The flipped classroom in medical education: A new standard in teaching.

Many medical educators, out of necessity imposed by the COVID-19 pandemic, had to flip their classrooms. However, instead of adapting to this new teaching style, many have proceeded in the manner that they have always used to create content, opening a slide deck and inserting content until they are satisfied with the result. When in fact, we know based on evidence and our own experience, that educators should first plan, organize, and storyboard before collecting information into a presentation [1,2]. If educators need to replace real-world teaching and interaction, we believe the next best option is video education, although there are other forms of prework that can be utilized to flip medical classrooms, including short readings and exercises. We discuss the case for flipping medical classrooms, the limitations, and how educators can get started flipping their classrooms today.

Lipid profile and long-term outcome in premature myocardial infarction.

BACKGROUND: Premature myocardial infarction (≤40 years) represents a rare disease with a distinct risk factor profile and a lipid phenotype that is characterized by a predominance of elevated triglyceride-rich lipoproteins. So far high-density and low-density lipoproteins remain the primary targets for risk stratification and treatment evaluation in coronary artery disease, but this strategy might be insensitive in patients with premature myocardial infarction. AIM: Aim of this study was to investigate the predictive value of different lipid fractions on long-term cardiovascular outcome in patients with premature myocardial infarction. METHODS: We prospectively enrolled 102 consecutive AMI survivors (≤40 years) in this prospective multicentre study and investigated the influence of the familial combined hypercholesterolaemia phenotype and a corresponding multimarker panel of different lipid fractions on cardiovascular outcome. RESULTS: Total cholesterol, non-HDL cholesterol, remnant cholesterol and Apo B lipoprotein were significantly higher in patients experiencing MACE as compared to those who did not. The familial combined hypercholesterolaemia phenotype was associated with an unfavourable cardiovascular outcome even after adjustment for potential cofounders (adjusted HR 3.04,95% CI, 1.26-7.34, P = 0.013). Remnant cholesterol revealed the strongest association with MACE (adj.HR 1.94, 95%CI. 1.30-2.99, P = 0.001). Interestingly LDL and HDL revealed no significant impact on cardiovascular outcome in this study cohort. CONCLUSION: Non-HDL and remnant cholesterol are strongly associated with an unfavourable outcome in patients with premature myocardial infarction and might be the preferred treatment target for lipid-lowering therapy.

Perioperative beta-blockers for preventing surgery-related mortality and morbidity.

BACKGROUND: Randomized controlled trials have yielded conflicting results regarding the ability of beta-blockers to influence perioperative cardiovascular morbidity and mortality. Thus routine prescription of these drugs in unselected patients remains a controversial issue. OBJECTIVES: The objective of this review was to systematically analyse the effects of perioperatively administered beta-blockers for prevention of surgery-related mortality and morbidity in patients undergoing any type of surgery while under general anaesthesia. SEARCH METHODS: We identified trials by searching the following databases from the date of their inception until June 2013: MEDLINE, Embase , the Cochrane Central Register of Controlled Trials (CENTRAL), Biosis Previews, CAB Abstracts, Cumulative Index to Nursing and Allied Health Literature (CINAHL), Derwent Drug File, Science Citation Index Expanded, Life Sciences Collection, Global Health and PASCAL. In addition, we searched online resources to identify grey literature. SELECTION CRITERIA: We included randomized controlled trials if participants were randomly assigned to a beta-blocker group or a control group (standard care or placebo). Surgery (any type) had to be performed with all or at least a significant proportion of participants under general anaesthesia. DATA COLLECTION AND ANALYSIS: Two review authors independently extracted data from all studies. In cases of disagreement, we reassessed the respective studies to reach consensus. We computed summary estimates in the absence of significant clinical heterogeneity. Risk ratios (RRs) were used for dichotomous outcomes, and mean differences (MDs) were used for continuous outcomes. We performed subgroup analyses for various potential effect modifiers. MAIN RESULTS: We included 88 randomized controlled trials with 19,161 participants. Six studies (7%) met the highest methodological quality criteria (studies with overall low risk of bias: adequate sequence generation, adequate allocation concealment, double/triple-blinded design with a placebo group, intention-to-treat analysis), whereas in the remaining trials, some form of bias was present or could not be definitively excluded (studies with overall unclear or high risk of bias). Outcomes were evaluated separately for cardiac and non-cardiac surgery.CARDIAC SURGERY (53 trials)We found no clear evidence of an effect of beta-blockers on the following outcomes.• All-cause mortality: RR 0.73, 95% CI 0.35 to 1.52, 3783 participants, moderate quality evidence.• Acute myocardial infarction (AMI): RR 1.04, 95% CI 0.71 to 1.51, 3553 participants, moderate quality evidence.• Myocardial ischaemia: RR 0.51, 95% CI 0.25 to 1.05, 166 participants, low quality evidence.• Cerebrovascular events: RR 1.52, 95% CI 0.58 to 4.02, 1400 participants, low quality evidence.• Hypotension: RR 1.54, 95% CI 0.67 to 3.51, 558 participants, low quality evidence.• Bradycardia: RR 1.61, 95% CI 0.97 to 2.66, 660 participants, low quality evidence.• Congestive heart failure: RR 0.22, 95% CI 0.04 to 1.34, 311 participants, low quality evidence.Beta-blockers significantly reduced the occurrence of the following endpoints.• Ventricular arrhythmias: RR 0.37, 95% CI 0.24 to 0.58, number needed to treat for an additional beneficial outcome (NNTB) 29, 2292 participants, moderate quality evidence.• Supraventricular arrhythmias: RR 0.44, 95% CI 0.36 to 0.53, NNTB five, 6420 participants, high quality evidence.• On average, beta-blockers reduced length of hospital stay by 0.54 days (95% CI -0.90 to -0.19, 2450 participants, low quality evidence).NON-CARDIAC SURGERY (35 trials)Beta-blockers significantly increased the occurrence of the following adverse events.• All-cause mortality: RR 1.25, 95% CI 1.00 to 1.57, 11,413 participants, low quality of evidence, number needed to treat for an additional harmful outcome (NNTH) 167.• Hypotension: RR 1.50, 95% CI 1.38 to 1.64, NNTH 16, 10,947 participants, high quality evidence.• Bradycardia: RR 2.23, 95% CI 1.48 to 3.36, NNTH 21, 11,033 participants, moderate quality evidence.We found a potential increase in the occurrence of the following outcomes with the use of beta-blockers.• Cerebrovascular events: RR 1.59, 95% CI 0.93 to 2.71, 9150 participants, low quality evidence.Whereas no clear evidence of an effect was found when all studies were analysed, restricting the meta-analysis to low risk of bias studies revealed a significant increase in cerebrovascular events with the use of beta-blockers: RR 2.09, 95% CI 1.14 to 3.82, NNTH 265, 8648 participants.Beta-blockers significantly reduced the occurrence of the following endpoints.• AMI: RR 0.73, 95% CI 0.61 to 0.87, NNTB 76, 10,958 participants, high quality evidence.• Myocardial ischaemia: RR 0.51, 95% CI 0.34 to 0.77, NNTB nine, 978 participants, moderate quality evidence.• Supraventricular arrhythmias: RR 0.73, 95% CI 0.57 to 0.94, NNTB 112, 8744 participants, high quality evidence.We found no clear evidence of an effect of beta-blockers on the following outcomes.• Ventricular arrhythmias: RR 0.68, 95% CI 0.31 to 1.49, 476 participants, moderate quality evidence.• Congestive heart failure: RR 1.18, 95% CI 0.94 to 1.48, 9173 participants, moderate quality evidence.• Length of hospital stay: mean difference -0.45 days, 95% CI -1.75 to 0.84, 551 participants, low quality evidence. AUTHORS' CONCLUSIONS: According to our findings, perioperative application of beta-blockers still plays a pivotal role in cardiac surgery, as they can substantially reduce the high burden of supraventricular and ventricular arrhythmias in the aftermath of surgery. Their influence on mortality, AMI, stroke, congestive heart failure, hypotension and bradycardia in this setting remains unclear.In non-cardiac surgery, evidence shows an association of beta-blockers with increased all-cause mortality. Data from low risk of bias trials further suggests an increase in stroke rate with the use of beta-blockers. As the quality of evidence is still low to moderate, more evidence is needed before a definitive conclusion can be drawn. The substantial reduction in supraventricular arrhythmias and AMI in this setting seems to be offset by the potential increase in mortality and stroke.

Long-term outcome and risk assessment in premature acute myocardial infarction: A 10-year follow-up study.

BACKGROUND: Premature acute myocardial infarction (AMI) is a rare disease carrying significant morbidity and mortality. Existing data on outcome in these patients is based on retrospective analysis of angiographic reports or refer to time periods with incomparable treatment regimes, making them unusable for risk assessment in times of widespread use of reperfusion therapy. Aim of this study was to assess the outcome of premature AMI in a prospectively recruited study population enrolled in the times of modern reperfusion therapy. METHODS: We included 102 consecutive AMI survivors (≤40years) in this prospective multicentre study. Outcome was assessed via retrieval query of the Austrian Death Registry and the centralized patient management system of Vienna. RESULTS: During a median follow up time of 10.3years (IQR:8.9-11.1), 23% of all patients experienced MACE, of those 6% died, 17% experienced re-AMI and 5% patients an ischemic stroke. Furthermore, forty patients underwent cardiac re-catheterization and twenty-five needed recurrent revascularization. MACE were associated among the classic cardiovascular risk factors with elevated levels of HbA1c (adj. HR 1.32; 95%CI 1.06-1.64; P=0.012), total cholesterol (adj. HR 2.16; 95%CI 1.27-3.48; P=0.004), and c-reactive protein (adj. HR 1.67; 95%CI 1.29-2.17; P=0-003) for an increase of 1-standard deviation. CONCLUSION: Although myocardial re-infarction was the driving force of morbidity in premature myocardial infarction, we observed an excellent long-term survival opposed to previous reports. We found that persistence risk factors rather than the clinical risk profile at baseline influences the outcome in these patients, emphasizing the importance of secondary prevention in young patients after AMI.

Soluble galectin-3 is associated with premature myocardial infarction.

BACKGROUND: Inflammatory responses are pivotal in the initiation and development of premature atherosclerotic lesions. Galectin-3 represents a valuable biomarker for both progression and destabilization of atherosclerotic lesions. This study aims to assess the involvement of galectin-3 in premature myocardial infarction. DESIGN: In this multicentre case-control study, we assessed circulating galectin-3 levels in 144 patients comprising 72 consecutive survivors of acute myocardial infarction (≤ 40 years) and 72 hospital controls frequency matched for age, gender and centre. RESULTS: Patients with acute myocardial infarction showed significantly higher galectin-3 levels as compared to controls in the acute phase of acute myocardial infarction (2552 ± 1992 vs. 1666 ± 829 pg/mL; P < 0·001) as well as in the stable phase 1 year after the index event (3692 ± 1774 vs. 1666 ± 829 pg/mL; P < 0·001). Circulating galectin-3 was significantly and independently associated with premature myocardial infarction in the logistic regression analysis (acute phase: adj. OR per 1-SD change 2·03, 95% CI 1·30-3·19; P = 0·002; stable phase: adj. OR of 6·54 (95% CI 2·56-16·68; P < 0·001). Moreover, we observed a significant correlation between circulating galectin-3 and leucocyte count (r = 0·35, P < 0·001), non-HDL cholesterol (r = 0·23, P = 0·014) and HDL cholesterol (r = -0·29, P = 0·002). CONCLUSION: We demonstrated that elevated levels of circulating galectin-3 are strongly associated with premature myocardial infarction. Galectin-3 might serve as link between dyslipidaemia as driving force of plaque formation with inflammation as initiator of plaque rupture in patients with premature acute myocardial infarction.

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.

Impaired antioxidant HDL function is associated with premature myocardial infarction.

BACKGROUND: There is growing evidence that the predictive value of HDL cholesterol levels for cardiovascular risk stratification is limited in patients with coronary artery disease (CAD). HDL function seems to be a more sensitive surrogate of cardiovascular risk estimation than simple serum levels. Therefore, we aimed to assess whether impaired antioxidant HDL function is involved in the development of premature acute myocardial infarction (AMI). METHODS: In this multicentre case-control study, we compared the antioxidant function of HDL, measured by the HDL inflammatory index (HII), and HDL particle size in 184 patients comprising 92 patients with AMI at a very young age (≤40 years of age) and 92 age- and gender-matched controls. RESULTS: Antioxidant capacities of HDL were significantly impaired in the acute phase of AMI (HII of 1·50 [IQR 1·10-1·74] vs. 0·56 [IQR 0·41-0·86] in controls, P < 0·001 as well as in the chronic stable phase 1 year after the event (HII of 0·85 [IQR 0·72-1·03] vs. 0·56 [IQR 0·41-0·86], P < 0·001) compared to controls. Moreover, HDL function in the stable phase remained significantly associated with premature MI in adjusted logistic regression analysis with an OR of 2·24 per SD increase of HII (95% CI 1·28-3·91; P = 0·005). Analyses of HDL size revealed a significant correlation between all HDL subfractions and HDL function in controls, whereas this correlation was lost for large and intermediate HDL in AMI patients. CONCLUSION: Impaired antioxidant function of HDL is independently associated with the development of premature AMI. The maintenance of HDL function might evolve into a significant therapeutic target, especially in patients with premature CAD.

Perioperative beta-blockers for preventing surgery-related mortality and morbidity.

BACKGROUND: Randomized controlled trials have yielded conflicting results regarding the ability of beta-blockers to influence perioperative cardiovascular morbidity and mortality. Thus routine prescription of these drugs in unselected patients remains a controversial issue. OBJECTIVES: The objective of this review was to systematically analyse the effects of perioperatively administered beta-blockers for prevention of surgery-related mortality and morbidity in patients undergoing any type of surgery while under general anaesthesia. SEARCH METHODS: We identified trials by searching the following databases from the date of their inception until June 2013: MEDLINE, EMBASE, the Cochrane Central Register of Controlled Trials (CENTRAL), Biosis Previews, CAB Abstracts, Cumulative Index to Nursing and Allied Health Literature (CINAHL), Derwent Drug File, Science Citation Index Expanded, Life Sciences Collection, Global Health and PASCAL. In addition, we searched online resources to identify grey literature. SELECTION CRITERIA: We included randomized controlled trials if participants were randomly assigned to a beta-blocker group or a control group (standard care or placebo). Surgery (any type) had to be performed with all or at least a significant proportion of participants under general anaesthesia. DATA COLLECTION AND ANALYSIS: Two review authors independently extracted data from all studies. In cases of disagreement, we reassessed the respective studies to reach consensus. We computed summary estimates in the absence of significant clinical heterogeneity. Risk ratios (RRs) were used for dichotomous outcomes, and mean differences (MDs) were used for continuous outcomes. We performed subgroup analyses for various potential effect modifiers. MAIN RESULTS: We included 89 randomized controlled trials with 19,211 participants. Six studies (7%) met the highest methodological quality criteria (studies with overall low risk of bias: adequate sequence generation, adequate allocation concealment, double/triple-blinded design with a placebo group, intention-to-treat analysis), whereas in the remaining trials, some form of bias was present or could not be definitively excluded (studies with overall unclear or high risk of bias). Outcomes were evaluated separately for cardiac and non-cardiac surgery. CARDIAC SURGERY (53 trials)We found no clear evidence of an effect of beta-blockers on the following outcomes.• All-cause mortality: RR 0.73, 95% CI 0.35 to 1.52, 3783 participants, moderate quality of evidence.• Acute myocardial infarction (AMI): RR 1.04, 95% CI 0.71 to 1.51, 3553 participants, moderate quality of evidence.• Myocardial ischaemia: RR 0.51, 95% CI 0.25 to 1.05, 166 participants, low quality of evidence.• Cerebrovascular events: RR 1.52, 95% CI 0.58 to 4.02, 1400 participants, low quality of evidence.• Hypotension: RR 1.54, 95% CI 0.67 to 3.51, 558 participants, low quality of evidence.• Bradycardia: RR 1.61, 95% CI 0.97 to 2.66, 660 participants, low quality of evidence.• Congestive heart failure: RR 0.22, 95% CI 0.04 to 1.34, 311 participants, low quality of evidence.Beta-blockers significantly reduced the occurrence of the following endpoints.• Ventricular arrhythmias: RR 0.37, 95% CI 0.24 to 0.58, number needed to treat for an additional beneficial outcome (NNTB) 29, 2292 participants, moderate quality of evidence.• Supraventricular arrhythmias: RR 0.44, 95% CI 0.36 to 0.53, NNTB six, 6420 participants, high quality of evidence.• On average, beta-blockers reduced length of hospital stay by 0.54 days (95% CI -0.90 to -0.19, 2450 participants, low quality of evidence). NON-CARDIAC SURGERY (36 trials)We found a potential increase in the occurrence of the following outcomes with the use of beta-blockers.• All-cause mortality: RR 1.24, 95% CI 0.99 to 1.54, 11,463 participants, low quality of evidence.Whereas no clear evidence of an effect was noted when all studies were analysed, restricting the meta-analysis to low risk of bias studies revealed a significant increase in all-cause mortality with the use of beta-blockers: RR 1.27, 95% CI 1.01 to 1.59, number needed to treat for an additional harmful outcome (NNTH) 189, 10,845 participants.• Cerebrovascular events: RR 1.59, 95% CI 0.93 to 2.71, 9150 participants, low quality of evidence.Whereas no clear evidence of an effect was found when all studies were analysed, restricting the meta-analysis to low risk of bias studies revealed a significant increase in cerebrovascular events with the use of beta-blockers: RR 2.09, 95% CI 1.14 to 3.82, NNTH 255, 8648 participants.Beta-blockers significantly reduced the occurrence of the following endpoints.• AMI: RR 0.73, 95% CI 0.61 to 0.87, NNTB 72, 10,958 participants, high quality of evidence.• Myocardial ischaemia: RR 0.43, 95% CI 0.27 to 0.70, NNTB seven, 1028 participants, moderate quality of evidence.• Supraventricular arrhythmias: RR 0.72, 95% CI 0.56 to 0.92, NNTB 111, 8794 participants, high quality of evidence.Beta-blockers significantly increased the occurrence of the following adverse events.• Hypotension: RR 1.50, 95% CI 1.38 to 1.64, NNTH 15, 10,947 participants, high quality of evidence.• Bradycardia: RR 2.24, 95% CI 1.49 to 3.35, NNTH 18, 11,083 participants, moderate quality of evidence.We found no clear evidence of an effect of beta-blockers on the following outcomes.• Ventricular arrhythmias: RR 0.64, 95% CI 0.30 to 1.33, 526 participants, moderate quality of evidence.• Congestive heart failure: RR 1.17, 95% CI 0.93 to 1.47, 9223 participants, moderate quality of evidence.• Length of hospital stay: mean difference -0.27 days, 95% CI -1.29 to 0.75, 601 participants, low quality of evidence. AUTHORS' CONCLUSIONS: According to our findings, perioperative application of beta-blockers still plays a pivotal role in cardiac surgery , as they can substantially reduce the high burden of supraventricular and ventricular arrhythmias in the aftermath of surgery. Their influence on mortality, AMI, stroke, congestive heart failure, hypotension and bradycardia in this setting remains unclear.In non-cardiac surgery, evidence from low risk of bias trials shows an increase in all-cause mortality and stroke with the use of beta-blockers. As the quality of evidence is still low to moderate, more evidence is needed before a definitive conclusion can be drawn. The substantial reduction in supraventricular arrhythmias and AMI in this setting seems to be offset by the potential increase in mortality and stroke.

Left atrial diameter and survival among renal allograft recipients.

BACKGROUND AND OBJECTIVES: Sequential echocardiography is routinely performed in patients with ESRD listed for transplantation. The benefit of this labor- and time-intensive measure, however, remains unclear. Thus, this study elucidated the various obtained routine echocardiography parameters that best predicted mortality and graft survival after renal transplantation. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: This study investigated 553 first renal transplant recipients listed in the Austrian Dialysis and Transplant Registry between 1992 and 2011 who had echocardiographic analysis at transplantation and survived at least 1 year. Cox proportional hazards models with the purposeful selection algorithms for covariables were used to identify predictors of mortality and graft loss. A Fine and Gray model was used to evaluate cause-specific death. RESULTS: During a median follow-up of 7.14 years, 81 patients died, and 59 patients experienced graft loss after the first year. The Kaplan-Meier analysis showed that 85% of patients with a left atrial diameter below the median of 53 mm were alive 10 years after transplantation, whereas only 70% of those patients with a left atrial diameter equal to or above the median had survived (P<0.001). In the multivariable model, left atrial diameter (per millimeter) independently predicted overall mortality (hazard ratio, 1.06; 95% confidence interval, 1.03 to 1.08; P<0.001) and cause-specific cardiac death (hazard ratio, 1.04; 95% confidence interval, 1.00 to 1.08; P=0.04). Functional graft loss was predicted by the right atrial diameter (hazard ratio, 1.04; 95% confidence interval, 1.02 to 1.07; P=0.001). CONCLUSION: The left atrial diameter determined at transplantation predicted overall and cardiac mortality. Patients with widely enlarged left atria exhibit a considerably reduced life expectancy. It remains to be determined, however, whether renal transplantation is futile in these patients.

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.

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

BACKGROUND: Low-density lipoprotein (LDL) cholesterol lowering has been established as one of the principal targets in preventive cardiology. Recently, assessment of LDL particle size and number as well as other lipid moieties has been presented as a more reliable method to quantify atherogenicity of the lipoprotein fractions. Thus, it was our aim to assess the influence of different lipoprotein fractions on premature myocardial infarction (≤ 40 years of age). METHODS AND RESULTS: We enrolled 302 patients into our multicentre case-control study, including 102 patients with myocardial infarction and 200 age-, gender- and centre-matched controls. The LDL and HDL Lipoprint System were used for lipid subfraction quantification. The lipid risk factors most strongly associated with premature acute myocardial infarction (AMI) in the adjusted model were non-HDL C (OR 5·02, 95% CI 2·75-9·15, P-value = 0·001), LDL-C (OR 4·35, 95% CI 2·5-7·57, P-value = 0·001), VLDL-C (OR 3·66, 95% CI 2·14-6·28, P-value = 0·001), large IDL-C (OR 3·15, 95% CI 1·94-5·12, P-value = 0·001), large LDL-C (OR 3·67, 95% CI 2·19-6·15, P-value = 0·001) and intermediate LDL-C (OR 1·96, 95% CI 1·25-3·06, P-value = 0·003). In contrast, small dense LDL was not significantly associated with premature myocardial infarction. CONCLUSION: Non-HDL cholesterol is most strongly associated with premature coronary artery disease and could serve as preferred risk predictor and therapeutic target in this young patient population (≤ 40 years). Besides, VLDL, LDL-C, large LDL, intermediate LDL and large IDL were significantly associated with premature myocardial infarction. Furthermore, our data suggest that risk prediction using small dense LDL particles might not be useful in young AMI survivors.

The effect of p22-PHOX (CYBA) polymorphisms on premature coronary artery disease (≤ 40 years of age).

Acute myocardial infarction at a young age is associated with high morbidity and long-term mortality. The NADPH oxidase system as a main source of reactive oxygen species in vascular cells has been implicated in development and progression of coronary artery disease (CAD). In our study, we investigated the effect of polymorphisms in the p22-PHOX (CYBA) gene on CAD in young patients (≤ 40 years). We prospectively recruited 302 subjects into our multi-centre case control study, including 102 young myocardial infarction patients (≤ 40 years) from two high-volume cardiac catheterisation hospitals and frequency-matched them on age, gender, and center to 200 hospital controls in an approximate 2:1 ratio per case patient. The homozygote c.-930A>G promoter polymorphism was significantly more prevalent in the controls than in the infarction patients. In the adjusted logistic regression analysis, we detected a protective effect of the c.-930A>G promoter polymorphism against premature myocardial infarction. Using a log-additive/per-allele model, we detected an unadjusted odds ratio (OR) of 0.63 (95% confidence interval [CI] 0.45-0.9, p-value 0.011). In the adjusted model the association was more pronounced with an OR of 0.5 (95% CI 0.3-0.81, p-value 0.005). The C242T polymorphism and the 640A>G polymorphism did not differ significantly between the study groups. Furthermore we could not detect a significant effect for these polymorphisms in the logistic regression analysis. The present study suggests a protective association between the c.-930A>G promoter polymorphism in the p22-PHOX (CYBA) gene and the development of myocardial infarction in young individuals (≤ 40 years).

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.

Electrical optimization of cardiac resynchronization in chronic heart failure is associated with improved clinical long-term outcome.

BACKGROUND: Cardiac resynchronization therapy (CRT) is an established treatment option for symptomatic chronic heart failure (CHF) patients with pharmacological baseline therapy, but not all patients benefit from device therapy. One reason for this may be inadequate device settings. In real-world practice, echocardiographic evaluation of atrioventricular (AV) delay is not performed in a high proportion of patients, as the effect of electrical optimization of CRT is an issue open for investigation. MATERIALS AND METHODS: We performed a retrospective observational study analysing the effect of AV-interval evaluation with echocardiography on long-term [32 (23?43) months] clinical outcome in 205 CHF patients. A stepwise Cox regression model including a co-morbidity score, failed AV-interval evaluation, satisfactory device function after the first implantation attempt, failure to reach 100% of the recommended renin-angiotensin system inhibitor and beta-blocker dose at follow-up and CRT device implantation compared with CRT in combination with an implanted cardioverter defibrillator (ICD) was applied. RESULTS: In the total study cohort, 124 (60.5%) patients had reached the primary combined endpoint death or cardiac hospitalization and 59 (28.8%) had died. Cox regression analysis revealed that failed AV-interval evaluation [HR = 1.72 (1.19-2.49), P = 0.004] non-optimized CHF pharmacotherapy dosages [HR = 2.12 (1.32-3.42), P = 0.002], the presence of a CRT/ICD combination device [HR = 1.87 (1.28-2.71), P = 0.001] and satisfactory device function after the first implantation attempt [HR = 0.44 (0.25-0.77), P = 0.004] were associated with the primary endpoint. CONCLUSION: Echocardiographic evaluation of the AV-interval in patients with CRT was independently associated with improved clinical outcome, impacting on daily clinical practice of HF patient care.

D-dimer testing in the diagnosis of transfemoral pseudoaneurysm after percutaneous transluminal procedures.

OBJECTIVE: Pseudoaneurysms are characterized by extravascular circulation and therefore may lead to an activation of the coagulation cascade. We investigated d-dimer levels in patients with and without postcatheterization femoral pseudoaneurysms and hypothesized that d-dimer levels correlate with the presence of pseudoaneurysms at the vascular access site. METHODS: Patients with clinical suspected groin pseudoaneurysms after transluminal procedures were eligible. We compared prospectively-collected laboratory values of quantitative d-dimer testing in patients with and without pseudoaneurysms as assessed by color-coded duplex sonography. Furthermore, we measured the peak systolic velocity at the arterial fistula of each pseudoaneurysm. RESULTS: In 48 (40%) of 120 consecutive patients, a pseudoaneurysm was found. The level of d-dimer values was significantly higher in patients with postcatheterization femoral pseudoaneurysms compared with controls (1.9 microg/mL [interquartile range (IQR), 1.34-2.78 microg/mL] vs 0.8 microg/mL [IQR, 0.53-1.14 microg/mL]; P < .001). Values of d-dimer below 0.67 microg/mL have been calculated with a sensitivity of 94% (87%-100%), a specificity of 38% (27%-50%), a positive predictive value of 50% (40%-60%), a negative predictive value of 90% (82%-99%), and a likelihood ratio of 1.52 (1.25-1.85) with regard to the presence of pseudoaneurysms. We also found a significant correlation of the peak systolic velocity at the arterial fistula and increasing d-dimer levels (r = 0.98, P < .0001). CONCLUSION: We found a significantly higher level of d-dimer values in patients with femoral pseudoaneurysms at the vascular access site. Therefore, d-dimer levels could be a potential serological marker in the diagnosis of pseudoaneurysms. A confirmation is warranted in a larger patient sample.

Glucose control is associated with patient survival in diabetic patients after renal transplantation.

INTRODUCTION: The efficacy of tight glycemic control for the prevention of death and renal failure in the general diabetic population is well established. However, in diabetic renal-allograft recipients, the effect of different treatment strategies on outcomes is undetermined. METHODS: We conducted a cohort study of 798 diabetic, renal-allograft recipients transplanted at the Medical University of Vienna between 1990 and 2004. We studied the influence of glucose parameters and diabetes treatment on mortality and graft loss. Marginal-structural models and multivariable Cox regression analysis were used to control for confounding. RESULTS: Maximal glucose levels but not HbA1c were independently associated with mortality. Being in the highest quartile of maximal glucose increased the adjusted risk of death by a factor of 2.2 (P value for trend 0.009). Furthermore, in patients receiving insulin, the risk of death was increased 1.7-fold (95% confidence interval 0.9-3.1) compared with diet and 2.0-fold (95% confidence interval 1.1-3.7) compared with oral medication. Maximal glucose, HbA1c, or diabetes treatment did not influence death-censored functional graft survival. DISCUSSION: In conclusion, maximal glucose levels and insulin treatment were independently associated with higher rates of mortality in our cohort of diabetic, renal-allograft recipients. However, graft survival was unaffected.

Elevated risk of myocardial infarction in very young immigrants from former Yugoslavia.

We performed a hospital based case-control study to assess if the risk of myocardial infarction at a very young age (< or =40 years) was elevated in immigrants from the region of former Yugoslavia. Patients were classified as "exposed" if they or both their parents were born in former Yugoslavia. Consecutive myocardial infarction patients were recruited in the immediate post-infarction period from two Viennese hospitals over a 3.5-year period. Control patients free of myocardial infarction were frequency matched on age, gender, centre, and time in an approximate 1:2 ratio. Logistic regression was used for the assessment of an association between Yugoslavian descent and myocardial infarction. Overall, we recruited 102 myocardial infarction patients and 200 controls. The median age of infarction patients was 37.3 years. Yugoslavian descent was strongly associated with myocardial infarction (crude OR 7.3, 95% CI 3-18). This association was attenuated after multivariate adjustment (OR 3.9, 95% CI 1.2-13) but remained statistically significant. Using Miettinen's formula for population attributable risk, we calculated that between 15.3% (adjusted) and 17.8% (unadjusted) of myocardial infarction cases in very young patients could be attributable to immigrants from the studied region. In conclusion, we found that the risk of developing myocardial infarction at a young age is elevated in immigrants from the region of former Yugoslavia and their offspring. Even though residual confounding cannot be ruled out definitively, this risk seems to be independent of established cardiovascular risk factors.

A journey straight through the heart: the story of a bullet.

Shunt malformations caused by a prior cardiac gunshot accident are a very rare cause for late deterioration of ventricular function. This case describes the long-term echocardiographic findings in a patient with a cardiac gunshot at age 13, presenting with progressive signs of congestive heart failure 25 years later.

Familial-combined hyperlipidaemia in very young myocardial infarction survivors (< or =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.