Atrial cardiomyopathy is closely associated with atrial fibrillation (AF), and some patients exhibit no dysfunction at rest but demonstrate evident changes in left atrial (LA) function and LA volume during exercise. This study aimed to identify distinguishing signs during exercise stress echocardiography (ESE) among patients in sinus rhythm (SR), with and without history of paroxysmal/persistent AF (PAF). A prospective cohort of 1055 patients in SR was enrolled across 12 centers. The main study cohort was divided into two groups: the modeling group (n = 513) and the verification group (n = 542). All patients underwent ESE, which included B-lines, LA volume index (LAVi), and LA strain of the reservoir phase (LASr). Age, resting and stress LAVi and LASr, and B-lines were identified as a combination of detectors for PAF in both groups. In the entire cohort, aside from resting and stress LAVi and LASr, additional parameters differentiating PAF and non-PAF patients were the presence of systemic hypertension, exercise E/e’ > 7, worse right ventricle (RV) contraction during exercise (∆ tricuspid annular plane systolic excursion < 5 mm), a lower left ventricular contractile reserve (< 1.6), and a reduced chronotropic reserve (heart rate reserve < 1.64). The composite score, summing all 9 items, yielded a score of > 4 as the best sensitivity (79%) and specificity (65%). ESE can complement rest echocardiography in the identification of previous PAF in patients with SR through the evaluation of LA functional reservoir and volume reserve, LV chronotropic, diastolic, and systolic reserve, and RV contractile reserve. A scoring system predicting the probability of PAF. The score was computed using the cutoff values as in the illustration. The score >4 demonstrated a sensitivity of 79% and a specificity of 65% of PAF.

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BACKGROUND Regional wall motion abnormality (RWMA) is considered a sensitive and specific marker of ischemia during stress echocardiography (SE). However, ischemia is a multifaceted entity associated with either coronary artery disease (CAD) or angina with normal coronary arteries (ANOCA), a distinction difficult to make using a single sign. We aimed to evaluate the diagnostic potential of the ABCDE-SE protocol for CAD detection. METHODS From the 2016-2022 SE-2030 study data bank, we selected 3229 patients (age= 66±12 years, 2089, 65% males), with known CAD (n=1792) or ANOCA (n= 1437). All patients were studied with both ABCDE-SE protocol and with coronary angiography, within 3 months. Step A assesses RWMA; step B, B-lines/diastolic function; step C, left ventricular contractile reserve; step D, coronary flow velocity reserve (CFVR) in the left anterior descending artery; step E, heart rate reserve. RESULTS SE response ranged from score 0 (all steps normal) to score 5 (all steps abnormal) . In CAD, the rate of abnormal results was 347 for A (19.4%), 547 (30.5%) for B, 720 (40.2%) for C, 615 (34.3%) for D, and 633 (35.3%) for E step. In ANOCA, the rate of abnormal results was 81 (5.6%) for A, 429 (29.9%) for B, 432 (30.1%) for C, 354 (24.6%) for D, and 445 (31.0%) for E step. The dominant "solitary phenotype" was step B in 109 (9.1%) patients. CONCLUSION Stress-induced ischemia presents with a wide range of diagnostic phenotypes, highlighting its complex nature. Utilizing a comprehensive approach such as the advanced ABCDE score, which combines multiple markers, proves to be more valuable than relying on a single marker in isolation.

Background: Left atrial (LA) myopathy with paroxysmal and permanent atrial fibrillation (AF) is frequent in chronic coronary syndromes (CCS) but sometimes occult at rest and elicited by stress. Aim: This study sought to assess LA volume and function at rest and during stress across the spectrum of AF. Methods: In a prospective, multicenter, observational study design, we enrolled 3042 patients [age = 64 ± 12; 63.8% male] with known or suspected CCS: 2749 were in sinus rhythm (SR, Group 1); 191 in SR with a history of paroxysmal AF (Group 2); and 102 were in permanent AF (Group 3). All patients underwent stress echocardiography (SE). We measured left atrial volume index (LAVI) in all patients and LA Strain reservoir phase (LASr) in a subset of 486 patients. Results: LAVI increased from Group 1 to 3, both at rest (Group 1 = 27.6 ± 12.2, Group 2 = 31.6 ± 12.9, Group 3 = 43.3 ± 19.7 mL/m2, p < 0.001) and at peak stress (Group 1 = 26.2 ± 12.0, Group 2 = 31.2 ± 12.2, Group 3 = 43.9 ± 19.4 mL/m2, p < 0.001). LASr progressively decreased from Group 1 to 3, both at rest (Group 1 = 26.0 ± 8.5%, Group 2 = 23.2 ± 11.2%, Group 3 = 8.5 ± 6.5%, p < 0.001) and at peak stress (Group 1 = 26.9 ± 10.1, Group 2 = 23.8 ± 11.0 Group 3 = 10.7 ± 8.1%, p < 0.001). Stress B-lines (≥2) were more frequent in AF (Group 1 = 29.7% vs. Group 2 = 35.5% vs. Group 3 = 57.4%, p < 0.001). Inducible ischemia was less frequent in SR (Group 1 = 16.1% vs. Group 2 = 24.7% vs. Group 3 = 24.5%, p = 0.001). Conclusions: In CCS, rest and stress LA dilation and reservoir dysfunction are often present in paroxysmal and, more so, in permanent AF and are associated with more frequent inducible ischemia and pulmonary congestion during stress.

Alcohol drinks, especially wine, have been described since 6,000 B.C. For many years in modern medicine, wine in moderation has been considered healthy for cardiovascular prevention, i.e., recommended by nutrition committees. Some regional guidelines still recommend one to two standard drinks per day. By the very recent (January 2023), World Health Organization and Canadian Guidance on alcohol emphasize that any alcoholic drink is hazardous to the health and the safe amount is zero. The risk starts with every single drop. It was also nicely summarized in the manuscript “Alcohol-dose question and the weakest link in a chemical interplay” (Explor Cardiol. 2023;1:15–25. doi: 10.37349/ec.2023.00003) especially from the standpoint of a researcher in the cardiovascular arena. The newest recommendations are based on observational studies and their meta-analysis, therefore establishing associations, pointing out that alcohol may somewhat prevent cardiovascular diseases and diabetes type 2, but with a significant increase in non-cardiovascular morbidity and mortality, especially cancers. Previous recommendations, therefore, may be obsolete as they were based on studies where abstainers from alcoholic beverages had inherent higher risks. The current controversy with conflicting guidelines for alcoholic beverage consumption in the era of precision medicine may stimulate more fundamental investigations up to genetic ones and find the cause-effect relations. In the era of precision medicine, it may come closer to discovering the causes of cancers and many other diseases, enabling predictions of reactions to alcoholic beverages by each person, not just in the population.

The 12-lead electrocardiogram (ECG) is a first-line diagnostic tool for patients with cardiac symptoms. As observed during the COVID-19 pandemic, the ECG is essential to the initial patient evaluation. The novel KardioPal three-lead-based ECG reconstructive technology provides a potential alternative to a standard ECG, reducing the response time and cost of treatment and improving patient comfort. Our study aimed to evaluate the diagnostic accuracy of a reconstructed 12-lead ECG obtained by the KardioPal technology, comparing it with the standard 12-lead ECG, and to assess the feasibility and time required to obtain a reconstructed ECG in a real-life scenario. A prospective, nonrandomized, single-center, adjudicator-blinded trial was conducted on 102 patients during the COVID-19 pandemic at the Dedinje Cardiovascular Institute in Belgrade. The KardioPal system demonstrated a high feasibility rate (99%), with high specificity (96.3%), sensitivity (95.8%), and diagnostic accuracy (96.1%) for obtaining clinically relevant matching of reconstructed 12-lead compared to the standard 12-lead ECG recording. This novel technology provided a significant reduction in ECG acquisition time and the need for personnel and space for obtaining ECG recordings, thereby reducing the risk of viral transmission and the burden on an already overwhelmed healthcare system such as the one experienced during the COVID-19 pandemic.

Assessment of the functional significance of coronary artery stenosis using invasive measurement of fractional flow reserve (FFR) or non-hyperemic indices has been shown to be safe and effective in making clinical decisions on whether to perform percutaneous coronary intervention (PCI). Despite strong evidence from clinical trials, utilization of these techniques is still relatively low worldwide. This may be to some extent attributed to factors that are inherent to invasive measurements like prolongation of the procedure, side effects of drugs that induce hyperemia, additional steps that the operator should perform, the possibility to damage the vessel with the wire, and additional costs. During the last few years, there was a growing interest in the non-invasive assessment of coronary artery lesions, which may provide interventionalist with important physiological information regarding lesion severity and overcome some of the limitations. Several dedicated software solutions are available on the market that could provide an estimation of FFR using 3D reconstruction of the interrogated vessel derived from two separated angiographic projections taken during diagnostic coronary angiography. Furthermore, some of them use data about aortic pressure and frame count to more accurately calculate pressure drop (and FFR). The ideal non-invasive system should be integrated into the workflow of the cath lab and performed online (during the diagnostic procedure), thereby not prolonging procedural time significantly, and giving the operator additional information like vessel size, lesion length, and possible post-PCI FFR value. Following the development of these technologies, they were all evaluated in clinical trials where good correlation and agreement with invasive FFR (considered the gold standard) were demonstrated. Currently, only one trial (FAVOR III China) with clinical outcomes was completed and demonstrated that QFR-guided PCI may provide better results at 1-year follow-up as compared to the angiography-guided approach. We are awaiting the results of a few other trials with clinical outcomes that test the performance of these indices in guiding PCI against either FFR or angiography-based approach, in various clinical settings. Herein we will present an overview of the currently available data, a critical review of the major clinical trials, and further directions of development for the five most widely available non-invasive indices: QFR, vFFR, FFRangio, caFFR, and AccuFFRangio.

Type of funding sources: None. Obesity and overweight play a key role in the development of cardiovascular disease or myocardial ischemia, particularly today, as does their relationship to traditional and non-traditional risk factors. Despite, diet and weight management are grossly under-met per desired body mass index (BMI) threshold goals among very high-risk patients with established atherosclerotic cardiovascular disease (ASCVD). Thus, we aimed to investigate the presence of overweight and obesity in patients with established atherosclerotic cardiovascular disease who were admitted to our center. Patients and methods: Out of 790 patients admitted in our center between May and October 2021, we analyzed 341 patients who underwent isolated coronary artery by-pass surgery. Risk factors were noted as well as previous drug therapy, previous COVID 19 infection and vaccination. Anthropometric data were measured and BMI was determined. Obesity was defined as a BMI >_30 kg/m2 and overweight as a BMI between 25 and 30 kg/m2 . Patients with a BMI >_40 kg/m2 were considered morbidly obese. Early cardiac rehabilitation (phase 1) was performed by using personalized approach in all patients. Out of 341 patients (64.68±7.91 years of age), 275 were males (80.6%). The total of 97 (28.44%) had previous myocardial infarction. Blood pressure was well controlled. Majority of the patients reached the step 2 goals according to EAPC Guidelines on prevention (130.7±6.45/75.27±6.54mmHg), and were adherent to prescribed drugs. Mean heart rate was 65±5.65/minute. Only 27% of females and 22% of males had normal weight with BMI between 18.5 and 24.9.kg/m2. The mean BMI was 27.76 kg/m2. 50% of males and females were overweight. Obesity was noted in 23% of females and 27% of males (0.7% morbidly obese. Early cardiac rehabilitation was performed in all patients and they were all referred to participate the phase 2 programs. Diet and body weight reduction in overweight and obese ASCVD patients should continue to be a priority given the impact on cardiovascular risk. There is a potential for optimizing management of overweight and obesity in patients. In addition to a better risk factor profile, weight loss also leads to a better quality of life. Cardiovascular prevention and rehabilitation programs should include weight loss intervention. Different forms of self-support and use of digital health might be used as a specific component of a comprehensive intervention to reduce total cardiovascular risk, extend life expectancy, and improve quality of life.

Background The COMET-CTO trial was a randomized prospective study that assessed long-term follow-up in patients with chronic total occlusion (CTO) in coronary arteries treated with percutaneous coronary intervention (PCI) or with optimal medical therapy (OMT). During the 9-month follow-up, the incidence of major adverse cardiac events (MACE) did not differ between the two groups; no death or myocardial infarction (MI) was observed. There was a significant difference in quality of life (QoL), assessed by the Seattle Angina Questionnaire (SAQ), in favor of the PCI group. Here we report long-term follow-up results (56 ± 12 months). Methods Between October 2015 and May 2017, a total of 100 patients with CTO were randomized into two groups of 50 patients: PCI CTO or OMT group. The primary endpoint of the current study was the incidence of MACE defined as cardiac death, MI, and revascularization [PCI or coronary artery bypass graft (CABG)]. As the secondary exploratory outcome, we analyzed all the cause-mortality rate. Results Out of 100 randomized patients, 92 were available for long-term follow-up (44 in the PCI group and 48 in the OMT group). The incidence of MACE did not differ significantly between the two groups (p = 0.363). Individual components of MACE were distributed, respectively: cardiac death (OMT vs. PCI group, 6 vs. 3, p = 0.489), MI (OMT vs. PCI group, 1 vs. 0, p = 1), and revascularization (PCI: OMT vs. PCI group, 2 vs. 2, p = 1; CABG: OMT vs. PCI group, 1 vs. 1, p = 1). There was no significant difference between the two groups regarding the individual component of MACE. Six patients died from non-cardiac causes [five deaths were reported in the OMT group and one death in the PCI group (p = 0.206)]. Kaplan-Meier survival curves for MACE did not differ significantly between the study groups (log-rank 0.804, p = 0.370). Regarding the secondary exploratory outcome, a total of 15 patients died at 56 ± 12 months (11 in the OMT and 4 in the PCI group) (p = 0.093). The Kaplan-Meier survival curves for all-cause mortality rates did not differ significantly between the two groups (log rank 3.404, p = 0.065). There were no statistically significant differences between OMT and PCI groups in all five SAQ domains. There was a significant improvement in three SAQ domains in the PCI group: PL (p < 0.001), AF (p = 0.007), and QoL (p = 0.001). Conclusion After 56 ± 12 months of follow-up, the incidence of MACE, as well as QoL measured by SAQ, did not differ significantly between the PCI and OMT groups.

Introduction: Landmark ISCHEMIA (ISCH) trial provided unique information, but the generalizability of its results into myocardial revascularization guidelines and practice has been met by unprecedented debate. Hypothesis: We aimed to compare the 5 year all-cause mortality (5y Mt) in our ISCH trial like patients (pts) with results in ISCH. Methods: After applying ISCH study inclusion/exclusion criteria we identified 854 pts from our prospective database of 2455 consecutive pts who had the first isolated CABG in 2012-2015 with complex CAD with 100% follow up (F-up) of 5y Mt. Results: Comparative characteristics of ISCH like and actual ISCH pts are presented in Table 1. Аll our pts underwent CABG, contrary to ISCH where CABG and PCI were used in 538 and 1532 pts, consecutively. Although in ISCH pts had high diversity of ethnicity, were older, had more DM2 (but less insulin dependent), and had previous PCI or CABG in 25%, our pts were strikingly sicker (lower LVEF, higher proportion of 3VD and proximal LAD, higher NYHA as well as more comorbidities) 5-year mortality was 8.9% compared to 9% in the Invasive arm of ISCH. Of note 48 h mortality from MI type 5 (post CABG) was 1.67% in ISCH, and 30-day Mt in our study was 1.30%, with complete revascularization in 95%. As expected by the disease severity treated by CABG early Mt was higher in our than ISCH pts (Figure 1). Conclusion: The present study findings outline that translation of results from the ISCHEMIA trial with practice-changing implications into recommendations for a local Heart Team discussion to advise the best treatment decision for patients with more complex forms of CAD is uncertain and requires further research activities.

Metabolic syndrome (Met Sy) as a highly debatable cluster of traditional risk factors is known to promote cardiometabolic-related morbidity and mortality, but its precise mechanisms remain to be determined. We sought to determine influence of MetSy on heart failure (HF) morbidity and mortality in the Seven Countries' Study as one of the oldest epidemiological studies. The Seven Countries Study encompassed 12,763 participants from 3 continents who were all healthy men of over 40 years at baseline and who underwent regular check ups every 5 years throughout over a 4 decades' span. Morbidity and mortality was adjudicated according to valid ICD and LPH coding. Using the IDF definition of the Metabolic Syndrome, 9,09% of participants were identified (Figure 1). HF was confirmed in 220 patients (16.4% alive at 40y follow up visit), while 8.2% died of HF as well in the same time-frame (Tables 1 & 2). Presence of MetSy has been shown to significantly influence HF mortality (Figures 2) with lowest survival of 22% for 300 months of follow up for patients with both MetSy and HF (Log rank test=4.405, p<0.0001). Metabolic syndrome treatment remains in the realm of risk factors' control that now we know influence both ischemic heart disease and heart failure of other origins. Historically, just emerging biomarkers' and targeted imaging weren't available to determine such at the time of HF diagnosis. Also, the sample consisted of men only, mainly Caucasian and a modest proportion of Asian and African-American now known to carry ethnic-specific burden of cardiovascular disease. All of the above, emphasizes the importance of more diversity, equity and inclusion-dedicated long term both observational, as well as interventional research. Type of funding sources: None.

Background The uneven lipid-lowering statin effects and statin intolerance raise interest regarding the involvement of coadministration of statins and dietary supplements. This study aimed to evaluate the effects of octacosanol supplementation on markers of redox status in cardiovascular patients on chronic atorvastatin therapy. Methods A double-blind, randomized, placebo-controlled, single-centre study was conducted. Redox status homeostasis parameters [i.e., advanced oxidation protein products (AOPP), pro-oxidant-antioxidant balance (PAB), total oxidant status (TOS), total antioxidant status (TAS), superoxide dismutase activity (SOD), total protein sulfhydryl (SHgroups), and paraoxonase 1 (PO N 1) activity] were assessed in 81 patients. According to favorable changes in lipid profile, patients were classified into two groups: responders (n = 35) and non-responders (n = 46), and followed for 13 weeks. A principal component analysis (PCA) was applied to explore the effect of octacosanol supplementation and the relationship between investigated parameters as predictors of responders' and non-responders' status. Results Significant decrease in Oxy-score value was found at the endpoint compared to baseline in responders' group (21.0 (13.4-25.5) versus 15.1 (12.4-18.0); P < 0.01). PCA analysis extracted 4 significant factors in the both groups, whereas extracted factors containing "octacosanol status" variable explained 14.7% and 11.5% of the variance in responders' and non-responders' subgroups, respectively. Conclusions Octacosanol supplementation leads to an improvement of lipid profile and markers of redox status in responders' group. New studies are needed to validate our results in order to find the best approach for personalized supplementation as a useful adjunct to standard statin therapy.

Evidence-based Clinical Guidelines (CGs) for Good Clinical Practice (GCP) have emerged to synthesize and systematize a wealth of knowledge from scientific journals that health professionals have been unable to follow. Today, the COVID 19 pandemic requires them more than ever. CGs are defined as a set of systematized claims, based on a systematic analysis of scientific evidence, that point to the performance of GCP; contain an assessment of the usefulness and harmfulness of various diagnostic and therapeutic options. "The Good": CG is necessary for health professionals, patients and society, because the knowledge gained in studies is insufficient to perform GCP in further practice. "The Bad": The shortcomings of the CG stem from; (a) there are still many unknowns in medicine, as funding for scientific research is inadequate; (b) the disunity of different institutions that make recommendations at the global, even local level results in different guidelines, although they are based on identical scientific papers as evidence; (c) most clinical scientific studies exclude groups of patients that make up a significant population in everyday practice and the guidelines more or less (do not) apply to them; (d) the impossibility of implementing the CG, because they are not backed by state regulatory bodies and / or the economy cannot follow them. "The Ugly": (a) the ambition of a large number of practitioners and researchers to be among the authors of the guidelines, although many do not have competence for the subject matter; (b) industry (equipment, drugs, supplements) most often funds scientific research and the interdependence of industry and the "dependence" of the authors of guidelines is often intertwined; and (c) publishing (un) intentionally falsified study results which then serve to "support" some guidelines. often in (un) intentional alliance with the editors of the world's elite medical journals.