Improving translational research in sex-specific effects of comorbidities and risk factors in ischaemic heart disease and cardioprotection: position paper and recommendations of the ESC Working Group on Cellular Biology of the Heart.

Ischaemic heart disease (IHD) is a complex disorder and a leading cause of death and morbidity in both men and women. Sex, however, affects several aspects of IHD, including pathophysiology, incidence, clinical presentation, diagnosis as well as treatment and outcome. Several diseases or risk factors frequently associated with IHD can modify cellular signalling cascades, thus affecting ischaemia/reperfusion injury as well as responses to cardioprotective interventions. Importantly, the prevalence and impact of risk factors and several comorbidities differ between males and females, and their effects on IHD development and prognosis might differ according to sex. The cellular and molecular mechanisms underlying these differences are still poorly understood, and their identification might have important translational implications in the prediction or prevention of risk of IHD in men and women. Despite this, most experimental studies on IHD are still undertaken in animal models in the absence of risk factors and comorbidities, and assessment of potential sex-specific differences are largely missing. This ESC WG Position Paper will discuss: (i) the importance of sex as a biological variable in cardiovascular research, (ii) major biological mechanisms underlying sex-related differences relevant to IHD risk factors and comorbidities, (iii) prospects and pitfalls of preclinical models to investigate these associations, and finally (iv) will provide recommendations to guide future research. Although gender differences also affect IHD risk in the clinical setting, they will not be discussed in detail here.

ESC working group cellular biology of the heart: position paper: improving the preclinical assessment of novel cardioprotective therapies.

Ischaemic heart disease (IHD) remains the leading cause of death and disability worldwide. As a result, novel therapies are still needed to protect the heart from the detrimental effects of acute ischaemia-reperfusion injury, in order to improve clinical outcomes in IHD patients. In this regard, although a large number of novel cardioprotective therapies discovered in the research laboratory have been investigated in the clinical setting, only a few of these have been demonstrated to improve clinical outcomes. One potential reason for this lack of success may have been the failure to thoroughly assess the cardioprotective efficacy of these novel therapies in suitably designed preclinical experimental animal models. Therefore, the aim of this Position Paper by the European Society of Cardiology Working Group Cellular Biology of the Heart is to provide recommendations for improving the preclinical assessment of novel cardioprotective therapies discovered in the research laboratory, with the aim of increasing the likelihood of success in translating these new treatments into improved clinical outcomes.

Assessment of central blood pressure in patients with type 2 diabetes: a comparison between SphygmoCor and invasively measured values.

BACKGROUND: The SphygmoCor is used for noninvasive assessment of ascending aortic blood pressure (BP). However, the validity of the SphygmoCor transfer function has not been tested in an exclusively type 2 diabetic patient sample. Calibration with systolic (SBP) and diastolic (DBP) brachial BP has previously been associated with substantial imprecision of central BP estimates. We hypothesized that different noninvasive calibration strategies might improve the accuracy of the estimated ascending aortic BPs. METHODS: In 34 patients with type 2 diabetes we estimated ascending aortic SBP and DBP using the SphygmoCor device and compared these data with invasively recorded data. The validity of the transfer function was assessed by calibrating with invasively recorded DBP and mean BP (MBP). The influence of noninvasive calibration strategies was assessed by calibrating with brachial oscillometric SBP+DBP vs. DBP+MBP using a form factor (ff) of 0.33 and 0.40, respectively. RESULTS: When calibrating with invasive BP, the difference between estimated and invasively measured ascending aortic SBP and DBP was -2.3±5.6/1.0±0.9 mm Hg. When calibrating with oscillometric brachial BPs, the differences were -9.6±8.1/14.1±6.2 mm Hg (calibration with SBP and DBP), -8.3±11.7/13.9±6.1 mm Hg (DBP and MBP; ff = 0.33), and 1.9±12.2/14.1±6.2 mm Hg (DBP and MBP; ff = 0.40), respectively. Calibration with the average of 3 brachial BPs did not improve accuracy. CONCLUSIONS: The SphygmoCor transfer function seems valid in patients with type 2 diabetes. Noninvasive calibration with DBP and MBP (ff = 0.40) enables accurate estimation of mean ascending aortic SBP at the group level. However, the wide limits of agreement indicate limited accuracy in the individual patient. CLINICAL TRIALS REGISTRATION: Clinical Trials No. NCT01538290.

Timely and optimal treatment of patients with STEMI.

Fibrinolysis is recommended in European and US guidelines for patients with ST-segment elevation myocardial infarction (STEMI) when a strategy of primary percutaneous coronary intervention (PPCI) is associated with ≥120 min delay from first medical contact (FMC), defined as call to the emergency medical services or self-presentation at hospital. Current evidence indicates that reperfusion therapy should be initiated as soon as possible after FMC. However, fibrinolysis cannot be initiated instantaneously at FMC, and PPCI is superior to fibrinolysis in reducing mortality if the extra time needed to perform PPCI instead of fibrinolysis (so-called PCI-related delay) is <120 min. During the past 10 years, the terms 'FMC-to-PPCI delay' and 'PCI-related delay' have been used in guidelines synonymously; however, a distinction should be made between the recommended FMC-to-PPCI delay and the acceptable PCI-related delay. In the future, an ideal recommendation would be to initiate reperfusion as soon as possible, preferably within 120 min of FMC in the case of PPCI. When the expected PCI-related delay is <120 min, PPCI should be the preferred reperfusion strategy, even if the FMC-to-PPCI delay is >120 min. Setting up a health-care system enabling prehospital diagnosis of STEMI with field triage of patients directly to catheterization laboratories at large-volume PCI centres (bypassing local hospitals, coronary care units, emergency departments, and intensive care units) will help to increase the proportion of patients with STEMI who will benefit from PPCI.

Global left ventricular longitudinal systolic strain for early risk assessment in patients with acute myocardial infarction treated with primary percutaneous intervention.

BACKGROUND: Left ventricular systolic function is a key determinant of outcome after ST-segment elevation myocardial infarction (STEMI). The aim of this study was to study speckle-tracking global longitudinal strain (GLS) for early risk evaluation in STEMI and compare it with left ventricular ejection fraction (LVEF), wall motion score index (WMSI), and end-systolic volume index (ESVI). METHODS: Five-hundred seventy-six patients underwent echocardiography ≤24 hours after primary percutaneous coronary intervention for STEMI. The end point was the composite of death, hospitalization with reinfarction, congestive heart failure, or stroke. Associations with outcome were assessed by multivariate Cox regression with adjustment for clinical parameters. Hazard ratios (HRs) for events within the first year are reported per absolute percentage GLS increase. RESULTS: During a median follow-up period of 24 months, 162 patients experienced at least one event. GLS was associated with the composite end point (adjusted HR, 1.20; 95% confidence interval [CI], 1.12-1.29) and also when controlling for LVEF (adjusted HR, 1.17; 95% CI, 1.07-1.29) and ESVI (adjusted HR, 1.18; 95% CI, 1.08-1.28). Although WMSI was significantly associated with outcome beyond any association accounted for by GLS, a borderline significant association was found after controlling for WMSI (adjusted HR for GLS, 1.10; 95% CI, 1.00-1.21). When GLS or WMSI was known, there was no significant association between LVEF or ESVI and outcome. CONCLUSIONS: In a large population of patients with STEMI, GLS and WMSI were comparable and both superior for early risk assessment compared with volume-based left ventricular function indicators such as LVEF and ESVI. Compared with WMSI, the advantage of GLS is the provision of a semiautomated quantitative measure.