Brain natriuretic peptide as a marker of cardiac involvement in hypertension.

Hypertensive patients with heart abnormalities have increased risk of cardiovascular events. Brain natriuretic peptide is a natriuretic peptide mainly of ventricular origin produced in response to pressure and stretch. We hypothesise that brain natriuretic peptide could be a useful marker of cardiac remodelling in hypertensive patients. We studied 36 consecutive community mild-to-moderate hypertensive patients and 11 well-matched normotensive controls with respect to clinical characteristics, brain natriuretic peptide, creatinine and echocardiography parameters (M-mode, 2-D arid transmitral pulsed Doppler). Brain natriuretic peptide levels were significantly higher in hypertensive patients than in controls [36.54 (IQR: 38.61) vs. 10.30 (IQR: 13.20) pg ml(-1), p<0.0001] and it was correlated with left ventricular mass index. Hypertensive patients with impairment of diastolic filling had significantly higher brain natriuretic peptide concentrations than patients with no abnormalities on echocardiography [61.16 (45.38) vs. 31.27 (18.10) pg ml(-1), p=0.001]. Multivariate analysis showed that only diastolic dysfunction and left ventricular mass index were significantly and independently related with brain natriuretic peptide concentrations in this population. In conclusion, impairment of diastolic function and left ventricular mass index are related to brain natriuretic peptide levels, thus giving the insight that this peptide can be a marker of ventricular remodelling in hypertensive patients.     

Brain natriuretic peptide as marker and factor of prognosis in chronic heart failure

The role of natriuretic peptides in pathogenesis of chronic heart failure (CHF) is reviewed. Main attention is given to significance of measurement of brain natriuretic peptide in the following clinical situations related to CHF: diagnosis of CHF, screening of patients with symptomless left ventricular dysfunction, differential diagnosis of edematous syndrome, indications to therapy and monitoring of its effectiveness, assessment of long term prognosis of patients with CHF. Possibilities of curative use of natriuretic peptides and inhibitors of vasopeptidases are also discussed.     

Brain natriuretic peptide as a preclinical marker of chronic pulmonary hypertension in patients with pulmonary embolism

Chronic thromboembolic pulmonary hypertension (CTPH) is a potential complication of pulmonary embolism (PE). Only few studies have assessed the role of brain natriuretic peptide (BNP) in patients with chronic pulmonary hypertension, and there are no data on the potential utility of BNP as a preclinical biomarker of CTPH. To assess the correlation between pulmonary artery systolic pressures (PAPs) and amino terminal proBNP (Nt-proBNP) and its value in the diagnosis of CTPH in patients with previous PE. Patients were evaluated with echocardiography at least 6 months after the index event. Pulmonary hypertension was defined as PAPs ≥40 mmHg at rest. Each subject underwent measurement of Nt-proBNP. Forty-nine patients were enrolled (mean age 64.5 ± 13.1 years; 22 men). Seven patients had CTPH, and two were symptomatic. There was a good correlation between PAP on echocardiography and Nt-proBNP (r 0.64; P = 0.00003). Nt-proBNP was elevated in 6 of 7 patients [sensitivity: 85.7%; 95% confidence interval (CI): 48.7, 97.4] and it was normal in 35 of 42 patients without CTPH (specificity: 76.2%; 95% CI: 61.5, 86.5%). Six of the 13 patients with high Nt-proBNP levels had CTPH, whereas 1 of 36 patients with normal Nt-proBNP levels had pulmonary hypertension. The resulting positive predictive value was 46.1% (95% CI: 19.2, 74.9), and the negative predictive value was 97.2% (95% CI: 85.5–99.9). In conclusion, Nt-proBNP correlates with PAPs and may be used to exclude preclinical or symptomatic CTPH in patients with previous PE. Prospective studies on a larger population are warranted to confirm our preliminary findings.     

Brain natriuretic peptide and cardiac autonomic function in type 2 diabetic patients

The present study tested the hypothesis that increased plasma brain natriuretic peptide (BNP) levels are related to cardiac autonomic dysfunction in type 2 diabetic patients. A total of 32 consecutive Japanese patients with type 2 diabetes were assigned to either a high-BNP (>or=18 pg/ml) group (n=12; age 57+/-13 years, mean+/-S.D.) or a normal-BNP (<18 pg/ml) group (n=20; 59+/-10 years). No patient had any overt structural heart disease. Cardiac autonomic function was assessed by measurements of baroreflex sensitivity (BRS), heart rate variability (HRV) and cardiac (123)I-metaiodobenzylguanidine (MIBG) scintigraphic findings. BRS was lower (p<0.005) in the high-BNP group than in the normal-BNP group. However, the components of HRV, and the early and delayed myocardial uptake of (123)I-MIBG and percentage washout rate of (123)I-MIBG were not significantly different between the groups. The plasma level of BNP negatively correlated with BRS (r=0.35, p=0.049). These findings suggest that increased plasma BNP levels were related to cardiac reflex parasympathetic dysfunction in our Japanese type 2 diabetic patients.     

Brain natriuretic peptide release in cardiac surgery patients

Brain natriuretic peptide (BNP) release is a marker of increased myocardial wall tension, which is elevated in patients with disturbed left ventricular function. As it is increasingly being used as a reliable marker for diagnosis, optimization of pharmacological treatment, and risk stratification, BNP measurement might be also relevant for patients undergoing cardiac surgery. Measured BNP levels can be used to predict postoperative complications and the risk of further cardiac events. Preoperative BNP levels support the decision for the timing of aortic valve replacement in asymptomatic severe aortic stenosis. An increase in BNP levels early predicts allograft rejection after cardiac transplantation or ineffective cardiac resynchronization therapy. Moreover, BNP levels can be used to differentiate between cardiac and non-cardiac reasons for acute dyspnea in the management of surgical patients. Finally, the application of recombinant human BNP seems to improve recovery after cardiac surgical procedures. Thus, BNP can be a helpful tool for monitoring and treating patients before, during, and after cardiac surgery to predict and improve the effectiveness of therapy and reduce hospitalization and costs.     

Discontinuation of imatinib in Japanese patients with chronic myeloid leukemia

It was recently recognized that some chronic myeloid leukemia patients with a complete molecular response could sustain that response after discontinuation of imatinib. To characterize the clinical outcomes and profiles of chronic phase chronic myeloid leukemia patients who could discontinue imatinib, we conducted a nationwide survey in Japan. Among 3,242 imatinib-treated chronic myeloid leukemia patients, we identified 50 who had discontinued imatinib for at least six months; of these we analyzed 43. Molecular recurrence was detected in 19 patients, and a complete molecular response rate was estimated to be 47% following imatinib discontinuation. Based on multivariate regression analysis, imatinib dose intensity and prior interferon-α administration were independently predictive of molecular recurrence within 12 months. The depth of the molecular response should be a factor influencing long-term sustained complete molecular response after discontinuation of imatinib. Additionally, an immunological mechanism modified by interferon-α might control chronic myeloid leukemia stem cells.     

Nilotinib is superior to imatinib as first-line therapy of chronic myeloid leukemia: the ENESTnd study

Nilotinib (Tasigna(?)) is a more potent BCR-ABL inhibitor than imatinib and was designed to overcome imatinib's deficiencies. Nilotinib has significant efficacy in patients with chronic myeloid leukemia (CML) in chronic phase, accelerated phase and blastic phase, following imatinib failure. Based on the results of the Evaluating Nilotinib Efficacy and Safety in Clinical Trials-Newly Diagnosed Patients (ENESTnd) study, the US FDA has granted accelerated approval of nilotinib for the treatment of adult patients with newly diagnosed Philadelphia chromosome-positive CML in chronic phase. Imatinib has changed our perceptions of the therapeutic power of targeted inhibition of a pathologically active kinase. Nilotinib, a designer agent built on the imatinib scaffold, has proven superior to its template agent by every significant surrogate marker we use in monitoring CML. Nilotinib's clinical superiority over imatinib, as demonstrated by the ENESTnd study, has established it as an agent that we believe is a significant further step towards the cure of CML.     

Brain natriuretic peptide levels and response to cardiac resynchronization therapy in heart failure patients

The authors used brain natriuretic peptide (BNP) as a reliable marker to identify nonresponders to cardiac resynchronization therapy (CRT) in patients with advanced heart failure. The study included 70 patients with left ventricular dysfunction (mean ejection fraction, 21+/-4%) and left bundle branch block (QRS duration, 164+/-25 milliseconds) treated with CRT. The authors reviewed data on New York Heart Association functional class, baseline ejection fraction, sodium, creatinine, QRS duration, and BNP levels 3 months before and after CRT therapy. The authors compared results of 42 patients who survived (973+/-192 days) after CRT implantation (responders) to those of 28 patients (nonresponders) who either expired (n=21) or underwent heart transplantation (n=5) or left ventricular assist device implantation (n=2) after an average of 371+/-220 days. Mean BNP levels after 3 months of CRT decreased in responders from 758+/-611 pg/mL to 479+/-451 pg/mL (P=.044), while in nonresponders there was increase in BNP levels from 1191+/-466 pg/mL to 1611+/-1583; P=.046. A rise in BNP levels was associated with poor response (death or need for transplantation or left ventricular assist device and impaired long-term outcome), which makes it a good predictor to identify such patients.     

Predictive parameters for imatinib failure in patients with chronic myeloid leukemia

Objective: Until recently, imatinib was the standard first-line treatment in chronic myeloid leukemia (CML). The inclusion of nilotinib and dasatinib as first-line options in CML raised a debate on treatment selection. The aim of our study was to analyze predictive parameters for imatinib response as the first-line treatment of CML patients.

Methods: The study included 168 consecutive patients with chronic phase Philadelphia-positive CML who were diagnosed and treated with Imatinib 400?mg once daily at a single university hospital. Numerous parameters were analyzed in terms of imatinib response including comorbidities as well as occurrence of second malignancies.

Results: After the median follow-up of 87 months in 61 patients (36.3%), the imatinib failure was verified. Cox regression analysis identified hepatomegaly (p?=?0.001), leukocytosis?≥?100?×?109/l (p?=?0.001), blood blasts?≥?1% (p?=?0.002), and the presence of additional cytogenetic aberrations (p?=?0.002) as predictors of Imatinib failure. Based on these findings, a new prognostic model was developed according to which imatinib failure had 17% (8/47) of patients in low risk, 34.9% (30/86) of patients in intermediate risk, and 76.7% (23/30) of patients in high-risk group (HR?=?3.973, 95% CI for HR 2.237–7.053, p?Conclusion: The new score allows better selection of patients who are suitable for treatment with imatinib and may guideline the clinical decision for front-line treatment of CML.     

High-dose imatinib mesylate therapy in newly diagnosed Philadelphia chromosome-positive chronic phase chronic myeloid leukemia

Imatinib mesylate (STI571) is effective in chronic phase chronic myelogenous leukemia (CML). However, most patients treated with 400 mg imatinib daily have variable levels of residual molecular disease. We treated 114 patients with newly diagnosed chronic phase CML with 400 mg imatinib twice daily. Overall, 109 patients (96%) had a major cytogenetic response (Philadelphia chromosome [Ph] < 35%), and 103 (90%) had a complete response (Ph 0%). With a median follow-up of 15 months, no patient has progressed to accelerated or blastic phase. The estimated 2-year survival rate was 94%. By quantitative polymerase chain reaction (QPCR) studies, 71 (63%) of 112 patients showed BCR-ABL/ABL percentage ratios decrease to less than 0.05%, and 31 (28%) to undetectable levels. Compared with standard-dose imatinib, high-dose imatinib was associated with significantly better complete cytogenetic response (P =.0005), major molecular response (QPRC < 0.05%; P =.00001), and complete molecular response (undetectable BCR-ABL; P =.001). High-dose imatinib was well tolerated but resulted in more frequent myelosuppression; 82% of patients continue to receive 600 mg or more of imatinib daily. In conclusion, high-dose imatinib induced higher rates of complete cytogenetic response and of molecular response in patients with newly diagnosed chronic phase CML.     

Late response to low-dose imatinib in patients with chronic phase chronic myeloid leukemia

Imatinib was the first BCR-ABL tyrosine kinase inhibitor to become clinically available. In this study, we retrospectively evaluated the long-term efficacy of low-dose imatinib (final maintenance dose <300?mg per day) due to intolerance, in comparison to optimal-dose imatinib (≥300?mg per day) in patients with Philadelphia chromosome-positive chronic myeloid leukemia in the chronic phase. The Kaplan-Meier estimates of the median time to complete cytogenetic response, major molecular response, and complete molecular response were longer for 31 patients receiving low-dose imatinib (360, 1360, and 1420?days, respectively) than 74 patients receiving optimal-dose imatinib (170, 420, and 720?days, respectively). However, the differences in response shrank over time and progression-free survival were comparable between the two groups. These findings suggest that long-term treatment with low-dose imatinib is an acceptable alternative for patients with intolerance to the optimal dose.     

普伐他汀对慢性心力衰竭患者血浆脑钠素水平及心功能的影响

目的探讨普伐他汀对慢性心力衰竭(CHF)患者血浆脑钠素(BNP)水平和心功能的影响.方法将56例CHF患者随机分为普伐他汀组(30例)和对照组(26例),2组均给予常规治疗,普伐他汀组另加普伐他汀10 mg,qn,疗程8周.测定治疗前、后左心室舒张末内径(LVDd)、左心室射血分数(LVEF)、血浆BNP浓度的变化.结果普伐他汀治疗8周后,血浆BNP浓度由(218.6±64.2)ng/L降至(149.4±50.1)ng/L(P＜0.01);LVEF由(34.4±3.4)%升至(45.4±4.9)%(P＜0.05),LVDd由(65.5±5.1)mm降至(45.4±4.9)mm(P＜0.05),与对照组比较均差异有统计学意义;且患者血浆BNP降低值与LVEF增加存在负相关(r=-0.71,P＜0.01),而与LVDd减少呈正相关(r=0.79,P＜0.05).结论普伐他汀能明显改善心功能,抑制血浆BNP增高.     

螺内酯对慢性心力衰竭患者血浆脑钠肽水平及心功能的影响

目的:探讨螺内酯对慢性心力衰竭(CHF)患者血浆脑钠肽(BNP)水平和心功能的影响。方法:64例CHF患者被随机分为常规对照组(32例)和螺内酯组(32例),两组均给予常规治疗,螺内酯组另加螺内酯20mg,2次/d,观察期3个月,测定治疗前、后左心室舒张末内径(LVEDd)、左心室射血分数(LVEF)、血浆BNP浓度的变化。结果:治疗3个月后,螺内酯组总有效率(90.6%)明显高于常规治疗组(81.3%,P0.05);两组治疗后BNP、LVEDd较治疗前有显著下降,LVEF较治疗前显著升高(P均0.01),螺内酯组血浆BNP浓度由(839±67)ng/L降至(359±51)ng/L(P0.01),LVEDd由(66.01±3.7)mm降至(59.1±2.4)mm(P0.05),LVEF由(36±1.2)%升至(49±5.9)%(P0.01),且明显优于常规对照组(P0.05)。结论:在常规心衰治疗的基础上加用螺内酯能明显改善心功能,显著降低血浆脑钠肽水平。