Marcel Lechin

Angiotensin-I Converting Enzyme Genotypes and Left Ventricular Hypertrophy in Patients With Hypertrophic Cardiomyopathy

BACKGROUNDnThe variability of the phenotypic expression of left ventricular hypertrophy (LVH) in patients with hypertrophic cardiomyopathy (HCM) indicates a potential role for additional modifying genes. Variants of angiotensin-I converting enzyme (ACE) gene have been implicated in cardiac hypertrophy. To assess whether ACE genotypes influence the phenotypic expression of hypertrophy, we determined the left ventricular mass index (LVMI) and extent of hypertrophy in 183 patients with HCM.nnnMETHODS AND RESULTSnLVMI was derived by the area-length method using two-dimensional echocardiograms. Extent of LVH was determined by a point score method (1 to 10 points). DNA was extracted from blood, and ACE genotyping was performed by polymerase chain reaction (PCR) with an established protocol. Amplification of DNA in the region of polymorphism by PCR of alleles I and D showed 490- and 190-bp products, respectively. ACE genotypes DD, ID, and II were present in 60, 90, and 33 patients with HCM, respectively. In genetically independent patients (n = 108), the mean LVMI (g/m2) was 148 +/- 35.3 in those with DD (n = 35) and 134.2 +/- 33.3 in those with ID and II (n = 73) genotypes (P = .046). LVH score was 6.69 +/- 1.71 in patients with DD and 5.55 +/- 2.19 in those with ID and II genotypes (P = .004). Regression analysis showed that ACE genotypes accounted for 3.7% and 6.5% of the variability of LVMI and LVH score (P = .046 and P = .008, respectively). In 26 patients from a single family, LVMI and LVH score were also greater in patients with DD than in those with ID and II genotypes. ACE genotypes accounted for 14.7% and 10.4% of the variability of the LVMI and extent of hypertrophy, respectively.nnnCONCLUSIONSnACE genotypes influence the phenotypic expression of hypertrophy in HCM.

Increased Levels of Free Serotonin in Plasma of Symptomatic Asthmatic Patients

BACKGROUNDnPrevious research has shown that symptomatic asthmatic patients have increased levels of norepinephrine, epinephrine, dopamine, free serotonin, and cortisol in plasma when compared with asymptomatic patients.nnnOBJECTIVEnWe investigated the relationship between plasma levels of catecholamines, free serotonin, and cortisol and clinical status and pulmonary function in symptomatic and asymptomatic patients with asthma.nnnMETHODSnWe compared clinical severity, spirometry, and neuroendocrine factors at weeks 0, 1, 2, 3, and 4 in 57 symptomatic (forced expiratory volume in one second [FEV1] < 70%) and 72 asymptomatic (FEV1 > 80%) asthmatic patients. We used multiple analyses of variance (repeated measures) to interpret the data. In addition, we used the Pearson Product Moment Test to investigate correlations among the different variables.nnnRESULTSnThe clinical severity rating and levels of free serotonin, norepinephrine, epinephrine, dopamine, and cortisol were significantly higher in symptomatic asthmatic patients than those in asymptomatic patients (P < .001, in all cases). FEV1 was significantly lower in symptomatic patients than in asymptomatic patients. In symptomatic patients, the level of free serotonin correlated positively with the clinical severity rating (r = .564, P < .01) and negatively with FEV1 (r = -.959, P < .001). In addition, the clinical severity rating showed a negative correlation with FEV1 (r = -.359, P < .01). No significant correlations were found in asymptomatic patients.nnnCONCLUSIONnOur finding that free serotonin was the only neuroendocrine factor closely associated with clinical severity and pulmonary function suggests that this factor plays an important role in the pathophysiology of acute asthma.

Plasma neurotransmitters, blood pressure, and heart rate during supine-resting, orthostasis, and moderate exercise conditions in major depressed patients.

Major depressed patients showed greater heart rate, noradrenaline, and free-serotonin values than normal. Conversely, platelet-serotonin values in major depressed patients were significantly lower than normal. Patients registered the normal differential blood pressure reduction during orthostasis. They also revealed progressive and significantly higher heart rate rises during orthostasis and exercise periods, when compared to normals. Whereas noradrenaline showed maximal rises during the two last periods, adrenaline only showed small but significant increase during exercise. The analysis of correlations, together with the above data, suggests that major depressed patients register maximal neural sympathetic activity as well as adrenal glands sympathetic hypoactivity. In addition, these patients show hyperparasympathetic activity, as reflected by the free-serotonin profile. Finally, the fact that both the Hamilton Depression Rating Scale and the self-rating Beck Depression Inventory correlated positively with noradrenaline/adrenaline ratio and free-serotonin values strongly suggests that both neural sympathetic and cholinergic mechanisms are involved in major depression.

Doppler echocardiographic assessment with the continuity equation of St. Jude Medical mechanical prostheses in the mitral valve position.

Evaluation of the St. Jude Medical (SJM) valve in the mitral position with Doppler echocardiography has usually involved the use of gradients across the valve and the application of the pressure half-time (PHT) method to derive a mitral valve area. The purpose of this study was, first, to determine the normal values of effective orifice areas for the SJM valve in the mitral position using the continuity equation, and second, to evaluate whether this parameter provides an improved assessment of valve function. Accordingly, Doppler echocardiography was performed in 40 patients within 6 weeks after valve replacement. All patients were clinically stable, without evidence of valvular dysfunction or aortic insufficiency. Valve size ranged from 23 to 33 mm and ventricular ejection fraction averaged 54 +/- 13%. Effective orifice area was derived by the continuity equation using stroke volume measured in the ventricular outflow tract, divided by the time-velocity integral of the SJM valve jet, and by PHT. Doppler-derived SJM valve mean gradient averaged 4 +/- 2 mm Hg. Effective area by the continuity equation averaged 1.82 +/- 0.36 cm2 (range 1.03 cm2 for a 23 mm valve to 2.63 cm2 for a 31 mm valve) and was smaller than by PHT (mean 3.10 +/- 0.65 cm2, p = 0.0001; range 1.38 to 4.78 cm2). Areas by both methods were smaller than the actual valve orifice area provided by the manufacturer (4.53 +/- 0.80 cm2, p = 0.0001).(ABSTRACT TRUNCATED AT 250 WORDS)

Plasma Neurotransmitters, Blood Pressure and Heart Rate during Supine Resting, Orthostasis and Moderate Exercise in Severely III Patients: A Model of Failing to Cope with Stress

BACKGROUNDnPrevious clinical research has shown that severely ill (somatic) as well as many psychosomatic patients show raised noradrenaline (NA), adrenaline (AD), cortisol, free serotonin (f5HT) and platelet aggregability. Conversely, they show reduced NA/AD plasma ratio and platelet serotonin (p5HT). They also show adrenal hyperresponsiveness to an oral glucose load. These findings are opposed to those observed in depressed patients who show adrenal gland sympathetic hyporesponsiveness and neural sympathetic hyperactivity.nnnOBJECTIVEnTo investigate adrenal gland and neural sympathetic systems as well as the other parameters in nondrepressed severely ill patients through the orthostasis exercise stress test which in normals triggers NA but no AD rise.nnnMETHODSnWe investigated 35 severely ill patients and their age- and sex-paired controls. Systolic, diastolic pulse pressure (PP), heart rate and neuroendocrine parameters were measured supine (0 min), at orthostasis (1 min) and exercise (5 min). A second test was performed 2 weeks later, after atropine injection. Multivariate analysis of variance, paired t test and Pearson product-moment test were employed.nnnRESULTSnThe normal PP orthostasis fall was not observed in patients. At this period, an abnormal AD peak substituted the normal NA peak. The normal p5HT-f5HT orthostasis-exercise peaks were absent in patients. Cortisol and platelet aggregability were raised in patients.nnnCONCLUSIONSnSeverely ill (somatic) patients responded to the orthostasis-exercise stress test with adrenal and corticosuprarenal but not neural sympathetic activity. They did not show the normal parasympathetic activity at orthostasis. This adrenal gland sympathetic hyperactivity registered in somatic patients is similar to that observed in mammals which fail to cope with stress and contrary to the profile registered in depressed subjects who show NA but not AD rise.

Plasma neurotransmitters, blood pressure, and heart rate during supine resting, orthostasis, and moderate exercise in dysthymic depressed patients

Dysthymic depressed patients showed platelet-serotonin (pS) + plasma-free serotonin values greater than normal as well as plasma noradrenaline values lower than normal during supine resting period (0). Conversely, no significant differences were observed in the 0 values of any other of the measured parameters: systolic, diastolic and differential blood pressure (SBP, DBP, DP), heart rate (HR), adrenaline (Ad), dopamine (DA), cortisol, and platelet aggregability between patients and controls. Although patients showed then normal DP reduction at orthostasis (1), this was not prevented by atropine as it does in controls. Patients but not normals showed significant rises of DBP at orthostasis and exercise (5) periods, which were positively correlated with NA rises. On the contrary, the abnormally raised resting fS values registered in patients showed progressive and significant reductions throughout the test that were negatively correlated with DBP-NA values. Adrenaline did not show the normal 5-fS peak. The above findings suggest that dysthymics show hypoactivity of the two branches of the sympathetic system (neural + adrenal) along with hyperparasympathetic activity. Furthermore, their low NA + high pS values contrast with the high NA + low pS registered in major depressed subjects.

Plasma Neurotransmitters and Functional Illness (Part 2 of 3)

Although the concept of functional illness has blurred boundaries, some consensus exists on its understanding among clinicians. In short, it is easier to conceive than to define functional illness. Se

1030-10 The Severity of Left Ventricular Hypertrophy is Greater in Patients with Hypertrophic Cardiomyopathy Due to Malignant Mutations

Genotype-phenotype correlation studies have shown that β myosin heavy chain (βMHC) mutations are determinants of frognosis in patients with hypertrophic cardiomyopathy (HCM). While Arg719Trp mutation is associated with a high incidence of sudden cardiac death (SCD) and an average life expectancy of 38 years, the Val606Met mutation is associated with a near normal life expectancy in the families studied here. However, it is unknown whether the prognostic significance of HCM mutations correlates with the degree of left ventricular hypertrophy (LVH) associated with each mutation. Accordingly, we determined the left ventricular mass index (LVMI) and the extent of LVH in 12 patients with the Arg719Trp mutation and five patients with the Val606Met mutation. Left ventricular mass was derived by the arealength method using 2-D echocardiograms and indexed for body surface area (BSA). Extent of LVH was determined using a semi-quantitative point score method that takes into account the extent of involvement of the septum, apex, and lateral wall of the left ventricle. The mean LVMI was 147.0xa0±xa036 g/m2 in patients with the Arg719Trp mutation and 111.7xa0±xa019 g/m2 in patients with the Val606 Met mutation (pxa0=xa00.020). Similarly the extent of hypertrophywas greater in patients with the Arg719Trp mutation than in those with the Val606Met mutation (5.92xa0±xa02.3 vs. 3.2xa0±xa01.5, respectively, pxa0=xa00.015). The mean septal thickness was also greater in patients with the Arg719Trp mutation than in those with the Val60 Met mutation, however, this was not statistically significant (2.03xa0±xa00.7 vs. 1.62xa0±xa00.26, pxa0=xa00.095). There was no difference in the mean BSA, age, or gender among the two groups of patients. In conclusion, HCM patients, due to a malignant mutation such as the Arg719Trp, have greater LVH than patients with a benign mutation such as the VaI606Met. These results indicate the grave prognosis of HCM mutations are associated with expression of greater hypertrophy. This provides an easily detectable clinical parameter to further stratify patients at risk of sudden death that are candidates for invasive interventions such as implantation of cardiac defibrillators.