Association of angiotensin-converting enzyme activity and polymorphism with echocardiographic measures in familial and nonfamilial hypertrophic cardiomyopathy

Angiotensin-converting enzyme (ACE) activity and polymorphism contribute significantly to the prognosis of patients with cardiomyopathy. The aim of this study was to determine the activity and type of ACE polymorphism in patients with familial and nonfamilial hypertrophic cardiomyopathy (HCM) and to correlate these with echocardiographic measurements (echo-Doppler). We studied 136 patients (76 males) with HCM (69 familial and 67 nonfamilial cases). Mean age was 41 ¡À 17 years. DNA was extracted from blood samples for the polymerase chain reaction and the determination of plasma ACE levels. Left ventricular mass, interventricular septum, and wall thickness were measured. Mean left ventricular mass index, interventricular septum and wall thickness in familial and nonfamilial forms were 154 ¡À 63 and 174 ¡À 57 g/m2 (P = 0.008), 19 ¡À 5 and 21 ¡À 5 mm (P = 0.02), and 10 ¡À 2 and 12 ¡À 3 mm (P = 0.0001), respectively. ACE genotype frequencies were DD = 35%, ID = 52%, and II = 13%. A positive association was observed between serum ACE activity and left ventricular mass index (P = 0.04). Logistic regression showed that ACE activity was twice as high in patients with familial HCM and left ventricular mass index ¡Ý190 g/m2 compared with the nonfamilial form (P = 0.02). No other correlation was observed between ACE polymorphisms and the degree of myocardial hypertrophy. In conclusion, ACE activity, but not ACE polymorphisms, was associated with the degree of myocardialhypertrophy in the patients with HCM.

Collagen content, but not the ratios of collagen type III/I mRNAs, differs among hypertensive, alcoholic, and idiopathic dilated cardiomyopathy

Cardiac interstitial fibrosis may contribute to ventricular dysfunction and the prognosis of patients with dilated cardiomyopathy. The objective of the present study was to determine if total myocardial collagen content and collagen type III/I (III/I ratio) mRNAs differ in hypertensive, alcoholic, and idiopathic dilated cardiomyopathy subjects. Echocardiography and exercise cardiopulmonary testing were performed in patients with idiopathic (N = 22), hypertensive (N = 12), and alcoholic (N = 11) dilated cardiomyopathy. Morphometric analysis of collagen was performed in fragments obtained by endomyocardial biopsy with picrosirius red staining. The collagen III/I ratio was determined by reverse transcription polymerase chain reaction. Samples of controls (N = 10) were obtained from autopsy. Echocardiographic variables and maximal oxygen uptake were not different among dilated cardiomyopathy groups. Collagen was higher in all dilated cardiomyopathy groups (idiopathic, hypertensive and alcoholic, 7.36 ± 1.09 percent) versus controls (1.12 ± 0.18 percent), P < 0.05. Collagen was lower in idiopathic dilated cardiomyopathy (4.97 ± 0.83 percent) than hypertensive (8.50 ± 1.11 percent) and alcoholic (10.77 ± 2.09 percent) samples (P < 0.005 for both). The collagen III/I ratio in all samples from dilated cardiomyopathy patients was higher compared to that in controls (0.29 ± 0.04, P < 0.05) but was the same in the samples from idiopathic (0.77 ± 0.07), hypertensive (0.75 ± 0.07), and alcoholic (0.81 ± 0.16) dilated cardiomyopathy groups. Because of the different physical properties of the types of collagen, the higher III/I ratio may contribute to progressive ventricular dilation and dysfunction in dilated cardiomyopathy patients.

N-terminal prohormone brain natriuretic peptide (NT-proBNP) as a noninvasive marker for restrictive syndromes

Constrictive pericarditis (CP) and restrictive cardiomyopathy share many similarities in both their clinical and hemodynamic characteristics and N-terminal prohormone brain natriuretic peptide (NT-proBNP) is a sensitive marker of cardiac diastolic dysfunction. The objectives of the present study were to determine whether serum NT-proBNP was high in patients with endomyocardial fibrosis (EMF) and CP, and to investigate how this relates to diastolic dysfunction. Thirty-three patients were divided into two groups: CP (16 patients) and EMF (17 patients). The control group consisted of 30 healthy individuals. Patients were evaluated by bidimensional echocardiography, with restriction syndrome evaluated by pulsed Doppler of the mitral flow and serum NT-proBNP measured by immunoassay and detected by electrochemiluminescence. Spearman correlation coefficient was used to analyze the association between log NT-proBNP and echocardiographic parameters. Log NT-proBNP was significantly higher (P < 0.05) in CP patients (log mean: 2.67 pg/mL; 95 percentCI: 2.43-2.92 log pg/mL) and in EMF patients (log mean: 2.91 pg/mL; 95 percentCI: 2.70-3.12 log pg/mL) compared with the control group (log mean: 1.45; 95 percentCI: 1.32-1.60 log pg/mL). There were no statistical differences between EMF and CP patients (P = 0.689) in terms of NT-proBNP. The NT-proBNP log tended to correlate with peak velocity of the E wave (r = 0.439; P = 0.060, but not with A wave (r = -0.399; P = 0.112). Serum NT-proBNP concentration can be used as a marker to detect the presence of diastolic dysfunction in patients with restrictive syndrome; however, serum NT-proBNP levels cannot be used to differentiate restrictive cardiomyopathy from CP.

Leptin levels in different forms of Chagas' disease

Leptin is produced primarily by adipocytes. Although originally associated with the central regulation of satiety and energy metabolism, increasing evidence indicates that leptin may be an important mediator in cardiovascular pathophysiology. The aim of the present study was to investigate plasma leptin levels in patient with Chagas' heart disease and their relation to different forms of the disease. We studied 52 chagasic patients and 30 controls matched for age and body mass index. All subjects underwent anthropometric, leptin and N-terminal pro-brain natriuretic peptide (NT-proBNP) measurements and were evaluated by echocardiography, 12-lead electrocardiogram (ECG), and chest X-ray. All patients had fasting blood samples taken between 8:00 and 9:00 am. Chagasic patients were divided into 3 groups: group I (indeterminate form, IF group) consisted of 24 subjects with 2 positive serologic reactions for Chagas' disease and no cardiac involvement as evaluated by chest X-rays, ECG and two-dimensional echocardiography; group II (showing ECG abnormalities and normal left ventricular systolic function, ECG group) consisted of 14 patients; group III consisted of 14 patients with congestive heart failure (CHF group) and left ventricular dysfunction. Serum leptin levels were significantly lower (P < 0.001) in the CHF group (1.4 ± 0.8 ng/mL) when compared to the IF group (5.3 ± 5.3 ng/mL), ECG group (9.7 ± 10.7 ng/mL), and control group (8.1 ± 7.8 ng/mL). NT-proBNP levels were significantly higher (P < 0.001) in the CHF group (831.8 ± 800.1 pg/mL) when compared to the IF group (53.2 ± 33.3 pg/mL), ECG group (83.3 ± 57.4 pg/mL), and control group (32 ± 22.7 pg/mL). Patients with Chagas' disease and an advanced stage of CHF have high levels of NT-ProBNP andlow plasma levels of leptin. One or more leptin-suppressing mechanisms may operate in chagasic patients.

N-terminal-pro-brain natriuretic peptide, but not brain natriuretic peptide, is increased in patients with severe obesity

Elevated body mass index (BMI) has been reported as a risk factor for heart failure. Prevention of heart failure through identification and management of risk factors and preclinical phases of the disease is a priority. Levels of natriuretic peptides as well as activity of their receptors have been found altered in obese persons with some conflicting results. We investigated cardiac involvement in severely obese patients by determining N-terminal-pro-brain natriuretic peptide (NT-proBNP) and brain natriuretic peptide (BNP) and attempting to correlate the levels of these peptides in serum and plasma, respectively, with BMI, duration of obesity, waist circumference, and echocardiographic parameters. Thirty-three patients with severe obesity (mean BMI: 46.39 kg/m², mean age: 39 years) were studied. The control group contained 30 healthy age-matched individuals (BMI: <25 kg/m², mean age: 43 years). The t-test and Spearman correlation were used for statistical analysis. Log-NT-proBNP was significantly higher (P = 0.003) in obese patients (mean 1.67, 95 percent CI: 1.50-1.83 log pg/mL) compared to controls (mean: 1.32, 95 percent CI: 1.17-1.47 log pg/mL). The Log-NT-proBNP concentration correlated with duration of obesity (r = 0.339, P < 0.004). No difference was detected in the Log-BNP concentration (P = 0.63) of obese patients (mean: 0.73, 95 percent CI: 0.46-1.00 log pg/mL) compared to controls (mean: 0.66, 95 percent CI: 0.51-0.81 log pg/mL). NT-proBNP, but not BNP, is increased in severely obese patients and its concentration in serum is correlated with duration of obesity. NT-proBNP may be useful as an early diagnostic tool for the detection of cardiac burden due to severe obesity.