A randomised trial of selective intracoronary hypothermia during primary PCI.

BACKGROUND: While experimental data suggest that selective intracoronary hypothermia decreases infarct size, studies in patients with ST-elevation myocardial infarction (STEMI) are lacking. AIMS: We investigated the efficacy of selective intracoronary hypothermia during primary percutaneous coronary intervention (PCI) to decrease infarct size in patients with STEMI. METHODS: In this multicentre randomised controlled trial, 200 patients with large anterior wall STEMI were randomised 1:1 to selective intracoronary hypothermia during primary PCI or primary PCI alone. Using an over-the-wire balloon catheter for infusion of cold saline and a pressure-temperature wire to monitor the intracoronary temperature, the anterior myocardium distal to the occlusion was selectively cooled to 30-33°C for 7-10 minutes before reperfusion (occlusion phase), immediately followed by 10 minutes of cooling after reperfusion (reperfusion phase). The primary endpoint was infarct size as a percentage of left ventricular mass on cardiovascular magnetic resonance imaging after 3 months. RESULTS: Selective intracoronary hypothermia was performed in 94/100 patients randomised to cooling. Distal coronary temperature decreased by 6°C within 43 seconds (interquartile range [IQR] 18-113). The median duration of the occlusion phase and reperfusion phase were 8.2 minutes (IQR 7.2-9.0) and 9.1 minutes (IQR 8.2-10.0), respectively. The infarct size at 3 months was 23.1±12.5% in the selective intracoronary hypothermia group and 21.6±12.2% in the primary PCI alone group (p=0.43). The left ventricular ejection fraction at 3 months in each group were 49.1±10.2% and 50.1±10.4%, respectively (p=0.53). CONCLUSIONS: Selective intracoronary hypothermia during primary PCI in patients with anterior wall STEMI was feasible and safe but did not decrease infarct size compared with standard primary PCI. (ClinicalTrials.gov: NCT03447834).

Continuous thermodilution and microvascular resistance reserve during the index procedure in acute coronary syndrome without obstructive coronary artery disease: A pilot study.

BACKGROUND: In 5%-25% of non-ST-elevation acute coronary syndrome (NSTE-ACS) patients, coronary angiography reveals no obstructive coronary arteries (MINOCA). Coronary microvascular disease (CMD) is a potential causal pathophysiological mechanism in these patients and can be diagnosed by continuous thermodilution assessment. Recently, the microvascular resistance reserve (MRR) has been introduced as a novel index to assess the vasodilatory capacity of the microcirculation. However, continuous thermodilution and MRR have never been investigated in the acute setting in MINOCA patients and invasive assessment of the microcirculation in these patients are currently lacking. AIMS: The objectives of the study were to investigate the incidence of CMD (MRR ≤ 2.7) in patients with MINOCA and to evaluate the feasibility and safety of continuous thermodilution-based assessment during index coronary angiography in the acute setting. METHODS: This study was a prospective, observational, pilot study investigating coronary physiology in the acute setting in MINOCA patients. Patients admitted with a diagnosis of NSTE-ACS were eligible for inclusion. RESULTS: In total, 19 MINOCA patients were included in this analysis; the mean age was 70 ± 9 years, and 79% were females. CMD was present in 6 patients (32%). Qrest was significantly higher in the MRR ≤ 2.7 group compared to the MRR > 2.7 group (0.076 [0.057-0.100] vs. 0.049 [0.044-0.071] L/min, p = 0.03). Rµ,rest was significantly lower in the MRR ≤ 2.7 group compared to the MRR > 2.7 group (1083 [710-1510] vs. 1563 [1298-1970] WU, p = 0.04). No periprocedural complications or hemodynamic instability have occurred during continuous thermodilution assessment during the index coronary angiography. CONCLUSION: In patients admitted for MINOCA undergoing immediate coronary angiography, continuous thermodilution assessment and MRR are feasible and safe in the acute setting, and evidence of functional CMD could be observed in one-third of the MINOCA patients.

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<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 (€5599 (2978-9625) vs €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.

National indication document and aortic valve replacement landscape in the Netherlands.

INTRODUCTION: Based on European guidelines, transcatheter aortic valve implementation (TAVI) could be the therapy of choice in patients with severe aortic stenosis aged ≥ 75 years. In the Netherlands, there has been a debate between healthcare providers and the National Health Care Institute regarding reimbursement for TAVI, which resulted in an indication document that defines TAVI patients who are eligible for reimbursement. This document has been effective since 1 January 2021. METHODS: We extracted data from the Netherlands Heart Registry for patients who underwent biological surgical aortic valve replacement (SAVR) or TAVI in the Netherlands from 2018 through 2021. We compared baseline characteristics and variables from the indication document for the subsequent years and age groups. We also analysed the annual SAVR/TAVI ratio. RESULTS: The total number of patients treated with SAVR or TAVI was constant in 2018-2021. Baseline characteristics of patients treated with TAVI did not differ throughout the years. The SAVR/TAVI ratio shifted towards a higher percentage of TAVI from 2018 to 2019. From 2019 to 2020, the TAVI percentage was constant. Since the implementation of the indication document (in 2021), a change in the SAVR/TAVI ratio was not found either. CONCLUSION: Since the implementation of the national indication document for AVR in 2021, no major effect was seen for the SAVR versus TAVI landscape in the Netherlands.

Direct admission versus interhospital transfer for revascularisation in non-ST-segment elevation myocardial infarction.

BACKGROUND: The differences in outcomes and process parameters for NSTEMI patients who are directly admitted to an intervention centre and patients who are first admitted to a general centre are largely unknown. HYPOTHESIS: There are differences in process indicators, but not for clinical outcomes, for NSTEMI who are directly admitted to an intervention centre and patients who are first admitted to a general centre. METHODS: We aim to compare process indicators, costs and clinical outcomes of non-ST-segment elevation myocardial infarction (NSTEMI) patients stratified by center of first presentation and revascularisation strategy. Hospital claim data from patients admitted with a NSTEMI between 2017 and 2019 were used for this study. Included patients were stratified by center of admission (intervention vs. general center) and subdivided by revascularisation strategy (PCI, CABG, or no revascularisation [noRevasc]). The primary outcome was length of hospital stay. Secondary outcomes included: duration between admission and diagnostic angiography and revascularisation, number of intracoronary procedures, clinical outcomes at 30 days (MACE: all-cause mortality, recurrent myocardial infarction and cardiac readmission) and total costs (accumulation of costs for hospital claims and interhospital ambulance rides). RESULTS: A total of 9641 NSTEMI events (9167 unique patients) were analyzed of which 5399 patients (56%) were admitted at an intervention center and 4242 patients to a general center. Duration of hospitalization was significantly shorter at direct presentation at an intervention centre for all study groups (5 days [2-11] vs. 7 days [4-12], p < 0.001). For PCI, direct presentation at an intervention center yielded shorter time to diagnostic angiography (1 day [0-2] vs. 1 day [1-2], p < 0.01) and revascularisation (1 day [0-3] vs. 4 days [1-7], p < 0.001) and less intracoronary procedures per patient (2 [1-2] vs. 2 [2-2], p < 0.001). For CABG, time to revascularisation was shorter (8 days [5-12] vs. 10 days [7-14], p < 0.001). Total costs were significantly lower in case of direct presentation in an intervention center for all treatment groups €10.211 (8750-18.192) versus €13.741 (11.588-19.381), p < 0.001) while MACE was similar 11.8% versus 12.4%, p = 0.344). CONCLUSION: NSTEMI patients who were directly presented to an intervention center account for shorter duration of hospitalization, less time to revascularisation, less interhospital transfers, less intracoronary procedures and lower costs compared to patients who present at a general center.

Early risk assessment in patients with suspected NSTE-ACS; a retrospective cohort study.

INTRODUCTION: Chest pain is among the most common reasons for Emergency Department (ED) presentation, while most patients should be considered low risk for Acute Coronary Syndrome (ACS). Management of these patients places a significant burden on our health care system. Various risk scores have been developed to facilitate the triage of patients with chest pain. However, it remains unclear which score performs best in identifying low risk patients, in various settings. The aim of this study was to determine which risk score performs best in ruling out non-ST elevation ACS (NSTE-ACS). METHODS: Data was collected from all patients >18 years presenting to the ED between 01 and 01-2019 and 01-07-2019, if they were suspected of NSTE-ACS. Primary endpoint was NSTE-ACS during presentation to the ED or hospitalization, according to the 2020 ESC guidelines. In a secondary analysis we determined the number low-risk patients, at set safety levels of 95% and 98%. RESULTS: A total of 536 patients were included, 192 (35.9%) were admitted to the hospital and NSTE-ACS occurred in 134 of 536 patients (25.0%). When areas under the curve (AUC) were compared, pre-HEART (0.869; CI 0.835-0.903), T-MACS (0.862; CI 0.825-0.898) and HEART (0.850; CI 0.815-0.885) performed best. At a safety level of 98%, the HEART score was the best performing risk score and identified 28.9% of patients as low risk, and missed 0 cases of NSTE-ACS. Followed by the pre-HEART score, which identified 18.3% of all patients as low risk, and missed 0% of NSTE-ACS. CONCLUSIONS: The newly developed pre-HEART score is both practical and has accurate diagnostic properties, closely followed by the HEART score, and T-MACS. New pre-hospital risk scores are promising and much needed. Future studies should focus on the usage of pre-hospital scores for triage of patients with chest pain, in order to reduce the burden on emergency health care.

Prehospital triage of patients with suspected non-ST-segment elevation acute coronary syndrome: Rationale and design of the TRIAGE-ACS study.

BACKGROUND: Patients with suspected non-ST-segment elevation acute coronary syndrome (NSTE-ACS) are currently transported and admitted to the nearest emergency department (ED) for risk stratification, diagnostic workup and treatment. Although such patients with NSTE-ACS can benefit from direct transfer to a PCI center for early invasive treatment, no reliable prehospital triage tools are available. Recently, the PreHEART score has been validated in the PreHEART study for prehospital triage of patients with suspected NSTE-ACS. METHODS: The primary objective of the TRIAGE-ACS study, a prospective cohort study, is to determine whether prehospital triage using the PreHEART score can significantly reduce time from first medical contact to final diagnostics and revascularization in patients in need of coronary revascularization. The first cohort (control cohort; n = 500) is observatory and is used as a reference group for the second cohort. In the second cohort (interventional cohort; n = 500) patients are stratified in the ambulance for direct transfer to either a PCI or a non-PCI center, based on the PreHEART score. These two cohorts will be compared with each other. In total, 1000 patients will be included. Follow-up for endpoints will be performed by reviewing the medical record after 30 days, 1 year, and 2 years. CONCLUSION: The TRIAGE-ACS study is the first prospective study to investigate the impact of prehospital triage using the PreHEART score on time to final invasive diagnostics and treatment in patients with NSTE-ACS in need of revascularization by transferring high risk patients directly to a PCI center and patients at a low risk of having an NSTE-ACS to a non-PCI center. Such triage strategy could potentially result in optimization of regional care for all ACS patients.

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.

Prehospital risk assessment in patients suspected of non-ST-segment elevation acute coronary syndrome: a systematic review and meta-analysis.

OBJECTIVE: To review, inventory and compare available diagnostic tools and investigate which tool has the best performance for prehospital risk assessment in patients suspected of non-ST-segment elevation acute coronary syndrome (NSTE-ACS). METHODS: Systematic review and meta-analysis. Medline and Embase were searched up till 1 April 2021. Prospective studies with patients, suspected of NSTE-ACS, presenting in the primary care setting or by emergency medical services (EMS) were included. The most important exclusion criteria were studies including only patients with ST-elevation myocardial infarction and studies before 1995, the pretroponin era. The primary end point was the final hospital discharge diagnosis of NSTE-ACS or major adverse cardiac events (MACE) within 6 weeks. Risk of bias was evaluated by the Quality Assessment of Diagnostic Accuracy Studies Criteria. MAIN OUTCOME AND MEASURES: Sensitivity, specificity and likelihood ratio of findings for risk stratification in patients suspected of NSTE-ACS. RESULTS: In total, 15 prospective studies were included; these studies reflected in total 26 083 patients. No specific variables related to symptoms, physical examination or risk factors were useful in risk stratification for NSTE-ACS diagnosis. The most useful electrocardiographic finding was ST-segment depression (LR+3.85 (95% CI 2.58 to 5.76)). Point-of-care troponin was found to be a strong predictor for NSTE-ACS in primary care (LR+14.16 (95% CI 4.28 to 46.90) and EMS setting (LR+6.16 (95% CI 5.02 to 7.57)). Combined risk scores were the best for risk assessment in an NSTE-ACS. From the combined risk scores that can be used immediately in a prehospital setting, the PreHEART score, a validated combined risk score for prehospital use, derived from the HEART score (History, ECG, Age, Risk factors, Troponin), was most useful for risk stratification in patients with NSTE-ACS (LR+8.19 (95% CI 5.47 to 12.26)) and for identifying patients without ACS (LR-0.05 (95% CI 0.02 to 0.15)). DISCUSSION: Important study limitations were verification bias and heterogeneity between studies. In the prehospital setting, several diagnostic tools have been reported which could improve risk stratification, triage and early treatment in patients suspected for NSTE-ACS. On-site assessment of troponin and combined risk scores derived from the HEART score are strong predictors. These results support further studies to investigate the impact of these new tools on logistics and clinical outcome. FUNDING: This study is funded by ZonMw, the Dutch Organisation for Health Research and Development. TRIAL REGISTRATION NUMBER: This meta-analysis was published for registration in PROSPERO prior to starting (CRD York, CRD42021254122).

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.

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.

Recovery of Absolute Coronary Blood Flow and Microvascular Resistance After Chronic Total Occlusion Percutaneous Coronary Intervention: An Exploratory Study.

Background This study aimed to investigate longitudinal physiological changes in the recanalized coronary chronic total occlusion (CTO) vessel and its dependent myocardium after successful percutaneous coronary intervention (PCI). Methods and Results In this pilot study, 25 patients scheduled for elective CTO PCI with viable myocardium and angiographically visible collaterals were included. Absolute coronary blood flow and absolute microvascular resistance were measured invasively using continuous thermodilution. Measurements were performed immediately after successful CTO PCI and at short-term follow-up. In a subgroup of patients, physiological measurements were performed at the predominant donor vessel before CTO PCI, immediately afterwards, and at follow-up. Absolute coronary blood flow in the recanalized CTO artery increased from 148±53 mL/min immediately after PCI to 221±77 mL/min at follow-up (P<0.001). In agreement, absolute resistance in the myocardial territory perfused by the CTO artery, decreased from 545±255 Wood units immediately after the procedure to 387±128 Wood units at follow-up (P=0.014). There were no significant changes in the absolute coronary blood flow and resistance in the predominant donor between baseline and follow-up. Positive remodeling of the distal CTO vessel with an increase in lumen diameter was observed. Conclusions After successful CTO PCI, blood flow in the recanalized artery and microvascular function of the dependent myocardium are not immediately normal but recover over time.