早期纠正贫血对慢性肾衰竭心血管病变影响的多中心临床研究

目的观察早期使用促红细胞生成素治疗贫血对透析前慢性肾衰竭(CRF)患者心血管病变的影响.方法采用多中心、前瞻性、对照临床研究.血肌酐(Scr)在147～400 μmol/L的CRF患者158例,按基线Hb水平分组.将Hb<110 g/L的患者分为2组,(1)治疗组86例,每周接受α-促红细胞生成素100～135 U/kg皮下注射;(2)对照Ⅰ组40例,未接受α-促红细胞生成素治疗;将Hb≥110 g/L的32例患者作为对照Ⅱ组,未接受α-促红细胞生成素治疗.行超声心动图检查,测左心室质量指数(LVMI)、血压等,随访时间2年.结果 3组患者基线临床资料(年龄、性别、原发病、营养状况、高血压的发生率、使用降压药物的种类和数量等)无明显差异(均P>0.05);治疗组、对照Ⅰ组、对照Ⅱ组患者左心室肥厚(LVH)的发生率分别为72.1%、72.5%、59.4%;LVMI与Hb水平呈负相关(r=-0.70, P<0.01),与Scr呈正相关(r=0.64, P<0.05).治疗24个月后,治疗组患者Hb水平较基线时明显上升(P<0.05),LVMI较基线时明显下降(P<0.05),LVH的发生率(55.8%)较治疗前降低16.3%,但平均动脉压、使用降压药物的数量与基线相比无明显差异.对照Ⅰ组与对照Ⅱ组患者Hb逐渐下降,LVMI明显增加,LVH发生率与基线相比明显增高(P<0.05).随访期间,Scr较基线增高1倍的患者比率,治疗组(3.4%)与对照Ⅰ组(15.0%)相比差异有统计学意义(P<0.05),而对照Ⅰ组与对照Ⅱ组(9.4%)相比无明显差异(P>0.05).结论轻中度CRF患者存在LVH,贫血是导致透析前CRF患者LVH的重要原因.用促红细胞生成素早期治疗贫血能使部分患者LVH逆转.透析前CRF患者用促红细胞生成素治疗并不加重高血压,并可能有助于延缓肾衰竭的进程.     

Predictors of congestive heart failure in patients on maintenance hemodialysis.

BACKGROUND: Cardiovascular disease is a major cause of death in patients on maintenance hemodialysis (HD). Predictors of congestive heart failure (CHF) events in patients on HD were investigated, focusing on left ventricular (LV) function. METHODS AND RESULTS: One hundred consecutive patients on HD were followed for at least 5 years after index examination performed 1 day after the last HD session. Tests included M-mode and Doppler echocardiography and plasma brain natriuretic peptide (BNP) and hemoglobin (Hb) concentration measurements. Patients with atrial fibrillation or poor echocardiographic images were excluded. Confounding factors included diabetes mellitus (DM), hypertension, age, HD duration, LV fractional shortening, E/A of transmitral flow velocity pattern, Tei index, LV mass index (LVMI), BNP level, Hb, and use of antihypertensive or antiarrhythmic drugs. Six CHF events occurred during 1,703+/-565 days. DM and Hb <10 g/dl were identified as independent predictors of CHF events in a stepwise Cox regression model after DM, LVMI, BNP, and Hb <10 g/dl were selected in the univariate analysis. The hazard ratio (confidence interval) was 10.96 (1.49-80.44) for DM, and 23.00 (2.41-219.76) for Hb <10 g/dl. The estimated hazard across time was constant (T_COV*DM; p=0.726, T_COV*Hb <10 g/dl; p=0.681) by time-dependent covariates analysis. CONCLUSION: In patients on maintenance HD, DM and anemia (Hb <10 g/dl), but not echo-derived cardiac function, predicted CHF events.     

Association of anemia with diastolic dysfunction among patients with coronary artery disease in the Heart and Soul Study

We performed a cross-sectional study to evaluate the association of anemia with diastolic dysfunction and left ventricular hypertrophy (LVH) in outpatients who had coronary artery disease. Logistic regression was used to examine the association of blood hemoglobin (Hb) concentrations with diastolic dysfunction and LVH in 822 participants in the Heart and Soul Study who had normal sinus rhythm and preserved systolic function (left ventricular ejection fraction >/=50%). Using transthoracic echocardiography, diastolic dysfunction was defined as diastolically dominant pulmonary vein flow, and LVH was defined as left ventricular mass index >90 g/m(2). Anemia (Hb <13 g/dl) was present in 24% of participants (197 of 822). The prevalence of diastolic dysfunction ranged from 8% in participants who did not have anemia (Hb >/=13 g/dl) to 13% in those who had moderate anemia (Hb 11 to 13 g/dl) to 24% in those who had severe anemia (Hb <11 g/dl, p = 0.004 for trend). After multivariable adjustment, moderate anemia (odds ratio [OR] 2.0, 95% confidence interval [CI] 1.1 to 3.6) and severe anemia (OR 6.6, 95% CI 1.9 to 24.9) remained strongly associated with diastolic dysfunction. In contrast, moderate anemia (OR 1.4, 95% CI 1.0 to 2.1) and severe anemia (OR 1.6, 95% CI 0.6 to 4.6) were not significantly associated with LVH. We found anemia to be strongly associated with diastolic dysfunction but not with LVH in this community-based sample of outpatients who had established coronary disease.     

L-carnitine supplementation decreases the left ventricular mass in patients undergoing hemodialysis.

BACKGROUND: Patients on long-term hemodialysis become deficient in carnitine and are frequently treated with carnitine supplementation to offset their renal anemia, lipid abnormality and cardiac dysfunction. The therapeutic value of carnitine supplementation on left ventricular hypertrophy (LVH) in patients with normal cardiac systolic function remains uncertain. METHODS AND RESULTS: The cardiac morphology and function of 10 patients given 10 mg/kg of L-carnitine orally, immediately after hemodialysis sessions 3 times per week for a 12-month period were compared with 10 untreated control patients. Using echocardiography, left ventricular fractional shortening (LVFS) and left ventricular mass index (LVMI) were measured before and after the study period. As a result, amounts of serum-free carnitine increased from 28.4+/-4.7 to 58.5+/-12.1 micromol/L. The LVMI decreased significantly from 151.8+/-21.2 to 134.0+/-16.0 g/m(2) in treated patients (p<0.01), yet the LVMI in untreated control patients did not change significantly (ie, from 153.3+/-28.2 to 167.1+/-43.1 g/m(2)). However, LVFS values remained unchanged in both groups. Although L-carnitine promoted a 31% reduction in erythropoietin requirements, hematocrit and blood pressure did not change during the study period. CONCLUSIONS: Supplementation with L-carnitine induced regression of LVH in patients on hemodialysis, even for those with normal systolic function.     

Effect of early correction of anemia with erythropoietin on left ventricular mass in predialysis patients: a multi-center trial

Objective To assess the effects of early correction of anemia with recombinant human erythropoietin (rHuEPO) on the development and progression of left ventricular hypertrophy (LVH) in patients with mild-to-moderate chronic renal insufficiency (CRI) who are not on hemodialysis. Methods A total of 158 patients with serum creatinine from 147μmol/L to 400μmol/L were enrolled in this prospective, multicenter study. Eighty-six patients with hemoglobin (Hb)<110g/L received rHuEPO treatment with a target Hb of > 110g/L (Group A). Forty patients with comparable Hb concentration ( <110g/L) but did not receive rHuEPO (Group B) and 32 patients with Hb≥110g/L and without rHuEPO treatment (Group C) were served as controls. Left ventricular mass index (LVMI) was evaluated by echocardiography at baseline and every 3 months for 2 years. Results There was no difference in age, gender, etiology of renal failure, blood pressure and cardiovascular risk factors among the 3 groups. At baseline, the prevalence of LVH was 72.1 % in group A, 72.5% in group B and 59.4% in group C. LVMI was inversely correlated with Hb levels (r=0.70, P<0.01). During the 2-year period, the mean LVMI decreased from 142.6±25.7g/m2 to 132.4±18.5 g/m2 in group A, while increased significantly in both group B and group C. The mean Hb concentration increased from 93.8±14.6g/L to 111.2±10.3g/L(P<0.05) in group A, but tended to decrease in group B and group C. There was no significant change of the mean blood pressure, number of anti-hypertensive drugs and serum creatinine concentrations in all 3 groups. However, patients' serum creatinine doubled more often in group B and group C than in group A. Conclusions LVH was common in predialysis CRI patients and was associated with the severity of anemia. Early intervention with rHuEPO may reverse LVH in these patients.     

Efficacy of erythropoietin on dialysis in patients with beta thalassemia minor

BACKGROUND: It is unknown whether chronic erythropoietin (EPO) treatment is able to normalize hemoglobin (Hb) levels and ameliorate cardiac remodeling avoiding blood transfusions in uremic blood transfusion-dependent patients with beta-thalassemia minor (beta-thal). METHODS: In 12 hemodialysis (HD) patients with beta-thal, requiring blood transfusions despite EPO therapy, we planned to increase Hb levels up to the target levels (11-12 g/dl) within a one-year period by administering progressively higher doses of EPO (correction phase). We also planned to maintain the Hb target for an additional year (maintenance phase). RESULTS: In the year before the study, patients required 3.3 +/- 0.9 units of packed red blood cells. At baseline, the Hb level obtained with an EPO dose of 212 +/- 73 U/kg/week i.v. was 8.2 +/- 0.8 g/dl. The EPO dose was gradually increased within the first year up to 458 +/- 78 U/kg/week at month 12 (correction phase) and then significantly tapered down during the maintenance phase (390 +/- 54 U/kg/week at month 24). During the correction phase, the Hb levels markedly increased (11.1 +/- 0.3 g/dl at month 12) and did not change in the maintenance phase. No blood transfusion was required throughout the 2 years of follow-up. Left ventricular (LV) mass index progressively decreased from the basal value of 144 +/- 12 to 124 +/- 11 g/m2 in the first year and normalized in all patients at month 24 (109 +/- 12 g/m2, p < 0.001); this occurred in the absence of any change of LV cavity volume index (<90 ml/m2). CONCLUSIONS: In HD transfusion-dependent patients with beta-thal, the administration of high EPO dose for 2 years permits the attainment and the maintenance of Hb targets without blood transfusions. This therapeutic approach permits a complete remission of concentric LV hypertrophy without any adverse effects on the vascular system.     

Angiotensin-converting enzyme gene polymorphism influences degree of left ventricular hypertrophy and its regression in patients undergoing operation for aortic stenosis.

Insertion (I)/deletion (D) polymorphism of the angiotensin-converting enzyme (ACE) gene has been associated with increased left ventricular hypertrophy (LVH) in patients with cardiomyopathy and congestive heart failure. Patients with aortic stenosis (AS) have varying degrees of LVH at a given valve area. The aim of this study was to examine the relation between ACE gene polymorphism and the degree of LVH in patients undergoing operation for AS. Eighty-two patients who underwent operation for AS with a stentless valve were followed prospectively with echocardiographic assessments of left ventricular mass index (LVMI). ACE gene polymorphism was determined by polymerase chain reaction. The genotype (DD, ID, and II) frequency was the same as in healthy controls. The pressure difference across the aortic valve did not differ between genotypes. Patients with the DD genotype of the ACE gene had a higher LVMI (197 +/- 47 g/m2) preoperatively than those with ID (175 +/- 41 g/m2) or II (155 +/- 43 g/m2) genotypes (p = 0.01). LVMI decreased significantly in DD (p <0.001) and ID (p <0.001) genotypes but not in the II genotype during follow-up (mean 15 months). There was a significant difference in regression of LVMI over time between genotypes (p = 0.0056), with no significant difference between genotypes at follow-up. The DD genotype of the ACE gene is associated with increased preoperative LVH in patients treated surgically for AS. The DD genotype appears to be an important factor which increases hypertrophic myocardial reactivity to pressure overload.     

Effects of anemia correction by erythropoiesis-stimulating agents on cardiovascular function in non-dialysis patients with chronic kidney disease

Anemia is a significant risk factor for patients with chronic kidney disease (CKD). Here, we investigated the effects of anemia correction on cardiac functions in CKD patients. Pre-dialysis CKD patients (n = 171) without known risk factors for cardiovascular disease (CVD) other than CKD with hemoglobin (Hb) concentrations < 10.0 g/dL were enrolled for evaluation of cardiac functions and biomarkers before and after the 16-week treatment of erythropoiesis-stimulating agents. The treatment significantly increased Hb concentrations in all patients who completed the study (n = 143, 8.91 ± 0.87 versus 11.27 ± 1.31 g/dL; n < 0.001) and among patients whose echocardiograms were available for evaluation (n = 77, 8.92 ± 0.94 versus 11.24 ± 1.13 g/dL; P < 0.001). The left ventricular mass index (LVMI) was decreased (121.3 ± 25.8 versus 114.7 ± 25.1 g/m², n = 77, P = 0.012) and significant correlation between the change in the LVMI and Hb concentration was noted (P = 0.011). The levels of B-type natriuretic peptide and human atrial natriuretic peptide, and the cardio-thoracic ratio were significantly increased among subjects with Hb concentrations < 11.0 g/dL at completion of the study. The changes in these parameters were significantly correlated with the Hb concentrations (P = 0.033, P = 0.011, and P < 0.001, respectively). No significant differences were observed in the electrocardiographic parameters. Correcting Hb levels higher than those conventionally recommended reduced left ventricular hypertrophy and myocardial stress, lowering risks for CVD in pre-dialysis CKD patients.     

Reverse remodeling of cardiac collagen protein expression after surgical therapy for experimental aortic stenosis

BACKGROUND AND AIM OF THE STUDY: Reversal of myocardial collagen gene expression was examined in parallel to left ventricular reverse remodeling after surgical correction of experimental aortic stenosis. METHODS: A standard growing sheep model (age at baseline 6-8 months) was used. Measurements were performed at baseline (point A) when inducing left ventricular hypertrophy (LVH) through supracoronary banding, at 8.3 +/- 1.0 months later at surgical correction (point B), and after another 10.1 +/- 2.0 months during final examinations (point C). Gene expression for collagen I and III was also studied. RESULTS: Left ventricular function was stable throughout the study. The left ventricular mass index (LVMI) was 82 +/- 21 g/m2 at point A, 150 +/- 33 g/m2 at B, and 78 +/- 18 g/m2 at C (p <0.01). Myocardial fiber diameter was 11.3 +/- 0.8, 15.9 +/- 1.2 and 11.4 +/- 1 microm at points A, B and C, respectively (p <0.01). Protein expression for collagen I was 0.71 +/- 0.2 (at A), 1.13 +/- 0.3 (at B) and 0.85 +/- 0.4 (at C) (p <0.01), while that for collagen III was 0.72 +/- 0.4 (at A), 1.26 +/- 0.8 (at B) and 0.83 +/- 0.3 (at C) (p <0.01). There was a significant correlation between changes in LVMI and myocardial collagen expression. CONCLUSION: Complete reverse remodeling with regression of LVH and myocardial collagen protein expression can be anticipated after surgical correction of experimental aortic stenosis.     

Ultrasonographic evaluation of cardiac and vascular hypertrophy in patients with essential hypertension]

High resolution ultrasonography allows the accurate and reproducible measurement of thickness and lumen diameter of carotid arteries. We investigated Common carotid (CCA) and bifurcation intima-media thickness in 40 hypertensive patients, 20 without left ventricular hypertrophy (LVH) (age 42 +/- 10 years) and 20 with LVH (age 44 +/- 12 years), all free from other important cardiovascular risk factors. Both carotid axes were scanned from different views (anterior, lateral, posterior) on traversal and longitudinal section, using a high resolution steerable (HRS) 5.0 MHz linear array. Carotid diameter and thickness from longitudinal section were measured. CCA parameters were taken 20 mm caudally to flow divider. Using the B-mode as a guide we assessed LVH presence with M-mode technique when left ventricular mass index (LVMI) > or = 135 g/m2 for men and > or = 110 g/m2 for women. In hypertensive patients with LVH, left ventricular mass was significantly higher than in those without LVH (156 +/- 38 vs 98 +/- 10 g/m2, p < 0.01). Even blood pressure was significantly higher in hypertrophic group (172 +/- 21/108 +/- 9 vs 158 +/- 11/99 +/- 12 mmHg, p < 0.01), while there was no difference in serum glycemia, triglycerides, total and fractioned cholesterol levels. The intima-media thickness scanned in both CCA and bifurcation resulted significantly higher in hypertensives with LVH (CCA: 0.85 +/- 0.02 mm vs 0.65 +/- 0.02 mm; BIF: 0.93 +/- 0.04 mm vs 0.70 +/- 0.03 mm, p < 0.01). We also noticed a statistically significant correlation between carotid wall thickness and left ventricular mass index.(ABSTRACT TRUNCATED AT 250 WORDS)     

Regression of left ventricular hypertrophy in hypertensive patients treated with indapamide SR 1.5 mg versus enalapril 20 mg: the LIVE study

OBJECTIVE: To compare the efficacy of indapamide sustained release (SR) 1.5 mg and enalapril 20 mg at reducing left ventricular mass index (LVMI) in hypertensive patients with left ventricular hypertrophy (LVH). DESIGN: The LIVE study (left ventricular hypertrophy regression, indapamide versus enalapril) was a 1 year, prospective, randomized, double-blind study. For the first time, a committee validated LVH before inclusion, provided on-going quality control during the study, and performed an end-study reading of all echocardiograms blinded to sequence. SETTING: European hospitals, general practitioners and cardiologists. PATIENTS: Hypertensive patients aged > or = 20 years with LVH (LVMI in men > 120 g/m2; LVMI in women > 100 g/m2). Data were obtained from 411 of 505 randomized patients. INTERVENTIONS: Indapamide SR 1.5 mg, or enalapril 20 mg, daily for 48 weeks. MAIN OUTCOME MEASURES: LVMI variation in the perprotocol population. RESULTS: Indapamide SR 1.5 mg significantly reduced LVMI (-8.4 +/- 30.5 g/m2 from baseline; P< 0.001), but enalapril 20 mg did not (-1.9 +/- 28.3 g/m2). Indapamide SR 1.5 mg reduced LVMI significantly more than enalapril 20 mg: -6.5 g/m2, P = 0.013 (-4.3 g/m2 when adjusted for baseline values; P = 0.049). Both drugs equally and significantly reduced blood pressures (P< 0.001), without correlation with LVMI changes. Indapamide SR progressively reduced wall thicknesses throughout the 1-year treatment period. In contrast, the effect of enalapril observed at 6 months was not maintained at 12 months. CONCLUSIONS: Indapamide SR 1.5 mg was significantly more effective than enalapril 20 mg at reducing LVMI in hypertensive patients with LVH.     

Left ventricular hypertrophy and geometry in untreated essential hypertension is associated with blood levels of aldosterone and procollagen type III amino-terminal peptide.

BACKGROUND: The present study examined the role of aldosterone in left ventricular hypertrophy (LVH) and geometry in patients with untreated essential hypertension (EHT), and investigated the contribution of myocardial fibrosis to the process of LVH. METHODS AND RESULTS: The relationship of the plasma aldosterone concentration (PAC) to LVH and left ventricular (LV) geometry was investigated in 57 consecutive patients with untreated EHT. PAC correlated with both LV mass index (LVMI: r=0.46, p=0.0004) and relative wall thickness (RWT: r=0.33, p=0.013). In patients with LVH (LVMI > or =125 g/m(2)), the serum concentration of procollagen type III amino-terminal peptide (PIIINP), a marker of myocardial fibrosis, correlated with RWT (r=0.46, p=0.029). These patients were divided into 2 groups: concentric hypertrophy (CH) with RWT > or =0.44, and eccentric hypertrophy (EH) with RWT <0.44. The serum PIIINP concentration was significantly higher in the CH group than in the EH group (0.52+/-0.02 ng/ml vs 0.44+/-0.03 ng/ml, respectively; p<0.05). CONCLUSIONS: Aldosterone may be involved in LVH and LV geometry, particularly in the development of CH. Myocardial fibrosis seems more strongly involved in the hypertrophic geometry of CH than with EH.     

Long-term effects of balloon angioplasty on left ventricular hypertrophy in adolescent and adult patients with native coarctation of the aorta. Up to 18 years follow-up results.

BACKGROUND: Little is known regarding the long-term follow-up results of balloon angioplasty (BA) for patients with native aortic coarctation (AC) on left ventricular hypertrophy (LVH) regression. OBJECTIVES: The purpose of this study was to define the long-term effect of BA of AC on LVH in adolescent and adult patients. METHODS: Follow-up data of 53 patients (36 male) mean age 24 +/- 9 years undergoing BA for discrete AC at median interval of 11.8 years (range 4-18 years) including cardiac catheterization, magnetic resonance imaging, and Echocardiography form the basis of this study. Patients were divided into two groups at 1 year after BA based on absence (group A) or presence (group B) of persistent hypertension and need for medication. RESULTS: Forty-nine patients had baseline LVH, BA produced an immediate reduction in peak AC gradient from 66 +/- 23 mm Hg (95% confidence interval [CI]: 59.5-72.7) to 10.8 +/- 7 mm Hg (95% CI: 8.8-12.5) (P < 0.0001). Follow-up catheterization 12 months later revealed a residual gradient of 6.2 +/- 6 mm Hg (95% CI: 4.4-7.9) (P < 0.001). The blood pressure had normalized without medication in 38 of the 49 patients (165 +/- 17 to 115 +/- 10 mm Hg). Left ventricular mass index (LVMI) decreased significantly (>20% decrease LVMI from baseline) in 48 patients (98%) at median interval 1.4 years (range 0.5-3 years) post BA, group A (38 patients) LVMI decreased from 132 +/- 30.7 g/m(2) (95% CI: 122-141.9) to 86 +/- 19.9 g/m(2) (95% CI: 79.5-92.5) (P < 0.0001). Similarly, in 10 patients (group B) the LVMI decreased from 157 +/- 38.7 g/m(2) (95% CI: 127-185) to 102 +/- 29 g/m(2) (95% CI: 105-151) (P < 0.0001) at follow-up. Mild (<20% decrease in LVMI) regressions were noted in one patient from group B. There was no progression to LVH in the four patients who had normal baseline LVMI. CONCLUSION: (1) Long-term results of BA for discrete AC are excellent and should be considered as first option for treatment of this disease; (2) Regression of LVH (> or =20% reduction in LVMI) occurred in 98% of patients after BA.     

Is ventricular repolarization heterogeneity a cause of serious ventricular tachyarrhythmias in aortic valve stenosis?

BACKGROUND: It is well known that there is a close relation between sudden cardiac death and serious ventricular tachyarrhythmias in patients with aortic valve stenosis (AS). QT dispersion (QTd) reflects the ventricular repolarization heterogeneity and has been proposed as an indicator for ventricular arrhythmias. HYPOTHESIS: This study investigated the QTd and its relevance to the clinical and echocardiographic variables. METHODS: In all, 51 patients (33 men, 18 women, mean age 56 +/- 12) with isolated AS and 51 age- and gender-matched healthy controls comprised the study group. Left ventricular mass index (LVMI) was calculated by the Devereux formula, and we used continuous-wave Doppler (n = 15) and cardiac catheterization (n = 36) for the determination of the maximum aortic valve pressure gradient (PG). RESULTS: Corrected QTd (QTcd) (89 +/- 39 vs. 49 +/- 15 ms, p < 0.001) and LVMI (176 +/- 69 g/m2 vs. 101 +/- 28 g/m2, p < 0.001) in patients with AS were significantly different from those in the control group. The group of 21 patients had a significantly greater number of 24-h mean ventricular premature beats (VPB) and mean number of couplet VT episodes than did the control group (p < 0.05). QTcd also correlated significantly well with LVMI (r = 0.58, p < 0.001), PG (r = 0.41, p = 0.003), and number of 24-h VPB (r = 0.56, p = 0.008). With respect to symptoms (e.g., angina, syncope, and dyspnea) patients without symptoms (n = 19) displayed less QTcd (71 +/- 31 vs. 100 +/- 39 ms, p = 0.007) and less LVMI (144 +/- 80 g/m2 vs. 195 +/- 57 g/m2, p = 0.01) than patients with symptoms. Statistical analysis was similar for all variables with uncorrected QTd values. CONCLUSION: We found that ventricular repolarization heterogeneity was greater in patients with AS than in controls. Our findings also showed that QTd in the patient group correlates well with LVMI, severity of AS, and PG. The present results suggest that serious ventricular arrhythmias in patients with AS may be due to spatial ventricular repolarization abnormality.     

Evaluation of left ventricular function and mass after Medtronic Freestyle versus homograft aortic root replacement using cardiovascular magnetic resonance

BACKGROUND AND AIM OF THE STUDY: Regression of left ventricular hypertrophy (LVH) after aortic valve replacement has traditionally been measured by echocardiography. However, cardiovascular magnetic resonance (CMR) can be used to measure left ventricular function and mass more accurately and reproducibly. This translates into fewer patients being needed to demonstrate significant changes. The study aim was to demonstrate the feasibility of using CMR to measure left ventricular mass index (LVMI) and function in patients from a prospective randomized trial, and to compare homografts with the Medtronic Freestyle root replacement. METHODS: Among 23 patients recruited, 17 had LVMI and function (end-diastolic volume (EDV), end-systolic volume (ESV), stroke volume (SV) and ejection fraction (EF)) measured pre- and postoperatively using CMR (eight homograft, nine Freestyle). RESULTS: Significant regression of LVH was seen in both groups one year postoperatively (homograft LVMI 145+/-44 g/m2 preoperative versus 83+/-23 g/m2 one year postoperatively; Freestyle LVMI 140+/-28 g/m2 versus 93+/-21 g/m2, respectively). At six months there was significant regression in the xenograft group (from 140+/-28 to 106+/-22 g/m2; p <0.05) and a trend towards regression in the homograft group (from 145+/-44 to 103+/-25 g/m2; p = NS). There was also a trend towards a reduction in EDV, ESV and SV, and an increase in EF over one year in both groups. CONCLUSION: Regression of LVH was measured using CMR in patients after aortic root replacement and coronary implantation with the homograft and Medtronic Freestyle root replacement. Despite the small number of patients studied, it was possible to demonstrate the extent and pattern of regression of left ventricular mass in the two groups.     

Optimal control of blood pressure can reverse left ventricular hypertrophy in uremic hypertensive hemodialysis patients

We investigated the effects of antihypertensive treatment on left ventricular hypertrophy (LVH) of long-term hemodialysis patients. In uremic patients, it is still controversial in antihypertensive effect to the regression of LVH. The left ventricular size and function of 39 uremic hypertensive long-term hemodialysis patients (27 men, 12 women, mean age 58.3) was evaluated with M-mode, 2-dimensional and Doppler echocardiography before, and 12 months after, the start of combined antihypertensive therapy. This therapy included angiotensin II converting enzyme inhibitors, beta-blockers and calcium antagonists. Patients were classified as responders or nonresponders, depending upon whether their systolic blood pressure (SBP) decreased by more than 10 mmHg after antihypertensive treatment for 12 months. Before treatment, 36 (92%) patients had LVH and diastolic dysfunction and three (8%) had systolic dysfunction. At the end of 12 months, only 25 (64%) patients had LVH, 30 (77%) had diastolic dysfunction and 2 (5%) had systolic dysfunction. Left ventricular mass index (LVMI) also decreased from 203.63 +/- 70.47 g/m2 to 178.57 +/- 67.31 g/m2. LVMI correlated with systolic blood pressure (SBP) but did not correlate with diastolic blood pressure (DBP). There were 26 responders and 13 non-responders. Among responders, both the SBP (153.91 +/- 13.24 mmHg vs 134.43 +/- 14.21 mmHg, p < 0.01) and DBP (90.39 +/- 7.89 mmHg vs 79.98 +/- 7.35 mmHg, p < 0.01) decreased significantly after antihypertensive therapy. Responders also exhibited progressive regression of LVH (LVMI decreased significantly from 208.52 +/- 72.03 g/m2 to 168.52 +/- 55.53 g/m2, p < 0.05). However, LVH regression was not found in nonresponders (LVMI showed 194.84 +/- 64.36 g/m2 vs 193.66 +/- 77.67 g/m2). We conclude that good control of blood pressure can reverse LVH in hypertensive hemodialysis patients.     

Intravenous iron alone for the treatment of anemia in patients with chronic heart failure.

OBJECTIVES: This study was undertaken to assess the hematologic, clinical, and biochemical response to intravenous iron in patients with chronic heart failure (CHF) and anemia. BACKGROUND: Anemia is common in patients with CHF and is associated with higher morbidity and mortality. The combination of erythropoietin (EPO) and iron increases hemoglobin (Hb) and improves symptoms and exercise capacity in anemic CHF patients. It is not known whether intravenous iron alone is an effective treatment for anemia associated with CHF. METHODS: Sixteen anemic patients (Hb < or =12 g/dl) with stable CHF (age 68.3 +/- 11.5 years, 12 men, 9 participants New York Heart Association [NYHA] functional class II and the remainder class III, left ventricular ejection fraction 26 +/- 13%) received a maximum of 1 g of iron sucrose by bolus intravenous injections over a 12-day treatment phase in an outpatient setting. Mean follow-up was 92 +/- 6 days. RESULTS: Hemoglobin rose from 11.2 +/- 0.7 to 12.6 +/- 1.2 g/dl (p = 0.0007), Minnesota Living with Heart Failure (MLHF) score fell (denoting improvement) from 33 +/- 19 to 19 +/- 14 (p = 0.02), 6-min walk distance increased from 242 +/- 78 m to 286 +/- 72 m (p = 0.01), and all patients recorded NYHA class II at study end (p < 0.02). Changes in MLHF score and 6-min walk distance related closely to changes in Hb (r = 0.76, p = 0.002; r = 0.56, p = 0.03, respectively). Of all baseline measurements, only iron and transferrin saturation correlated with increases in Hb (r = 0.60, p = 0.02; r = 0.60, p = 0.01, respectively). There were no adverse events relating to drug administration or during follow-up. CONCLUSIONS: Intravenous iron sucrose, when used without concomitant EPO, is a simple and safe therapy that increases Hb, reduces symptoms, and improves exercise capacity in anemic patients with CHF. Further assessment of its efficacy should be made in a multicenter, randomized, placebo-controlled trial.     

The effect of valsartan on regression of left ventricular hypertrophy in type 2 diabetic patients

AIM: The aim of the present study was to examine the effects of an angiotensin II receptor antagonist, valsartan, on echocardiographically proven left ventricular hypertrophy (LVH) in patients with type 2 diabetes. METHODS: Outpatients with type 2 diabetes mellitus were recruited at Niigata University Hospital. The left ventricular mass index (LVMI) was calculated by echocardiography. LVH was considered to be present if the LVMI was > 131 g/m(2) in males and > 100 g/m(2) in females. Patients with LVH received a low dose (40 mg/day) of valsartan for 12 months. This low dose had no clinical effect on blood pressure. RESULTS: Of the 38 patients who entered the study, 14 (36.8%) had LVH. After only 6 months of valsartan therapy, the mean LVMI decreased significantly, from 126.5 +/- 27.8 to 119.0 +/- 23.5 g/m(2) (p < 0.01 vs. baseline). Also, a significant decrease was observed after 12 months (116.5 +/- 30.9 g/m(2), p < 0.05 vs. baseline). Compared to baseline, there were no significant differences after treatment in body mass index, glycosylated haemoglobin (HbA(1c)), systolic blood pressure and diastolic blood pressure. CONCLUSIONS: In type 2 diabetic patients with LVH, treatment with a low dose of valsartan, an angiotensin II receptor antagonist, for 12 months, reduced LVMI, with no reduction in systemic blood pressure. This drug may be safely administered to type 2 diabetic patients with LVH. The long-term risk-reduction effects will have to be evaluated in further trials.     

Effects of angiotensin II receptor blockade-based therapy with losartan on left ventricular hypertrophy and geometry in previously treated hypertensive patients

BACKGROUND: The 2003 European Society of Hypertension/European Society of Cardiology (ESH/ESC) guidelines recommend angiotensin II receptor antagonists (AIIRAs) as a first-line therapy in hypertensives with left ventricular hypertrophy (LVH). AIM: We investigated the long-term effects of an AIIRA-based therapy on left ventricular (LV) structure and geometry in previously, unsatisfactorily treated essential hypertensive patients. METHODS: Sixty-eight consecutive patients referred to our hypertension hospital outpatient clinic with: (i) LVH (LV mass index, LVMI 51 g/m(2.7) in men and 47 g/m(2.7) in women), (ii) uncontrolled clinic blood pressure (BP140 and/or 90 mmHg) and (iii) antihypertensive therapy not including angiotensin-converting enzyme (ACE) inhibitors or AIIRAs were selected for this study. Two-dimensionally guided M-mode echocardiograms were carried out at baseline and after 6, 12, 18 and 24 months of follow-up. In all patients, losartan (50-100 mg/day, mean dose 82 mg/day) was added as first step to the previous therapy. Additional drugs, tailored to the single patient, were added, if necessary, to achieve target BP values (<140/90 mmHg). RESULTS: Overall, 59 patients completed the study with the primary efficacy measurements (LVMI) at all appropriate times. A significant reduction in both clinic systolic BP and diastolic BP was found across the entire period of study respect to baseline (-17/10, -22/12, -24/13 and -26/14 mmHg at 6, 12, 18 and 24 months, p < 0.001 respectively), leading to target clinic BP in 75.6% of cases. LVMI was significantly lower after 1 year of treatment (-11 +/- 12%, p < 0.05) with a further significant reduction at the end of treatment (-22 +/- 18%, p < 0.01). The proportion of patients achieving normalization of LVMI was 47.4% and more importantly, the prevalence of concentric LVH fell from 38.9% to 6.7% (p < 0.01). CONCLUSIONS: Our findings indicate that long-term intensive treatment based on the AIIRA losartan induced a normalization of LVH in about 50% of patients and more importantly caused an almost complete regression of concentric LVH, the most dangerous adaptive pattern. The transition from concentric to normal or eccentric LV geometry may have in these high-risk patients a favourable prognostic implication in addition to the recognized positive effect of reducing LVMI.     

Anemia is an independent predictor for elevated plasma levels of natriuretic peptides in patients undergoing cardiac catheterization for coronary artery disease.

BACKGROUND: It is unknown whether the association of anemia with elevated plasma levels of B-type and atrial natriuretic peptides (BNP and ANP) is mediated by the hemodynamic effects of anemia. METHODS AND RESULTS: The study group comprised 237 consecutive patients (BNP, median [interquartile range], 28.3 [9.5-77.1] pg/ml; ANP, 17.8 [8.5-39.0] pg/ml) undergoing determination of hemoglobin (Hb) and natriuretic peptide levels and cardiac catheterization for evaluation of coronary artery disease (CAD). Hb correlated with BNP (r=-0.36, p<0.001) and ANP (r=-0.35, p<0.001). Patients with anemia (Hb <12 g/dl for females; <13 g/dl for males, n=63) were more likely to be older with reduced body mass index and renal function, greater severity of CAD and to have higher heart rate, mean pulmonary capillary wedge pressure, and cardiac output. Anemia was a significant predictor for elevated (>third quartile value) natriuretic peptide levels and the predictive value remained significant after adjustment for other predictors, including increased left ventricular end-diastolic pressure and differences in clinical and hemodynamic variables between patients with and without anemia (adjusted odds ratio [95% confidence interval] for elevated BNP and ANP levels, 7.39 [2.76-19.8] and 2.56 [1.08-6.07], respectively). CONCLUSION: Anemia is an independent predictor for elevated natriuretic peptide levels in patients with known or suspected CAD.