BRCA status and platinum sensitivity in advanced ovarian cancer according to Chemotherapy Response Score.

OBJECTIVE: To evaluate a relation between BRCA1/2 status and the Chemotherapy Response Score in patients with epithelial ovarian cancer undergoing neoadjuvant chemotherapy and interval debulking surgery. METHODS: Data were retrospectively collected on patients with unresectable disease undergoing three or four cycles of neoadjuvant chemotherapy and interval debulking surgery at the Gynecologic Oncology Unit of the Catholic University of the Sacred Heart from January 2016 to December 2020. All patients were assessed for BRCA1/2 somatic mutation at diagnosis. The omental specimens obtained at the interval surgery were evaluated according to Bohm's Chemotherapy Response Score System. RESULTS: A total of 172 patients were included in the analysis, 69 (40%) patients were BRCA1/2 mutation carriers and 103 (60%) patients were wild type. In the wild-type group (BRCAwt), 73 (70.9%) patients had a Chemotherapy Response Score of 1 or 2 and 30 (29.1%) patients had a score of 3. In the BRCA1/2 carriers group (BRCAmut), 39 (56.5%) patients had a score of 1 or 2 and 30 (43.5%) patients had a score of 3. Among the BRCAwt group, those with a Chemotherapy Response Score of 3 had a prolonged median progression-free survival (22 vs 15 months, p=0.003). Among the BRCAmut carriers group, no differences were found (30 vs 27 months, p=0.55). No difference in overall survival was observed in either the BRCAmut carriers population (p=0.23) or the BRCAwt population (60 vs 44 months, p=0.06). CONCLUSIONS: Patients with BRCA1/2mut seem to achieve a score of 1, 2 or 3 with the same frequency. In contrast, patients with BRCAwt seem to have a score of 1 or 2 more frequently than a score of 3. In patients with BRCA1/2mut, this score may not be an indicator of chemosensitivity.

Anti-inflammatory therapy in ischaemic heart disease: from canakinumab to colchicine.

Four large trials have recently evaluated the effects of anti-inflammatory drugs in the secondary prevention of major cardiovascular events (MACE) in over 25 000 patients followed for 1.9-3.7 years. CANTOS tested subcutaneous canakinumab [an anti-interleukin (IL) 1ß antibody] 300 mg every 3 months against placebo in patients with a history of myocardial infarction (MI) and serum C-reactive protein (CRP) >2 mg/L, demonstrating efficacy in preventing MACE but increased rates of fatal infections. COLCOT (in patients with recent MI) and LoDoCo2 (in patients with chronic coronary syndromes) tested oral colchicine (an NLRP3 inflammasome inhibitor) 0.5 mg daily vs. placebo, demonstrating prevention of MACE with a slightly increased risk of pneumonia in COLCOT (0.9 vs. 0.4%) but not in LoDoCo2. CIRT tested oral methotrexate (an anti-rheumatic anti-nuclear factor-kB) 15-20 mg per week against placebo in ischaemic heart disease patients with diabetes or metabolic syndrome, without significant reduction in MACE rates or in circulating IL6 or CRP levels, and with increased risk of skin cancers. In summary, canakinumab and colchicine have shown efficacy in preventing MACE in ischaemic heart disease patients, but only colchicine has acceptable safety (and cost) for use in secondary cardiovascular prevention. Clinical results are expected with the anti-IL6 ziltivekimab.

MicroRNAs in Valvular Heart Diseases: Biological Regulators, Prognostic Markers and Therapeutical Targets.

miRNAs have recently attracted investigators' interest as regulators of valvular diseases pathogenesis, diagnostic biomarkers, and therapeutical targets. Evidence from in-vivo and in-vitro studies demonstrated stimulatory or inhibitory roles in mitral valve prolapse development, aortic leaflet fusion, and calcification pathways, specifically osteoblastic differentiation and transcription factors modulation. Tissue expression assessment and comparison between physiological and pathological phenotypes of different disease entities, including mitral valve prolapse and mitral chordae tendineae rupture, emerged as the best strategies to address miRNAs over or under-representation and thus, their impact on pathogeneses. In this review, we discuss the fundamental intra- and intercellular signals regulated by miRNAs leading to defects in mitral and aortic valves, congenital heart diseases, and the possible therapeutic strategies targeting them. These miRNAs inhibitors are comprised of antisense oligonucleotides and sponge vectors. The miRNA mimics, miRNA expression vectors, and small molecules are instead possible practical strategies to increase specific miRNA activity. Advantages and technical limitations of these new drugs, including instability and complex pharmacokinetics, are also presented. Novel delivery strategies, such as nanoparticles and liposomes, are described to improve knowledge on future personalized treatment directions.

Association between Obesity and Atrial Function in Patients with Non-Valvular Atrial Fibrillation: An Echocardiographic Study.

Background: Obesity is a public health problem which prevalence has increased worldwide and is associated with different degrees of hemodynamic alterations and structural cardiac changes. The aim of the study is to investigate the impact of body mass index (BMI) on left atrial function using standard and advanced echocardiography in a population of patients with non-valvular atrial fibrillation (AF). Methods: 395 adult patients suffering from non-valvular AF, divided into three tertiles based on BMI value, carry out a cardiological examination with standard and advanced echocardiography. Results: Peak atrial longitudinal strain (PALS), a measure of left atrial function, is lower in the tertile with highest BMI (14.3 ± 8.2%) compared to both the first (19 ± 11.5%) and the second tertile (17.7 ± 10.6%) in a statistically significant manner (p < 0.002). Furthermore, BMI is significantly associated independent with the PALS by multilinear regression analysis, even after correction of the data for CHA2DS2-VASc score, left ventricular mass index, left ventricular ejection fraction, E/E' ratio and systolic pulmonary arterial pressure (coefficient standardized ß = -0.127, p < 0.02; Cumulative R2 = 0.41, SEE = 0.8%, p < 0.0001). Conclusions: BMI could be considered an additional factor in assessing cardiovascular risk in patients with non-valvular atrial fibrillation, in addition to the well-known CHA2DS2-VASc score.

Blockchain technology in Cardiovascular Medicine: a glance to the future? Results from a social media survey and future perspectives.

The leverage of digital facilities in medicine for disease diagnosis, monitoring, and medical history recording has become increasingly pivotal. However, the advancement of these technologies poses a significant challenge regarding data privacy, given the highly sensitive nature of medical information. In this context, the application of Blockchain technology, a digital system where information is stored in blocks and each block is linked to the one before, has the potential to enhance existing technologies through its exceptional security and transparency. This paradigm is of particular importance in cardiovascular medicine, where the prevalence of chronic conditions leads to the need for secure remote monitoring, secure data storage and secure medical history updating. Indeed, digital support for chronic cardiovascular pathologies is getting more and more crucial. This paper lays its rationale in three primary aims: 1) to scrutinize the existing literature for tangible applications of blockchain technology in the field of cardiology; 2) to report results from a survey aimed at gauging the reception of blockchain technology within the cardiovascular community, conducted on social media; 3) to conceptualize a web application tailored specifically to cardiovascular care based on blockchain technology. We believe that Blockchain technology may contribute to a breakthrough in healthcare digitalization, especially in the field of cardiology; in this context, we hope that the present work may be inspiring for physicians and healthcare stakeholders.

Right Ventricular Myocardial Involvement in Anderson-Fabry Disease at Diagnosis: Evaluation with Three-Dimensional Strain Imaging.

Background: Right ventricular (RV) involvement in Anderson-Fabry disease (AFD) is well known in the advanced stages of the disease RV hypertrophies, but little is known about the early involvement. The aim of our study was to assess RV function in AFD patients at diagnosis. Methods: A total of 23 AFD patients and 15 controls comparable for age and sex were recruited. A complete 2D standard echo with 3D volumetric and strain analysis of RV was performed. Results: Two patient populations, comparable for clinical baseline characteristics were considered. RV free wall thickness was significantly increased in the AFD group. No significant differences in standard RV indices (TAPSE, transverse diameter, tissue Doppler velocities of the lateral tricuspid annulus) were found. A 3D volumetric analysis showed reduced RV ejection fraction and lower values of longitudinal septal, free wall and global longitudinal strain (GLS) in AFD patients. RV free wall thickness significantly correlated with both free wall RV LS and RV GLS. In multiple linear regression analysis, RV free wall thickness was independently associated with RV GLS even after correction for age and heart rate. Conclusions: In AFD patients, 3D echocardiography allows for the identification of early subclinical functional impairment of RV. RV dysfunction is independently associated with RV hypertrophy.

Molecular Insights of SARS-CoV-2 Antivirals Administration: A Balance between Safety Profiles and Impact on Cardiovascular Phenotypes.

The COVID-19 pandemic has resulted in a complex clinical challenge, caused by a novel coronavirus, partially similar to previously known coronaviruses but with a different pattern of contagiousness, complications, and mortality. Since its global spread, several therapeutic agents have been developed to address the heterogeneous disease treatment, in terms of severity, hospital or outpatient management, and pre-existing clinical conditions. To better understand the rationale of new or old repurposed medications, the structure and host-virus interaction molecular bases are presented. The recommended agents by EDSA guidelines comprise of corticosteroids, JAK-targeting monoclonal antibodies, IL-6 inhibitors, and antivirals, some of them showing narrow indications due to the lack of large population trials and statistical power. The aim of this review is to present FDA-approved or authorized for emergency use antivirals, namely remdesivir, molnupinavir, and the combination nirmatrelvir-ritonavir and their impact on the cardiovascular system. We reviewed the literature for metanalyses, randomized clinical trials, and case reports and found positive associations between remdesivir and ritonavir administration at therapeutic doses and changes in cardiac conduction, relatable to their previously known pro-arrhythmogenic effects and important ritonavir interactions with cardioactive medications including antiplatelets, anti-arrhythmic agents, and lipid-lowering drugs, possibly interfering with pre-existing therapeutic regimens. Nonetheless, safety profiles of antivirals are largely questioned and addressed by health agencies, in consideration of COVID-19 cardiac and pro-thrombotic complications generally experienced by predisposed subjects. Our advice is to continuously adhere to the strict indications of FDA documents, monitor the possible side effects of antivirals, and increase physicians' awareness on the co-administration of antivirals and cardiovascular-relevant medications. This review dissects the global and local tendency to structure patient-based treatment plans, for a glance towards practical application of precision medicine.

The effectiveness and safety of pulmonary autograft as living tissue in Ross procedure: a systematic review.

Background: Reports on effectiveness and safety after the implant of pulmonary autograft (PA) living tissue in Ross procedure, to treat both congenital and acquired disease of the aortic valve and left ventricular outflow tract (LVOT), show variable durability results. We undertake a quantitative systematic review of evidence on outcome after the Ross procedure with the aim to improve insight into outcome and potential determinants. Methods: A systematic search of reports published from October 1979 to January 2021 was conducted (PubMed, Ovid Medline, Ovid Embase and Cochrane library) reporting outcomes after the Ross procedure in patients with diseased aortic valve with or without LVOT. Inclusion criteria were observational studies reporting on mortality and/or morbidity after autograft aortic valve or root replacement, completeness of follow-up >90%, and study size n≥30. Forty articles meeting the inclusion criteria were allocated to two categories: pediatric patient series and young adult patient series. Results were tabulated for a clearer presentation. Results: A total of 342 studies were evaluated of which forty studies were included in the final analysis as per the eligibility criteria. A total of 8,468 patients were included (7,796 in pediatric cohort and young adult series and 672 in pediatric series). Late mortality rates were remarkably low alongside similar age-matched mortality with the general population in young adults. There were differences in implantation techniques as regard the variability in stress and the somatic growth that recorded conflicting outcomes regarding the miniroot vs the subcoronary approach. Discussion: The adaptability of lung autograft to allow for both stress variability and somatic growth make it an ideal conduit for Ross's operation. The use of the miniroot technique over subcoronary implantation for better adaptability to withstand varying degrees of stress is perhaps more applicable to different patient subgroups.

Myocardial Cell Preservation from Potential Cardiotoxic Drugs: The Role of Nanotechnologies.

Cardiotoxic therapies, whether chemotherapeutic or antibiotic, represent a burden for patients who may need to interrupt life-saving treatment because of serious complications. Cardiotoxicity is a broad term, spanning from forms of heart failure induction, particularly left ventricular systolic dysfunction, to induction of arrhythmias. Nanotechnologies emerged decades ago. They offer the possibility to modify the profiles of potentially toxic drugs and to abolish off-target side effects thanks to more favorable pharmacokinetics and dynamics. This relatively modern science encompasses nanocarriers (e.g., liposomes, niosomes, and dendrimers) and other delivery systems applicable to real-life clinical settings. We here review selected applications of nanotechnology to the fields of pharmacology and cardio-oncology. Heart tissue-sparing co-administration of nanocarriers bound to chemotherapeutics (such as anthracyclines and platinum agents) are discussed based on recent studies. Nanotechnology applications supporting the administration of potentially cardiotoxic oncological target therapies, antibiotics (especially macrolides and fluoroquinolones), or neuroactive agents are also summarized. The future of nanotechnologies includes studies to improve therapeutic safety and to encompass a broader range of pharmacological agents. The field merits investments and research, as testified by its exponential growth.

The New Challenge for Heart Endocarditis: From Conventional Prosthesis to New Devices and Platforms for the Treatment of Structural Heart Disease.

Infective endocarditis is a sinister condition with considerable morbidity and mortality. Its relevance in the current era is compounded by the increased use of implanted devices such as replacement valves or cardiac implantable electronic devices. These infections are caused by multiple different bacteria with different virulence, pathogenicity, and antimicrobial resistance. Unlike in native endocarditis, the presence of foreign tissue permits sustenance by inflammatory and thrombotic processes as the artificial surfaces promote inflammatory responses and hypercoagulability. Prevention of these infections has been suggested with the use of homografts in combination with antibiotics. Others have attempted to use "low fouling coats" with little clinical success thus far. The use of antibiotic prophylaxis plays a pivotal part in reducing the incidence of prosthesis-related endocarditis. This remains especially crucial with the increasing use of transcatheter heart valve therapies. The widespread use of cardiac implantable electronic devices such as permanent pacemakers, implantable cardioverter defibrillators, and cardiac resynchronization therapy devices has also heralded a noticeable increase in cases of infectious endocarditis affecting complex equipment which can be difficult to treat. Multimodality strategies are needed with input from surgeons and cardiologists to ensure treatment is both prompt and successful, tailored to the individual needs of the patients.

Thromboembolic Complications of SARS-CoV-2 and Metabolic Derangements: Suggestions from Clinical Practice Evidence to Causative Agents.

Severe Acute Respiratory Syndrome (SARS) Coronavirus (CoV)-2 is a recently identified positive sense single-strand RNA (ssRNA) ß-coronavirus. The viral spike proteins infect human hosts by binding to the cellular receptor angiotensin-converting enzyme 2 (ACE2). The infection causes a systemic illness involving cell metabolism. This widespread involvement is implicated in the pathophysiology of the illness which ranges from mild to severe, requiring multi organ support, ranging from oxygen supplementation to full cardiovascular and respiratory support. Patients with multiple co-existing comorbidities are also at a higher risk. The aim of this review is to explore the exact mechanisms by which COVID-19 affects patients systemically with a primary focus on the bleeding and thrombotic complications linked with the disease. Issues surrounding the thrombotic complications following administration of the ChAdOx1 nCoV-19 (Astra-Zeneca-Oxford) vaccine have also been illustrated. Risk stratification and treatment options in these patients should be tailored according to clinical severity with input from a multidisciplinary team.

COVID-19 Pathogenesis: From Molecular Pathway to Vaccine Administration.

The Coronavirus 2 (SARS-CoV-2) infection is a global pandemic that has affected millions of people worldwide. The advent of vaccines has permitted some restitution. Aside from the respiratory complications of the infection, there is also a thrombotic risk attributed to both the disease and the vaccine. There are no reliable data for the risk of thromboembolism in SARS-CoV-2 infection in patients managed out of the hospital setting. A literature review was performed to identify the pathophysiological mechanism of thrombosis from the SARS-CoV-2 infection including the role of Angiotensin-Converting Enzyme receptors. The impact of the vaccine and likely mechanisms of thrombosis following vaccination were also clarified. Finally, the utility of the vaccines available against the multiple variants is also highlighted. The systemic response to SARS-CoV-2 infection is still relatively poorly understood, but several risk factors have been identified. The roll-out of the vaccines worldwide has also allowed the lifting of lockdown measures and a reduction in the spread of the disease. The experience of the SARS-CoV-2 infection, however, has highlighted the crucial role of epidemiological research and the need for ongoing studies within this field.

Nonsurgical Management of a Papillary Fibroelastoma of the Aortic Valve.

We report the case of a 63-year-old woman who had an incidental echocardiographic diagnosis of papillary fibroelastoma (PFE) of the right coronary cusp of the aortic valve. The patient was informed about the embolic risk due to the pedunculated mass located on the aortic valve but she refused the proposed surgical removal. She was followed up yearly, and each follow-up included an echocardiographic evaluation of the mass. The lady is taking lysine acetylsalycilate 160 mg daily, and after more than 19 years later, she does not complain any symptoms or complications as a result of possible embolic episodes. If on one hand, our report is provocative for PFE nonsurgical management; on the other, we do believe that in symptomatic patients PFE located in the left heart chambers, the standard of care remains surgical excision after diagnosis. Anyway, our analysis shows that further data in this issue are needed in asymptomatic patients, and surgical indication should be proposed considering carefully the risk-benefit balance.

Percutaneous versus Surgical Intervention for Severe Aortic Valve Stenosis: A Systematic Review.

Aortic stenosis is a disease that is increasing in prevalence and manifests as decreased cardiac output, which if left untreated can result in heart failure and ultimately death. It is primarily a disease of the elderly who often have multiple comorbidities. The advent of transcatheter aortic valve therapies has changed the way we treat these conditions. However, long-term results of these therapies remain uncertain. Recently, there has been an increasing number of studies examining the role of both surgical aortic valve replacement and transcatheter aortic valve replacement. We therefore performed a systematic review using Ovid MEDLINE, Ovid Embase, and the Cochrane Library. Two investigators searched papers published between January 1, 2007, and to date using the following terms: "aortic valve stenosis," "aortic valve operation," and "transcatheter aortic valve therapy." Both strategies in aortic stenosis treatment highlighted specific indications alongside the pitfalls such as structural valve degeneration and valve thrombosis which have a bearing on clinical outcomes. We propose some recommendations to help clinicians in the decision-making process as technological improvements make both surgical and transcatheter therapies viable options for patients with aortic stenosis. Finally, we assess the role of finite element analysis in patient selection for aortic valve replacement. THVT and AVR-S are both useful tools in the armamentarium against aortic stenosis. The decision between the two treatment strategies should be best guided by a strong robust evidence base, ideally with a long-term follow-up. This is best performed by the heart team with the patient as the center of the discussion.

The Choice of Pulmonary Autograft in Aortic Valve Surgery: A State-of-the-Art Primer.

The Ross procedure has long been seen as an optimal operation for a select few. The detractors of it highlight the issue of an additional harvesting of the pulmonary artery, subjecting the native PA to systemic pressures and the need for reintervention as reasons to avoid it. However, the PA is a living tissue and capable of adapting and remodeling to growth. We therefore review the current evidence available to discuss the indications, contraindications, harvesting techniques, and modifications in a state-of-the-art narrative review of the PA as an aortic conduit. Due to the lack of substantial well-designed randomized controlled trials (RCTs), we also highlight the areas of need to reiterate the importance of the Ross procedure as part of the surgical armamentarium.

The Use of Radial Artery for CABG: An Update.

We used the radial artery as a second target conduit for coronary artery bypass grafting since 1971. However, randomized clinical studies have demonstrated differences in clinical outcomes between the radial artery and other grafts because these trials are underpowered. As we proceed toward 50 years of experience with radial artery grafting, we examined the literature to define the best second-best target vessel for coronary artery bypass grafting. The literature was reviewed with emphasis, and a large number of randomized controlled trials, propensity-matched observational series, and meta-analyses were identified with a large patient population who received arterial conduit and saphenous vein grafts. The radial artery has been shown to be effective and safe when used as a second target conduit for coronary artery bypass grafting. Results and patency rates were superior to those for saphenous vein grafting. It has also been shown that the radial artery is a safe and effective graft as a third conduit into the territory of the artery right coronary artery. However, there is little evidence based on a few comparable series limiting the use of the gastroepiploic artery. In its fifth decade of use, we can finally deduced that the aorto-to-coronary radial bypass graft is the conduit of choice for coronary operations after the left internal thoracic artery to the left anterior descending artery.

Precision Phenomapping of Acute Coronary Syndromes to Improve Patient Outcomes.

Acute coronary syndromes (ACS) are a global leading cause of death. These syndromes show heterogeneity in presentation, mechanisms, outcomes and responses to treatment. Precision medicine aims to identify and synthesize unique features in individuals, translating the acquired data into improved personalised interventions. Current precision treatments of ACS include immediate coronary revascularisation driven by ECG ST-segment elevation, early coronary angiography based on elevated blood cardiac troponins in patients without ST-segment elevation, and duration of intensified antithrombotic therapy according to bleeding risk scores. Phenotypically stratified analyses of multi-omic datasets are urgently needed to further refine and couple the diagnosis and treatment of these potentially life-threatening conditions. We provide definitions, examples and possible ways to advance precision treatments of ACS.

Trends in Managing Cardiac and Orthopaedic Device-Associated Infections by Using Therapeutic Biomaterials.

Over the years, there has been an increasing number of cardiac and orthopaedic implanted medical devices, which has caused an increased incidence of device-associated infections. The surfaces of these indwelling devices are preferred sites for the development of biofilms that are potentially lethal for patients. Device-related infections form a large proportion of hospital-acquired infections and have a bearing on both morbidity and mortality. Treatment of these infections is limited to the use of systemic antibiotics with invasive revision surgeries, which had implications on healthcare burdens. The purpose of this review is to describe the main causes that lead to the onset of infection, highlighting both the biological and clinical pathophysiology. Both passive and active surface treatments have been used in the field of biomaterials to reduce the impact of these infections. This includes the use of antimicrobial peptides and ionic liquids in the preventive treatment of antibiotic-resistant biofilms. Thus far, multiple in vivo studies have shown efficacious effects against the antibiotic-resistant biofilm. However, this has yet to materialize in clinical medicine.

Exploring the Operative Strategy for Secondary Mitral Regurgitation: A Systematic Review.

BACKGROUND: Mitral valve disease surgery is an evolving field with multiple possible interventions. There is an increasing body of evidence regarding the optimal strategy in secondary mitral regurgitation where the pathology lies within the ventricle. We conducted a systematic review to identify the benefits and limitations of each surgical option. METHODS: A systematic review of the literature was performed to identify pertinent randomized controlled trials (RCTs), propensity-matched observational series, and meta-analyses which were considered initially and followed by unmatched observational series using the MEDLINE, Ovid EMBASE, and Cochrane Library. RESULTS: We identified 6 different strategies for treating secondary mitral valve regurgitation: mitral valve replacement, restrictive mitral annuloplasty, surgical revascularization (with and without mitral annuloplasty), subvalvular procedures (papillary muscle approximation, papillary muscle relocation, ring and string procedure), and procedures directly targeting the mitral valve (edge-to-edge repair and anterior leaflet enlargement) alongside transcatheter heart valve therapy. We also highlighted the role of left ventricular assist devices in the management of this condition. The benefits and limitations of each intervention are highlighted. CONCLUSION: There is currently no unanimous and shared strategy for the optimal treatment of patients with secondary IMR. The management of patients with secondary mitral regurgitation must be entrusted to a multidisciplinary Heart Team to ensure ideal intervention and patient matching for the best outcomes.

CoreValve vs. Sapien 3 Transcatheter Aortic Valve Replacement: A Finite Element Analysis Study.

AIM: to investigate the factors implied in the development of postoperative complications in both self-expandable and balloon-expandable transcatheter heart valves by means of finite element analysis (FEA). MATERIALS AND METHODS: FEA was integrated into CT scans to investigate two cases of postoperative device failure for valve thrombosis after the successful implantation of a CoreValve and a Sapien 3 valve. Data were then compared with two patients who had undergone uncomplicated transcatheter heart valve replacement (TAVR) with the same types of valves. RESULTS: Computational biomechanical modeling showed calcifications persisting after device expansion, not visible on the CT scan. These calcifications determined geometrical distortion and elliptical deformation of the valve predisposing to hemodynamic disturbances and potential thrombosis. Increased regional stress was also identified in correspondence to the areas of distortion with the associated paravalvular leak. CONCLUSION: the use of FEA as an adjunct to preoperative imaging might assist patient selection and procedure planning as well as help in the detection and prevention of TAVR complications.