Danijela Trifunovic

Regional difference of microcirculation in patients with asymmetric hypertrophic cardiomyopathy: transthoracic Doppler coronary flow velocity reserve analysis.

OBJECTIVE To evaluate, by noninvasive coronary flow velocity reserve (CFVR), whether patients with asymmetric hypertrophic cardiomyopathy (HC), with or without left ventricular outflow tract obstruction, demonstrate significant regional differences of CFVR. METHODS We evaluated 61 patients with HC (27 men; mean age 49 ± 16 years), including 20 patients with hypertrophic obstructive cardiomyopathy (HOCM) and 41 patients without obstruction (HCM). The control group included 20 age- and sex-matched subjects. Transthoracic Doppler echocardiography CFVR of the left anterior descending coronary artery (LAD) and the posterior descending coronary artery (PD) were performed, including calculation of relative CFVR as the ratio between CFVR LAD and CFVR PD. RESULTS Compared with the controls, all the patients with HC had lower CFVR LAD (2.12 ± 0.53 vs 3.34 ± 0.67; P < .001) and CFVR PD (2.29 ± 0.49 vs 3.21 ± 0.65; P < .001). CFVR LAD in HOCM group in comparison with the HCM group was significantly lower (1.93 ± 0.42 vs 2.22 ± 0.55; P = .047), due to higher basal diastolic coronary flow velocities (0.40 ± 0.09 vs 0.33 ± 0.07 m/sec; P = .002), with similar hyperemic diastolic flow velocities (0.71 ± 0.16 vs 0.76 ± 0.19 m/sec; P = .330), respectively. There was no significant difference in CFVR PD between patients with HOCM and those with HCM (2.33 ± 0.46 vs 2.27 ± 0.50; P = .636), respectively. Relative CFVR was lower in the HOCM group compared with the HCM group (0.84 ± 0.16 vs 0.98 ± 0.14; P = .001). By multivariable regression analysis, left ventricular outflow tract gradient was the independent predictor of CFVR LAD (B = -0.24; P = .008) and relative CFVR (B = -0.34; P = .016). CONCLUSIONS CFVR LAD and relative CFVR were significantly lower in patients with HOCM compared with patients with HCM. Regional differences of CFVR are present only in patients with significant left ventricular outflow tract obstruction, which suggests that obstruction per se, by increasing wall stress in basal conditions, leads to higher basal diastolic coronary flow velocities and results in lower CFVR in LAD compared with PD.

Diagnostic value of NT-proBNP in identifying impaired coronary flow reserve in asymptomatic moderate or severe aortic stenosis

AIM NT-proBNP has been shown to be a reliable biochemical marker for left ventricular wall stress. The relationship between NT-proBNP and coronary flow reserve (CFR) was evaluated in patients with significant asymptomatic aortic stenosis (AS). METHODS A total of 74 patients with moderate or severe AS, mean age 66.68 ± 10.02 years (56.75% males), were enrolled in this prospective study. All patients underwent coronary angiography and had no obstructive coronary disease (defined as having no stenosis >50% in diameter). They had all undergone standard transthoracic Doppler-echo study and adenosine stress transthoracic-echo for CFR measurement and laboratory analysis for NT-proBNP measurement. RESULTS The median NT-proBNP value was significantly increased (417.0 pg/ml; interquartile range [IQR]: 176.8-962.2 pg/ml). NT-proBNP was significantly higher in the group with CFR ≤2.5 (median: 549.0 pg/ml; IQR: 311.5-1131.0 pg/ml; as opposed to median: 291.5 pg/ml; IQR: 123.0-636.2 pg/ml; W = 452; p = 0.012). NT-proBNP showed significant negative correlation with CFR (ρ = -0.377, p = 0.001). There was also significant correlation between NT-proBNP and E/E´, S´ and aortic valve resistance. The NT-proBNP value of 334.00 pg/ml was determined as the best cut-off value for the diagnosis of CFR ≤2.5 (area under the curve: 0.67; 95%CI: 0.54-0.79; p < 0.01) and the sensitivity and specificity were 74 and 64%, respectively. CONCLUSION Elevated NT-proBNP can indicate patients with impaired CFR in asymptomatic moderate or severe AS patients with preserved ejection fraction and nonobstructive coronary arteries.

Time-dependent changes of plasma adiponectin concentration in relation to coronary microcirculatory function in patients with acute myocardial infarction treated by primary percutaneous coronary intervention

BACKGROUND AND PURPOSE To analyze plasma adiponectin kinetics in patients with ST-segment elevation myocardial infarction (STEMI) treated by primary percutaneous coronary intervention (pPCI) and its association with coronary flow reserve (CFR), an index of coronary microcirculatory function. METHODS A total of 96 consecutive patients with the first anterior STEMI treated by pPCI without heart failure were included. CFR was assessed on the 7th day after pPCI. Plasma adiponectin was measured on admission before pPCI, and on the 2nd and 7th day after pPCI. RESULTS Adiponectin concentration was the highest on admission, declined to the lowest level on the 2nd day, and rose on the 7th day remaining below admission values. Impaired coronary microcirculatory function (CFR<2) was observed in 41% of the patients. Adiponectin concentrations significantly positively correlated with CFR, and the strongest correlation was with the 2nd day adiponectin (r=0.489, p<0.001). In multivariate models, adiponectin concentrations were independent predictors of impaired CFR [on admission: odds ratio (OR) 0.175, confidence interval (CI): 0.047-0.654, p=0.010; 2nd day: OR 0.146, 95% CI: 0.044-0.485, p=0.002; 7th day: OR 0.198, CI: 0.064-0.611, p=0.005]. The best power to predict impaired CFR was the 2nd day adiponectin. Delta values of adiponectin (differences between adiponectin concentrations) did not correlate with CFR. CONCLUSIONS In patients with the first anterior STEMI treated by pPCI plasma adiponectin concentrations before and after pPCI are strongly associated with CFR. Our results support the hypothesis that low adiponectin, especially during the early post-pPCI period, carries the risk for impaired coronary microcirculatory function in STEMI patients.

Time-dependent changes of myeloperoxidase in relation to in-hospital mortality in patients with the first anterior ST-segment elevation myocardial infarction treated by primary percutaneous coronary intervention.

OBJECTIVES To analyze the prognostic value of myeloperoxidase (MPO) in relation to in-hospital mortality and to identify the optimum time point for sampling in patients with the first anterior ST-segment elevation myocardial infarction (STEMI) treated by primary percutaneous coronary intervention (pPCI). DESIGN AND METHODS A total of 100 consecutive patients with the first anterior STEMI undergoing pPCI were included. Blood samples were collected at baseline, 4, 8, 12, 18, 24, 48 and 168 hours (h) after pPCI. RESULTS MPO concentrations have showed a biphasic pattern over time; the highest MPO levels were at4h and 24h after pPCI. In-hospital mortality was 6%. MPO at 24h significantly correlated with troponin I as well as heart failure. After multivariate adjustment, MPO at 24h was an independent predictor of the in-hospital mortality (OR 3.34, 95% CI 1.13-9.86, P=0.029). CONCLUSIONS In patients with the first anterior STEMI treated by pPCI, MPO at 24h after procedure was an independent predictor of the in-hospital mortality.

PREDICTION OF CARDIOVASCULAR MORTALITY IN FUNCTIONALLY DISABLED ELDERLY – A POSSIBLE NEW SCORE / KARDIOVASKULARNI MORTALITET KOD FUNKCIONALNO ZAVISNIH STARIH OSOBA - MOGUĆI PREDIKTIVNI SKOR

Summary Background: We investigated the traditional and new bio- markers as predictors of cardiovascular mortality in the func- tionally disabled elderly who are living in a community. Methods: This prospective study included 253 participants (78.3% women) aged 65 and over who were monitored for 32 months. Receiver operating curve analysis and the Cox proportional hazard model were used to identify univariate and multivariate predictors of cardiovascular mortality. The Kaplan-Meier survival curve and Log rank test were used for survival analysis. Results: During the study, 43.1% participants died from car- diovascular diseases. Cutoff points of multivariate predictors were used to build a score system. The risk score was positive in patients with three or more of the following predictors: albumin <40 g/L, body mass index <25 kg/m2, total serum bilirubin <10.5 (imol/L, blood urea nitrogen >6.5 mmol/L and high-sensitivity C-reactive protein >2.25 mg/L. The rel- ative risk for cardiovascular mortality for someone with a positive vs. negative score was 3.91 (95% Cl: 2.55-5.98; P< 0.001). There was no change in risk after adjustment for age; sex, traditional cardiovascular risk factors, comorbidities and a number of disabilities. Conclusions: Presence of lo* grade inflammation, malnulri tion and early signs of renal dy sfunction are essential for car- diovascular risk among the functional disabled elderly and may be assessed using the proposed new inflammatory m3lnuhffion-renal involved score (1MRIS). Kratak sadržaj Uvod: Istraživali smo tradicionalne faktore rizika i nove bio- markere kao prediktore za kardiovaskularni mortalitet kod funkcionalno zavisnih starih osoba koje žive u zajednici. Metode: Ova prospektivna studija obuhvatila je 253 učesni- ka starih 65 i vise godina (78,3% žena) koji su praćeni 32 meseca. ROC kriva (engl. receiver operating characteristic curve) i Coxov proporcioni hazardni model korišćeni su za identifikaciju univarijantnih i multivarijantnih prediktora kar- diovaskularnog mortaliteta. Kaplan-Meierova kriva preživlja- vanja i Log rank test korišćeni su za analizu preživljavanja. Rezultati: Tokom studije 43,1% učesnika je umrlo od kar- diovaskularnih bolesti. Na osnovu graničnih (cutoff) skoro- va multivarijantnih prediktora napravljen je prediktivni skor za kardiovaskularni mortalitet. Ovaj skor je bio pozitivan kod učesnika sa tri i vise od sledećih prediktora: albumin <40 g/L, indeks telesne mase <25 kg/m2, ukupni serum- ski bilirubin <10,5 (jmol/L, urea >6,5 mmol/L i visokosen- zitivni C-reaktivni protein >2,25 mg/L. Relativni rizikza kar- diovaskularni mortalitet ukoliko neko ima pozitivan skor bio e 3,91 (95% Cl: 2,55-5,98; P<0,001). Nije bilo promene u riziku nakon prilagođavanja za starost, pol, tradicionalne faktore rizika, komorbiditete i stepen funkcionalne zavisnosti. Zaključak: Prisustvo inflamacije niskog stepena, malnutrici- je i početni znaci bubrežne disfunkcije su esencijalni za procenu kardiovaskularnog rizika kod funkcionalno zavisnih starih osoba i mogu biti procenjeni na osnovu novog pre- diktivnog skora nazvanog IMRIS (engl. inflammatory-mal- nutrition-renal involved skor).

Assessment of Coronary Microcirculation with Myocardial Contrast Echocardiography

Myocardial contrast echocardiography has been used in clinical arena and for scientific research extensively in the last fifteen years. This non-invasive, bed-side and radiation free imaging technique offers several important possibilities: better delineation of the endocardial border, more reliable assessment of the left ventricular wall motion abnormalities, both in rest and during stress, and myocardial perfusion evaluation. Here we provide an overview on different applications of the myocardial contrast echocardiography in the ischemic heart disease with the special focus on perfusion studies and evaluation of coronary microcirculation.

Silent diabetic cardiomyopathy in everyday practice: a clinical and echocardiographic study

BackgroundWhether type 2 diabetes mellitus (DM) in the absence of hypertension (HTA) and coronary artery disease (CAD) affects left ventricular (LV) phenotype and function among asymptomatic DM patients that can be easily discovered in everyday practice, what is the clinical risk profile for diabetic cardiomyopathy and how HTA and CAD modulate LV structure and function above diabetic cardiomyopathy, are still incompletely answered questions.MethodsIn 210 DM patients (group I: 70 asymptomatic DM patients without HTA and CAD; group II: 70 DM patients with HTA and no CAD; group III: 70 DM patients with CAD and no HTA) and 80 healthy individuals, comprehensive echocardiography including speckle tracking strain and strain rate analysis, was done.ResultsCompared to control DM patients without HTA and CAD had increased LV mass, more frequently concentric remodeling, impaired LV relaxation and lower LV ejection fraction (EF), fraction of shortening (FS) and mitral annular plane excursion (MAPSE). Addition of HTA further impaired EF, FS and MAPSE and aggravated diastolic dysfunction, whereas concomitant CAD further impaired FS and MAPSE. Peak global longitudinal strain (Slong) and early diastolic longitudinal strain rate (SRlong E) were impaired in group I compared to control, even when EF was preserved. Peak circumferential strain (Scirc) was impaired only when DM was associated with HTA or CAD. In multivariate analysis DM was significantly and independently from HTA, CAD, age, gender and body mass index associated with: increased LV mass, concentric LV remodeling, lower EF, FS, MAPSE, Slong, SRlongE and distorted diastolic parameters. DM duration, glycosylated hemoglobin, microalbuminuria and retinopathy, were not independent predictors of LV geometry and function.ConclusionDM per se has strong and independent influence on LV phenotype and function that can be detected by conventional and speckle tracking echocardiography in everyday clinical practice, even in asymptomatic patients. We could not confirm that these changes were independently related to duration of DM, quality of metabolic control and presence of microvascular complications. Concomitant HTA or CAD furthermore distorted LV systolic and diastolic function.

Oxidized Low Density Lipoprotein and High Sensitive C-Reactive Protein in Non-Diabetic, Pre-Diabetic and Diabetic Patients in the Acute Phase of the First Myocardial Infarction Treated by Primary Percutaneous Coronary Intervention / Oksidovani Lipoprotein Niske Gustine I Visokosenzitivni C-Reaktivni Protein Kod Nedijabetičara, Predijabetičara I Dijabetičara U Akutnoj Fazi Prvog Infarkta Miokarda Lečenog Primarnom Perkutanom Koronarnom Intervencijom

Summary Background: Oxidized low density lipoprotein (ox-LDL) and high-sensitive C-reactive protein (hs-CRP) are elevated in diabetes mellitus (DM) and associated with accelerated atherosclerosis. Little is known about their dynamics in the acute phase of ST segment elevation myocardial infarction (STEMI), especially in relation to the presence of DM and pre-diabetes (pre-DM). This study aimed to analyze timedependent changes in ox-LDL and hs-CRP regarding the presence of pre-DM and DM in STEMI patients treated by primary percutaneous coronary intervention (pPCI). Methods: In 103 consecutive patients with the first anterior STEMI ox-LDL and hs-CRP were measured before pPCI, on day 2 and day 7 after pPCI. Results: Patients were classified into: non-diabetics, pre-diabetics and diabetics. In each group the maximal ox-LDL concentration was found on admission, decreased on day 2 and reached the lowest values on day 7 (p<0.001). Diabetics had the highest ox-LDL concentrations compared to pre-diabetics and non-diabetics (on admission: p=0.028, on day 2: p=0.056, on day 7: p=0.004). hs-CRP concentration rose from admission, reached its peak on day 2 and decreased on day 7, in each group (p<0.001). Significant differences in hs-CRP concentrations were found between non-diabetics and pre-diabetics on admission (p=0.018) and day 2 (p=0.026). In a multivariate analysis DM was an independent determinant of high ox-LDL concentrations. Both ox-LDL and hs-CRP significantly correlated with Killip class, left ventricular ejection fraction, NT-proBNP and peak troponin I. Conclusions: In patients with the first STEMI treated by pPCI there were significant differences in ox-LDL and hs-CRP concentrations between non-diabetics, pre-diabetics and diabetics. Ox-LDL and hs-CRP concentrations were related to heart failure parameters. Kratak sadržaj Uvod: Oksidovani lipoprotein niske gustine (ox-LDL) i vi- sokosenzitivni C-reaktivni protein (hs-CRP) povišeni su u dijabetes melitusu (DM) i povezani sa ubrzanom atero- sklerozom. Malo je poznata njihova dinamika u akutnoj fazi infarkta miokarda sa elevacijom ST segmenta (STEMI), na- ročito uzavisnosti od prisustva DM ili predijabetesa (pre-DM). Ova studija je analizirala promenu koncentracija ox-LDL i hs-CRP u akutnoj fazi STEMI u odnosu na prisustvo pre- DM i DM kod bolesnika lečenih primarnom perkutanom koronarnom intervencijom (pPKI). Metode: Kod 103 konsekutivna bolesnika sa prvim pred- njim STEMI, hs-CRP i ox-LDL mereni su pre pPCI, drugog i sedmog dana nakon pPKI. Rezultati: Bolesnici su podeljeni u tri grupe: nedijabetičari, predijabetičari i dijabetičari. U svakoj grupi maksimalna koncentracija ox-LDL bila je na prijemu, smanjivala se drugog dana i postizala najniže vrednosti sedmog dana (p<0,001). Dijabetičari su uvek imali najviše vrednosti ох- LDL u poređenju sa predijabetičarima i nedijabetičarima (na prijemu: p=0,028, drugog dana: p=0,056 i sedmog dana: p=0,004). Koncentracija hs-CRP je u svakoj grupi rasla od prijema, postizala maksimalne vrednosti drugog dana i smanjivala se sedmog dana (p<0,001). Značajna razlika u koncentraciji hs-CRP između nedijabetičara i predijabetičara registrovana je na prijemu (p=0,018) i dru- gog dana (p=0,026). U multivarijantnoj analizi DM je bio nezavisan prediktor visokih koncentracija ox-LDL. I ox-LDL i hs-CRP su značajno korelisali sa Killip klasom, ejekcionom frakcijom leve komore, koncentracijom NT-proBNP i mak- simalnom vrednošču troponina I. Zaključak: Kod bolesnika sa prvim STEMI lečenim pPKI postojale su značajne razlike u koncentraciji ox-LDL i hs- CRP između nedijabetičara, predijabetičara i dijabetičara. Koncentracije ox-LDL i hs-CRP značajno su korelisale sa parametrima srčane insuficijencije.

The Natural History of Viral Myocarditis: Pathogenetic Role of Adrenergic System Dysfunction in the Development of Idiopathic Dilated Cardiomyopathy

The pathogenetic mechanisms of progression from viral myocarditis to dilated cardiomyopathy remain uncertain and controversial. With recent developments in molecular analyses of tissue specimens, new techniques of viral gene amplification and biochemical analyses, a causal link has become increasingly apparent.1-3 Perhaps the main breakthrough in the understanding of this complex clinical issue has been the demonstration of persistence of viral RNAIDNA in the myocardium beyond 90 days after inoculation, confirmed by polymerase chain reaction. Although viral myocarditis has various clinical presentations, only severe cases cause substantial cardiac injury and the development of dilated cardiomyopathy. In addition to the inflammatory injury to the myocytes, various other mechanisms are likely to be involved.4 Several studies have revealed both T-cell-immune-mediated and viral-induced cardiac injury as the predominant pathophysiologic mechanisms.4-5 However, apoptotic cell death may be another explanation behind the adverse clinical evolution of acute myocarditis.6 In addition, there is experimental and clinical evidence of the detrimental effects of a heightened sympathetic activity in acute myocarditis. Several investigators have examined the effects of exercise during Coxsackie virus B3-induced myocarditis in mice.7-9 Swimming or running on a treadmill were used as exercise stressors, increasing the heart rate and blood pressure, effects mostly mediated by catecholarnines. More extensive cardiac lesions were regularly observed in exercised than in nonexercised Coxsackie virus B3-infected mice.10 In a short-term hemodynamic study in humans, Popovic et al. showed beneficial effects of metoprolol with or without nitroglycerin, in 11 patients with biopsy-proven lymphocytic myocarditis and left ventricular dysfunction.11

Successful establishment of a left ventricular assist device program in an emerging country: one year experience

Background The primary goal of this study was to evaluate the outcomes of patients with end-stage heart failure (HF) who underwent continuous flow left ventricular assist device (CF-LVAD) in a developing country and to compare to those reported by more developed countries. The secondary goal was on determining factors that may be connected to improved survival. Methods We prospectively analyzed 47 consecutive patients who underwent CF-LVAD at our institution. After one year the survival and adverse event profiles of patients were evaluated. At 3, 6 and 12 months, the cardiac, renal and liver function outcomes were assessed. Results The 30-day, 6-month and 1-year survival rates were 89%, 85% and 80%, respectively. A significant improvement in dimensions and ejection fraction of left ventricle, BNP, functional capacity, blood urea nitrogen (BUN) and total bilirubin (P<0.05 for all) were noticed 3 months post-CF-LVAD implantation, and patients were stable throughout the entire first year follow up. In the group of patients with baseline renal dysfunction (RD) there were significant improvements of renal function (P=0.004), with no changes on follow up. 57% of patients exhibited some kind of adverse event, commonly in the form of bleeding. In multivariate Cox regression analysis renal failure was found to be as an independent risk factor for the overall survival (HR =13.1, P<0.001). Conclusions In conclusion, our data extends previous findings from centers of developed countries, that CF-LVAD is an adequate treatment option for patients suffering from end-stage HF, and encourages expansion of CF-LVAD implantation in developing countries with nascent HT program.