Cardiovascular disease and COVID-19: a consensus paper from the ESC Working Group on Coronary Pathophysiology & Microcirculation, ESC Working Group on Thrombosis and the Association for Acute CardioVascular Care (ACVC), in collaboration with the European Heart Rhythm Association (EHRA).

The cardiovascular system is significantly affected in coronavirus disease-19 (COVID-19). Microvascular injury, endothelial dysfunction, and thrombosis resulting from viral infection or indirectly related to the intense systemic inflammatory and immune responses are characteristic features of severe COVID-19. Pre-existing cardiovascular disease and viral load are linked to myocardial injury and worse outcomes. The vascular response to cytokine production and the interaction between severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) and angiotensin-converting enzyme 2 receptor may lead to a significant reduction in cardiac contractility and subsequent myocardial dysfunction. In addition, a considerable proportion of patients who have been infected with SARS-CoV-2 do not fully recover and continue to experience a large number of symptoms and post-acute complications in the absence of a detectable viral infection. This conditions often referred to as 'post-acute COVID-19' may have multiple causes. Viral reservoirs or lingering fragments of viral RNA or proteins contribute to the condition. Systemic inflammatory response to COVID-19 has the potential to increase myocardial fibrosis which in turn may impair cardiac remodelling. Here, we summarize the current knowledge of cardiovascular injury and post-acute sequelae of COVID-19. As the pandemic continues and new variants emerge, we can advance our knowledge of the underlying mechanisms only by integrating our understanding of the pathophysiology with the corresponding clinical findings. Identification of new biomarkers of cardiovascular complications, and development of effective treatments for COVID-19 infection are of crucial importance.

Gender Disparities on Access to Care and Coronary Disease Management.

Mortality decline in women to a lesser extent than in men with coronary artery disease (CAD) has provoked a bigger interest in some already existing dilemmas and questions. Many studies carried out in the past three decades did not provide us with precise conclusions. Moreover, various challenges in the prevention, diagnosis, treatment and outcome of CAD in women are still remaining. The meta-analysis and the systematic review conducted in the last years have offered novel approaches to understanding CAD gender disparities in access to care and coronary disease management in women, but women are more likely to experience less favorable short- and long-term outcomes than men do. The reasons for these findings should lie in several known segments in the CAD pathophysiological mechanisms different in women and ultimately leading to a lower quality of care. Clinical presentation in women, which is often characterized by atypical chest pain and a higher prevalence of non-obstructive CAD when evaluated invasively, places women to the false-negative diagnosis of CAD and influences inadequate access to care. Clinical presentation and diagnostic methods, as well as the appropriate treatment options insufficiently examined in women, need to be better defined. The traditional CAD risk factors have a greater impact on women than on men. Unique CAD risk factors only seen in women, have recently been recognized with more attention. However, it is important to note that even in women with obstructive CAD and typical clinical presentation, invasive therapy and pharmacologic therapy are not always implemented as recommended by guidelines as in men. Women are underrepresented in CAD trials, and in current guidelines, gender differences in CAD management have not yet been justified. The underestimation of the risk of CAD in women, followed by its underdiagnosis and undertreatment, might be one of the reasons for a worse prognosis in women in comparison with men.

Three-Year Impact of Immediate Invasive Strategy in Patients With Non-ST-Segment Elevation Myocardial Infarction (from the RIDDLE-NSTEMI Study).

Previous studies compared clinical outcomes of early versus delayed invasive strategy in patients with non-ST-elevation acute coronary syndrome up to 1-year follow-up, but long-term data remain scarce. Our aim was to evaluate the long-term effects of immediate invasive intervention in patients with Non-ST-Segment Elevation Myocardial Infarction (NSTEMI). The Randomized Study of Immediate Versus Delayed Invasive Intervention in Patients With Non-ST-Segment Elevation Myocardial Infarction (RIDDLE-NSTEMI) was a randomized, investigator-initiated, parallel-group trial that assigned 323 patients with NSTEMI (1:1) to either immediate (median time to intervention 1.4 hours) or delayed invasive strategy (61.0 hours). The primary end point was the composite of death or new myocardial infarction (MI). At 3 years, immediate invasive intervention was associated with a lower rate of death or new MI, compared with a delayed invasive strategy (12.3% vs 22.5%, hazard ratio 0.50, 95% confidence interval 0.29 to 0.87, p = 0.014). The observed benefit of immediate intervention was mainly driven by an increased early reinfarction risk in delayed strategy, with similar new MI rates beyond 30 days (4.4% in the immediate and 5.6% in the delayed group, p = 0.61). Three-year mortality was 9.3% in the immediate invasive strategy, and 10.0% in the delayed strategy (p = 0.83). High baseline Global Registry of Acute Coronary Events score (>140) was associated with a significant increase in long-term mortality, regardless of the timing of invasive intervention. In conclusion, whereas immediate invasive intervention significantly reduced the early risk of new MI, the timing of invasive intervention appears to have no significant impact on clinical outcomes beyond 30 days, which seem to mostly be related to the baseline clinical risk profile.

Sex and age differences and outcomes in acute coronary syndromes.

BACKGROUND: There is conflicting information about sex differences in presentation, treatment, and outcome after acute coronary syndromes (ACS) in the era of reperfusion therapy and percutaneous coronary intervention. The aim of this study was to examine presentation, acute therapy, and outcomes of men and women with ACS with special emphasis on their relationship with younger age (≤65years). METHODS: From January 2010 to June 2015, we enrolled 5140 patients from 3 primary PCI capable hospitals. Patients were registered according to the International Survey of Acute Coronary Syndrome in Transitional Countries (ISACS-TC) registry protocol (ClinicalTrials.gov: NCT01218776). The primary outcome was the incidence of in-hospital mortality. RESULTS: The study population was constituted by 2876 patients younger than 65years and 2294 patients older. Women were older than men in both the young (56.2±6.6 vs. 54.1±7.4) and old (74.9±6.4 vs. 73.6±6.0) age groups. There were 3421 (66.2%) patients with ST elevation ACS (STE-ACS) and 1719 (33.8%) patients without ST elevation ACS (NSTE-ACS). In STE-ACS, the percentage of patients who failed to receive reperfusion was higher in women than in men either in the young (21.7% vs. 15.8%) than in the elderly (35.2% vs. 29.6%). There was a significant higher mortality in women in the younger age group (age-adjusted OR 1.52, 95% CI: 1.01-2.29), but there was no sex difference in the older group (age-adjusted OR 1.10, 95% CI: 0.87-1.41). Significantly sex differences in mortality were not seen in NSTE-ACS patients. CONCLUSIONS: In-hospital mortality from ACS is not different between older men and women. A higher short-term mortality can be seen only in women with STEMI and age of 65 or less.

Immediate Versus Delayed Invasive Intervention for Non-STEMI Patients: The RIDDLE-NSTEMI Study.

OBJECTIVES: This study aimed to assess the clinical impact of immediate versus delayed invasive intervention in patients with non-ST-segment myocardial infarction (NSTEMI). BACKGROUND: Previous studies found conflicting results on the effects of earlier invasive intervention in a heterogeneous population of acute coronary syndromes without ST-segment elevation. METHODS: We randomized 323 NSTEMI patients to an immediate-intervention group (<2 h after randomization, n = 162) and a delayed-intervention group (2 to 72 h, n = 161).The primary endpoint was the occurrence of death or new myocardial infarction (MI) at 30-day follow-up. RESULTS: Median time from randomization to angiography was 1.4 h and 61.0 h in the immediate-intervention group and the delayed-intervention group, respectively (p < 0.001). At 30 days, the primary endpoint was achieved less frequently in patients undergoing immediate intervention (4.3% vs. 13%, hazard ratio: 0.32, 95% confidence interval: 0.13 to 0.74; p = 0.008). At 1 year, this difference persisted (6.8% in the immediate-intervention group vs. 18.8% in delayed-intervention group; hazard ratio: 0.34, 95% confidence interval: 0.17 to 0.67; p = 0.002). The observed results were mainly attributable to the occurrence of new MI in the pre-catheterization period (0 deaths + 0 MIs in the immediate-intervention group vs. 1 death + 10 MIs in the delayed-intervention group). The rate of deaths, new MI, or recurrent ischemia was lower in the immediate-intervention group at both 30 days (6.8% vs. 26.7%; p < 0.001) and 1 year (15.4% vs. 33.1%; p < 0.001). CONCLUSIONS: Immediate invasive strategy in NSTEMI patients is associated with lower rates of death or new MI compared with the delayed invasive strategy at early and midterm follow-up, mainly due to a decrease in the risk of new MI in the pre-catheterization period. (Immediate Versus Delayed Invasive Intervention for Non-STEMI Patients [RIDDLE-NSTEMI]; NCT02419833).

Feasibility of semi-quantitative assessment of left ventricular contractile reserve in dilated cardiomyopathy.

BACKGROUND: We and others have shown previously that left ventricular (LV) contractile reserve assessed quantitatively by high-dose dobutamine stress-echocardiography (DSE) has prognostic implications in patients with dilated cardiomyopathy. PURPOSE: To assess the feasibility of semi-quantitative assessment of LV contractile reserve by differently skilled operators in patients with dilated cardiomyopathy. METHODS: High-dose DSE was performed in 63 consecutive patients, mean age 50 ± 10 years and ejection fraction (EF) 19 ± 8%. LVEF was calculated 1) using Simpson's biplane formula, and 2) semi-quantitatively (5% increments) by novice and experienced echocardiographers, and by a DSE expert. Patients were considered to have preserved LV contractile reserve if LVEF dobutamine-induced change was ≥5%. RESULTS: Twenty-seven (45.8%) patients died during the 5-year follow-up. The feasibility of the assessment was 89%, 94%, and 98% for novice and experienced readers and DSE expert, respectively. Kaplan-Meier analysis showed that LV contractile reserve assessed semi-quantitatively by DSE expert and experienced reader achieved the best prognostic separation (log rank 19.63 and 18.99, respectively, p < 0.001 for both), followed by quantitative assessment (log rank 9.76, p = 0.0018) and assessment by novice reader (log rank 8.76, p = 0.012). Areas under the curves were similar for quantitative and semi-quantitative assessment of LV contractile reserve. CONCLUSIONS: Our data indicate that semi-quantitative assessment of LV contractile reserve is feasible by differently skilled operators.

[Characteristics, outcome and predictors of one year mortality rate in patients with acute heart failure].

BACKGROUND/AIM: Acute heart failure (AHF) is one of the most common diseases in emergency medicine, associated with poor prognosis and high in-hospital and long-term mortality. The aim of this study was to investigate characteristics, outcomes and one year mortality of patients with AHF in the local population. METHODS: This prospective study consisted of 64 consecutive unselected patients treated in the Coronary Care Unit of the Emergency Centre (Clinical Center of Serbia, Belgrade) and were followed for one year after the discharge. RESULTS: Mean age of the patients was 63.6 +/- 12.6 years and 59.4% were males. Acute congestion (43.8%) and pulmonary edema (39.1%) were the most common presentations of AHF. Mean left ventricular ejection fraction (LVEF) was 39.7% +/- 9.25%, while 44.4% of the patients had LVEF > or = 50%. At discharge, 55.9% of the patients received therapy with P-blockers, 94.9% diuretics, out of which 47.7% spironolactone, 94.9% patients were given ACE-inhibitors or angiotensin receptor blockers (ARB). The 12-month all-cause mortality was 26.5%. Independent predictors of one year mortality were previous hospitalization due to heart disease, reduced LVEF, reduced fraction of shortening (FS) and a higher tricuspid velocity. CONCLUSION: One year mortality of our patients with AHF was high, similar to the known European studies. Independent predictors of one year mortality were previous hospitalization due to heart disease, reduced LVEF and LVFS and a higher tricuspid velocity.

[Are de novo acute heart failure and acutely worsened chronic heart failure two subgroups of the same syndrome?].

INTRODUCTION: Acute heart failure (AHF) is one of the most common diseases in emergency medicine, associated with poor prognosis and high in-hospital and long-term mortality. OBJECTIVE: To investigate clinical presentation of patients with de novo AHF and acute worsening of chronic heart failure (CHF) and to identify differences in blood levels of biomarkers and echocardiography findings. METHODS: This prospective study comprised 64 consecutive patients being grouped according to the onset of the disease into patients with the de novo AHF (45.3%), and patients with acute worsening of CHF (54.7%). RESULTS: Acute congestion (60%) was the most common manifestation of de novo AHF, whereas pulmonary oedema (43.1%) was the most common manifestation of acutely decompensated CHF. Patients with acutely decompensated CHF had significantly higher blood values of creatinine (147.10 vs 113.16 micromol/l; p < 0.05), urea (12.63 vs. 7.82 mmol/l; p < 0.05), BNP (1440.11 vs. 712.24 pg/ml; p < 001) and NTproBNP (9097.00 vs. 2827.70 pg/ml; p < 0.01) on admission, and lower values of M-mode left ventricular ejection fraction (LVEF) during hospitalization (49.44% vs. 42.94%; p < 0.05). The follow-up after one year revealed still significantly higher BNP (365.49 vs. 164.02 pg/ml; p < 0.05) and lower average values of both LVEF in patients with acutely worsened CHF (46.62% vs. 54.41% and 39.52% vs. 47.88%; p < 0.05). CONCLUSION: Considering differences in clinical severity on admission, echocardiography and natriuretic peptide values during hospitalization and after one year follow-up, de novo AHF and acutely worsened CHF are two different subgroups of the same syndrome.

A novel mobile transtelephonic system with synthesized 12-lead ECG.

The problem of synthesizing the standard 12-lead electrocardiogram (ECG) from the signals recorded using three special ECG leads is studied in detail. The implementation of that concept into the design of a new mobile ECG transtelephonic system is presented. The system has two separate units: a stationary diagnostic-calibration center and a mobile ECG device with integrated electrodes. The patient records by himself three special leads with the mobile ECG recorder and sends data via cellular phone to the personal computer in the diagnostic center where standard 12-lead ECG is numerically reconstructed on the base of the patient transformation matrix previously calculated into the calibration process. The experimental study shows high accuracy of the reconstructed ECG.