Onco-Hypertension: A Continuously Developing Field between Cancer and Hypertension.

The prognosis of cancer patients has greatly improved in the last years, owing to the development of novel chemotherapeutic agents. However, this progress comes with an increasing occurrence of cardiovascular adverse reactions. A serious side effect is arterial hypertension (HT), which is the most frequent comorbidity encountered in cancer patients, influencing the outcomes in cancer survivors. Even though secondary HT related to specific chemotherapeutic agents, such as vascular endothelial growth factor inhibitors, is usually mild and reversible, in rare instances it can be severe, leading to discontinuation of chemotherapy. In addition, HT per se has been studied as a potential risk factor for cancer development. The relationship is even more complex than previously thought, as concerning evidence recently highlighted the potential oncogenic effects of antihypertensive drugs, particularly thiazide diuretics, which may increase the risk of skin cancer. As a result, in light of the similar risk factors and overlapping pathophysiological mechanisms between HT and cancer, a promising concept of onco-hypertension has emerged, aiming to improve the understanding of the complicated interplay between these two pathologies and maintain a balance between the efficacy and risks of both antihypertensive drugs and chemotherapy agents.

The portrait of a stranger: the hypereosinophilic syndrome with cardiac involvement.

INTRODUCTION: Hypereosinophilic syndrome is a rare clinical condition, and cardiac involvement confers a poor prognosis. Hypereosinophilic myocarditis is a medical emergency and targeted treatment should be started promptly even before a definitive diagnosis could be made. CASE PRESENTATION: A 27-year-old female patient is hospitalized for exertional dyspnea, chest pain, and fatigue for the past 2 weeks. She also describes left leg paresthesias. Clinical examination was in normal limits. ECG showed sinus tachycardia, QS pattern in V1-V4, and diffuse flattened T waves. Laboratory tests revealed increased inflammatory markers, hypereosinophilia, elevated cardiac enzymes, high NT-proBNP. Echocardiography revealed LV dysfunction (EF 31%), while cardiac MRI showed diffuse delayed enhancement with predominant subendocardial disposition. The electromyogram was suggestive of left tibial nerve neuropathy. We interpreted the case as eosinophilic myocarditis with an urgent requirement of therapy and initiated high-dose glucocorticoid therapy and the GDMT 4-pillar heart failure treatment. We excluded common infectious, myeloproliferative syndromes, and frequent associated autoimmune diseases. With prednisone, the eosinophil count rapidly normalized and we gradually tapered the dose by 5 mg per week, however continuing with heart failure therapy. At monthly follow-up visits, there was a significant clinical improvement, with normalization of the eosinophilic count, and a near-normalization of myocardial function. The only symptom that persisted was paresthesias linked to left tibial neuropathy. CONCLUSION: The surprisingly rapid and favorable course of the disease offers a high index of suspicion for a toxic or a reactive transitory etiology, however still unidentified. In our case, the cause of eosinophilia remained unknown, although we managed to narrow down the possible etiologies. A surprisingly good clinical response was obtained with non-specific treatment targeting mainly hyperosinophilic myocarditis.

Progress in Biomaterials for Cardiac Tissue Engineering and Regeneration.

Cardiovascular diseases are one of the leading global causes of morbidity and mortality, posing considerable health and economic burden on patients and medical systems worldwide. This phenomenon is attributed to two main motives: poor regeneration capacity of adult cardiac tissues and insufficient therapeutic options. Thus, the context calls for upgrading treatments to deliver better outcomes. In this respect, recent research has approached the topic from an interdisciplinary perspective. Combining the advances encountered in chemistry, biology, material science, medicine, and nanotechnology, performant biomaterial-based structures have been created to carry different cells and bioactive molecules for repairing and restoring heart tissues. In this regard, this paper aims to present the advantages of biomaterial-based approaches for cardiac tissue engineering and regeneration, focusing on four main strategies: cardiac patches, injectable hydrogels, extracellular vesicles, and scaffolds and reviewing the most recent developments in these fields.

Cardiovascular Disease as a Consequence or a Cause of Cancer: Potential Role of Extracellular Vesicles.

Both cardiovascular disease and cancer continue to be causes of morbidity and mortality all over the world. Preventing and treating heart disease in patients undergoing cancer treatment remain an important and ongoing challenge for improving the lives of cancer patients, but also for their survival. Despite ongoing efforts to improve patient survival, minimal advances have been made in the early detection of cardiovascular disease in patients suffering from cancer. Understanding the communication between cancer and cardiovascular disease can be based on a deeper knowledge of the molecular mechanisms that define the profile of the bilateral network and establish disease-specific biomarkers and therapeutic targets. The role of exosomes, microvesicles, and apoptotic bodies, together defined as extracellular vesicles (EVs), in cross talk between cardiovascular disease and cancer is in an incipient form of research. Here, we will discuss the preclinical evidence on the bilateral connection between cancer and cardiovascular disease (especially early cardiac changes) through some specific mediators such as EVs. Investigating EV-based biomarkers and therapies may uncover the responsible mechanisms, detect the early stages of cardiovascular damage and elucidate novel therapeutic approaches. The ultimate goal is to reduce the burden of cardiovascular diseases by improving the standard of care in oncological patients treated with anticancer drugs or radiotherapy.

The platelet to lymphocyte ratio in heart failure: a comprehensive review.

Introduction: At the crossroads of heart failure (HF) and systemic inflammation, platelets and lymphocytes are both influenced as well as actively participating in the bidirectional relationship. The platelet to lymphocyte ratio (PLR) could therefore be a marker of severity. This review aimed to assess the role of PLR in HF. Methods: We searched the PubMed (MEDLINE) database using the keywords "platelet", "thrombocyte", "lymphocyte", "heart failure", "cardiomyopathy", "implantable cardioverter defibrillator", "cardiac resynchronization therapy" and "heart transplant". Results: We identified 320 records. 21 studies were included in this review, with a total of 17,060 patients. PLR was associated with age, HF severity, and comorbidity burden. Most studies reported the predictive power for all-cause mortality. Higher PLR was associated with in-hospital and short-term mortality in univariable analysis, however, it was not consistently an independent predictor for this outcome. PLR > 272.9 associated an adjusted HR of 3.22 (95%CI 1.56 - 5.68, p<0.001) for 30-day fatality. During long-term follow-up from 6 months to 5 years, PLR was an independent predictor of mortality in most studies, with cut-off values ranging from > 150 to > 194.97 and adjusted HR from 1.47 (95%CI 1.06 - 2.03, p=0.019) to 5.65 (95%CI 2.47-12.96, p<0.001). PLR > 173.09 had an adjusted OR 2.89 (95%CI 1.17-7.09, p=0.021) for predicting response to cardiac resynchronization therapy. PLR was not associated with outcomes after cardiac transplant or implantable cardioverter-defibrillator. Conclusion: Increased PLR could be an auxiliary biomarker of severity and survival prognosis in HF patients.

Prognostic Impact of Severe Atrial Functional Tricuspid Regurgitation in Atrial Fibrillation Patients.

Background and Aim: Atrial fibrillation (AF) is an epidemic disease with a significant global health impact. Atrial functional tricuspid regurgitation (AF-TR) is a more recently acknowledged complication of AF. The main purpose of this study was to determine the prognostic value of severe AF-TR in patients with AF, and its determinants. Methods: In this retrospective, observational study, we included AF patients admitted consecutively to a tertiary clinical hospital between January 2018 and February 2020, irrespective of cause of hospitalization. Patients with organic TR, significant pulmonary hypertension, left ventricular ejection fraction < 50%, those with implanted cardiac devices and those with in-hospital mortality were excluded. Severe TR was defined according to current guidelines. Median follow-up time was 34 (28−39) months. Primary endpoint was all-cause mortality. Results: We included 246 AF patients, with a mean age of 71.5 ± 9.4 years. 86.2% had AF-TR, while 8.1% had severe AF-TR. Mortality rate was 8.5%. Right atrial diameter (p = 0.005), systolic pulmonary artery pressure (sPAP) (p = 0.015) and NT-proBNP (p = 0.026) were independent predictors for the presence of severe valvular dysfunction. In multivariable survival analysis, severe AF-TR, was an independent predictor of all-cause mortality (HR 5.4, 95% CI 1.1−26.2, p = 0.035). Conclusion: Severe AF-TR was an independent predictor of mortality in AF patients, while mild/moderate AF-TR apparently had no impact on prognosis.

The Management of Hypertensive Emergencies-Is There a "Magical" Prescription for All?

Hypertensive emergencies (HE) represent high cardiovascular risk situations defined by a severe increase in blood pressure (BP) associated with acute, hypertension mediated organ damage (A-HMOD) to the heart, brain, retina, kidneys, and large arteries. Blood pressure values alone do not accurately predict the presence of HE; therefore, the search for A-HMOD should be the first step in the management of acute severe hypertension. A rapid therapeutic intervention is mandatory in order to limit and promote regression of end-organ damage, minimize the risk of complications, and improve patient outcomes. Drug therapy for HE, target BP, and the speed of BP decrease are all dictated by the type of A-HMOD, specific drug pharmacokinetics, adverse drug effects, and comorbidities. Therefore, a tailored approach is warranted. However, there is currently a lack of solid evidence for the appropriate treatment strategies for most HE. This article reviews current pharmacological strategies while providing a stepwise, evidence based approach for the management of HE.

Non-Invasive Assessment of Congestion by Cardiovascular and Pulmonary Ultrasound and Biomarkers in Heart Failure.

Worsening chronic heart failure (HF) is responsible for recurrent hospitalization and increased mortality risk after discharge, irrespective to the ejection fraction. Symptoms and signs of pulmonary and systemic congestion are the most common cause for hospitalization of acute decompensated HF, as a consequence of increased cardiac filling pressures. The elevated cardiac filling pressures, also called hemodynamic congestion, may precede the occurrence of clinical congestion by days or weeks. Since HF patients often have comorbidities, dyspnoea, the main symptom of HF, may be also caused by respiratory or other illnesses. Recent studies underline the importance of the diagnosis and treatment of hemodynamic congestion before HF symptoms worsen, reducing hospitalization and improving prognosis. In this paper we review the role of integrated evaluation of biomarkers and imaging technics, i.e., echocardiography and pulmonary ultrasound, for the diagnosis, prognosis and treatment of congestion in HF patients.

Biomaterials as Haemostatic Agents in Cardiovascular Surgery: Review of Current Situation and Future Trends.

Intraoperative haemostasis is of paramount importance in the practice of cardiovascular surgery. Over the past 70 years, topical haemostatic methods have advanced significantly and today we deal with various haemostatic agents with different properties and different mechanisms of action. The particularity of coagulation mechanisms after extracorporeal circulation, has encouraged the introduction of new types of topic agents to achieve haemostasis, where conventional methods prove their limits. These products have an important role in cardiac, as well as in vascular, surgery, mainly in major vascular procedures, like aortic dissections and aortic aneurysms. This article presents those agents used for topical application and the mechanism of haemostasis and offers general recommendations for their use in the operating room.

Importance of Visual Estimation of Coronary Artery Stenoses and Use of Functional Evaluation for Appropriate Guidance of Coronary Revascularization-Multiple Operator Evaluation.

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.

Cardiovascular Stents: A Review of Past, Current, and Emerging Devices.

One of the leading causes of morbidity and mortality worldwide is coronary artery disease, a condition characterized by the narrowing of the artery due to plaque deposits. The standard of care for treating this disease is the introduction of a stent at the lesion site. This life-saving tubular device ensures vessel support, keeping the blood-flow path open so that the cardiac muscle receives its vital nutrients and oxygen supply. Several generations of stents have been iteratively developed towards improving patient outcomes and diminishing adverse side effects following the implanting procedure. Moving from bare-metal stents to drug-eluting stents, and recently reaching bioresorbable stents, this research field is under continuous development. To keep up with how stent technology has advanced in the past few decades, this paper reviews the evolution of these devices, focusing on how they can be further optimized towards creating an ideal vascular scaffold.

Diagnosis of Cardiac Abnormalities in Muscular Dystrophies.

Muscular disorders are mainly characterized by progressive skeletal muscle weakness. There are several aspects that can be monitored, which are used to differentiate between the types of muscular disorders, ranging from the targeted muscle up to the mutated gene. An aspect that holds critical importance when managing muscular dystrophies is that most of them exhibit cardiac abnormalities. Therefore, cardiac imaging is an essential part of muscular disorder monitoring and management. In the first section of the review, several cardiac abnormalities are introduced; afterward, different muscular dystrophies' pathogenesis is presented. Not all muscular dystrophies necessarily present cardiac involvement; however, the ones that do are linked with the cardiac abnormalities described in the first section. Moreover, studies from the last 3 years on muscular disorders are presented alongside imaging techniques used to determine cardiac abnormalities.

The Road to Better Management in Resistant Hypertension-Diagnostic and Therapeutic Insights.

Resistant hypertension (R-HTN) implies a higher mortality and morbidity compared to non-R-HTN due to increased cardiovascular risk and associated adverse outcomes-greater risk of developing chronic kidney disease, heart failure, stroke and myocardial infarction. R-HTN is considered when failing to lower blood pressure below 140/90 mmHg despite adequate lifestyle measures and optimal treatment with at least three medications, including a diuretic, and usually a blocker of the renin-angiotensin system and a calcium channel blocker, at maximally tolerated doses. Hereby, we discuss the diagnostic and therapeutic approach to a better management of R-HTN. Excluding pseudoresistance, secondary hypertension, white-coat hypertension and medication non-adherence is an important step when diagnosing R-HTN. Most recently different phenotypes associated to R-HTN have been described, specifically refractory and controlled R-HTN and masked uncontrolled hypertension. Optimizing the three-drug regimen, including the diuretic treatment, adding a mineralocorticoid receptor antagonist as the fourth drug, a ß-blocker as the fifth drug and an α1-blocker or a peripheral vasodilator as a final option when failing to achieve target blood pressure values are current recommendations regarding the correct management of R-HTN.

Deep neural networks for ECG-free cardiac phase and end-diastolic frame detection on coronary angiographies.

Invasive coronary angiography (ICA) is the gold standard in Coronary Artery Disease (CAD) imaging. Detection of the end-diastolic frame (EDF) and, in general, cardiac phase detection on each temporal frame of a coronary angiography acquisition is of significant importance for the anatomical and non-invasive functional assessment of CAD. This task is generally performed via manual frame selection or semi-automated selection based on simultaneously acquired ECG signals - thus introducing the requirement of simultaneous ECG recordings. In this paper, we evaluate the performance of a purely image based workflow relying on deep neural networks for fully automated cardiac phase and EDF detection on coronary angiographies. A first deep neural network (DNN), trained to detect coronary arteries, is employed to preselect a subset of frames in which coronary arteries are well visible. A second DNN predicts cardiac phase labels for each frame. Only in the training and evaluation phases for the second DNN, ECG signals are used to provide ground truth labels for each angiographic frame. The networks were trained on 56,655 coronary angiographies from 6820 patients and evaluated on 20,780 coronary angiographies from 6261 patients. No exclusion criteria related to patient state (stable or acute CAD), previous interventions (PCI or CABG), or pathology were formulated. Cardiac phase detection had an accuracy of 98.8 %, a sensitivity of 99.3 % and a specificity of 97.6 % on the evaluation set. EDF prediction had a precision of 98.4 % and a recall of 97.9 %. Several sub-group analyses were performed, indicating that the cardiac phase detection performance is largely independent from acquisition angles, the heart rate of the patient, and the angiographic view (LCA / RCA). The average execution time of cardiac phase detection for one angiographic series was on average less than five seconds on a standard workstation. We conclude that the proposed image based workflow potentially obviates the need for manual frame selection and ECG acquisition, representing a relevant step towards automated CAD assessment.

Intravenous Administration of Allogenic Cell-Derived Microvesicles of Healthy Origins Defend Against Atherosclerotic Cardiovascular Disease Development by a Direct Action on Endothelial Progenitor Cells.

Atherosclerosis and cardiovascular disease development is the outcome of intermediate processes where endothelial dysfunction and vascular inflammation are main protagonists. Cell-derived microvesicles (MVs), endothelial progenitor cells (EPCs), and circulating microRNAs (miRNAs) are known as biomarkers and potential regulators for atherosclerotic vascular disease, but their role in the complexity of the inflammatory process and in the mechanism of vascular restoration is far from clear. We aimed to evaluate the biological activity and functional role of MVs, in particular of the EPCs-derived MVs (MVEs), of healthy origins in reducing atherosclerotic vascular disease development. The experiments were performed on hamsters divided into the following groups: simultaneously hypertensive-hyperlipidemic (HH group) by combining two feeding conditions for 4 months; HH with retro-orbital sinus injection containing 1 × 105 MVs or MVEs from control hamsters, one dose per month for 4 months of HH diet, to prevent atherosclerosis (HH-MVs or HH-MVEs group); and controls (C group), age-matched normal healthy animals. We found that circulating MV and MVE transplantation of healthy origins significantly reduces atherosclerosis development via (1) the mitigation of dyslipidemia, hypertension, and circulating EPC/cytokine/chemokine levels and (2) the structural and functional remodeling of arterial and left ventricular walls. We also demonstrated that (1) circulating MVs contain miRNAs; this was demonstrated by validating MVs and MVEs as transporters of Ago2-miRNA, Stau1-miRNA, and Stau2-miRNA complexes and (2) MV and MVE administration significantly protect against atherosclerotic cardiovascular disease via transfer of miR-223, miR-21, miR-126, and miR-146a to circulating late EPCs. It should be mentioned that the favorable effects of MVEs were greater than those of MVs. Our findings suggest that allogenic MV and MVE administration of healthy origins could counteract HH diet-induced detrimental effects by biologically active miR-10a, miR-21, miR-126, and miR-146a transfer to circulating EPCs, mediating their vascular repair function in atherosclerosis processes.

The riddle of the right ventricle.

Right ventricular (RV) myxoma is a very rare finding. Its differential diagnosis includes cardiac thrombus, and its risk of life-threatening complications mandates early diagnosis followed by surgical resection. We report the case of a patient with an incidental RV mass and a difficult differential diagnosis. A 66-year-old woman, first assessed in neurosurgery due to a lumbar herniated disc, was referred to cardiology for examination before proceeding to surgery. She complained of dyspnea on exertion present for the last few months and reported no fainting or syncope. Clinical examination showed intermittent pulmonary systolic murmur. Transthoracic echocardiography revealed an oval-shaped sessile mobile mass (42∕18 mm) attached to the anterior RV wall. Computed tomography confirmed the presence of a RV mass with lower attenuation than the myocardium and extension towards the pulmonary trunk, without other abdominal or pulmonary masses that would suggest a thrombus. Cardiac magnetic resonance imaging described an ovoid mass (47∕16 mm) in the right ventricle, "clinging" to the apical trabeculae, swinging during the cardiac cycle, causing partial obstruction of the pulmonary valve during systole. The patient underwent surgical resection of the tumor. Macroscopic specimen showed a translucent polypoid mass with hemorrhagic areas. Microscopy confirmed the diagnosis of RV myxoma. The case illustrates the difficulty of establishing the correct etiological diagnosis of a cardiac mass, especially when located in the right ventricle. Multimodality imaging remains the cornerstone of noninvasive tissue characterization of cardiac masses, still requiring histopathological confirmation, particularly in the setting of conflicting imaging results.

Platelets of Healthy Origins Promote Functional Improvement of Atherosclerotic Endothelial Progenitor Cells.

The purpose was to evaluate the effect of platelets on functional properties of late endothelial progenitor cells (EPCs), in the direct co-culture conditions, and to investigate the involved mediators, in experimental induced atherosclerosis. The late EPCs obtained from two animal groups, hypertensive-hyperlipidemic (HH) and control (C) hamsters, named late EPCs-HH and late EPCs-C, were co-incubated with or without platelets isolated from both groups. Our results have showed that exposure to platelets from control animals: (i) promoted the late EPCs-C capacity to form colonies and capillary-like structures, and also to proliferate and migrate; (ii) improved the functional properties of late EPCs-HH; (iii) strengthened the direct binding EPCs-platelets; (iv) increased SDF-1α,VEGF, PDGF, and reduced CD40L, IL-1ß,-6,-8 levels; and (v) enhanced miR-223 and IGF-1R expressions. Platelets from HH group diminished functional abilities for both EPC types and had opposite effects on these pro-angiogenic and pro-inflammatory molecules. Furthermore, testing the direct effect of miR-223 and IGF-1R on late EPCs disclosed that these molecular factors improve late EPC functional properties in atherosclerosis in terms of stimulation of the proliferation and migration abilities. In conclusion, in vitro exposure to platelets of healthy origins had a positive effect on functional properties of atherosclerotic late EPCs. The most likely candidates mediating EPC-platelet interaction can be SDF-1α, VEGF, CD40L, PDGF, IL-1ß,-6,-8, miR-223, and IGF-1R. The current study brings evidences that the presence of healthy origin platelets is of utmost importance on functional improvement of EPCs in atherosclerosis.

Target Organ Damage and Cardiovascular Risk in a Hypertensive Roma Sample Population in Romania.

BACKGROUND: The largest European Roma community resides in Romania, but there is still little published data on cardiovascular (CV) risk factors and disease in this group. This study addresses the prevalence of arterial hypertension, associated CV disease risk, and target organ damage (TOD) in a Roma community from Bucharest, Romania. METHODS: This is a cross-sectional community-based participatory research to assess for CV risk factors, TOD and CV disease, including 806 Roma ethnics (18-83 years) integrated in the local community, 36.16% males. Evaluation included physical examination with blood pressure, pulse wave velocity and anklebrachial measurements, laboratory tests, ECG, echocardiography and fundoscopy. RESULTS: Prevalence of hypertension was 33.62%, awareness 76.38%, higher in females (p>0.01), and control rate 44.39%. Compared to age-matched normotensives, hypertensives had more left ventricle hypertrophy and more frequently increased pulse pressure. Differences in TOD were attenuated between newly and previously diagnosed, controlled and uncontrolled, hypertensives. Cardiovascular disease was almost absent in normotensives. Ten-year risk for fatal CV disease followed an increasing trend from normotension to long standing hypertension. CONCLUSION: This is the first dedicated study to thoroughly assess TOD and risk for fatal CV disease in a Romanian Roma population. Hypertension was less prevalent than in the general population, with similar awareness, possibly as a consequence of integration in the surrounding community. Fatal CV disease risk followed the trend of increasing prevalence of risk factors, and hypertension played an important role in its modulation.

Patient autonomy and disclosure of material information about hospital-acquired infections.

Hospital-acquired infections are nowadays a major health care problem worldwide. The morbidity and mortality associated with them are highest in intensive care units, but their effects are identifiable in virtually any medical department. Information about hospital-acquired infections, especially about their preventive measures, are rarely presented nowadays in a correct fashion to patients. This article aims to present, in a structured manner, the theoretical and practical aspects related to disclosure of hospital-acquired infections-related information to patients and its importance in preventing their spread. We will analyze both the conceptual framework for disclosing medical information related to nosocomial infections (autonomy, veracity, social justice, the principle of double effect, the precautionary principle, and nonmaleficence) and the practicalities regarding the disclosure of proper information to patients.