LV-predominant arrhythmogenic cardiomyopathy related to pathogenic DSP-variant.

Key Clinical Message: In contrast to previously thought, arrhythmogenic cardiomyopathy can occur exclusively in the left ventricle in association with autosomal dominant mutation, even without any skin manifestations. Abstract: We present a case of a 43-year-old male with left ventricle (LV)-predominant arrhythmogenic cardiomyopathy (ACM) caused by a novel p.Q1830 mutation in the desmoplakin (DSP) gene. The patient had a significant family history of sudden cardiac death (SCD) and presented with presyncope and exertional dyspnea. The patient's electrocardiography (ECG) showed frequent premature ventricular complexes (PVCs) with bigeminy and couplet patterns. Cardiac magnetic resonance imaging (CMR) revealed late gadolinium enhancement of the left ventricle (LV) and ventricular systolic dysfunction, suggesting LV-predominant arrhythmogenic cardiomyopathy. The patient was started on guideline-directed medical therapy (GDMT), and an implantable cardioverter-defibrillator (ICD) was implanted for primary prevention. The patient reported significant improvement in his heart failure symptoms at the 2-year follow-up. The article highlights the importance of timely diagnosis with multimodality imaging and genetic testing and management of the rare DSP-related LV-predominant ACM associated with a high risk of SCD.

Radioligand therapy (RLT) used to treat cardiac metastasis of pancreatic neuroendocrine tumor.

Radioligand Therapy (RLT) in the form of [177Lu] Lu-DOTA-TATE (Lutathera®) is a promising treatment for pancreatic neuroendocrine tumors (pNETs) with cardiac metastasis. We present a patient treated with [177Lu] Lu-DOTA-TATE that showed shrinkage of metastasis after four treatments at 7.4 GBq every 8 weeks.

Development and Functionalization of a Novel Chitosan-Based Nanosystem for Enhanced Drug Delivery.

Nowadays, infection diseases are one of the most significant threats to humans all around the world. An encouraging strategy for solving this issue and fighting resistant microorganisms is to develop drug carriers for a prolonged release of the antibiotic to the target site. The purpose of this work was to obtain metronidazole-encapsulated chitosan nanoparticles using an ion gelation route and to evaluate their properties. Due to the advantages of the ionic gelation method, the synthesized polymeric nanoparticles can be applied in various fields, especially pharmaceutical and medical. Loading capacity and encapsulation efficiency varFied depending on the amount of antibiotic in each formulation. Physicochemical characterization using scanning electron microscopy revealed a narrow particle size distribution where 90% of chitosan particles were 163.7 nm in size and chitosan-loaded metronidazole nanoparticles were 201.3 nm in size, with a zeta potential value of 36.5 mV. IR spectra revealed characteristic peaks of the drug and polymer nanoparticles. Cell viability assessment revealed that samples have no significant impact on tested cells. Release analysis showed that metronidazole was released from the chitosan matrix for 24 h in a prolonged course, implying that antibiotic-encapsulated polymer nanostructures are a promising drug delivery system to prevent or to treat various diseases. It is desirable to obtain new formulations based on drugs encapsulated in nanoparticles through different preparation methods, with reduced cytotoxic potential, in order to improve the therapeutic effect through sustained and prolonged release mechanisms of the drug correlated with the reduction of adverse effects.

Understanding How Minerals Contribute to Optimal Immune Function.

Sufficient mineral supply is vital not only for the innate immune system but also for the components of the adaptive immune defense, which encompass defense mechanisms against pathogens and the delicate balance of pro- and anti-inflammatory regulation in the long term. Generally, a well-balanced diet is capable of providing the necessary minerals to support the immune system. Nevertheless, specific vulnerable populations should be cautious about obtaining adequate amounts of minerals such as magnesium, zinc, copper, iron, and selenium. Inadequate levels of these minerals can temporarily impair immune competence and disrupt the long-term regulation of systemic inflammation. Therefore, comprehending the mechanisms and sources of these minerals is crucial. In exceptional circumstances, mineral deficiencies may necessitate supplementation; however, excessive intake of supplements can have adverse effects on the immune system and should be avoided. Consequently, any supplementation should be approved by medical professionals and administered in recommended doses. This review emphasizes the crucial significance of minerals in promoting optimal functioning of the immune system. It investigates the indispensable minerals required for immune system function and the regulation of inflammation. Moreover, it delves into the significance of maintaining an optimized intake of minerals from a nutritional standpoint.

Beyond the norm: A rare case of cardiac and extracardiac metastatic urothelial carcinoma.

Screening echocardiography aids in identifying cardiac emboli causes and asymptomatic cardiac metastases in high-grade neoplasms. Conversely, cardiac MRI provides advanced tissue characterization and broader extracardiac assessment.

Second-generation extracellular matrix patch for epicardial infarct repair.

Current myocardial infarction treatments focus on improving hemodynamics rather than addressing the problem of lost myocardium impairing left ventricular function. Epicardial infarct repair with a bioactive patch placed on the ischemic area is an emerging approach to promote endogenous myocardial repair. We report the use of a second-generation CorMatrix-extracellular matrix (ECM) patch as an adjunct to surgical revascularization in treating a young patient with diffuse, multivessel coronary artery disease unamenable to PCI and a large anterior myocardial infarction. The progressive myocardial scar shrinkage and increase in left ventricular ejection fraction from 10 to 51% are generally not observed with surgical revascularization therapy alone, suggesting this new patch has adjunctive potential to current revascularization therapy.

Post-Coronary Artery Bypass Grafting Outcomes of Patients with/without Type-2 Diabetes Mellitus and Chronic Kidney Disease Treated with SGLT2 Inhibitor Dapagliflozin: A Single-Center Experience Analysis.

INTRODUCTION: Increasingly, SGLT2 inhibitors save patients with heart failure and comorbidities such as type-2 diabetes mellitus (T2DM) and chronic kidney disease (CKD); the inhibition of sodium-glucose cotransporter 2 (SGLT2) was first studied in patients with diabetes as a solution to lower glucose levels by preventing glucose reabsorption and facilitating its elimination; in the process, researchers took notice of how SGLT2 inhibitors also seemed to have beneficial cardiovascular effects in patients with both diabetes and cardiovascular disease. AIM: Our single-center prospective study assesses outcomes of post-coronary artery bypass grafting (CABG) rehabilitation and SLGT2 inhibition in CABG patients with/without T2DM and with/without CKD. MATERIALS AND METHODS: One hundred twenty consecutive patients undergoing CABG were included in the analysis. Patients were divided into four subgroups: diabetes patients with chronic kidney disease (T2DM + CKD), diabetes patients without chronic kidney disease (T2DM-CKD), prediabetes patients with chronic kidney disease (PreD+CKD), and prediabetes patients without chronic kidney disease (PreD-CKD). Echocardiographic and laboratory investigations post-surgery (phase I) and 6 months later (phase II) included markers for cardiac ischemia, glycemic status, and renal function, and metabolic equivalents were investigated. RESULTS: One hundred twenty patients participated, mostly men, overweight/obese, hypertensive, smokers; 65 had T2DM (18 with CKD), and 55 were prediabetic (17 with CKD). The mean ejection fraction increased by 8.43% overall but significantly more in the prediabetes group compared to the T2DM group (10.14% vs. 6.98%, p < 0.05). Overall, mean heart-type fatty-acid-binding protein (H-FABP) levels returned to normal levels, dropping from 68.40 ng/mL to 4.82 ng/mL (p = 0.000), and troponin data were more nuanced relative to an overall, strongly significant decrease of 44,458 ng/L (p = 0.000). Troponin levels in patients with CKD dropped more, both in the presence of T2DM (by 82,500 ng/L, p = 0.000) and in patients without T2DM (by 73,294 ng/L, p = 0.047). As expected, the overall glycated hemoglobin (HbA1c) levels improved significantly in those with prediabetes (from 6.54% to 5.55%, p = 0.000); on the other hand, the mean HbA1c changed from 7.06% to 6.06% (p = 0.000) in T2DM, and the presence or absence of CKD did not seem to make any difference: T2DM+CKD 7.01-6.08% (p = 0.000), T2DM-CKD 7.08-6.04% (p = 0.000), PreD+CKD 5.66-4.98% (p = 0.014), and PreD-CKD 6.03-4.94% (p = 0.00). Compared to an overall gain of 11.51, the GFRs of patients with CKD improved by 18.93 (68.15-87.07%, p = 0.000) in the presence of established diabetes and 14.89 (64.75-79.64%, p = 0.000) in the prediabetes group. CONCLUSIONS: Regarding the patients' cardiac statuses, the results from our single-center analysis revealed a significant decrease in ischemic risk (H-FABP and hs-cTnI levels) with improvements in mean ejection fraction, glycemic status, and renal function in patients post-CABG with/without T2DM, with/without CKD, and with SGLT2 inhibitor dapagliflozin treatment while undergoing cardiac rehabilitation.

Distinct Patterns of Blood Cytokines Beyond a Cytokine Storm Predict Mortality in COVID-19.

BACKGROUND: COVID-19 comprises several severity stages ranging from oligosymptomatic disease to multi-organ failure and fatal outcomes. The mechanisms why COVID-19 is a mild disease in some patients and progresses to a severe multi-organ and often fatal disease with respiratory failure are not known. Biomarkers that predict the course of disease are urgently needed. The aim of this study was to evaluate a large spectrum of established laboratory measurements. PATIENTS AND METHODS: Patients from the prospective PULMPOHOM and CORSAAR studies were recruited and comprised 35 patients with COVID-19, 23 with conventional pneumonia, and 28 control patients undergoing elective non-pulmonary surgery. Venous blood was used to measure the serum concentrations of 79 proteins by Luminex multiplex immunoassay technology. Distribution of biomarkers between groups and association with disease severity and outcomes were analyzed. RESULTS: The biomarker profiles between the three groups differed significantly with elevation of specific proteins specific for the respective conditions. Several biomarkers correlated significantly with disease severity and death. Uniform manifold approximation and projection (UMAP) analysis revealed a significant separation of the three disease groups and separated between survivors and deceased patients. Different models were developed to predict mortality based on the baseline measurements of several protein markers. A score combining IL-1ra, IL-8, IL-10, MCP-1, SCF and CA-9 was associated with significantly higher mortality (AUC 0.929). DISCUSSION: Several newly identified blood markers were significantly increased in patients with severe COVID-19 (AAT, EN-RAGE, myoglobin, SAP, TIMP-1, vWF, decorin) or in patients that died (IL-1ra, IL-8, IL-10, MCP-1, SCF, CA-9). The use of established assay technologies allows for rapid translation into clinical practice.

A Rare Presentation of Cardiac Lipoma as an Acute Coronary Syndrome: A Case Report and Review of Literature.

Cardiac lipomas are rare benign cardiac tumors that are seldom symptomatic. We present a case of a 49-year-old female who presented with one week of substernal chest pain and uncontrolled hypertension. Initial workup showed left ventricular hypertrophy with non-specific intraventricular delay and T wave inversion in leads I and aVL on electrocardiogram (EKG), troponinemia, and elevated brain natriuretic peptide levels. A transthoracic echocardiogram showed mildly reduced left ventricular ejection fraction and severe segmental hypokinesis of the left ventricle. The patient was admitted to the hospital as a case of non-ST elevation myocardial infarction (NSTEMI), and appropriate treatment was commenced. The patient underwent an urgent coronary angiogram that showed no significant epicardial coronary artery disease. Subsequently, a gadolinium-enhanced cardiac MRI (CMR) was performed to rule out underlying structural abnormalities, which demonstrated a well-demarcated cardiac mass involving the left ventricular wall with characteristic features of cardiac lipoma. The patient had a favorable prognosis with conservative management, and she was discharged home in stable condition with a close follow-up for repeat CMR. Although more studies are required, we suggest that cardiac MRI should be considered in patients with NSTEMI and non-revealing coronary angiography to rule out underlying cardiac tumors such as cardiac lipoma.

Third-Generation Cephalosporin-Loaded Chitosan Used to Limit Microorganisms Resistance.

From their discovery, antibiotics have significantly improved clinical treatments of infections, thus leading to diminishing morbidity and mortality in critical care patients, as well as surgical, transplant and other types of medical procedures. In contemporary medicine, a significant debate regarding the development of multi-drug resistance involves all types of pathogens, especially in acute care hospitals due to suboptimal or inappropriate therapy. The possibility of nanotechnology using nanoparticles as matrices to encapsulate a lot of active molecules should increase drug efficacy, limit adverse effects and be an alternative helping to combat antibiotic resistance. The major aim of this study was to obtain and to analyze physico-chemical features of chitosan used as a drug-delivery system in order to stop the antibiotic resistance of different pathogens. It is well known that World Health Organization stated that multidrug resistance is one of the most important health threats worldwide. In last few years, nano-medicine emerged as an improved therapy to combat antibiotic-resistant infections agents. This work relies on enhancement of the antimicrobial efficiency of ceftriaxone against gram(+) and gram(-) bacteria by antibiotic encapsulation into chitosan nanoparticles. Physicochemical features of ceftriaxone-loaded polymer nanoparticles were investigated by particle size distribution and zeta potential, Fourier-transform infrared spectroscopy (FTIR), Thermal Gravimetric Analysis (TG/TGA), Scanning Electron Microscopy (SEM) characteristics techniques. The obtained results revealed an average particle size of 250 nm and a zeta potential value of 38.5 mV. The release profile indicates an incipient drug deliverance of almost 15%, after 2 h of approximately 83%, followed by a slowed drug release up to 24 h. Characteristics peaks of chitosan were confirmed by FTIR spectra indicating a similar structure in the case of ceftriaxone-loaded chitosan nanoparticles. A good encapsulation of the antibiotic into chitosan nanoparticles was also provided by thermo-gravimetric analysis. Morphological characteristics shown by SEM micrographs exhibit spherical nanoparticles of 30-250 nm in size with agglomerated architectures. Chitosan, a natural polymer which is used to load different drugs, provides sustained and prolonged release of antibiotics at a specific target by possessing antimicrobial activity against gram(+) and gram(-) bacteria. In this research, ceftriaxone-loaded chitosan nanoparticles were investigated as a carrier in antibiotic delivery.

Horseshoe thrombus in a patient with mechanical prosthetic mitral valve: A case report and review of literature.

Patients with prosthetic cardiac valves are at high risk for thromboembolic complications and need life long anticoagulation with warfarin, which can be associated with variable dose requirements and fluctuating level of systemic anticoagulation and may predispose to thromboembolic and or hemorrhagic complications. Prosthetic cardiac valve thrombosis is associated with high morbidity and mortality. A high index of suspicion is essential for prompt diagnosis. Transthoracic echocardiography, and if required transesophageal echocardiography are the main diagnostic imaging modalities. Medically stable patients can be managed with thrombolytic therapy and anticoagulation, while some patients may require surgical thrombectomy or valve replacement. We present a case report of a patient with prosthetic mitral valve and an unusually large left atrial thrombus with both thromboembolic and hemorrhagic complications.

Comparison of different cardiac risk scores for coronary artery disease in symptomatic women: do female-specific risk factors matter?

BACKGROUND: Cardiovascular diseases remain the leading cause of death in women and there is a need for more accurate risk assessment scores. The aims of our study were to compare the accuracy of several widely used cardiac risk assessment scores in predicting the likelihood of obstructive coronary artery disease (CAD) on CT coronary angiography (CTCA) in symptomatic women and to explore which female-specific risk factors were independent predictors of obstructive CAD on CTCA and whether adding these risk factors to pre-test probability scores would improve their predictive value. METHODS AND RESULTS: Data were obtained from a cohort of 228 consecutively included symptomatic women undergoing evaluation for CAD and referred for CTCA. Obstructive CAD was defined as ≥50% luminal stenosis on CTCA. Pre-test probability for CAD was calculated according to the Diamond and Forrester score, New score, Duke clinical score, and an updated Diamond and Forrester score. Female-specific factors were obtained by a written questionnaire. Pre-test probability scores were compared with ROC analysis and showed that only the New score and the updated Diamond and Forrester score were significant predictive scores for obstructive CAD on CTCA (area under the curve, AUC, 0.67, p < 0.01; AUC 0.61, p = 0.04, respectively). Multivariable logistic regression analysis identified that gestational diabetes mellitus (GDM) and oestrogen status were independent predictors of obstructive CAD when adjusted for the pre-test probability scores. The updated Diamond and Forrester score was used for net reclassification improvement (NRI) analysis, since the New score already accounts for oestrogen status. Adding GDM and oestrogen status to the updated Diamond and Forrester score resulted in a significant NRI (p = 0.04). CONCLUSIONS: There is a large variability in prediction of obstructive CAD using different pre-test probability risk scores in symptomatic women. Logistic regression analysis revealed that oestrogen status and GDM were independently associated with the occurrence of obstructive stenosis on CTCA. The predictive ability of cardiac pre-test probability scores improved significantly with the addition of oestrogen status and GDM.

Left ventricular thrombus formation after acute myocardial infarction as assessed by cardiovascular magnetic resonance imaging.

INTRODUCTION: Left ventricular (LV) thrombus formation is a feared complication of myocardial infarction (MI). We assessed the prevalence of LV thrombus in ST-segment elevated MI patients treated with percutaneous coronary intervention (PCI) and compared the diagnostic accuracy of transthoracic echocardiography (TTE) to cardiovascular magnetic resonance imaging (CMR). Also, we evaluated the course of LV thrombi in the modern era of primary PCI. METHODS: 200 patients with primary PCI underwent TTE and CMR, at baseline and at 4 months follow-up. Studies were analyzed by two blinded examiners. Patients were seen at 1, 4, 12, and 24 months for assessment of clinical status and adverse events. RESULTS: On CMR at baseline, a thrombus was found in 17 of 194 (8.8%) patients. LV thrombus resolution occurred in 15 patients. Two patients had persistence of LV thrombus on follow-up CMR. On CMR at four months, a thrombus was found in an additional 12 patients. In multivariate analysis, thrombus formation on baseline CMR was independently associated with, baseline infarct size (g) (B=0.02, SE=0.02, p<0.001). Routine TTE had a sensitivity of 21-24% and a specificity of 95-98% compared to CMR for the detection of LV thrombi. Intra- and interobserver variation for detection of LV thrombus were lower for CMR (κ=0.91 and κ=0.96) compared to TTE (κ=0.74 and κ=0.53). CONCLUSION: LV thrombus still occurs in a substantial amount of patients after PCI-treated MI, especially in larger infarct sizes. Routine TTE had a low sensitivity for the detection of LV thrombi and the interobserver variation of TTE was large.

Cardiac involvement with amyloidosis: mechanisms of disease, diagnosis and management.

The amyloidoses represent a group of clinical disorders of diverse etiologies that have as a common pathophysiologic denominator the deposition of misfolded protein based amyloid fibrils in the interstitial space of various organs. They are uncommon diseases with protean clinical presentations. Cardiac involvement is the determining factor for a patient's prognosis. Clinicians have to maintain a high index of suspicion and actively search for signs and symptoms of cardiac involvement in patients with preexisting conditions known to be associated with the development of amyloidosis. Early diagnosis and accurate fibril typing are the first steps in managing the disease. Judicious use of various diagnostic modalities such as serum markers and imaging studies, and good communication among all the physicians involved in the care of these sick and frail patients, are keys to a better outcome.

Treatment and outcomes of nonagenarians with ST-elevation myocardial infarction.

There is no age limit for reperfusion therapy in the current guidelines for the treatment of patients with ST-elevation myocardial infarction (STEMI). Reperfusion therapy, although associated with better outcomes, is not always offered to the oldest patients. A retrospective analysis at our institution of all patients ≥ 90 years of age with a diagnosis of acute coronary syndrome at discharge from 2004 to 2008 identified 24 patients with STEMI. The majority of patients were Caucasian, females, hypertensive, with a low incidence of dementia and diabetes. Only 29% of patients presented to the hospital in less than 6 hours. Thirteen patients were treated with percutaneous coronary intervention (PCI) and 11 patients were treated medically. The in-hospital mortality was 23% in the PCI group and 36% in the medical therapy group. Kaplan-Meier analysis demonstrated a survival benefit favoring PCI, which disappeared when only patients presenting after 6 hours to the hospital were analyzed. PCI-treated patients had no procedure-associated complications and had a good prognosis if they survived to hospital discharge. PCI should be offered to nonagenarians presenting with STEMI.

Prognostic value of delayed gadolinium enhancement MRI in patients with ischemic cardiomyopathy.

BACKGROUND: Cardiovascular magnetic resonance imaging (CMR) with delayed contrast enhancement (DCE) using Gadolinium (Gd)-based magnetic contrastagents, is a technique which visualizes myocardial infarction (MI) as regions of bright signal (hyperenhancement) compared to normal myocardium. The prognostic value of DCE in patients with ischemic cardiomyopathy has not been fully characterized. METHODS: All patients with a history of coronary artery disease (CAD) who underwent DCE-CMR imaging between September 1999 and July 2004 were included. CMR-variables were: left ventricular ejection fraction (LVEF), wall motion, mitral regurgitation (MR) and DCE scores. The patient's clinical status was assessed using the New York Heart Association-classification (NYHA). RESULTS: One hundred and ninety-three patients (age 63+/-11, 42 women), including 160 with prior MI, were studied. The mean LVEF was 40+/-14%. Most patients (88%) were in NYHA-class I or II, and 8% had moderate or severe MR. Thirteen patients died during follow-up. Patients who died had a lower baseline LVEF and more significant MR compared to survivors (P=0.04). A higher DCE score was associated with more significant MR (P=0.01). No significant association was demonstrated between NYHA-class and DCE (P=0.34) or between DCE score andmortality (P=0. 8). CONCLUSION: The study reinforces the important prognostic value of resting LVEF and MR severity in patients with CAD and is the first to demonstrate an association between the degree of DCE and MR severity in these patients. Further investigations including a larger number of patients are needed to fully assess the prognostic value of DCE-CMR in ischemic cardiomyopathy.