Intravenous atrial natriuretic peptide prevents left ventricular remodeling in patients with first anterior acute myocardial infarction

OBJECTIVES: The study evaluates the effect of atrial natriuretic peptide (ANP) compared with nitroglycerin (GTN) on left ventricular (LV) remodeling after first anterior acute myocardial infarction (AMI). BACKGROUND: Compared with GTN, ANP suppresses the renin-angiotensin-aldosterone system and endothelin-1 (ET-1), which stimulate LV remodeling. METHODS: Sixty patients with a first anterior AMI were randomly divided into the ANP (n = 30) or GTN (n = 30) groups after direct percutaneous transluminal coronary angioplasty. We evaluated LV ejection fraction (LVEF), end-diastolic volume index (LVEDVI) and end-systolic volume index (LVESVI) at the acute phase and after one month. We also measured neurohumoral factors during study drug infusion. RESULTS: There was no difference in the baseline characteristics or LVEF (46.9+/-1.0 vs. 46.8+/-1.3%) between the two groups. Although there was no difference in hemodynamics during the infusion periods, the LVEF was significantly improved after one month compared with the baseline value in both groups, but it was improved more in the ANP group than in the GTN group (54.6+/-1.1%, 50.8+/-1.3%, p < 0.05). Left ventricular enlargement was prevented in the ANP group (LVEDVI, 85.8+/-3.1 ml/m2 to 87.3+/-2.7 ml/m2; p = ns, LVESVI, 45.6+/-1.8 ml/m2 to 41.0+/-2.1 ml/m2, p < 0.05) but not in the GTN group (LVEDVI, 86.2+/-4.1 to 100.2+/-3.7, p < 0.01; LVESVI, 46.3+/-2.8 ml/m2 to 51.1+/-3.0 ml/m2, p = ns). During the infusion, ANP suppressed plasma levels of aldosterone, angiotensin II and ET-1 compared with GTN. CONCLUSIONS: These findings indicate that in patients with a first anterior AMI, an ANP infusion can prevent LV remodeling better than can GTN, and effectively suppresses aldosterone, angiotensin II and ET-1.     

Effects of reperfusion on left ventricular ejection fraction and volume after acute myocardial infarction.

The effects of reperfusion on left ventricular (LV) function and volume were studied in patients with evolving acute myocardial infarction (AMI). We analyzed the LV ejection fraction and volume in patients who had been admitted within 24 h of the onset of their first AMI with culprit lesion of #6, #7 and #1 (American Heart Association classification). Sixty-five patients (Re group) received successful reperfusion therapy within 6 h after the AMI. The other 60 patients (Oc group), who were admitted from 6 to 24 h after the AMI, received conservative therapy. Patients with re-obstruction of the culprit lesion after reperfusion therapy were excluded from the Re group. Patients with spontaneous recanalization following conservative therapy were excluded from the Oc group. The LV ejection fraction (LVEF), LV end-systolic volume index (LVESVI), and LV end-diastolic volume index (LVEDVI) were measured using a modified Dodge's formula by left ventriculography performed 4 weeks after the AMI. LVEF in the Re group was significantly greater than in the Oc group (57 +/- 12 vs 49 +/- 11%) (mean +/- SD, p less than 0.01). LVESVI in the Re group was significantly smaller than in the Oc group (30 +/- 13 vs 38 +/- 16 ml/m2, p less than 0.01). Although LVEDVI was not significantly different between the 2 groups, in patients with a responsible coronary lesion of segment #6, LVEDVI in the Re group was significantly smaller than in the Oc group (67 +/- 14 vs 77 +/- 18 ml/m2, p less than 0.05). Although LVEF and LV volume correlated in both groups, the correlation was weak (r = 0.40-0.42), suggesting that LV volume was not dependent solely on LV functional recovery. The incidence of ventricular aneurysm in the Re group was significantly lower than in the Oc group (15.4 vs 45.0%, p less than 0.01). Multivariate analysis selected reperfusion of the responsible coronary artery as one of the factors significantly associated with a reduction of LVEDVI, LVESVI, an improvement of LVEF, and a decrease in the rate of aneurysm formation. In summary, our results indicated that reperfusion improved EF, reduced LV volume, and decreased the rate of aneurysm formation as compared to non-reperfusion, which suggests that reperfusion therapy is beneficial for both functional recovery and ventricular remodeling.     

Plasma and pericardial fluid natriuretic peptide levels in postinfarction ventricular dysfunction

AIMS: In the present study we examined plasma and pericardial fluid ANP and BNP concentrations in postinfarction ventricular dysfunction. The association of peptide levels to left ventricular (LV) dysfunction and to the localization of the myocardial infarction (MI) was studied. METHODS AND RESULTS: Plasma and pericardial fluid samples were obtained from 37 patients undergoing coronary bypass surgery. According to the ECG and preceding coronary angiography, the patients were divided into three groups: previous anterior myocardial infarction (MI) (n=12), previous inferior/posterior MI (n=15) and no history of MI (n=10). When compared to the control group with no MI, the patients with anterior MI had elevated plasma ANP and BNP (134+/-13 vs. 81+/-15 pg/ml, P<0.01 and 95+/-10 pg/ml vs. 26+/-8 pg/ml, P<0.01, respectively) and pericardial fluid BNP (473+/-60 pg/ml vs. 57+/-8 pg/ml, P<0.001) levels. The plasma natriuretic peptide concentrations were not increased in the patients with inferior/posterior MI, but the pericardial fluid BNP concentrations were greater than in the patients with no history of MI (129+/-35 pg/ml vs. 57+/-8 pg/ml, P<0.05). Six of the 12 patients with previous anterior MI had LVEF> or =45%. Despite their normal LV systolic function, these patients had increased plasma and pericardial fluid BNP levels when compared to the group with no history of MI (68+/-18 pg/ml vs. 26+/-8 pg/ml, P<0.05 and 534+/-258 pg/ml vs. 57+/-8 pg/ml, P<0.01, respectively). CONCLUSIONS: Previous anterior myocardial infarction was associated with increased cardiac BNP production even if the LV systolic function was normal (LVEF> or =45%). The high pericardial fluid BNP concentrations in postinfarction patients suggest that the BNP synthesis and release are augmented in the ventricular myocardium independent from the LVEF.     

Clinical significance of acute-phase brain natriuretic peptide in acute myocardial infarction treated with direct coronary angioplasty

OBJECTIVES: To investigate the relationship between brain natriuretic peptide (BNP) plasma concentration levels and the clinical course, mortality and success of left ventricular remodeling by direct percutaneous coronary intervention (PCI) in patients with acute myocardial infarction. METHODS: One hundred thirty consecutive first-acute myocardial infarction patients were successfully reperfused by direct PCI. BNP plasma concentration levels were assessed at 24 hr from onset, and patients were divided into the high (> or = 290 pg/ml) plasma BNP group (H-BNP group; n = 65) or low (< 290 pg/ml) plasma BNP subset (L-BNP group; n = 65). Left ventriculography was performed in both the acute (following reperfusion therapy) and chronic (20 +/- 8 days after onset) stages to evaluate left ventricular ejection fraction (LVEF), left ventricular end-diastolic volume index (LVEDVI) and regional wall motion (RWM). Differences between the parameters at the two stages (chronic stage--acute stage) were expressed as delta LVEF, delta LVEDVI, and delta RWM. RESULTS: There were significantly more major complications in the H-BNP group than in the L-BNP group. There was significantly higher mortality in the H-BNP group (p < 0.01). Multivariate analysis identified only BNP plasma concentration as an independent predictor of mortality (p < 0.05). There were no significant differences in left ventricular function in the acute stage between the groups, but LVEF, LVEDVI, and RWM were all significantly worse in the chronic stage in the H-BNP group compared with the L-BNP group. Moreover, delta LVEF (p < 0.001), delta LVEDVI (p < 0.05), and delta RWM (p < 0.01) were also significantly worse in the H-BNP group. CONCLUSIONS: Early-phase BNP plasma concentrations after successful PCI in patients with acute myocardial infarction may be correlated closely with major complications, and may be of prognostic importance. BNP plasma concentration may also be an indicator of left ventricular remodelling.     

Cardioprotective effects of magnesium sulfate in patients undergoing primary coronary angioplasty for acute myocardial infarction.

BACKGROUND: Experimental evidence indicates that magnesium sulfate may have potential cardioprotective properties as an adjunct to coronary reperfusion. The present study was designed to examine the hypothesis that magnesium might have beneficial effects on left ventricular (LV) function and coronary microvascular function in patients with acute myocardial infarction (AMI). METHODS AND RESULTS: The study population of 180 consecutive patients with a first AMI (anterior or inferior) underwent successful primary coronary intervention. Patients were randomized to treatment with either intravenous magnesium (magnesium group, n=89) or normal saline (control group, n=91). Pre-discharge left ventriculograms were used to assess LV ejection fraction (LVEF), regional wall motion (RWM) within the infarct-zone and LV end-diastolic volume index. The Doppler guidewire was used to assess coronary flow velocity reserve (CFVR) as an index of coronary microvascular function. Magnesium group subjects showed significantly better LV systolic function (LVEF 63+/-9% vs 55+/-13%, p<0.001; RWM: -1.01+/-1.29 SD/chord vs -1.65+/-1.11 SD/chord, p=0.004), significantly smaller LV end-diastolic volume index (63+/-17 ml/m(2) vs 76+/-20 ml/m(2), p<0.001), and significantly higher CFVR (2.95+/-0.76 vs 2.50+/-0.99, p=0.023) than controls. CONCLUSION: Magnesium sulfate as an adjunct to primary coronary intervention shows favorable functional outcomes in patients with AMI.     

Predictive factors of deteriorating left ventricular function after direct percutaneous coronary intervention for acute anterior myocardial infarction

OBJECTIVES: To evaluate useful predictors for the deterioration of left ventricular function after direct percutaneous coronary intervention in patients with acute myocardial infarction. METHODS: This study included 96 consecutive patients with first acute anterior myocardial infarction reperfused successfully by direct percutaneous coronary intervention within 6 hr of the onset, who underwent left ventriculography in the acute (soon after reperfusion therapy) and chronic (20 +/- 8 days after onset) phases. The left ventricular ejection fraction (LVEF), and the difference in LVEF (delta LVEF) between the two stages were calculated. The patients were divided into two groups according to the delta LVEF (low delta LVEF group: delta LVEF < 0%, n = 30; high delta LVEF group: delta LVEF > or = 0%, n = 66). RESULTS: There were significantly more patients with diabetes mellitus (53% vs 18%, p = 0.0009), older age (73 +/- 11 vs 67 +/- 12 years, p = 0.003) and complete occlusion of the culprit artery (13% vs 35%, p = 0.03) in the low delta LVEF group than in the high delta LVEF group. Left ventricular end-diastolic volume index (LVEDVI: 75 +/- 14 vs 62 +/- 15 ml/m2, p = 0.002) in the chronic stage and delta LVEDVI(5 +/- 8 vs -3 +/- 14 ml/m2, p = 0.04) were significantly worse in the low delta LVEF group than in the high delta LVEF group. Multivariate analysis identified diabetes mellitus as the only independent predictor of reduction of LVEF (odds ratio 4.44, 95% confidence interval 1.27-15.52, p = 0.02). CONCLUSIONS: Some patients with acute anterior myocardial infarction treated by direct percutaneous coronary intervention had reduction of the LVEF. There was a close relationship between reduction of the LVEF and left ventricular remodeling. Diabetes mellitus was the most useful predictor of reduction of the LVEF.     

Aldosterone receptor antagonism induces reverse remodeling when added to angiotensin receptor blockade in chronic heart failure.

OBJECTIVES: The objective of this study was to determine if adding spironolactone to an angiotensin II receptor blocker improves left ventricular (LV) function, mass, and volumes in chronic heart failure. BACKGROUND: Add-on spironolactone therapy substantially improves clinical outcomes among patients with severe heart failure (HF) on standard therapy. However, the value of combining spironolactone with an angiotensin II receptor blocker on LV reverse remodeling in mild-to-moderate systolic HF is unclear. METHODS: Fifty-one systolic HF patients with left ventricular ejection fraction (LVEF) <40% were randomly assigned to receive 1-year treatment of candesartan and spironolactone (combination group) or candesartan and placebo (control group). Reverse remodeling was assessed by serial cardiac magnetic resonance imaging and echocardiographic tissue Doppler imaging (TDI). RESULTS: There were significant improvements in LVEF (35 +/- 3% vs. 26 +/- 2%, p < 0.01) and reduction of LV end-diastolic volume index (121 +/- 16 ml/m2 vs. 155 +/- 14 ml/m2, p = 0.001), end-systolic volume index (88 +/- 17 ml/m2 vs. 120 +/- 15 ml/m2, p < 0.0005), and LV mass index (81 +/- 6 g/m2 vs. 93 +/- 6 g/m2, p = 0.002) in the combination group at 1 year. In addition, there was significant increase in peak basal systolic velocity and strain by TDI, decrease in index of filling pressure, and increase in cyclic variation integrated backscatter. In the control group, there were no significant changes in all these parameters after 1 year. CONCLUSIONS: The addition of spironolactone to candesartan has significant beneficial effects on LV reverse remodeling in patients with mild-to-moderate chronic systolic HF.     

Restrictive filling pattern predicts pulmonary hypertension and is associated with increased BNP levels and impaired exercise capacity in patients with heart failure

BACKGROUND: Left ventricular (LV) diastolic dysfunction is a common finding in patients with systolic heart failure (HF). Severe diastolic dysfunction, which is defined as LV restrictive filling pattern (RFP), is associated with more severe HF, increased sympathetic activity and reduced exercise capacity. It has also been shown to be a predictor of lower survival rate in patients with HF. AIM: To evaluate associations between LV diastolic RFP and BNP levels, systolic pulmonary pressure and exercise capacity in patients with clinically stable HF. METHODS: In 56 patients with HF and low LVEF a standard echocardiographic study and cardiopulmonary exercise test were performed. Levels of BNP using RIA method were also measured. RESULTS: Restrictive filling pattern (E/A >2 or 1< E/A <2 and DTE < or =130 ms) was diagnosed in 26 patients. The RFP group showed increased levels of BNP (90.6+/-66 vs. 50.4+/-61 pg/ml; p=0.003), significantly reduced peak VO2 (15.4+/-4.1 vs. 17.8+/-4.9 ml/kg/min; p=0.046), increased VE/VCO2 slope (36.3+/-5.9 vs. 31.9+/-6.3; p=0.01), and elevated PASP (pulmonary artery systolic pressure measured by echo-Doppler) (49.3+/-13.8 vs. 37.2+/-12.6 mmHg; p=0.02). Prevalence of pulmonary hypertension was significantly higher in the RFP group. A significant correlation between DTE and peak VO2 (r=0.28; p=0.02) and inverse correlations between DTE and BNP levels (r=-048; p=0.003), VE/VCO2 slope (r=-0.35; p=0.02) and PASP (r=-0.39; p=0.03) were found. In logistic regression analysis only RFP was independently associated with pulmonary hypertension. CONCLUSIONS: The restrictive filling pattern is an independent predictor of pulmonary hypertension and is associated with increased BNP levels and worse result of cardiopulmonary exercise test.     

Left ventricular volume characteristics and its relationship with right ventricle after repair of tetralogy of Fallot

In order to study the left ventricular volume characteristics and right ventricular influence on left ventricle, cardiac catheterization and biplane cineangiography was performed in 61 patients after repair of tetralogy of Fallot. Preoperative left ventricular volume size was also measured in 25 patients. Postoperative left ventricular end-diastolic volume index (LVEDVI) was 93 +/- 22 ml/m2 (mean +/- standard deviation) and it was 140 +/- 29% of normal left ventricular volume. Left ventricular ejection fraction (LVEF) was 60 +/- 6%. Left ventricular size significantly increased from 109 +/- 25% to 140 +/- 23% of normal by corrective surgery (p less than 0.001). Left ventricular volume characteristics are correlated with right ventricle. LVEDVI increased with increasing right ventricular end-diastolic volume index (RVEDVI) and decreased right ventricular ejection fraction (RVEF). LVEDVI (ml/m2) = 60 + 0.29 RVEDVI (ml/m2), r = 0.52, p less than 0.001, LVEDVI (ml/m2) = 141 - 0.90 RVEF (%), r = -0.30, p less than 0.02. LVEF decreased with increasing RVEDVI and decreased RVEF. LVEF (%) = 68 - 0.075 RVEDVI (ml/m2), r = -0.51, p less than 0.001, LVEF (%) = 43 + 0.32 RVEF (%), r = 0.40, p less than 0.001. On the contrary there was no relationship between right ventricular volume characteristics and right ventricular systolic pressure. There were two cases whose LVEF was less than 50%. In one case right ventricular systolic pressure was as high as 98 mmHg. In the other patient RVEDVI was 299 ml/m2 (453% of normal right ventricular volume) because of severe pulmonary regurgitation.(ABSTRACT TRUNCATED AT 250 WORDS)     

Wall stress modulates brain natriuretic peptide production in pressure overload cardiomyopathy

OBJECTIVES: We postulated that both diastolic and systolic load modulate B-type natriuretic peptide (BNP) production in human pressure overload hypertrophy/failure. BACKGROUND: In isolated myocytes, diastolic stretch induces BNP messenger ribonucleic acid expression. However, the mechanism of the BNP release in human hypertrophy remains controversial. METHODS: In 40 patients with symptomatic aortic stenosis (AS), left ventricular (LV) performance and systolic and diastolic wall stress were calculated from combined invasive and echocardiographic data. Plasma BNP was determined by the rapid point-of-care bedside analyzer (Biosite Triage, Biosite Diagnostics Inc., San Diego, California). RESULTS: A significant relationship was observed between plasma BNP and pulmonary capillary wedge pressure (p < 0.001), fractional shortening (p = 0.001), and aortic valve area (p = 0.006). Furthermore, a significant correlation was noted between BNP and LV mass index (p = 0.005) as well as between BNP and markers of diastolic load such as LV end-diastolic wall stress (p = 0.011), indexed LV end-diastolic volume (p < 0.001), and isovolumic relaxation time (p = 0.02). Preoperative BNP levels were elevated in patients with AS compared with patients without AS. Plasma BNP was higher in AS patients with impaired versus normal preload reserve (297 +/- 56 pg/ml vs. 168 +/- 44 pg/ml; p = 0.017) and in AS patients with clinical deterioration after valve replacement compared with those without (399 +/- 82 pg/ml vs. 124 +/- 41 pg/ml; p = 0.011). CONCLUSIONS: In patients with AS, BNP appears to be regulated not only by systolic but also by diastolic load. This supports the hypothesis that myocardial stretch modulates BNP production in human pressure overload hypertrophy/failure.     

Independent effects of both right and left ventricular function on plasma brain natriuretic peptide

BACKGROUND: Brain natriuretic peptide (BNP) is increased in heart failure; however, the relative contribution of the right and left ventricles is largely unknown. AIM: To investigate if right ventricular function has an independent influence on plasma BNP concentration. METHODS: Right (RVEF), left ventricular ejection fraction (LVEF), and left ventricular end-diastolic volume index (LVEDVI) were determined in 105 consecutive patients by first-pass radionuclide ventriculography (FP-RNV) and multiple ECG-gated equilibrium radionuclide ventriculography (ERNV), respectively. BNP was analyzed by immunoassay. RESULTS: Mean LVEF was 0.51 (range 0.10-0.83) with 36% having a reduced LVEF (<0.50). Mean RVEF was 0.50 (range 0.26-0.78) with 43% having a reduced RVEF (<0.50). The mean LVEDVI was 92 ml/m2 with 22% above the upper normal limit (117 ml/m2). Mean BNP was 239 pg/ml range (0.63-2523). In univariate linear regression analysis LVEF, LVEDVI and RVEF all correlated significantly with log BNP (p<0.0001). In a multivariate analysis only RVEF and LVEF remained significant. The parameter estimates of the final adjusted model indicated that RVEF and LVEF influence on log BNP were of the same magnitude. CONCLUSION: BNP, which is a strong prognostic marker in heart failure, independently depends on both left and right ventricular systolic function. This might, at least in part, explain why BNP holds stronger prognostic value than LVEF alone.     

Predischarge low-dose dobutamine test and prediction of left ventricular function at 1 year in patients with a first anterior myocardial infarction

BACKGROUND: It is unclear whether spontaneous improvement in contractility following acute myocardial infarction (AMI) is related to severity of predischarge systolic dysfunction and can be predicted by isotopic ventriculography with a low-dose dobutamine test (DBT). HYPOTHESIS: Spontaneous improvement in contractility would be similar in patients with more preserved and those with depressed ventricular function, and a DBT test could predict it. METHODS: Left ventricular ejection fraction (LVEF), regional contractility score (RCS), and left ventricular end-diastolic volume index (EDVI) at predischarge, during DBT, and at 1 year were analyzed in 43 patients with a first anterior ST-elevation AMI. RESULTS: Changes produced by DBT in patients with LVEF < 40%, RCS > or = 3, or EDVI > or = 70 ml/m2 were smaller than in those observed at 1 year (LVEF: 30 +/- 5-35 +/- 7%, p < 0.001, vs. 39 +/- 10%, p = 0.005; RCS: 4.9 +/- 1.4-4.6 +/- 2.0, NS, vs. 3.4 +/- 2.0, p < 0.02; EDVI: 92 +/- 14-86 +/- 22, NS, vs. 78 +/- 23 ml/m2, p < 0.03). In contrast, in patients with EF > or = 40%, RCS < 3 or EDVI < 70 ml/m2, changes with DBT tended to be greater than those observed at 1 year (LVEF: 52 +/- 8-57 +/- 11%, p < 0.004 vs. 55 +/- 11%, p < 0.04); RCS: 1.1 +/- 0.9-0.8 +/- 0.8, NS, vs. 1.1 +/- 1.1, NS; and EDVI: 51 +/- 9-47 +/- 11, p < 0.005, vs. 54 +/- 13 ml/m2, NS). CONCLUSIONS: Among patients with a first anterior AMI, spontaneous improvement in contractility at 1 year was greatest in those with a more depressed ventricular function or a dilated ventricle, but its magnitude was underestimated by a predischarge DBT test.     

Relation of left ventricular dilation during acute myocardial infarction to systolic performance, diastolic dysfunction, infarct size and location

The quantification of left ventricular (LV) volumes and assessment of their relation to systolic and diastolic dysfunction, infarct size and anatomic location were performed in 54 patients with a first acute myocardial infarction (AMI). Blood pool radionuclide angiography was used to assess LV end-diastolic, end-systolic, and stroke volume indexes, ejection fraction and peak diastolic filling rate. Infarct size was estimated from plasma MB creatine kinase activity. Substantial LV dilation occurred within the initial 24 hours of AMI. The peak diastolic filling rate was low, even in those patients with a normal ejection fraction. In comparison with inferior AMI (n = 25), patients with anterior AMI (n = 29) had a larger end-diastolic volume index (105 +/- 8 vs 81 +/- 4 ml/m2, p less than 0.01) and end-systolic volume index (64 +/- 7 vs 37 +/- 4 ml/m2, p less than 0.001), but similar stroke volume index (41 +/- 3 vs 43 +/- 2 ml/m2, difference not significant). No significant relation was noted between infarct size estimated by MB creatine kinase and any volumetric index. On repeat study (day 10 after AMI), end-diastolic and end-systolic volume indexes increased further (p less than 0.05 vs day 1) but ejection fraction and peak diastolic filling rate were unchanged. It was concluded that: (1) LV dilation occurs within hours of AMI in both inferior and anterior AMI, but is more marked in the latter; (2) significant LV diastolic dysfunction is the rule, even in patients with preserved LV systolic function; and (3) LV dilation is an early compensatory mechanism that maintains normal stroke volume, even in patients with severely reduced LV function.     

Usefulness of left ventricular mass in predicting recovery of left ventricular systolic function in patients with symptomatic idiopathic dilated cardiomyopathy

Prognosis of idiopathic dilated cardiomyopathy (IDC) is variable. We determined the prognostic value of left ventricular (LV) mass and systolic and diastolic function in patients with IDC of <12 months duration. Clinical and echocardiographic assessment was performed at baseline and at 8+/-6 months follow-up in 25 patients (47+/-13 years) with IDC and an LV ejection fraction (LVEF1) of <40% (22+/-7%). Based on a follow-up LVEF (LVEF2) of < or >40%, patients were divided into unimproved (n = 13, LVEF2 = 21+/-9%) and improved groups (n = 12, LVEF2 = 51+/-11%). There was no difference in the LVEF1 (22+/-8% vs. 22+/-6%), LV end-systolic (5.7+/-0.8 vs. 5.8+/-0.9 cm) or end-diastolic (6.5+/-0.6 vs. 6.6+/-0.9 cm) dimension, wall stress (102+/-26 vs 99+/-28 g/cm2), end-systolic (1.7+/-0.3 vs. 1.8+/-0.2) or end-diastolic (1.7+/-0.3 vs. 1.6+/-0.1) sphericity, dp/dt (582+/-163 vs. 678+/-222 mm Hg/s), or right ventricular fractional shortening (20+/-9% vs. 27+/-7%, p = 0.06) in unimproved and improved groups. LV mass was lower (1.00+/-0.21 vs. 1.38+/-0.27 g/ml, p = 0007) and mitral inflow E-wave deceleration time shorter (97+/-42 vs. 164+/-58 ms, p = 0007) in the unimproved versus the improved group. On Pearson correlation analysis, LV mass (r = 0.62, p = 0.001), deceleration time (r = 0.68, p = 0.0002), wall motion score index (r = -0.47, p = 02), and dp/dt (r = 0.52, p = 03) were the significant predictors of LVEF2. There was correlation between LV mass (grams per milliliter) and deceleration time (r = 0.61, p = 0.001). During follow-up, death occurred in 1, and readmission for worsening heart failure in 4 patients in the unimproved group versus no hospitalization in the improved group. Thus, in patients with recent onset IDC, LV mass and diastolic function determine late outcome.     

Concentration of BNP, endothelin 1, pro-inflammatory cytokines (TNF-alpha, IL-6) and exercise capacity in patients with heart failure treated with carvedilol

BACKGROUND: Recent studies on the pathophysiology of heart failure indicate the role of neurohormones and immune and inflammatory processes as potential mechanisms involved in the pathogenesis and clinical course of chronic heart failure (CHF). AIM: To analyse the relationship between concentrations of brain natriuretic peptide (BNP), endothelin-1 (ET-1), inflammatory cytokines (TNF-alpha, IL-6) and cardiopulmonary stress test parameters, and to evaluate their changes during carvedilol treatment. METHODS: The study included 86 patients (81 men and 5 women) aged from 35 to 70 years (56.8+/-9.19) with symptomatic heart failure and left ventricular ejection fraction <40%, receiving an inhibitor of angiotensin II converting enzyme, diuretic and/or digoxin but not beta-blockers. All patients at baseline, and then at 3 and 12 months after treatment, underwent a panel of studies to assess functional capacity according to NYHA, echocardiographic and cardiopulmonary stress test (CPX) parameters, and serum concentrations of BNP, ET-1, TNF-alpha and IL-6. Before introducing carvedilol we found a weak relationship between concentrations of BNP, ET-1, IL-6 and decreased VO2 peak. RESULTS: At 12 months exercise tolerance was significantly improved (exercise stress testing prolonged by 143.9 s, p=0.001) and an increase in metabolic equivalent (MET) by 1.41 (p=0.001) was observed. The VO2 peak was nonsignificantly increased by a mean of 0.9 ml/kg/min. In patients with baseline VO2 peak <14 ml/kg/min the concentrations of ET-1 and TNF-alpha were significantly higher than in the remaining ones, and after treatment they were significantly reduced. In these patients VO2 peak%N was also significantly increased (39.5+/-7.5 vs. 50.1+/-15,0; p=0.013). The number of patients with VO2 peak <14 ml/kg/min also significantly decreased from 39 to 21 (p=0.013). CONCLUSIONS: In patients with HF decreased value of VO2 peak is associated with LV systolic function disorders and increased levels of BNP, ET-1, TNF-alpha and IL-6. Chronic treatment with carvedilol improves LV systolic function, exercise tolerance and peak oxygen consumption and is associated with significant decrease of BNP, ET-1, TNF-alpha and IL-6 concentrations.     

Impact of chronotropic effect of cilostazol after acute myocardial infarction: insights from change in left ventricular volume and function.

BACKGROUND: Cilostazol, a phosphodiesterase inhibitor, is an antiplatelet agent with positive chronotropic effect, the impact of which on left ventricular (LV) volume and function in acute myocardial infarction (AMI) was evaluated in the present study. METHODS AND RESULTS: In 56 patients with AMI treated with primary coronary stenting, serial echocardiographic studies within 24 h and at 6 months were performed. Patients received a conventional antiplatelet regimen either without cilostazol (group 1, n=29) or with cilostazol (group 2, n=27). At 6 months, the difference in the change in heart rate between group 1 and group 2 was statistically significant (9.9 beats/min; p=0.04). However, changes in LV end-systolic volume (LVESV) (7.1+/-8.2 vs 10.0+/-21.7 ml, p=0.60), LV ejection fraction (EF) (8.2+/-9.9 vs 9.0+/-12.6%, p=0.85) and the ratio of early mitral inflow velocity to the mitral annular velocity (E/E') (0.6+/-3.7 vs -1.7+/-3.2) were not different between the 2 groups. Cardiac event rate was similar between the 2 groups. On multivariate regression analyses, cilostazol therapy had no significant influence on the changes in LVESV, LVEF or E/E'. CONCLUSIONS: In this study, the addition of cilostazol on conventional drug therapy had no adverse influence on LV remodeling or LV function after AMI.     

在不同类型冠心病患者中测定脑钠肽与CD62P的临床意义

目的通过测定不同类型冠心病患者血浆脑钠肽(BNP)与P-选择素(CD62P)的水平,探讨两者相关性及其临床意义。方法将105例行冠状动脉造影的入院患者分为冠心病(CHD)组和对照组(C组),CHD组根据临床诊断分为急性心肌梗死(AMI)小组32例,不稳定型心绞痛小组32例,稳定型心绞痛小组21例,20例冠状动脉造影正常为对照组。所有患者术前抽取静脉血,BNP和CD62P分别采取酶联免疫吸附法和流式细胞法检测。结果 (1)与对照组相比,CHD组的血浆BNP水平(283±42)ng/Lvs(14±4)ng/L,P0.05和CD62P(9.4±3.6)%vs(3.3±1.4)%,P0.05明显增高。(2)CHD不同小组间血浆BNP和CD62P的水平均存在显著性差异(F=21.5、13.6,均P0.01),尤其AMI小组升高明显。(3)经Pearson相关分析显示,BNP与高敏C反应蛋白(hs-CRP)(r=0.62,P0.01)、CD62P(r=0.23,P0.05)呈正相关,BNP与左室射血分数(LVEF)呈负相关(r=-0.42,P0.01);CD62P与hs-CRP呈正相关(r=0.33,P0.05),与LVEF无相关性(r=0.13,P0.05)。(4)多元线性回归分析发现,hs-CRP、LVEF与BNP呈独立相关(回归系数β分别为0.609和-0.412,均P0.001)。结论 (1)BNP和CD62P参与了冠心病的发生和发展,CD62P反应了冠状动脉的炎症状态,两者均与斑块的不稳定性有关,对CHD的诊断、治疗和危险分层有一定的指导意义。(2)血浆BNP水平与左室收缩功能及hs-CRP独立相关。     

Effects of intravenous atrial natriuretic peptide on cardiac sympathetic nerve activity and left ventricular remodeling in patients with first anterior acute myocardial infarction.

OBJECTIVES: We sought to evaluate the effects of atrial natriuretic peptide (ANP) on cardiac sympathetic nerve activity (CSNA) and left ventricular (LV) remodeling in patients with first anterior acute myocardial infarction (AMI) after primary coronary angioplasty. BACKGROUND: The activation of the renin-angiotensin-aldosterone system (RAAS) prevents the uptake of norepinephrine in the myocardium. Atrial natriuretic peptide, a circulating hormone of cardiac origin, has vasodilatory and diuretic properties, and can inhibit the RAAS. METHODS: We studied 50 patients with first anterior AMI who were randomly assigned to receive ANP (group A) or isosorbide dinitrate (group B) before and after primary coronary angioplasty. The ANP or ISDN was continuously infused >48 h. The extent score (ES) was determined from 99mTc-pyrophosphate scintigraphy to evaluate the area of initial myocardial damage 3 to 5 days after primary angioplasty. The LV end-diastolic volume (LVEDV) and LV ejection fraction (LVEF) were determined by left ventriculography 2 weeks later. The delayed heart/mediastinum count (H/M) ratio, delayed total defect score (TDS), and washout rate (WR) were determined from 123I-meta-iodobenzylguanidine scintigraphy after 3 weeks. RESULTS: After primary angioplasty, age, gender, risk factors, peak serum creatine phosphokinase concentration, recanalization time, and ES were similar in the 2 groups. However, in group A (n = 25), the TDS was significantly lower (34 +/- 8 vs. 41 +/- 8; p < 0.05), the H/M ratio was significantly higher (1.96 +/- 0.18 vs. 1.74 +/- 0.23; p < 0.05), and the WR was significantly lower (35 +/- 8% vs. 44 +/- 12%; p < 0.005) than in group B (n = 25). Moreover, the LVEDV and LVEF in group A were better than in group B (LVEDV: 85.5 +/- 28.5 ml vs. 106.3 +/- 39.4 ml [p < 0.05]; LVEF: 47.9 +/- 10.2% vs. 41.5 +/- 11.8% [p < 0.05]). CONCLUSIONS: Intravenous ANP improves CSNA and prevents LV remodeling in patients with first anterior AMI.     

Relevance of coronary microvascular flow impairment to long-term remodeling and systolic dysfunction in hypertrophic cardiomyopathy.

OBJECTIVES: This study sought to evaluate whether the entity of microvascular dysfunction, assessed by positron emission tomography (PET), predicts the long-term development of left ventricular (LV) remodeling and systolic dysfunction in hypertrophic cardiomyopathy (HCM). BACKGROUND: A subgroup of patients with HCM developed LV dilation and systolic impairment. A causal role of coronary microvascular dysfunction has been suggested as the underlying pathophysiological mechanism. METHODS: Fifty-one patients (New York Heart Association functional class I to II) were followed up for 8.1 +/- 2.1 years after measurement of resting and dipyridamole (Dip) myocardial blood flow (MBF). Left ventricular systolic dysfunction was defined as an ejection fraction (LVEF) <50%. RESULTS: The Dip-MBF was blunted in HCM patients compared with a group of healthy control patients (1.50 +/- 0.69 ml/min/g vs. 2.71 +/- 0.94 ml/min/g; p < 0.001). At final evaluation, 11 patients (22%) had an LVEF <50%; in most (n = 7), systolic dysfunction was associated with a significant increase in LV cavity dimensions (>5 mm) during follow-up. These 11 patients showed lower Dip-MBF than the 40 with preserved LV function (1.04 +/- 0.38 ml/min/g vs. 1.63 +/- 0.71 ml/min/g, respectively; p = 0.001); Dip-MBF was particularly blunted in five patients with clinical progression to severe heart failure symptoms or death (Dip-MBF 0.89 +/- 0.15 ml/min/g). At multivariate analysis, the two independent predictors of systolic dysfunction were Dip-MBF in the lowest tertile (<1.1 ml/min/g; relative hazard, 7.5; p = 0.038) and an end-diastolic LV dimension in the highest tertile (>45 mm; relative hazard, 12.3; p = 0.031). CONCLUSIONS: Severe microvascular dysfunction is a potent long-term predictor of adverse LV remodeling and systolic dysfunction in HCM. Our findings indicate microvascular dysfunction as a potential target for prevention of disease progression and heart failure in HCM.     

Doppler echocardiography-derived index of myocardial performance (TEI index): comparison with brain natriuretic peptide levels in various heart disease.

Plasma brain natriuretic peptide (BNP) has diagnostic and prognostic value in heart failure. Cardiac dysfunction varies from systolic or diastolic dysfunction alone to the combination of both. In the present study, Doppler echocardiographic parameters, including the Doppler echocardiography-derived index (TEI index), were compared with plasma BNP levels in 74 patients with various heart diseases. Blood sampling was performed before an echocardiographic examination was conducted. The TEI index was defined as the summation of isovolumic contraction and relaxation time divided by ejection time. In patients with left ventricular (LV) systolic dysfunction (ejection fraction <50%), the TEI index and BNP were increased significantly compared with patients with normal LV systolic function (p<0.05). Patients with a TEI index > or =0.45 showed significantly increased BNP levels compared with patients with a TEI index <0.45, irrespective of LV systolic function (241.4+/-451.2 vs 65.9+/-81.8pg/ml; p<0.05). The TEI index was significantly higher in patients with a BNP > or =73pg/ml than in patients with BNP <73pg/ml (0.57+/-0.24 vs 0.46+/-0.17; p<0.05). Other echocardiographic parameters did not correlate significantly with levels of plasma BNP. Of the echocardiographic parameters, a simple Doppler index (TEI index) that combines systolic and diastolic function can detect LV dysfunction in patients with high levels of plasma BNP in various heart diseases.