Therapeutic benefits of increasing natriuretic peptide levels

Natriuretic peptides play an important role in water and salt homeostasis and in the regulation of the cardiovascular system. In recent years, exogenous administration of natriuretic peptides has primarily been used to improve our understanding of the role of natriuretic peptides. Also, it became evident that natriuretic peptides may be used therapeutically. Because of their peptide character, they cannot be administered orally and, therefore, may be used for short-term intravenous therapy only. In recent years, inhibitors of neutral endopeptidase, which degrades natriuretic peptides to inactive metabolites, have been investigated. This review focuses on the potential benefits of increasing natriuretic peptide levels, either through exogenous administration or inhibiting the degradation of endogenous natriuretic peptide

Individual dosage of digoxin in patients with heart failure

Backgroud: After the publication of DIG trial, the therapeutic target of serum digoxin concentration (SDC) for the treatment of heart failure (HF) has been lowered (0.40-1.00 ng/ml). However, the majority of equations to calculate digoxin dosages were developed for higher SDCs. Recently, a new equation was validated in Asian population for low SDCs by Konishi et al., but results in Caucasians are unknown. Aim: This study was aimed to test the Konishi equation in Caucasians specifically targeting low SDCs. Furthermore, the Konishi equation was compared with other frequently used equations. Design: This was a prospective, multicenter study. Methods: Clinically indicated digoxin was given in 40 HF patients. The dosage was calculated with the Konishi equation. The SDC was measured at 1 and 6 months after starting digoxin. Adherence to digoxin was monitored with a specific questionnaire. Results: After exclusion of patients admitting poor adherence, we found a reasonable correlation between predicted and measured SDC (r = 0.48; P < 0.01) by the Konishi equation. Excluding patients with poor adherence and relevant worsening of renal function, the measured SDC (n = 54 measurements) was within the pre-defined therapeutic range in 95% of the cases. The mean, maximal and minimal measured SDC were 0.69 ± 0.19, 1.00 and 0.32 ng/ml, respectively. The correlation was weaker for the Jelliffe, the Koup and Jusko, and the Bauman equations. Conclusions: This study supports the clinical validity of the Konishi equation for calculating individual digoxin dosage in Caucasians, targeting SDCs according to current HF guideline

Limited diagnostic yield of non-invasive coronary angiography by 16-slice multi-detector spiral computed tomography in routine patients referred for evaluation of coronary artery disease

Aims Multislice spiral computed tomography (MSCT) is a promising non-invasive method to diagnose coronary artery disease (CAD). As no detailed comparative evaluation in consecutive patients referred for evaluation of CAD has been reported, this prospective study evaluating 2384 coronary segments in 149 consecutive patients was performed. Methods and results The coronary artery tree was analysed in 16 segments both for coronary angiography (CA) and MSCT; a luminal narrowing ≥50% based on visual assessment was considered significant. By MSCT, 77% of 2110 angiographically assessable segments could be evaluated, 94% per patient in proximal and 70% in distal segments (P<0.001). Sensitivity of MSCT to detect significant stenoses was 30% in all, but only 10% in peripheral segments. The main limitations were calcifications in 34% of segments and motion artefacts in 24% of patients. Overall diagnostic sensitivity for the presence of significant CAD was 86% but specificity was only 49%. Conclusion When compared with invasive CA, 16-slice MSCT is of limited diagnostic value for the diagnosis of CAD in consecutive patients. Despite a clinically useful sensitivity for the overall diagnosis of significant CAD, specificity is low. Thus, relevant decisions regarding the need of and suitability for possible revascularization procedures cannot be based on MSCT findings alon

How reliable are left ventricular ejection fraction cut offs assessed by echocardiography for clinical decision making in patients with heart failure?

We aimed to study the potential influence of the variability in the assessment of echocardiographically measured left ventricular ejection fraction (LVEF) on indications for the implantation of internal cardioverter defibrillator and/or cardiac resynchronization devices in heart failure patients. TIME-CHF was a multicenter trial comparing NT-BNP versus symptom-guided therapy in patients aged ≥60years. Patients had their LVEF assessed at the recruiting centre using visual assessment, the area-length or biplane Simpson's method. Echocardiographic data were transferred to the study core-lab for re-assessment. Re-assessment in the core-lab was done with biplane Simpson's method, and included an appraisal of image quality. 413 patients had the LVEF analyzed at the recruiting centre and at the core lab. Image quality was optimal in 191 and suboptimal in 222. Overall, the correlation between LVEF at the recruiting centres and at the core-lab was good, independent of image quality (R²=0.62). However, when a LVEF≤30% or ≥30% was used as a cut-off, about 20% of all patients would have been re-assigned to having either a LVEF above or below the cut-off, this proportion was not significantly influenced by image quality. We conclude that correlation between LVEF assessed by different centres based on the same ultrasound data is good, regardless of image quality. However, one fifth of patients would have been re-assigned to a different category when using the clinically important cut-off of 30

Results of surgery for irreversible moderate to severe mitral valve regurgitation secondary to myocardial infarction

Objective: Moderate to severe irreversible mitral regurgitation secondary to myocardial infarction is an independent risk factor for reduced long-term survival. Late effects of correction of mitral incompetence concomitant with coronary artery bypass grafting (CABG) are less well known and the choice of mitral valve procedure is still debated. Methods: From 1988 to 1998, 93 consecutive patients (mean age 63±9 years) were treated for moderate to severe irreversible mitral regurgitation secondary to myocardial infarction; 84 were in NYHA functional class III-IV and 19 were in cardiogenic shock. Thirty-seven patients underwent emergency surgery. Perioperative intraaortic balloon pump (IABP) was necessary in 33 patients. Follow-up ranged from 6 months to 12 years (mean 51 months±41). Results: Mitral valve was repaired in 30 patients and replaced in 63. Replacement was preferably performed in patients with major displacement of papillary muscle and in patients with acute papillary muscle rupture. CABG (3.4 distal anastomoses) was performed in all patients and was complete in 92%. Early mortality was 15% (14/93). Multivariable analysis identified need for IABP (P=0.005) and COPD (P=0.02) as risk factors for early death. Emergency surgery had only a trend (P=0.15) for increased mortality; age, low ejection fraction, repair vs. replacement had no influence. Actuarial survival rates at 1, 5 and 10 years were 81, 65 and 56%, respectively. Late survival was similar in patients with replacement or repair (P=0.46). At last follow-up, all but one patient were in NYHA functional class I or II. Conclusions: Combined mitral valve procedure and myocardial revascularization, as complete as possible, for moderate to severe mitral regurgitation secondary to myocardial infarction achieve satisfactory early and late outcome despite the increased operative mortality. Acute papillary muscle rupture, severe restriction of the mitral valve by major displacement of the papillary muscle are better managed by valve replacemen

Long-term benefit-risk balance of drug-eluting vs. bare-metal stents in daily practice: does stent diameter matter? Three-year follow-up of BASKET

Aims To assess the long-term benefit-risk ratio of drug-eluting (DES) vs. bare-metal stents (BMS) relative to stent size. Methods and results All 826 consecutive BASKET (BAsel Stent Kosten-Effektivitäts Trial) patients randomized 2:1 to DES vs. BMS were followed after 3 years. Data were analysed separately for patients with small stents (<3.0 mm vessel/<4.0 mm bypass grafts, n = 268) vs. only large stents (≥3.0 mm native vessels, n = 558). Clinical events were related to stent thrombosis. Three-year clinical target-vessel revascularization rates remained borderline reduced after DES [9.9 vs. 13.9% (BMS), P = 0.07], particularly in patients with small stents (10.7 vs. 19.8%, P = 0.03; large stents: 9.5 vs. 11.5%, P = 0.44). Cardiac death/myocardial infarction (MI) rates (12.7 vs. 10.0%, P = 0.30) were similar, however, death/MI beyond 6 months was higher after DES [9.1 vs. 3.8% (BMS), P = 0.009], mainly due to increased late death/MI in patients with large stents (9.7 vs. 3.1%, P = 0.006). The results paralleled findings for stent thrombosis. Conclusion The clinical benefit of DES was maintained at no overall increased risk of death or death/MI up to 3 years. However, death/MI rates were increased in DES vs. BMS patients beyond 6 months, particularly in patients with large stents, paralleling findings for stent thrombosis. Thus, stent size seems to influence the 3-year benefit-risk ratio after DES implantatio