Implementation of Microcirculation Examination in Clinical Practice-Insights from the Nationwide POL-MKW Registry.

Background and Objectives: The assessment of coronary microcirculation may facilitate risk stratification and treatment adjustment. The aim of this study was to evaluate patients' clinical presentation and treatment following coronary microcirculation assessment, as well as factors associated with an abnormal coronary flow reserve (CFR) and index of microcirculatory resistance (IMR) values. Materials and Results: This retrospective analysis included 223 patients gathered from the national registry of invasive coronary microvascular testing collected between 2018 and 2023. Results: The frequency of coronary microcirculatory assessments in Poland has steadily increased since 2018. Patients with impaired IMR (≥25) were less burdened with comorbidities. Patients with normal IMR underwent revascularisation attempts more frequently (11.9% vs. 29.8%, p = 0.003). After microcirculation testing, calcium channel blockers (CCBs) and angiotensin-converting enzyme inhibitors were added more often for patients with IMR and CFR abnormalities, respectively, as compared to control groups. Moreover, patients with coronary microvascular dysfunction (CMD, defined as CFR and/or IMR abnormality), regardless of treatment choice following microcirculation assessment, were provided with trimetazidine (23.2%) and dihydropyridine CCBs (26.4%) more frequently than those without CMD who were treated conservatively (6.8%) and by revascularisation (4.2% with p = 0.002 and 0% with p < 0.001, respectively). Multivariable analysis revealed no association between angina symptoms and IMR or CFR impairment. Conclusions: The frequency of coronary microcirculatory assessments in Poland has steadily increased. Angina symptoms were not associated with either IMR or CFR impairment. After microcirculation assessment, patients with impaired microcirculation, expressed as either low CFR, high IMR or both, received additional pharmacotherapy treatment more often.

Patient satisfaction survey of the "Healthy Heart" pharmaceutical care service - evaluation of pharmacy labelling with pharmaceutical pictograms.

INTRODUCTION: Low adherence is a major challenge in healthcare worldwide, being particularly dangerous for patients with chronic diseases, such as cardiovascular diseases and heart failure, where strict adherence is essential. Non-adherence is observed in almost half of patients, and the consequences encompass a lack of therapeutic effects, health deterioration, decreased quality of life, and even death. For cardiovascular patients, the great importance of health education and pharmaceutical education can be provided within pharmaceutical care in community pharmacies. Therefore, our study aimed at evaluating the level of satisfaction with the "Healthy Heart" pharmaceutical service, in which patients received pictograms with dosage information affixed to their medication. MATERIAL AND METHODS: The study was designed for patients who had been prescribed an antiplatelet medication for the first time. The patients were recruited by 577 pharmacies that took part in the study after completing a special course. Ultimately, 1590 patients were enrolled in the study. The project ran from November 2019 to January 2022. RESULTS: Most of patients had a positive attitude to the "Healthy Heart" pharmaceutical service. More than 85% of the respondents were of the opinion that the pictograms facilitated the use of the medication, and 81.7% of the respondents stated that the system of labels helped in adherence. Over 66% of the respondents thought that such labels should be included in pharmacy services, and 77.92% of the participants reported that this system of labelling medications should be offered through all pharmacies. CONCLUSIONS: Pharmaceutical labels in the pharmacists' everyday practice can largely improve patient adherence. These efforts, provided as part of their pharmaceutical services, can have a huge influence on optimisation of patient health outcomes.

Harnessing the parallax for better spatial awareness.

Despite easy access to imaging diagnostic procedures and an abundance of spatial data, most cardiac interventions are still performed under two-dimensional fluoroscopy. Incorporating anatomical data from scans into procedures plans has the potential to improve the swiftness and outcomes of percutaneous cardiac interventions. Therefore, procedure planning based on the specific anatomy is becoming a new standard of excellence in interventional cardiology. Still, we often tend to disregard specific spatial relations and the actual direction of catheter tip movement inside the body, relying on a try and error approach. The precise spatial orientation of instruments and prosthetic devices is crucial, especially during structural heart interventions. Here, we present how deliberate movements of objects under fluoroscopy can reveal the spatial orientation of catheters and other devices. We also propose a novel "two-point rule" for identifying three-dimensional relations between points in space. Understanding and applying this rule might substantially increase the spatial awareness of operators performing cardiovascular interventions. Although the concept is pretty simple, using it "live" during interventional cardiology procedures requires thorough understanding and practice. We propose the "two-point rule" as a crucial rule to develop expertise in spatial orientation under fluoroscopy and ensure high-quality outcomes.

Role of copeptin in diagnosis and outcome prediction in patients with heart failure: a systematic review and meta-analysis.

BACKGROUND/CONTEXT: Heart failure (HF) is a heterogeneous condition characterized by increased morbidity and mortality. OBJECTIVE: This systematic review and meta-analysis of 19 studies was conducted to evaluate the role of copeptin in diagnosis and outcome prediction in HF patients. MATERIALS AND METHODS: A systematic literature search for clinical trials reporting copeptin levels in HF patients was performed using EMBASE, PubMed, Cochrane Register of Controlled Trials, and Google Scholar. Articles from databases published by 2 January 2022, that met the selection criteria were retrieved and reviewed. The random effects model was used for analyses. RESULTS: Pooled analysis found higher mean copeptin levels in HF vs. non-HF populations (43.6 ± 46.4 vs. 21.4 ± 21.4; MD= 20.48; 95% CI: 9.22 to 31.74; p < 0.001). Pooled analysis of copeptin concentrations stratified by ejection fraction showed higher concentrations in HFrEF vs. HFpEF (17.4 ± 7.1 vs. 10.1 ± 5.5; MD= -4.69; 95% CI: -7.58 to -1.81; p = 0.001). Copeptin level was higher in patients with mortality/acute HF-related hospitalization vs. stable patients (31.3 ± 23.7 vs. 20.4 ± 12.8; MD= -13.06; 95% CI: -25.28 to -0.84; p = 0.04). Higher copeptin concentrations were associated with mortality and observed in all follow-up periods (p < 0.05). CONCLUSIONS: The present meta-analysis showed that elevated copeptin plasma concentrations observed in HF patients are associated with an increased risk of all-cause mortality, thus copeptin may serve as predictor of outcome in HF.

Cardiac mortality in patients randomised to elective coronary revascularisation plus medical therapy or medical therapy alone: a systematic review and meta-analysis.

AIMS: The value of elective coronary revascularisation plus medical therapy over medical therapy alone in managing stable patients with coronary artery disease is debated. We reviewed all trials comparing the two strategies in this population. METHODS AND RESULTS: From inception through November 2020, MEDLINE, EMBASE, Google Scholar, and other databases were searched for randomised trials comparing revascularisation against medical therapy alone in clinically stable coronary artery disease patients. Treatment effects were measured by rate ratios (RRs) with 95% confidence intervals, using random-effects models. Cardiac mortality was the pre-specified primary endpoint. Spontaneous myocardial infarction (MI) and its association with cardiac mortality were secondary endpoints. Further endpoints included all-cause mortality, any MI, and stroke. Longest follow-up data were abstracted. The study is registered with PROSPERO (CRD42021225598). Twenty-five trials involving 19 806 patients (10 023 randomised to revascularisation plus medical therapy and 9783 to medical therapy alone) were included. Compared with medical therapy alone, revascularisation yielded a lower risk of cardiac death [RR 0.79 (0.67-0.93), P < 0.01] and spontaneous MI [RR 0.74 (0.64-0.86), P < 0.01]. By meta-regression, the cardiac death risk reduction after revascularisation, compared with medical therapy alone, was linearly associated with follow-up duration [RR per 4-year follow-up: 0.81 (0.69-0.96), P = 0.008], spontaneous MI absolute difference (P = 0.01) and percentage of multivessel disease at baseline (P = 0.004). Trial sequential and sensitivity analyses confirmed the reliability of the cardiac mortality findings. All-cause mortality [0.94 (0.87-1.01), P = 0.11], any MI (P = 0.14), and stroke risk (P = 0.30) did not differ significantly between strategies. CONCLUSION: In stable coronary artery disease patients, randomisation to elective coronary revascularisation plus medical therapy led to reduced cardiac mortality compared with medical therapy alone. The cardiac survival benefit after revascularisation improved with longer follow-up times and was associated with fewer spontaneous MIs.

Intraventricular Thrombus Formation and Embolism in Takotsubo Syndrome: Insights From the International Takotsubo Registry.

OBJECTIVE: Takotsubo syndrome (TTS) is characterized by acute left ventricular dysfunction, which can contribute to intraventricular thrombus and embolism. Still, prevalence and clinical impact of thrombus formation and embolic events on outcome of TTS patients remain unclear. This study aimed to investigate clinical features and outcomes of patients with and without intraventricular thrombus or embolism. Additionally, factors associated with thrombus formation or embolism, as well as predictors for mortality, were identified. Approach and Results: TTS patients enrolled in the International Takotsubo Registry at 28 centers in Australia, Europe, and the United States were dichotomized according to the occurrence/absence of intraventricular thrombus or embolism. Patients with intraventricular thrombus or embolism were defined as the ThrombEmb group. Of 1676 TTS patients, 56 (3.3%) patients developed intraventricular thrombus and/or embolism following TTS diagnosis (median time interval, 2.0 days [range, 0-38 days]). Patients in the ThrombEmb group had a different clinical profile including lower left ventricular ejection fraction, higher prevalence of the apical type, elevated levels of troponin and inflammatory markers, and higher prevalence of vascular disease. In a Firth bias-reduced penalized-likelihood logistic regression model apical type, left ventricular ejection fraction ≤30%, previous vascular disease, and a white blood cell count on admission >10×103 cells/µL emerged as independent predictors for thrombus formation or embolism. CONCLUSIONS: Intraventricular thrombus or embolism occur in 3.3% of patients in the acute phase of TTS. A simple risk score including clinical parameters associated with intraventricular thrombus formation or embolism identifies patients at increased risk. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifier: NCT01947621.

Coexistence and outcome of coronary artery disease in Takotsubo syndrome.

AIMS: Takotsubo syndrome (TTS) is an acute heart failure syndrome, which shares many features with acute coronary syndrome (ACS). Although TTS was initially described with angiographically normal coronary arteries, smaller studies recently indicated a potential coexistence of coronary artery disease (CAD) in TTS patients. This study aimed to determine the coexistence, features, and prognostic role of CAD in a large cohort of patients with TTS. METHODS AND RESULTS: Coronary anatomy and CAD were studied in patients diagnosed with TTS. Inclusion criteria were compliance with the International Takotsubo Diagnostic Criteria for TTS, and availability of original coronary angiographies with ventriculography performed during the acute phase. Exclusion criteria were missing views, poor quality of angiography loops, and angiography without ventriculography. A total of 1016 TTS patients were studied. Of those, 23.0% had obstructive CAD, 41.2% had non-obstructive CAD, and 35.7% had angiographically normal coronary arteries. A total of 47 patients (4.6%) underwent percutaneous coronary intervention, and 3 patients had acute and 8 had chronic coronary artery occlusion concomitant with TTS, respectively. The presence of CAD was associated with increased incidence of shock, ventilation, and death from any cause. After adjusting for confounders, the presence of obstructive CAD was associated with mortality at 30 days. Takotsubo syndrome patients with obstructive CAD were at comparable risk for shock and death and nearly at twice the risk for ventilation compared to an age- and sex-matched ACS cohort. CONCLUSIONS: Coronary artery disease frequently coexists in TTS patients, presents with the whole spectrum of coronary pathology including acute coronary occlusion, and is associated with adverse outcome. TRIAL REGISTRATION: ClinicalTrials.gov number: NCT01947621.

Cardiac arrest in takotsubo syndrome: results from the InterTAK Registry.

AIMS: We aimed to evaluate the frequency, clinical features, and prognostic implications of cardiac arrest (CA) in takotsubo syndrome (TTS). METHODS AND RESULTS: We reviewed the records of patients with CA and known heart rhythm from the International Takotsubo Registry. The main outcomes were 60-day and 5-year mortality. In addition, predictors of mortality and predictors of CA during the acute TTS phase were assessed. Of 2098 patients, 103 patients with CA and known heart rhythm during CA were included. Compared with patients without CA, CA patients were more likely to be younger, male, and have apical TTS, atrial fibrillation (AF), neurologic comorbidities, physical triggers, and longer corrected QT-interval and lower left ventricular ejection fraction on admission. In all, 57.1% of patients with CA at admission had ventricular fibrillation/tachycardia, while 73.7% of patients with CA in the acute phase had asystole/pulseless electrical activity. Patients with CA showed higher 60-day (40.3% vs. 4.0%, P < 0.001) and 5-year mortality (68.9% vs. 16.7%, P < 0.001) than patients without CA. T-wave inversion and intracranial haemorrhage were independently associated with higher 60-day mortality after CA, whereas female gender was associated with lower 60-day mortality. In the acute phase, CA occurred less frequently in females and more frequently in patients with AF, ST-segment elevation, and higher C-reactive protein on admission. CONCLUSIONS: Cardiac arrest is relatively frequent in TTS and is associated with higher short- and long-term mortality. Clinical and electrocardiographic parameters independently predicted mortality after CA.

Role of P2Y Receptors in Platelet Extracellular Vesicle Release.

Platelet extracellular vesicles (PEVs) are potential new biomarkers of platelet activation which may allow us to predict and/or diagnose developing coronary thrombosis before myocardial necrosis occurs. The P2Y1 and P2Y12 receptors play a key role in platelet activation and aggregation. Whereas the P2Y1 antagonists are at the preclinical stage, at present, the P2Y12 antagonists are the most effective treatment strategy to prevent stent thrombosis after percutaneous coronary intervention. Despite an increasing number of publications on PEVs, the mechanisms underlying their formation, including the role of purinergic receptors in this process, remain an active research field. Here, we outline the clinical relevance of PEVs in cardiovascular disease, summarize the role and downstream signalling of P2Y receptors in platelet activation, and discuss the available evidence regarding their role in PEV formation.

Community pharmacy during the COVID-19 pandemic: a cross-sectional study.

INTRODUCTION: The COVID-19 pandemic has proved that community pharmacies play a pivotal role in providing medicines, information and safety measures to prevent the spread of SARS-CoV-2. PURPOSE: The study aimed to get to know opinions of pharmacy staff and owners on the functioning of the community pharmacy during the outbreak of the COVID-19 pandemic. MATERIALS AND METHODS: To collect opinions about functioning of the community pharmacy during the pandemic, we conducted cross-sectional study among pharmacy staff and owners of pharmacies. RESULTS: The study group included 456 respondents mostly associated with independent pharmacies (55.7%), from cities less than 100,000 inhabitants (38.8%). The number of patients as well as filled prescriptions increased during the pandemic. Respondents provided patients with advice on cold (81.6%), sore throat (77.0%) and acherelated complaints (68.6%). Most of participants (64.5%) declared that they informed patients about COVID-19. The safety measures in community pharmacies included: a safety regulations poster during the pandemic (97.1%), handwashing in accordance with recommended guidelines (96.3%) and using protective gloves by the pharmacy staff (89.9%). According to 60.7% of participants, the community pharmacy was properly prepared for the pandemic by the owner, however, respondents from independent pharmacies indicate this more frequently (p=0.0001). CONCLUSIONS: Respondents are aware of the role of community pharmacies in the healthcare system during the pandemic, nevertheless, more attention needs to be paid by public authorities and governmental institutions to patient safety in the community pharmacy.

Safety and efficacy of self-apposing Stentys drug-eluting stent in left main coronary artery PCI: Multicentre LM-STENTYS registry.

BACKGROUND: There is a paucity of data on left main (LM) percutaneous coronary intervention (PCI) therapy with dedicated DES platforms. The LM-STENTYS is a multicenter registry aimed at evaluating clinical outcome after PCI of LM performed with a self-apposing Stentys DES implantation. METHODS: The registry consists of 175 consecutive patients treated with Stentys DES implanted to LM. The primary endpoint was the composite of major adverse cardiac and cerebral events (MACCE) defined as cardiac death, myocardial infarction (MI), target lesion revascularization (TLR), and stroke assessed after 1 year. The secondary endpoint was stent thrombosis (ST) at 1 year. RESULTS: The median age was 69 years (IQR, 62-78 years). Acute coronary syndrome (ACS) was the presenting diagnosis in 117 (66.9%) patients [74 (63.2%) unstable angina, 31 (26.5%) NSTEMI, 12 (10.3%) STEMI] and stable angina (SA) was present in 58 (33.1%) patients. The median SYNTAX score was 23.0 (IQR, 18.7-32.2) in the SA group and 25.0 (IQR, 20.0-30.7) in the ACS group. During 1-year follow-up in the SA group two (3.4%) MACCE occurred, both of them were cardiac deaths. In ACS patients there were 19 (16.2%) MACCE [9 (7.7%) cardiac deaths, 11 (9.4%) MIs, 11(9.4%) TLR, 1(0.9%) stroke]. Altogether, three (1.7%) cases of acute ST were noted, all of them in ACS subset. CONCLUSION: LM PCI using self-apposing Stentys DES showed favorable clinical outcomes at 1-year in patients with SA. Events of ST in the ACS group warrant further research.

Clinical Features and Outcomes of Takotsubo (Stress) Cardiomyopathy.

BACKGROUND: The natural history, management, and outcome of takotsubo (stress) cardiomyopathy are incompletely understood. METHODS: The International Takotsubo Registry, a consortium of 26 centers in Europe and the United States, was established to investigate clinical features, prognostic predictors, and outcome of takotsubo cardiomyopathy. Patients were compared with age- and sex-matched patients who had an acute coronary syndrome. RESULTS: Of 1750 patients with takotsubo cardiomyopathy, 89.8% were women (mean age, 66.8 years). Emotional triggers were not as common as physical triggers (27.7% vs. 36.0%), and 28.5% of patients had no evident trigger. Among patients with takotsubo cardiomyopathy, as compared with an acute coronary syndrome, rates of neurologic or psychiatric disorders were higher (55.8% vs. 25.7%) and the mean left ventricular ejection fraction was markedly lower (40.7±11.2% vs. 51.5±12.3%) (P<0.001 for both comparisons). Rates of severe in-hospital complications including shock and death were similar in the two groups (P=0.93). Physical triggers, acute neurologic or psychiatric diseases, high troponin levels, and a low ejection fraction on admission were independent predictors for in-hospital complications. During long-term follow-up, the rate of major adverse cardiac and cerebrovascular events was 9.9% per patient-year, and the rate of death was 5.6% per patient-year. CONCLUSIONS: Patients with takotsubo cardiomyopathy had a higher prevalence of neurologic or psychiatric disorders than did those with an acute coronary syndrome. This condition represents an acute heart failure syndrome with substantial morbidity and mortality. (Funded by the Mach-Gaensslen Foundation and others; ClinicalTrials.gov number, NCT01947621.).

Increased Proangiogenic Activity of Mobilized CD34+ Progenitor Cells of Patients With Acute ST-Segment-Elevation Myocardial Infarction: Role of Differential MicroRNA-378 Expression.

OBJECTIVE: Proangiogenic effects of mobilized bone marrow-derived stem/progenitor cells are essential for cardiac repair after myocardial infarction. MicroRNAs (miRNA/miR) are key regulators of angiogenesis. We investigated the differential regulation of angio-miRs, that is, miRNAs regulating neovascularization, in mobilized CD34+ progenitor cells obtained from patients with an acute ST-segment-elevation myocardial infarction (STEMI) as compared with those with stable coronary artery disease or healthy subjects. APPROACH AND RESULTS: CD34+ progenitor cells were isolated from patients with STEMI (on day 0 and day 5), stable coronary artery disease, and healthy subjects (n=27). CD34+ progenitor cells of patients with STEMI exhibited increased proangiogenic activity as compared with CD34+ cells from the other groups. Using a polymerase chain reaction-based miRNA-array and real-time polymerase chain reaction validation, we identified a profound upregulation of 2 known angio-miRs, that are, miR-378 and let-7b, in CD34+ cells of patients with STEMI. Especially, we demonstrate that miR-378 is a critical regulator of the proangiogenic capacity of CD34+ progenitor cells and its stimulatory effects on endothelial cells in vitro and in vivo, whereas let-7b upregulation in CD34+ cells failed to proof its effect on endothelial cells in vivo. CONCLUSIONS: The present study demonstrates a significant upregulation of the angio-miRs miR-378 and let-7b in mobilized CD34+ progenitor cells of patients with STEMI. The increased proangiogenic activity of these cells in patients with STEMI and the observation that in particular miR-378 regulates the angiogenic capacity of CD34+ progenitor cells in vivo suggest that this unique miRNA expression pattern represents a novel endogenous repair mechanism activated in acute myocardial infarction.

Profiling and validation of circulating microRNAs for cardiovascular events in patients presenting with ST-segment elevation myocardial infarction.

AIMS: MicroRNAs (miRNA) are important non-coding modulators controlling patterns of gene expression. However, profiling and validation of circulating miRNA levels related to adverse cardiovascular outcome has not been performed in patients with an acute coronary syndrome (ACS). METHODS AND RESULTS: In a multicentre, prospective ACS cohort, 1002 out of 2168 patients presented with ST-segment elevation myocardial infarction (STEMI). Sixty-three STEMI patients experienced an adjudicated major cardiovascular event (MACE, defined as cardiac death or recurrent myocardial infarction) within 1 year of follow-up. From a miRNA profiling in a matched derivation case-control cohort, 14 miRNAs were selected for validation. Comparing 63 cases vs. 126 controls, 3 miRNAs were significantly differentially abundant. In patients with MACE, miR-26b-5p levels (P = 0.038) were decreased, whereas miR-320a (P = 0.047) and miR-660-5p (P = 0.01) levels were increased. MiR-26b-5p has been suggested to prevent adverse cardiomyocyte hypertrophy, whereas miR-320a promotes cardiomyocyte death and apoptosis, and miR-660-5p has been related to active platelet production. This suggests that miR-26b-5p, miR-320a, and miR-660-5p may reflect alterations of different pathophysiological pathways involved in clinical outcome after ACS. Consistently, these three miRNAs reliably discriminated cases from controls [area under the receiver-operating characteristic curve (AUC) in age- and sex-adjusted Cox regression for miR-26b-5p = 0.707, miR-660-5p = 0.683, and miR-320a =0.672]. Combination of the three miRNAs further increased AUC to 0.718. Importantly, addition of the three miRNAs to both, the Global Registry of Acute Coronary Events (GRACE) score and a clinical model increased AUC from 0.679 to 0.720 and 0.722 to 0.732, respectively, with a net reclassification improvement of 0.20 in both cases. CONCLUSION: This is the first study performing profiling and validation of miRNAs that are associated with adverse cardiovascular outcome in patients with STEMI. MiR-26b-5p, miR-320a, and miR-660-5p discriminated for MACE and increased risk prediction when added to the GRACE score and a clinical model. These findings suggest that the release of specific miRNAs into circulation may reflect the activation of molecular pathways that impact on clinical outcome after STEMI.