The association between myocardial ischemia and myocardial dysfunction in adult patients with systemic right ventricle - A single centre multimodality study.

BACKGROUND: The exact interaction of factors leading to myocardial dysfunction and fibrosis of the systemic right ventricle (SRV) is not completely understood. Myocardial ischemia and injury associated with a supply-demand mismatch of the pressure overloaded SRV are thought to play an important role, however studies confirming this are lacking. METHODS: Adult SRV patients were included in this single centre cohort study. All patients underwent a comprehensive diagnostic and imaging workup. A two-day stress-rest SPECT was performed to assess myocardial perfusion. SRV ischemia was defined as decreased segmental tracer uptake during exercise with significant improvement at rest. Contrast enhanced cardiac magnetic resonance imaging (CMR) was also performed in a subgroup of patients without contraindication, to assess focal myocardial fibrosis. Differences between patients with and without SRV ischemia were assessed. RESULTS: Twenty-three SRV patients (15 with transposition of the great arteries after atrial switch procedure and 8 with congenitally corrected transposition of the great arteries; 5 (22%) females; mean age 38 ± 11 years) were included. Seven (30%) patients had SRV ischemia on SPECT. Late gadolinium enhancement on CMR was more common in patients with SRV ischemia (p = 0.002). However, there was no association between SRV ischemia and different echocardiographic or CMR parameters of SRV systolic function, laboratory markers (high-sensitivity troponin I and NT-proBNP) and exercise capacity. CONCLUSIONS: Our multimodality study showed that SRV ischemia in adult SRV patients was associated with more focal myocardial fibrosis, but not with functional or imaging markers of SRV function.

Impairment of myocardial perfusion correlates with heart failure severity in patients with non-compaction cardiomyopathy.

AIMS: Non-compaction cardiomyopathy (NCM) is a congenital heart disease characterized by an arrest of the myocardial compaction process. Although NCM patients have impaired formation of microvasculature, the functional impact of these changes remains undefined. We sought to analyse a potential correlation between myocardial ischemia and heart failure severity in NCM patients. METHODS AND RESULTS: We enrolled 41 NCM patients (28 male and 13 female), aged 21-70 years. In all patients, we have determined left ventricular end-diastolic volume (LVEDV), left ventricular ejection fraction (LVEF), and global longitudinal strain (GLS) by echocardiography. At the same time, serum levels of N-terminal pro-B-type natriuretic peptide (NT-proBNP) have been measured, and myocardial single-photon emission computed tomography at rest and on stress was used to define significant myocardial ischemia defined as summed difference score ≥ 2. Myocardial ischemia has been demonstrated in 11 patients (27%, Group A), and 30 patients showed no significant ischemic changes (73%, Group B). The groups did not differ in sex, age, kidney, or liver function. When compared with Group B, Group A had significantly lower LVEF (35 ± 15% in Group A vs. 53 ± 11% in Group B, P < 0.001), higher LVEDV (188 ± 52 mL vs. 136 ± 52 mL, P = 0.007), lower GLS (-9.9 ± 5.2% vs. -14.5 ± 4.1%, P = 0.001), and higher NT-proBNP levels (1691 ± 1883 pg/mL vs. 422 ± 877 pg/mL, P = 0.006). Overall, higher summed difference score was associated with lower LVEF (r = -0.48, P = 0.001), higher LVEDV (r = 0.39, P = 0.012), lower GLS (r = 0.352, P = 0.024), and higher levels of NT-proBNP (r = 0.66, P < 0.001). CONCLUSIONS: The presence of myocardial ischemia in patients with NCM is associated with worse left ventricular function, dilation of the left ventricle, and more pronounced neurohumoral activation.

Endothelial function is impaired in patients with primary antiphospholipid syndrome.

INTRODUCTION: The aim of this study was to evaluate endothelial function in patients with primary antiphospholipid syndrome (PAPS). PATIENTS AND METHODS: Flow mediated (FMD) and glyceryl trinitrate (GTN) induced dilation of the right brachial artery were studied in 25 patients with PAPS and 25 controls matched by age, sex and conventional risk factors for atherosclerosis. Fibrinogen, D-dimer, adhesion molecules, tissue plasminogen activator (t-PA) and plasminogen activator inhibitor-1 (PAI-1) antigens and activities were measured. RESULTS: Mean (SD) FMD was significantly lower in PAPS than in controls (8+/-5% vs. 15+/-6%, P<0.001); GTN-induced dilation did not differ between the groups. There was a correlation between the baseline diameter of the brachial artery and duration of the disease (-0.56, P<0.05) and between GTN induced dilation and duration of the disease (0.51, P<0.05). Concentrations of vascular cell adhesion molecule-1 (P<0.001), intracellular adhesion molecule-1 (P<0.001) and fibrinogen (P<0.05) were higher in patients than in controls but no differences were observed for D-dimer, t-PA and PAI-1 antigens and activities. There was correlation between concentration of vascular cell adhesion molecule-1 and FMD (-0.35, P<0.05) and between intracellular adhesion molecule-1 and FMD (-0.41, P<0.05). CONCLUSIONS: This study shows that endothelial function is impaired in patients with primary APS, possibly contributing to accelerated atherosclerosis and thromboembolic complications in these patients.

Unprovoked proximal venous thrombosis is associated with an increased risk of asymptomatic pulmonary embolism.

INTRODUCTION: Pulmonary embolism (PE) is common in patients with deep venous thrombosis (DVT). The outcome of DVT with concomitant symptomatic PE is worse than the outcome of isolated DVT. The risk factors for DVT and simultaneous asymptomatic PE have not been systematically studied yet. AIM: To evaluate the frequency and risk factors for asymptomatic PE in patients with DVT. PATIENTS/METHODS: In 155 consecutive patients with a first episode of DVT and no PE symptoms, a ventilation-perfusion lung scan was performed. Body mass index (BMI) and waist-to-hip ratio (WHR) were calculated and concentrations of D-dimer, high-sensitivity CRP (hsCRP), tissue plasminogen activator (t-PA) and troponin were measured. Laboratory tests for thrombophilia were performed. RESULTS: Asymptomatic PE was present in 36% of patients. No differences in gender, age, BMI and WHR were found between the patients with and without PE. PE was more common in patients with proximal DVT than in those with distal DVT (42% vs. 17%, p<0.01), and in patients with unprovoked DVT compared to patients with provoked DVT (51% vs. 28%, p<0.01). The risk of silent PE was the highest in patients with unprovoked proximal DVT (OR, 6.9; 95% CI, 2.3-21.0). Patients with asymptomatic PE had significantly higher values of D-dimer, hsCRP, t-PA and troponin than patients with isolated DVT. CONCLUSIONS: Asymptomatic PE affected more than one third of patients with a first DVT. Unprovoked proximal DVT is the most important risk factor for the occurrence of silent PE.

Impairment of the vasodilatation capability of the brachial artery in patients with idiopathic venous thrombosis.

AIM: Determination of the functional capability of the peripheral arteries is increasingly used as an early marker of vessel disease. The aim of this study was to evaluate flow-mediated (FMD) and glyceryl trinitrate-mediated (NMD) dilation of the brachial artery in patients with idiopathic venous thrombosis (VT). METHODS: Flow-mediated brachial artery dilatation and the dilatation response to glyceryl trinitrate were measured using high-resolution ultrasound in 97 subjects (49 eligible patients of both sexes, mean age 51.5 ± 14.6 years, with idiopathic venous thrombosis, and 48 age-matched healthy controls). RESULTS: Compared to the control group, FMD was significantly reduced in the group of patients with idiopathic venous thrombosis -4.9% (95% CI 1.1-8.7%) vs. 12.7% (95% CI 7.8-17.6%), p<0.001. Patients also had diminished NMD of the brachial artery -12.5% (95% CI 6.6-18.4%) vs. 18.5% (95% CI 10.1-26.9%), p<0.001. In patients, significantly higher levels of circulatory markers (P-selectin, von Willebrand factor) of endothelial dysfunction were registered. CONCLUSIONS: Idiopathic venous thrombosis is associated with impaired flow- and GTN-mediated vasodilatory response of the brachial artery. This may suggest involvement of the functional deterioration of the vessel wall in the pathogenesis of idiopathic VT and indicate a relationship between VT and atherothrombosis.