Hermann Blessberger

Perioperative -Blockers for Preventing Surgery-Related Mortality and Morbidity: A Systematic Review and Meta-Analysis

BACKGROUND:Perioperative &bgr;-blockers are suggested to reduce cardiovascular mortality, myocardial–ischemia/infarction, and supraventricular arrhythmias after surgery. We reviewed the evidence regarding the effectiveness of perioperative &bgr;-blockers for improving patient outcomes after cardiac and noncardiac surgery. METHODS:Eleven large databases were searched from the time of their inception until October 2005. Various online-resources were consulted for the identification of unpublished trials and conference abstracts. We included randomized, controlled trials comparing perioperative &bgr;-blockers with either placebo or the standard-of-care. Of the 3680 retrieved titles, 69 met inclusion criteria for analysis. Odds ratios (OR) assuming random effects were computed in the absence of significant clinical heterogeneity. RESULTS:&bgr;-Blockers reduced the frequency of ventricular tachyarrhythmias [OR (cardiac surgery): 0.28, 95% CI 0.13–0.57; OR (noncardiac surgery): 0.56, 95% CI 0.21–1.45], atrial fibrillation/flutter [OR (cardiac surgery): 0.37, 95% CI 0.28–0.48], other supraventricular arrhythmias [OR (cardiac surgery): 0.25, 95% CI 0.18–0.35; OR (noncardiac surgery): 0.43, 95% CI 0.14–1.37], and myocardial ischemia [OR (cardiac surgery): 0.49, 95% CI 0.17–1.4; OR (noncardiac surgery): 0.38, 95% CI 0.21–0.69]. Length of hospitalization was not reduced [weighted mean difference (cardiac surgery): −0.35 days, 95% CI −0.77–0.07; weighted mean difference (noncardiac surgery): −5.59 days, 95% CI −12.22–1.04] and, in contrast to previous reports, &bgr;-blockers did not reduce mortality [OR (cardiac surgery): 0.55, 95% CI 0.17–1.83; OR (noncardiac surgery): 0.78, 95% CI 0.33–1.87], and they had no influence on the occurrence of perioperative myocardial infarction [OR (cardiac surgery): 0.89, 95% CI 0.53–1.5; OR (noncardiac surgery): 0.59; 0.25–1.39]. CONCLUSIONS:&bgr;-Blockers reduced perioperative arrhythmias and myocardial ischemia, but they had no effect on myocardial infarction, mortality, or length of hospitalization.

Familial-combined hyperlipidaemia in very young myocardial infarction survivors (≤40 years of age)

AIMS Myocardial infarction (MI) in very young individuals is a rare disease associated with an unfavourable prognosis. Familial-combined hyperlipidaemia (FCHL) increases the risk for MI in individuals below 60 years; however, its role in very young MI patients below 40 years is not as well established. We investigated the prevalence and impact of FCHL in these very young MI patients. METHODS AND RESULTS We prospectively enrolled 102 consecutive MI survivors (< or =40 years) from two high-volume cardiac catheterization centres. Patients were frequency-matched for age, gender, and centre to 200 hospital controls free from coronary heart disease. Myocardial infarction patients were invited to send family members for FCHL screening. Overall, 37 families were screened. Familial-combined hyperlipidaemia was diagnosed using a nomogram, which takes into account total cholesterol, triglycerides, and Apo B(100) levels. Thirty-eight acute myocardial infarction (AMI) patients (38%) and five controls (2.5%) displayed the FCHL phenotype, 21 of these MI patients sent family members for screening, and FCHL was confirmed in 16 families (76%). The FCHL phenotype was associated with a 24-fold increased adjusted risk for MI (95% CI 7.5-81, P < 0.001). Of all lipid parameters, VLDL-cholesterol, and non-HDL-cholesterol were most strongly associated with MI. CONCLUSIONS The present study suggests that the FCHL phenotype seems to be a major risk factor for the occurrence of MI at a very young age. It remains to be determined whether this excessively increased risk can be favourably modified by therapeutic interventions.

Relative importance of different lipid risk factors for the development of myocardial infarction at a very young age (≤ 40 years of age)

Eur J Clin Invest 2012; 42 (6): 631–636

Premature myocardial infarction is associated with low serum levels of Wnt-1.

OBJECTIVE Besides its effects on glucose and lipid metabolism, the Wnt pathway has been increasingly implicated in the regulation of proliferation, migration and survival of vascular cells. In addition, defective Wnt signaling has been identified in a family with autosomal dominant early coronary artery disease. The aim of this study was to investigate whether premature coronary artery disease is associated with features of decreased Wnt signaling. METHODS AND RESULTS We prospectively enrolled 100 consecutive young survivors of myocardial infarction (MI≤40 years of age) from two high-volume cardiac catheterization centers and 100 sex and age matched hospital controls. We determined serum levels of Wnt-1 and its antagonist Dkk-1 by ELISA. MI patients showed significantly lower Wnt-1 levels as compared to controls (151 ng/mL, IQR 38-473 ng/mL vs. 233 ng/mL, IQR 62-1756; p<0.005) whereas Dkk-1 was not different at baseline. Wnt-1 levels remained stable over time, whereas Dkk-1 significantly increased at one-year follow-up from 3557, IQR 2306-5810 pg/mL to 4973, IQR 3293-7093 pg/mL (p<0.001). In the stable phase of the disease, Wnt-1 levels were lower (p<0.005) and Dkk-1 levels were significantly higher (p<0.001) as compared to controls. Wnt-1 at follow-up was associated with glucose, HbA1c, non-HDL-, HDL-cholesterol and triglyceride levels but no other features of the metabolic syndrome. CONCLUSION This study establishes an association between low Wnt-1 and high Dkk-1 serum levels and premature myocardial infarction. Wnt-1 is associated with markers of glucose and lipid metabolism. Further research elucidating the role of Wnt pathways in premature coronary artery disease and metabolic syndrome is warranted.

Markers of bone metabolism in premature myocardial infarction (≤ 40 years of age)

INTRODUCTION Acute myocardial infarction (AMI) at young age is a rare disease with a poor prognosis. Bone metabolism parameters such as 1,25 (OH)₂ vitamin D₃, 25 (OH) vitamin D₃ and osteocalcin have been recently implicated in the development of coronary heart disease (CHD). We evaluated the role of these serum markers in a study population of very young AMI survivors (≤ 40 years). METHODS AND RESULTS We prospectively enrolled 302 subjects into our multi-center case control study, including 102 young myocardial infarction patients (≤ 40 years) and 200 control subjects who were frequency-matched on gender and age in an approximate 2:1 ratio per case patient. In the adjusted logistic regression analysis, we used baseline laboratory measurements for the first analysis (acute phase analysis) and measurements from one-year follow-up visits (stable phase analysis). In both, elevated levels of 25 (OH) vitamin D₃ (acute phase: OR per IQR 2.02, 95% CI 1.13-3.58, p = 0.017; stable phase: OR 4.07, 95% CI 1.8-9.21, p = 0.001) and 1,25 (OH)₂ vitamin D₃ (acute phase: OR 2.82, 95% CI 1.7-4.7, p < 0.001; stable phase: OR 4.57, 95% CI 2.31-9.05, p < 0.001) were associated with premature AMI. Conversely, osteocalcin was inversely associated with premature myocardial infarction (acute phase: OR 0.53, 95% CI 0.28-1.03, p = 0.059; stable phase: OR 0.26, 95% CI 0.12-0.6, p < 0.001). The observed associations were independent of the acute phase of myocardial infarction. CONCLUSION In our study, elevated levels of 25 (OH) vitamin D₃ and 1,25 (OH)₂ vitamin D₃, as well as decreased levels of osteocalcin were associated with myocardial infarction in very young patients. The precise mechanism and implications of these findings will have to be elucidated in future studies.

Predictors of response to renal denervation for resistant arterial hypertension: a single center experience.

Background: Renal denervation (RDN) has been shown to reduce blood pressure in patients with resistant arterial hypertension (RAH). We aimed to investigate predictors for response to RDN. Methods: Patients suffering from RAH underwent RDN after exclusion of secondary causes of hypertension. Ambulatory blood pressure measurement (ABPM) for 24 h was performed at baseline, 6 and 12 months after RDN. Response was defined as a at least 5 mmHg 24 h SBP drop at 6 months. A linear regression model was used to analyze an association between baseline variables and response to RDN. Results: In total, 45.6% of patients were responders to RDN. In those, there was a significant reduction in ABPM values at 6 and 12 months (12 months: 24 h SBP: −17.2 ± 9.0 mmHg, P < 0.01; 24 h DBP: −9.0 ± 11.6 mmHg, P < 0.01). Per 10 mmHg increase in baseline 24 h SBP, there was a 5.5 mmHg 24 h SBP reduction at 6 months. Per kg/m2 increase in BMI, 24 h SBP increased by 0.7 mmHg at 6 months. Per increment in antihypertensive drugs used at baseline, there was a 2.7 mmHg 24 h SBP reduction at 6 months. Conclusion: Out of a wide range of baseline variables, elevated systolic ABPM values, BMI and the number of antihypertensive drugs used were associated with response. One has to consider the Hawthorne effect, the regression to the mean phenomenon, the actual effect of sympathetic denervation and the interaction of therapy modification when interpreting data from RDN registries without a control arm.

Echo Doppler parameters predict response to cardiac resynchronization therapy.

Background  Cardiac resynchronization therapy (CRT) has been shown to reduce heart failure related morbidity and mortality. However, approximately 30% of patients do not respond to CRT. We investigated the usefulness of Echo Doppler parameters to predict reverse remodelling, functional improvement and mortality following CRT.

Premature myocardial infarction is strongly associated with increased levels of remnant cholesterol

BACKGROUND Remnant cholesterol has been defined as the cholesterol present in triglyceride-rich remnant lipoproteins. Elevated levels of remnant cholesterol have been associated with increased cardiovascular risk. Acute myocardial infarction (AMI) in very young individuals (≤40 years) represents a rare disease with a typical risk factor profile and a lipid phenotype that is characterized by a predominance of elevated triglyceride-rich lipoproteins. OBJECTIVE The aim of this study was to investigate the role of remnant cholesterol in premature AMI. METHODS We prospectively enrolled 302 patients into our multicenter case-control study comprising 102 consecutive myocardial infarction survivors (≤40 years) and 200 hospital controls. Myocardial infarction patients were frequency matched for age, gender, and center. Remnant cholesterol was calculated from standard lipid parameters. RESULTS Remnant cholesterol was 1.7-fold higher in premature AMI patients compared with controls (61.1 ± 36.8 vs 35.8 ± 16.8 mg/dL; P < .001). Remnant cholesterol was the lipid fraction most strongly associated with premature myocardial infarction (odds ratio 3.87; 95% confidence interval 2.26-6.64; P < .001) for an increase of 1-standard deviation. This observation was independent from clinical risk factors and plasma lipid levels. CONCLUSIONS Remnant cholesterol is strongly associated with premature myocardial infarction, can be easily calculated, and might serve as a new potent risk marker in this young patient population.

Characterization of Von Willebrand Factor Multimer Structure in Patients With Severe Aortic Stenosis

Acquired von Willebrand syndrome (AVWS) associated with severe aortic stenosis (AS) has been frequently subclassified into a subtype 2A based on the deficiency of high-molecular-weight (HMW) multimers as it is seen in inherited von Willebrand disease (VWD) type 2A. However, the multimeric phenotype of VWD type 2A does not only include an HMW deficiency but also a decrease in intermediate-molecular-weight (IMW) multimers and an abnormal inner triplet band pattern. These additional characteristics have not been evaluated in AVWS associated with severe AS. Therefore, we recruited N = 31 consecutive patients with severe AS and performed a high-resolution Western blot with densitometrical band quantification to characterize the von Willebrand factor (VWF) multimeric structure and reevaluate the AVWS subtype classification. Study patients showed an isolated HMW VWF multimer deficiency without additional abnormalities of the IMW portions and the inner triplet structure in 65%. In conclusion, the multimeric pattern of AVWS associated with severe AS does neither resemble that seen in AVWS type 2A nor that seen in inherited VWD type 2A. Therefore, a subclassification into a type 2A should not be used.

Economic assessment of traditional surgical intervention versus use of a new innovative radiofrequency based surgical system in device replacements

Introduction Intra-operative complications like mechanical damages to the leads, infections and hematomas during generator replacements of implantable pacemakers and defibrillators contribute to additional costs for hospitals. The aim of this study was to evaluate operation room use, costs and budget impact of generator replacements using either a traditional surgical intervention (TSI) with scissors, scalpel and electrocautery vs. a new radiofrequency energy based surgical system, called PEAK PlasmaBladeTM (PPB). Materials and methods We conducted a retrospective analysis of a population including 508 patients with TSI and 254 patients with PPB who underwent generator replacement at the Kepler University Hospital in Linz or the St. Josef Hospital in Braunau, Austria. The economic analysis included costs of resources used for intra-operative complications (lead damages) and of procedure time for TSI vs. PPB. Results Proportion of males, mean age and type of generator replaced were similar between the two groups. Lead damages occurred significantly more frequent with TSI than with PPB (5.3% and 0.4%; p< 0.001) and the procedure time was significantly longer with TSI than with PPB (47.9±24.9 and 34.1±18.1 minutes; p<0.001). Shorter procedure time and a lower rate of lead damages with PPB resulted in per patient cost savings of €81. Based on estimated 2,700 patients annually undergoing generator replacement in Austria, the use of PPB may translate into cost savings of €219,600 and 621 saved operating facility hours. Conclusion PPB has the potential to minimize the risk of lead damage with more efficient utilization of the operating room. Along with cost savings and improved quality of care, hospitals may use the saved operating room hours to increase the number of daily surgeries.