Cardiac contractility modulation in patients with heart failure - A review of the literature.

Experimental in vivo and in vitro studies showed that electric currents applied during the absolute refractory period can modulate cardiac contractility. In preclinical studies, cardiac contractility modulation (CCM) was found to improve calcium handling, reverse the foetal myocyte gene programming associated with heart failure (HF), and facilitate reverse remodeling. Randomized control trials and observational studies have provided evidence about the safety and efficacy of CCM in patients with HF. Clinically, CCM therapy is indicated to improve the 6-min hall walk, quality of life, and functional status of HF patients who remain symptomatic despite guideline-directed medical treatment without an indication for cardiac resynchronization therapy (CRT) and have a left ventricular ejection fraction (LVEF) ranging from 25 to 45%. Although there are promising results about the role of CCM in HF patients with preserved LVEF (HFpEF), further studies are needed to elucidate the role of CCM therapy in this population. Late gadolinium enhancement (LGE) assessment before CCM implantation has been proposed for guiding the lead placement. Furthermore, the optimal duration of CCM application needs further investigation. This review aims to present the existing evidence regarding the role of CCM therapy in HF patients and identify gaps and challenges that require further studies.

When anticoagulation management in atrial fibrillation becomes difficult: Focus on chronic kidney disease, coagulation disorders, and cancer.

Anticoagulation therapy (AT) is fundamental in atrial fibrillation (AF) treatment but poses challenges in implementation, especially in AF populations with elevated thromboembolic and bleeding risks. Current guidelines emphasize the need to estimate and balance thrombosis and bleeding risks for all potential candidates of antithrombotic therapy. However, administering oral AT raises concerns in specific populations, such as those with chronic kidney disease (CKD), coagulation disorders, and cancer due to lack of robust data. These groups, excluded from large direct oral anticoagulants trials, rely on observational studies, prompting physicians to adopt individualized management strategies based on case-specific evaluations. The scarcity of evidence and specific guidelines underline the need for a tailored approach, emphasizing regular reassessment of risk factors and anticoagulation drug doses. This narrative review aims to summarize evidence and recommendations for challenging AF clinical scenarios, particularly in the long-term management of AT for patients with CKD, coagulation disorders, and cancer.

[Régurgitation mitrale sévère due à la sarcoïdose cardiaque : une présentation clinique inhabituelle ; une étude de cas et des recherches antérieures]. / Severe mitral regurgitation due to cardiac sarcoidosis : An unusual clinical presentation ; a case report and review of the literature.

Sarcoidosis is a granulomatous inflammatory disease that may involve multiple organ systems, including the heart. Cardiac manifestations are not rare and include atrial and ventricular arrhythmias, conduction abnormalities, congestive heart failure, valvular dysfunction, pericarditis, and sudden death. Although, cardiac sarcoidosis (CS) remains a diagnostic and therapeutic challenge. This article describes a case of a patient with a history of pulmonary sarcoidosis who presented with congestive heart failure, on the basis of severe mitral regurgitation secondary to cardiac infiltration and summarizes the published evidence regarding CS and mitral regurgitation.

Aortic Stiffness: A Major Risk Factor for Multimorbidity in the Elderly.

Multimorbidity, the coexistence of multiple health conditions in an individual, has emerged as one of the greatest challenges facing health services, and this crisis is partly driven by the aging population. Aging is associated with increased aortic stiffness (AoStiff), which in turn is linked with several morbidities frequently affecting and having disastrous consequences for the elderly. These include hypertension, ischemic heart disease, heart failure, atrial fibrillation, chronic kidney disease, anemia, ischemic stroke, and dementia. Two or more of these disorders (multimorbidity) often coexist in the same elderly patient and the specific multimorbidity pattern depends on several factors including sex, ethnicity, common morbidity routes, morbidity interactions, and genomics. Regular exercise, salt restriction, statins in patients at high atherosclerotic risk, and stringent blood pressure control are interventions that delay progression of AoStiff and most likely decrease multimorbidity in the elderly.

Optimal Anticoagulation on TAVI Patients Based on Thrombotic and Bleeding Risk and the Challenge Beyond: A Systematic Review and Meta-Analysis.

Transcatheter Aortic Valve Replacement (TAVR) has been established as the treatment of choice for symptomatic aortic stenosis, while it is expanding in all risk-related group categories of patients, gaining gradually ground over the surgical approach. However, complications and adverse events are yet to be effectively limited and diminished with thrombotic and hemorrhagic events being rooted as a crucial topic of discussion. Favorable anticoagulation pharmacotherapy options are constantly being revised and tested, whilst guidelines are being modified to meet current clinical evidence. This review aims to systematically assess already existing guidelines on anticoagulation in post-TAVI patients and examine novel regimens for the specific use, like apixaban, rivaroxaban, and other anticoagulants, essentially constructing a holistic point of view on future progress on this matter. The added complexity brought by coagulation-affecting comorbidities such as atrial fibrillation, coronary artery disease, and more contributes to the direct association of the topic to the quality of healthcare as a public service. The literature was systematically searched to examine the effectiveness and safety of various anticoagulation treatments and cross-evaluate them based on the according category of patients that were assigned to. Clinical trials, observational studies and systematic reviews were included and, eventually, conclusive remarks and future considerations were developed and presented. In the category of patients without prior indication to anticoagulation, SAPT was proven safer and still effective, when antiplatelet therapies were compared, while a comparison of antiplatelet versus anticoagulation strategies noted the first one, with limited data, as the optimal one. Lastly, direct oral anticoagulants were shown to be safe substitutes for vitamin K antagonists for patients with prior indication to anticoagulation.

Cardiac Rehabilitation After TAVI -A Systematic Review and Meta-Analysis.

Despite the increasing popularity of Transcatheter aortic valve implantation (TAVI) in patients with high surgical risk, there is no current guideline for the management of patients following the intervention. This systematic review and meta-analysis aims to summarize and analyse all clinical data and evidence regarding the effectiveness and outcomes of CR following TAVI. The first meta-analysis measured the walked distance in the Six-Minute Walk Test (6MWT) and the second meta-analysis included studies that showed the Barthel Index (BI) before and after CR. The mean distance walked prior to CR was 235.88 ± 69.36 m increased to 292.12 ± 54.92 m after rehabilitation, signifying a moderate clinically relevant effect size (0.593 (0.42, 0.76); P=0.00). The mean BI score before CR was 76.6 ± 11.5 which increased to 89.8 ± 5.5 after the programme and similarly demonstrated a significant standardized mean improvement (0.75 (0.57, 0.93); I= 0.00). Exercise-based CR in patients with aortic stenosis treated with TAVI demonstrated a significant improvement in exercise tolerance and functional independence shown by the 6MWT and BI.

Study Level Meta-Analysis of Transcatheter Aortic Valve Implantation With the ACURATE neo Self-Expanding Transcatheter Heart Valve.

The ACURATE neo transcatheter aortic valve is a self-expanding device. Several studies have investigated safety and efficacy, but meta-analysis and pooled data are lacking. We aimed to provide a comprehensive systematic review and meta-analysis on the clinical outcomes of transcatheter aortic valve implantation with the ACURATE neo valve. A systematic literature search for eligible records was conducted. The primary endpoint was device success as designated by Valve Academic Research Consortium-2 criteria. The secondary endpoints (time frame: 30 days) were all-cause mortality, stroke, myocardial infarction, need for new permanent pacemaker, major vascular complications, major bleeding, acute kidney injury stage II or III, and paravalvular regurgitation grade moderate or severe (II or III). Our search yielded a total of 355 records, 20 of those (n = 5858 ACURATE neo receivers) were included in our meta-analysis. Device success was achieved in 94.5% (95% confidence interval [CI], 91.4-96.5%) of the patients. The 30-day all-cause mortality incidence proportion was 1.8% (95% CI, 1.3-2.4%). New pacemaker implantation was required in 7.7% (95% CI, 6.4-9.2%) of the patients, stroke occurred in 1.9% (95% CI, 1.6-2.3%), myocardial infarction in 0.5% (95% CI, 0.3-0.7%), major bleeding in 5.0% (95% CI, 3.9-6.5%), major vascular complication in 5.6% (95% CI, 4.0-7.8%), acute kidney injury stage ≥2 in 2.5% (95% CI, 1.8-3.4%), and paravalvular leak grade ≥moderate was observed in 4.3% (95% CI, 3.0-6.2%). Balloon predilatation and postdilatation incidence was 93.9% (95% CI, 87.0-97.3%) and 43.2% (95% CI, 37.9-48.6%), respectively. ACURATE neo appears to be safe and effective in our analysis with high device success incidence, low mortality, and low new pacemaker implantations.

Artificial intelligence supporting cancer patients across Europe-The ASCAPE project.

INTRODUCTION: Breast and prostate cancer survivors can experience impaired quality of life (QoL) in several QoL domains. The current strategy to support cancer survivors with impaired QoL is suboptimal, leading to unmet patient needs. ASCAPE aims to provide personalized- and artificial intelligence (AI)-based predictions for QoL issues in breast- and prostate cancer patients as well as to suggest potential interventions to their physicians to offer a more modern and holistic approach on cancer rehabilitation. METHODS AND ANALYSES: An AI-based platform aiming to predict QoL issues and suggest appropriate interventions to clinicians will be built based on patient data gathered through medical records, questionnaires, apps, and wearables. This platform will be prospectively evaluated through a longitudinal study where breast and prostate cancer survivors from four different study sites across the Europe will be enrolled. The evaluation of the AI-based follow-up strategy through the ASCAPE platform will be based on patients' experience, engagement, and potential improvement in QoL during the study as well as on clinicians' view on how ASCAPE platform impacts their clinical practice and doctor-patient relationship, and their experience in using the platform. ETHICS AND DISSEMINATION: ASCAPE is the first research project that will prospectively investigate an AI-based approach for an individualized follow-up strategy for patients with breast- or prostate cancer focusing on patients' QoL issues. ASCAPE represents a paradigm shift both in terms of a more individualized approach for follow-up based on QoL issues, which is an unmet need for cancer survivors, and in terms of how to use Big Data in cancer care through democratizing the knowledge and the access to AI and Big Data related innovations. TRIAL REGISTRATION: Trial Registration on clinicaltrials.gov: NCT04879563.

Soluble suppression of tumorigenicity 2 (sST2) for predicting disease severity or mortality outcomes in cardiovascular diseases: A systematic review and meta-analysis.

OBJECTIVES: Soluble suppression of tumorigenicity 2 (sST2) is a member of the interleukin-1 receptor family. It is raised in various cardiovascular diseases, but its value in predicting disease severity or mortality outcomes has been controversial. Therefore, we conducted a systematic review and meta-analysis to determine whether sST2 levels differed between survivors and non-survivors of patients with cardiovascular diseases, and whether elevated sST2 levels correlated with adverse outcomes. METHODS: PubMed and Embase were searched until 23rd June 2021 for studies that evaluated the relationship between sST2 levels and cardiovascular disease severity or mortality. RESULTS: A total of 707 entries were retrieved from both databases, of which 14 studies were included in the final meta-analysis. In acute heart failure, sST2 levels did not differ between survivors and non-survivors (mean difference [MD]: 24.2 ± 13.0 ng/ml; P = 0.06; I 2: 95%). Elevated sST2 levels tend to be associated with increased mortality risk (hazard ratio [HR]: 1.12, 95 %CI: 0.99-1.27, P = 0.07; I 2: 88%). In chronic heart failure, sST2 levels were higher in non-survivors than in survivors (MD: 0.19 ± 0.04 ng/ml; P = 0.001; I 2: 0%) and elevated levels were associated with increased mortality risk (HR: 1.64, 95% CI: 1.27-2.12, P < 0.001; I 2: 82%). sST2 levels were significantly higher in severe disease compared to less severe disease (MD: 1.56 ± 0.46 ng/ml; P = 0.001; I 2: 98%). Finally, in stable coronary artery disease, sST2 levels were higher in non-survivors than survivors (MD: 3.0 ± 1.1 ng/ml; P = 0.005; I 2: 80%) and elevated levels were significantly associated with increased mortality risk (HR: 1.32, 95% CI: 1.04-1.68, P < 0.05; I 2: 57%). CONCLUSIONS: sST2 significantly predicts disease severity and mortality in cardiovascular disease and is a good predictor of mortality in patients with stable coronary artery disease and chronic heart failure.

Contemporary Role of Cardiac Magnetic Resonance in the Management of Patients with Suspected or Known Coronary Artery Disease.

Cardiac magnetic resonance imaging (CMR) is a useful non-invasive radiation-free imaging modality for the management of patients with coronary artery disease (CAD). CMR cine imaging provides the "gold standard" assessment of ventricular function, late gadolinium enhancement (LGE) provides useful data for the diagnosis and extent of myocardial scar and viability, while stress imaging is an established technique for the detection of myocardial perfusion defects indicating ischemia. Beyond its role in the diagnosis of CAD, CMR allows accurate risk stratification of patients with established CAD. This review aims to summarize the data regarding the role of CMR in the contemporary management of patients with suspected or known coronary artery disease.

Current issues on simultaneous TAVR (Transcatheter Aortic Valve Replacement) and EVAR (Endovascular Aneurysm Repair).

Simultaneous EVAR and TAVR is technically feasible and is a reliable option in high-risk patients.

Anomaly Detection Trusted Hardware Sensors for Critical Infrastructure Legacy Devices.

Critical infrastructures and associated real time Informational systems need some security protection mechanisms that will be able to detect and respond to possible attacks. For this reason, Anomaly Detection Systems (ADS), as part of a Security Information and Event Management (SIEM) system, are needed for constantly monitoring and identifying potential threats inside an Information Technology (IT) system. Typically, ADS collect information from various sources within a CI system using security sensors or agents and correlate that information so as to identify anomaly events. Such sensors though in a CI setting (factories, power plants, remote locations) may be placed in open areas and left unattended, thus becoming targets themselves of security attacks. They can be tampering and malicious manipulated so that they provide false data that may lead an ADS or SIEM system to falsely comprehend the CI current security status. In this paper, we describe existing approaches on security monitoring in critical infrastructures and focus on how to collect security sensor-agent information in a secure and trusted way. We then introduce the concept of hardware assisted security sensor information collection that improves the level of trust (by hardware means) and also increases the responsiveness of the sensor. Thus, we propose a Hardware Security Token (HST) that when connected to a CI host, it acts as a secure anchor for security agent information collection. We describe the HST functionality, its association with a host device, its expected role and its log monitoring mechanism. We also provide information on how security can be established between the host device and the HST. Then, we introduce and describe the necessary host components that need to be established in order to guarantee a high security level and correct HST functionality. We also provide a realization-implementation of the HST overall concept in a FPGA SoC evaluation board and describe how the HST implementation can be controlled. In addition, in the paper, two case studies where the HST has been used in practice and its functionality have been validated (one case study on a real critical infrastructure test site and another where a critical industrial infrastructure was emulated in our lab) are described. Finally, results taken from these two case studies are presented, showing actual measurements for the in-field HST usage.

Association of QT dispersion with mortality and arrhythmic events-A meta-analysis of observational studies.

BACKGROUND: The risk stratification of coronary heart disease (CHD) and/or heart failure (HF) patients with easily measured electrocardiographic markers is of clinical importance. The aim of this meta-analysis is to indicate whether increased QT dispersion (QTd) is associated with fatal and nonfatal outcomes in patients with CHD and/or HF. METHODS: We systematically searched MEDLINE and Cochrane databases without restrictions until August 15, 2018 using the keyword "QT dispersion". Studies including data on the association between QTd and all-cause mortality, sudden cardiac death (SCD) or arrhythmic events in patients with HF and/or CHD were classified as eligible. RESULTS: In the analysis including patients with CHD and/or HF, we found that QTd did not differ significantly in patients with SCD compared to no SCD patients while QTd was significantly greater in the group of all-cause mortality patients and in patients who experienced a sustained ventricular arrhythmia. Subgroup analysis showed that in myocardial infarction studies, QTd was significantly higher in patients with an arrhythmic event compared to arrhythmic event-free patients while a nonsignificant difference was found in QTd in patients who died from any cause compared to survivors. Similarly, in HF patients, the QTd was significantly greater in patients with an arrhythmic event while a nonsignificant difference was found regarding all-cause mortality and SCD outcomes. CONCLUSIONS: QTd has a prognostic role for stratifying myocardial infarction or HF patients who are at higher risk of arrhythmic events. However, no prognostic role was found regarding all-cause mortality or SCD in this patient population.

Impact of ß-thalassemia trait carrier state on inflammatory status in patients with newly diagnosed hypertension.

BACKGROUND: B-thalassemia carrier state or thalassemia minor confers cardiovascular protection through favorable lipidemic and blood pressure profile. However, its impact on inflammatory status-a common denominator of the above conditions-has not been addressed. METHODS: We investigated a wide range of inflammatory markers [white blood cell (WBC) count, homocysteine, C-reactive protein (CRP), serum amyloid A (SAA), fibrinogen, plasminogen, fibronectin, plasminogen activator inhibitor-1 (PAI-1), and uric acid] in a large cohort of 15 805 newly diagnosed hypertensive patients (8299 men, 7506 women); 626 of them (4.0%) had thalassemia minor. RESULTS: The levels of WBC, homocysteine, CRP, SAA, fibrinogen, and PAI-1 were significantly lower in thalassemia minor patients, but not of plasminogen, fibronectin, and uric acid. In multivariate linear regression analyses, the lower values of WBC (<0.001), CRP (<0.001), homocysteine (<0.001), fibrinogen (<0.001), and PAI-1 (0.008), but not of SAA, were independently associated with thalassemia minor. The interaction between thalassemia minor and body mass index had a significant impact only on WBC and CRP (P for the interaction 0.010 and 0.005, respectively), whereas the interaction between thalassemia minor and sex had a significant impact only on fibrinogen (P for the interaction 0.007). CONCLUSION: Thalassemia minor is followed by a favorable inflammatory profile that may contribute to the overall better cardiovascular health of the carriers.

Cancer antigen-125 and risk of atrial fibrillation: a systematic review and meta-analysis.

BACKGROUND: Cancer antigen-125 (Ca-125) is traditionally recognised as a tumour marker and its role in cardiovascular diseases has been studied only in recent years. Whether Ca-125 is elevated in patients with atrial fibrillation (AF) and its levels predict the risk of AF remains controversial. Therefore, we conducted a systematic review and meta-analysis of the association between Ca-125 levels and AF. METHODS: PubMed and EMBASE databases were searched until 1 June 2017 for studies that evaluated the association between Ca-125 and AF. Inclusion criteria included studies that compare Ca-125 in patients with and without AF, or those reporting HRs/ORs for risk of AF stratified by Ca-125 levels. RESULTS: A total of 39 entries were retrieved from the databases, of which 10 studies were included in the final meta-analysis. Ca-125 was significantly higher in patients with AF compared with those in sinus rhythm (mean difference=16 U/mL, 95% CI 2 to 30 U/mL, P<0.05; I2: 98%). Ca-125 significantly increased the risk of AF (HR: 1.39, 95% CI 1.06 to 1.82, P<0.05; I2: 84%). CONCLUSION: Ca-125 was significantly higher in patients with AF than in those in sinus rhythm, and high Ca-125 is predictive of AF occurrence. However, the high heterogeneity observed means there is an uncertainty in the relationship between Ca-125 and AF, which needs to be confirmed by larger prospective studies.

Fibroblast growth factor 21 in cardio-metabolic disorders: a systematic review and meta-analysis.

BACKGROUND: Fibroblast growth factor 21 is a signalling protein involved in cell differentiation, morphogenesis, proliferation and metabolism. Recent studies have associated increased levels of FGF21 in the development of cardiovascular diseases, whereas others have reported no significant associations. Therefore, this systematic review and meta-analysis evaluated the value in predicting the risk of cardio-metabolic disorders and mortality. METHODS: PubMed and EMBASE were searched until 5th September 2017 for studies that evaluated the roles of FGF21 levels in cardio-metabolic disorders. RESULTS: A total of 183 and 301 entries were retrieved; 24 studies met the inclusion criteria. Four studies were identified by an additional search. Therefore, 28 studies were included in the final meta-analysis. High FGF21 levels significantly predicted the incidence of coronary artery disease (hazard ratio [HR]: 1.29; 95% confidence interval [CI]: 1.06-1.55; P < 0. 01; I2 = 48%) and the risk of metabolic syndrome (HR: 1.70, 95% CI: 1.35-2.15; P < 0.0001 I2 = 24%). In diabetes mellitus, FGF21 predicted disease incidence or progression (HR: 1.35, 95% CI: 1.06-1.72, P < 0.05, I2 = 69%) and worsening renal failure (HR: 1.06, 95% CI: 1.03-1.09, P < 0.0001, I2 = 47%). FGF21 also predicted all-cause mortality (HR: 3.00, 95% CI: 1.23-7.33; P < 0.05; I2 = 51%), and cardiovascular mortality (HR: 2.33, 95% CI: 1.08-4.99, P < 0.05, I2 = 75%). CONCLUSION: FGF21 significantly predicts the incidence of coronary artery disease, the risks of metabolic syndrome, diabetes mellitus and renal progression in diabetes. It also predicted all-cause and cardiovascular mortality.

Pancreatitis and myocarditis coexistence due to infection by Coxsackie B1 and B4 viruses.

Myocarditis can be a rare late manifestation of acute pancreatitis caused by Coxsackie virus infection. Clinicians should be aware of potentially life-threatening myocarditis because immediate recognition and management are the cornerstones in achieving a better outcome.

A "tilt" toward cinefluoroscopy.

Fluoroscopy permits rapid and straightforward assessment of mechanical valve function and allows a distinction between normal and malfunctional prostheses, acting as a complementary diagnostic step.