Comprehensive Angiography-Derived Functional Assessment of Epicardial and Microvascular Coronary Disease. Correlation With Non-invasive Myocardial Stress Imaging.

Coronary angiography (CA) is poorly correlated with non-invasive myocardial stress imaging (NSI) and myocardial ischemia is often observed in patients with unobstructed coronary arteries. Moreover, the diagnostic performance of combined epicardial and microcirculatory angiography-derived physiological assessment and its correlation with NSI remains unknown. A total of 917 coronary vessels in 319 patients who underwent both CA and NSI were included in this multicenter observational retrospective analysis. Quantitative flow ratio (QFR) and angiography-derived index of microcirculatory resistance (IMRangio) analyses were performed to estimate coronary epicardial and microcirculatory function respectively. NSI demonstrated evidence of myocardial ischemia in 76% of the cases. IMRangio (36 [22 to 50] vs 29 [21 to 41], p <0.001) was significantly higher and QFR (0.92 [0.78 to 0.99] vs 0.97 [0.91 to 0.99], p <0.001) was significantly lower in vessels subtending ischemic territories. Overall, the diagnostic accuracy of QFR was moderate (area under the curve of receiver operating characteristic [AUCROC] 0.632 [95% confidence interval [CI] 0.589 to 0.674], p <0.0001) but it was higher in patients with normal microcirculatory function (AUCROC = 0.726 [95% CI 0.669 to 0.784], p <0.0001, p Value for AUCROC comparison = 0.009). Combined QFR/IMRangio assessment provided incremental diagnostic performance compared with the evaluation of epicardial or microcirculatory districts in isolation (p Value for AUC comparison <0.0001) and it was able to identify the predominant mechanism of myocardial ischemia in 77% of the patients with positive NSI. Our study suggests the value of a combined angiography-derived assessment of epicardial and microvascular function for the definition of the predominant mechanism of myocardial ischemia in patients with suspected coronary artery disease.

Circadian assessment of heart failure using explainable deep learning and novel multi-parameter polar images.

BACKGROUND AND OBJECTIVE: Heart failure (HF) is a multi-faceted and life-threatening syndrome that affects more than 64.3 million people worldwide. Current gold-standard screening technique, echocardiography, neglects cardiovascular information regulated by the circadian rhythm and does not incorporate knowledge from patient profiles. In this study, we propose a novel multi-parameter approach to assess heart failure using heart rate variability (HRV) and patient clinical information. METHODS: In this approach, features from 24-hour HRV and clinical information were combined as a single polar image and fed to a 2D deep learning model to infer the HF condition. The edges of the polar image correspond to the timely variation of different features, each of which carries information on the function of the heart, and internal illustrates color-coded patient clinical information. RESULTS: Under a leave-one-subject-out cross-validation scheme and using 7,575 polar images from a multi-center cohort (American and Greek) of 303 coronary artery disease patients (median age: 58 years [50-65], median body mass index (BMI): 27.28 kg/m2 [24.91-29.41]), the model yielded mean values for the area under the receiver operating characteristics curve (AUC), sensitivity, specificity, normalized Matthews correlation coefficient (NMCC), and accuracy of 0.883, 90.68%, 95.19%, 0.93, and 92.62%, respectively. Moreover, interpretation of the model showed proper attention to key hourly intervals and clinical information for each HF stage. CONCLUSIONS: The proposed approach could be a powerful early HF screening tool and a supplemental circadian enhancement to echocardiography which sets the basis for next-generation personalized healthcare.

A Retrospective Observational Real-Word Analysis of the Adherence, Healthcare Resource Consumption and Costs in Patients Treated with Bisoprolol/Perindopril as Single-Pill or Free Combination.

INTRODUCTION: The present real-world analysis aims to compare the drug utilization, hospitalizations and direct healthcare costs related to the use of single-pill combination (SPC) or free-equivalent combination (FEC) of perindopril and bisoprolol (PER/BIS) in a large Italian population. METHODS: This observational retrospective analysis was based on administrative databases covering approximately 7 million subjects across Italy. All adult subjects receiving PER/BIS as SPC or FEC between January 2017-June 2020 were included. Subjects were followed for 1 year after the first prescription of PER/BIS as FEC (± 1 month) or SPC. Before comparing the SPC and FEC cohorts, propensity score matching (PSM) was applied to balance the baseline characteristics. Drug utilization was investigated as adherence (defined by the proportion of days covered, PDC) and persistence (evaluated by Kaplan-Meier curves). Hospitalizations and mean annual direct healthcare costs (due to drug prescriptions, hospitalizations and use of outpatient services) were analyzed during follow-up. RESULTS: The original cohort included 11,440 and 6521 patients taking the SPC and FEC PER/BIS combination, respectively. After PSM, two balanced SPC and FEC cohorts of 4688 patients were obtained (mean age 70 years, approximately 50% male, 24% in secondary prevention). The proportion of adherent patients (PDC ≥ 80%) was higher for those on SPC (45.5%) than those on FEC (38.6%), p < 0.001. The PER/BIS combination was discontinued by 35.8% of patients in the SPC cohort and 41.7% in the FEC cohort (p < 0.001). The SPC cohort had fewer cardiovascular (CV) hospitalizations (5.3%) than the free-combination cohort (7.4%), p < 0.001. Mean annual total healthcare costs were lower in the SPC (1999€) than in the FEC (2359€) cohort (p < 0.001). CONCLUSION: In a real-world setting, patients treated with PER/BIS SPC showed higher adherence, lower risk of drug discontinuation, reduced risk of CV hospitalization, and lower healthcare costs than those on FEC of the same drugs.

Patients with cardiovascular conditions often need to take many pills. This may result in patients not taking their pills as prescribed (i.e., low adherence) and compromise the potential benefits derived from prescription of cardiovascular protective drugs. Simplifying treatment by combining drugs into a single pill can improve adherence and, consequently, patient outcomes. In this analysis using data from real clinical practice, we explored whether using a single pill of perindopril and bisoprolol is associated with higher levels of adherence, lower proportion of patients with hospitalizations and lower economic costs than using the same drugs prescribed as free-equivalent combination in a large sample of the Italian population of approximately 7 million people. We identified two groups of patients taking single pill or free-equivalent combination of perindopril and bisoprolol (4688 patients in each cohort). Over 1-year follow-up, patients taking single pill were more likely to be adherent and were less likely to stop taking their treatment. They also had fewer cardiovascular hospitalizations with shorter hospital admission and had lower healthcare direct costs. In conclusion, simplifying treatment by combining perindopril and bisoprolol in a single pill instead of two may have a positive effect on adherence, outcomes and healthcare costs already after 1 year.

Atherosclerosis, Diabetes Mellitus, and Cancer: Common Epidemiology, Shared Mechanisms, and Future Management.

The involvement of cardiovascular disease in cancer onset and development represents a contemporary interest in basic science. It has been recognized, from the most recent research, that metabolic syndrome-related conditions, ranging from atherosclerosis to diabetes, elicit many pathways regulating lipid metabolism and lipid signaling that are also linked to the same framework of multiple potential mechanisms for inducing cancer. Otherwise, dyslipidemia and endothelial cell dysfunction in atherosclerosis may present common or even interdependent changes, similar to oncogenic molecules elevated in many forms of cancer. However, whether endothelial cell dysfunction in atherosclerotic disease provides signals that promote the pre-clinical onset and proliferation of malignant cells is an issue that requires further understanding, even though more questions are presented with every answer. Here, we highlight the molecular mechanisms that point to a causal link between lipid metabolism and glucose homeostasis in metabolic syndrome-related atherosclerotic disease with the development of cancer. The knowledge of these breakthrough mechanisms may pave the way for the application of new therapeutic targets and for implementing interventions in clinical practice.

Non-Invasive Modalities in the Assessment of Vulnerable Coronary Atherosclerotic Plaques.

Coronary atherosclerosis is a complex, multistep process that may lead to critical complications upon progression, revolving around plaque disruption through either rupture or erosion. Several high-risk features are associated with plaque vulnerability and may add incremental prognostic information. Although invasive imaging modalities such as optical coherence tomography or intravascular ultrasound are considered to be the gold standard in the assessment of vulnerable coronary atherosclerotic plaques (VCAPs), contemporary evidence suggests a potential role for non-invasive methods in this context. Biomarkers associated with deleterious pathophysiologic pathways, including inflammation and extracellular matrix degradation, have been correlated with VCAP characteristics and adverse prognosis. However, coronary computed tomography (CT) angiography has been the most extensively investigated technique, significantly correlating with invasive method-derived VCAP features. The estimation of perivascular fat attenuation as well as radiomic-based approaches represent additional concepts that may add incremental information. Cardiac magnetic resonance imaging (MRI) has also been evaluated in clinical studies, with promising results through the various image sequences that have been tested. As far as nuclear cardiology is concerned, the implementation of positron emission tomography in the VCAP assessment currently faces several limitations with the myocardial uptake of the radiotracer in cases of fluorodeoxyglucose use, as well as with motion correction. Moreover, the search for the ideal radiotracer and the most adequate combination (CT or MRI) is still ongoing. With a look to the future, the possible combination of imaging and circulating inflammatory and extracellular matrix degradation biomarkers in diagnostic and prognostic algorithms may represent the essential next step for the assessment of high-risk individuals.

Estimation of the economic burden of atrial fibrillation-related stroke in Greece.

BACKGROUND: Stroke is aleading cause of death and disability, with atrial fibrillation (AF) being among key risk factors and AF-related stroke inflicting significant burden on healthcare systems and society. The present study was undertaken for estimating the total annual socioeconomic burden of AF-related stroke in Greece and identifying the key cost contributors. RESEARCH DESIGN AND METHODS: A cost-of-illness model was developed for estimating the total annual economic burden of AF-related stroke in Greece, from asocietal perspective (year 2018). Atargeted literature review and an advisory board consisting of key experts in the management of AF and AF-related stroke were performed for collecting local resource use and epidemiological data. RESULTS: The total annual socioeconomic burden of AF-related stroke was estimated at €175million, in 2018. Direct and indirect costs accounted for 59% and 41%, respectively. Main contributors were informal care (21.1%), patients' productivity losses (19.7%) and hospitalizations (15.0%), accounting for more than half of the total costs of AF-related stroke events.Conclusion: A F-related stroke imposes asignificant socioeconomic burden in Greece. Despite results relying on estimations, it seems that ensuring efficient reallocation of resources in appropriate prevention and early intervention strategies could decrease AF-related stroke's burden but also enhance healthcare systems' efficiency. ABBREVIATIONS: AF=atrial fibrillation.

The mystery of "missing" visits in an emergency cardiology department, in the era of COVID-19.; a time-series analysis in a tertiary Greek General Hospital.

BACKGROUND: In the era of the current COVID-19 health crisis, the aim of the present study was to explore population behavior as regards the visits in the Εmergency Cardiology department (ECD) of a tertiary General Hospital that does not hospitalize SARS-CoV-2 infected patients METHODS AND RESULTS: Daily number of visits at the EDC and admissions to Cardiology Wards and Intensive Care Unit of a tertiary General Hospital, in Athens, Greece, were retrieved from hospital's database (January 1st-April 30th 2018, 2019 and 2020). A highly significant reduction in the visits at ECD of the hospital during March and April 2020 was observed as compared with January and February of the same year (p for linear trend < ·001); in particular the number of visits was 41.1% lower in March 2020 and 32.7% lower in April 2020, as compared to January 2020. As the number of confirmed COVID-19 cases throughout the country increased (i.e., from February 26th to April 2nd) the number of visits at ECD decreased (p = 0.01), whereas, the opposite was observed in the period afterwards (p = 0.01).The number of acute Myocardial infarctions (MI) cases in March 2020 was the lowest compared to the entire three year period (p < 0·001); however, the number of acute MI cases in April 2020 was doubled as compared to March 2020, but still was lower than the preceding years (p < 0·001). CONCLUSIONS: It is hard to explain the mystery of the "missing" emergency hospital visits. However, if this decline in cardiovascular disease related hospital visits is "true", it is something that needs to be rigorously studied, to learn how to keep these rates down.

Impact of single-pill combination therapy on adherence, blood pressure control, and clinical outcomes: a rapid evidence assessment of recent literature.

OBJECTIVE: The 2018 European Society of Cardiology/European Society of Hypertension Guidelines for the management of arterial hypertension raised the need for evidence to support the use of single-pill combination (SPC) therapy in preference to free-dosed therapy for hypertension. This systematic rapid evidence assessment sought to determine if initiating SPC therapy improves adherence, blood pressure (BP) control and/or cardiovascular outcomes vs. initiation of free-dose combination therapy. METHODS: Rapid evidence assessment conducted in MEDLINE, EMBASE, and Cochrane Library (1 January 2013-11 January 2019) to identify studies investigating SPC therapy for adults with hypertension. Information on adherence/persistence, BP lowering/goal attainment, and cardiovascular outcomes/events were extracted via two-phase screening process. Studies not focusing on adherence, persistence, or compliance with SPC therapy were excluded. Methodological quality was assessed using appropriate scales. RESULTS: Of 863 citations, 752 failed to meet inclusion or were duplicates. Twenty-nine studies remained following full-text screening. Just four studies (14%) were randomized controlled studies; 25 (86%) were observational. A range of SPC therapies were studied, with calcium channel blocker/angiotensin receptor blocker combinations most common (11/29 studies). Adherence and persistence were generally higher with SPC vs. free-dose combination therapy; 15 studies (54%) directly compared adherence and four (14%) compared persistence. Patients achieving BP targets ranged from 25 to 89%. Despite all studies investigating patients with hypertension only 16 (55%) reported change in BP. Few studies reported on cardiovascular outcomes. Methodological reporting was often suboptimal. CONCLUSION: Adherence and/or persistence were generally higher in patients taking antihypertensives as SPC vs. free-dose combination; however, methodological reporting was suboptimal to facilitate comparison. Specifically designed, well reported studies are required to determine if the increased adherence/persistence seen in patients on SPC regimen leads to improved BP control and/or cardiovascular outcomes.

Economic evaluation of trimetazidine in the management of chronic stable angina in Greece.

BACKGROUND: To evaluate the cost-effectiveness of trimetazidine (TMZ) as add-on therapy to standard-of-care (SoC) compared to SoC alone in patients with chronic stable angina who did not respond adequately to first line therapy with b-blockers, nitrates or calcium channel antagonists in Greece. METHODS: A Markov model with 3-month cycles and 1-year time horizon was developed to assess the comparators. The analysis was conducted from a third-party payer perspective. The clinical inputs and utility values were extracted from the published literature. Resource consumption data were obtained from local experts, using a questionnaire developed for the purpose of the study and were combined with unit cost data (in €2016) obtained from official sources. Cost effectiveness was assessed by calculating the incremental cost effectiveness ratio (ICER). Probabilistic sensitivity analysis (PSA) was performed to account for uncertainty and variation in the input parameters of the model. RESULTS: The analysis showed that the cost of TMZ plus SoC was €1755.57 versus €1751.76 of SoC alone. In terms of health outcomes, TMZ plus SoC was associated with 0.6650 QALYs versus 0.6562 QALYs for SoC alone. The incremental analysis resulted in an ICER of €430.67 per QALY gained. PSA revealed that the probability of TMZ plus SoC being cost-effective over SoC was 89 %, at a threshold of €34,000 per QALY gained. CONCLUSION: The results indicate that TMZ as add -on treatment may be a highly cost-effective option for the symptomatic treatment of patients with chronic stable angina in Greece relative to SoC alone.