Influence of complete myocard revascularization on the recovery of left ventricles distolic function

Jedan od glavnih uzroka dijastoličkog poremećaja srčanog mišića je ishemijska bolest srca, koje je u moderno doba poprimila epidemijske razmjere. Od kada je utvrđeno da je izolirana dijastolička disfunkcija srčanog mišića prediktor povećanog morbiditeta i mortaliteta, došla je u fokus interesa. Cilj ovog istraživanja je bio utvrditi postoji li razlika u oporavku izolirane dijastoličke disfunkcije u kompletno revaskulariziranih bolesnika u usporedbi s inkompletno revaskulariziranim. Postavljena je hipoteza da je oporavak dijastoličke funkcije bolji u anatomski kompletno revaskulariziranih bolesnika nego u onih koji su inkompletno revaskularizirani. Procjena dijastoličke funkcije rađena je ultrazvukom srca uz tkivni dopler i invazivno mjerenje krajnjeg dijastoličkog tlaka lijeve klijetke, kako je i određeno protokolom. Kao parameter dijastoličke disfunkcije korišten je i BNP, te se željelo utvrditi da li je BNP jednako dobar pokazatelj dijastoličke disfunkcije kao i ultrazvuk srca. U studiju je uključeno 65 bolesnika sa stabilnom koronarnom bolešću određenih za revaskularizaciju PCI procedurom s prethodno dokazanom izoliranom dijastoličkom disfunkcijom koji su podijeljeni su u dvije usporedive skupine; 33 bolesnika u skupini gdje je postignuta inkompletna revaskularizacija i 32 bolesnika u skupini s kompletnom revaskularizacijom. Neposredno prije zahvata kod svih je bolesnika invazivnim mjerenjem registrirana patološka vrijednost LVEDP-a. Među skupinama nije bilo statistički značajne razlike u distribuciji dijastoličkog poremećaja na početku istraživanja (p=0,638), kao niti u sistoličkoj funkciji lijeve klijetke (p=0,283). U skupini inkompletne revaskularizacije bilo je statistički značajno više bolesnika sa šećernom bolešću (p=0,028), prethodno preboljelim infarktom miokarda (p=0,035) te prethodno učinjenim intervencijama na koronarnim arterijama (p=0,035). Vrijednosti BNP-a su na početku istraživanja povišene kod svih bolesnika, bez statističke razlike među skupinama (p=0,733); više vrijednosti BNP-a su povezane s težim stupnjevima dijastoličkog poremećaja uz statističku značajnost samo za skupinu inkompletne revaskularizacije. Neposredno nakon zahvata registriran je pad LVEDP-a u 49,5 % slučajeva, LVEDP je ostao nepromijenjen u 9,2% slučajeva, a u 41,5% se tranzitorno povisio. U razdoblju od 3 mjeseca 65 DOKTORSKI RAD 8. SAŽETAK nakon revaskularizacije registriran je izvrstan oporavak dijastoličkog poremećaja u obje promatrane skupine (p<0,001), bez razlike među skupinama. Oporavak perzistira i nakon 6 mjeseci i dalje je statistički značajan u obje skupine (p=0,001), također bez značajne razlike među promatranim skupinama. Vrijednosti BNP-a nakon zahvata padaju kod svih bolesnika, bez značajne razlike među skupinama. Samo je u skupini inkompletne revaskularizacije registrirana statistički značajna poveznica BNP-a s težinom dijastoličkog poremećaja kako na početku, tako i na kraju istraživanja, dok se u skupini kompletne revaskularizacije nije registriralo statističke značajnosti. Zaključno, nema jasnog perakutnog oporavka dijastoličkog disfunkcije neposredno nakon revaskularizacije, nego se dijastolička funkcija tranzitorno može i pogoršati. Oporavak je izvrstan u razdoblju od 3 mjeseca i perzistira na kontroli od 6 mjeseci. Nema statistički značajne razlike u oporavku dijastoličkog poremećaja među promatranim skupinama. Ultrazvuk srca s tkivnim doplerom i dalje ostaje metoda izbora u procjeni dijastoličkog poremećaja, a BNP nije dovoljno pouzdan da se sam koristi u procjeni izolirane dijastoličke disfunkcije. Anatomska kompletnost revaskularizacije nije presudna u oporavku dijastoličkog poremećaja, već striktno poštivanje indikacije za revaskularizacijom i procjenom vijabiliteta miokarda te težnjom za postizanjem funkcionalno kompletne revaskularizacije.One of the major causes of diastolic dysfunction is ischemic heart disease that has reached the epidemic proportions these days. Since the isolated diastolic dysfunction was recognized as an important morbidity and mortality predictor, it came to a focus of interest. The aim of this study is to evaluate the importance of revascularization completeness in isolated diastolic dysfunction recovery. The hypothesis is that the recovery is better is the group with complete revascularization achieved. The evaluation of diastolic function was done by echocardiogram including tissue Doppler and directly, invasively. BNP was used as an additive parameter in assessing the diastolic function recovery and we tried to determine if the BNP was as good as the ultrasound in diastolic dysfunction assessment. This study included 65 patients with previously recognized isolated diastolic dysfunction that met criteria for PCI revascularization. Two comparable groups of patients were identified; one with complete revascularization achieved (32 patients) and another one with incomplete one (33 patients). At the beginning, before the intervention, all patients had pathological LVEDP measured directly, invasively. In the incomplete revascularization group, the proportion of patients that had diabetes mellitus, previous myocardial infarction and previous PCI procedure was statistically higher (p=0,028, p=0,035, p=0,035), consecutively, but there was no statistical difference in left ventricle systolic function between two groups (p=0,238), what represents the basis of our study and makes the groups comparable. Furthermore, no statistical difference was found in diastolic dysfunction distribution at the beginning between two groups (p=0,638). Immediately after PCI procedure, LVEDP was measured again and in 49,5% patients the decrease of LVEDP was registred, in 9,2% patients LVEDP was the same as at the beginning and in 41,5% patients the LVEDP raised transitionally. According to these results we can conclude that there is no acute recovery of diastolic function immediately after revascularization by default. The short-time recovery (3 months period) was excellent, in both groups, regardless of completeness of revascularization (p<0,001). Excellent recovery persists during long-time follow-up period as well (6 month period), with no statistical differences in two groups (p<0,001 for both groups). Considering BNP, we can conclude that the higher levels of BNP are in concordance with heavier degrees of diastolic dysfunction in the group of 67 DOKTORSKI RAD 9. SUMMARY incomplete revascularization (near the limit of statistical significance p=0,058), and for the complete revascularization group statistically irrelevant. Furthermore, we found a clear correlation (statistically significant) between the BNP levels and the degree of diastolic dysfunction in the beginning and at the end of the study, but only for the incomplete revascularization group. We found no statistically significant correlation in the complete revascularization group. Inclusively, there is no acute recovery immediately after revascularization by default, but diastolic function could deteriorate temporarily. Recovery is excellent in 3 months period and it persists in 6 months period, as well. There is no statistical difference in diastolic function recovery between our two groups. Echocardiography including tissue Doppler still remains the method of choice in assessing the diastolic dysfunction, and BNP is not good enough to be the only parameter in evaluation of isolated diastolic dysfunction. The anatomical completeness of revascularization is not crucial in diastolic disfunction recovery, but diastolic dysfunction recovery is much more depending on the revascularization indication and on the judgement of myocardial viability and tendency of achiving functionally completed revascularization

Pathophysiology of hormone-resistant prostate cancer

Androgen-deprivation therapy (ADT) has been for many years the cornerstone of metastatic prostate carcinoma (PC) treatment. It is very well documented that the majority of cancer cells in prostate gland remain androgen responsive what was the basis for androgen suppression in treatment. Nevertheless, after some time or sometimes initially, PCa cells become resistant to castration serum level of testosteron, because of some genetic and epigenetic changes that make them independent from hormone activation. There are two therories – the clonal theory and the adaptation theory of how some carcinoma cells become castration-resistant. It has been shown recently, that PCa cells can still use androgen receptor as a major signaling pathway, by activation of enzyme machinery or de novo production of androgen within the cells

Echocardiographic Assessment of Revascularization Completeness Impact on Diastolic Dysfunction in Ischemic Heart Disease

Diastolic dysfunction indicates a functional abnormality of diastolic relaxation, filling, or distensibility of the left ventricle (LV), regardless of whether the LVEF is normal or abnormal. Diastolic dysfunction is practically always pro- gressive and connected with higher morbidity and mortality rates, and, if not treated may lead to a diastolic heart fail- ure. The golden standard for evaluation of diastolic function is echocardiography. One of the most important causes of diastolic dysfunction is ischemic heart disease. The revascularization of chronic myocardial ischemia can be partial (in- complete) or complete. Previous data have shown that the completeness of revascularization could have influence on clin- ical outcomes. The aim of this study was to asses, by means of echocardiography, the impact of completeness of revascula- rization on diastolic dysfunction in ischemic heart disease. This study included 65 consecutive patients with previously recognized diastolic dysfunction that met criteria for PCI revascularization. Two groups of patients were identified; one with complete revascularization achieved and another one with incomplete one. There were no statistical differences be- tween two groups considering gender, age, arterial hypertension, hyperlipoproteinaemia, previous CABG and left ventricle systolic function. In the incomplete revascularization group, the proportion of patients that had diabetes mellitus, previ- ous myocardial infarction and previous PCI procedure were statistically higher (p<0.05). The diastolic function recovery was statistically significant in both groups (p<0.001), and there was no statistically significant difference in recovery be- tween the two groups. Lack of recovery was registered in 18.2% patients with incomplete revascularization achieved, and 15.6% in the complete group, which was not significant, but shows a trend. The causes of somewhat worse recovery in the incomplete revascularization group could be attributed to the higher proportion of diabetics, to the somewhat older popu- lation and ultimately to the incomplete revascularization. The E/A ratio on diastolic transmitral flow as well as the E/E lat ratio on tissue doppler were found as the best echocardiographic parameters in diastolic function evaluation. In fol- low up recovery after complete or incomplete revascularization the tissue doppler (E/E lat) was recognized as the best parameter. In conclusion, we found that echocardiographic assessment of diastolic function recovery was a safe method, and our results showed that even in incomplete revascularization group of patients the recovery of diastolic function could be as good as in the complete one, if the indication for revascularization was correct