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(1) Background: Acute ST-segment elevation myocardial infarction (STEMI) remains one of the main morbidity and mortality contributors worldwide. Its main treatment, primary percutaneous coronary intervention (pPCI), can only be performed with a high anticoagulation regimen, usually with heparin. There is still not enough evidence regarding the timing of heparin administration. (2) Methods: We conducted a multicenter observational study of 614 consecutive STEMI patients treated between 2017 and 2019. We split the population in two groups: one that received heparin at the first medical contact, as early as possible, and the second group that received heparin at the PCI capable center or in the cath lab. (3) Results: There was a significantly higher rate of infarct-related artery (IRA) patency at the time of the coronary angiogram in the pre-transfer heparin group than in the on-site heparin group, 44.7% vs. 37.3%, p = 0.042. Also, the early heparin group received shorter and wider stents. There was no difference in bleeding rates or in the in-hospital and two-year mortality rates. (4) Conclusions: Early administration of heparin leads to a higher rate of reperfusion in the IRA, before pPCI, with significant related benefits, such as better stent implantation parameters, without increased bleeding rates. [ABSTRACT FROM AUTHOR]

Atrial fibrillation (AFib) is characterized by a complex genetic component. We aimed to investigate the association between variations in genes related to cardiac ion handling and AFib in a cohort of Romanian patients with hypertrophic cardiomyopathy (HCM). Forty-five unrelated probands with HCM were genotyped by targeted next-generation sequencing (NGS) for 24 genes associated with cardiac ion homeostasis. Subsequently, the study cohort was divided into two groups based on the presence (AFib+) or absence (AFiB−) of AFib detected during ECG monitoring. We identified two polymorphisms (rs1805127 located in KCNE1 and rs55742440 located in SCN1B) linked to AFib susceptibility. In AFib+, rs1805127 was associated with increased indexed left atrial (LA) maximal volume (LAVmax) (58.42 ± 21 mL/m2 vs. 32.54 ± 6.47 mL/m2, p < 0.001) and impaired LA strain reservoir (LASr) (13.3 ± 7.5% vs. 24.4 ± 6.8%, p < 0.05) compared to those without respective variants. The rs55742440 allele was less frequent in patients with AFib+ (12 out of 25, 48%) compared to those without arrhythmia (15 out of 20, 75%, p = 0.05). Also, AFib+ rs55742440 carriers had significantly lower LAVmax compared to those who were genotype negative. Among patients with HCM and AFib+, the rs1805127 variant was accompanied by pronounced LA remodeling, whereas rs55742440's presence was related to a milder LA enlargement. [ABSTRACT FROM AUTHOR]

Atrial fibrillation (AF), the most frequently encountered arrhythmia worldwide, is associated with increased cardiovascular morbidity and mortality. Left atrial (LA) and antral region of the pulmonary veins (PVs) remodeling are risk factors for AF perpetuation. Among the methods of LA fibrosis quantification, bipolar voltage mapping during three-dimensional electro-anatomical mapping is less studied. The main aim of this study was to analyze the relationship between the degree of LA fibrosis quantified in low-voltage areas and the efficacy of AF radiofrequency catheter ablation. All consecutive patients with AF ablation were included, and the degree of LA fibrosis was measured based on the low-voltage areas in the LA and the antral region of PVs (<0.5 mV for patients in sinus rhythm and <0.25 mV for patients in AF at the time of the ablation procedure). The efficacy of AF ablation was determined by the rate of recurrence after a blanking period of three months. A total of 106 patients were included; from these, 38 (35.8%) had AF recurrence after RF ablation, while 68 (64.2%) were free of events. The area and percentage of LA fibrosis were significantly higher in the patients with AF recurrence (p = 0.018 and p = 0.019, respectively). However, no significant differences were found between the patients with and without AF recurrence in terms of the area and percentage of PVs fibrosis (p = 0.896 and p = 0.888, respectively). Moreover, LA fibrosis parameters proved to be excellent predictors for AF recurrence (areas under the curve of 0.834 and 0.832, respectively, p < 0.001) even after adjustment for LA indexed volume and CHA2DS2-VASc score. In conclusion, LA fibrosis measured on bipolar voltage maps increases the risk of AF recurrence after the RF catheter ablation procedure. [ABSTRACT FROM AUTHOR]

During the coronavirus pandemic 2019 (COVID-19), some studies showed differences in the profile of subjects presenting with acute coronary syndromes as well as in overall mortality due to the delay of presentation and other complications. The purpose of this study was to compare the profile and outcomes, with emphasis on all-cause in-hospital mortality, of ST-elevation myocardial infarction (STEMI) subjects presenting to the emergency department during the pandemic period compared with a control group from the previous year, 2019. The study enrolled 2011 STEMI cases, which were divided into two groups—pre-pandemic (2019–2020) and pandemic period (2020–2022). Hospital admissions for a STEMI diagnosis sharply decreased during the COVID-19 period by 30.26% during the first year and 25.4% in the second year. This trend was paralleled by a significant increase in all-cause in-hospital mortality: 11.5% in the pandemic period versus 8.1% in the previous year. There was a significant association between SARS-CoV-2 positivity and all-cause in-hospital mortality, but no correlation was found between COVID-19 diagnosis and the type of revascularization. However, the profile of subjects presenting with STEMI did not change over time during the pandemic; their demographic and comorbid characteristics remained similar. [ABSTRACT FROM AUTHOR]

Coagulase-negative staphylococci (CoNS) are an emergent aetiology of infective endocarditis (IE) on native valves in previously healthy individuals, its presence is associated with prosthetic valves or with other cardiac implants. The identification of CoNS in cultures was customarily seen as contamination, but more recent epidemiological studies have revealed an increasing number of causative and virulent new CoNS species. Starting from two clinical cases of community-acquired CoNS IE on native valves, the review debates the difficulties in identifying CoNS as the causal pathogens, comprising differentiation of contamination from infection in IE, alongside the challenges raised by antibiotic resistance. Even if the risk of CoNS IE is more increased in subjects with prosthetic materials or other foreign devices and immunodeficiencies, native valve infections with these staphylococci are increasing and should be considered important pathogens in IE. Despite the lack of sensitive and specific tools to correctly differentiate contamination from infection in CoNS endocarditis, a comprehensive evaluation with clinical and paraclinical data accurately succeeds in establishing the diagnosis. The genetic profile of CoNS predisposes to antibiotic multi-resistance, making the treatment of IE challenging; the rapid identification of antibiotic susceptibility is essential to prescribe the appropriate therapy and improve outcomes. [ABSTRACT FROM AUTHOR]

β-blocker poisoning is frequently observed because of its primary use for the treatment of cardiovascular diseases. The management of β-blocker toxicity is dependent on the cardiovascular response and the severity of presentation. The present study describes the case of a patient with combined drug intoxication, β-blocker, digoxin, benzodiazepines, acetaminophen and opiates in a suicidal attempt. A 63-year-old female was found somnolent and in a confused state at her residence following intentional poly-drug ingestion. Upon presentation, she was found to be hemodynamically unstable and was thus treated with vasopressors. The toxicological screening performed upon presentation was positive for polydrug ingestion. On day 3, the patient developed chest pain and ST-segment elevation in anterior leads, while transthoracic echocardiographic assessment disclosed a non-dilated left ventricle with moderate dysfunction and akinesia of the apex. Coronary angiogram revealed normal coronary arteries and, subsequently, the diagnosis of Takotsubo cardiomyopathy (TTC) was suspected. Supportive treatment was initiated with favorable evolution and left ventricular ejection fraction normalization. The management of hemodynamic instability with vasopressors should be judiciously administered in the treatment of β-blocker poisoning, in view of the adverse effects on cardiac functions, including stress cardiomyopathy. [ABSTRACT FROM AUTHOR]

Ischemic heart disease represent a heavy burden for the medical systems irrespective of the methods used for diagnosis and treatment of such patients in the daily medical routine. The present paper depicts the protocol of a study whose main aim is to develop, implement and test an artificial intelligence algorithm and cloud based platform for fully automated PCI guidance using coronary angiography images. We propose the utilisation of multiple artificial intelligence based models to produce three-dimensional coronary anatomy reconstruction and assess function- post-PCI FFR computation- for developing an extensive report describing and motivating the optimal PCI strategy selection. All the relevant artificial intelligence model outputs (anatomical and functional assessment–pre- and post-PCI) are presented to the clinician via a cloud platform, who can then take the utmost treatment decision. The physician will be provided with multiple scenarios and treatment possibilities for the same case allowing a real-time evaluation of the most appropriate PCI strategy planning and follow-up. The artificial intelligence algorithms and cloud based PCI selection workflow will be verified and validated in a pilot clinical study including subjects prospectively to compare the artificial intelligence services and results against annotations and invasive measurements. [ABSTRACT FROM AUTHOR]

Cardiovascular disease (CVD) is the number one cause of death worldwide, and coronary artery disease (CAD) is the most prevalent CVD, accounting for 42% of these deaths. In view of the limitations of the anatomical evaluation of CAD, Fractional Flow Reserve (FFR) has been introduced as a functional diagnostic index. Herein, we evaluate the feasibility of using deep neural networks (DNN) in an ensemble approach to predict the invasively measured FFR from raw anatomical information that is extracted from optical coherence tomography (OCT). We evaluate the performance of various DNN architectures under different formulations: regression, classification—standard, and few-shot learning (FSL) on a dataset containing 102 intermediate lesions from 80 patients. The FSL approach that is based on a convolutional neural network leads to slightly better results compared to the standard classification: the per-lesion accuracy, sensitivity, and specificity were 77.5%, 72.9%, and 81.5%, respectively. However, since the 95% confidence intervals overlap, the differences are statistically not significant. The main findings of this study can be summarized as follows: (1) Deep-learning (DL)-based FFR prediction from reduced-order raw anatomical data is feasible in intermediate coronary artery lesions; (2) DL-based FFR prediction provides superior diagnostic performance compared to baseline approaches that are based on minimal lumen diameter and percentage diameter stenosis; and (3) the FFR prediction performance increases quasi-linearly with the dataset size, indicating that a larger train dataset will likely lead to superior diagnostic performance. [ABSTRACT FROM AUTHOR]

Ischemic heart disease is one of the most important causes of mortality and morbidity worldwide. Revascularization of coronary stenosis inducing ischemia, either by percutaneous or surgical intervention, significantly reduces major adverse cardiovascular events and improves quality of life. However, in cases of intermediate lesions, classified by a diameter stenosis between 50 and 90% by European guidelines and 40–70% in American counterparts with no clear evidence of ischemia, the indication of revascularization and impact is determined using various methods that altogether comprehensively evaluate the lesions. This review will discuss the various techniques to assess intermediate stenoses, highlighting indications and advantages, but also drawbacks. Fractional flow rate (FFR) and instantaneous wave-free ratio (iFR) are the gold standard for the functional evaluation of intermediate lesions, but there are clinical circumstances in which these pressure-wire-derived indices are not accurate. Complementary invasive investigations, mainly intravascular ultrasound and/or optical coherence tomography, offer parameters that can be correlated with FFR/iFR and additional insights into the morphology of the plaque guiding the eventual percutaneous intervention in terms of length and size of stents, thus improving the outcomes of the procedure. The development of artificial intelligence and machine learning with advanced algorithms of prediction will offer multiple scenarios for treatment, allowing real-time selection of the best strategy for revascularization. [ABSTRACT FROM AUTHOR]

The inflammatory hypothesis of atherosclerosis is appealing in acute coronary syndromes, but the dynamics and precise role are not established. The study investigates the levels of C reactive protein (CRP), interleukin 1β (IL-1β) and stromal-derived factor 1α (SDF-1α) at the time of acute myocardial infarction (AMI) and at 1 and 6 months afterwards, compared with a control group. In the acute phase of AMI, CRP and SDF-1α were significantly higher, while IL-1β showed lower levels compared with controls. CRP positively correlated with coronary stenosis severity (rho = 0.3, p=.05) and negatively related with left ventricle ejection fraction (LVEF) at 1 month (rho= −0.43, p=.05). IL-1β weakly correlated with the severity of coronary lesions (rho =0.29, p=.02) and strongly with LVEF (rho= −0.8, p=.05). SDF-1α, slightly correlated with LVEF at 1 month (rho = 0.22, p=.01) and with the severity of coronary atherosclerosis (rho= −0.41, p=.003). CRP, IL-1β and SDF-1α have important dynamic in the first 6 months after AMI and CRP and SDF-1α levels correlated with the severity of coronary lesions and LVEF at 1 month after the acute ischaemic event. [ABSTRACT FROM AUTHOR]

Background and Objectives: biomarker-based studies are the cornerstone of precision medicine, providing key data for tailored medical care. Enrollment of the planned number of patients is a critical determinant of a successful clinical trial. Moreover, for inclusive medical care, patients from different socio-demographic backgrounds must be recruited. Still, a significant number of trials fail to reach these prerequisites. Designing the informed consent forms based on the patients’ feedback could optimize accrual. We aimed to explore the attitudes of patients from a Romanian tertiary cardiology center towards participation in biomarker-based clinical trials. Materials and Methods: three hundred forty inpatients were interviewed based on a semi-structured questionnaire which included four sections: demographics, personal medical history, attitudes and trust. Results: Roughly, 62.5% of the respondents were interested in enrolling, while altruistic reasons were the most frequently expressed. Clear exposure of the possible risks was most valued (37.78%), followed by the possibility of directly communicating with the research team (23.78%). The most frequently chosen answer by acutely ill patients was improvement of their health, whereas chronically ill individuals indicated the possibility of withdrawal without affecting the quality of medical care. Importantly, the participation rate could be improved if the invitation to enrollment were made by both the current physician and the study coordinator (p = 0.0001). The level of trust in researchers was high in more than 50% of the respondents, and was correlated with therapeutic compliance and with the desire to join a biomarker study. Conclusions: the information gained will facilitate a tailored approach to patient enrollment in future biomarker-based studies in our clinic. [ABSTRACT FROM AUTHOR]

Anti-platelet treatment challenges in Glanzmann thrombasthenia-clinical practice when data lacks Glanzmann thrombasthenia is a rare bleeding disorder characterized by defective or low levels of glycoprotein (GP) IIb/IIIa.1 The GP IIb/IIIa receptor is activated when the platelets are stimulated by adenosine diphosphate (ADP), epinephrine, collagen, or thrombin and its presence is essential for haemostasis since it enables platelet aggregation. Cardiovascular disease treatment in bleeding disorders such as Glanzmann thrombasthenia is challenging seen that the classic treatment consisting in antiplatelets exposes this category of subjects to higher haemorrhagic events. [Extracted from the article]

Infective endocarditis (IE) is associated with high mortality if left untreated and is associated with many complications such as: septic emboli, abscesses, valvular rupture or congestive heart failure. We present below the case of a 69-year-old male who presented to the emergency room for exertional dyspnea, malaise and fatigue, symptoms that started for several months with progressive worsening. The cardiac examination highlighted a systolic murmur in the mitral area in concordance with the echocardiographic findings that revealed severe mitral regurgitation along with a degenerative-myxomatous appearance of the mitral valve, suggestive for Barlow's disease, as well as a hyperechogenic mass on the mitral valve. Empirical therapy was initiated intravenously with vancomycin and gentamicin after three blood cultures were harvested. The blood cultures were positive for Staphylococcus (S.) epidermidis and given the antibiogram's susceptibility to vancomycin and daptomycin, the treatment was subsequently continued only with vancomycin. Albeit coagulase negative staphylococci such as S. epidermidis are usually found at patients with risk factors: valvular prostheses, implantable devices, hemodialysis or intravascular catheters, in our case the patient had no such risk factors, but instead developed IE on a native, degenerated valve. The patient was referred to the cardiovascular surgeon and subsequently, a prosthetic, bidisc mitral valve was implanted along with tricuspid annuloplasty. The recovery was uneventful and at 6 months of follow-up the patient was asymptomatic with no complications. [ABSTRACT FROM AUTHOR]

• Arrhythmia stratification risk is essential in hypertrophic cardiomyopathy (HCM). • Non-sustained ventricular tachycardia correlates to mechanical dispersion (MD). • Left and right ventricular MD improve arrhythmia risk stratification in HCM. Ventricular arrhythmias are the most frequent cause of sudden cardiac death in individuals with hypertrophic cardiomyopathy (HCM). In the present study we investigated if combined left ventricular (LV) and right ventricular (RV) mechanical dispersion (MD) are correlated with ventricular arrhythmias. We aimed also to analyze if MD enhances the arrhythmic risk stratification in HCM. The cohort included 47 subjects with HCM and 36 healthy individuals. All the studied population underwent clinical, 24-h electrocardiographic (ECG) monitoring for detection and description of non-sustained ventricular tachycardia (NSVT) in terms of number of events, maximal rate and length and comprehensive transthoracic echocardiography, including strain rate imaging. MD was calculated as standard deviation of time from the peak of R wave on ECG to maximum LV or RV shortening in 17 LV and 3 RV segments. HCM subjects with NSVT on ECG monitoring had increased LVMD (81 ± 18 ms vs 42 ± 8 ms) and RVMD (52 ± 26 vs 25 ± 23 ms) compared with the HCM group without NSVT or compared with the healthy controls. On receiver operating characteristic curves the cut-off values associated with optimal specificity and sensitivity were 62 ms for LVMD and 39 ms for RVMD. LVMD (OR = 1.86, 95% CI 1–1.06, p = 0.01) and RVMD (OR = 1.04, 95% CI 1.01–1.07, p = 0.003) were the only independent variables that correlated with longer and faster NSVT and furthermore improved the risk stratification of NSVTs. In a cohort of subjects with HCM, LVMD and RVMD correlates with the presence of NSVT on ECG monitoring. Combined LVMD and RVMD may improve the risk stratification of HCM with NSVT. [ABSTRACT FROM AUTHOR]

The knowledge about the Human Immunodeficiency Virus (HIV) discovered almost 40 years ago and the related disease has known a paramount evolution, from an almost deadly infection to a chronic, controlled one. Many insights into the molecular, pathophysiology and medical management of this infection have been made over time. The discoveries around HIV infection have brought progress also in other fields, such as immunodeficiency related infections and drug resistance. Even with the advances made in the field of HIV, many aspects have not been discovered: an efficient vaccine, treatment which can induce a cure or the ideal prevention method. [ABSTRACT FROM AUTHOR]

The association between endocarditis with Streptococcus gallolyticus and the development of colorectal cancer is well known, making the endoscopic surveillance at least annually mandatory for patients with this type of endocarditis or bacteraemia. If the link between these two is recognized, the role the bacteria as the promotor of neoplasia is still uncertain and sometimes called into question, whereas many hypotheses have been proposed. [ABSTRACT FROM AUTHOR]

Background: Visual estimation (VE) of coronary stenoses is the first step during invasive coronary angiography. The aim of this study was to evaluate the accuracy of VE together with invasive functional assessment (IFA) in defining the functional significance (FS) of coronary stenoses based on the opinion of multiple operators. Methods: Fourteen independent operators visually evaluated 133 coronary lesions which had a previous FFR measurement, indicating the degree of stenosis (DS), FS and IFA intention. We determined the accuracy of FS prediction using several scenarios combining individual and group decision, considering IFA as deemed necessary by the operator or only in intermediate lesions. Results: The accuracy of VE in predicting FS was largely variable between operators (average 66.1%); it improved significantly when IFA was used either as per operator's opinion (86.3%; p < 0.0001) or only in intermediate DS (82.9; p < 0.0001). There was no significant difference between using IFA per observer's opinion or only in intermediate DS lesions (p = 0.166). The poorest accuracy of VE for FS was obtained in intermediate DS lesions (59.1%). Conclusions: There are significant inter-observer differences in reporting the degree of DS, while the accuracy of VE prediction of FS is also largely dependent on the operator, and the worst performance is obtained in the evaluation of intermediate DS. [ABSTRACT FROM AUTHOR]

References 1 Popescu S., Preda M., Marinescu C., Simionescu M., Burlacu A. Dual Stem Cell Therapy Improves the Myocardial Recovery Post-Infarction through Reciprocal Modulation of Cell Functions. Extracellular vesicles (EV) are recently discovered cell-derived elements encompassing apoptotic bodies, ectosomes and exosomes. We designed this Special Issue with the belief that biomedical research will pave the road which in the near future will lead us to find remedies and cures for the cardiovascular diseases. Cardiovascular diseases have attracted our full attention not only because they are the main cause of mortality and morbidity in many countries but also because the therapy for and cure of these maladies are among the major challenges of the medicine in the 21st century. [Extracted from the article]

Hypertrophic cardiomyopathy (HCM) and arterial hypertension (HTN) are conditions with different pathophysiology, but both can result in left-ventricular hypertrophy (LVH). The role of left-atrial (LA) functional changes detected by two-dimensional speckle-tracking echocardiography (STE) in indicating LVH etiology is unknown. Methods: We aimed to characterize LA mechanics using STE in LVH patients with HCM and HTN. LA 2D volumetric and STE parameters were analyzed in 86 LVH patients (43 HCM and 43 isolated HTN subjects) and 33 age- and sex-matched controls. Results: The volumetric study showed that LA reservoir and conduit function were impaired in the HCM group compared to controls, while, in the HTN group, only LA conduit function was deteriorated. The HCM group had all three STE-derived LA functions impaired compared to controls. The HTN group, consistently with volumetric analysis, had solely LA conduit function reduced compared to controls. Ratios of LA booster-pump strain (S) and strain rate (SR) to interventricular septum (IVS) thickness were the most accurate parameters to discriminate between HCM and HTN. The subgroup harboring sarcomeric pathogenic (P)/likely pathogenic (LP) variants had reduced LA booster-pump S and SR compared with the genotype-negative subgroup. Conclusions: LA reservoir, conduit, and pump functions are decreased in HCM compared to HTN patients with similar LVH. We report the ratios between LA contraction S/SR and IVS thickness as novel parameters with high accuracy in discriminating LVH due to HCM. The presence of P/LP variants in sarcomeric or sarcomeric-associated genes could be associated with more severe LA dysfunction. [ABSTRACT FROM AUTHOR]

Despite diagnostic and therapeutic advances, coronary artery disease and especially its extreme manifestation, ST elevation myocardial infarction (STEMI), remain the leading causes of morbidity and mortality worldwide. Early and prompt diagnosis is of great importance regarding the prognosis of STEMI patients. In recent years, microRNAs (miRNAs) have emerged as promising tools involved in many pathophysiological processes in various fields, including cardiovascular diseases. In acute coronary syndromes (ACS), circulating levels of miRNAs are significantly elevated, as an indicator of cardiac damage, making them a promising marker for early diagnosis of myocardial infarction. They also have prognostic value and great potential as therapeutic targets considering their key function in gene regulation. This review aims to summarize current information about miRNAs and their role as diagnostic, prognostic and therapeutic targets in STEMI patients. [ABSTRACT FROM AUTHOR]

Background: The aim of this study was to explore the rare variants in a cohort of Romanian index cases with hypertrophic cardiomyopathy (HCM). Methods: Forty-five unrelated probands with HCM were screened by targeted next generation sequencing (NGS) of 47 core and emerging genes connected with HCM. Results: We identified 95 variants with allele frequency < 0.1% in population databases. MYBPC3 and TTN had the largest number of rare variants (17 variants each). A definite genetic etiology was found in 6 probands (13.3%), while inconclusive results due to either known or novel variants were established in 31 cases (68.9%). All disease-causing variants were detected in sarcomeric genes (MYBPC3 and MYH7 with two cases each, and one case in TNNI3 and TPM1 respectively). Multiple variants were detected in 27 subjects (60%), but no proband carried more than one causal variant. Of note, almost half of the rare variants were novel. Conclusions: Herein we reported for the first time the rare variants identified in core and putative genes associated with HCM in a cohort of Romanian unrelated adult patients. The clinical significance of most detected variants is yet to be established, additional studies based on segregation analysis being required for definite classification. [ABSTRACT FROM AUTHOR]

Pediatric inherited cardiomyopathies (CMPs) and channelopathies (CNPs) remain important causes of death in this population, therefore, there is a need for prompt diagnosis and tailored treatment. Conventional evaluation fails to establish the diagnosis of pediatric CMPs and CNPs in a significant proportion, prompting further, more complex testing to make a diagnosis that could influence the implementation of lifesaving strategies. Genetic testing in CMPs and CNPs may help unveil the underlying cause, but needs to be carried out with caution given the lack of uniform recommendations in guidelines about the precise time to start the genetic evaluation or the type of targeted testing or whole-genome sequencing. A very diverse etiology and the scarce number of randomized studies of pediatric CMPs and CNPs make genetic testing of these maladies far more particular than their adult counterpart. The genetic diagnosis is even more puzzling if the psychological impact point of view is taken into account. This review aims to put together different perspectives, state-of-the art recommendations—synthetizing the major indications from European and American guidelines—and psychosocial outlooks to construct a comprehensive genetic assessment of pediatric CMPs and CNPs. [ABSTRACT FROM AUTHOR]

Background and aim: Most of detected variants in cardiogenetic panels are still classified as variants of unknown significance, requiring supplementary analyses for a definite classification. Performing further in-depth studies on such vast number of candidates is unfeasible. We sought to prioritise the novel nonsynonymous missense variants identified in titin gene (TTN) in a cohort of Romanian index cases with hypertrophic cardiomyopathy (HCM). Methods: 45 unrelated probands with HCM were screened by targeted next generation sequencing (NGS) covering all TTN exons. A stepwise strategy was used to select and prioritize the candidate variants for subsequent investigation. Results: Using rigorous bioinformatic filtering, 7 novel TTN nonsynonymous missense variants were identified and were the subject of in silico sequential analysis. 4 of the 7 variants were predicted to be possibly pathogenic by the Mendelian Clinically Applicable Pathogenicity (M-CAP) algorithm. Of these, three sequence variants (c.30392G>T, c.2518G>T, and c.49G>T) were also predicted to be destabilizing according to the second computational tool (TITINdb) and were designated as likely function-impacting. Conclusions: Herein we presented our strategy to hand-pick the novel TTN missense variants to be considered for further experimental studies. By applying various in silico tools, we restricted the list of sequence variants to be investigated to those most likely to be disease-associated, and thus reducing the need to perform expensive and time-consuming additional studies. [ABSTRACT FROM AUTHOR]

Background: In acute coronary syndrome (ACS), a number of previous studies tried to identify the risk factors that are most likely to influence the rate of in-stent restenosis (ISR), but the contribution of these factors to ISR is not clearly defined. Thus, the need for a better way of identifying the independent predictors of ISR, which comes in the form of Machine Learning (ML)., Objectives: The aim of this study is to evaluate the relationship between ISR and risk factors associated with ACS and to develop and validate a nomogram to predict the probability of ISR through the use of ML in patients undergoing percutaneous coronary intervention (PCI)., Methods: Consecutive patients presenting with ACS who were successfully treated with PCI and who had an angiographic follow-up after at least 3 months were included in the study. ISR risk factors considered into the study were demographic, clinical and peri-procedural angiographic lesion risk factors. We explored four ML techniques (Random Forest (RF), support vector machines (SVM), simple linear logistic regression (LLR) and deep neural network (DNN)) to predict the risk of ISR. Overall, 21 features were selected as input variables for the ML algorithms, including continuous, categorical and binary variables., Results: The total cohort of subjects included 340 subjects, in which the incidence of ISR observed was 17.68% ( n  = 87). The most performant model in terms of ISR prediction out of the four explored was RF, with an area under the receiver operating characteristic (ROC) curve of 0.726. Across the predictors herein considered, only three predictors were statistically significant, precisely, the number of affected arteries (≥2), stent generation and diameter., Conclusion: ML models applied in patients after PCI can contribute to a better differentiation of the future risk of ISR., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (© 2023 Scafa-Udriște, Itu, Puiu, Stoian, Moldovan and Popa-Fotea.)

Atherosclerosis and its complications are a major cause of morbidity and mortality worldwide in spite of the improved medical and invasive treatment in terms of revascularization. Atherosclerosis is a dynamic, multi-step process in which inflammation is a ubiquitous component participating in the initiation, development, and entanglements of the atherosclerotic plaque. After activation, the immune system, either native or acquired, is part of the atherosclerotic dynamics enhancing the pro-atherogenic function of immune or non-immune cells, such as endothelial cells, smooth muscle cells, or platelets, through mediators such as cytokines or directly by cell-to-cell interaction. Cytokines are molecules secreted by the activated cells mentioned above that mediate the inflammatory component of atherosclerosis whose function is to stimulate the immune cells and the production of further cytokines. This review provides insights of the cell axis activation and specific mechanisms and pathways through which inflammation actuates atherosclerosis., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (© 2023 Popa-Fotea, Ferdoschi and Micheu.)

The concepts underlying hypertrophic cardiomyopathy (HCM) pathogenesis have evolved greatly over the last 60 years since the pioneering work of the British pathologist Donald Teare, presenting the autopsy findings of "asymmetric hypertrophy of the heart in young adults". Advances in human genome analysis and cardiac imaging techniques have enriched our understanding of the complex architecture of the malady and shaped the way we perceive the illness continuum. Presently, HCM is acknowledged as "a disease of the sarcomere", where the relationship between genotype and phenotype is not straightforward but subject to various genetic and nongenetic influences. The focus of this review is to discuss key aspects related to molecular mechanisms and imaging aspects that have prompted genotype-phenotype correlations, which will hopefully empower patient-tailored health interventions.

Despite optimal interventional and medical therapy, ischemic heart disease is still an important cause of morbidity and mortality worldwide. Although not included in standard of care rehabilitation, stem cell therapy (SCT) could be a solution for prompting cardiac regeneration. Multiple studies have been published from the beginning of SCT until now, but overall no unanimous conclusion could be drawn in part due to the lack of appropriate end-points. In order to appreciate the impact of SCT, multiple markers from different categories should be considered: Structural, biological, functional, physiological, but also major adverse cardiac events or quality of life. Imaging end-points are among the most used - especially left ventricle ejection fraction (LVEF) measured through different methods. Other imaging parameters are infarct size, myocardial viability and perfusion. The impact of SCT on all of the aforementioned end-points is controversial and debatable. 2D-echocardiography is widely exploited, but new approaches such as tissue Doppler, strain/strain rate or 3D-echocardiography are more accurate, especially since the latter one is comparable with the MRI gold standard estimation of LVEF. Apart from the objective parameters, there are also patient-centered evaluations to reveal the benefits of SCT, such as quality of life and performance status, the most valuable from the patient point of view. Emerging parameters investigating molecular pathways such as non-coding RNAs or inflammation cytokines have a high potential as prognostic factors. Due to the disadvantages of current techniques, new imaging methods with labelled cells tracked along their lifetime seem promising, but until now only pre-clinical trials have been conducted in humans. Overall, SCT is characterized by high heterogeneity not only in preparation, administration and type of cells, but also in quantification of therapy effects., Competing Interests: Conflict-of-interest statement: Authors declare no conflict of interests for this article. No financial support.