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Inotropes improve right heart function in patients undergoing aortic valve replacement for aortic stenosis.

UNLABELLED: The administration of inotropes after aortic valve replacement (AVR) for aortic stenosis (AS) is controversial. Issues include the risk of left ventricular (LV) systolic outflow obstruction (LVOTO) and the proper treatment of diastolic dysfunction for patients in whom LV systolic function is often preserved and subsequently improved. In this study, we assessed the hemodynamic benefits of inotropes for patients undergoing AVR for AS. Thirty-four patients were prospectively randomized to one of three groups: epinephrine, milrinone, or placebo. Hemodynamic and echocardiographic data were obtained before and immediately after cardiopulmonary bypass (CPB). Data were also obtained before and after increases in ventricular preload to assess the effects of inotropes on diastolic function. The use of inotropes was associated with significantly larger increases in right ventricular (RV) (placebo, 0.5%; epinephrine, +9%; milrinone, +8%; P < 0.01) and LV (placebo, +7%; epinephrine, +18%; milrinone, +20%; P = 0.07) ejection fractions (EF) and cardiac output after CPB. Changes in cardiac output and index were more strongly correlated with changes in RVEF (r = 0.56, P < 0.01; r = 0.47, P < 0.01, respectively) than with LVEF (r = 0.22, r = 0.08). Of all patients receiving epinephrine or milrinone, only one (1 of 22) had a decrease in RVEF, whereas 6 of 12 patients receiving placebo had a reduction in RVEF from pre-CPB to post-CPB. Correspondingly, for LVEF, 1 of 22 patients receiving inotropes had a decrease in LVEF, whereas 3 of 12 placebo patients had a reduction in LVEF from pre-CPB to post-CPB. No patient had evidence of LVOTO. Inotropes improved hemodynamics after AVR for AS. This was attributable more to improved RV function than to changes in LV function. Although there were no changes in diastolic function, it is possible that this study did not allow significant timing to observe benefits of inotropes on diastolic function in this setting. IMPLICATIONS: Compared with placebo, both epinephrine and milrinone similarly improved biventricular performance after aortic valve replacement, with a greater impact on right ventricular function. Choice of either inotropic drug should be driven by blood pressure and hemodynamic goals in this setting.

Adrenergic alpha-Agonists↗

[Medical treatment of chronic congestive heart failure].

Medical treatment in congestive heart failure has been largely improved during the last 15 years. Treatment of left ventricular systolic dysfunction using angiotensin-converting-enzyme inhibitor is now confirmed in all NYHA classes, due to the important reduction in morbi-mortality. Betablockers have to be systematically associated in symptomatic classes. Among other drugs, only spironolactone has been shown efficient in severe NYHA classes. Diuretics in case of congestive symptoms, digoxin in order to reduce the frequency of hospitalization, and nitrates as adding therapy in severe classes may be also prescribed. However, treatment of left ventricular diastolic dysfunction remains under debate since up to date, no medication has shown a confirmed efficacy.

Drug Therapy, Combination↗

Continuous measurement of the pressure-volume relationship in experimental heart failure produced by rapid ventricular pacing in conscious dogs.

The contractile function of the left ventricle has been defined within the framework of the pressure-volume relationship. We employed a conductance catheter, together with a high-fidelity micromanometer, to obtain accurate pressure and volume data continuously on a beat-to-beat basis in conscious dogs. Reproducibility of conductance volumetry was proven by repeated in situ measurements of left ventricular volume on separate days in the same dog. Heart failure, produced by rapid ventricular pacing, was characterized by impaired systolic shortening, depressed contractility indices and incomplete left ventricular relaxation. The magnitude of the cardiotonic effects of dobutamine was significantly attenuated after development of heart failure. Dobutamine improved left ventricular early relaxation but did not affect chamber distensibility. In heart failure, the load sensitivity of relaxation was enhanced and the force-frequency response attenuated. This may elucidate the mechanisms of early diastolic dysfunction and the deleterious effect of an increase in heart rate in the failing heart. Thus, the conductance catheter provided a reliable and simple method of obtaining left ventricular volume continuously in conscious dogs.

Animals↗

Effects of CPAP on right ventricular myocardial performance index in obstructive sleep apnea patients without hypertension.

OBJECTIVES: Obstructive sleep apnoea (OSA) might cause right ventricular dysfunction and pulmonary hypertension. We aimed to determine the effects of nasal continuous positive airway pressure (CPAP) therapy on right ventricular myocardial performance index (MPI) in OSA patients without hypertension. METHODS: 49 subjects without hypertension, diabetes mellitus, any cardiac and pulmonary disease had overnight polysomnography and echocardiography. In 18 moderate-severe OSA (apnea-hypopnea index > or = 15) patients, right ventricular free wall diameter (RVFWD) was measured by M-mode, and right ventricular MPI was calculated as (isovolumic contraction time+ isovolumic relaxation time) / pulmonary ejection time using Doppler at baseline and after 6 months CPAP therapy. RESULTS: Mean age was 46.5 +/- 4.9 year. Patients had high body mass index (BMI: 30.6 +/- 4,0 kg/m2), but there was no change in either BMI or blood pressures after 6 months. Right ventricular end-diastolic and end-systolic diameters were in normal limits at baseline, and did not change after CPAP usage. Baseline RVFWD (7.1 +/- 2.1 mm) significantly decreased after CPAP therapy (6.2 +/- 1.7 mm, p < 0.001). 15 of patients (83%) had right ventricular diastolic dysfunction at baseline, and it was completely improved in 11 of them (73%) by CPAP usage. Right ventricular global dysfunction was shown in 11 patients (61%) with a high MPI (62.2 +/- 9.3%) at baseline; and MPI was significantly decreased after CPAP therapy (47.3 +/- 8.4%, p < 0.0001), and it was completely corrected in 4 of them (36%). CONCLUSION: CPAP therapy significantly decreases RVFWD and improves right ventricular diastolic and global functions (MPI) in OSA patients without hypertension.

Adult↗

Myocardial dysfunction in treated adult hypopituitarism: a possible explanation for increased cardiovascular mortality.

OBJECTIVE: To assess cardiac structure and function in patients with treated hypopituitarism and to determine their relation to the degree of growth hormone deficiency and body composition pattern. DESIGN: 26 patients with treated hypopituitarism were studied by cross sectional and Doppler echocardiography and by exercise testing. The results were analysed and their relation to the degree of growth hormone deficiency and body composition determined. SETTING: All tests were performed in the department of cardiology and the unit of metabolic medicine at a tertiary referral centre. PATIENTS: Patients with hypopituitarism referred for endocrine assessment. MAIN OUTCOME MEASURES: Left ventricular mass, left ventricular diastolic function, and exercise capacity in patients with hypopituitarism and their relation to growth hormone deficiency. RESULTS: Mean (SD) serum concentration of insulin-like growth factor 1 (IGE-1), a measure of growth hormone deficiency, was 82.4 (45) micrograms/l. Lean body mass calculated by measuring total body potassium was 50 (9) kg. All patients had a normal left ventricular mass index and a normal left ventricular ejection fraction. Eight patients had abnormal left ventricular diastolic function. There was a significant correlation between IGF-1 and left ventricular mass (r = 0.45, p less than 0.02). Lean body mass was also significantly correlated with left ventricular mass (r = 0.78, p less than 0.0001) and left ventricular diastolic function (r = -0.63, p less than 0.01). The mean exercise duration was 8.6 (3.6) minutes. There was a significant correlation between serum IGF-1 and the rate-pressure product on exercise (r = 0.47, p less than 0.01). Seven patients had planar ST segment depression greater than 0.1 mV during exercise testing. In five of these patients there was rapid resolution of ST segment depression immediately after exercise. Two patients developed considerable ST segment depression, and subsequent coronary angiography showed normal coronary arteries. Exercise-induced ST segment depression was not related to the severity or duration of growth hormone deficiency or serum cholesterol concentration. CONCLUSIONS: This study suggests that left ventricular mass and the rate-pressure product are related to the degree of growth hormone deficiency, that left ventricular diastolic dysfunction is frequently seen in hypopituitarism, and that these patients may have ischaemic-like ST segment changes during exercise testing. These findings may explain the increased cardiovascular mortality in patients with hypopituitarism and may also have implications for growth hormone replacement therapy in adults.

Adult↗

Humoral and cardiac effects of TIPS in cirrhotic patients with different "effective" blood volume.

The aim of this study was to evaluate the cardiac effects of transjugular intrahepatic portosystemic shunts (TIPS) in cirrhotic patients with different effective blood volume. Two-dimensional echocardiography was performed before and 7 and 28 days after TIPS insertion in 7 cirrhotic patients with PRA <4 ng/mL/h (group A, normal effective blood volume) and 15 with PRA >4 ng/mL/h (group B, reduced effective blood volume). Before TIPS, most cirrhotic patients showed diastolic dysfunction as indicated by reduced early maximal ventricular filling velocity (E)/late filling velocity (A) ratio. Patients of group B differed from patients of group A because of smaller left ventricular volumes and stroke volume, indicating central underfilling. After TIPS insertion, portal decompression was associated with a significant increase of cardiac output (CO) and a decrease of peripheral resistances. The most important changes were recorded in patients of group B, who showed a significant increase of both the end-diastolic left ventricular volumes and the E/A ratio and a significant decrease of PRA. In conclusion, these results show that the hemodynamic effects of TIPS differ according to the pre-TIPS effective blood volume. Furthermore, TIPS improves the diastolic cardiac function of cirrhotic patients with effective hypovolemia. This result is likely due to a TIPS-related improvement of the fullness of central blood volume.

Aged↗

[Effect of complex therapy including ATP-long on left ventricular diastolic function in patients with ischemic heart disease at rest and under isometric load].

The study comprised 34 patients with ischemic heart disease (IHD) stable functional class I-II extertional angina with impaired relaxation type diastolic dysfunction of the left ventricle. Instituted in all patients before and after the combined treatment involving the use of ATP-Long (group I) or ATP solution injectable i.m. (group II) was dopplercardiometry in rest and at the peak of isometric load. The course of ATP treatments administration was ten days in duration. The use in a combined treatment IHD patients of ATP-Long, a new metabolic-action type drug preparation of Ukraine, permits improving parameters of the diastole temporal patterns, as evidenced by results of the studies made.

Adenosine Triphosphate↗

Prognostic value of diastolic filling parameters derived using a novel image processing technique in patients > or = 70 years of age with congestive heart failure.

Conventional echocardiographic characterization of diastolic function requires manual analysis of Doppler E-and A-wave amplitudes, deceleration times, isovolumic relaxation times, and pulmonary venous flow patterns. Mathematic modeling of the suction pump activity of the heart permits characterization of diastolic function through model-based image processing, which relies solely on transmitral Doppler images. This automated method uniquely specifies the entire E-wave contour using 3 parameters (x(o), k, and c) that determine E-wave amplitude, width, and rate of decay. Moreover, the index beta = c2 - 4k, reflecting the balance between chamber viscosity and stiffness/recoil, represents a novel parameter for characterizing diastolic function. We analyzed Doppler E waves from 39 patients (mean age 79 years, 61% women, mean ejection fraction 47%) using the model-based image processing technique. A value of beta <-900 was selected as indicative of severe diastolic dysfunction. Of 17 subjects with beta <-900, 8 (47%) were no longer alive at 1 year. Of 22 subjects with beta >-900, all were alive (p = 0.001). The index beta, dichotomized at <-900, had a predictive accuracy of 0.769 (30 of 39), a negative predictive value of 1.0 (22 of 22 alive), and a positive predictive value of 0.471 (8 of 17 deceased) for 1-year vital status. Of 14 subjects with deceleration time < or =160 ms, 5 (36%) were deceased at 1 year, whereas for deceleration time >160 ms, 22 of 25 patients were alive (p = NS). Of 16 subjects with ejection fraction <45%, 6 (38%) were deceased at 1 year. Of 23 subjects with ejection fraction >45%, 21 were alive at 1 year (p = 0.074). On multivariate analysis, beta dichotomized at -900 was the strongest independent predictor of 1-year mortality. We conclude that evaluation of diastolic function using model-based image processing provides valuable prognostic information in elderly patients with heart failure.

Aged↗

Left ventricular systolic and diastolic function after anthracycline chemotherapy in childhood.

BACKGROUND: In childhood, late cardiotoxicity is characterized by inappropriately thin wall and consequent increased end-systolic wall stress, but the associations of impaired left ventricular geometry and function occurring under these circumstances need further investigation. HYPOTHESIS: The purpose of this study was to assess anthracycline late effects on the relationships occurring between increased end-systolic stress (ESS) and changes in both M-mode systolic measurements (i.e., endocardial and midwall fractional shortening) and Doppler diastolic indices in the pediatric age. METHODS: The population consisted of 101 children treated with anthracyclines for at least 12 months and 91 healthy children. Using M-mode echocardiography, end-systolic wall stress was calculated as index of afterload, and endocardial and midwall fractional shortening as systolic indices. Doppler transmitral measurements were made as diastolic indices. RESULTS: Patients treated with anthracyclines showed significantly lower relative wall thickness and left ventricular mass index, greater end-systolic wall stress, reduced endocardial and midwall fractional shortening and peak E/A ratio, prolonged deceleration, and isovolumic relaxation times. Direct relationships were found between end-systolic wall stress and both endocardial and midwall shortening. The use of midwall shortening in the relation showed a greater, but not significant increase (from 3 to 6%) in the proportion of patients with depressed systolic function than did endocardial shortening. In the anthracycline group, end-systolic wall stress was also inversely related to relative wall thickness and directly to isovolumic relaxation time. CONCLUSIONS: In childhood, reduced myocardial thickness and increased afterload explain much of systolic and diastolic dysfunction of late anthracycline toxicity. Midwall fractional shortening does not seem to add useful information for identifying subsets of children more prone to the development of heart failure.

Adolescent↗

Cardiac function in children post-orthotopic liver transplantation: echocardiographic parameters and biochemical markers of subclinical cardiovascular damage.

Tacrolimus and cyclosporin A (CsA), the mainstay of preventive therapy for solid organ rejection, may cause various side-effects, such as hypertension and nephrotoxicity. Furthermore, tacrolimus is associated with cardiac hypertrophy. In the immediate post-transplant period, both drugs raise the levels of Endothelin-1 (ET), a potent vasoconstrictor; and of B-type Natriuretic Peptide (BNP), a sensitive marker of left ventricular volume overload, which may precede echocardiographic changes of cardiac dysfunction. The aim of the study was to investigate the presence of cardiac damage, by echocardiography and by the biochemical markers BNP and ET, in post-orthotopic liver transplantation (OLT) children, receiving long-term immunosuppressive therapy. ET (ELISA) and BNP (RIA) were measured in plasma of 18 children, post-OLT and 18 healthy controls. Children post-OLT were echocardiographically assessed for left ventricular mass (interventricular septum and posterior wall dimensions), systolic function (ejection fraction, fractional shortening) and diastolic parameters (mitral valve E and A waves, deceleration time, isovolumic relaxation time). None of the post-transplant recipients had a history or physical examination consistent with cardiac disease and all recipients were normotensive. Echocardiography revealed no systolic or diastolic dysfunction in any of the recipients. The mean ET and BNP levels tended to be higher among children post-liver transplant, compared with healthy controls (ET: 4.22 +/- 5.35 pg/mL vs. 2.1 +/- 2.0 pg/mL; BNP: 7.05 +/- 4.4 pg/mL vs. 5.87 +/- 2.0 pg/mL, respectively, mean +/- s.d.) although differences did not reach statistical significance. Three children (17%) had elevated BNP and/or ET levels. A strong correlation was observed between ET and BNP levels in post-OLT children (r = 0.79, p < or = 0.05). No correlation was found between ET or BNP levels and echocardiographic findings. In children receiving long-term immunosuppressive therapy post-OLT, although cardiac function is grossly preserved, ET and BNP levels tend to be higher than in healthy, age-matched children. Thus, elevated levels of BNP and/or ET may identify patients with early cardiac damage.

Adolescent↗

Does a gender-related effect of growth hormone (GH) replacement exist on cardiovascular risk factors, cardiac morphology, and performance and atherosclerosis? Results of a two-year open, prospective study in young adult men and women with severe GH deficiency.

CONTEXT: GH secretion and response to GH replacement are gender-related. OBJECTIVE: The objective of this study was to investigate the effects of GH deficiency (GHD) and replacement on the cardiovascular system according to gender. DESIGN: The design was open and prospective. SETTING: The study was conducted at a university hospital. SUBJECTS: Subjects included 36 severe adult-onset GHD patients (18 men, 20 women, aged < 45 yr); 36 gender-, age-, and body mass index-matched healthy subjects served as controls. INTERVENTIONS: Subjects received GH replacement at a median dose of 6.5 microg/kg.d in men and 7.7 microg/kg.d in women for 2 yr. MAIN OUTCOME MEASURES: Homeostasis model assessment index, total to HDL cholesterol ratio, fibrinogen and C-reactive protein levels, left ventricular mass index, blood pressure, heart rate, diastolic filling, and systolic function at rest and at peak exercise and intima-media thickness (IMT) at common carotid arteries were measured. RESULTS: Basal prevalence and/or degree of insulin resistance, lipid alterations, compromised cardiac function, and IMT were similar in women and men. Diastolic dysfunction was more prevalent in men (61 vs. 25%, P = 0.036). After GH replacement, IGF-I levels normalized in all patients. Lipid profile, fibrinogen, and C-reactive protein levels normalized in all cases. The total to HDL ratio (P = 0.04) was higher in women than men. The homeostasis model assessment index persisted higher in GHD patients than controls and decreased only in GHD men (P = 0.017). Left ventricular mass index normalized during treatment in both women and men, abnormal diastolic function persisted in three women (P = 0.031), and abnormal systolic performance persisted in six women and one man (P = 0.13). IMT decreased similarly in women and men, persisting higher than in controls. Exercise performance normalized in all. CONCLUSIONS: Two-year GH replacement has similar beneficial effects on cardiac and exercise performance and atherosclerosis in women and men with severe GHD.

Adult↗

Detection of preclinical left ventricular dysfunction in Fabry disease: the contribution of tissue Doppler.

INTRODUCTION: Fabry disease is a rare X-linked lysosomal storage disorder caused by a deficiency of alpha-galactosidase, which results in progressive intracellular accumulation of glycosphingolipids in various tissues. Cardiac involvement is frequent, with left ventricular (LV) hypertrophy (concentric, apical or asymmetric septal) as the most common finding. Evaluating LV systolic dysfunction with conventional echocardiography is not sufficiently sensitive to detect impaired myocardial function early in the course of the disease. Doppler myocardial imaging can quantify changes in global and regional longitudinal myocardial function with great precision. AIM: To identify parameters of cardiac dysfunction in patients with Fabry disease with no cardiac symptoms using conventional or Doppler echocardiography and tissue Doppler (including tissue tracking, strain and strain rate). METHODS: Four patients with Fabry disease (3 female; mean age 47 +/- 17 years) and 29 healthy controls (19 female and 10 male; mean age 38 +/- 14 years) were studied with conventional echocardiography and tissue Doppler imaging using a Vivid 7 scanner. The following parameters were measured: LV dimensions, ejection fraction (using Simpson's rule), systolic and diastolic velocities and tissue tracking of the mitral annulus at six sites (apical views). LV peak systolic strain and strain rate were obtained in 12 segments from apical views. RESULTS: Two patients had LV hypertrophy (one concentric and one apical). Diastolic impairment was detected in three patients by reduced flow propagation velocity of early transmitral flow (Vp) and E/Vp ratio. Mitral annulus systolic velocities were lower in Fabry disease than in the controls. Peak systolic strain and strain rate were diminished in all segments in three patients, showing impaired myocardial systolic function. The results are presented for each of the four patients. CONCLUSIONS: In patients with Fabry disease, with no cardiac symptoms and normal LV systolic function on conventional echocardiography, diastolic dysfunction was detected by Vp and E/Vp ratio regardless of LV hypertrophy. However, tissue Doppler imaging was able to detect impaired myocardial systolic function, particularly in patients with LV hypertrophy.

Adult↗

[Disorders of diastolic function in chronic left ventricular insufficiency].

Abnormalities in the diastolic function of the left ventricular pump are the common determinant and, above all, the earliest manifestation of all forms of chronic left ventricular failure, whether or not the left ventricular systolic function is abnormal. Congestive signs, in particular, are directly related to abnormalities of ventricular filling. Primary diastolic dysfunction is the cause of left ventricular failure in about 40 p. 100 of the cases, but it may also be observed in almost all cardiopathies. In myocardial ischaemia the pressure-volume relation is displaced upwards owing to a slowed down, inhomogeneous and incomplete relaxation. Left ventricular hypertrophy, whether it is due to excessive pressure (arterial hypertension, aortic stenosis) or reflects a primary hypertrophic cardiomyopathy, is associated with a slowing down of ventricular relaxation and a reduction of left ventricular diastolic distensibility, even though the ventricular pump systolic function remains normal for a long time. Outside alterations in the distensibility of the ventricular muscle, ventricular dilatation alters ventricular filling by forcing the ventricle to function on the vertical part of its diastolic pressure-volume relation. Nowadays, the aged hearts is the most frequent cause of heart failure with normal systolic function. In all cases dysrhythmias and atrioventricular desynchronization act as aggravating factors. Treatment is often difficult since positively inotropic drugs or arterial vasodilators frequently have a modest or even deleterious effect.

Aged↗

A SERCA2 pump with an increased Ca2+ affinity can lead to severe cardiac hypertrophy, stress intolerance and reduced life span.

Abnormal Ca(2+) cycling in the failing heart might be corrected by enhancing the activity of the cardiac Ca(2+) pump, the sarco(endo)plasmic reticulum Ca(2+)-ATPase 2a (SERCA2a) isoform. This can be obtained by increasing the pump's affinity for Ca(2+) by suppressing phospholamban (PLB) activity, the in vivo inhibitor of SERCA2a. In SKO mice, gene-targeted replacement of SERCA2a by SERCA2b, a pump with a higher Ca(2+) affinity, results in cardiac hypertrophy and dysfunction. The stronger PLB inhibition on cardiac morphology and performance observed in SKO was investigated here in DKO mice, which were obtained by crossing SKO with PLB(-/-) mice. The affinity for Ca(2+) of SERCA2 was found to be further increased in these DKO mice. Relative to wild-type and SKO mice, DKO mice were much less spontaneously active and showed a reduced life span. The DKO mice also displayed a severe cardiac phenotype characterized by a more pronounced concentric hypertrophy, diastolic dysfunction and increased ventricular stiffness. Strikingly, beta-adrenergic or forced exercise stress induced acute heart failure and death in DKO mice. Therefore, the increased PLB inhibition represents a compensation for the imposed high Ca(2+)-affinity of SERCA2b in the SKO heart. Limiting SERCA2's affinity for Ca(2+) is physiologically important for normal cardiac function. An improved Ca(2+) transport in the sarcoplasmic reticulum may correct Ca(2+) mishandling in heart failure, but a SERCA pump with a much higher Ca(2+) affinity may be detrimental.

Animals↗

Abnormal cardiac function in the streptozotocin-induced non-insulin-dependent diabetic rat: noninvasive assessment with doppler echocardiography and contribution of the nitric oxide pathway.

OBJECTIVES: We sought to evaluate in vivo and in vitro left ventricular (LV) geometry and function in streptozotocin-induced diabetic rats and the possible role of the nitric oxide (NO) pathway. BACKGROUND: Diabetes results in cardiac dysfunction; however, the specific abnormalities are unknown. Because decreased NO contributes to abnormal vascular function in diabetics, we hypothesized that NO pathway abnormalities may contribute to diabetic cardiomyopathy. METHODS: Control rats and those with non-insulin-dependent diabetes mellitus (NIDDM) underwent echocardiography, hemodynamic assessment, isolated heart perfusion and measurement of exhaled NO and LV endothelial constitutive nitric oxide synthase (ecNOS). RESULTS: Diabetic rats had increased LV mass (3.3 +/- 0.6 vs. 2.6 +/- 0.3 g/g body weight [BW], p < 0.001) and cavity dimensions (diastolic 2.0 +/- 0.1 vs. 1.8 +/- 0.2 cm/cm tibial length [TL], p < 0.05). Diabetic rats had prolonged isovolumic relaxation time (IVRT) (40 +/- 8 vs. 26 +/- 6 ms, p < 0.0001), increased atrial contribution to diastolic filling (0.47 +/- 0.09 vs. 0.30 +/- 0.08 m/s, p < 0.0001), and elevated in vivo LV end-diastolic pressure (7 +/- 6 vs. 2 +/- 1 mm Hg, p = 0.04). Diabetic rats had increased chamber stiffness. Shortening was similar in both groups, despite reduced meridional wall stress in diabetics, suggesting impaired systolic contractility. Exhaled NO was lower in diabetic rats (1.8 +/- 0.2 vs. 3.3 +/- 0.3 parts per billion, p < 0.01) and correlated with Doppler LV filling. The ecNOS was similar between the groups. CONCLUSIONS: Diabetic cardiomyopathy is characterized by LV systolic and diastolic dysfunction, the latter correlating with decreased exhaled NO. The NO pathway is intact, suggesting impaired availability of NO as contributor to cardiomyopathy.

Animals↗

[Correlation of B-type natriuretic peptide (NT-proBNP) levels and conventional and tissue Doppler echocardiographic parameters of left ventricular diastolic function in patients with hypertrophic cardiomyopathy].

INTRODUCTION: Preload-independent pulsed tissue Doppler echocardiography (TDI) and conventional pulsed Doppler echocardiography were used to assess the global left ventricular diastolic function in patients with hypertrophic cardiomyopathy (HCM). Levels of B-type natriuretic peptide (BNP) could be elevated in patients with isolated left ventricular diastolic dysfunction. AIM: The study was to investigate the correlation between BNP levels and the parameters measured by conventional echocardiography and TDI in patients with HCM. PATIENTS: 32 consecutive patients with HCM (21 male, 11 female, mean age 47 +/- 14 years) were studied. Inclusion criteria were: normal sinus rhythm; ejection fraction > or = 50%; absence of moderate to severe mitral regurgitation or prosthetic mitral valve. METHODS: In addition to the conventional transmitral flow patterns (E, A, E/A, DT, IVRT) myocardial early (Ea) and late diastolic (Aa) velocities were measured at the lateral and septal border of the mitral annulus by ATL HDI 5000 ultrasound system. Ea/Aa and E/Ea ratios were calculated. NT-proBNP levels were measured by Roche-Elecsys test (immunoassay). Because the distribution of BNP values did not appear to be normal, the values were transformed into a natural logarithm (InBNP). RESULTS: Mean BNP level was 543 +/- 845 pg/ml. BNP levels negatively correlated with lateral Aa values (r = -0.59, p < 0.001). No significant relationship was observed between BNP levels and other echocardiographic parameters. By stepwise multiple linear regression analysis the only significant predictor of InBNP was lateral Aa value, too (r = -0.467, p < 0.05). CONCLUSION: Significant correlation was found between BNP levels and a single TDI parameter characterizing left atrial systolic function, but there was no significant correlation between BNP levels and global left ventricular diastolic function characterized by either conventional echocardiographic or TDI parameters.

Adult↗

Myocardial extracellular matrix remodeling in transgenic mice overexpressing tumor necrosis factor alpha can be modulated by anti-tumor necrosis factor alpha therapy.

Myocardial fibrosis caused by maladaptive extracellular matrix (ECM) remodeling is implicated in the dysfunction of the failing heart. Matrix metalloproteinases (MMPs) regulate ECM remodeling, and are regulated by cytokines. Transgenic mice with cardiac-specific overexpression of tumor necrosis factor alpha (TNF-alpha) (TNF1.6) develop heart failure. We hypothesized that modulation of TNF-alpha and/or MMP activity might alter the myocardial ECM remodeling process and the development of heart failure. To test this hypothesis, we took advantage of the TNF1.6 mice and studied soluble and total collagens and collagen type profiling by using hydroxyproline quantification, Sircol collagen assay, Northern blot analysis, and immunohistochemistry and studied myocardial function by using echocardiography. Progressive ventricular hypertrophy and dilation in the TNF1.6 mice were accompanied by a significant increase in MMP-2 and MMP-9 activity, an increase in collagen synthesis, deposition, and denaturation, and a decrease in undenatured collagens. In young TNF1.6 mice, these changes in the ECM were associated with marked diastolic dysfunction as demonstrated by significantly reduced transmitral Doppler echocardiographic E/A wave ratio. Anti-TNF-alpha treatment with adenoviral vector expressing soluble TNF-alpha receptor type I attenuated both MMP-2 and MMP-9 activity, prevented further collagen synthesis, deposition and denaturation, and preserved myocardial diastolic function in young, but not old, TNF1.6 mice. The results suggest a critical role of TNF-alpha and MMPs in myocardial matrix remodeling and functional regulation and support the hypothesis that both TNF-alpha and MMPs may serve as potential therapeutic targets in the treatment of heart failure.

Animals↗

The role of Doppler echocardiography in the assessment of left ventricular diastolic function.

The role of Doppler echocardiography of transmitral filling velocities in the assessment of diastolic function in man has not been adequately defined. It is now appreciated that multiple interacting factors such as loading conditions influence the transmitral velocity profile independent of intrinsic left ventricular diastolic function. Extrapolating the status of diastolic function from the transmitral velocity profile is complicated by these factors. The load dependence of ventricular filling has tempered the initial enthusiasm for the clinical application of the Doppler technique. In the present review, studies examining invasive parameters of diastolic function and Doppler indices of diastolic filling are discussed to gain greater insight and understanding of the role of Doppler echocardiography in the noninvasive assessment of diastolic function. These studies have demonstrated a relatively consistent influence of left ventricular relaxation, chamber stiffness, and left atrial pressure on the transmitral velocity filling profile. Impairment of relaxation impedes early filling and may result in a compensatory increase in atrial contribution to filling. An independent decrease in left atrial pressure from altered loading conditions may also reduce filling in early diastole. Increased left ventricular chamber stiffness (i.e., noncompliant left ventricle) impairs atrial contribution to filling and may enhance early filling. Theoretically, reduced left atrial contractility may decrease atrial contribution to filling. Pulmonic vein flow demonstrating increased retrograde flow during atrial systole helps to exclude impaired left atrial contractility. An increased left atrial pressure from altered loading conditions may also augment early filling. Therefore, an invasive or clinical assessment of left atrial pressure as being increased, decreased, or normal greatly aids in the interpretation of the transmitral filling velocity profile when inferences on the status of diastolic function are being made. Diastolic dysfunction is likely when a given pattern of filling cannot be explained on the basis of left atrial pressure. In situations where reasonable estimates on the status of left atrial pressure cannot be done, striking alterations in the transmitral velocity filling profile may be useful.

Animals↗