Jadranka Separovic Hanzevacki

Inhibition of methyldigoxin-induced arrhythmias by pentadecapeptide BPC 157: A relation with NO-system

Pentadecapeptide BPC 157 (GEPPPGKPADDAGLV, MW 1419) reversed congestive heart failure and various arrhythmias, influenced the NO-system and showed no proarrhythmic effect. In therapy analogy, we challenged rats with digitalis, to show attenuation by BPC 157 and the relation between the NO-system and digitalis toxicity. (i). BPC 157 prophylactic effect. Development of cumulative intravenous digitalis toxicity, BPC 157 (50 microg, 10 microg, 10 ng/kg applied intravenously immediately before a methyldigoxin increment regimen (2.0/1.5/1.5/1.0 mg/kg at 15 min-intervals, total dose 6.0 mg/kg/45 min)) reduced the number of ventricular premature beats, prolonged the time before onset of ventricular tachycardia, reduced ventricular tachycardia and AV-block duration (microg-regimes) or reduced mainly the AV-block duration (ng-regimen). (ii). BPC 157 therapy. Advanced methyldigoxin toxicity (6.0 mg/kg i.v. bolus). BPC 157 applied at the 20th second of the grade 3 AV-block shortened AV-blocks, mitigated a further digitalis toxicity course. Ventricular tachycardias were either avoided (50 microg), or markedly reduced (10 microg, 10 ng). Fatal outcome was either avoided (50 microg), reduced (10 microg), or only delayed (10 ng) (iii) BPC 157, L-NAME, l-arginine, L-NAME+l-arginine application. L-NAME-application (5 mg/kg i.p.) aggravated methyldigoxin-arrhythmias. l-arginine (200 mg/kg i.p.) alone had no effect but blunted L-NAME-exaggeration (L-NAME+l-arginine). In this respect, BPC 157 (50 microg/kg i.p.) was prophylactically and therapeutically more effective: the antagonism of L-NAME with BPC 157 produced an effect similar to BPC 157 alone. In conclusion, digitalis-induced arrhythmias in rats could be prevented and counteracted by pentadecapeptide BPC 157, mainly through an interaction with the NO-system.

Mortal Furosemide-Hypokalemia-Disturbances in Rats NO-System Related Shorten Survival by L-NAME. Therapy Benefit with BPC 157 Peptide More Than With L-Arginine

Background: We focused on NO-system-relations (worsening/amelioration) of furosemide (100 mg/kg intraperitoneally)-diuresis-hypokalemia mortal course in rats and beneficial effect of BPC 157 therapy. Methods: Electrocardiographically 90-150 min post-furosemide application duration of PR, RR, QRS, QT intervals, P, R, S, T waves and its amplitude as well were analysed along with appearance of AV block, ventricular premature beats, ventricular tachycardia. Clinically, skeletal muscle myoclonal activity and lethality at 150 min were also analysed. Results: All NO-system-related agents (alone and/or combined, before/after furosemide) not changed hypokalemia and all averted to some extent furosemide-forced diuresis. NOS-blocker, L-NAME (5 mg/kg intraperitoneally) accelerated mortality, aggravated cardiac and extra-cardiac manifestations, thereby, NO-systemrelated. Prevented hypokalemia-mortality was with NO-precursor L-arginine (100 mg/kg intraperitoneally) and stable gastric pentadecapeptide BPC 157 (10 ug, 10 ng/kg intraperitoneally/intragastrically). Specifically, BPC 157 showed most complete benefit. i. BPC 157 given 15 min before furosemide. All BPC 157 regimens maintained sinus rhythm, had no ventricular premature beats, ventricular tachycardia, AV block, no prolongation of intervals and waves without reduction of amplitude. ii. BPC 157 given 90 min after furosemide (with hypokalemia, 3rd grade AV block and/ or ventricular tachycardia being present). Within 5-10 minutes, BPC 157 regimens normalized P, R, S, T waves, PR, RR, QRS, QT interval duration, R, S, T wave amplitude, total AV block and terminated ventricular tachycardia. Likewise, BPC 157 eliminated skeletal muscle myoclonus. Conclusion: L-NAME/L-arginine was mutual counteraction while BPC 157 completely eliminated L-NAME (arrhythmias, myoclonus, mortality), without an additive benefit when combined with L-arginine. Thus, we showed potentially effective therapeutic interventions for acute hypokalemia.

Impact of mild patient prosthesis mismatch on quality of life in patients with preserved ejection fraction after isolated aortic valve replacement for aortic stenosis

AIM To analyze whether PPM affects QOL and functional status in patients after isolated AVR for aortic stenosis (AS) with preserved left ventricular ejection fraction (LVEF). METHODS Consecutive patients who underwent AVR in University Hospital Center Zagreb for isolated severe symptomatic AS and preserved EF were enrolled. Echo data was obtained from complete transthoracic examinations prior and after surgery by offline analysis. Patients were divided into two groups according to the presence of PPM (effective orifice area (EOA)/body surface area (BSA)<0,85cm2/m2). QOL was assessed by telephone interview using Short Form 36-Item Health Survey (SF-36) along with functional NYHA status estimation. RESULTS A total of 45 pts were included (23 female), and divided in PPM (n=26), and non-PPM group (n=19). Both groups were similar in pts age, LVEF, AVA/BSA prior surgery. After surgery, 57% of pts had PPM categorized as mild PPM. During follow-up of 2,5years, 3 pts had died and 10 were lost from following. There was no difference in NYHA status after surgery between groups (p=0,758). SF36 results showed no difference between groups. However, there was a significant improvement in Physical functioning (47,50% vs 75,47%,p=0,000) and Role limitation due to physical health (41,41% vs 81,25%, p=0,007) scores in the whole study population after AVR. Males had significantly better Energy/fatigue (p=0,034), Social functioning (p=0,004) and Pain (p=0,017) scores. CONCLUSIONS Mild to moderate PPM showed no clinical relevance. All patients revealed improvement in QOL after AVR, while male sex was related to better functioning scores irrespectively of PPM.

The case of 28 year-old female after Senning procedure with persistent atrial flutter and severe triscuspid regurgitation.

E-mail: jbulum@gmail.com Transposition of the great vessels (TGA) is a rare condition with incidence of 1:5,000. The most common variant is dtransposition or complete transposition. Pivotal surgical procedure (Senning, 1957) has dramatically improved survival. However, typical long term complications include pressure overload of the systemic right ventricle with tricuspid regurgitation and atrial arrhythmias. Most of the patients are in NYHA I-II functional status 30 years after the operation but only 40-50% of them remain in sinus rhythm, while 30% of patients had minimally one episode of atrial flutter. A 28 year-old female was admitted to our Department in November 2011. When she was 9 months old, she underwent Senning procedure because of d-TGA. She was asymptomatic on beta-blocker until the age of 26 when she experienced palpitations and reduced effort tolerance. In addition, she was planning a pregnancy. Echocardiography showed the dilated and hypertrophic systemic right ventricle with reduced systolic function, and moderate to severe tricuspid regurgitation. Atrial conduits have a normal function. Cardiovascular magnetic resonance imaging showed a right ventricular hypertrophy without signs of fibrosis, and preserved Proπireni saaeetak / Extended abstract

Case report: Disappearance of left atrial appendage thrombus on dabigatran therapy

3. Morita S, Ajiro Y, Uchida Y, Iwade K. Dabigatran for left atrial thrombus. Eur Heart J. 2013; 34(35):2745. UvOD: Učinak dabigatrana je dobro poznat u prevenciji moždanog udara i tromboembolija u nevalvularnoj fibrilaciji atrija, kao i prevencije duboke venske tromboze pri operaciji kuka i koljena, no učinak dabigatrana na već formirani tromb u aurikuli lijevog atrija nije potpuno jasan. Prikazujemo dva slučaja otapanja tromba u aurikuli lijevog atrija (LAA) pod terapijom dabigatranom .

Inducible left-ventricular intracavity gradient during dobutamine stress echocardiography — a condition worth noting

Cardiologia CROATICA Objectives: To evaluate the incidence and left ventricular (LV) morphologic characteristics of patients developing dynamic intraventricular obstruction induced during dobutamine stress echocardiography (DSE). Methods: We studied 77 patients (42 men 55%; mean age 61±12 years) referred for standard high-dose DSE due to exertional dyspnoea or chest pain. The patients were divided into two groups — group I consisted of patients who developed a significant left-ventricular (LV) intracavitary gradient (>20 mmHg) during DSE (33 patients, 45% men, mean age 58.6 ± 12.5 years) and group II consisted of patients without an inducible gradient (44 patients 61% men; mean age 62.5 ± 10.7 years). The intracavitary gradient was defined as a late-peaking left ventricular Doppler velocity profile exceeding basal velocity by 1 m/sec. Results: 43% of the studied patients developed the gradient during high stages of dobutamine infusion (>20 mcg/kg/ min). Mean intracavitary gradient was 75.1 mmHg (range 20-135 mmHg). Patients in group I had statistically smaller LV cavity dimensions (Table 1) but their ejection fraction and fractional shortening were greater. These measurements were done using the Teicholtz method which is based on measuring the radial function of the LV (Table 1). Hypertension was present in a larger percentage of patients in the group I compared to the group II, however not reaching statistical significance (group I 30%, group II 18%, p = 0.28). According to patient histories somewhat more patients in the group I (27%) experienced symptoms like dyspnoea or chest pain during dobutamine infusion than in the group II (18%). The DSE study (Figure 1) was positive for inducible ischaemia in a significantly greater number of patients in the group II, compared to the patients developing the gradient (88% to 12%). Conclusion: An inducible LV intracavitary gradient occurred in a large number (43%) of patients referred to DSE in our centre. These patients had significantly smaller LV cavity dimensions which, together with notably increased radial function, likely contributes to the development of the gradient. Higher values of LV radial function measurements are common in hypertension. Indeed, we noted a higher inciProπireni saæetak / Extended abstract

Global radial strain is reduced in healthy heart transplant patients

Cardiologia CROATICA Background: Allograft rejection and vasculopathy in heart transplant (HTx) patients require timely recognition, with coronary angiography and endomyocardial biopsy being the diagnostic gold standards. Finding a non-invasive alternative remains the major objective. Speckle tracking echocardiography (STE) permits early recognition of myocardial dysfunction. The reduction in strain has been shown to denote both rejection and vasculopathy. However, deformation indices are also reduced in “healthy” HTx recipients ≥1 year after transplantation when compared with control subjects. Whether the reduction in strain is a chronic progressive process or the immediate result of transplantation (due to allograft ischaemia, denervation, cardioplegia etc.) has not yet been established. Hence, the lack of STE reference values in HTx population, especially during early post-transplant period, is one of the reasons that strain has not been used to follow-up these patients. The aim of the study was to evaluate whether radial deformation parameters are reduced in “healthy” HTx recipients during the first post-transplant year. Methods: Two-dimensional STE was used to evaluate radial strain in 15 “healthy” patients up to 6 months following heart transplantation. Patients were excluded if they had histologic evidence of acute rejection (>1A ISHLT), reduced LVEF (<55%), significant coronary vasculopathy (epicardial coronary narrowing >50% assessed by coronary angiography), wide QRS-complex (>120 ms), significant valvular disease or major cardiac events. Frame rates of ≈50 to 70s to avoid speckle decorrelation and good image quality for accurate tracking were mandatory. Segmental radial strain analysis was performed at the LV basal, middle and apical levels, and values were averaged to determine global radial strain. The results were then compared with the healthy normal subjects’ values, using recent meta-analysis data. Results: Global radial strain was significantly lower in transplant patients when compared with control subjects — mean 39.2% (95% CI 33.5 to 44.9%) vs. 47.3% (95% CI 43.6 to 51.0%), p 0.008. Conclusions: The reduction of global radial strain in “healthy” HTx subjects during early post-transplant period may be an immediate consequence of the transplant procedure. The baseline strain values should be obtained in all transplant patients soon after the transplantation, so that these values can later be used as a reference for early detection of myocardial abnormalities.