Antagonist mineralokortikoidnih receptora eplerenon u suvremenom liječenju kardiovaskularnih bolesnika

Aldosterone and eplerenone are mineralocorticoid receptor antagonists with one of the main roles in the treatment of heart failure, as demonstrated by large randomized controlled trials. Effects on patient outcomes are the result of blocking the renin-angiotensin-aldosterone system, which improves cardiac remodeling. Besides heart failure, mineralocorticoid receptor antagonists are used in treatment of patients with resistant arterial hypertension. This review focuses on the pharmacokinetics, pharmacodynamics, clinical effects, and safety profile of eplerenone.Velika randomizirana kontrolirana istraživanja dokazala su središnju ulogu antagonista mineralokortikoidnih receptora spironolaktona i eplerenona u liječenju bolesnika sa zatajivanjem srca. Svoje brojne pozitivne učinke ostvaruju blokiranjem reninsko-angiotenzinsko aldosteronskog sustava, što uzrokuje smanjenje negativne remodelacije miokarda te u konačnici bolje ishode za bolesnika. Osim u zatajivanju srca, antagonisti mineralokortikoidnih receptora imaju ulogu u liječenju bolesnika s rezistentnom hipertenzijom. Ovaj pregledni članak usredotočen je na farmakokinetiku, farmakodinamiku, kliničku primjenu i sigurnosni profil eplerenona

Everything in Moderation – Athlete\u27s Heart

Brojna klinička istraživanja dokazala su jasne koristi tjelesne aktivnosti za kardiovaskularno, ali i opće zdravlje svakoga čovjeka. Tjelesna aktivnost izaziva fiziološki odgovor organizma koji dovodi do različitih prilagodba pojedinih organskih sustava, a primjer jedne od njih jest i sportsko srce – benigni i reverzibilni odgovor kardiovaskularnog sustava na ponavljanu i intenzivnu tjelesnu aktivnost. Neke bolesti miokarda mogu dijeliti slične elektrokardiografske, ehokardiografske i druge karakteristike sa sportskim srcem. Pravodobno prepoznavanje takvih bolesti ključno je za zaštitu zdravlja svih koji se bave intenzivnijom tjelesnom aktivnosti rekreativno ili profesionalno.Numerous clinical studies have demonstrated obvious benefits of physical activity for cardiovascular, as well as general health of every human being. Physical activity induces a physiological response resulting in different adaptations of individual organ systems. One of such adaptations is the athlete\u27s heart representing a benign and reversible reaction of the cardiovascular system to repeated and intensive physical activity. Some of the myocardial diseases may share electrocardiographic, echocardiographic and other features similar to those of the athlete\u27s heart. Timely recognition of such diseases is crucial to the health of everyone who is engaged in a more intensive physical activity, either recreationally or professionally

Post-transplant lymphoproliferative disorder after heart transplantation

Post-transplant lymphoproliferative disorder (PTLD) is a heterogeneous group of lymphoid neoplasms associated with immunosuppression following solid organ transplantation or allogeneic hematopoietic stem cell transplantation. Mismatch for cytomegalovirus (CMV), such as when a seronegative recipient receives an organ from a seropositive donor, was shown to be associated with a seven-fold increase in PTLD. A 20-year-old male patient was admitted to the hospital due to back and abdominal pain. He had underwent a heart transplant 6 years ago due to postmyocarditic dilated cardiomyopathy and soon after the transplant, he had developed CMV pneumonitis. At examination, abdominal ultrasound showed multiple lesions of the liver, and patohystology of the lesion biopsy revealed PTLD, i.e. Non-Hodgkin’s diffuse large B cell lymphoma, for which the patient received 8 cycles of chemotherapy (R-CHOP protocol). Nine months after the first dose, the patient was admitted to the hospital due to simptoms of heart failure (NYHA IV) and echocardiography revealed significantly reduced cardiac function (LVEF 25%). Graft rejection was excluded with heart biopsy and it was concluded the etiology of heart failure was anthracycline (Doxorubicin) toxicity. Given the severity of the patient’s condition, he was again listed for heart transplant, and ultimately, retransplanted. Eight years after the retransplant, the patient is in excellent overall condition. Heart transplant patients have about a 1- 6% risk to develop the PTLD. The incidence of chronic Doxorubicin cardiotoxicity is about 1.7%. This patient had developed both, but, fortunately, with timely and right therapy the outcome can be successful

Lower platelet count early after the heart transplantation is associated with lower rates of cellular-mediated rejection within 24 months after heart transplantation

Background: Decrease in platelet count following the induction with polyclonal anti-thymocyte globulin (ATG) is deemed as an adverse event, while decrease in lymphocyte count represents a therapeutic goal1. Still, the effect on platelets may represent an important part of ATG anti-rejection mechanisms. Patients and Methods: This was a retrospective single-center study of consecutive HTx (heart transplantation) patients (pts) from February 2010 to February 2018 in University Hospital Centre Zagreb. All pts received rATG (Thymoglobulin®) 1.5 mg/kg daily during the first 5 days. Complete blood count with differential was assessed on days 0, 7 and 14 after HTx. The incidence of cellular-mediated rejection (ACR) was monitored for two years after HTx. ACR was classified according to ISHLT classification from 1990 and expressed as ACR of grade 1B or higher (≥1B). Results: A total of 159 pts were transplanted. Median age was 55 years (IQR, 47-62 years), 76% were male. A total of 27 pts (17 %) experienced ACR ≥1B during 24 months. Pts with ACR of grade ≥1B had higher platelet count on day 7 (145 vs 104 x 103/μL, p<0.001). They also had higher the absolute lymphocyte count (ALC) on the same day, but this did not reach statistical significance (162 vs 130 x 103/μL, p=0.19) and there was no correlation between ALC and platelet counts on day 7 (Pearson’s correlation coefficient was 0.064, p=0.459). Conversely, more rejection was observed in pts with higher ALC on day 14 (326 vs 190 x 103/μL, p=0.035), with a trend towards statistical significance in the relationship with higher platelet count (210 vs 199 x 103/μL, P=0.076). In the univariate analysis, higher platelet count on day 7, younger recipient age and negative pre-transplant Cytomegalovirus (CMV) IgG serology were found as predictors of the ACR ≥1B in the first 2 years after HTx (Table 1). In multivariable model, platelet count on day 7 and pre-transplant CMV serostatus were independent predictors of rejection. ROC analysis of the aforementioned model showed a satisfying AUC of 0.75. Conclusion: Decrease in platelet count following the induction with rATG is strongly related to less graft rejection that is independent from the lymphodepleting effect. This indicates the importance of platelet involvement in anti-rejection mechanisms of ATG induction, and consequently a possible rationale for targeting platelets in future immunosuppressive regimens

From left ventricular hypertrophy to Waldenström macroglobulinemia: a case report

Background: Left ventricular hypertrophy (LVH) is a common cardiac finding generally caused by an adaptation of the myocardium to increased pressure or volume load, or systemic conditions or genetic mutations1. Amyloidosis still remains a mysterious disease, with extremely diverse palette of symptoms and poor prognosis, caused by extracellular deposits of autological proteins with a fibrillar ultrastructure and specific properties. According to anatomical and clinical criteria, it can be presented as systemic or localized type2