Relation between cardiac magnetic resonance-assessed interstitial fibrosis and diastolic dysfunction in heart failure due to dilated cardiomyopathy.

Background: Dilated cardiomyopathy (DCM) is distinguished by left ventricle (LV) dilation accompanied by systolic dysfunction. However, some studies suggested also a high prevalence of LV diastolic dysfunction (LVDD), similar to a general cohort of heart failure (HF) with reduced ejection fraction (LVEF). The bulk of evidence, mostly arising from basic studies, suggests a causative link between cardiac fibrosis (CF) and LVDD. However, still, there remains a scarcity of data on LVDD and CF. Therefore, the aim of the study was to investigate the association between CF and LVDD in DCM patients. Methods: The study population was composed of 102 DCM patients. Replacement CF was evaluated qualitatively (late gadolinium enhancement - LGE) and quantitively (LGE extent); interstitial cardiac fibrosis was assessed via extracellular volume (ECV). Based on echocardiography patients were divided into normal and elevated left atrial pressure (nLAP, eLAP) groups. Results: 42 % of patients had eLAP. They displayed higher troponin and NT-proBNP. Both groups did not differ in terms of LGE presence and extent; however, eLAP patients had larger ECV: 30.1 ± 5.6 % vs. 27.8 ± 3.9 %, p = 0.03. Moreover, ECV itself was found to be an independent predictor of LVDD (OR = 0.901; 95 %CI 0.810-0.999; p = 0.047; normalised for LVEF and RVOT diameter). Conclusions: More than two-in-five DCM patients had at least moderate LVDD. The mere presence or extent of replacement cardiac fibrosis is similar in patients with nLAP and eLAP. On the other hand, interstitial cardiac fibrosis is more pronounced in those with a higher grade of LVDD. ECV was found to be an independent predictor of LVDD in DCM.

Relationships between Pulmonary Hypertension Risk, Clinical Profiles, and Outcomes in Dilated Cardiomyopathy.

Pulmonary hypertension (PH) in patients with heart failure (HF) contributes to a poorer prognosis. However, in those with dilated cardiomyopathy (DCM), the true prevalence and role of PH is unclear. Therefore, this study aimed to analyze the profile of DCM patients at various levels of PH risk, determined via echocardiography, and its impact on outcomes. The 502 DCM in- and out-patient records were retrospectively analyzed. Information on patient status was gathered after 45.9 ± 31.3 months. Patients were divided into 3 PH-risk groups based on results from echocardiography measurements: low (L, n = 239, 47.6%), intermediate (I, n = 153, 30.5%), and high (H, n = 110, 21.9%). Symptom duration, atrial fibrillation, ventricular tachyarrhythmia, ejection fraction, right atrial area, and moderate or severe mitral regurgitation were found to be independently associated with PH risk. During the follow-up period, 83 (16.5%) DCM patients died: 29 (12.1%) in L, 31 (20.3%) in I, and 23 (20.9%) in H. L-patients had a significantly lower risk of all-cause death (L to H: HR 0.55 (95%CI 0.32-0.98), p = 0.01), while no differences in prognosis were found between I and H. In conclusion, over one in five DCM patients had a high PH risk, and low PH risk was associated with better prognoses.

The role of 99mTc-HMPAO-labelled white blood cell scintigraphy in the diagnosis of cardiac device-related infective endocarditis.

AIMS: The hybrid technique of single-photon emission tomography and computed tomography with technetium99m-hexamethylpropyleneamine oxime-labelled leucocytes (99mTc-HMPAO-SPECT/CT) is an emerging diagnostic technique in patients with cardiac device-related infective endocarditis (CDRIE). This prospective study assessed the 99mTc-HMPAO-SPECT/CT diagnostic profile and its added value to the modified Duke criteria (mDuke) in CDRIE diagnostic work-up. METHODS AND RESULTS: The study examined 103 consecutive patients with suspected CDRIE, who underwent 99mTc-HMPAO-SPECT/CT. Diagnostic accuracy was calculated based on a final clinical CDRIE diagnosis, including microbiology, echocardiography, and a 6-month follow-up. Subsequently, we compared the diagnostic value of the initial mDuke classification with a classification including 99mTc-HMPAO-SPECT/CT positive results as an additional major CDRIE criterion: mDuke-SPECT/CT.Overall, CDRIE was diagnosed in 31 (31%) patients, whereas 35 (34%) 99mTc-HMPAO-SPECT/CT were positive. 99mTc-HMPAO-SPECT/CT was characterized by 86% accuracy, 0.69 Cohen's kappa coefficient, 84% sensitivity, 88% specificity, 93% negative, and 74% positive predictive values. The original mDuke displayed 83% accuracy, 0.52 kappa, whereas mDuke-SPECT/CT had 88% accuracy, and 0.73 kappa. Compared with mDuke, mDuke-SPECT/CT showed significantly higher sensitivity (87% vs. 48%, P < 0.001). According to mDuke, 49.5% of patients had possible CDRIE, and after reclassification, that figure dropped to 37%. Furthermore, having assessed the diagnosis categorization improvement following the incorporation of 99mTc-HMPAO-SPECT/CT, the net reclassification index value was found to be 31.4%. CONCLUSION: In patients with CDRIE, 99mTc-HMPAO-SPECT/CT provides high diagnostic accuracy, whereas a negative scan excludes CDRIE with high probability. Inclusion of 99mTc-HMPAO-SPECT/CT into mDuke diagnostic criteria yields significantly higher sensitivity and a reduction in possible CDRIE diagnoses.

Kinetics of selected serum markers of fibrosis in patients with dilated cardiomyopathy and different grades of diastolic dysfunction of the left ventricle.

BACKGROUND: Fibrosis of the extracellular matrix (ECM) in dilated cardiomyopathy (DCM) is common and compromises both systolic and diastolic function. The aim of this study was to investigate the kinetics of ECM fibrosis markers over a 12 month follow-up in patients with DCM based on the severity of diastolic dysfunction (DD). METHODS: Seventy consecutive DCM patients (48 ± 12.1 years, ejection fraction 24.4 ± 7.4%) were included in the study. The grade of DD was determined using the ASE/EACVI algorithm. Markers of ECM fibrosis were measured at baseline and at 3 and 12 month follow-ups: collagen type I and III (PICP, PINP, PIIICP, PIIINP), transforming growth factor beta-1 (TGF1-b), connective tissue growth factor (CTGF) and galectin-3 were measured. RESULTS: Patients were divided into three groups according to DD severity: 30 patients with grade I, 18 with grade II and 22 with grade III of DD. Levels of PICP, PINP were increased over a 12-month period, while PIIINP decreased and PIIICP unchanged. Levels of TGF1-b decreased from the 3 to the 12-month points in grade I and II DD, and in grade III they remained unchanged. Levels of CTGF decreased over 12 months in grade III DD but were unchanged in grades I and II. Galectin-3 levels remained the same over all observation periods, irrespective of DD grade. CONCLUSIONS: Regardless of the DD grade, markers of collagen type I synthesis increased, markers of collagen type III decreased. Levels of TGF and CTGF had a tendency to decrease. Galectin-3 was revealed not to be a marker discriminating the severity of DD.

The burden of atrial fibrillation and its prognostic value in patients with dilated cardiomyopathy.

BACKGROUND: Atrial fibrillation (AF) is the most common arrhythmia in patients with dilated cardiomyopathy (DCM). However, the epidemiology as well as clinical and prognostic significance of AF in DCM are poorly defined. AIMS: We aimed to assess the impact and prognostic value of AF in DCM as well as to investigate the concept of AF­induced DCM. METHODS: Hospital records of 285 patients with DCM from 2012 to 2018 with follow-up were analyzed. RESULTS: Atrial fibrillation was present in 89 patients (31%). They were older, more frequently male, hadhigher body mass index, New York Heart Association class, heart rate (HR), creatinine levels, and larger atria (all P < 0.05) than patients without AF. During follow­up (mean [SD], 35 [24] months), death occurred in 20 of the 82 available patients with AF and 22 of the 188 patients without AF (24% and 12%, respectively; P = 0.007). Atrial fibrillation was independently associated with a worse outcome (hazard ratio, 2.4; 95% CI, 1.3-4.3) and was found to be the major cause of DCM in 21 patients (24%). The diagnostic accuracy of the most optimal predictive model for AF­induced DCM was 0.935 (95% CI, 0.903-0.967). Despite numerical differences, survival was similar in DCM patients with and without AF (P = 0.15). CONCLUSIONS: Almost one­third of patients with DCM had AF. Most of the parameters analyzed differed between patients with and without AF, and AF was found to be an independent prognostic factor of DCM. One­fourth of patients with DCM and AF met the diagnostic criteria for AF­induced DCM.

99mTc-HMPAO-labeled leukocyte SPECT/CT and transthoracic echocardiography diagnostic value in infective endocarditis.

Infective endocarditis (IE) is a life-threatening disease, establishing a diagnosis is often challenging. The aim of this prospective study was to evaluate and compare the diagnostic performance of the combined use of single photon emission tomography and computed tomography with technetium99m-hexamethylpropyleneamineoxime-labeled leukocytes (99mTc-HMPAO-SPECT/CT) with transthoracic echocardiography (TTE) in patients with suspected IE. We enrolled 40 consecutive patients (12 females, 28 males, mean age: 58.6 ± 18) with suspected IE in the years 2015-2016. All patients underwent clinical evaluation, TTE and 99mTc-HMPAO-SPECT/CT for the assessment of lesions typical for IE. Scans were evaluated for the presence and location of increased radioactivity foci, corresponding to the accumulation of radiolabeled leukocytes in inflammatory lesions. After 6 months, the patients were re-evaluated clinically and with TTE. Final IE diagnosis was established in 14 (35%) patients. Lesions typical for IE were shown in 28 (70%) TTEs and 16 (40%) 99mTc-HMPAO-SPECT/CTs. The latter tests were characterized by 90% accuracy, 93% sensitivity, 88% specificity, 96% negative predictive value (NPV), 81% positive predictive value (PPV). TTE demonstrated 60% accuracy, 93% sensitivity, 42% specificity, 92% NPV, and 46% PPV. 99mTc-HMPAO-SPECT/CT was characterized by a lower number of false-positive results compared to TTE (3 vs. 15). In patients with suspected IE, 99mTc-HMPAO-SPECT/CT yields a smaller number of false-positive results, significantly higher diagnostic accuracy, specificity and PPV than TTE. It helps to differentiate IE infectious and sterile echocardiographic lesions and reduces by 27% the number of misdiagnosed IE classified in the 'possible IE' category by modified Duke Criteria.

12-month patterns of serum markers of collagen synthesis, transforming growth factor and connective tissue growth factor are similar in new-onset and chronic dilated cardiomyopathy in patients both with and without cardiac fibrosis.

BACKGROUND: The dynamics of the extracellular matrix (ECM) fibrosis process in dilated cardiomyopathy (DCM) may be assessed non-invasively by means of serum markers of fibrosis. AIM: To explore the kinetics of serum markers of fibrosis during a 12-month follow-up in DCM. METHODS: We included 70 consecutive DCM patients (pts) (48±12.1years, EF 24.4±7.4%) with new-onset (n=35, duration <6months) and chronic DCM (n=35, >6months). Markers of collagen type I and III synthesis - procollagens type I and III carboxy- and amino-terminal peptides (PICP, PINP, PIIICP, PIIINP), and ECM metabolism controlling factors - tumor growth factor beta-1 (TGF1-ß), and connective tissue growth factor (CTGF) - were measured in serum at baseline, and at 3- and 12-month follow-up. All pts underwent endomyocardial biopsy to determine the presence and extent of ECM fibrosis. RESULTS: Markers of collagen type I synthesis (PICP and PINP) were almost homogenously increased over the 3- and 12-month period, whereas PIIINP values decreased and PIIICP levels were unchanged in new-onset and chronic DCM, and in pts with and without ECM fibrosis. Both TGF-ß and CTGF levels decreased over the observation period. Kinetics of serum markers of collagen synthesis and fibrosis controlling factors did not differ between DCM pts categorized according to disease duration and fibrosis status. CONCLUSIONS: The kinetics of collagen type I and III synthesis in DCM move in opposite directions, with production of collagen type I consistently increasing, and the synthesis of collagen type III decreasing. Levels of TGF and CTGF, which are proven fibrosis-stimulating factors, had a tendency to decrease. Regardless of disease duration or fibrosis status, the kinetics of serum markers of collagen synthesis, TGF and CTGF were similar in DCM. A better understanding of the kinetics of serum markers of fibrosis in DCM may help to develop more tailored therapeutic approaches to fibrosis.

Left ventricular reverse remodeling is not related to biopsy-detected extracellular matrix fibrosis and serum markers of fibrosis in dilated cardiomyopathy, regardless of the definition used for LVRR.

Left ventricular reverse remodeling (LVRR) is reported in dilated cardiomyopathy (DCM) patients (pts). However, numerous definitions of LVRR exist. Measurements of serum markers of fibrosis provide insight into myocardial fibrosis. The relationship between LVRR and fibrosis is poorly understood. From July 2014 until October 2015, we included 63 consecutive DCM pts (48 ± 12.1 years, EF 24.4 ± 7.4%) with completed baseline and 3-month follow-up echocardiograms. LVRR was assessed on the basis of four differing definitions. Procollagens type I and III carboxy- and amino-terminal peptides (PICP, PINP, PIIICP, and PIIINP), collagen 1, ostepontin, tumor growth factor beta-1, connective tissue growth factor, and matrix metalloproteinases (MMP-2, MMP-9), and their tissue inhibitor (TIMP-1) were measured in serum. In addition, all pts underwent right ventricular endomyocardial biopsy. Depending on the definition chosen, LVRR could be diagnosed in between 14.3 and 50.8% pts. Regardless of the LVRR definition used, the frequency of LVRR was similar in fibrosis negative and positive DCM. Minor differences of markers of fibrosis were detected between pts with and without LVRR. For every LVRR definition, adjusted and unadjusted models were constructed to evaluate the predictive value of serum fibrosis parameters. Only an increase of TIMP-1 by 1 ng/ml was found to independently increase the probability of LVRR by 0.016%. The choice of a particular definition of LVRR determines the final diagnosis, and this has a profound impact on subsequent management. LVRR is unrelated to biopsy-detected ECM fibrosis. Serum markers of fibrosis are only weakly related to LVRR, and are not of use in the prediction of LVRR.

Carotid artery stenting according to the tailored-CAS algorithm is associated with a low complication rate at 30 days: data from the TARGET-CAS study.

BACKGROUND: The rate of early complications of carotid artery stenting (CAS) should not exceed 3% in asymptomatic and 6% in symptomatic patients. However, some recent studies/registries failed to reach this threshold, fueling a debate on the role of CAS in the treatment of patients with carotid artery stenosis. AIM: To evaluate 30-day safety of CAS using different embolic protection devices and different stent types according to the tailored-CAS algorithm and to identify risk factors for complications. METHODS: Between 2002 and 2010, we performed 1176 CAS procedures in 1081 patients (age 38-86 years, mean 66.3 ± 8.4 years, 51.5% symptomatic) according to the tailored-CAS algorithm that included extracranial ultrasound and computed tomography angiography to select the most appropriate embolic protection device (EPD) and stent type. Proximal EPD and closed-cell (CC) stents were preferentially used for high-risk lesions (HR - soft/thrombus-containing/tight/ulcerated, 36.14% of all lesions) and in symptomatic patients. RESULTS: Procedural success rate was 99.8%. In symptomatic patients, proportion of HR lesions was higher (41.1%) than in the asymptomatic group (30.8%, p = 0.001) and the usage of CC stents (76.2% vs 71.7%, p = 0.103) and proximal EPD (P-EPD, 34.8% vs 27.7% among asymptomatic patients, p = 0.010) was more frequent. CC stents were used in 82.4% of CAS procedures involving HR lesions (vs 69.1% for non-HR lesions, p < 0.01), and P-EPD were used in 83.1% of procedures involving HR lesions (vs 2.5% for non-HR lesions, p < 0.001). In-hospital complications included 6 (0.55%) deaths, 1 (0.08%) major stroke and 19 (1.61%) minor strokes. No myocardial infarctions (MI) were noted. Among 7 (0.59%) cases of hyperperfusion syndrome, 2 were fatal. Thirty-day complication rate (death/any stroke/MI) was 2.38%. Age > 75 years was a predictor of death (p = 0.015), and prior neurological symptoms were a predictor of death/stroke (p = 0.030). There were 4 cases of periprocedural embolic cerebral artery occlusion, all treated with combined intracranial mechanical and local thrombolytic therapy. CONCLUSIONS: CAS with EPD and stent type selection on the basis of thorough non-invasive diagnostic work-up (tailored- -CAS) is safe. Advanced age was associated with an increased risk of death and the presence of prior neurological symptoms was a predictor of death/stroke at 30 days. With the tailored-CAS approach, high-risk lesion features (soft/thrombus- -containing/tight/ulcerated) are eliminated as a risk factor. Hyperperfusion syndrome is a severe CAS complication which may lead to intracranial bleeding and death. Acute, iatrogenic embolic cerebral artery occlusion is rare and may be managed by combined intracranial mechanical and local thrombolytic therapy.

Treatment strategies in severe symptomatic carotid and coronary artery disease.

Coexistent carotid artery stenosis (CS) and multivessel coronary artery disease (CAD) is not infrequent. One in 5 patients with multivessel CAD has a severe CS, and CAD incidence reaches 80% in those referred for carotid revascularization. We reviewed treatment strategies for concomitant severe CS and CAD. We performed a literature search (MEDLINE) with terms including carotid artery stenting (CAS), coronary artery bypass grafting (CABG), carotid endarterectomy (CEA), stroke, and myocardial infarction (MI). The main therapeutic option for CS-CAD has been (simultaneous or staged) CEA-CABG. This, however, is associated with a high risk of MI (in those with CEA prior to CABG) or stroke (CABG prior to CEA), and the cumulative major adverse event rate (MAE - death, stroke or MI) reaches 10-12%. With increasing adoption of CAS, a sequential strategy of CAS followed by CABG has emerged. Registries (usually single-centre) indicate an MAE rate of ≈7% for CAS followed by CABG (frequently after >30 days, due to double antiplatelet therapy). Recently, 1-stage CAS-CABG has been introduced. This involves different antiplatelet regimens and, in some centers, preferred off-pump CABG, with a cumulative MAE of 1.4-4.5%. No randomized trial comparing different treatment strategies in CS-CAD has been conducted, and thus far reported series are prone to selection/reporting bias. In addition to the established surgical treatment (CEA-CABG, sequential/simultaneous), hybrid revascularization (CAS-CABG) is emerging as a viable therapeutic option. Larger, preferably multi-centre, studies are required before this can become widely applied.

Increased thrombin generation and platelet activation are associated with deficiency in high molecular weight multimers of von Willebrand factor in patients with moderate-to-severe aortic stenosis.

BACKGROUND: High molecular weight von Willebrand factor (vWF) multimers (HMWM) are often deficient in patients with severe aortic stenosis (AS) owing to shear stress-enhanced proteolysis of vWF. It has also been reported that AS is associated with increased activation of blood coagulation. OBJECTIVE: To investigate whether patients with AS with a deficiency in vWF HMWM have enhanced thrombin generation and platelet activation in vivo. DESIGN: Based on the analysis of vWF HMWM performed using immunolocalisation, 11 subjects with vWF HMWM deficiency (low %HMWM group) were identified and compared with 42 patients with AS with a normal distribution of vWF HMWM (normal %HMWM group). Plasma thrombin markers thrombin-antithrombin complexes (TAT) and prothrombin factor 1+2 (F1.2) plus platelet activation markers soluble CD40 ligand (sCD40L), ß-thromboglobulin and P-selectin were also measured. PATIENTS: 48 consecutive patients with severe AS and five with moderate AS, free of angiographically-proven coronary artery disease and clinically overt bleeding, were studied. RESULTS: Patients in the low %HMWM group had 34.8% higher maximal transvalvular gradient (p = 0.0003) and 44.8% higher mean gradient (p = 0.0002) than those in the normal %HMWM group. Thrombin formation was enhanced in the low %HMWM group (F1.2, 284.5 ± 63.7 vs 216.9 ± 62.5 pmol/l, p = 0.004; thrombin-antithrombin, 4.89 ± 1.3 vs 4.06 ± 0.9 µg/l, p = 0.02) and both markers showed inverse correlations with the percentage of vWF HMWM (r = -0.59, p = 0.002; r = -0.42, p = 0.03, respectively). In the low %HMWM group sCD40L (279.4 ± 60.7 vs 221.4 ± 41.7 pmol/l, p = 0.003) and ß-thromboglobulin (73.1 ± 9.2 vs 64.5 ± 8.5 IU/ml, p = 0.04), but not P-selectin, were also higher than in the remaining patients with AS. CONCLUSION: Patients with advanced AS deficient in vWF HMWM are characterised by enhanced thrombin formation and platelet activation. This observation indicates the ambivalent impact of high shear stress in AS on haemostasis and might help explain two aspects of AS-Heyde syndrome and increased risk of thromboembolism.

Fibrin presence within aortic valves in patients with aortic stenosis: association with in vivo thrombin generation and fibrin clot properties.

A role of coagulation in the pathogenesis of aortic stenosis (AS) is unknown. The aim of this study was to investigate the fibrin (Fn) presence and its determinants in calcified stenotic aortic valve leaflets. Twenty-one patients with dominant AS and 17 well-matched patients with dominant aortic insufficiency (AI) undergoing aortic valve replacement were studied. Immunofluorescence analysis was performed on decalcified leaflets using antibodies against human Fn and tissue factor (TF). Fn-positive (41.4%) and TF-positive (25.3%) areas were increased in AS valves compared with AI valves (7.9% and 5.9%, respectively, both p<0.001). Patients with AS had elevated plasma D-dimer (236.4 ± 28 ng/ml, p=0.002) and prothrombin fragment 1+2 (F1.2) (261.7 ± 27.1 pM, p=0.005) compared to AI subjects (142.8 ± 10 ng/ml and 131.2 ± 1.3 pM, respectively). In AS patients Fn-positive areas correlated with TF-positive areas (r=0.68, p=0.0005), D-dimer (r=0.45, p=0.018), F1.2 (r=0.64, p=0.002), the time required for plasma fibrin clot formation (r=0.44, p=0.015) and maximum absorbance of fibrin clots (r=-0.38, p<0.0001), but not with clot permeability or lysis time. Thickness of Fn layer within AS valves was associated with maximum transvalvular gradient (r =0.41, p=0.048). Patients with maximal gradient above 75 mmHg (n=11) showed significant associations between Fn-positive area and both maximal (r =0.63) and mean (r =0.67) transvalvular gradients. Large fibrin amounts, mostly co-localised with TF, are present within the valve leaflets of patients with advanced AS. In vivo thrombin generation and fibrin clot formation are associated with the extent of Fn presence within leaflets, which might contribute to the AS progression.

The use of a novel type of distal protection system (FiberNet®) in the percutaneous management of saphenous vein graft disease.

Percutaneous intervention in saphenous vein grafts is associated with a high risk of distal embolisation by plaque material, 'no flow' phenomenon and clinical complications such as myocardial infarction or death. According to randomised trial evidence, intervention in a degenerated vein graft should be performed using an embolic protection device (EPD), since this strategy significantly reduces periprocedural and 30 day adverse event rate. FiberNet® is a novel distal protection system with unique characteristics of a low crossing profile (0.031'' for vessel size 3.5-5 mm), 'cotton wool'-like three dimensional design and a small pore size (40 µm). The FiberNet® does not require a separate delivery sheath and self-achieves its optimal apposition to the vessel wall; the EPD system also contains a dedicated aspiration catheter. We present the use of FiberNet® in a 77 year-old patient who had undergone coronary artery bypass grafting 20 years ago and currently presented with CCS class III angina due to a significant stenosis of the saphenous vein graft to the marginal branch. The procedure involved the use of a novel mesh-covered stent (MGuard®) designed to 'trap' the plaque material between the stent and the vessel wall. It was technically successful and clinically uncomplicated, and the patient remains well six months later.

Evidence for tissue factor expression in aortic valves in patients with aortic stenosis.

INTRODUCTION: The role of blood coagulation in the pathogenesis of aortic stenosis (AS) is unknown. Recently, tissue factor (TF) expression in stenotic aortic valves has been reported in animal model. OBJECTIVES: The aim of the study was to investigate TF expression in valve leaflets obtained from AS patients and to determine its associations with circulating coagulation markers and echocardiographic variables. PATIENTS AND METHODS: We studied 20 patients (10 men, 10 women) with dominant AS (age 62.9 +/-9.6, years, mean gradient 43.62 +/-14.62 mmHg), and 20 well-matched patients with dominant aortic insufficiency (AI) undergoing elective aortic valve replacement. Immunofluorescence was measured on decalcified leaflets using antibodies against human TF and macrophages. Prothrombin fragment 1+2 (F1+2) and circulating TF were determined in plasma prior to surgery. RESULTS: AS valves were characterized by an increased (all, p <0.001) percentage of TF-positive (24.6%) and macrophage-containing (27.3%) areas detected mainly on the aortic side of the leaflets, compared with AI valves (6.3% and 7.4%, respectively). Patients with AS had elevated F1+2 (262.1 +/-27.8 pmol/l, p <0.001) and plasma TF (median 131.8, interquartile range [91.42-310.56] pg/ml, p = 0.018) compared with AI subjects (136.1 +/-11.9 pmol/l, 65.38 [49.51-87.81] pg/ml, respectively). Percentage of TF-positive areas correlated with plasma TF (r = 0.68, p <0.0001), but not with F1+2. Maximum transvalvular gradient >75 mmHg, but not the aortic valve area, showed associations with percentage of TF-positive areas (r = 0.88, p = 0.0039). CONCLUSIONS: This study is the first full-length report demonstrating the presence of TF associated with macrophage infiltration in human aortic valve leaflets in AS patients.

Effect of aortic valve stenosis on haemostasis is independent from vascular atherosclerotic burden.

OBJECTIVE: The aim of study was to assess whether activation of blood coagulation and platelets is enhanced in aortic stenosis (AS) and if so, to determine factors that might modulate these processes. PATIENTS/METHODS: Seventy-five patients with AS (48 males, 27 females, aged 65+/-10 years) were enrolled in the study. A control group comprised 75 age- and sex-matched subjects. We determined markers of thrombin generation (thrombin-antithrombin complex [TAT], prothrombin fragment 1+2 [F1+2]), platelet activation (soluble CD40 ligand [sCD40L], beta-thromboglobulin [beta-TG], P-selectin) in peripheral blood plasma. The extent of atherosclerosis in the carotid and coronary arteries was assessed as a potential confounding factor. RESULTS: Mean concentrations of thrombin and platelet markers were higher approximately two-fold in the AS group than in controls (p<0.005 for all comparisons). Maximal gradient was positively associated with TAT (r=0.61, p<0.001), F1+2 (r=0.60, p<0.001), sCD40L (r=0.52, p<0.01) and beta-TG (r=0.70, p<0.001). Aortic valve area (AVA) negatively associated only with one platelet marker, beta-TG (r=-0.30, p<0.05). The presence of concomitant atherosclerotic plaque in the carotid (in 65% of patients) or coronary arteries (in 43% of patients) did not influence thrombin generation and platelet activation in patients with AS. CONCLUSIONS: AS predisposes to prothrombotic state. Maximal gradient as an index of turbulent flow associated with activation of coagulation and platelets. In contrast, the small aortic valve area was not closely related to these parameters.

Internal carotid artery stenosis in patients with degenerative aortic stenosis.

BACKGROUND: In patients with severe degenerative aortic stenosis (DAS) the operative mortality risk is 3% for isolated aortic valve replacement (AVR), but it significantly increases in patients with concomitant coronary artery disease (CAD) and internal carotid artery stenosis (ICAS). AIM: To assess the frequency of ICAS > or = 50% and factors determining its occurrence in patients with severe calcified DAS referred for AVR. METHODS: The study included 104 patients (67 men), aged 63.4+/-8.4 years, with symptomatic moderate-to-severe DAS (aortic valve area <1.5 cm2) undergoing coronary angiography prior to valve surgery. In all patients Doppler ultrasound of carotid arteries was performed with the assessment of lumen stenosis. RESULTS: Significant CAD, defined as at least one lumen reduction > or = 50% in a main coronary artery, was found in 44 (42.3%) patients and ICAS > or = 50% in 13 (12.5%) patients. Among patients with DAS, 12 (27.3%) out of 44 patients with significant CAD and 1 (1.7%) out of 60 patients without CAD had ICAS > or = 50% (p <0.001). The frequency of ICAS > or = 50% increased with advancing CAD, occurring in 4 (25%) out of 16 patients with 1-vessel CAD, 3 (25%) out of 12 with 2-vessel CAD and (31.3%) out of 16 patients with 3-vessel CAD (p <0.001). The independent ICAS predictors by multivariate regression analysis were identified as: concomitant CAD (p <0.001), diabetes (p=0.054), cigarette smoking (p=0.08) and decreased left ventricular ejection fraction (p=0.039). ICAS > or = 50% was found to be an independent predictor of CAD (p=0.002). CONCLUSIONS: ICAS > or = 50% occurs in 13% of patients with isolated DAS and in 27% of those with DAS and CAD. Independent ICAS risk factors were identified as CAD, diabetes and cigarette smoking. Duplex ultrasound of carotid arteries should be considered in patients with DAS and concomitant CAD prior to AVR.

[Comparison of myocardial contrast echocardiography and 99mTc MIBI single photon emission computed tomography in the assessment of myocardial perfusion in patients with acute myocardial infarction]. / Porównawcza analiza przydatnosci echokardiografii kontrastowej i badania scyntygraficznego w ocenie perfuzji miesnia sercowego u chorych ze swiezym zawalem serca.

UNLABELLED: The myocardial perfusion assessment in myocardial infarction is crucial to proper therapeutical decisions and patient's prognosis. The aim of the study to assess the efficacy of intravenous contrast echocardiography (MCE) in detecting myocardial perfusion defects in patients with acute myocardial infarction compared with 99mTc MIBI SPECT study. MATERIAL AND METHODS: 86 patients (mean age 58.4 +/- 11.2) underwent primary percutaneous coronary (PCI) for acute anterior myocardial infarction. TIMI grade flow, myocardial blush grade (TMPG), corrected TIMI frame count (cTFC) and segmental contractility and segmental perfusion were estimated in real time before and immediately after PCI, using injections of intravenous Optison. MCE performed before PCI described the risk area as the sum of segments with the lack of perfusion. A MCE perfusion defect size after PCI < 25% of the MCE perfusion defect size before PCI was used to define myocardial reperfusion. MCE was repeated on the third day after PCI. All patients underwent a rest 99mTc MIBI SPECT study (SPECT) on the third day after PCI. RESULTS: Based on MCE, 54 patients had reperfusion ("reflow" group) and 32 had non-reperfusion ("no-reflow" group). Patients from the non-reperfusion group showed a higher creatine kinase peak (p = 0.0034), higher kinase-MB (p = 0.0033) and higher troponine level (p = 0.0629), longer time span between the onset of pain and reperfusion (p = 0.003), and worse baseline regional contractile function (p = 0.0022). All angiographic parameters were worse in this group before as well as after PCI: more often TIMI 0 or 1, TMPG 0 or 1 in patients from "no-reflow" group was observed. These patients had higher cTFC than ones from "reflow" group. The agreement between MCE and SPECT for detecting perfusion abnormality was 87%. CONCLUSIONS: MCE facilitated identification of myocardial perfusion abnormalities in patients with acute myocardial infarction, whereas serial MCE facilitated identification of patients with early and late improvement of myocardial perfusion. MCE correlated very well with SPECT images in assessing perfusion defect.

The prognostic value of contrast echocardiography in the prediction of the recovery of left ventricular function in patients with acute anterior myocardial infarction.

INTRODUCTION: The immediate and complete restoration of perfusion in patients with acute myocardial infarction (MI) leads to the survival of myocardial cells in the initially ischaemic risk area and makes the recovery of left ventricular contractile function possible. AIM: The goal of the study was to assess the utility of contrast echocardiography (CE) in the prediction of left ventricular function recovery in patients with AMI treated by percutaneous coronary intervention (PCI). METHODS: Eighty six patients (aged 58.4+/-11.2) with anterior AMI, treated by PCI of the left anterior descending coronary artery, were included in the study. Two-dimensional and contrast (Optison) echocardiography were performed immediately before and after PCI, and three days post-PCI. Myocardial contrasting was assessed using the following criteria: 0 -- lack of perfusion; 0.5 -- partial perfusion; 1 -- normal perfusion. On the third day post-PCI, the regional myocardial contrast index was evaluated as the mean value in dyssynergic left ventricular segments (LVRCstI). After three months, the left ventricular regional contractility index (LVRCtrctI) was calculated as the sum of points in the segments which were dyssynergic in the initial study, divided by their number. RESULTS: 90% of segments with perfusion defects three days post-PCI demonstrated contractility defects (hypokinesia or akinesia) three months post-PCI. LVRCstI three days post-PCI correlated strongly with LVRCtrctI three months post-PCI (R2=0.7696). The sensitivity, specificity and accuracy of EC three days post-PCI in the prediction of recovery of left ventricular function were 88%, 80% and 86%, respectively. CONCLUSIONS: The presence of myocardial perfusion in the region supplied by the infarct-related artery three days post-MI is indicative of myocardial survival and predicts the recovery of contractile function in this region in long-term observation.

Regression of left ventricular hypertrophy with moexipril, an angiotensin-converting enzyme inhibitor, in hypertensive patients.

Left ventricular hypertrophy (LVH) is a common complication of essential hypertension and an independent risk factor for the development of cardiovascular disease. Therefore, antihypertensive treatment should decrease blood pressure (BP) and reverse LVH. However, antihypertensive drugs have been shown to have different effects on LVH despite similar effects on BP reduction. Although lowering BP produces a beneficial effect on LVH per se, meta-analyses of clinical trials have indicated that angiotensin-converting enzyme (ACE) inhibitors decrease left ventricular mass (LVM) to a greater extent than do some other antihypertensives. The aim of this study was to evaluate the effect of a 24-week treatment with the ACE inhibitor moexipril (15 mg once daily) on the regression of LVH in hypertensive patients. This was a multicenter, international, single-blind, single-group, nonrandomized study. After a wash-out placebo period of 2 weeks, 15 mg moexipril once daily was administered for 24 weeks followed by a 2-week follow-up placebo period. Subjects with mild to moderate essential hypertension were screened; those with LVH [defined as an LVM indexed for body surface area (LVMIs) >111 g/m in men and LVMIs >106 g/m in women] were eligible to participate in this study. Echocardiograms were recorded on videotape and sent to a centralized laboratory for reading by 2 independent experts blinded for treatment, center, and visit; the mean values of these readings were calculated and used for analysis. Valid echocardiographic data were obtained from 72 patients (50 males, 22 females) with a mean age of 49 +/- 11 years. Analysis showed significant decrease of LVMIs (121 +/- 20 versus 103 +/- 17 g/m; P < 0.001) and BP (152 +/- 12/96 +/- 9 versus 140 +/- 13/86 +/- 9 mm Hg; P < 0.001) with moexipril. For patients who met LVMI inclusion criteria after centralized, blinded readings, the decrease from baseline in LVMIs was 23.4 g/m. The decrease in LVMIs was independent from the regression to the mean phenomenon as observed from the follow-up placebo period. Moexipril 15 mg once daily administered for 24 weeks resulted in a significant reversal of LVH in patients with essential hypertension. The result compares favorably with results previously obtained in trials of similar duration with other ACE inhibitors.