Current spectrum and outcomes of infarct-related cardiogenic shock: insights from the CULPRIT-SHOCK registry and randomized controlled trial.

AIMS: We analysed consecutive patients with acute myocardial infarction complicated by cardiogenic shock (CS) who were enrolled into the CULPRIT-SHOCK randomized controlled trial (RCT) and those with exclusion criteria who were included into the accompanying registry. METHODS AND RESULTS: In total, 1075 patients with infarct-related CS were screened for CULPRIT-SHOCK in 83 specialized centres in Europe; 369 of them had exclusion criteria for the RCT and were enrolled into the registry. Patients were followed over 1 year. The mean age was 68 years and 260 (25%) were women. 13.5%, 30.9%, and 55.6% had one-vessel, two-vessel, and three-vessel coronary artery disease (CAD), respectively. Significant left main (LM) coronary artery stenosis was present in 8.0%. 54.2% of the patients had cardiac arrest before admission. Thrombolysis in myocardial infarction (TIMI) 3 patency of the infarct vessel after percutaneous coronary intervention was achieved in 83.6% of all patients. Mechanical circulatory support was applied in one-third of patients. Total mortality after 30 days and 1 year was 47.6% and 52.9%. Mortality after 1 year was highest in patients with LM coronary artery stenosis (63.5%), followed by three-vessel (56.6%), two-vessel (49.8%), and one-vessel CAD (38.6%), respectively. Mechanical complications were rare (21/1008; 2.1%) but associated with a high mortality of 66.7% after 1 year. CONCLUSION: In specialized centres in Europe, short- and long-term mortality of patients with infarct-related CS treated with an invasive strategy is still high and mainly depends on the extent of CAD. Therefore, there is still a need for improvement of care to improve the prognosis of infarct-related CS.

Exercise electrocardiography for pre-test assessment of the likelihood of coronary artery disease.

OBJECTIVES: To develop a tool including exercise electrocardiography (ExECG) for patient-specific clinical likelihood estimation of patients with suspected obstructive coronary artery disease (CAD). METHODS: An ExECG-weighted clinical likelihood (ExECG-CL) model was developed in a training cohort of patients with suspected obstructive CAD undergoing ExECG. Next, the ExECG-CL model was applied in a CAD validation cohort undergoing ExECG and clinically driven invasive coronary angiography and a prognosis validation cohort and compared with the risk factor-weighted clinical likelihood (RF-CL) model for obstructive CAD discrimination and prognostication, respectively.In the CAD validation cohort, obstructive CAD was defined as >50% diameter stenosis on invasive coronary angiography. For prognosis, the endpoint was non-fatal myocardial infarction and death. RESULTS: The training cohort consisted of 1214 patients (mean age 57 years, 57% males). In the CAD (N=408; mean age 55 years, 53% males) and prognosis validation (N=3283; mean age 57 years, 57% males) cohorts, 11.8% patients had obstructive CAD and 4.4% met the endpoint. In the CAD validation cohort, discrimination of obstructive CAD was similar between the ExECG-CL and RF-CL models: area under the receiver-operating characteristic curves 83.1% (95% CIs 77.5% to 88.7%) versus 80.7% (95% CI 74.6% to 86.8%), p=0.14. In the ExECG-CL model, more patients had very low (≤5%) clinical likelihood of obstructive CAD compared with the RF-CL (42.2% vs 36.0%, p<0.01) where obstructive CAD prevalence and event risk remained low. CONCLUSIONS: ExECG incorporated into a clinical likelihood model improves reclassification of patients to a very low clinical likelihood group with very low prevalence of obstructive CAD and favourable prognosis.

Venoarterial extracorporeal membrane oxygenation or standard care in patients with cardiogenic shock complicating acute myocardial infarction: the multicentre, randomised EURO SHOCK trial.

BACKGROUND: Cardiogenic shock (CGS) occurs in 10% of patients presenting with acute myocardial infarction (MI), with in-hospital mortality rates of 40-50% despite revascularisation. AIMS: The EURO SHOCK trial aimed to determine if early use of venoarterial extracorporeal membrane oxygenation (VA-ECMO) could improve outcomes in patients with persistent CGS following primary percutaneous coronary intervention (PPCI). METHODS: This multicentre, pan-European trial randomised patients with persistent CGS 30 minutes after PPCI of the culprit lesion to receive either VA-ECMO or continue with standard therapy. The primary outcome measure was 30-day all-cause mortality in an intention-to-treat analysis. Secondary endpoints included 12-month all-cause mortality and 12-month composite of all-cause mortality or rehospitalisation due to heart failure. RESULTS: Due to the impact of the COVID-19 pandemic, the trial was stopped before completion of recruitment, after randomisation of 35 patients (standard therapy n=18, VA-ECMO n=17). Thirty-day all-cause mortality occurred in 43.8% of patients randomised to VA-ECMO and in 61.1% of patients randomised to standard therapy (hazard ratio [HR] 0.56, 95% confidence interval [CI]: 0.21-1.45; p=0.22). One-year all-cause mortality was 51.8% in the VA-ECMO group and 81.5% in the standard therapy arm (HR 0.52, 95% CI: 0.21-1.26; p=0.14). Vascular and bleeding complications occurred more often in the VA-ECMO arm (21.4% vs 0% and 35.7% vs 5.6%, respectively). CONCLUSIONS: Due to the limited number of patients recruited to the trial, no definite conclusions could be drawn from the available data. Our study demonstrates the feasibility of randomising patients with CGS complicating acute MI but also illustrates the challenges. We hope these data will inspire and inform the design of future large-scale trials.

Basic mechanisms in cardiogenic shock: part 1-definition and pathophysiology.

Cardiogenic shock mortality rates remain high despite significant advances in cardiovascular medicine and the widespread uptake of mechanical circulatory support systems. Except for early invasive angiography and percutaneous coronary intervention of the infarct-related artery, the most widely used therapeutic measures are based on low-quality evidence. The grim prognosis and lack of high-quality data warrant further action. Part 1 of this two-part educational review defines cardiogenic shock and discusses current treatment strategies. In addition, we summarize current knowledge on basic mechanisms in the pathophysiology of cardiogenic shock, focusing on inflammation and microvascular disturbances, which may ultimately be translated into diagnostic or therapeutic approaches to improve the outcome of our patients.

Basic mechanisms in cardiogenic shock: part 2 - biomarkers and treatment options.

Cardiogenic shock mortality rates remain high despite significant advances in cardiovascular medicine and the widespread uptake of mechanical circulatory support systems. Except for early invasive angiography and percutaneous coronary intervention of the infarct-related artery, all other widely used therapeutic measures are based on low-quality evidence. The grim prognosis and lack of high-quality data warrant further action. Within Part 2 of this two-part educational review on basic mechanisms in cardiogenic shock, we aimed to highlight the current status of translating our understanding of the pathophysiology of cardiogenic shock into clinical practice. We summarize the current status of biomarker research in risk stratification and therapy guidance. In addition, we summarized the current status of translating the findings from bench-, bedside, and biomarker studies into treatment options. Several large randomized controlled trials (RCTs) are underway, providing a huge opportunity to study contemporary cardiogenic shock patients. Finally, we call for translational, homogenous, biomarker-based, international RCTs testing novel treatment approaches to improve the outcome of our patients.

Impact of Center Volume on Outcomes in Myocardial Infarction Complicated by Cardiogenic Shock: A CULPRIT-SHOCK Substudy.

Background Little is known about the impact of center volume on outcomes in acute myocardial infarction complicated by cardiogenic shock. The aim of this study was to investigate the association between center volume, treatment strategies, and subsequent outcome in patients with acute myocardial infarction complicated by cardiogenic shock. Methods and Results In this subanalysis of the randomized CULPRIT-SHOCK (Culprit Lesion Only PCI Versus Multivessel PCI in Cardiogenic Shock) trial, study sites were categorized based on the annual volume of acute myocardial infarction complicated by cardiogenic shock into low-/intermediate-/high-volume centers (<50; 50-100; and >100 cases/y). Subjects from the study/compulsory registry with available volume data were included. Baseline/procedural characteristics, overall treatment, and 1-year all-cause mortality were compared across categories. n=1032 patients were included in this study (537 treated at low-volume, 240 at intermediate-volume, and 255 at high-volume centers). Baseline risk profile of patients across the volume categories was similar, although high-volume centers included a larger number of older patients. Low-/intermediate-volume centers had more resuscitated patients (57.5%/58.8% versus 42.2%; P<0.01), and more patients on mechanical ventilation in comparison to high-volume centers. There were no differences in reperfusion success despite considerable differences in adjunctive pharmacological/device therapies. There was no difference in 1-year all-cause mortality across volume categories (51.1% versus 56.5% versus 54.4%; P=0.34). Conclusions In this study of patients with acute myocardial infarction complicated by cardiogenic shock, considerable differences in adjunctive medical and mechanical support therapies were observed. However, we could not detect an impact of center volume on reperfusion success or mortality.

Composition, structure, and function of heart teams: a joint position paper of the ACVC, EAPCI, EACTS, and EACTA focused on the management of patients with complex coronary artery disease requiring myocardial revascularization.

Contemporary cardiovascular medicine is complex, dynamic, and interactive. Therefore, multidisciplinary dialogue between different specialists is required to deliver optimal and patient-centred care. This has led to the concept of explicit collaborations of different specialists caring for patients with complex cardiovascular diseases-that is 'heart teams'. These teams are particularly valuable to minimize referral bias and improve guideline adherence as so to be responsive to patient preferences, needs, and values but may be challenging to coordinate, especially in the acute setting. This position paper-jointly developed by four cardiovascular associations-is intended to provide conceptual and practical considerations for the composition, structure, and function of multidisciplinary teams. It focuses on patients with complex coronary artery diseases in both elective and urgent setting and provide guidance on how to implement the heart team both in chronic and in acute coronary syndromes patients, including cases with mechanical complications and haemodynamic instability; it also discuss strategies for clear and transparent patient communication and provision of a patient-centric approach. Finally, gaps in evidence and research perspectives in this context are discussed.

2020 Update of the quality indicators for acute myocardial infarction: a position paper of the Association for Acute Cardiovascular Care: the study group for quality indicators from the ACVC and the NSTE-ACS guideline group.

AIMS: Quality indicators (QIs) are tools to improve the delivery of evidence-base medicine. In 2017, the European Society of Cardiology (ESC) Association for Acute Cardiovascular Care (ACVC) developed a set of QIs for acute myocardial infarction (AMI), which have been evaluated at national and international levels and across different populations. However, an update of these QIs is needed in light of the accumulated experience and the changes in the supporting evidence. METHODS AND RESULTS: The ESC methodology for the QI development was used to update the 2017 ACVC QIs. We identified key domains of AMI care, conducted a literature review, developed a list of candidate QIs, and used a modified Delphi method to select the final set of indicators. The same seven domains of AMI care identified by the 2017 Study Group were retained for this update. For each domain, main and secondary QIs were developed reflecting the essential and complementary aspects of care, respectively. Overall, 26 QIs are proposed in this document, compared to 20 in the 2017 set. New QIs are proposed in this document (e.g. the centre use of high-sensitivity troponin), some were retained or modified (e.g. the in-hospital risk assessment), and others were retired in accordance with the changes in evidence [e.g. the proportion of patients with non-ST segment elevation myocardial infarction (NSTEMI) treated with fondaparinux] and the feasibility assessments (e.g. the proportion of patients with NSTEMI whom risk assessment is performed using the GRACE and CRUSADE risk scores). CONCLUSION: Updated QIs for the management of AMI were developed according to contemporary knowledge and accumulated experience. These QIs may be applied to evaluate and improve the quality of AMI care.

Composition, structure, and function of heart teams: a joint position paper of the ACVC, EAPCI, EACTS, and EACTA focused on the management of patients with complex coronary artery disease requiring myocardial revascularization.

Contemporary cardiovascular medicine is complex, dynamic, and interactive. Therefore, multidisciplinary dialogue between different specialists is required to deliver optimal and patient-centred care. This has led to the concept of explicit collaborations of different specialists caring for patients with complex cardiovascular diseases-that is 'heart teams'. These teams are particularly valuable to minimize referral bias and improve guideline adherence as so to be responsive to patient preferences, needs, and values but may be challenging to coordinate, especially in the acute setting. This position paper-jointly developed by four cardiovascular associations-is intended to provide conceptual and practical considerations for the composition, structure, and function of multidisciplinary teams. It focuses on patients with complex coronary artery diseases in both elective and urgent setting and provide guidance on how to implement the heart team both in chronic and in acute coronary syndromes patients, including cases with mechanical complications and haemodynamic instability; it also discusses strategies for clear and transparent patient communication and provision of a patient-centric approach. Finally, gaps in evidence and research perspectives in this context are discussed.

Endothelialitis plays a central role in the pathophysiology of severe COVID-19 and its cardiovascular complications.

This clinical review paper discusses the pathophysiology of the pulmonary and cardiovascular manifestations of a SARS-CoV-2 infection and the ensuing implications on acute cardiovascular care in patients presenting with a severe COVID-19 syndrome admitted to an intensive acute cardiac care unit. The high prevalence of old age, obesity, diabetes, hypertension, heart failure, and ischaemic heart disease in patients who develop a severe to critical COVID-19 syndrome suggests shared pathophysiological mechanisms. Pre-existing endothelial dysfunction and an impaired innate immune response promote the development by the viral infection of an acute endothelialitis in the pulmonary microcirculation complicated by abnormal vasoconstrictor responses, luminal plugging by inflammatory cells, and intravascular thrombosis. This endothelialitis extends into the systemic circulation what may lead to acute myocardial injury, myocarditis, and thromboembolic complications both in the arterial and venous circulation.

Impact of clinical and haemodynamic factors on coronary flow reserve and invasive coronary flow capacity in non-obstructed coronary arteries: a patient-level pooled analysis of the DEBATE and ILIAS studies.

AIMS: Coronary flow reserve (CFR) is a physiological index for the assessment of myocardial flow impairment due to focal or microcirculatory coronary artery disease (CAD). Coronary flow capacity (CFC) is another flow-based concept in diagnosing ischaemic heart disease, based on hyperaemic average peak velocity (hAPV) and CFR. We evaluated clinical and haemodynamic factors which potentially influence CFR and CFC in non-obstructed coronary arteries. METHODS AND RESULTS: Intracoronary Doppler flow velocity measurements to obtain CFR and CFC were performed after inducing hyperaemia in 390 non-obstructed vessels of patients who were scheduled for elective percutaneous coronary intervention (PCI) of another vessel. Akaike's information criterion (AIC) revealed age, female gender, history of myocardial infarction, hypercholesterolaemia, diastolic blood pressure, oral nitrates and rate pressure product as independent predictors of CFR and CFC. After regression analysis, age and female gender were associated with lower CFR and age was associated with worse CFC in angiographically non-obstructed vessels. CONCLUSIONS: Age and female gender are associated with lower CFR, and age with worse CFC in an angiographically non-obstructed coronary artery. CFC seems to be less sensitive to variations in clinical and haemodynamic parameters than CFR and is therefore a promising tool in contemporary clinical decision making in the cardiac catheterisation laboratory.

Clinical Outcomes According to ECG Presentations in Infarct-Related Cardiogenic Shock in the Culprit Lesion Only PCI vs Multivessel PCI in Cardiogenic Shock Trial.

BACKGROUND: The impact of ECG presentations of acute myocardial infarction (AMI) in cardiogenic shock is unknown. RESEARCH QUESTION: In myocardial infarction with cardiogenic shock, is there a difference in the outcomes and effect of revascularization strategies between non-ST-segment elevation myocardial infarction (NSTEMI) and left bundle branch block myocardial infarction (LBBBMI) vs ST-segment elevation myocardial infarction (STEMI)? STUDY DESIGN AND METHODS: Cardiogenic shock patients from the CULPRIT-SHOCK trial with NSTEMI or LBBBMI were compared with STEMI patients for 30-day and 1-year all-cause mortality. The interaction between ECG presentation and the effect of revascularization strategies on outcomes was evaluated. RESULTS: Of 665 cardiogenic shock patients analyzed, 55.9% demonstrated STEMI, 29.3% demonstrated NSTEMI, and 14.7% demonstrated LBBBMI. Patients differed in mean age (68.0 years in STEMI patients, 71.0 years in NSTEMI patients, and 73.5 years in LBBBMI patients; P = .015), cardiovascular risk factors, and angiographic severity. No difference was found in the 30-day risk of death between NSTEMI and STEMI patients (48.7% vs 43.0%; adjusted OR [aOR], 1.05; 95% CI, 0.66-1.67; P = .85), nor between LBBBMI and STEMI patients (59.2% vs 43.0%; aOR, 1.31; 95% CI, 0.73-2.34; P = .36). Although the univariate risk of death by 1 year was higher in NSTEMI and LBBBMI patients compared with STEMI patients, ECG presentation was not an independent risk factor of mortality after adjustment (NSTEMI vs STEMI: 56.4% vs 46.8%; aOR, 1.21; 95% CI, 0.76-1.92; P = .42; LBBBMI vs STEMI: 69.4% vs 46.8%; aOR, 1.59; 95% CI, 0.89-2.84; P = .12). ECG presentation did not modify the effect of the revascularization strategy on 30-day and 1-year mortality (P = .91 and P = .97 for interaction). INTERPRETATION: In patients with cardiogenic shock, NSTEMI and LBBBMI presentations reflect higher-risk profiles than STEMI presentations, but are not independent risk factors of mortality. ECG presentations did not modify the treatment effect, supporting culprit-lesion-only percutaneous coronary intervention as the preferred strategy across the AMI spectrum.

Clinical characterization of the first Belgian SCN5A founder mutation cohort.

AIMS: We identified the first Belgian SCN5A founder mutation, c.4813 + 3_4813 + 6dupGGGT. To describe the clinical spectrum and disease severity associated with this mutation, clinical data of 101 SCN5A founder mutation carriers and 46 non-mutation carrying family members from 25 Belgian families were collected. METHODS AND RESULTS: The SCN5A founder mutation was confirmed by haplotype analysis. The clinical history and electrocardiographic parameters of the mutation carriers and their family members were gathered and compared. A cardiac electrical abnormality was observed in the majority (82%) of the mutation carriers. Cardiac conduction defects, defined as PR or QRS prolongation on electrocardiogram (ECG), were most frequent, occurring in 65% of the mutation carriers. Brugada syndrome (BrS) was the second most prevalent phenotype identified in 52%, followed by atrial dysrythmia in 11%. Overall, 33% of tested mutation carriers had a normal sodium channel blocker test. Negative tests were more common in family members distantly related to the proband. Overall, 23% of the mutation carriers were symptomatic, with 8% displaying major adverse events. As many as 13% of the patients tested with a sodium blocker developed ventricular arrhythmia. One family member who did not carry the founder mutation was diagnosed with BrS. CONCLUSION: The high prevalence of symptoms and sensitivity to sodium channel blockers in our founder population highlights the adverse effect of the founder mutation on cardiac conduction. The large phenotypical heterogeneity, variable penetrance, and even non-segregation suggest that other genetic (and environmental) factors modify the disease expression, severity, and outcome in these families.

Veno-arterial extracorporeal membrane oxygenation (ECMO) in patients with cardiogenic shock: rationale and design of the randomised, multicentre, open-label EURO SHOCK trial.

AIMS: Cardiogenic shock (CGS) occurs in 6-10% of patients with acute coronary syndromes (ACS). Mortality has fallen over time from 80% to approximately 50% consequent on acute revascularisation but has plateaued since the 1990s. Once established, patients with CGS develop adverse compensatory mechanisms that contribute to the downward spiral towards death, which becomes difficult to reverse. We aimed to test in a robust, prospective, randomised controlled trial whether early support with veno-arterial extracorporeal membrane oxygenation (VA-ECMO) provides clinical benefit by improving mortality and morbidity. METHODS AND RESULTS: The EURO SHOCK trial will test the benefit or otherwise of mechanical cardiac support using VA-ECMO, initiated early after acute percutaneous coronary intervention (PCI) for CGS. The trial sets out to randomise 428 patients with CGS complicating ACS, following primary PCI (P-PCI), to either very early ECMO plus standard pharmacotherapy, or standard pharmacotherapy alone. It will be conducted in 39 European centres. The primary endpoint is 30-day all-cause mortality with key secondary endpoints: 1) 12-month all-cause mortality or admission for heart failure, 2) 12-month all-cause mortality, 3) 12-month admission for heart failure. Cost-effectiveness analysis (including quality of life measures) will be embedded. Mechanistic and hypothesis-generating substudies will be undertaken. CONCLUSIONS: The EURO SHOCK trial will determine whether early initiation of VA-ECMO in patients presenting with ACS-CGS persisting after PCI improves mortality and morbidity.

Risk stratification scores for patients with acute heart failure in the Emergency Department: A systematic review.

AIMS: This study aimed to systematically identify and summarise all risk scores evaluated in the emergency department setting to stratify acute heart failure patients. METHODS AND RESULTS: A systematic review of PubMed and Web of Science was conducted including all multicentre studies reporting the use of risk predictive models in emergency department acute heart failure patients. Exclusion criteria were: (a) non-original articles; (b) prognostic models without predictive purposes; and (c) risk models without consecutive patient inclusion or exclusively tested in patients admitted to a hospital ward. We identified 28 studies reporting findings on 19 scores: 13 were originally derived in the emergency department (eight exclusively using acute heart failure patients), and six in emergency department and hospitalised patients. The outcome most frequently predicted was 30-day mortality. The performance of the scores tended to be higher for outcomes occurring closer to the index acute heart failure event. The eight scores developed using acute heart failure patients only in the emergency department contained between 4-13 predictors (age, oxygen saturation and creatinine/urea included in six scores). Five scores (Emergency Heart Failure Mortality Risk Grade, Emergency Heart Failure Mortality Risk Grade 30 Day mortality ST depression, Epidemiology of Acute Heart Failure in Emergency department 3 Day, Acute Heart Failure Risk Score, and Multiple Estimation of risk based on Emergency department Spanish Score In patients with Acute Heart Failure) have been externally validated in the same country, and two (Emergency Heart Failure Mortality Risk Grade and Multiple Estimation of risk based on Emergency department Spanish Score In patients with Acute Heart Failure) further internationally validated. The c-statistic for Emergency Heart Failure Mortality Risk Grade to predict seven-day mortality was between 0.74-0.81 and for Multiple Estimation of risk based on Emergency department Spanish Score In patients with Acute Heart Failure to predict 30-day mortality was 0.80-0.84. CONCLUSIONS: There are several scales for risk stratification of emergency department acute heart failure patients. Two of them are accurate, have been adequately validated and may be useful in clinical decision-making in the emergency department i.e. about whether to admit or discharge.