Perspective on statistical power and equivalences tests.

The use of both sexes or genders should be considered in experimental design, analysis, and reporting. Since there is no requirement to double the sample size or to have sufficient power to study sex differences, challenges for the statistical analysis can arise. In this article we focus on the topics of statistical power and ways to increase this power. We also discuss the choice of an appropriate design and statistical method, and include a separate section on equivalence tests needed to show the absence of a relevant difference.

"Expression of concern": publication bias for positive preclinical cardioprotection studies.

The present analysis reports on the robustness of preclinical cardioprotection studies with infarct size as endpoint which were published in Basic Research in Cardiology, Cardiovascular Research, and Circulation Research between January 2013 and December 2023. Only 26 out of 269 papers with technically robust analysis of infarct size by triphenyltetrazolium chloride staining, magnetic resonance imaging or single photon emission tomography applied a prospective power analysis. A retrospective power calculation revealed that only 75% of the reported data sets with statistically significant positive results from all these studies had a statistical power of ≥ 0.9, and an additional 9% had a statistical power ≥ 0.8. The remaining 16% of all significant positive data sets did not even reach the 0.8 threshold. Only 13% of all analyzed data sets were neutral. We conclude that neutral studies are underreported and there is indeed a significant lack of robustness in many of the published preclinical cardioprotection studies which may contribute to the difficulties of translating cardioprotection to patient benefit.

Coronary Artery Bypass Graft Surgery in Patients With Acute Coronary Syndromes After Primary Percutaneous Coronary Intervention: A Current Report From the North-Rhine Westphalia Surgical Myocardial Infarction Registry.

Background Coronary artery bypass grafting has remained an important treatment option for acute coronary syndromes, particularly in patients (1) with ongoing ischemia and large areas of jeopardized myocardium, if percutaneous coronary intervention (PCI) cannot be performed; (2) following successful PCI of the culprit lesion with further indication for coronary artery bypass grafting; and (3) where PCI is incomplete, not sufficient, or failed. Methods and Results We aimed to analyze coronary artery bypass grafting outcome following prior PCI in acute coronary syndromes from the North-Rhine-Westphalia surgical myocardial infarction registry comprising 2616 patients. Primary end points were in-hospital all-cause mortality and major adverse cardio-cerebral event. Patients were 68±11 years of age, had 3-vessel and left main-stem disease in 80.4% and 45.3%, presenting a logistic EuroSCORE of 15.1% in unstable angina, 20.3% in non-ST-segment-elevation myocardial infarction, and 23.5% in ST-segment-elevation myocardial infarction. A history of PCI was present in 36.2% and PCI was performed within 24 hours before surgery in 5.2% in unstable angina, 5.9% in non-ST-segment-elevation myocardial infarction, and 16.1% in ST-segment-elevation myocardial infarction. PCI failed in 5.3% in unstable angina, 6.8% in non-ST-segment-elevation myocardial infarction and 17.2% in ST-segment-elevation myocardial infarction, and 28.8% of patients presented with cardiogenic shock. In-hospital mortality without PCI was 7.4%, but increased to 8.7% with prior PCI >24 hours, 14.5% with prior PCI <24 hours, and 14.1% with failed PCI (P<0.003). The in-hospital major adverse cardio-cerebral event rate was 16.4% without PCI, but 17.4% with prior PCI >24 hours, 25.6% with prior PCI <24 hours, and 41.3% with failed PCI (P=0.014). Multivariable logistic regression analysis showed prior PCI (P=0.039), as well as failed PCI (P=0.001) to be predictors for in-hospital all-cause mortality and major adverse cardio-cerebral event. Conclusions In the current PCI era, immediately prior or failed PCI before coronary artery bypass grafting in acute coronary syndromes is associated with high perioperative risk, cardiogenic shock, and increased morbidity and mortality.

Turn alternation and the influence of environmental factors on search routes through branched structures by ladybirds (Coccinella septempunctata and Adalia bipunctata).

Turn alternation is a locomotory behaviour wherein an animal makes consecutive turns in opposite directions (left-then-right or right-then-left). It has been suggested that its adaptive function is to maintain locomotion in a relatively constant general direction while negotiating obstacles. Previous work has focussed on the use of turn alternation in prey species in artificial horizontal mazes. In the first study presented here, we tested whether predatory seven-spot ladybirds (Coccinella septempunctata) exhibit turn alternation when repeatedly presented with consecutive choice turning decisions on vertically oriented twigs. Our findings suggest that turn alternation occurs vertically as well as horizontally, on plant structures as well as terrestrially, and in a type of animal (predatory insect) in which turn alternation has received little attention. In the second study presented here, we tested whether characteristics of branched structures explored by two-spot ladybirds (Adalia bipunctata) influence turning decisions. Our findings suggest that ladybirds exhibit preferences for thicker over thinner, straighter over more deviating headings, and higher over lower turning choice options at bifurcations. These exploratory studies indicate that while turn alternation is an observable phenomenon in ladybirds, it is not the only predictor of searching behaviour on branched structures.

Surgical revascularization for acute coronary syndromes: a report from the North Rhine-Westphalia surgical myocardial infarction registry.

OBJECTIVES: The aim of this was to analyse current outcomes in patients referred to coronary artery bypass grafting (CABG) for acute coronary syndromes (ACSs), including ST-elevation or non-ST-elevation ACS (non-ST-segment elevation myocardial infarction) or unstable angina. METHODS: Patients (n = 2432) undergoing CABG for ACS between January 2010 and December 2017 were prospectively entered into a surgical myocardial infarction registry in North Rhine-Westphalia, Germany. Key end points were in-hospital all-cause mortality (IHM) and major adverse cardio-cerebral events (MACCE). Predictors for IHM and MACCE were analysed by multivariable logistic regression. RESULTS: Patients (78% males) were referred for CABG for unstable angina (25%), non-ST-segment elevation myocardial infarction (50%), and ST-segment elevation myocardial infarction (25%). The mean patient age was 68 ± 11 years, logistic EuroSCORE was 19 ± 18% and three-vessel and left main stem diseases were diagnosed in 81% and 45% of patients, respectively. On-pump CABG with cardiac arrest or beating heart was performed in 92% and 2%, respectively, with only 6% off-pump surgery and 6% multiple arterial revascularization (3.1 ± 1.0 grafts, 93% left internal thoracic artery). Emergency CABG was performed in 23% of patients (42% in ST-segment elevation myocardial infarction; P < 0.001). The total IHM and MACCE rates were 8.1% and 17.5% and were highest in ST-segment elevation myocardial infarction patients with 12.6% and 28.5%, respectively (P < 0.001). Key predictors for IHM and MACCE were female gender, elevated troponin, left ventricular ejection fraction, inotropic support, logistic EuroSCORE, cardiopulmonary bypass and aortic clamp time and the need for emergency CABG. CONCLUSIONS: Surgical myocardial revascularization in patients with ACS is still linked to substantial in-hospital mortality. Emergency CABG for patients with ACS was associated with poorer outcomes.

Intraoperative Hemoadsorption in Patients With Native Mitral Valve Infective Endocarditis.

BACKGROUND: Cardiac surgery in patients with infective endocarditis is associated with high mortality owing to postoperative septic multiorgan failure. Hemoadsorption therapy may improve surgical outcomes by reducing the circulating cytokines. We aimed to evaluate the clinical effects of intraoperative hemoadsorption in patients with mitral valve endocarditis. METHODS: Eligible candidates were patients with infective endocarditis of the native mitral valve undergoing cardiac surgery between January 2014 and July 2018. Patients with intraoperative hemoadsorption (hemoadsorption) were compared with surgery without hemoadsorption (control). The end points were the incidence of postoperative sepsis, sepsis-associated death, and 30-day mortality. Furthermore, postoperative need for epinephrine and norepinephrine and systemic vascular resistance were evaluated. RESULTS: A total of 58 consecutive patients were included: 30 in the hemoadsorption group and 28 in the control group. Postoperative sepsis occurred in 5 patients in the hemoadsorption group and in 11 in the control group (P = .05). No sepsis-associated death occurred in the hemoadsorption group, whereas five septic patients in the control group died (P = .02). Thirty-day mortality was 10% in the hemoadsorption group versus 18% in the control group (P = .39). On intensive care unit admission, the cumulative need for epinephrine and norepinephrine was 0.15 versus 0.24 µg/kg body weight/min (P = .01) and the median systemic vascular resistance was 1413 versus 1010 dyn·s·cm-5 (P = .02) in the hemoadsorption versus control group, respectively. CONCLUSIONS: Intraoperative hemoadsorption might reduce the incidence of postoperative sepsis and sepsis-related death. In addition, patients with intraoperative hemoadsorption showed greater hemodynamic stability. These data suggest that intraoperative hemoadsorption may improve surgical outcome in patients with mitral valve endocarditis.

Early Clinical Outcomes of Surgical Myocardial Revascularization for Acute Coronary Syndromes Complicated by Cardiogenic Shock: A Report From the North-Rhine-Westphalia Surgical Myocardial Infarction Registry.

Background Coronary artery bypass grafting for acute coronary syndrome complicated by cardiogenic shock ( CS ) is associated with a high mortality. This registry study aimed to distinguish between early surgical outcomes of CS patients with non- ST -segment-elevation myocardial infarction ( NSTEMI ) and ST -segment-elevation myocardial infarction ( STEMI ). Methods and Results Patients with NSTEMI (n=1218) or STEMI (n=618) referred for coronary artery bypass grafting were enrolled in a prospective multicenter registry between 2010 and 2017. CS was present in 227 NSTEMI (18.6%) and 243 STEMI patients (39.3%). Key clinical end points were in-hospital mortality ( IHM ) and major adverse cardiocerebral events ( MACCEs ). Predictors for IHM and MACCEs were identified using multivariable logistic regression analysis. STEMI patients with CS were younger, had a lower prevalence of diabetes mellitus and multivessel disease, and exhibited higher myocardial injury (troponin 9±17 versus 3±6 ng/mL) before surgery compared with patients with NSTEMI ( P<0.05). Emergency coronary artery bypass grafting was performed more often in STEMI (58%) versus NSTEMI (40%; P=0.002). On-pump surgery with cardioplegia was the preferred surgical technique in CS . IHM and MACCE rates were 24% and 49% in STEMI patients with CS and were higher compared with NSTEMI ( IHM 15% versus MACCE 34%; P<0.001). Predictors for IHM and MACCE in CS were a reduced ejection fraction and a higher European System for Cardiac Operative Risk Evaluation score. Conclusions Surgical revascularization in NSTEMI and STEMI patients with CS is associated with a substantial but not prohibitive IHM and MACCE rate. Worse early outcomes were found for patients with STEMI complicated by CS compared with NSTEMI patients.

Underestimation of Pearson's product moment correlation statistic.

Pearson's product moment correlation coefficient (more commonly Pearson's r) tends to underestimate correlations that exist in the underlying population. This phenomenon is generally unappreciated in studies of ecology, although a range of corrections are suggested in the statistical literature. The use of Pearson's r as the classical measure for correlation is widespread in ecology, where manipulative experiments are impractical across the large spatial scales concerned; it is therefore vital that ecologists are able to use this correlation measure as effectively as possible. Here, our literature review suggests that corrections for the issue of underestimation in Pearson's r should not be adopted if either the data deviate from bivariate normality or sample size is greater than around 30. Through our simulations, we then aim to offer advice to researchers in ecology on situations where both distributions can be described as normal, but sample sizes are lower than around 30. We found that none of the methods currently offered in the literature to correct the underestimation bias offer consistently reliable performance, and so we do not recommend that they be implemented when making inferences about the behaviour of a population from a sample. We also suggest that, when considering the importance of the bias towards underestimation in Pearson's product moment correlation coefficient for biological conclusions, the likely extent of the bias should be discussed. Unless sample size is very small, the issue of sample bias is unlikely to call for substantial modification of study conclusions.

Liver transplantation for hepatocellular carcinoma with live donors or extended criteria donors: a propensity score-matched comparison.

BACKGROUND: To compare patient survival after liver transplantation (LT) for hepatocellular carcinoma (HCC) from live donors (LD) or extended criteria donors (ECD). METHODS: Data from consecutive LT procedures for HCC involving either LD or ECD were reviewed. Patient survival was our primary outcome. Re-transplantation (Re-LT), ischemic type bile lesions (ITBL), and tumor recurrence represented secondary outcomes. The primary outcome was statistically analyzed using Kaplan-Meier estimates and Cox proportional hazards regression; logistic regression analyses were used for statistical analysis of the secondary outcomes. Propensity score was calculated based on patient age, sex, hepatitis C viral infection (HCV), laboratory model for end-stage liver disease (labMELD) score, bridging treatment, Milan criteria, α-fetoprotein levels, and tumor grade. RESULTS: The study evaluated 109 recipients undergoing LT from either LD (n=57) or ECD (n=52). LT procedure (hazard ratio [HR] 2.349, 95% confidence interval [CI] 1.151-4.794, P=0.0190), age (HR 1.075, 95%CI 1.020-1.133, P=0.0074) and labMELD score (HR 1.082, 95%CI 1.021-1.147, P=0.0075) reached significance by Cox proportional hazards regression. After adjustment with the propensity score (stratification with 5 strata), the LT procedure was still significant (HR 2.401, 95%CI 1.114-5.175, P=0.0253). Tumor grade (odds ratio [OR] 9.628, 95%CI 1.120-82.752, P=0.0391), labMELD score (OR 1.224, 95%CI 1.019-1.471, P=0.0306), and Milan criteria (OR 6.375, 95%CI 1.239-32.796, P=0.0267) gained statistical significance by logistic regression analysis for Re-LT, ITBL, and tumor recurrence, respectively. CONCLUSIONS: LT for HCC showed superior patient survival with ECD rather than LD grafts. Re-LT, ITBL, and tumor recurrence showed no significant differences between the two groups. However, the diverging criteria for the definition of ECD grafts represent a considerable limitation for the wide application of this policy.

The number of strata in propensity score stratification for a binary outcome.

INTRODUCTION: Non-interventional and other observational studies have become important in medical research. In such observational, non-randomized studies, groups usually differ in some baseline covariates. Propensity scores are increasingly being used in the statistical analysis of these studies. Stratification, also called subclassification, based on propensity scores is one of the possible methods. There is the quasi-standard of using five strata. In this paper we focus on a binary outcome and evaluate the above-mentioned standard of using five strata. MATERIAL AND METHODS: Bias and power for different numbers of strata are investigated with a simulation study. The methods are illustrated using data from a study where patients with diabetes mellitus and triple vessel disease undergoing coronary artery bypass surgery with and without previous percutaneous coronary intervention were compared. RESULTS: We show that more than five strata can be more powerful and give less biased results. However, using more than ten strata hardly gives any further benefit. CONCLUSIONS: When applying a stratification, more than five strata may be preferable, especially because of increased power. Our simulation study does not show a clear winner; hence a useful strategy could be to work with five as well as with ten strata.

Impact of electrical defibrillation on infarct size and no-reflow in pigs subjected to myocardial ischemia-reperfusion without and with ischemic conditioning.

Ventricular fibrillation (VF) occurs frequently during myocardial ischemia-reperfusion (I/R) and must then be terminated by electrical defibrillation. We have investigated the impact of VF/defibrillation on infarct size (IS) or area of no reflow (NR) without and with ischemic conditioning interventions. Anesthetized pigs were subjected to 60/180 min of coronary occlusion/reperfusion. VF, as identified from the ECG, was terminated by intrathoracic defibrillation. The area at risk (AAR), IS, and NR were determined by staining techniques (patent blue, triphenyltetrazolium chloride, and thioflavin-S). Four experimental protocols were analyzed: I/R (n = 49), I/R with ischemic preconditioning (IPC; n = 22), I/R with ischemic postconditioning (POCO; n = 22), or I/R with remote IPC (RIPC; n = 34). The incidence of VF was not different between I/R (44%), IPC (45%), POCO (50%), and RIPC (33%). IS was reduced by IPC (23 ± 12% of AAR), POCO (31 ± 16%), and RIPC (22 ± 13%, all P < 0.05 vs. I/R: 41 ± 12%). NR was not different between protocols (I/R: 17 ± 15% of AAR, IPC: 15 ± 18%, POCO: 25 ± 16%, and RIPC: 18 ± 17%). In pigs with defibrillation, IS was 50% larger than in pigs without defibrillation but independent of the number of defibrillations. Analysis of covariance confirmed the established determinants of IS, i.e., AAR, residual blood flow during ischemia (RMBFi), and a conditioning protocol, and revealed VF/defibrillation as a novel covariate. VF/defibrillation in turn was associated with larger AAR and lower RMBFi. Lack of dose-response relation between IS and the number of defibrillations excluded direct electrical injury as the cause of increased IS. Obviously, AAR size and RMBFi account for both IS and the incidence of VF. IS and NR are mechanistically distinct phenomena.NEW & NOTEWORTHY Ventricular fibrillation/defibrillation is associated with increased infarct size. Electrical injury is unlikely the cause of such association, since there is no dose-response relation between infarct size and number of defibrillations. Ventricular fibrillation, in turn, is associated with a larger area at risk and lower residual blood flow.

No protection of heart, kidneys and brain by remote ischemic preconditioning before transfemoral transcatheter aortic valve implantation: Interim-analysis of a randomized single-blinded, placebo-controlled, single-center trial.

BACKGROUND: Remote ischemic preconditioning (RIPC) reduces myocardial injury and improves clinical outcome in patients undergoing coronary revascularization, but only in the absence of propofol-anesthesia. We investigated whether RIPC provides protection of heart, kidneys and brain and improves outcome in patients undergoing transfemoral transcatheter aortic valve implantation (TF-TAVI). METHODS: Patients undergoing TF-TAVI were randomized to receive RIPC (3cycles of 5min left upper arm ischemia and 5min reperfusion) or placebo. The primary endpoint was myocardial injury, reflected by the area under the curve for serum troponin I concentrations (AUC-TnI) over the first 72h. Secondary endpoints included the incidences of periprocedural myocardial infarction, delayed gadolinium enhancement on postprocedural cardiac MRI, acute kidney injury, periprocedural stroke, and the incidence and volume of new lesions on postprocedural cerebral MRI. All-cause and cardiovascular mortality and major adverse cardiac and cerebrovascular events (MACCE) were assessed over 1-year follow-up. A prespecified interim-analysis was performed after the last patient had completed 1-year follow-up (NCT02080299). RESULTS: 100 consecutive patients were enrolled between September 2013 and June 2015. There were no significant between-group differences in the primary endpoint of peri-interventional myocardial injury (ratio RIPC/placebo AUC-TnI: 0.87, 95% CI: 0.57-1.34, p=0.53) or the secondary endpoints of cardiac, renal and cerebral impairment. There was no significant treatment effect in subgroup-analyses of patients undergoing cardiac or cerebral MRI. Mortality and MACCE did not differ. No RIPC-related adverse events were observed. CONCLUSIONS: RIPC did neither protect heart, kidneys and brain nor improve clinical outcome in patients undergoing TF-TAVI.

Quantification and characterisation of released plaque material during bioresorbable vascular scaffold implantation into right coronary artery lesions by multimodality intracoronary imaging.

AIMS: We aimed to compare intravascular ultrasound with virtual histology (VH-IVUS), optical coherence tomography (OCT) and near-infrared spectroscopy (NIRS) for their ability to quantify the true amount and characterise the nature of released plaque material during bioresorbable vascular scaffold (BVS) implantation into right coronary artery (RCA) lesions using a distal occlusion and aspiration device. METHODS AND RESULTS: Seventeen patients underwent BVS implantation into the right coronary artery under distal protection with intracoronary imaging using VH-IVUS, OCT and NIRS. The amount of released plaque material and its lipid content (LC) were determined. Necrotic core volume and minimal fibrous cap thickness correlated with the amount of released plaque material (r=0.80 and r=-0.65, respectively) and its LC (r=0.75 and r=-0.78, respectively), but not maximal lipid core burden index (LCBI). OCT-identified thin-cap fibroatheromata (TCFA) were associated with the greatest amount of released plaque material compared to non-TCFA (46.8 [29.0;49.2] mg vs. 14.2 [11.3;19.4] mg; p=0.003) and LC (4.4 [4.0;4.8] mg vs. 2.0 [1.8;2.5] mg; p=0.000). CONCLUSIONS: VH-IVUS and OCT but not NIRS parameters quantify and characterise the amount of released plaque material. TCFA is associated with the highest amount of released plaque material and may therefore benefit from the use of protection devices.

Confounders of Cardioprotection by Remote Ischemic Preconditioning in Patients Undergoing Coronary Artery Bypass Grafting.

OBJECTIVES: Remote ischemic conditioning (RIC) by repetitive blood pressure cuff inflation/deflation around a limb provides cardioprotection in patients undergoing coronary artery bypass grafting (CABG). Cardioprotection is confounded by risk factors, comorbidities and comedications. We aimed to identify confounders that possibly attenuate the protection provided by RIC. METHODS: In a retrospective analysis of our single-center, randomized, double-blind trial of patients undergoing elective CABG with/without RIC prior to ischemic cardioplegic arrest, we analyzed demographics, medications and intraoperative variables. The primary end point was myocardial injury, as reflected by the area under the curve for serum troponin I (TnI) from baseline to 72 h after surgery. RESULTS: In models with 2 independent variables and in the multivariate analysis, age and aortic cross-clamp time impacted on TnI release. Subgroup analyses confirmed RIC-induced protection in all age tertiles. There was no protection with an aortic cross-clamp time ≤56 min (RIC/control = 1.026 not significant), but there was protection with 57-75 min (RIC/control = 0.757; p = 0.0348) and ≥76 min (RIC/control = 0.735; p = 0.0277). Gender, ß-blockers, statins, angiotensin-converting enzyme (ACE) inhibitors or angiotensin receptor blockers (ARBs) and intraoperative nitroglycerine did not impact on TnI release. CONCLUSION: Age, gender, ß-blockers, statins, ACE inhibitors, ARBs and intraoperative nitroglycerine have no significant impact on RIC-induced cardioprotection during CABG. However, greater myocardial ischemia/reperfusion injury at longer cross-clamp time facilitates the detection of protection by RIC.

Intraaortic Protection From Embolization in Patients Undergoing Transaortic Transcatheter Aortic Valve Implantation.

PURPOSE: Transcatheter aortic valve implantation (TAVI) results in the dislodgement of debris with risk of cerebral lesions or stroke. The EMBOL-X protection device (Edwards Lifesciences, Irvine, CA) is positioned within the ascending aorta to capture such debris. DESCRIPTION: Between July 2012 and April 2014 we randomly assigned 30 high-risk patients to undergo transaortic TAVI with the SAPIEN XT prosthesis (Edwards Lifesciences) combined with either the EMBOL-X device (group-1, n = 14) or without (group-2, n = 16). Periprocedural cerebral lesions were assessed by diffusion-weighted magnetic resonance imaging (DW-MRI) at baseline and within 7 days post-procedurally. EVALUATION: New foci of restricted diffusion on cerebral DW-MRI were found in 69% in group-2 and 50% in group-1. Lesion size was smaller in patients treated with the EMBOL-X device than in those without (88 ± 60 vs 168 ± 217 mm(3), p = 0.27, t = 1.2, degrees of freedom = 10). Transaortic TAVI patients treated with the EMBOL-X device had significantly smaller lesion volumes in the supply region of the middle cerebral artery (33 ± 29 vs 76 ± 67 mm(3), p = 0.04). There were no neurologic events after transaortic TAVI. CONCLUSIONS: The intraaortic protection device seems to reduce both the incidence and the volume of new cerebral lesions (ClinicalTrials.gov number, NCT01735513).

On the variety of methods for calculating confidence intervals by bootstrapping.

Researchers often want to place a confidence interval around estimated parameter values calculated from a sample. This is commonly implemented by bootstrapping. There are several different frequently used bootstrapping methods for this purpose. Here we demonstrate that authors of recent papers frequently do not specify the method they have used and that different methods can produce markedly different confidence intervals for the same sample and parameter estimate. We encourage authors to be more explicit about the method they use (and number of bootstrap resamples used). We recommend the bias corrected and accelerated method as giving generally good performance; although researchers should be warned that coverage of bootstrap confidence intervals is characteristically less than the specified nominal level, and confidence interval evaluation by any method can be unreliable for small samples in some situations.

Conventional aortic valve replacement or transcatheter aortic valve implantation in patients with previous cardiac surgery.

BACKGROUND: Clinical outcomes were compared among patients with previous cardiac surgery undergoing transcatheter aortic valve implantation (TAVI) or surgical aortic valve replacement (AVR). METHODS: Between 2007 and 2014 a total of 142 consecutive patients with previous cardiac surgery were treated by TAVI either by the transfemoral (n=68) or transapical access (n=74), and 236 patients underwent a surgical redo-AVR. Of these patients, propensity analysis (m:n) matched 62 (group 1, TAVI) and 51 patients (group 2, redo-AVR). A multivariate logistic regression model was constructed. Moreover, mortality was compared between both groups by Cox regression. RESULTS: Both groups differed significantly (p<0.01) in regard to age and preoperative risk scores (EuroSCORE and STS-Score). Thirty-day mortality was 14.5% (9/62) in group 1 and 5.8% (3/51) in group 2 (p=0.23). Risk-adjusted multivariable analysis revealed only the logistic EuroSCORE to be strongly correlated with 30-day mortality (p=0.01). Multivariate analysis showed no difference in 30-day mortality between both groups (p=0.21). Multivariate Cox regression revealed New York Heart Association functional class (p=0.001), logistic EuroSCORE (p=0.01), and STS-Score (p=0.03) to be strongly associated with overall mortality. Moreover, evaluating overall mortality, Cox regression showed no difference between both groups (p=0.36). CONCLUSIONS: The present study shows that in patients with cardiac reoperation, TAVI comes with similar outcomes when compared to surgical AVR. On the other hand, conventional redo-AVR is still a valuable and safe treatment option.

Heart rate reduction and longevity in mice.

Heart rate correlates inversely with life span across all species, including humans. In patients with cardiovascular disease, higher heart rate is associated with increased mortality, and such patients benefit from pharmacological heart rate reduction. However, cause-and-effect relationships between heart rate and longevity, notably in healthy individuals, are not established. We therefore prospectively studied the effects of a life-long pharmacological heart rate reduction on longevity in mice. We hypothesized, that the total number of cardiac cycles is constant, and that a 15% heart rate reduction might translate into a 15% increase in life span. C57BL6/J mice received either placebo or ivabradine at a dose of 50 mg/kg/day in drinking water from 12 weeks to death. Heart rate and body weight were monitored. Autopsy was performed on all non-autolytic cadavers, and parenchymal organs were evaluated macroscopically. Ivabradine reduced heart rate by 14% (median, interquartile range 12-15%) throughout life, and median life span was increased by 6.2% (p = 0.01). Body weight and macroscopic findings were not different between placebo and ivabradine. Life span was not increased to the same extent as heart rate was reduced, but nevertheless significantly prolonged by 6.2%.