic inflammation contribute to global cardiovascular status. We assessed echocardiographic characteristics and atherosclerotic disease risk in 201 survivors of childhood cancer with and without exposure to cardiotoxic treatments at a median of 11 years after diagnosis (range, 3 to 32 years) and in 76 sibling controls. The 156 exposed survivors had below normal left ventricular (LV) mass, wall thickness, contractility, and fractional shortening and above normal LV afterload. The 45 unexposed survivors also had below normal LV mass overall, and females had below normal LV wall thickness. Exposed and unexposed survivors, compared with siblings, had higher levels of N-terminal pro-brain natriuretic peptide (81.7 and 69.0 pg/mL, respectively, v 39.4 pg/mL), higher mean fasting serum levels of non-high-density lipoprotein cholesterol (126.5 and 121.1 mg/dL, respectively, v 109.8 mg/dL), higher insulin levels (10.4 and 10.5 μU/mL, respectively, v 8.2 μU/mL), and higher levels of high-sensitivity C-reactive protein (2.7 and 3.1 mg/L, respectively, v 0.9 mg/L; P < .001 for all comparisons). Age-adjusted, predicted-to-ideal 30-year risk of myocardial infarction, stroke, or coronary death was also higher for exposed and unexposed survivors compared with siblings (2.16 and 2.12, respectively, v 1.70; P < .01 for both comparisons). Childhood cancer survivors not receiving cardiotoxic treatments nevertheless have cardiovascular abnormalities, systemic inflammation, and an increased risk of atherosclerotic disease. Survivorship guidelines should address cardiovascular concerns, including the risk of atherosclerotic disease and systemic inflammation, in exposed and unexposed survivors.

Prevalence of residual left ventricular structural changes after one year of antihypertensive treatment in patients of African descent : role of 24-hour pulse pressure

One year of antihypertensive therapy may normalise left ventricular (LV) structure in 51% of hypertensive patients of European descent. Whether similar effects can be achieved in patients of African descent, who have a high prevalence of concentric LV hypertrophy (LVH) and remodelling, is unknown. In 103 hypertensive patients in the Baragwanath Hypertension study we evaluated the prevalence of residual LV structural changes (echocardiography) after four and 13 months of stepwise antihypertensive therapy. After 13 months of therapy, 24-hour blood pressure control was achieved in 47% of patients. At baseline, 51.5% of patients had concentric LVH, 19% eccentric LVH and 12% concentric LV remodelling. Despite changes in LV mass index (p < 0.01) and relative wall thickness (p < 0.05) with treatment, the proportion of patients with a normal LV mass or geometry increased only from 17.5 to 25% (p > 0.05), while 26% remained with concentric LVH (p < 0.001 compared to baseline), 25% with eccentric LVH and 23% with concentric LV remodelling (p < 0.05 compared to baseline). Residual structural changes were associated with 24-hour pulse pressure (p = 0.02), but not with 24-hour systolic or diastolic blood pressure or clinic blood pressure. Even after a year of antihypertensive therapy, a high proportion (74%) of hypertensives of African ancestry retained residual LV structural changes, an effect that was associated with 24-hour pulse pressure but not systolic or diastolic blood pressures or clinic blood pressure in this ethnic group.

Left Ventricular Volumes, Mass and Function Normalized to the Body Surface Area, Age and Gender From CMR in a Large Cohort of Well-Treated Thalassemia Major Patients without Myocardial Iron Overload

Abstract 1090Introduction. Cardiovascular Magnetic Resonance (CMR) allows an accurate and reproducible quantification of left ventricular (LV) parameters. In Thalassemia major (TM) patients different “normal” LV values have been reported due to chronic anemia and eventually pre-existing iron burdens. Moreover, in this population it is unknown the influence of sex and age on LV parameters and no ranges of normal have been reported using MASS® software. The aim of this study was to establish the ranges for normal LV volumes, mass and ejection fraction normalized to the influence of body surface area (BSA), age and sex from CMR in a large cohort of well-treated TM patients without myocardial iron overload.Methods. Among the 923 TM patients who underwent CMR within the MIOT network for the assessment of cardiac iron overload, function and fibrosis, we selected 142 patients with no known risk factors or history of cardiac disease, normal electrocardiogram, no myocardial fibrosis and no myocardial iron overload (all the cardiac segments with a normal T2* value). All patients had been regularly transfused and chelated since early childhood. Moreover, we studied 71 healthy subjects matched for age and sex. LV function parameters were quantitatively evaluated in a standard way by SSFP cine images using MASS® software. LV end-diastolic volume, end-systolic volume, stroke volume, and mass were normalized to BSA (EDVI, ESVI, SVI, massI).Results. The table shows the comparison of the CMR parameters with differentiation for sex and age in TM patients and healthy subjects and the cut-off of normality defined as mean – or + 2 standard deviation (SD). TM patients showed significantly lower BSA than the controls (P<0.0001). Significantly higher EDVI and SVI were found only for males < 14 years and > 30 years. Significantly higher LVEF were found only for males < 14 years. In TM patients all LV volumes indexes were significantly larger in males than in females (P<0.0001 in all cases). The EF was not different between the sexes. In males the ESVI and the EF were significant different among the age groups (P=0.006 and P=0.001, respectively). In females no significant differences were detected among the age groups.<1414–2020–3030–40>=40TMHPTMHPTMHPTMHPTMHPMalesN=7N=7N=6N=6N=25N=15N=23N=11N=6N=5EDVI (ml/m2)94 ± 18 (130)75 ± 110.03496 ± 20 (136)91 ± 200.715103 ± 17 (137)101 ± 130.68692 ± 15 (122)80 ± 110.02294 ± 9 (112)75 ± 110.013ESVI (ml/m2)31 ± 6 (43)24 ± 60.05838 ± 8 (54)35 ± 140.67038 ± 8 (54)39 ± 90.67632 ± 6 (44)29 ± 60.16029 ± 6 (41)28 ± 100.816SVI (ml/m2)63 ± 14 (91)51 ± 70.05057 ± 12 (81)56 ± 80.86865 ± 10 (85)62 ± 90.43359 ± 10 (79)51 ± 100.02764 ± 8 (80)47 ± 80.007Mass I (g/m2)57 ± 7 (71)68 ± 50.00757 ± 13 (83)71 ± 70.04366 ± 12 (90)77 ± 120.00662 ± 12 (86)66 ± 100.18468 ± 16 (100)74 ± 110.536EF (%)66 ± 4 (58)54 ± 6<0.000160 ± 2 (56)66 ± 140.32263 ± 3 (57)62 ± 60.52065 ± 3 (59)65 ± 80.97268 ± 6 (56)62 ± 90.234FemalesN=2N=2N=8N=6N=24N=6N=33N=8N=8N=5EDVI (ml/m2)63 ± 8 (79)62 ± 40.95181 ± 8 (97)80 ± 90.86683 ± 16 (115)78 ± 90.49977 ± 11 (99)79 ± 100.66982 ± 19 (120)77 ± 160.614ESVI (ml/m2)23 ± 1 (25)22 ± 80.82330 ± 6 (42)31 ± 30.78930 ± 8 (46)30 ± 40.88326 ± 6 (38)29 ± 70.21628 ± 8 (44)28 ± 120.974SVI (ml/m2)40 ± 7 (54)41 ± 40.91949 ± 3 (55)49 ± 60.89253 ± 9 (71)48 ± 60.23451 ± 6 (63)50 ± 80.91554 ± 11 (76)49 ± 60.394Mass I (g/m2)34 ± 3 (40)59 ± 190.29647 ± 8 (63)56 ± 60.04053 ± 9 (71)54 ± 120.89352 ± 9 (70)55 ± 130.46551 ± 12 (75)56 ± 50.344EF (%)63 ± 3 (57)46 ± 170.38863 ± 4 (55)62 ± 40.69465 ± 5 (55)62 ± 30.13766 ± 5 (56)63 ± 70.27166 ± 4 (58)63 ± 70.254Conclusions. In a large cohort of well-treated TM patients significant differences in LV parameters compared to controls were limited to males < 14 years and > 30 years. Due to the influence of BSA, sex and age, appropriate “normal” reference ranges normalized these variables should be used to avoid misdiagnosis of cardiomiopathy in TM patients. Disclosures:No relevant conflicts of interest to declare.

Left Atrial Remodeling and Response to Valsartan in the Prevention of Recurrent Atrial Fibrillation

Background— Left atrial (LA) dilation precedes or appears early after the onset of atrial fibrillation (AF) and factors in perpetuating the arrhythmia. Angiotensin receptor blockers were proposed for reversing LA remodeling. We evaluated the effect of valsartan on LA remodeling in patients with a recent episode of AF and the effect of LA size on AF recurrence (AFr). Methods and Results— LA and left ventricular (LV) echocardiographic variables were measured at baseline and 6 and 12 months in 340 patients from GISSI-AF, a trial testing valsartan prevention of AFr. Reversal of remodeling was considered as a decrease in LA size over 12 months. Changes in patients with and without recurrence and the relationship to duration of AFr were analyzed. Patients were 68.4±8.8 years old, with history of hypertension (85.3%) and cardioversion in the previous 2 weeks (87.4%) or ≥2 AFr in the previous 6 months (40.4%). Baseline LA maximal volume (LAVmax) was severely increased (&gt;40 mL/m 2 ); LV dimensions and function were relatively normal. Over 12 months, 54.4% of patients had AFr. LAVmax was unchanged by rhythm, time, or randomized treatment. Higher baseline LAVmax and lower LA emptying fraction were linearly related to increasing AFr duration during follow-up. Conclusions— GISSI-AF patients in sinus rhythm and history of AF showed severely increased LAVmax with mostly normal LV volume, mass, and systolic and diastolic function. Valsartan for 1 year did not reverse LA remodeling or prevent AFr. Half of the patients without AFr had severe LA dilation; therefore, mechanisms other than structural remodeling triggered recurrence. Clinical Trial Registration— URL: http://www.clinicaltrials.gov . Unique identifier: NCT00376272.

Prognostic Impact of Left Ventricular Mass Severity According to the Classification Proposed by the American Society of Echocardiography/European Association of Echocardiography

The American Society of Echocardiography (ASE) and European Association of Echocardiography (EAE) recommend the use of quantitative estimation of left ventricular (LV) mass and defined partition values for mild, moderate, and severe hypertrophy. However, the prognostic implications associated with this categorization are unknown. In this observational cohort study of unselected adults undergoing echocardiography for any indication, LV hypertrophy was assessed using the ASE/EAE-recommended formula and measurement convention from LV linear dimensions indexed to body surface area. Mortality and incident hospitalizations for cardiovascular disease were the outcomes of this study. Of 2,545 subjects (mean age, 61.9 ± 15.8 years; 56.3% women), 52.9% had normal LV mass, and 15.4% had mild, 12.1% moderate, and 19.6% severe LV hypertrophy. During a mean follow-up period of 2.5 ± 1.2 years, 121 deaths and 292 incident hospitalizations for cardiovascular disease occurred. In multivariate models including age, gender, LV ejection fraction, wall motion score index, significant valvular disease, and atrial fibrillation, the adjusted hazard ratios for death were 1.81 (95% confidence interval [CI], 1.03-3.20; P= .041) for mild, 2.31 (95% CI, 1.33-4.01; P= .003) for moderate, and 2.30 (95% CI, 1.39-3.79, P= .001) for severe LV hypertrophy. The adjusted hazard ratios for incident cardiovascular hospitalizations were 1.24 (95% CI, 0.84-1.82; P= .277) for mild, 2.02 (95% CI, 1.42-2.88; P= .0001) for moderate, and 2.38 (95% CI, 1.75-3.22, P < .0001) for severe LV hypertrophy. After adjustment for known risk predictors, there was a 1.3-fold risk for death and cardiovascular disease events per category of LV mass (P= .001). In a cohort study of unselected adult outpatients, the categorization of LV mass according to the ASE/EAE recommendations offered prognostic information independently of age, gender, and other known predictors.

Left ventricular hypertrophy reclassification and death: application of the Recommendation of the American Society of Echocardiography/European Association of Echocardiography

Despite the American Society of Echocardiography (ASE)/European Association of Echocardiography (EAE) recommended the use of left ventricular (LV) mass to diagnose left ventricular hypertrophy (LVH), several laboratories continue to use only the septal thickness by M-mode because it appears easier to measure. Aim of the study was to investigate the discrepancy between the categorization of LVH severity based on measurement of septal thickness and indexed LV mass and the relative prognostic utility of these two methods. Observational cohort study. Unselected adults (>18 years) referred to the echocardiography laboratory for any indication had septal thickness and LV mass measured by the ASE/EAE formula using LV linear dimensions indexed to body surface area. LVH was categorized as absent, mild, moderate, and severe according to the ASE/EAE guideline sex-specific categorization cut-offs for septal thickness and LV mass. Follow-up for death was obtained from the national death index. A total of 2545 subjects (mean age 61.9 ± 15.8, 53% women, mean diastolic septal thickness 10.3 ± 2.2 mm, and mean indexed LV mass 107.5 ± 37.3 g/m(2)) were enrolled. Agreement between the two methods in classifying LVH degree across the four categories was 52.6% (Kappa = 0.29, 95% confidence interval (CI): 0.26-0.32, P < 0.001). Of the 2513 subjects without severely thickened septum, 472 (18.9%) had severely abnormal indexed LV mass. Vice versa, of the 2045 individuals without severely abnormal indexed LV mass, only 4 (0.1%) were classified as severe LVH by septal thickness. After a mean follow-up of 2.5 ± 1.2 years 121 (4.7%) deaths occurred. Using indexed LV mass partition values there was a graded association between LVH degree and survival. Compared with patients with normal indexed LV mass, the adjusted hazard ratio (HR) for death from all causes was 2.17 for mild (95% CI: 1.23-3.81, P = 0.007), 3.04 for moderate (95% CI: 1.76-5.24, P < 0.001), and 3.81 for severe (95% CI: 2.43-5.97, P < 0.001) LVH by indexed LV mass. The area under the receiver-operator characteristic (ROC) curve for the four degrees of LVH by indexed LV mass was superior [area under the curve (AUC) = 0.66] to that of the septal thickness partition values (AUC = 0.58, P = 0.0004). In a large cohort study of unselected adult outpatients referred to the echocardiography laboratory, the measurements of indexed LV mass applying the ASE/EAE recommended cut-offs yielded remarkable discrepancy in the diagnosis of LVH severity and offered prognostic information beyond that provided by septal thickness only criteria.

Left ventricular hypertrophy

Left ventricular hypertrophy

Risk Stratification and Serious Ventricular Arrhythmias: The Importance of Left Ventricular Hypertrophic Remodeling in Patients with Depressed Ejection Fraction

Previous studies indicate an association between ventricular arrhythmias and left ventricular (LV) structural and functional remodeling. There has been emphasis on LV systolic dysfunction, yet little is known about LV structural remodeling and arrhythmias. Accordingly, we studied the extent of LV hypertrophy (LVH) as well as the patterns of hypertrophic remodeling and their relation to ventricular tachycardia/fibrillation (VT/VF) in patients with depressed ejection fraction (EF) and an implantable cardioverter-defibrillator (ICD). Of 565 patients who underwent implantation of a single or dual chamber ICD between 2006 and 2009, 127 had echocardiographic evidence of LV dysfunction and were followed in our device clinic. Standard echocardiographic Methods were used. LVH was defined as mass > 95 g/m2 in women and > 115 g/m2 in men. A relative wall thickness partition value of 0.42 was used to differentiate concentric vs. eccentric geometry. Serious ventricular arrhythmias were defined as VT/VF requiring anti-tachycardia pacing and/or ICD discharge. This diagnosis was made and confirmed by ICD interrogation and medical record review. Data are mean +/- SD. In the 127 patients, VT/VF occurred in 29 (23%). The average EF was 29 +/- 9%, LV mass was 115 +/- 33 g/m2, and LV end-diastolic dimension was 58 +/- 8 mm. The average age was 66 +/- 13 years; 78% were male. Clinical characteristics: hypertension: 69%, NYHA functional class I/II: 87%, diabetes: 31%, atrial fibrillation: 34%. VT/VF was significantly more prevalent in the 60 patients with LVH vs. 67 patients with normal LV mass (37% vs. 10%; p=0.0006). There was a trend towards more VT/VF in patients with LV enlargement vs. those with normal LV size (30% vs. 17%; p=ns), and in patients with eccentric hypertrophy vs. those with concentric remodeling/hypertrophy (38% vs. 20%; p=ns). There was no significant difference in clinical characteristics, indication for ICD, ischemic etiology, cardiac medications, and EF in patients with and without VT/VF. In patients with LV systolic dysfunction, we found a significant relationship between serious ventricular arrhythmias requiring device therapy and LVH. There was a trend towards more VT/VF in patients with LV enlargement and/or eccentric hypertrophy vs. those with concentric remodeling/hypertrophy. These data provide a rationale for improving risk stratification of patients with LV systolic dysfunction.

Cardiac geometry in children receiving chronic peritoneal dialysis: findings from the International Pediatric Peritoneal Dialysis Network (IPPN) registry.

Left ventricular hypertrophy (LVH) is an independent risk factor and an intermediate end point of dialysis-associated cardiovascular comorbidity. We utilized a global pediatric registry to assess the prevalence, incidence, and predictors of LVH as well as its evolution in the longitudinal follow-up in dialyzed children. Cross-sectional echocardiographic, clinical, and biochemical data were evaluated in 507 children on peritoneal dialysis (PD), and longitudinal data were evaluated in 128 patients. The 95(th) percentile of LV mass index relative to height age was used to define LVH. The overall LVH prevalence was 48.1%. In the prospective analysis, the incidence of LVH developing de novo in patients with normal baseline LV mass was 29%, and the incidence of regression from LVH to normal LV mass 40% per year on PD. Transformation to and regression from concentric LV geometry occurred in 36% and 28% of the patients, respectively. Hypertension, high body mass index, use of continuous ambulatory peritoneal dialysis, renal disease other than hypo/dysplasia, and hyperparathyroidism were identified as independent predictors of LVH. The use of renin-angiotensin system (RAS) antagonists and high total fluid output (sum of urine and ultrafiltration) were protective from concentric geometry. The risk of LVH at 1 year was increased by higher systolic BP standard deviation score and reduced in children with renal hypo/dysplasia. Using height-adjusted left ventricular mass index reference data, LVH is highly prevalent but less common than previously diagnosed in children on PD. Renal hypo/dysplasia is protective from LVH, likely because of lower BP and polyuria. Hypertension, fluid overload, and hyperparathyroidism are modifiable determinants of LVH.

Differences in Fabry Cardiomyopathy Between Female and Male Patients: Consequences for Diagnostic Assessment

We hypothesized that Fabry cardiomyopathy in female patients might differ substantially from that in male patients and sought to prove this hypothesis in a large cohort consisting of 104 patients with Fabry disease. Fabry cardiomyopathy in male patients is characterized by left ventricular (LV) hypertrophy, impaired myocardial function, and subsequent progressive myocardial fibrosis. In contrast, the occurrence of these 3 cardiomyopathic hallmarks in female patients remains unknown. In 104 patients (58 females, age 42 ± 16 years; 46 males, age 42 ± 13 years) with genetically proven Fabry disease, LV hypertrophy, regional myocardial deformation and myocardial fibrosis were assessed by standard echocardiography, strain rate imaging, and cardiac magnetic resonance (CMR) imaging-guided late enhancement (LE). In men, end-diastolic left ventricular wall thickness (LVWT) ranged from 6 to 19.5 mm (LV mass CMR 55 to 200 g/m(2)), and LE was never seen with LVWT <12 mm (LV mass <99 g/m(2)). In contrast in female patients, LVWT ranged from 5 to 15.5 mm, LV mass ranged from 39 to 146 g/m(2), and LE was already detectable with an LVWT of 9 mm (LV mass 56 g/m(2)). When LV mass was examined in CMR, LE was detected in 23% of the female patients without hypertrophy (n=9), whereas LE was never seen in male patients with normal LV mass. LE was always associated with low systolic strain rate, but the severity of impairment was independent of LVWT in female patients (lateral strain rate in patients with LV hypertrophy with LE -0.7 ± 0.2 s(-1); patients without LV hypertrophy with LE -0.8 ± 0.2 s(-1); p=0.45). In contrast to male patients, the loss of myocardial function and the development of fibrosis do not necessarily require myocardial hypertrophy in female patients with Fabry disease. Thus, in contrast to actual recommendations, initial cardiac staging and monitoring should be based on LV hypertrophy and on replacement fibrosis in female patients with Fabry disease.

Relation of Concentric Remodeling to Adverse Outcomes in Patients With Stable Coronary Artery Disease (from the Heart and Soul Study)

Concentric remodeling (CR) is defined as increased left ventricular (LV) wall thickness with normal total LV mass. When encountered in populations with hypertension or patients undergoing aortic valve replacement, some studies have shown that CR predicts cardiovascular (CV) events and stroke. To expand our understanding of the prognostic implications of this common echocardiographic finding, we examined the association of CR and adverse CV events in ambulatory patients with coronary artery disease (CAD). We tested the hypothesis that finding CR on echocardiogram in ambulatory CAD independently predicts heart failure hospitalizations and CV death. Transthoracic echocardiograms were recorded in 973 participants from the Heart and Soul Study. Participants were divided into 4 groups: normal, CR, concentric LV hypertrophy, and eccentric LV hypertrophy. CV events were determined by 2 independent adjudicators and these were analyzed by Cox proportional hazards models. After mean 4.9 ± 1.5 years of follow-up, adverse outcomes occurred more frequently in those with concentric and eccentric LV hypertrophy but not in those with CR. After multivariate adjustment, concentric and eccentric LV hypertrophies were associated with increased risk of death and heart failure hospitalization, whereas CR was not. In conclusion, our hypothesis was not supported because CR was not associated with adverse CV events in our cohort of patients with stable CAD.

Cardiovascular risk in subjects with left ventricular concentric remodeling at baseline examination: a meta-analysis

It is debated whether subjects with concentric remodeling (CR, normal left ventricular mass index (LVMI) and increased relative wall thickness (RWT)) are at higher cardiovascular risk than those with normal geometry (NG, normal LVMI and RWT). The aim of this study was to perform a meta-analysis of studies evaluating cardiovascular events in subjects with CR and NG according to baseline classification. We searched for articles evaluating cardiovascular outcome in subjects with CR compared with those with NG, and reporting adjusted hazard ratio (HR) and 95% confidence interval (CI). Six studies were included in the meta-analysis. The pooled population consisted of 7465 subjects with CR and NG. During the follow-up, they experienced 852 events. When compared with NG, the overall adjusted HR was 1.36 (95% CI 1.03-1.78) for CR, P<0.03. There was some heterogeneity between studies. Subgroup meta-analysis showed that increased cardiovascular risk in subjects with CR was more relevant in studies evaluating hypertensive and Caucasian subjects and reporting both fatal and non-fatal events. Cardiovascular risk is significantly higher in subjects with CR than in those with NG. This aspect is more evident in studies including hypertensive patients and Caucasian populations and reporting global cardiovascular risk.

Low-Gradient “Severe” Aortic Stenosis With Normal Systolic Function

Aortic stenosis (AS) is a progressive valvular disease that carries significant morbidity and mortality when hemodynamically significant. Traditionally, in normal-flow conditions, AS has been defined as severe when the transvalvular pressure gradient is >50 mm Hg and the effective aortic valve area (AVA) is significantly reduced. Some patients, however, manifest a restricted AVA but have a paradoxically low pressure gradient with a normal ejection fraction (EF). Low-gradient “severe” AS (LGSAS) with preserved left ventricular EF (LVEF) remains not well understood but has been thought to portend a very poor prognosis on the basis of recent retrospective studies.1,2 A new study by Jander et al3 in the current issue of Circulation sheds further light on this entity and has considerable implications for not only the prognosis of patients with LGSAS but also for how we define severe AS. Article see p 887 The study by Jander et al3 evaluated a large number of patients (n=1525) with asymptomatic AS in the prospective Simvastatin and Ezetimibe in Aortic Stenosis (SEAS) study, with peak transaortic velocity by Doppler between 2.5 and 4 m/s and a LVEF ≥55%. Of these, 12% (n=184) had moderate stenosis (AVA: 1 to 1.5 cm2) and 29% (n=435) had low-gradient “severe” stenosis (valve area <1.0 cm2 and mean gradient ≤40 mm Hg); the remaining majority had mild stenosis. The moderate AS group had higher flow with slightly higher mean gradient than the LGSAS group (31 versus 26 mm Hg), with a larger valve area (1.19 versus 0.82 cm2). Patients with LGSAS were older, had smaller body habitus, were more often women, had slightly higher blood pressure, and had smaller ventricles at end diastole but with similar EF. It is noteworthy that, in this study, patients with LGSAS had normal LV mass (99±31 …

Left Ventricular Volumes, Mass and Function normalized to the body surface area, age and gender from CMR in a large cohort of well-treated Thalassemia Major patients without myocardial iron overload

Cardiovascular Magnetic Resonance (CMR) allows an accurate and reproducible quantification of left ventricular (LV) parameters. In Thalassemia major (TM) patients have been reported different “normal” LV values due to chronic anemia and eventually pre-existing iron burdens. Moreover, in this population it is unknown the influence of sex and age on LV parameters and no ranges of normal have been reported using MASS® software. The aim of this study was to establish the ranges for normal LV volumes, mass and ejection fraction normalized to the influence of body surface area(BSA), age and sex from CMR in a large cohort of well-treated TM patients without myocardial iron overload.

Response to Method Errors or Unexplained Biological Information?

To the Editor: We thank Drs de Simone and Devereux1 for their comments and their continued contributions to the subject of allometric normalization of left ventricular mass (LVM). The authors confirm the important residual relationship between height and LVM/height2.7 in an independent cohort and present population-attributable risk (PAR) estimates of LV hypertrophy (LVH) defined by LVM/height2.7 and by LVM/height.1.7 These data are best interpreted in light of the definition and usefulness of PAR estimates and the overcorrection induced by normalizing LVM to height,2.7 resulting in the residual relationship between height and LVM/height.2.7 PAR is the portion of the incidence of a disease in the population that is due to the exposure, representing the proportional reduction in average disease risk that would be achieved by eliminating the exposure from the population while distributions of other risk factors remain unchanged (assuming the exposure is causal).2 In a multi-factorial disease setting like cardiovascular disease, the focus of interest is the risk associated with the modifiable exposure while other risk factors (particularly nonmodifiable factors such as height) are kept unchanged.2,3 Given the relationship between height and LVM/height,2.7 PAR estimates for LVH defined by LVM/height2.7 will not only reflect LVH-associated risk but also height-related risk, whatever its mechanism may …

105 Left ventricular twist in patients with Friedreich Ataxia and normal left ventricular ejection fraction and mass

Iron deposits, diffuse fibrosis and focal necrosis are found in Friedreich's cardiomyopathy. We hypothesized that subclinical left ventricular (LV) dysfunction might occur in patients with Friedreich ataxia (FA) who present with normal LV ejection fraction (LVEF) and mass. Twelve patients with FA (mean age: 36 ± 18 years) and twelve age-matched healthy controls (mean age: 36 ± 17 years) were submitted to standard echocardiography. Short axis basal and apical views were analyzed using speckle tracking software. LV twist was defined as the net difference between the apical and basal rotation. The two groups did not differ in terms of LVEF (65 ± 4% and 65 ± 6% in patients and in controls, respectively) and in systolic mitral annular velocities (7.6 ± 1.3 cm/s in patients and 8.3 ± 1.2 cm/s in controls). A slightly higher LV mass index (M-mode, American Society of Echocardiography convention) was observed in the patient group (93 ± 23 g/m_ versus 86 ± 18 g/m_, p = NS). The LV filling parameters did not differ between the 2 groups. However, early diastolic mitral annular velocity (Ea) was lower and the ratio of early transmitral flow velocity to Ea was higher in Friedreich ataxia patients (table). Peak LV twist was significantly reduced in patients as compared to controls, unlike early diastolic LV untwisting (at 5%, 10% and 15% of diastole) which was not significantly different. In patients with FA and normal LVEF and mass, the detection of a reduction in LV twist and an alteration in mitral annular diastolic velocities suggests the presence of subtle myocardial dysfunction. Evaluation of these parameters may prove useful as outcome measures for the assessment and follow-up of new therapies in the early stages of the disease.Empty CellFriedreich patientsControlsP valueE wave velocity (cm/s)73 ± 1073 ± 10NSE/A1.7 ± 0.71.95 ± 0.7NSEa (cm/s)9.3 ± 1.912.1 ± 3.40.02E/Ea8.6 ± 2.16.6 ± 1.90.03Peak LV twist (°)9.2 ± 3.412.1 ± 2.40.02

Method Errors or Unexplained Biological Information?

To the Editor: Left ventricular mass (LVM) is an indicator of cardiovascular status, integrating multiple adverse pathophysiologic influences and a potent, independent predictor of prognosis, making definition of optimal methods to distinguish abnormal from normal LVM a matter of high clinical priority. Different methods have been used to account for body size in the definition of “normal” LVM, and there is agreement that the ratiometric approach is not sufficient to capture the extend of abnormalities, especially in obese populations.1 In the July issue of Hypertension , Chirinos et al2 studied apparently normal members of 2 adult populations aged 35 to 55 and 45 to 84 years old and proposed a new exponent of body height (height1.7) to normalize LVM. This exponent is substantially lower than the allometric signal (height2.7) that we initially proposed,3 from a normal-weight population including infants, children, adolescents, adults, and elderly. It is also lower than other allometric powers (2.5 to 3.0) identified in other young populations and even lower than the exponent of 2 proposed by the Framingham Heart Study in an adult population. The allometric approach to identify left ventricular hypertrophy (LVH) increases the prevalence of LVH, without decreasing the LVH-associated relative risk,4,5 thus increasing the population risk attributable (PAR) to LVH.4,5 PAR is the proportion of the incident disease (cardiovascular event) …

Characteristics of left ventricular rotational mechanics in patients with systemic amyloidosis, systemic hypertension and normal left ventricular mass

Recently, two-dimensional (2D) speckle-tracking echocardiography has enabled assessment of a particular behaviour of left ventricular (LV) motion defined as twisting/untwisting. The aim of our study is to evaluate whether in early stage of hypertension and systemic amyloidosis, subclinical alteration of LV twist and untwist is already present even if no LV hypertrophy is evidenced. Forty-seven patients with light chain immunoglobulin amyloidosis (AL) entered the study and were classified having cardiac amyloidosis (CA) or not (NCA) if the mean value of LV wall thickness was ≥12 mm or not. Twenty-two consecutive patients with history of arterial essential hypertension (Hyp Group) and no sign of LV hypertrophy were enrolled. A total of 26 asymptomatic healthy subjects, age-matched, were analysed as control group. All three groups of patients and healthy subjects underwent traditional and 2D speckle-tracking echocardiography evaluation. LV diameters, volumes, wall thickness, mass, ejection fraction, E/A and E/E' ratio were evaluated. Twisting and untwisting rates were significantly increased in NCA and Hyp group when compared with CA and control group. Moreover, despite similar LV mass and diastolic dysfunction degree, untwisting rate peak was significantly delayed in NCA when compared with Hyp group. In patients with CA, untwisting rate delay was similar to patients with NCA. Our results show that amyloidosis and systemic hypertension produce both LV twist and untwist rate enhancement before LV hypertrophy is developed. In patients with amyloidosis irrespectively of LV infiltration degree, a significant LV untwisting rate peak delay occurs suggesting that different aetiology of cardiac involvement could differently affect LV untwisting rate.

THE CONTRIBUTION OF THE EKG / ECHOCARDIOGRAPHIC MASS RATIO TO THE DIAGNOSIS OF CARDIAC AL AMYLOIDOSIS IN UNEXPLAINED LV HYPERTROPHY: 4C.05

Background: In cardiac amyloidosis (AL) the increase in wall thickness caused by extracellular amyloid deposition leads to marked increases in left ventricular (LV) mass. At variance with other forms of cardiac hypertrophy, this is often associated with abnormally low electrocardiographic (EKG) voltages, due to amyloid negative effects on intracardiac electrical conduction. Although such a discrepancy (low EKG “electrical” LV mass / high echo-derived LV mass) might be a powerful diagnostic clue, this is often missed since almost 40% of cardiac AL patients do not strictly fulfil the definition of “EKG low voltages” (<5 mV in all peripheral leads). Methods: To evaluate the possible relevance of this finding, we compared an index of the EKG/ echo mass estimate in patients with cardiac AL (n = 218), non-cardiac AL (n = 69), hypertension with different degrees of LV hypertrophy (n = 125), and in normotensive patients with normal LV mass (n = 99). Echo-derived LV mass was estimated via the Devereux's formula (g/m2), whereas QRS score (the sum of QRS voltages in the peripheral leads, mV) was used as an index of “electrical” LV mass. EKG/Echo ratio was expressed as [mV/(g/m2)]. Patients with other potential causes of low EKG voltages (large pericardial effusions, obesity, chronic obstructive lung disease, and severe peripheral oedema) were excluded. Results: The EKG/echo mass ratio was superimposable in non-cardiac AL, normotensive, and hypertensive subjects [0.51±0.12, 0.54±0.13, and 0.49±0.15 mV/(g/m2), respectively]. In contrast, the EKG/echo mass ratio was markedly depressed in patients with cardiac AL [0.19±0.10 mV/(g/m2), p<0.001]. The area under the ROC curve for the detection of cardiac AL involvement was high: 0.96 (95% CI, 0.93 to 0.98). The best cutoff for the diagnosis of heart involvement was 0.33 mV/(g/m2), giving a 93.8% sensitivity and a 91.1% specificity. Conclusions: In patients with unexplained LV hypertrophy, an abnormally low EKG/echo mass ratio might be a powerful clue suggesting the diagnosis of cardiac amyloidosis, overcoming the limited diagnostic accuracy of the presence of “EKG low voltages”.

LEFT VENTRICULAR HYPERTROPHY AND INFLAMMATION IN TYPE 2 DIABETIC PATIENTS: PP.17.126

Introduction: The association between diabetes and adverse cardiovascular outcome may be partially explained by the strong independent association of type 2 diabetes with cardiovascular target organ damage, such as left ventricular hypertrophy (LVH), a well-known predictor of cardiovascular events independent of coronary artery disease. The aim of the present study is to evaluate the relation of LVH to fibrinogen and C-reactive protein (CRP) as markers of inflammation and susceptibility to atherothrombosis. Methods and Subjects: We selected 50 adults with type 2 diabetes. 32 were women and 18 were men, mean age 45 ± 14.Hypertension was defined by systolic blood pressure (sBP) 140 mmHg and/or diastolic blood pressure (dBP) 90 mmHg. Diabetes was defined by fasting plasma glucose levels 126 mg/dl or by specific treatment. BMI was calculated by the standard formula. Echocardiography Methods: The prevalence of left ventricular abnormalities has been determined by bidimensional echocardiography. The left ventricular mass index (LVMI) has been evaluated according to the method of Devereux and Reichek. Participant's laboratory data were examined in the morning after an overnight fast 12 h. The levels of CRP and fibrinogen have been measured. Results: From 50 participants, 22 (44%) presented LVH, which was associated with higher BMI and CRP, fibrinogen levels, left ventricular hypertrophy, markers of inflammation. We found relationships between fibrinogen and concentric LVH (p < 0,001) and also between CRP with concentric hypertrophy (p < 0.005). Conclusions: 22 patients presented concentric LVH, 10 patients eccentric LVH, and 18 patients normal LV mass. Concentric LVH was associated with elevated markers of systemic inflammation and susceptibility to atherothrombosis (CRP and fibrinogen levels) independently of clinically overt cardiovascular disease and traditional cardiovascular risk factors. No correlation was found between CRP and fibrinogen and eccentric LVH.