Rationale and design of SAVI-AoS:A physiologic study of patients with symptomatic moderate aortic valve stenosis and preserved left ventricular ejection fraction

Background: Moderate aortic valve stenosis occurs twice as often as severe aortic stenosis (AS) and carries a similarly poor prognosis. Current European and American guidelines offer limited insight into moderate AS (MAS) patients with unexplained symptoms. Measuring valve physiology at rest while most patients experience symptoms during exertion might represent a conceptual limitation in the current grading of AS severity. The stress aortic valve index (SAVI) may delineate hemodynamically significant AS among patients with MAS. Objectives: To investigate the diagnostic value of SAVI in symptomatic MAS patients with normal left ventricular ejection fraction (LVEF ≥ 50%): aortic valve area (AVA) > 1 cm2 plus either mean valve gradient (MG) 15–39 mmHg or maximal aortic valve velocity (AOV max) 2.5–3.9 m/s. Short-term objectives include associations with symptom burden, functional capacity, and cardiac biomarkers. Long-term objectives include clinical outcomes. Methods and results: Multicenter, non-blinded, observational cohort. AS severity will be graded invasively (aortic valve pressure measurements with dobutamine stress testing for SAVI) and non-invasively (echocardiography during dobutamine and exercise stress). Computed tomography (CT) of the aortic valve will be scored for calcium, and hemodynamics simulated using computational fluid dynamics. Cardiac biomarkers and functional parameters will be serially monitored. The primary objective is to see how SAVI and conventional measures (MG, AVA and Vmax) correlate with clinical parameters (quality of life survey, 6-minute walk test [6MWT], and biomarkers). Conclusions: The SAVI-AoS study will extensively evaluate patients with unexplained, symptomatic MAS to determine any added value of SAVI versus traditional, resting valve parameters

Predicting the infarct-related artery in STEMI from the surface ECG: independent validation of proposed criteria

Aims: This study independently evaluated the diagnostic performance of electrocardiographic (ECG) criteria to predict the infarct-related artery (IRA) in patients with an acute ST-segment elevation myocardial infarction (STEMI). While a number of ECG criteria have been proposed to predict the IRA in STEMI, many of these "rules" came from modestly sized populations and did not undergo external validation. Therefore, we aimed to evaluate popular criteria from the literature in an independent cohort. Methods and results: All acute STEMI cases over a 10-year period from a single hospital were retrospectively identified. We excluded patients with a missing pre-intervention ECG, irretrievable angiographic films, prior coronary artery bypass grafting, left bundle branch block, ventricular pacing, or not meeting strict STEMI criteria. After review of the angiograms for the IRA, cases with either no or multiple culprits were excluded. We included 480 subjects meeting STEMI criteria in inferior leads (192, 40%), anterior leads (184, 38%), both anterior and inferior leads (88, 18%), isolated lateral leads (nine, 2%), or a posterior pattern (seven, 1%). Notably, every pattern except isolated lateral STEMI included an IRA in both the right and left coronary arteries. Conclusions: Existing ECG criteria to predict the IRA in STEMI have modest diagnostic performance when externally validated, and lower than in the original reports. Distinguishing the level of obstruction in the left anterior descending artery remains especially challenging. Hence, their use should be pragmatic when selecting an initial catheter for treating STEMI, since discordances will occur when compared to the actual angiogram

Potential effects of the hydrostatic pressure gradient on hyperemic and nonhyperemic pressure ratios

: When measuring hyperemic and nonhyperemic pressure ratios with traditional sensor-tipped wires, the inevitable hydrostatic pressure gradient (HPG) may influence treatment decisions. This study aimed to simulate and analyze the effect of a hydrostatic pressure gradient on different indices of functional lesion severity. A hypothetical Pd-Pa height difference and subsequent hydrostatic pressure gradient based on previous literature was applied to the pressure measurements from the CONTRAST study. The effect on three indices of functional lesion severity (FFR, Pd/Pa, and dPR) was assessed and possible reclassifications in functional significance by the different indices were analyzed. In 602 pressure tracings, simulated hydrostatic pressure gradients led to an absolute change in Pd of 3.18 ± 1.30 mmHg, resulting in an overall increase in FFR, Pd/Pa, and dPR of 0.02 ± 0.04 for all indices (P = 0.69). Reclassification due to the hydrostatic pressure gradient when using dichotomous cutoff values occurred in 13.4, 22.3, and 20.6% for FFR, Pd/Pa, and dPR, respectively. The effect of hydrostatic pressure gradient correction differed among the coronary arteries and was most pronounced in the left anterior descending. When considering the gray zone for the different functional indices, the hydrostatic pressure gradient resulted in reclassification in only one patient out of the complete patient population (1/602; 0.17%). The hydrostatic pressure gradient can influence functional lesion assessment when using dichotomous cutoff values. When taking the gray zone into account, its effect is limited.NEW & NOTEWORTHY This study systematically simulated the effect of hydrostatic pressure gradients (HPG) on real-world hyperemic and nonhyperemic pressure ratios, showing correction for HPG leads to reclassification in functional significance from 13.4 to 22.3% for different functional indices. This was most pronounced in nonhyperemic pressure ratios. A new pressure guidewire (Wirecath) is unaffected by HPG. The ongoing PW-COMPARE study (NCT04802681) prospectively analyzes the magnitude and importance of HPG by simultaneous FFR measurements

Hypothermia for Cardioprotection in Patients with St-Elevation Myocardial Infarction: Do Not Give It the Cold Shoulder Yet!

The timely revascularization of an occluded coronary artery is the cornerstone of treatment in patients with ST-elevation myocardial infarction (STEMI). As essential as this treatment is, it can also cause additional damage to cardiomyocytes that were still viable before reperfusion, increasing infarct size. This has been termed "myocardial reperfusion injury". To date, there is still no effective treatment for myocardial reperfusion injury in patients with STEMI. While numerous attempts have been made to overcome this hurdle with various experimental therapies, the common denominator of these therapies is that, although they often work in the preclinical setting, they fail to demonstrate the same results in human trials. Hypothermia is an example of such a therapy. Although promising results were derived from experimental studies, multiple randomized controlled trials failed to do the same. This review includes a discussion of hypothermia as a potential treatment for myocardial reperfusion injury, including lessons learned from previous (negative) trials, advanced techniques and materials in current hypothermic treatment, and the possible future of hypothermia for cardioprotection in patients with STEMI

Hypothermia for Cardioprotection in Patients with St-Elevation Myocardial Infarction: Do Not Give It the Cold Shoulder Yet!

The timely revascularization of an occluded coronary artery is the cornerstone of treatment in patients with ST-elevation myocardial infarction (STEMI). As essential as this treatment is, it can also cause additional damage to cardiomyocytes that were still viable before reperfusion, increasing infarct size. This has been termed “myocardial reperfusion injury”. To date, there is still no effective treatment for myocardial reperfusion injury in patients with STEMI. While numerous attempts have been made to overcome this hurdle with various experimental therapies, the common denominator of these therapies is that, although they often work in the preclinical setting, they fail to demonstrate the same results in human trials. Hypothermia is an example of such a therapy. Although promising results were derived from experimental studies, multiple randomized controlled trials failed to do the same. This review includes a discussion of hypothermia as a potential treatment for myocardial reperfusion injury, including lessons learned from previous (negative) trials, advanced techniques and materials in current hypothermic treatment, and the possible future of hypothermia for cardioprotection in patients with STEMI

Prehospital risk assessment and direct transfer to a percutaneous coronary intervention centre in suspected acute coronary syndrome

Objective: Prehospital risk stratification and triage are currently not performed in patients suspected of non-ST-segment elevation acute coronary syndrome (NSTE-ACS). This may lead to prolonged time to revascularisation, increased duration of hospital admission and higher healthcare costs. The preHEART score (prehospital history, ECG, age, risk factors and point-of-care troponin score) can be used by emergency medical services (EMS) personnel for prehospital risk stratification and triage decisions in patients with NSTE-ACS. The aim of the current study was to evaluate the effect of prehospital risk stratification and direct transfer to a percutaneous coronary intervention (PCI) centre, based on the preHEART score, on time to final invasive diagnostics or culprit revascularisation. Methods: Prospective, multicentre, two-cohort study in patients with suspected NSTE-ACS. The first cohort is observational (standard care), while the second (interventional) cohort includes patients who are stratified for direct transfer to either a PCI or a non-PCI centre based on their preHEART score. Risk stratification and triage are performed by EMS personnel. The primary endpoint of the study is time from first medical contact until final invasive diagnostics or revascularisation. Secondary endpoints are time from first medical contact until intracoronary angiography (ICA), duration of hospital admission, number of invasive diagnostics, number of inter-hospital transfers and major adverse cardiac events at 7 and 30 days.Results: A total of 1069 patients were included. In the interventional cohort (n=577), time between final invasive diagnostics or revascularisation (42 (17-101) hours vs 20 (5-44) hours, p&amp; lt;0.001) and length of hospital admission (3 (2-5) days vs 2 (1-4) days, p=0.007) were shorter than in the observational cohort (n=492). In patients with NSTE-ACS in need for ICA or revascularisation, healthcare costs were reduced in the interventional cohort (&amp; euro;5599 (2978-9625) vs &amp; euro;4899 (2278-5947), p=0.02).Conclusion: Prehospital risk stratification and direct transfer to a PCI centre, based on the preHEART score, reduces time from first medical contact to final invasive diagnostics and revascularisation, reduces duration of hospital admission and decreases healthcare costs in patients with NSTE-ACS in need for ICA or revascularisation. Trial registration: NCT05243485. &amp; copy; Author(s) (or their employer(s)) 2023. No commercial re-use. See rights and permissions. Published by BMJ.</p

Prehospital risk assessment and direct transfer to a percutaneous coronary intervention centre in suspected acute coronary syndrome

Objective: Prehospital risk stratification and triage are currently not performed in patients suspected of non-ST-segment elevation acute coronary syndrome (NSTE-ACS). This may lead to prolonged time to revascularisation, increased duration of hospital admission and higher healthcare costs. The preHEART score (prehospital history, ECG, age, risk factors and point-of-care troponin score) can be used by emergency medical services (EMS) personnel for prehospital risk stratification and triage decisions in patients with NSTE-ACS. The aim of the current study was to evaluate the effect of prehospital risk stratification and direct transfer to a percutaneous coronary intervention (PCI) centre, based on the preHEART score, on time to final invasive diagnostics or culprit revascularisation. Methods: Prospective, multicentre, two-cohort study in patients with suspected NSTE-ACS. The first cohort is observational (standard care), while the second (interventional) cohort includes patients who are stratified for direct transfer to either a PCI or a non-PCI centre based on their preHEART score. Risk stratification and triage are performed by EMS personnel. The primary endpoint of the study is time from first medical contact until final invasive diagnostics or revascularisation. Secondary endpoints are time from first medical contact until intracoronary angiography (ICA), duration of hospital admission, number of invasive diagnostics, number of inter-hospital transfers and major adverse cardiac events at 7 and 30 days.Results: A total of 1069 patients were included. In the interventional cohort (n=577), time between final invasive diagnostics or revascularisation (42 (17-101) hours vs 20 (5-44) hours, p&amp; lt;0.001) and length of hospital admission (3 (2-5) days vs 2 (1-4) days, p=0.007) were shorter than in the observational cohort (n=492). In patients with NSTE-ACS in need for ICA or revascularisation, healthcare costs were reduced in the interventional cohort (&amp; euro;5599 (2978-9625) vs &amp; euro;4899 (2278-5947), p=0.02).Conclusion: Prehospital risk stratification and direct transfer to a PCI centre, based on the preHEART score, reduces time from first medical contact to final invasive diagnostics and revascularisation, reduces duration of hospital admission and decreases healthcare costs in patients with NSTE-ACS in need for ICA or revascularisation. Trial registration: NCT05243485. &amp; copy; Author(s) (or their employer(s)) 2023. No commercial re-use. See rights and permissions. Published by BMJ.</p

Prehospital risk assessment and direct transfer to a percutaneous coronary intervention centre in suspected acute coronary syndrome

Objective: Prehospital risk stratification and triage are currently not performed in patients suspected of non-ST-segment elevation acute coronary syndrome (NSTE-ACS). This may lead to prolonged time to revascularisation, increased duration of hospital admission and higher healthcare costs. The preHEART score (prehospital history, ECG, age, risk factors and point-of-care troponin score) can be used by emergency medical services (EMS) personnel for prehospital risk stratification and triage decisions in patients with NSTE-ACS. The aim of the current study was to evaluate the effect of prehospital risk stratification and direct transfer to a percutaneous coronary intervention (PCI) centre, based on the preHEART score, on time to final invasive diagnostics or culprit revascularisation. Methods: Prospective, multicentre, two-cohort study in patients with suspected NSTE-ACS. The first cohort is observational (standard care), while the second (interventional) cohort includes patients who are stratified for direct transfer to either a PCI or a non-PCI centre based on their preHEART score. Risk stratification and triage are performed by EMS personnel. The primary endpoint of the study is time from first medical contact until final invasive diagnostics or revascularisation. Secondary endpoints are time from first medical contact until intracoronary angiography (ICA), duration of hospital admission, number of invasive diagnostics, number of inter-hospital transfers and major adverse cardiac events at 7 and 30 days.Results: A total of 1069 patients were included. In the interventional cohort (n=577), time between final invasive diagnostics or revascularisation (42 (17-101) hours vs 20 (5-44) hours, p&amp; lt;0.001) and length of hospital admission (3 (2-5) days vs 2 (1-4) days, p=0.007) were shorter than in the observational cohort (n=492). In patients with NSTE-ACS in need for ICA or revascularisation, healthcare costs were reduced in the interventional cohort (&amp; euro;5599 (2978-9625) vs &amp; euro;4899 (2278-5947), p=0.02).Conclusion: Prehospital risk stratification and direct transfer to a PCI centre, based on the preHEART score, reduces time from first medical contact to final invasive diagnostics and revascularisation, reduces duration of hospital admission and decreases healthcare costs in patients with NSTE-ACS in need for ICA or revascularisation. Trial registration: NCT05243485. &amp; copy; Author(s) (or their employer(s)) 2023. No commercial re-use. See rights and permissions. Published by BMJ.</p

Ultrastructural Characteristics of Myocardial Reperfusion Injury and Effect of Selective Intracoronary Hypothermia: An Observational Study in Isolated Beating Porcine Hearts

In acute myocardial infarction (AMI), myocardial reperfusion injury may undo part of the recovery after revascularization of the occluded coronary artery. Selective intracoronary hypothermia is a novel method aimed at reducing myocardial reperfusion injury, but its presumed protective effects in AMI still await further elucidation. This proof-of-concept study assesses the potential protective effects of selective intracoronary hypothermia in an ex-vivo, isolated beating heart model of AMI. In four isolated Langendorff perfused beating pig hearts, an anterior wall myocardial infarction was created by inflating a balloon in the mid segment of the left anterior descending (LAD) artery. After one hour, two hearts were treated with selective intracoronary hypothermia followed by normal reperfusion (cooled hearts). In the other two hearts, the balloon was deflated after one hour, allowing normal reperfusion (control hearts). Biopsies for histologic and electron microscopic evaluation were taken from the myocardium at risk at different time points: before occlusion (t = BO); 5 minutes before reperfusion (t = BR); and 10 minutes after reperfusion (t = AR). Electron microscopic analysis was performed to evaluate the condition of the mitochondria. Histological analyses included evaluation of sarcomeric collapse and intramyocardial hematoma. Electron microscopic analysis revealed intact mitochondria in the hypothermia treated hearts compared to the control hearts where mitochondria were more frequently damaged. No differences in the prespecified histological parameters were observed between cooled and control hearts at t = AR. In the isolated beating porcine heart model of AMI, reperfusion was associated with additional myocardial injury beyond ischemic injury. Selective intracoronary hypothermia preserved mitochondrial integrity compared to nontreated controls