Therapeutic Options for the Management of the Cardiorenal Syndrome

Patients with heart failure often present with impaired renal function, which is a predictor of poor outcome. The cardiorenal syndrome is the worsening of renal function, which is accelerated by worsening of heart failure or acute decompensated heart failure. Although it is a frequent clinical entity due to the improved survival of heart failure patients, still its pathophysiology is not well understood, and thus its therapeutic approach remains controversial and sometimes ineffective. Established therapeutic strategies, such as diuretics and inotropes, are often associated with resistance and limited clinical success. That leads to an increasing concern about novel options, such as the use of vasopressin antagonists, adenosine A1 receptor antagonists, and renal-protective dopamine. Initial clinical trials have shown quite encouraging results in some heart failure subpopulations but have failed to demonstrate a clear beneficial role of these agents. On the other hand, ultrafiltration appears to be a more promising therapeutic procedure that will improve volume regulation, while preserving renal and cardiac function. Further clinical studies are required in order to determine their net effect on renal function and potential cardiovascular outcomes. Until then, management of the cardiorenal syndrome remains quite empirical

Cardiac Tumors

Cardiac tumors represent a relatively rare, yet challenging diagnosis. Secondary tumors are far more frequent than primary tumors of the heart. The majority of primary cardiac tumors is benign in origin, with primary malignant tumors accounting for 25% of cases. Metastatic tumors usually arise from lung, breast, renal cancer, melanomas, and lymphomas. Clinical manifestations of cardiac tumors depend on the size and location of the mass and the infiltration of adjacent tissues rather than the type of the tumor itself. Echocardiography is the main diagnostic tool for the detection of a cardiac mass. Other imaging modalities (C-MRI, C-CT, 3D Echo) may offer further diagnostic information and the establishment of the diagnosis is made with histological examination. Management depends on the type of the tumor and the symptomatology of the patient

Isothiocyanates Potentiate Tazemetostat-Induced Apoptosis by Modulating the Expression of Apoptotic Genes, Members of Polycomb Repressive Complex 2, and Levels of Tri-Methylating Lysine 27 at Histone 3 in Human Malignant Melanoma Cells

In this study, we utilized an in vitro model consisting of human malignant melanoma as well as non-tumorigenic immortalized keratinocyte cells with the aim of characterizing the therapeutic effectiveness of the clinical epigenetic drug Tazemetostat alone or in combination with various isothiocyanates. In doing so, we assessed markers of cell viability, apoptotic induction, and expression levels of key proteins capable of mediating the therapeutic response. Our data indicated, for the first time, that Tazemetostat caused a significant decrease in viability levels of malignant melanoma cells in a dose- and time-dependent manner via the induction of apoptosis, while non-malignant keratinocytes were more resistant. Moreover, combinatorial treatment protocols caused a further decrease in cell viability, together with higher apoptotic rates. In addition, a significant reduction in the Polycomb Repressive Complex 2 (PRC2) members [e.g., Enhancer of Zeste Homologue 2 (EZH2), Embryonic Ectoderm Development (EED), and suppressor of zeste 12 (SUZ12)] and tri-methylating lysine 27 at Histone 3 (H3K27me3) protein expression levels was observed, at least partially, under specific combinatorial exposure conditions. Reactivation of major apoptotic gene targets was determined at much higher levels in combinatorial treatment protocols than Tazemetostat alone, known to be involved in the induction of intrinsic and extrinsic apoptosis. Overall, we developed an optimized experimental therapeutic platform aiming to ensure the therapeutic effectiveness of Tazemetostat in malignant melanoma while at the same time minimizing toxicity against neighboring non-tumorigenic keratinocyte cells

Chemical Characterization and Biological Evaluation of \u3ci\u3eEpilobium parviflorum\u3c/i\u3e Extracts in an In Vitro Model of Human Malignant Melanoma

Malignant melanoma is an aggressive type of skin cancer characterised by high metastatic capacity and mortality rate. On the other hand, Epilobium parviflorum is known for its medicinal properties, including its anticancer potency. In this context, we aimed to (i) isolate various extracts of E. parviflorum, (ii) characterize their phytochemical content, and (iii) determine their cytotoxic potential in an in vitro model of human malignant melanoma. To these ends, we utilized various spectrophotometric and chromatographic (UPLC-MS/MS) approaches to document the higher content of the methanolic extract in polyphenols, soluble sugars, proteins, condensed tannins, and chlorophylls -a and -b as opposed to those of dichloromethane and petroleum. In addition, the cytotoxicity profiling of all extracts was assessed through a colorimetric-based Alamar Blue assay in human malignant melanoma (A375 and COLO-679) as well as non-tumorigenic immortalized keratinocyte (HaCaT) cells. Overall, the methanolic extract was shown to exert significant cytotoxicity, in a timeand concentration-dependent manner, as opposed to the other extracts. The observed cytotoxicity was confined only to human malignant melanoma cells, whereas non-tumorigenic keratinocyte cells remained relatively unaffected. Finally, the expression levels of various apoptotic genes were assessed by qRT-PCR, indicating the activation of both intrinsic and extrinsic apoptotic cascades. Supplement attached below

Multimarker Approach in Cardiovascular Risk Prediction

Various biomarkers express different pathways and pathophysiologic mechanisms of cardiovascular disease, such as inflammation, oxidative stress, myocardial injury, activation of the neurohormonal pathways, myocardial stress and renal function. Current thinking supports the notion that the combination of these biomarkers could increase their diagnostic and prognostic value. The multimarker approach offers benefits since it increases the diagnostic and prognostic information and may help in the design of a strategy for prevention or management of cardiovascular diseases. The purpose of the current review is to describe the characteristics of promising biomarkers which have shown an important additive value in the assessment of cardiovascular risk. Also, an extended reference is made regarding studies that address the prognostic value of multimarker models in the settings of primary prevention of cardiovascular disease and secondary prevention for patients with acute coronary syndromes, chronic coronary artery disease and heart failure.</jats:p

Cardiac Arrest Caused by Torsades de Pointes Tachycardia after Successful Atrial Flutter Radiofrequency Catheter Ablation

A 66-year-old woman underwent successful radiofrequency catheter ablation for long-lasting, drug refractory fast atrial flutter. Two days later she had a cardiac arrest due to torsades de pointes (TdP) tachycardia attributed to relative sinus bradycardia and QT interval prolongation. After successful resuscitation further episodes of TdP occurred, which were treated with temporary pacing. Because of concomitant systolic dysfunction due to ischemic and valvular heart disease she was finally treated with an implantable defibrillator. In conclusion we strongly advise prolonged monitoring for 2 or more days for patients with structural heart disease following successful catheter ablation for long lasting tachyarrhythmias

Ibutilide for the Cardioversion of Paroxysmal Atrial Fibrillation during Radiofrequency Ablation of Supraventricular Tachycardias

Direct current electrical cardioversion (DC-ECV) is the preferred treatment for the termination of paroxysmal atrial fibrillation (AF) that occurs during radiofrequency ablation (RFA) of supraventricular tachycardias (SVT). Intravenous Ibutilide may be an alternative option in this setting. Thirty-four out of 386 patients who underwent SVT-RFA presented paroxysmal AF during the procedure and were randomized into receiving ibutilide or DC-ECV. Ibutilide infusion successfully cardioverted 16 out of 17 patients (94%) within  min. DC-ECV was successful in all patients (100%) within  min. Efficacy and total time to cardioversion did not differ between the study groups. No adverse events were observed. RFA was successfully performed in 16 patients (94%) in the ibutilide arm and in all patients (100%) in the DC-ECV arm, p = NS. In conclusion, ibutilide is a safe and effective alternative treatment for restoring sinus rhythm in cases of paroxysmal AF complicating SVT-RFA.</jats:p

Hypertrophic cardiomyopathy with midventricular obstruction and apical aneurysm formation in a single family: case report

<p>Abstract</p> <p>Background</p> <p>Hypertrophic cardiomyopathy (HCM) is an extremely heterogeneous disease. An under recognized and very often missed subgroup within this broad spectrum concerns patients with left ventricular (LV) apical aneurysms in the absence of coronary artery disease.</p> <p>Case presentation</p> <p>We describe a case of HCM with midventricular obstruction and apical aneurysm formation in 3 patients coming from a single family. This HCM pattern was detected by 2D-echocardiography and confirmed by cardiac magnetic resonance imaging. A cardioverter defibrillator was implanted in one of the patients because of non-sustained ventricular tachycardia detected in 24-h Holter monitoring and an abrupt drop in systolic blood pressure during maximal exercise test. The defibrillator activated 8 months after implantation by suppression of a ventricular tachycardia providing anti-tachycardia pacing. The patient died due to refractory heart failure 2 years after initial evaluation. The rest of the patients are stable after a 2.5-y follow-up period.</p> <p>Conclusion</p> <p>The detection of apical aneurysm by echocardiography in HCM patients may be complicated. Ventricular tachycardia arising from the scarred aneurysm wall may often occur predisposing to sudden death.</p