Bradycardia during optical timolol therapy: its delayed remission after timolol discontinuation and unexpected further relapse.

Optical betablockers (BBs), including nonselective BB timolol, are commonly used for the management of primary open angle glaucoma and ocular hypertension. About 80% of topically administered timolol is systemically absorbed, which can rarely induce such complications as bradycardia, bronchospasm and depression. A CASE REPORT: The authors describe a case of a 67-year-old female referred because of significant bradycardia and a suggestion of pacemaker implantation. She had no cardiovascular history besides hyperlipidemia and mild hyperglycemia, so her previous treatment was focused on glaucoma due to which she had been using optical timolol for several years. Moreover, she suffered from depression which was treated with venlafaxine and sertraline. Over a few months, she started feeling weak and dizzy. Her daily heart rate (HR) markedly decreased to 40-45/min. 24-hour ECG monitoring revealed multiple episodes of nodal rhythm and of sinoatrial block and the lowest HR of 33/min; bradycardia defined as HR less than 45/min constituted over 40% of the time recorded. Close observation with repeated 24-hour ECG monitoring after timolol discontinuation showed lasting several-daylong gradual bradycardia remission; after 2, 9, 16 and 23 days, bradycardia constituted 19.9%, 13.9%, 0.2% and 0% of the time recorded, respectively. Genetic testing of cytochrome P450 2D6 revealed the presence of the c.506 -1G>A variant with one non-functional allele (CYP2D6 *4/-) which might have slowed down timolol metabolism in the context of simultaneous antidepressants use, so venlafaxine and sertraline were reduced. However, during follow-up, incremental bradycardia relapse, suggestive of an underlying sinus node dysfunction, was observed.

Brugada phenocopy in pulmonary embolism - clinicopathological case study and literature review.

Brugada syndrome (BrS) is an inherited channelopathy characterized on ECG by coved (type 1) or saddle-back (type 2) ST-segment elevation (STE) of 2 or more mm in the right precordial leads and is associated with an increased risk of malignant ventricular arrhythmias. The term Brugada phenocopy (BrPh) indicates conditions that may reversibly induce Brugada-like ECG pattern in patients without true BrS; e.g.: metabolic abnormalities, mechanical heart compression, ischemia, myocarditis/pericarditis, and pulmonary embolism (PE). Only 9 cases of BPh associated with PE have been described so far. The authors present another case of a 41-year-old-male and analyze the clinical data of all 10 subjects (7 males and 3 females). Type 1 of ECG Brugada pattern was present in 7 patients (including ours), type 2 was found in 2 persons; in 1 case ECG pattern was not defined. In 7 patients STE was prominent (5 mm or more in at least 1 lead). STE was limited to V1-V2 leads in 4 persons, extended to V3 in 3 patients and even to V4 in 3 other patients, which correlated with the significant right ventricular (RV) dilatation. Concomitant left ventricular (LV) systolic dysfunction was reported only in 1 patient, which suggested that paradoxical embolization of coronary artery was not the mechanism of BrS-like STE. Clinical course of PE was usually severe (5 individuals were treated with thrombolysis) and in 3 cases it ended with death. The autopsy was only performed on our patient. It showed diffuse (ischemic) injury of RV and LV secondary to RV overload, decreased cardiac output and severe oxygen deficiency in myocardium, which could have led to BrS pattern in ECG.

[Rivaroxaban-resistant right ventricular thrombus, successfully treated with vitamin K antagonist in a patient with dilated cardiomyopathy]. / Oporna na rywaroksaban skrzeplina w prawej komorze, skutecznie leczona antagonista witaminy K u chorego z kardiomiopatia rozstrzeniowa.

Rivaroxaban, a selective inhibitor of active factor X belongs to the group of direct-acting oral anticoagulants (DOAC), more and more often replacing vitamin K antagonists (VKA) in venous thromboembolic disease and nonvalvular atrial fibrillation. Attempts are also being made to use DOAC to treat locally formed intracardiac thrombi, mainly in the left atrium and its appendage, in atrial fibrillation and in heart failure. Rarely diagnosed local right ventricular thrombus (RVT) may be a complication of dilated cardiomyopathy (DCM). CASE REPORT: The authors present a case of a 40-year-old male with DCM and RVT located in the apex, which was imaged in echocardiography, magnetic resonance and multislice computed tomography. During treatment with rivaroksaban (2x15 mg: 4 weeks; 1x20 mg: 4 months) diminishing of RVT was not observed. After 2 months of VKA use complete resolution of RVT was noted. The case presented is probably the first described RVT treated with rivaroxaban. The authors conclude that in some cases, anticoagulation with VKA may be more effective than DOAC in intracardiac thrombi therapy, especially when it is meticulously monitored. Overlapping effect on RVT due to anticoagulants use with a different mechanism of action cannot be excluded.

[Multiple right ventricular thrombi in arrhythmogenic right ventricular cardiomyopathy - a case report]. / Mnogie skrzepliny w prawej komorze w przebiegu arytmogennej kardiomiopatii prawej komory - opis przypadku.

Typical complications of arrhythmogenic right ventricular cardiomyopathy (ARVC) are heart failure and ventricular arrhythmias which may lead to sudden cardiac death. Intracardiac thrombosis is diagnosed only in 2-4% of patients. The authors present a case of a 50-year-old male admitted to hospital due to symptomatic ventricular tachycardia. Echocardiography and cardiac magnetic resonance showed advanced ARVC with multiple right ventricular thrombi. The biggest one was localized in the inflow tract below the tricuspid valve, whereas the smallest one beneath it, on the inferior wall; the remaining two - in the apex. Chest computed tomography did not confirm pulmonary embolism. Disappearance of thrombi was observed after 4 weeks of anticoagulation. Detection and appropriate treatment of intracardiac thrombi in ARVC may have relevance in prevention of sudden death, not related to arrhythmia, and is of special importance before cardioverterdefibrillator implantation.

[Isolated tricuspid valve infective endocarditis in a patient with a urological history]. / Izolowane infekcyjne zapalenle wsierdzia na zastawce trójdzielnej u chorego z wywiadem urologicznym.

Infective endocardits of the tricuspid valve (TVIE) occurs mainly in addicted-intravenous drug users, in the presence of intracardiac electrodes or central venous catheters, and in some congenital heart diseases; rarely, in other conditions. The authors present a case of a 61-year-old male with TVIE as a result of complicated transurethral resection of bladder papilloma. The onset of TVIE was insidious, with low back pain, followed by pulmonary symptoms. Echocardiography showed large vegetations on the tricuspid valve; blood culture was positive for methycylin-resistant, coagulase-negative staphylococcus. Fever remission and negative bacteriological blood examination results were achieved following treatment with linezolid; however, because of advanced tricuspid valve destruction, valve replacement was necessary.

The effect of atorvastatin treatment on lipid profile and adhesion molecule levels in hypercholesterolemic patients: relation to low-density lipoprotein receptor gene polymorphism.

Inflammation has been indicated to play a major role in the development of atherosclerosis. The beneficial effect of statins has been suggested to be related to their anti-inflammatory properties. We have studied plasma levels of soluble adhesion molecules in patients with hypercholesterolemia before and after 3 months of treatment with atorvastatin and evaluated possible relations to the mutations in low-density lipoprotein receptor (LDLR) gene. In patients with no LDLR gene polymorphism (group A), lower baseline levels of total cholesterol and LDL cholesterol were found than in patients with LDLR gene polymorphism (group B). The soluble adhesion molecules sICAM-1, sE-selectin and sP-selectin, but not sVCAM-1 and sL-selectin, were higher in group B than in group A. sICAM-1 levels decreased in group A by 7% (p = 0.007) and in group B by 21% (p = 0.039), whereas levels of sVCAM-1 decreased in group A by 12% (p = 0.001) and in group B patients by 19% (p = 0.039). Atorvastatin did not change sE-selectin nor sP-selectin levels in group A. However, in group B, the treatment reduced E-selectin and sP-selectin levels by 39% (p = 0.007) and 24% (p = 0.007), respectively. Atorvastatin attenuates the inflammatory reaction in hypercholesterolemic patients, but in patients with LDLR gene polymorphism, this effect is more profound.

Monogenic hypercholesterolaemias--an evaluation of apolipoprotein B100 and LDL receptor gene polymorphisms.

INTRODUCTION: Normally the N-terminal domain of the LDL receptor (LDLR) binds to low-density lipoprotein through apolipoprotein B100. Mutations within the LDL receptor and/or apolipoprotein B-100 genes compromising this process may lead to congenital monogenic hypercholesterolaemias known as familial hypercholesterolaemia or familial defective apolipoprotein B-100. These diseases are inherited as autosomal dominant traits. AIM: To search for LDLR and apoB100 gene mutations in a Polish population of patients with hypercholesterolaemia and to determine their types and locations. An attempt was also made to evaluate the influence of identified gene mutations on the modification of protein product sequence and the severity of its functional impairment. METHODS: LDLR and apoB100 gene analyses using PCR, SSCP and automated sequencing techniques were performed in 190 hypercholesterolaemic patients. Flow cytometry was used to measure the influence of Cys152Trp mutation in the LDLR gene on ligand binding and internalisation. The OLA method was used for the preparation of adequate genetic markers allowing rapid detection of one of the most deleterious mutations of the apoB100 gene. RESULTS AND CONCLUSIONS: Three brand new mutations, not reported so far, have been detected--Pro2712Leu and Ile3532 in the apoB100 gene, and Cys347Ser in the LDLR gene--and numerous changes in the nucleotide sequence of the LDL receptor gene have been confirmed. The observations of functionality of the mutated receptor gene with flow cytometry suggested the dysfunction of LDLR due to Cys152Trp polymorphism reported in many studies.