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Background Previous studies showed prolonged patient and system delay in female patients with acute coronary syndromes (ACS) which is thought to be a major driver of discrepancies in their cardiovascular (CV) outcomes. Indeed, timely management is particularly important in patients with ST-segment elevation myocardial infarction (STEMI), as increased total ischemic time augments infarct size and relates to poor CV survival. However, contemporary evidence on sex-specific differences in ACS management and discrepancies in outcomes is limited and controversial. Purpose We sought to systematically investigate whether a sex-gap in symptom-to-door (STD), door-to-balloon (DTB)/door-to-PCI (DTP) time exists in a prospective ACS cohort and if such differences translate into different rates of major adverse cardiovascular events (MACE) at one year. Methods From 2009 to 2019, 4'930 ACS patients with a main diagnosis of NSTEMI (43.3%), STEMI (53.3%) or unstable angina (3.4%) were enrolled in the multicentre, prospective SPUM-ACS study of which 4'671 completed follow-up at one year. STD, DTB and DTP time was analyzed. The primary endpoint, a composite measure of all-cause death, nonfatal myocardial infarction, nonfatal stroke and ischemia-driven revascularization, was adjudicated by an independent clinical endpoint committee. Kaplan-Meier and multivariate-adjusted Cox proportional hazard regression models were used for time-to-event analyses. Results A total of 1'019 (20.7%) women and 3'911 (79.3%) men with a main diagnosis of ACS were included in the study. At presentation, women were older (69.6±12.0 vs. 62.2±12.1 years, P Conclusions Women with a main diagnosis of STEMI show considerably higher prehospital delay, thus prolonged total ischemic time which is mainly driven by increased STD time. Intriguingly, this does not translate into higher rates of MACE compared to men at one year. Women with ACS may particularly benefit from measures aimed at reducing prehospital delay, as this may further improve long-term prognosis after the acute event. Funding Acknowledgement Type of funding sources: Other. Main funding source(s): Swiss National Science Foundation - SNFFoundation for Cardiovascular Research - Zurich Heart House

Background: Ischemic time has prognostic importance in ST-elevation myocardial infarction patients. Mobile intensive care unit use can reduce components of total ischemic time by appropriate triage of ST-elevation myocardial infarction patients. Methods: Data from the Acute Coronary Survey in Israel registry 2000–2010 were analyzed to evaluate factors associated with mobile intensive care unit use and its impact on total ischemic time and patient outcomes. Results: The study comprised 5474 ST-elevation myocardial infarction patients enrolled in the Acute Coronary Survey in Israel registry, of whom 46% ( n=2538) arrived via mobile intensive care units. There was a significant increase in rates of mobile intensive care unit utilization from 36% in 2000 to over 50% in 2010 ( p1 (odds ratio=1.32, pConclusions: Among patients with ST-elevation myocardial infarction, the utilization of mobile intensive care units is associated with increased rates of primary reperfusion, a reduction in the time interval to reperfusion, and a reduction in one-year adjusted mortality.

Gene expression levels are dynamic molecular phenotypes that respond to biological, environmental, and technical perturbations. Here we use a novel replicate-classifier approach for discovering transcriptional signatures and apply it to the Genotype-Tissue Expression data set. We identified many factors contributing to expression heterogeneity, such as collection center and ischemia time, and our approach of scoring replicate classifiers allows us to statistically stratify these factors by effect strength. Strikingly, from transcriptional expression in blood alone we detect markers that help predict heart disease and stroke in some patients. Our results illustrate the challenges and opportunities of interpreting patterns of transcriptional variation in large-scale data sets.

Background Metoprolol administration before reperfusion has shown relevant cardioprotective effect in the AMI in preclinical setting. However, the translation to clinical arena has controversial results. The time at drug administration in the context of total duration of ischemia have been pointed as fundamental aspects to be studied. Purpose evaluate the cardioprotective effect of metoprolol administration regarding to the total time of ischemia, using a swine model of reperfused AMI. Methods 50 pigs were subjected to 3 temporary protocols of left anterior descending (LAD) coronary artery occlusion followed by reperfusion. 30 pigs undergoing 40 minutes of ischemia (T40) were randomized 2:1 to intravenous placebo or metoprolol administrated 20 minutes after LAD occlusion.10 pigs undergoing 20 minutes of ischemia 20 (T20) and 10 pig undergoing 60 minutes of ischemia 60 (T60) were randomized 1:1 to intravenous placebo or metoprolol. Before reperfusion a CT study was performed to stablish the area at risk (AAR). CMR was performed at 7 and 45 days after AMI. Results 48 subjects comprised the 7-day CMR follow-up (1 dead in the metoprolol T40,1 dead in the placebo T40) while 41 subjects comprised the 45-day CMR follow-up (5 deceases in the placebo T40 group, and 2 in the placebo T60 group). AAR was similar among groups (Table 1, Panel B). At 7-day follow-up, IS washigher in the placebo groups as compared to the metoprolol groups, but only reach significant difference in the T40 (29,67% vs. 22,85%, p=0.04, Table 1, Panel A). LVEF measured at 45-day follow-up was higher in the metoprolol groups vs the control groups, but the differences were statistically significance in the T40 (32,76% vs 39,68% p=0.04, Panel C). Table 1 20 mins. Ischemia (T20) 40 mins. Ischemia (T40) 60 mins. Ischemia (T60) P PLACEBO METOPROL P value PLACEBO METOPROL P value PLACEBO METOPROL P value AAR 32 (28.14–37.89) 33.41 (28.12–38.32) 0.82 32.99 (29.25–35.83) 31.42 (26.94–37.83) 0.72 33.28 (29.68–41.14) 33.93 (28.17–40.69) 0.80 0.98 IS 1.96 (0.92–3.61) 0 (0–0.65) 0.063 29.67 (27.23–35.35) 22.85 (14.53–28.10) 0.042 36.21 (33.55–40.91) 33.78 (39.36–35.39) 0.31 Conclusions Metoprolol administrated early before reperfusion reduced IS and improved medium-term LVEF compared to placebo. But only T40 receiving metoprolol shownsignificant protection vs placebo. These findings suggest a relevant effect of metoprolol ischemic/reperfusion injury, but depending on the total ischemic time, establishing a potential temporary cardioprotection opportunity window.

Background Graft failure caused by allograft rejection and vasculopathy is the most common cause of mortality after heart transplantation. To detect an early allograft rejection, endomyocardial biopsy is still needed. Tissue characterization by T1-mapping and Late gadolinium enhancement is well established in acute and chronic myocardial tissue alterations. Therefore several studies investigated T1-mapping as a potential noninvasive parameter to monitor cardiac allograft vasculopathy and allograft rejection. However it is unclear if T1 is also influenced by pretransplant ischemic time and elapsed time since transplantation. Purpose It was the aim of our study to examine the influence of ischemic and elapsed time since transplantation to the cardiac allograft tissue characteristics measured by CMR T1 relaxation times. Methods Allograft transplant patients underwent stress CMR on a yearly routine. T1-maps were acquired using a modified look locker sequence (MOLLI 3(2)3(2)5) in the midventricular septum. Uni- and multi linear regression analysis was used to predict T1 by ischemic time, time since transplantation, troponin and NT-Pro-BNP. Results 49 cardiac allograft transplanted patients underwent stress CMR (mean age 58.6±11.7 years, left ventricular ejection fraction 62.1±6.8%; indexed enddiastolic volume 68.4±14.7 ml/m2; native T1 1120±51 ms, extracellular volume 0.27±0.04). A significant correlation was found between T1 and NT-Pro-BNP (1519±3639 pg/ml, p=0.003) and a trend for troponin (17.0±12.8 ng/dl, p=0.051). We saw no correlation between T1 and the ischemic time (198.4±44.9 minutes, p=0.1172) and elapse time since transplantation (47±7 month, p=0.9868). In the multivariate regression analysis none of the four parameters were independently associated with the T1 time (p=0.1017). Table 1 Characteristics Mean ± SD p Ischemic time (minutes) 198.4±44.9 0.1172 Time since transplant (month) 47±7 0.9868 NT-Pro-BNP (pg/ml) 1519±3639 0.003 Troponine (ng/dl) 17.0±12.8 0.051 Conclusion There was no significant effect of pretransplant ischemic time and elapse time since transplantation on native T1 times, whereas native T1 was significantly correlated with troponine and NT-Pro-BNP-Levels. T1 is excellently suited to detect acute changes in allograft transplant patients without being influenced by aging of the transplanted heart and the heart's pretransplant condition.

Background: Pre-hospital delay in myocardial infarction (MI) patients' is of great concern. The total ischemic time, i.e., between symptom onset and reperfusion therapy is the most important factor ...

We examined the usefulness of the modified single-patch technique for the surgical management of complete atrioventricular septal defect (AVSD). Sixty-one patients undergoing total correction for complete AVSD from January 1997 to December 2006 were classified to the modified single-patch technique group (18 patients) and the classical one-/two-patch technique group (43 patients). The surgical outcomes of the modified single-patch technique were compared with those of the classical-patch technique. Aortic cross-clamp time was shorter in the modified single-patch technique group (110.8+/-27.5 min vs. 134.4+/-42.5 min, P=0.03). During the follow-up period, two patients required reoperation for atrioventricular valve dysfunction in the modified single-patch technique group vs. three patients in the classical-patch technique group (P=0.63). One late death occurred in the modified single-patch technique and two late deaths in the classical-patch technique group (P=0.90). There was no significant difference in surgical outcomes between the two groups. And the modified single-patch technique has the advantage of relative simplicity and shorter ischemic time, and thus it is thought to be a feasible surgical option for the repair of complete AVSD.

With liberalization of donor eligibility criteria, donor hearts are being harvested from remote locations, increasing ischemic times. The aim of this study was to examine the effect of total ischemic time (TIT) on length of stay in the intensive care unit (LOS in ICU) and its economic consequences. The study population included recipients without prior mechanical support undergoing heart transplantation between 1998 and 2008 at a single institution. The mean age of the 72 recipients (56 men, 16 women) was 50.6 years (range 15-68 years) and the mean donor age was 41.5 years (range 11-61 years). The median TIT was 181.2 min (range 107-243) and median LOS in ICU was 11.5 days (range 3-107 days). There was a statistically significant linear relationship between TIT and LOS in ICU r(72)=0.317, P=0.004. Each 5 min and 38 s of TIT equated to one more day in ICU. An ischemic time >180 min was associated with higher LOS in ICU, renal failure, and a more frequent use of nitric oxide in our cohort. For longer distance harvesting, the reduction of TIT by the fastest possible transport (learjet, helicopter) would have economic advantages with regards to the high cost of treatment in ICU.

Normothermic blood cardioplegia has recently generated interest as an alternative method of myocardial protection during cardiopulmonary bypass (CPB) surgery. One disadvantage is the obligatory interruption of coronary flow during the distal coronary anastomosis. This study was designed to determine the safe normothermic ischemic time of the arrested and decompressed heart. Under normothermic CPB (37 degrees C), initial cardioplegic arrest was induced with 750 cc of warm (37 degrees C) hyperkalemic blood cardioplegia in 21 adult dogs. The heart then received warm blood cardioplegia either continuously (50 cc/min), every 5 min (250 cc each) or every 10 min (350 cc each) for a total equivalent ischemic time of 30 min (n = 7 in each group). Left ventricular pressure-volume (PV) loops were measured by micromanometer and conductance (volume) catheters before, at 60 and 90 min after aortic cross-clamping. Systolic function was measured as the preload recruitable stroke work area derived from the stroke work-end diastolic volume relationship, and the diastolic stiffness constant (k) was derived from the exponential diastolic PV relationship. The q5 min group sustained minor deterioration in diastolic function while its systolic function was well maintained during recovery. There were significant reductions in both the diastolic and systolic functions in the q10 min group. The maximum drops in the septal wall pH during aortic cross-clamping were 0.05 +/- 0.02 (not significant), 0.19 +/- 0.06 (P0.05), and 0.40 +/- 0.09 (P0.01) for the continuous, q5 min and q10 min groups, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

Bretschneider HTK solution is commonly used for myocardial preservation. In order to evaluate its protective effect for heart transplantation, a retrospective study was initiated in cooperation with Eurotransplant and five heart transplant centers. Seventy-six female and 524 male patients who underwent cardiac transplantations between 1981 and 1991 were included in this study. Using standardized questionnaires, donor and recipient laboratory data, immunosuppressive therapy and the preoperative, intraoperative and postoperative organ function were documented. The average ischemic time of the donor hearts was 160 min, ranging from 75 min - 304 min