Two-dimensional Guided M-mode Echocardiography Research Articles

Fatty liver index and left ventricular mass: prospective associations from two independent cohorts.

Heart disease is the most common cause of death in patients with nonalcoholic fatty liver disease (NAFLD). Emerging data have shown that NAFLD may affect subclinical myocardial remodeling, mainly left ventricular hypertrophy; however, evidence from the prospective studies is still lacking. Prospective analyses were performed to investigate the association of fatty liver index (FLI) with left ventricular mass (LVM) among 1962 participants from the Bogalusa Heart Study (BHS, 1995-2010) and 1547 participants from the Cardiovascular Risk in Young Finns Study (YFS, 2001-2011) free of cardiovascular diseases (CVD) at baseline. LVM was assessed by two-dimensional guided M-mode echocardiography and indexed (LVMI) to body height (m2.7). Multivariable regression models were applied after adjustment for traditional CVD risk factors. In both cohorts, we observed significant and positive associations between FLI and LVM (BHS: β=0.59, P < 0.001; YFS: β=0.41, P < 0.001) and LVMI (BHS: β=0.14, P < 0.001; YFS: β=0.09, P < 0.001). In addition, we found that the relationship between FLI and LVMI was stronger in women than men (BHS: P-interaction = 0.01; YFS: P-interaction < 0.01); and the relationship between FLI and LVM/LVMI was stronger in black than white individuals (LVM: P-interaction = 0.02; LVMI: P-interaction = 0.04). Moreover, we found that the associations of FLI with LVM and LVMI were attenuated by high physical activity, especially in BHS (P-interaction = 0.02). Our findings from two independent prospective cohorts indicate that FLI is positively associated with LVM/LVMI, independent of traditional cardiovascular risk factors. Such relationships are more pronounced among women and black individuals and are attenuated by high physical activity.

Study of Vitamin D Status in Patients with Dilated Cardiomyopathy at a Teaching Hospital in North India.

Background/Introduction:Recent studies have indicated a much broader role to Vitamin D than simply the regulation of calcium metabolism alone. Vitamin D likely confers physiologically relevant pleiotropic functions that include cardioprotective and immunomodulatory effect, and its deficiency could lead to increased risk of cardiovascular disease and heart failure.Aim:The aim of our work was to evaluate the presence of hypovitaminosis D in patients with dilated cardiomyopathy (DCMP) and to study any correlation of echocardiographic parameters with Vitamin D deficiency.Patients and Methods:In an observational case–control hospital-based study, 56 patients diagnosed to have DCMP and 60 age-, gender-, and body mass index-matched controls who were patients of other medical illnesses were included in the study. Each subject underwent transthoracic two-dimensional guided M-mode echocardiography, and Vitamin D, parathyroid hormone (PTH), and N-terminal pro-B-type natriuretic peptide (NT-ProBNP) were assessed.Results:Mean 25-hydroxyvitamin D3 [25(OH) D3] levels were significantly lower (14.5 ± 7.4 ng/ml vs. 28.2 ± 12 ng/ml, P = 0.001), whereas PTH (90.5 ± 28.5 pg/ml vs. 57 ± 20.2 pg/ml, P = 0.02) and NT-proBNP levels were significantly greater in patients with DCMP than controls. In DCMP group, 24/56 patients had severe Vitamin D deficiency, whereas in control group, 10/60 patients had severe hypovitaminosis D. There was a significant negative correlation between 25(OH) D3 concentrations and left ventricular (LV) end-diastolic and LV end-systolic dimensions.Conclusion:Patients with DCMP had lower Vitamin D levels than controls, and Vitamin D deficiency had a significant correlation with cardiac function. Therefore, screening for Vitamin D deficiency along with prompt treatment is recommended in patients with DCMP.

Effect of enzyme replacement therapy on serum asymmetric dimethylarginine levels, coronary flow reserve and left ventricular hypertrophy in patients with Fabry disease.

BackgroundFabry disease (FD) is a rare disorder and one of the causes of progressive renal and cardiac dysfunction. FD results from an X-linked recessive lysosomal storage disorder caused by a defect in the gene encoding lysosomal α-galactosidase A. Although accumulation of globotriaosylceramide leads to renal and cardiac manifestations, the precise mechanisms remain unclear. Coronary microvascular dysfunction may be one of the causes of cardiac complications in FD. We aimed to assess coronary flow reserve (CFR) and the effect of enzyme replacement therapy (ERT) on coronary microvascular dysfunction.MethodsFour FD patients who had never received ERT were included. The serum asymmetric dimethylarginine (ADMA) level, as a marker of endothelial dysfunction, was measured. Two-dimensional guided M-mode echocardiography was performed to measure left ventricular wall mass. Adenosine-triphosphate stress transthoracic Doppler echocardiography was used to measure CFR before starting ERT and at 3, 6 and 12 months.ResultsAll the patients tolerated ERT without any side effects. At the baseline, two patients had impaired CFR, increased left ventricular mass index (LVMI) and elevated serum ADMA levels. Twelve months after starting ERT, CFR was increased in all patients, and LVMI and serum ADMA levels decreased in two patients. Furthermore, serum ADMA levels significantly correlated with CFR (r = −0.576, P < 0.05) and LVMI (r = 0.874, P < 0.0001).ConclusionsThe results suggest that ERT prevented the progression of cardiac abnormalities, possibly by improving coronary microvascular dysfunction. ADMA may be a useful surrogate marker in FD.

Association of left ventricular mass with the AGTR1 A1166C polymorphism

The A1166C polymorphism is located within the microRNA-155 binding site of the human angiotensin II (Ang II) type-1 receptor (AGTR1) gene. The C allele interferes with the base-pairing complementariness between AGTR1 mRNA and microRNA-155 and thereby increases AGTR1 protein expression in vitro. We hypothesized that left ventricular (LV) mass is associated with the AGTR1 A1166C polymorphism. Among 708 individuals (mean age, 49.4 years; 51.8% women) randomly recruited in a white European population, we measured LV structure by two-dimensional guided M-mode echocardiography, the AGTR1 A1166C polymorphism and the 24-h urinary aldosterone. We applied a mixed model to assess phenotype-genotype associations while adjusting for covariables and accounting for relatedness. The AA (49.1%), AC (42.8%), and CC (8.1%) genotypes were in Hardy-Weinberg equilibrium. Using a recessive model, CC homozygotes compared to A-allele carriers showed significant increases (P < 0.021) in LV mass index (+5.78 ± 2.25 g/m(2)), mean wall thickness (MWT) (+0.48 ± 0.15 mm), interventricular septum (IVS) (+0.60 ± 0.18 mm) and posterior wall thickness (PWT) (+0.34 ± 0.15 mm), but lower 24-h urinary aldosterone excretion (geometric mean, 22.4 vs. 19.0 nmol; P = 0.050). Sensitivity analyses in 552 participants untreated for hypertension were confirmatory. LV mass index is associated with the AGTR1 A1166C polymorphism. Further research should clarify to what extent this association might be mediated via different expression of AGTR1 as modulated by microRNA-155.

Abstract 9851: Tenascin-C Deficiency Promotes Maladaptive Left Ventricular Remodeling and Impairs Cardiac Function in Chronic Pressure-Overload

Background: Tenascin-C (TnC) is a matricellular protein that is generally expressed during embryogenesis and in pathological settings; however, little is known about the role of TnC in maladaptive LV remodeling in response to chronic pressure-induced hypertrophy. Methods: Aortic constriction was performed in TnC null mice and control wild type mice (all mice in C57BL6 background). The aorta between the celiac and superior mesenteric arteries was constricted by tying a silk ligature against a 28-gauge needle for to yield a~33% narrowing of the aortic luminal diameter when the needle is removed. The LV size and function was assessed by two-dimensional guided M-mode echocardiography. Aortic blood pressure proximal to the constriction site was calculated by adding the pressure gradient across the constriction (measured by pulse Doppler) to the post-constriction blood pressure measured in the tail using a special cuff. LV mass was measured after euthanizing the mice at one month and histology was used to estimate myocardial fibrosis. Results: Before aortic constriction, LV size, EF and shortening fraction were similar in TnC null and wild type control mice. One month after constriction, the LV end diastolic diameter was larger in TnC null compared to wild type control mice (4.6 ± 0.5 vs 3.7 ± 0.2; p&lt;0.001), the LVEF was lower in TnC null compared to wild type control mice (47.3 ± 10.7 vs. 60.7 ± 3.8; p&lt;0.001), the fractional LV shortening was lower in TnC null compared to wild type control mice (24.2 ± 5.9 vs. 31.9 ± 2.6; p&lt;0.001), the heart weight in mg/gram of body weight was higher in TnC null compared to wild type control mice (6.9 ± 1 vs. 5.1 ± 0.1; p&lt;0.05). Collagen staining revealed that LV fibrosis was abundant in TnC null mice whereas it was scant in wild type control mice. There were no significant differences in the calculated proximal aortic blood pressure, the pressure gradient across the constriction, or the tail blood pressure or total body weight between the two groups of mice. Conclusions: TnC gene deletion is associated with maladptive LV remodeling, reduced LV systolic function and increased LV fibrosis in response to chronic pressure overload identifying a potentially beneficial role for TnC in myocardial response to pressure overload.

ZFP260 Is an Inducer of Cardiac Hypertrophy and a Nuclear Mediator of Endothelin-1 Signaling

Pressure and volume overload induce hypertrophic growth of postnatal cardiomyocytes and genetic reprogramming characterized by reactivation of a subset of fetal genes. Despite intense efforts, the nuclear effectors of cardiomyocyte hypertrophy remain incompletely defined. Endothelin-1 (ET-1) plays an important role in cardiomyocyte growth and is involved in mediating the neurohormonal effects of mechanical stress. Here, we show that the phenylephrine-induced complex-1 (PEX1), also known as zinc finger transcription factor ZFP260, is essential for cardiomyocyte response to ET-1 as evidenced in cardiomyocytes with PEX1 knockdown. We found that ET-1 enhances PEX1 transcriptional activity via a PKC-dependent pathway which phosphorylates the protein and further potentiates its synergy with GATA4. Consistent with a role for PEX1 in cardiomyocyte hypertrophy, overexpression of PEX1 is sufficient to induce cardiomyocyte hypertrophy in vitro and in vivo. Importantly, transgenic mice with inducible PEX1 expression in the adult heart develop cardiac hypertrophy with preserved heart function. Together, the results identify a novel nuclear effector of ET-1 signaling and suggest that PEX1 may be a regulator of the early stages of cardiac hypertrophy.

E0370 Relation of cardiovascular risk factors to left ventricular geometric remodelling in young adults

ObjectiveIt is well known that left ventricular (LV) structural alterations were associated with increased cardiovascular risk factors in a middle-aged and older population; however, cardiovascular risk factors are more prevalence...

Association of the beta-1 adrenergic receptor carboxyl terminal variants with left ventricular hypertrophy among diabetic and non-diabetic survivors of acute myocardial infarction

BackgroundThe beta-1 adrenergic receptor (β1AR) plays a fundamental role in the regulation of cardiovascular functions. It carries a nonsynonymous single nucleotide polymorphism in its carboxyl terminal tail (Arg389Gly), which has been shown to associate with various echocardiographic parameters linked to left ventricular hypertrophy (LVH). Diabetes mellitus (DM), on the other hand, represents a risk factor for LVH. We investigated the possible association between the Arg389Gly polymorphism and LVH among non-diabetic and diabetic acute myocardial infarction (AMI) survivors.MethodsThe study population consisted of 452 AMI survivors, 20.6% of whom had diagnosed DM. Left ventricular parameters were measured with two-dimensional guided M-mode echocardiography 2-7 days after AMI, and the Arg389Gly polymorphism was determined using a polymerase chain reaction-restriction fragment length polymorphism assay.ResultsThe Arg389 homozygotes in the whole study population had a significantly increased left ventricular mass index (LVMI) when compared to the Gly389 carriers (either Gly389 homozygotes or Arg389/Gly389 heterozygotes) [62.7 vs. 58.4, respectively (p = 0.023)]. In particular, the Arg389 homozygotes displayed thicker diastolic interventricular septal (IVSd) measures when compared to the Gly389 carriers [13.2 vs. 12.3 mm, respectively (p = 0.004)]. When the euglycemic and diabetic patients were analyzed separately, the latter had significantly increased LVMI and diastolic left ventricular posterior wall (LVPWd) values compared to the euglycemic patients [LVMI = 69.1 vs. 58.8 (p = 0.001) and LVPWd = 14.2 vs. 12.3 mm (p < 0.001), respectively]. Furthermore, among the euglycemic patients, the Arg389 homozygotes displayed increased LVMI and IVSd values compared to the Gly389 carriers [LVMI = 60.6 vs. 56.3, respectively (p = 0.028) and IVSd = 13.1 vs. 12.0 mm, respectively (p = 0.001)]. There was no difference in the LVMI and IVSd values between the diabetic Arg389 homozygotes and Gly389 carriers.ConclusionsThe data suggest an association between the β1AR Arg389Gly polymorphism and LVH, particularly the septal hypertrophy. The Arg389 variant appears to confer a higher risk of developing LVH than the corresponding Gly389 variant among patients who have suffered AMI. This association cannot be considered to be universal, however, since it does not appear to exist among diabetic AMI survivors.

Left Ventricular Geometric Patterns in Normotensive Type 2 Diabetic Patients in Nigeria: An Echocardiographic Study

Left ventricular hypertrophy has been linked with diabetes mellitus and abnormal glucose tolerance in several studies. Most previous studies have been carried out in the western world with dearth of data in native Africans. A total of 122 type 2 diabetic patients with a mean age of 55.0+/-8.5 years and another 90 normal patients with a mean age of 55.4+/-8.7 years were recruited for the study. Two-dimensional guided M-mode echocardiography was performed on each patient. In the diabetic patients, 49.2% had normal geometry, 23.0% had concentric hypertrophy, 13.0% had concentric remodeling, and 14.8% had eccentric hypertrophy. In the control group, 72.2% had normal geometry, 4.4% had concentric hypertrophy, 11.2% had concentric remodeling, and 12.2% had eccentric hypertrophy. In a multiple regression analysis, there was significant difference in the geometric pattern of the diabetics and controls (chi(2)=11.09, P<.001). Diabetes mellitus is independently associated with left ventricular structural changes in Nigerian diabetics.

Exercise training delays cardiac dysfunction and prevents calcium handling abnormalities in sympathetic hyperactivity-induced heart failure mice

Exercise training (ET) is a coadjuvant therapy in preventive cardiology. It delays cardiac dysfunction and exercise intolerance in heart failure (HF); however, the molecular mechanisms underlying its cardioprotection are poorly understood. We tested the hypothesis that ET would prevent Ca(2+) handling abnormalities and ventricular dysfunction in sympathetic hyperactivity-induced HF mice. A cohort of male wild-type (WT) and congenic alpha(2A)/alpha(2C)-adrenoceptor knockout (alpha(2A)/alpha(2C)ARKO) mice with C57BL6/J genetic background (3-5 mo of age) were randomly assigned into untrained and exercise-trained groups. ET consisted of 8-wk swimming session, 60 min, 5 days/wk. Fractional shortening (FS) was assessed by two-dimensional guided M-mode echocardiography. The protein expression of ryanodine receptor (RyR), phospho-Ser(2809)-RyR, sarcoplasmic reticulum Ca(2+) ATPase (SERCA2), Na(+)/Ca(2+) exchanger (NCX), phospholamban (PLN), phospho-Ser(16)-PLN, and phospho-Thr(17)-PLN were analyzed by Western blotting. At 3 mo of age, no significant difference in FS and exercise tolerance was observed between WT and alpha(2A)/alpha(2C)ARKO mice. At 5 mo, when cardiac dysfunction is associated with lung edema and increased plasma norepinephrine levels, alpha(2A)/alpha(2C)ARKO mice presented reduced FS paralleled by decreased SERCA2 (26%) and NCX (34%). Conversely, alpha(2A)/alpha(2C)ARKO mice displayed increased phospho-Ser(16)-PLN (76%) and phospho-Ser(2809)-RyR (49%). ET in alpha(2A)/alpha(2C)ARKO mice prevented exercise intolerance, ventricular dysfunction, and decreased plasma norepinephrine. ET significantly increased the expression of SERCA2 (58%) and phospho-Ser(16)-PLN (30%) while it restored the expression of phospho-Ser(2809)-RyR to WT levels. Collectively, we provide evidence that improved net balance of Ca(2+) handling proteins paralleled by a decreased sympathetic activity on ET are, at least in part, compensatory mechanisms against deteriorating ventricular function in HF.

Intravascular volume dependency of left ventricular mass calculation by two-dimensional guided M-mode echocardiography

Increased left ventricular mass (LVM) is an independent risk factor for cardiovascular morbidity and mortality, and may be used for risk stratification. Two-dimensional echocardiography, the most commonly used technique for estimation of LVM, uses the third power of the left ventricular internal diameter (LVID) for the calculation. To determine whether a decrease in intravascular volume after dialysis may cause inaccurate estimation of LVM by echocardiography. Thirty-eight patients undergoing hemodialysis due to chronic renal failure constituted the study group (14 women [37%] and 24 men [63%], mean age +/- SD 38.7+/-10.9 years). LVID, and interventricular and posterior wall thicknesses were measured by two-dimensionally guided M-mode echocardiography. Stroke volume and cardiac output were calculated using left ventricular outflow tract diameter and the pulsed-wave Doppler time-velocity integral obtained from left ventricular outflow tract. LVM was calculated by using Devereux's formula, and was indexed for body surface area and height. All echocardiographic parameters were measured or calculated before and after dialysis (on the same day), and then compared. There were no significant changes in wall thickness; however, LVID, LVM, the LVM/body surface index and the LVM/height index significantly decreased after dialysis (P<0.001 for each parameter). There was a significant correlation between the change in LVID and the change in LVM (P<0.001, r=0.59). Stroke volume and cardiac output also decreased significantly after hemodialysis (P<0.001 for each parameter). Intravascular volume-dependent change in LVID causes inaccurate estimation of LVM, so volume status should be kept in mind, especially in serial assessment of LVM.

Exercise training improves the net balance of cardiac Ca2+ handling protein expression in heart failure

The molecular basis of the beneficial effects associated with exercise training (ET) on overall ventricular function (VF) in heart failure (HF) remains unclear. We investigated potential Ca(2+) handling abnormalities and whether ET would improve VF of mice lacking alpha(2A)- and alpha(2C)-adrenoceptors (alpha(2A)/alpha(2C)ARKO) that have sympathetic hyperactivity-induced HF. A cohort of male wild-type (WT) and congenic alpha(2A)/alpha(2C)ARKO mice in a C57BL/J genetic background (5-7 mo of age) was randomly assigned into untrained and trained groups. VF was assessed by two-dimensional guided M-mode echocardiography. Cardiac myocyte width and ventricular fibrosis were evaluated with a computer-assisted morphometric system. Sarcoplasmic reticulum Ca(2+) ATPase (SERCA2), phospholamban (PLN), phospho-Ser(16)-PLN, phospho-Thr(17)-PLN, phosphatase 1 (PP1), and Na(+)-Ca(2+) exchanger (NCX) were analyzed by Western blotting. ET consisted of 8-wk running sessions of 60 min, 5 days/wk. alpha(2A)/alpha(2C)ARKO mice displayed exercise intolerance, systolic dysfunction, increased cardiac myocyte width, and ventricular fibrosis paralleled by decreased SERCA2 and increased NCX expression levels. ET in alpha(2A)/alpha(2C)ARKO mice improved exercise tolerance and systolic function. ET slightly reduced cardiac myocyte width, but unchanged ventricular fibrosis in alpha(2A)/alpha(2C)ARKO mice. ET significantly increased the expression of SERCA2 (20%) and phospho-Ser(16)-PLN (63%), phospho-Thr(17)-PLN (211%) in alpha(2A)/alpha(2C)ARKO mice. Furthermore, ET restored NCX and PP1 expression in alpha(2A)/alpha(2C)ARKO to untrained WT mice levels. Thus, we provide evidence that Ca(2+) handling is impaired in this HF model and that overall VF improved upon ET, which was associated to changes in the net balance of cardiac Ca(2+) handling proteins.

Effects On Cardiac Adaptations Of Training In Young Soccer Players And Swimmers

Background Top-level training induces morphologic cardiac adaptations; the most relevant change is cardiac hypertrophy. There are many data about so called “athlete' s heart” in adults, but is not jet clear the effect of the training in young subjects 's heart. Objective To assess physiological cardiac adaptation in elite soccer players and swimmers, in childhood and adolescence. Subjects and methods We study 423 highly trained athletes (119 swimmers, 304 soccer players) and 131 non-trained controls. We considered three groups comparable by age (8 to 18 years) and Body Surface Area (1,00 to 1,99 m2). and for each group the athletes and controls were divided in ten classes of BSA (class A:1–1.09 m2; class B:1.10–1.19; class C:1.20–1.29; class D:1.30–1.39; class E:1.40–1.49; class F:1.50–1.59; class G:1.60–1.69;class H:1.70–1.79; class I:1.80–1.89; class L:1.90–1.99). Left ventricular morphology was studied with two-dimensional guided M-mode echocardiography. Parameters measured included: End-diastolic diameter, End-diastolic volume, Posterior wall thickness (PP), Interventricular septum thickness (IVS), Left ventricular mass (LVM), Left ventricular Mass index (LVMi) in the different BSA classes. The data for athletes and non-athletes were compared. Results Our results show that IVS and PW were greater in athletes than in controls, particularly in soccer player in A-D classes. All other BSA classes swimmers had the greater one (IVS:p < 0.02; PW:p < 0.03). The value of LVM and LVMi grews with BSA increment in athletes and controls. These values became statistically signified by BSA greater than 1,60 m2. particularly in swimmers than in soccers. TDV was greater in athletes by E class. Swimmers had volume greater than soccer players in all BSA classes over 1.40 m2, becoming statistically signified by this BSA class. Soccer players had LVM and LVMi statistically greater than controls only in BSA classes over 1.80 m2. Conclusion Cardiac adaptation to intensive training in elite prepuberal swimmers and soccer players includes a mild increase in left ventricular dimension, in septal wall thickness, in posterior wall thickness, in end-diastolic volume and diameter. The differences became significant in adolescence (BSA > 1,60 m2), showing in this period the main adaptation to sport. Parameters measured defined also the characteristic of “athlete's heart” in two different shapes: dominance of volume and diameter respect on wall thickness in swimmers, and on the other hand an harmonic growth in soccer players.

A novel model of cryoinjury-induced myocardial infarction in the mouse: a comparison with coronary artery ligation

Mouse myocardial infarction (MI) models are frequently used research tools. The most commonly applied model is coronary artery ligation. However, coronary ligation often gives rise to apical aneurysmatic infarcts of variable size. Other infarct models include cryoinfarction, which produces reproducible infarcts of the anterior wall. Thus far, this model has not been extensively described in mice. Therefore, we developed a murine cryoinfarction model and compared it with coronary ligation. Studies were performed under isoflurane anesthesia with a follow-up of 4 and 8 wk. Cryoinfarction was induced using a 2- or 3-mm cryoprobe. Two-dimensional guided M-mode echocardiography was used to assess fractional shortening and left ventricular (LV) dimensions at baseline and end point. At end point, hemodynamics were assessed using a 1.4-Fr Millar catheter. Pressure-diameter relations were constructed by combining echocardiography and hemodynamic data. Histological and morphometric analyses of infarct and remote areas were performed. At 4 wk, 3-mm cryoinfarction resulted in decreased LV fractional shortening as well as decreased global LV contractility and relaxation, which was comparable with coronary ligation. No adverse remodeling was observed at this time point, in contrast with the ligation model. However, progressive LV remodeling occured between 4 and 8 wk after cryoinfarction with a further decline in hemodynamic parameters and LV pump function. Histologically, cryoinfarction resulted in highly reproducible, transmural, cone-shaped infarcts with reperfusion at the macrovascular level. These results indicate that the cryoinfarction model represents the anterior myocardial infarct with modest adverse remodeling and may thus be representative for infarcts encountered in clinical practice.

Long-term improvement of QT dispersion is unaffected by short-term changes in blood pressure during treatment of systemic hypertension with enalapril.

We report the reduction of QT and QTc dispersion in patients treated for 7 years with enalapril for systemic hypertension with left ventricular (LV) hypertrophy. We assess the correlation between QT dispersion and LV mass during this period and at the end of an 8-week period of suspension of enalapril treatment after 5 years. Twenty-four previously untreated patients with this condition took enalapril (20 mg twice daily) for 7 years, except during an 8-week period following 5-year follow-up. Cardiovascular parameters were determined by two-dimensional guided M-mode echocardiography, and QT interval was measured, in a pretreatment placebo phase, 8 weeks and 1, 3, 5, and 7 years after the start of the therapy, at the end of the 8-week suspension effected after 5 years, and 8 weeks after the end of the suspension. Therapy rapidly reduced blood pressure (BP) from 156/105 mmHg to normal values: 134/84 mmHg after 8 weeks' treatment, 130-84 mmHg at 7-year follow-up (P < 0.001 with respect to the placebo phase). LV mass index decreased progressively until at 5-year follow-up the reduction had reached 39% (P < 0.001), after which neither LV mass nor any other structural parameter underwent any further significant change. During this time, QT dispersion (DeltaQT) and the dispersion of "corrected" QT (DeltaQTc) decreased significantly: DeltaQT (from 61 +/- 21 to 37 +/- 13 ms) and DeltaQTc (from 67 +/- 27 to 41 +/- 16 ms). After suspension of treatment for 8 weeks following 5-year follow-up, DeltaQT was 40 +/- 14 ms and DeltaQTc was 44 +/- 17 ms; there were no significant changes either in DeltaQT and DeltaQTc or LV hypertrophy although BP had returned to pretreatment values (BP: 150 +/- 16; 101 +/- 10 mmHg). Long-term enalapril treatment of hypertensive patients with LV hypertrophy induces marked regression of LV mass and improvement of QT dispersion. These improvements occur on a longer timescale than improvement in BP, and are not affected by transient changes in BP values.

Cardiac adaptation to intensive training in prepubertal swimmers.

Despite the increasing involvement of child athletes in intensive training regimens, little is known about the influence of such training on autonomic regulation and cardiac structure and function. Twenty-five highly trained (12-14 h weekly for at least 4 years) swimmers (aged 11.9 +/- 1.6 years; 15 males, 10 females) and 20 non-training normal children who served as controls (aged 11.3 +/- 0.6 years; 14 males, 6 females) were studied. Heart rate variability analysis in the time and frequency domains was performed on 15 min resting heart rate acquisitions. Left ventricular morphology and systolic function was studied with two-dimensional guided M-mode echocardiography. The transmitral flow velocity profile was assessed with pulsed Doppler. Parameters measured included the peak early (E) and peak late (A) transmitral flow velocity and their ratio (E/A). Left atrial (LA) volumes were determined at mitral valve (MV) opening (maximal, Vmax), at onset of atrial systole (P wave of the ECG, Vp), and at MV closure (minimal, Vmin) from the apical 2- and 4-chamber views, using the biplane area-length method. LA systolic function was assessed with the LA active emptying volume (ACTEV) = Vp-Vmin and the LA active emptying fraction (ACTEF) = ACTEV/Vp. Average NN (967.1 +/- 141.8 vs. 768.4 +/-85.6 ms, P < 0.0001), logSDNN (1.89 +/- 0.14 vs. 1.80 +/- 0.17 ms, P < 0.05), logPNN 50% (1.66 +/- 0.23 vs. 1.46 +/- 0.35, p < 0.05), and logHF power (3.13 +/- 0.32 vs. 2.95 +/- 0.26 ms2, p < 0.05) were greater in swimmers than in controls. Left ventricular end-diastolic diameter was greater (32.3 +/- 3.3 vs. 29.5 +/- 3.3 mm m(-2), P < 0.02) in swimmers than in controls, whereas the left ventricular septal (5.9 +/- 1 vs. 5.6 +/- 0.8 mm m(-2), P = NS) and posterior wall thickness (5.7 +/-0.9 vs. 5.4 +/- 0.8 mm m(-2), P = NS) were similar in the two groups. The E/A ratio was greater (2.2 +/- 0.49 vs. 1.78 +/- 0.36, P < 0.003) whereas the A velocity was lower (0.41 +/- 0.09 vs. 0.50 +/- 0.13 m s(-1), P < or = 0.02) in swimmers than in controls. Vmax was greater (18.6 +/-4.8 vs. 14.9 +/-5.3 cm m(-2), P < 0.03), whereas ACTEF was lower (36 +/- 12% vs. 44.2 +/- 12%, P < 0.04) in swimmers than in controls. Cardiac adaptation to intensive training in prepubertal swimmers includes vagal predominance, a mild increase in left ventricular dimensions without significant changes in septal or posterior wall thickness, and increased LA size associated with depressed LA systolic function. Evaluation of LA size and systolic function may contribute to a better understanding of the characteristics of the 'athlete's heart' in children and to the differential diagnosis between left ventricular adaptive and pathologic changes.

G protein β 3 subunit gene 825T allele is associated with increased left ventricular mass in young subjects with mild hypertension

Background A nucleotide substitution (C→T) at position 825 of the gene GNB3 encoding the β 3 subunit of heterotrimeric G proteins is associated with alternative splicing and enhanced signal transduction. There is accumulating evidence from different populations that the 825T allele is associated with increased prevalence of hypertension, obesity, and left ventricular hypertrophy. However, it is unclear to what extent the 825T allele has a direct influence on left ventricular structure, independently of the effects of pressure and body mass index. Therefore we explored whether the GNB3 825T allele is associated with increased left ventricular mass index in a selected and homogeneous group of young, never treated, mild hypertensives. Procedures Young subjects (n = 207, aged 18 to 45 years) were genotyped at the GNB3 825 locus. In each patient, 24-h ambulatory blood pressure (BP) measurement and two-dimensional guided M-mode echocardiography combined with Doppler sonography were performed. Results: The genotype distribution among patients was in Hardy-Weinberg equilibrium. Patients carrying the 825T allele had an increased left ventricular mass index (95.1 ± 1.5 v 89.7 ± 1.5 g/m 2; P = .01) in comparison to those with CC genotype. The association between left ventricular mass index and 825T allele was independent of gender, age, BP, heart rate, alcohol intake, and physical activity. Conclusions: In young patients with mild hypertension without heart disease the 825T allele is associated with an increased left ventricular mass index. These hypothesis-generating data suggest that GNB3 825T allele may be considered as one genetic marker predisposing to an increase in left ventricular mass in hypertensives, and justifies larger studies.

Chagas' heart disease: evolutive evaluation of electrocardiographic and echocardiographic parameters in patients with the indeterminate form.

To identify and associate potential electrocardiographic and echocardiographic changes in patients with the indeterminate form of Chagas' disease during long-term follow-up. One hundred sixty patients underwent standard electrocardiography and two-dimensional guided M-mode echocardiography for left ventricular ejection fraction determination. Patients were followed up for 98.6+/-30.4 months, undergoing repeat electrocardiographic studies at 6-month intervals and echocardiographic studies at 12-month intervals. Based on the electrocardiographic findings, the patients were divided into group I, 125 patients (78.6%) with normal electrocardiograms throughout follow-up, and group II, 34 patients (21.3%) who developed electrocardiographic changes. Group II was further divided into group IIA (9 patients, 5.6%) with permanent electrocardiographic changes, group IIB (14 patients, 8.8%) with transitory electrocardiographic changes, and group IIC (11 patients, 6.9%) with changes appearing only on the final electrocardiogram. Left ventricular ejection fractions remained normal in the entire population studied and did not differ among groups. The indeterminate form of Chagas' disease clearly represents a benign condition with a favorable long-term prognosis. Although some patients develop electrocardiographic changes, left ventricular systolic function is well preserved.

Effect of the angiotensin II type 2-receptor gene (+1675 G/A) on left ventricular structure in humans

OBJECTIVESOur study goal was to analyze whether gene variants of angiotensin II type 2-receptor (AT2-R) modulate the effects of angiotensin II on the left ventricle (LV).BACKGROUNDExperimental data suggest that angiotensin II modifies ventricular growth responses via angiotensin II type 1-receptors (AT1-R) and AT2-R.METHODSIn 120 white, young male subjects with normal or mildly elevated blood pressure, we assessed plasma angiotensin II and aldosterone concentrations (RIA), 24-h urinary sodium excretion, 24-h ambulatory blood pressure and LV structure (two-dimensional guided M-mode echocardiography). The intronic +1675 G/A polymorphism of the X-chromosomal located AT2-R gene was investigated by single-strand conformational polymorphism analysis and DNA-sequencing.RESULTSHypertensive subjects with the A-allele had a greater LV posterior (11.0 ± 1.3 vs. 9.9 ± 1.3 mm, p < 0.001), septal (11.8 ± 1.4 vs. 10.1 ± 1.2 mm, p < 0.001) and relative wall thickness (0.44 ± 0.06 vs. 0.39 ± 0.06, p < 0.01) as well as LV mass index (138 ± 23 vs. 120 ± 13 g/m2, p < 0.001) than those with the G-allele. Confounding factors (i.e., body mass index and surface area, plasma angiotensin II, sodium excretion, systolic and diastolic ambulatory blood pressure) were similar between the two genotypes. In normotensive subjects, relative wall thickness (0.36 ± 0.05 vs. 0.35 ± 0.05) and LV mass index (115 ± 21 vs. 112 ± 17 g/m2) were nearly identical across the two genotypes, with similar confounding variables.CONCLUSIONSOur data indicate that the X-chromosomal located +1675 G/A-polymorphism of the AT2-R gene is associated with LV structure in young male humans with early structural changes of the heart due to arterial hypertension.

Association Between TGF-β Gene Polymorphism and Left Ventricular Hypertrophy in Essential Hypertension

P61 The aim of the study was to evaluate the possible association between two TGF-β1 gene polymorphisms and left ventricular hypertrophy in a group of essential hypertensive patients (EH). Ninety-three non treated EH underwent 24-hour ambulatory blood pressure, two-dimensional guided M-mode echocardiography in order to measure left ventricular mass index (LVMI), and TGF-β1 Leu 10 /Pro and Arg 25 /Pro polymorphism genotyping. As shown in the table, 24-h SBP and DBP were significantly higher in homozygous patients for the Arg 25 allele of the TGF-β1 gene. Likewise, homozygous patients for the Leu 10 allele and homozygous patients for the Arg 25 allele of the TGF-β1 gene had significanlty higher LVMI. We conclude that these TGF-β1 gene polymorphisms are associated with the severity of blood pressure and left ventricular hypertrophy in EH patients.