Intramyocardial plasmid-encoding human vascular endothelial growth factor A165/basic fibroblast growth factor therapy using percutaneous transcatheter approach in patients with refractory coronary artery disease (VIF-CAD).

BACKGROUND: VIF-CAD randomized, placebo-controlled, double-blind trial was an attempt to induce therapeutic angiogenesis by percutaneous intramyocardial transfer of bicistronic (vascular endothelial growth factor/fibroblast growth factor [VEGF/FGF]) plasmid (pVIF) in patients with refractory heart ischemia. Myocardial perfusion, clinical symptoms, exercise tolerance, left ventricular function, and safety were assessed. METHODS: Fifty-two patients with refractory coronary artery disease were randomized to receive VEGF/FGF plasmid (n = 33) or placebo plasmid (n = 19) into myocardial region showing stress-induced perfusion defects. Repeat stress and rest technetium Tc 99m sestamibi single-photon emission computed tomography at 5 months was the primary efficacy measure. Secondary assessment included Canadian Cardiovascular Society class and exercise tolerance at 5 and 12 months. RESULTS: Rest- and stress-induced perfusion defects did not differ between groups. Canadian Cardiovascular Society functional class improved after 5 (P = .0210) and 12 months (P = .0607) in the treatment group. The exercise tolerance of treated patients improved: total exercise time increased marginally (P = .0541); maximum workload (P = .0419) and total test distance (P = .0473) increased significantly, compared to placebo. CONCLUSION: Bicistronic VEGF/FGF plasmid therapy did not improve myocardial perfusion measured by single-photon emission computed tomography. However, treated patients experienced improvement with respect to exercise tolerance and clinical symptoms. Intramyocardial VEGF/FGF bicistronic plasmid transfer seemed safe throughout the follow-up period of 1 year.

Cardioverter-defibrillator lead-related thrombus treated with prolonged anticoagulation in patient with prothrombotic disorder.

Following an accidental finding of a large atrial lead-related thrombus in a 33-year-old woman with suspected prothrombotic disorder, a conservative treatment with low molecular weight heparin injections and close transthoracic and transesophageal echocardiographic monitoring was used. It led to a complete resolution of the thrombus in 4 weeks without the need for a high-risk operation in this patient.

Significance of dyslipidaemia in patients with heart failure of unexplained aetiology.

BACKGROUND: Dyslipidaemia has been studied in the prognosis of heart failure (HF). Little is known about the role of dyslipidaemia in the aetiopathogenesis of dilated cardiomyopathy (DCM). AIM: To assess (1) serum lipid levels in DCM considering the severity of heart failure; (2) the association between DCM and lipid abnormalities; (3) prognostic significance of lipids in DCM. METHODS: The study group consisted of 100 patients with angiographically proven DCM [mean age 42 years, 80% males, 65% in NYHA class III-IV, mean left ventricular ejection fraction (LVEF) 32%], whose fasting serum lipids had been assessed during diagnosis between 1992 and 2001. Patients' lipid levels were compared with those observed in healthy controls (n=100), age-, gender-, and BMI-matched and related to findings reported in population samples from WHO Pol-MONICA studies from: 1993 (n=526), 1997/1998 (n=526) and 2001 (n=1364). Three (3%) patients received lipid-lowering drugs. Transplant-free survival was assessed in the study group. In the statistical analysis, nonparametric Wilcoxon test and uni- and multivariate logistic and Cox regression analyses were used. RESULTS: Serum total cholesterol (TC), LDL (LDL-C) and HDL cholesterol (HDL-C) tended to be lower (differences NS) in NYHA class III-IV patients vs. class I-II (TC: 196.9+/-45.5 vs. 207.9+/-47.1 mg/dl, LDL-C 126.2+/-37.5 vs. 128.5+/-42.7 mg/dl, HDL-C 44.2+/-11.3 vs. 44.7+/- +/-13.7 mg/dl, respectively), and triglycerides (TG) were lower in advanced HF vs. NYHA class I-II (135.9+/-51 vs. 170.3+/-63.4 mg/dl, p=0.004). In DCM patients HDL-C was lower than in controls (44.1+/-12.1 vs. 54.3+/-17.6 mg/dl, p <0.001), and TG level was higher (147.9+/-58.1 vs. 114.1+/-61.6 mg/dl, p <0.001). HDL-C and TG levels in controls were similar to those observed in population samples. Multivariate analysis with age, low HDL (defined as <40 mg/dl for males, and <50 mg/dl for females), and hyperTG (TG l150 mg/dl) showed that both low HDL-C (OR=2.31; 95% CI 1.2-4.457, p=0.0122), and hyperTG (OR=1.978, 95% CI 1.029-3.799, p=0.0407) were independently associated with DCM. Low HDL-C level occurred more frequently in female DCM patients vs. in males (65 vs. 33.8%, p=0.022). There was a trend towards more frequent occurrence of hyperTG in male patients vs. females (42.5 vs. 20%, p=0.11). The mean follow-up time was 7.32+/-4.7 years. In Cox univariate analysis low TC tended to be a prognostic factor (p=0.067), but in Cox multivariate analysis only NYHA class (HR=1.7, 95% CI 1.136-2.541; p=0.01) and LVEF (HR=0.963, 95% CI 0.932-0.996; p=0.027) turned out to be independent predictors of poor outcome. CONCLUSION: Dyslipidaemia might play a role in the aetiopathogenesis of DCM. Low TC is not an independent prognostic factor in DCM.

Comparison of prognostic value of epicardial blood flow and early ST-segment resolution after primary coronary angioplasty. ANIN--Myocardial Infarction Registry.

BACKGROUND: TIMI scale is commonly used for angiographic assessment of reperfusion effectiveness and early risk stratification in patients treated with primary angioplasty for ST-elevation myocardial infarction (STEMI). Since ST-resolution analysis allows a noninvasive insight into the reperfusion status at the myocardial tissue level, it may be a better predictor of outcome after primary angioplasty. AIM: To compare the prognostic value of the reperfusion effectiveness evaluation based on either the epicardial blood flow assessment according to the TIMI scale, or ST-segment resolution analysis in patients treated with primary coronary angioplasty for STEMI. METHODS: 324 consecutive patients treated within 12 hours from the pain onset were studied. Based on the analysis of maximal ST-segment elevation/depression identified in a single ECG lead recorded after the procedure (maxSTE), patients were classified into groups of high versus medium/low risk. Independently, distinguished were groups with restored normal (TIMI 3) and abnormal (TIMI 0-2) final blood flow in infarct related artery. RESULTS: The 30-day and one-year mortality rates were higher in the high-risk maxSTE group (25% of all patients) than in the other patients (14.8% vs. 2.5%, p<0.001 and 18.5% vs. 5.4%, p<0.001 respectively). In subjects (82%) with restored TIMI grade 3 blood flow, mortality at one-month and one-year was lower than in the group with abnormal final blood flow (3.1% vs. 15.6%, p=0.001 and 6.2% vs. 18.8%, p=0.005). Comparison in multivariate analysis revealed that maxSTE stratification but not final TIMI grade assessment remained an independent predictor of both, 30-day and one-year mortality (high vs. medium/low-risk category; OR 5.3, 95% CI 1.6-16.7, p=0.005, and OR 3.3, 95% CI 1.4-7.8, p=0.007, respectively). Furthermore, maxSTE proved to stratify the risk of death even in subgroup of patients with restored normal blood flow (OR 6.2, 95% CI 1.4-27.8, p=0.016, and OR 3.0, 95% CI 1.1-8.7, p=0.039, respectively). CONCLUSIONS: Analysis of extent of maximal ST-segment elevation or depression identified in a single ECG lead after primary coronary angioplasty allows better prognosis of subsequent 30-day and one-year mortality than the assessment of final epicardial blood flow, stratifying risk of death even in a subgroup of patients with restored normal blood flow.

Assessment of the inflammatory process by endomyocardial biopsy in patients with dilated cardiomyopathy based on pathological and immunohistochemical methods.

INTRODUCTION: Myocarditis may lead to dilated cardiomyopathy (DCM) in immunogenetically predisposed individuals. The diagnosis of myocardial inflammation is currently based on histopathological and immunohistochemical methods. Previous studies indicate that inflammatory cardiomyopathy occurs in approximately 50% of patients with DCM. AIM: The goal of the study was to assess the inflammatory process in patients with DCM by endomyocardial biopsy using histopathological and immunohistochemical methods. METHODS: Endomyocardial biopsy specimens was examined using routine histopathological methods and immunochemical staining for T lymphocytes (CD3(+), n=84), major histocompatibility complex I (HLA ABC, n=48) and II (HLA DPQR, n=84) antigens and the adhesion molecules ICAM-1 (n=51) and VCAM-1 (n=48) in 84 patients (69 male, 15 female; mean age 35.0+/-10.5 years) with angiographically-confirmed DCM. Familial disease occurrence was noted in 14 (16.7%) patients. Cardiac samples obtained from 18 patients who died of non-cardiovascular causes were used as a control group. RESULTS: Myocarditis was diagnosed, according to the Dallas criteria, in 8 (9.5%) patients. The frequency of inflammatory cardiomyopathy, defined as the presence of >2 CD3(+) T lymphocytes per high-power field (hpf) in myocardial biopsy, was 14.3%. When broader criteria were applied (presence of >2.0 CD3(+) lymphocytes/hpf and/or 1.5 CD3(+) lymphocytes/hpf in multiple foci and increased expression of class I/II HLA), inflammatory cardiomyopathy was diagnosed in 32.1% of patients. Inflammatory activation of the endothelium, indicated by increased expression of at least three adhesion molecules (class I and II HLA, ICAM-1, VCAM-1), was present in 22 (45.8%) patients. The expression of HLA DPQR, HLA ABC and ICAM-1 was observed on the endothelium of capillaries and larger vessels, interstitial cells, and the surface of activated lymphocytes; immunohistochemical reactions were diffuse. In patients with markedly elevated expression of the aforementioned adhesion molecules, the expression was also present on cardiomyocyte cell membranes. VCAM-1 was restricted to the endothelium of individual small veins. The control group did not demonstrate any signs of myocarditis, inflammatory cardiomyopathy or inflammatory endothelial activation. CONCLUSIONS: The application of immunohistochemical methods to myocardial biopsy in order to identify the inflammatory cell phenotype and the presence of adhesion molecules permits the diagnosis of inflammatory cardiomyopathy in 14% or 32% of patients, depending on the criteria used, while conventional pathology allows for this diagnosis in 9% of patients. The observed frequency of inflammatory cardiomyopathy, defined as the presence of >2 CD3(+) T lymphocytes/hpf in the myocardium, was lower (14%) than in previous studies, while the frequency of inflammatory endothelial activation was similar (45%).

Percutaneous retrieval of centrally embolized fragments of central venous access devices or knotted Swan-Ganz catheters. Clinical report of 14 retrievals with detailed angiographic analysis and review of procedural aspects.

INTRODUCTION: Totally implantable venous access systems (TIVAS), Swan-Ganz (SG) and central venous catheters (CVC) allow easy and repetitive entry to the central cardiovascular system. Fragments of them may be released inadvertently into the cardiovascular system during their insertion or as a result of mechanical complications encountered during long-term utilization. AIM: To present results of percutaneous retrieval of embolized fragments of central venous devices or knotted SG and review the procedural aspects with a series of detailed angiographies. MATERIAL AND METHODS: Between January 2003 and December 2012 there were 14 (~0.025%) successful retrievals in 13 patients (44 ±16 years, 15% females) of embolized fragments of TIVAS (n = 10) or CVC (n = 1) or of dislodged guide-wires (n = 2) or knotted SG (n = 1). RESULTS: Foreign bodies with the forward end located in the right ventricle (RV), as well as those found in the pulmonary artery (PA), often required repositioning with a pigtail catheter as compared to those catheter fragments which were located in the right atrium (RA) and/or great vein and possessed an accessible free end allowing their direct ensnarement with the loop snare (57.0% (4/7) vs. 66.7% (2/3) vs. 0.0% (0/3); p = 0.074 respectively). Procedure duration was 2-3 times longer among catheters retrieved from the PA than among those with the forward edge located in the RV or RA (30 (18-68) vs. 13.5 (11-37) vs. 8 min (8-13); p = 0.054 respectively). The SG catheter knotted in the vena cava superior (VCS) was encircled with the loop snare introduced transfemorally, subsequently cut at its skin entrance and then pulled down inside the 14 Fr vascular sheath. CONCLUSIONS: By using the pigtail catheter and the loop snare, it is feasible to retrieve centrally embolized fragments or knotted central venous access devices.

Acute myocardial infarction complicated by cardiogenic shock. In-hospital and mid-term results of invasive treatment in the National Institute of Cardiology, Warsaw-Anin.

BACKGROUND: Mortality in acute myocardial infarction (MI) complicated by cardiogenic shock approaches 90%, regardless of the type of pharmacological treatment. AIM: To assess in-hospital and mid-term results of invasive treatment of patients with acute MI with ST segment elevation (STEMI) complicated by cardiogenic shock. METHODS: From a prospective registry of all patients admitted to our institution for urgent coronary angiography due to acute coronary syndrome between February 2001 and June 2002, patients with STEMI, symptom duration up to 12 hours and cardiogenic shock diagnosed on admission were identified. The in-hospital and mid-term outcome of 37 patients (mean age 65 years, range 54-77, 68% of males) treated with primary percutaneous coronary intervention (PCI) was analysed. RESULTS: Of the 41 patients with STEMI and cardiogenic shock, total occlusion or critical stenosis of a coronary artery were found in 38 patients. One patient with the occlusion of three main coronary arteries underwent urgent surgical revascularisation and remains alive after an 18-month follow-up. In the remaining 37 patients primary PCI of an infarct-related artery was performed (stent implantation in 70%, abciximab administration in 54%) which restored normal blood flow (TIMI grade 3 flow) in 54% of subjects. In patients with TIMI grade 3 flow the in-hospital mortality was 25%. Of the whole PCI-treated group, 18 (48.6%) patients died during stay in our institution, an additional two - after transfer to another hospital, and one - during a 19-month follow-up period. The remaining 16 patients remain alive (median follow-up of 8 months). CONCLUSIONS: Invasive treatment of patients with STEMI complicated by cardiogenic shock significantly reduces mortality in this high-risk population. The mid-term results in patients discharged from hospital are good. Invasive treatment of acute MI should be accessible for all patients with extensive acute MI.

[Level of angiotensin II and aldosterone in plasma is often elevated in patients with heart failure treated with converting enzyme inhibitors--preliminary results]. / Poziom angiotensyny II i aldosteronu w osoczu jest czesto podwyzszony u chorych z niewydolnoscia serca leczonych inhibitorami konwertazy angiotensyny--doniesienie wstepne.

In large randomised trials, ACE inhibitors (ACEI) have been shown to reduce mortality, morbidity and improve quality of life in patients (pts) with congestive heart failure. However, long-term prognosis of patients in the community remains poor. It has been suggested that one of the reasons may be inadequate neuroendocrine suppression with current treatment strategies. To address this issue we measured plasma levels of angiotensin II (AII) and aldosterone (Ald) in 41 patients (36 males, mean age 52 +/- 2 y) referred to our department for diagnostic evaluation, who were treated with clinically appropriate doses of ACEI. The mean angiographic left ventricular ejection fraction was 22 +/- 8%, left ventricular end diastolic diameter was 72 +/- 10 mm, and NYHA class was 2.6 +/- 0.7. Plasma levels of All and Ald were measured by radioimmunoassay. They did not differ significantly in comparison with the control group of 5 healthy individuals (4.8 +/- 8.2 pg/ml vs 4.1 +/- 3.2 pg/ml for angiotensin II and 129 +/- 93 pg/ml vs 78 +/- 29 pg/ml for aldosterone). A high variability of the results was seen between the individual patients. Full suppression of All (< 2.0 pg/ml) was achieved in 21 patients (58%), 10 pts (28%) showed intermediate levels (2.0-10.0 pg/ml), and 5 patients (14%) demonstrated markedly increased All levels (> 10 pg/ml). Full suppression of Ald (< 80 pg/ml) was seen in only 15 patients (37%), 14 patients (34%) had intermediate levels (80-140 pg/ml) and 12 patients (29%) showed high plasma levels of Ald (> 140 pg/ml). There was a weak, but significant, correlation between All and Ald levels in the study group (r = 0.49, p < 0.05). These preliminary results suggest inadequate neuroendocrine suppression in a substantial proportion of patients, despite using clinically relevant doses of ACE inhibitors. The determination of All and Ald levels may be a helpful tool in monitoring the efficacy of treatment in CHF and may help identify patients who would benefit from other treatment strategies.

Lumen and calcium characteristics within calcified coronary lesions. Comparison of computed tomography coronary angiography versus intravascular ultrasound.

INTRODUCTION: Computed tomography coronary angiography (CTCA) is a diagnostic method used for exclusion of coronary artery disease. However, lower accuracy of CTCA in assessment of calcified lesions is a significant factor impeding applicability of CTCA for assessment of coronary atherosclerosis. AIM: To provide insight into lumen and calcium characteristics assessed with CTCA, we compared these parameters to the reference of intravascular ultrasound (IVUS). MATERIAL AND METHODS: Two hundred and fifty-two calcified lesions within 97 arteries of 60 patients (19 women, age 63 ±10 years) underwent assessment with both 2 × 64 slice CT (Somatom Definition, Siemens) and IVUS (s5, Volcano Corp.). Coronary lumen and calcium dimensions within calcified lesions were assessed with CTCA and compared to the reference measurements made with IVUS. RESULTS: On average CTCA underestimated mean lumen diameter (2.8 ±0.7 mm vs. 2.9 ±0.8 mm for IVUS), lumen area (6.4 ±3.4 mm(2) vs. 7.0 ±3.7 mm(2) for IVUS, p < 0.001) and total calcium arc (52 ±35° vs. 83 ±54°). However, analysis of tertiles of the examined parameters revealed that the mean lumen diameter, lumen area and calcium arc did not significantly differ between CTCA and IVUS within the smallest lumens (1(st) tertile of mean lumen diameter at 2.1 mm, and 1(st) tertile of lumen area at 3.7 mm(2)) and lowest calcium arc (mean of 40°). CONCLUSIONS: Although, on average, CTCA underestimates lumen diameter and area as well as calcium arc within calcified lesions, the differences are not significant within the smallest vessels and calcium arcs. The low diagnostic accuracy of CTCA within calcified lesions may be attributed to high variance and not to systematic error of measurements.

Familial dilated cardiomyopathy: evidence for clinical and immunogenetic heterogeneity.

BACKGROUND: There is increasing awareness of the familial nature of dilated cardiomyopathy (DCM). Mutations in the genes coding for cytoskeletal and sarcomere proteins have been identified. Phenotyping of familial DCM (FDCM) may help to improve genetic diagnosis. The aim of our study was to evaluate the clinical features, pattern of transmission, and immunogenetic data of FDCM. MATERIAL/METHODS: We obtained family histories in order to construct pedigrees and prospectively evaluated 204 family members of 27 patients with angiographically proven DCM. FDCM was defined as more than 1 person with DCM in a family. The study protocol included repeated clinical examination, electrocardiography, echocardiography and blood sampling. RESULTS: Among the families, we identified the following phenotypes: DCM with conduction defects (n=2), early onset DCM with a rapid course in male relatives (n=2), and DCM preceded by ventricular arrhythmia (n=1). The remaining families presented with a heterogeneous course of the disease. The disease was transmitted in an autosomal dominant fashion in 14 of our pedigrees, possibly X-linked in three and indeterminate in 10 sib-pairs. The frequency of the DRB1*04 allele was low in probands with the disease (3/20, 15%); heterozygozity for DRB1*03/DRB1*04, known to increase susceptibility to IDDM1, was identified in 2 of 20 DCM probands (10%). CONCLUSIONS: Familial dilated cardiomyopathy is a heterogeneous disorder; autosomal dominant transmission is most common. The distinct clinical phenotypes and specific immunogenetic features found in some families indicate that different pathogenetic mechanisms can lead to the