Petri Tuomainen

Utility of plasma apelin and other indices of cardiac dysfunction in the clinical assessment of patients with dilated cardiomyopathy.

Apelin is a recently discovered peptide ligand reported to be involved in the regulation of cardiovascular homeostasis. The exact role of apelin in the pathophysiology of congestive heart failure has remained obscure, and the reported circulating levels of apelin in patients with heart failure have been contradictory. To establish the role of apelin in the assessment of cardiac dysfunction we measured plasma apelin levels in 65 patients with congestive heart failure caused by idiopathic dilated cardiomyopathy (IDC) and 14 healthy volunteers by specific radioimmunoassay. IDC patients were carefully examined including echocardiography, both-sided cardiac catheterization and cardiopulmonary exercise test. In addition, plasma levels of N-terminal pro-brain natriuretic peptide (NT-proBNP), N-terminal pro-atrial natriuretic peptide (NT-proANP), interleukin (IL)-6, tumor necrosis factor alpha (TNF-alpha), epinephrine and norepinephrine were determined. Plasma apelin levels were similar in IDC patients (median 26.5 pg/ml, range<3.40-97.6 pg/ml) and in control subjects (median 24.1 pg/ml, range 19.0-28.7 pg/ml; p=NS). Unlike the levels of NT-proBNP, IL-6, TNF-alpha, and norepinephrine, plasma apelin levels did not reflect the severity of heart failure. Our study demonstrates that although disturbed apelin-APJ signalling in heart may play a role in the pathophysiology of heart failure, circulating apelin levels cannot be applied in the clinical assessment of patients with chronic left ventricular dysfunction.

Coenzyme Q10 and selenium in statin-associated myopathy treatment

The objective of this study was to evaluate the possible benefits of coenzyme Q10 and selenium supplementation administered to patients with statin-associated myopathy (SAM). Sixty eligible patients entered the pilot study. Laboratory examination (CoQ10, selenium, creatin kinase) and intensity of SAM (visual scale) were performed at baseline, after 1 month, and at the end of study at month 3. Plasma levels of CoQ10 increased from 0.81 ± 0.39 to 3.31 ± 1.72 μmol/L in the active group of patients treated by CoQ10, compared with the placebo (p = 0.001). Also, the symptoms of SAM significantly improved in the active group (p < 0.001): the intensity of muscle pain decreased from 6.7 ± 1.72 to 3.2 ± 2.1 (p < 0.01, -53.4 ± 28.2%); muscle weakness decreased from 7.0 ± 1.63 to 2.8 ± 2.34 (p < 0.01, -60 ± 24.0%); muscle cramps decreased from 5.33 ± 2.06 to 1.86 ± 2.42, p < 0.01, -65 ± 28%); tiredness decreased from the initial 6.7 ± 1.34 to 1.2 ± 1.32 (p < 0.01, -82 ± 22%). We did not observe any significant changes in the placebo group. In conclusion, supplementation of statin-treated patients with CoQ10 resulted in a decrease in the symptoms of SAM, both in absolute numbers and intensity. Additional selenium supplementation was not associated with any statistically significant decrease of SAM. However, it is not possible to draw any definite conclusions, even though this study was carried out in double-blind fashion, because it involved a small number of patients.

A novel mutation, Arg71Thr, in the δ-sarcoglycan gene is associated with dilated cardiomyopathy

Approximately 20–35% of cases of idiopathic dilated cardiomyopathy are familial. DCM-associated mutations have been reported in 13 genes including the desmin, δ-sarcoglycan, and metavinculin genes. This study screened for variants in these genes in Finnish patients with DCM. All coding regions of the desmin and δ-sarcoglycan genes and the metavinculin-specific exon of the vinculin gene were screened in 52 DCM patients from eastern Finland by PCR-SSCP. We detected a novel mutation, Arg71Thr, in the δ-sarcoglycan gene in two members of a small DCM family. One of the mutation carriers fulfills diagnostic criteria for DCM and is also symptomatic. The other mutation carrier has slightly dilated left ventricle and well preserved systolic function. Therefore carriers of the Arg71Thr mutation had a relatively mild phenotype and a late onset of the disease. Disease-associated mutations were not found in the desmin gene or the metavinculin-specific exon of the vinculin gene. We conclude that the desmin and δ-sarcoglycan genes are not predominant disease-causing genes in patients with DCM in eastern Finland.

Titanium-nitride-oxide coated stents versus paclitaxel-eluting stents in acute myocardial infarction: a 12-months follow-up report from the TITAX AMI trial.

AIMS The aim of this study was to evaluate the effectiveness of titanium-nitride-oxide (TITANOX)-coated stent and paclitaxel-eluting stent (PES) in patients presenting with acute myocardial infarction (MI). METHODS AND RESULTS A total of 425 patients presenting with acute non-ST-elevation MI or ST-elevation MI were randomly assigned to receive TITANOX-coated stent or PES. The primary end point was a composite of MI, target lesion revascularisation (TLR) or death from cardiac causes. At 12 months, there was no significant difference between patients receiving TITANOX-coated stent or PES in the rates of primary end point (10.3% vs. 12.8%, P=0.5), MI (4.2% vs. 8.1%, P=0.1), or TLR (9.3% vs. 7.1%, P=0.5), respectively. The incidence of stent thrombosis, defined according to Academic Research Consortium classification, was significantly lower in the TITANOX group compared to the PES group (0.9% vs. 4.3%, P=0.03). CONCLUSIONS TITANOX-coated stent and PES resulted in comparable clinical outcomes during 12 months follow-up among patients treated for acute MI.

Two-year follow-up after percutaneous coronary intervention with titanium-nitride-oxide-coated stents versus paclitaxel-eluting stents in acute myocardial infarction

Background and aims. The aim of this study was to evaluate the long-term effects of the titanium-nitride-oxide-coated (TITANOX) stent and the paclitaxel-eluting stent (PES) in patients who had undergone a percutaneous coronary intervention for acute myocardial infarction (MI). Methods and results. The TITAX-AMI trial randomly assigned 425 patients with MI to receive either a TITANOX stent or a PES. The primary end-point was a composite of MI, target lesion revascularization, or death from cardiac causes. At 12 months, there was no significant difference between patients receiving TITANOX stent or PES in the rate of primary end-point (10.3% versus 12.8%, P=0.5). After 2 years of follow-up, a significantly lower rate of primary end-point was observed in the TITANOX stent group compared with the PES group (11.2% versus 21.8%, HR 2.2, 95% confidence interval (CI) 1.3–3.8, P=0.004). This difference was driven by a reduced rate of MI (5.1% versus 15.6%, P<0.001) and cardiac death (0.9% versus 4.7%, P=0.02) in favour of the TITANOX stent. Definite stent thrombosis occurred in 0.5% and 6.2% of the patients (P=0.001), respectively. Conclusions. The implantation of a TITANOX stent resulted in better clinical outcome compared with a PES during 2 years of follow-up among patients treated for acute MI.

Two novel mutations in the β-myosin heavy chain gene associated with dilated cardiomyopathy

Dilated cardiomyopathy (DCM) is familial in approximately 20–35% of cases of idiopathic DCM. Several mutations in the different sarcomere protein genes have been reported to cause DCM.

Five-year clinical outcome of titanium-nitride-oxide-coated bioactive stents versus paclitaxel-eluting stents in patients with acute myocardial infarction: Long-term follow-up from the TITAX AMI trial

BACKGROUND The TITAX-AMI randomized controlled trial demonstrated a better clinical outcome with titanium-nitride-oxide-coated bioactive stents (BAS) as compared with paclitaxel-eluting stents (PES) at 2-year follow-up, in patients with acute myocardial infarction (MI) undergoing early percutaneous coronary intervention (PCI). We sought to present the 5-year clinical outcome of the TITAX-AMI trial. METHODS A total of 425 patients with acute MI were randomly assigned to receive either BAS (214), or PES (211). The primary endpoint was major adverse cardiac events (MACE): a composite of cardiac death, recurrent MI or ischemia-driven target lesion revascularization (TLR). Clinical follow-up was performed to 5 years. RESULTS The 5-year cumulative incidence of MACE was significantly lower in patients assigned to BAS as compared with those assigned to PES (16.4% versus 25.1%, respectively, p=0.03). Similarly, the 5-year rates of cardiac death and recurrent MI were significantly lower in patients assigned to BAS (1.9% versus 5.7%, and 8.4% versus 18.0%, p=0.04 and p=0.004, respectively). Yet, the rates of ischemia-driven TLR were similar between the two study groups (11.2% versus 10.9%, respectively, p=0.92). The rate of definite stent thrombosis (ST) was again significantly lower in patients assigned to BAS (0.9% versus 7.1%, respectively, p=0.001). CONCLUSIONS In the current prospective randomized TITAX-AMI trial, among patients presenting with acute MI who underwent early PCI, BAS achieved a better clinical outcome as compared with PES at 5-year follow-up, as reflected by lower cumulative rates of overall MACE, cardiac death, recurrent MI, and definite ST; yet, with statistically similar rates of ischemia-driven TLR.

Cardiac sympathetic activity is associated with inflammation and neurohumoral activation in patients with idiopathic dilated cardiomyopathy

Background:  Idiopathic dilated cardiomyopathy (IDC) is characterized by sympathetic nervous overactivity, inflammation and neurohumoral activation; however, their interrelationships are poorly understood.

Idiopathic dilated cardiomyopathy and chronic atrial fibrillation

Atrial fibrillation (AF) is common in idiopathic dilated cardiomyopathy (IDC). We explored the clinical characteristics of IDC patients with chronic AF compared with those with sinus rhythm (SR).

Early vascular healing after titanium-nitride-oxide-coated stent versus platinum-chromium everolimus-eluting stent implantation in patients with acute coronary syndrome.

Data on early vascular healing response of novel stent designs are scarce. In this randomized prospective trial, we sought to compare early neointimal coverage of cobalt–chromium-based titanium–nitride–oxide-coated bioactive stents (CoCr-BAS) versus platinum–chromium everolimus-eluting stents (PtCr-EES) at 2-month follow-up in patients with acute coronary syndrome (ACS). Forty patients with ACS were randomized to receive either CoCr-BAS (n = 19) or PtCr-EES (n = 21). Neointimal strut coverage and strut apposition were examined by optical coherence tomography; and coronary flow reserve (CFR), fractional flow reserve (FFR) and index of microcirculatory resistance (IMR) were assessed using a coronary pressure wire at 2 months. Two patients in the PtCr-EES underwent OCT out of the time frame of the study, and were excluded from analysis. At 63 ± 8 days, 302 cross-sections (3412 struts) were analysed in the CoCr-BAS group, and 324 cross-sections (3460 struts) in the PtCr-EES group. Median [IQR] neointimal thickness was 203 [108] µm and 42.2 [41] µm for CoCr-BAS and PtCr-EES, respectively (p < 0.001). Median [IQR] percentage of uncovered struts was 1.2 [2.8] % versus 11.3 [17.7] %, respectively (p < 0.001). Flow measurements were comparable between the two groups (p > 0.05 for all). CoCr-BAS showed earlier and more adequate neointimal coverage of struts at 2 months, compared with PtCr-EES, but with more neointimal hyperplasia. Functional healing as assessed by CFR, FFR, and IMR was similar between the two stent arms.