Vitamin D Deficiency Predicts Poor Clinical Outcomes in Heart Failure Patients Undergoing Cardiac Resynchronization Therapy.

BACKGROUND AND AIMS: Resynchronization therapy (CRT) improves mortality and induces reverse remodeling in heart failure (HF) patients with reduced ejection fraction and wide QRS. Nonetheless, some patients do not improve despite the optimal medical therapy and right indications for device implantation. Therefore, finding biomarkers suitable for identification of those patients is crucial. Vitamin D plays a classic hormonal role in the regulation of bone metabolism and also has physiological functions in wide range of nonskeletal tissues. Based on recent studies, low levels of vitamin D seem to directly contribute to pathogenesis and worsening of HF. We planned to assess the role of vitamin D levels on clinical outcomes of HF patients undergoing CRT. METHODS AND RESULTS: We enrolled 136 HF patients undergoing CRT. Total plasma vitamin D levels were measured at baseline and 6 months later. Primary endpoint was 5-year all-cause mortality; secondary endpoint was lack of good clinical response, defined as less than 15% increase of left ventricular ejection fraction after six months. During follow-up, 58 patients reached the primary, and 45 patients reached the secondary endpoint. Vitamin D levels less than 24.13 ng/mL predicted 5-year mortality (p = 0.045) and poor clinical response (p = 0.03) after adjusting to all significant baseline predictors. CONCLUSION: Our study showed that vitamin D deficiency has a significant impact in heart failure patients; it is an independent predictor of lack of midterm clinical response and long-term mortality in patients undergoing CRT. Therefore, monitoring vitamin D status of heart failure patients could be of clinical significance.

The level of complement C3 is associated with the severity of atherosclerosis but not with arterial calcification in peripheral artery disease.

AIM: Recent evidences show correlations between atherosclerosis and the serum level of third component of complement (C3). However, there is less data on the connection of C3 and the severity of atherosclerosis. The aim of our study was to evaluate the association of serum C3 levels with atherosclerosis and arterial calcification in patients with chronic lower extremity atherosclerosis. METHODS: In a single centre cross-sectional study 103 patients and 109 healthy controls were examined. Sera were analyzed for C3. To identify the severity of atherosclerosis and calcification, ankle-brachial Doppler index, angiographic Bollinger score, arterial calcification score and carotid intima-media thickness was determined. RESULTS: Serum level of C3 was significantly higher in the lower extremity atherosclerosis group than in healthy patients (P=0.00004). In the patient group, serum level of C3, C4 was significantly and inversely associated with ABI (r=-0.246, P=0.014), (r=-0.259, P=0.011). C3 inversely correlates with Bollinger score (r= -0.357, P=0.028). Among our patients no correlation was found between C3 levels and CS (P=0.672, r=-0.046) or between C3 levels and carotid IMT (r=0.104, P=0.351). The serum levels of different complement components were associated with C-reactive protein, Hba1c, peptide-C and insulin. CONCLUSION: Our results suggest that C3 serum levels are associated with ABI and angiographic parameters of atherosclerosis, but do not relate to the severity of calcification.

Left ventricular untwisting in athlete's heart: key role in early diastolic filling?

Untwisting contributes to left ventricular filling through suction generation. We sought to investigate diastolic function and untwisting dynamics in different forms of left ventricular hypertrophy: in athlete's heart and hypertrophic cardiomyopathy. Elite athletes in kayaking, canoeing and rowing (n=28), patients with hypertrophic cardiomyopathy (HCM, n=15) and healthy sedentary volunteers (n=13) were compared. Left ventricular volumes, wall thickness-to-volume ratio were assessed by cardiac MRI. Following conventional and tissue Doppler measurements, untwist and untwist rate were determined by speckle tracking echocardiography. Wall thickness-to-volume ratio describing remodelling was significantly higher in HCM, but similar in athletes and controls (athlete vs. HCM vs. control: 0.107±0.019 vs. 0.271±0.091 vs. 0.104±0.012 mm×m²/ml, mean±SD, p<0.001). Mitral lateral annulus e' velocity referred to diastolic dysfunction in HCM (15.3±3.6 vs. 7.9±3.3 vs. 15.0±3.0 cm/s, p<0.01). At time point of mitral valve opening, untwist and untwist rate were significantly different: the highest values were measured in athletes, while the lowest were found in HCM (untwist: 51.3±19.1 vs. 11.6±10.4 vs. 35.9±16.3%; untwist rate: -32.5±13.0 vs. -10.6±10.8 vs. -23.0±7.7°/s, p<0.05). Untwisting correlated with E/A, e' and E/e'. Athlete's heart is characterized by increased untwist and untwist rate, which can aid diastolic function. Evaluation of untwisting dynamics may help to distinguish pathological hypertrophy.

Serum fetuin-A levels inversely correlate with the severity of arterial calcification in patients with chronic lower extremity atherosclerosis without renal disease.

AIM: Fetuin-A is a hepatic glycoprotein that inhibits extraosseous calcification. Lower serum fetuin-A concentration was associated with severe arterial calcification in patients with end stage renal disease. We evaluated the association of serum fetuin-A levels and the severity of atherosclerosis in patients with peripheral vascular disease having normal renal function. METHODS: In this cross-sectional study among 93 chronic atherosclerotic patients with lower extremity vascular disease, systemic atherosclerosis and calcification was assessed by ultrasound (carotid intima-media thickness/IMT/, calcification at the abdominal aorta, carotid and femoral bifurcations, aortic and mitral valves) and angiography (Bollinger score). Standard serum markers of inflammation, diabetes, renal function, ankle-brachial indexes and traditional risk factors for atherosclerosis were noted and Fontaine classification was applied for the severity of symptoms. RESULTS: The patients mean (SD) age was 59.95 (7.61) years, 78% were men, 35% had diabetes. Serum fetuin-A level showed significant negative correlation with ultrasound calcification score (P=0.018, r=-0.257) and Bollinger angiographic score (P=0.035, r=-0.347). Fetuin-A did not correlate with IMT or Fontaine classification. Fetuin-A also showed significant correlation with albumin, transferrin and hemoglobin A1c (r=0.287, 0.305 and 0.219, respectively at P<0.05). Logistic regression analysis confirmed the association between fetuin-A and calcification score (OR: 3.03, CI: 1.05-8.7), P=0.039) independent of traditional risk factors. CONCLUSION: Our data show that serum fetuin-A levels inversely correlate with the severity of atherosclerosis in nonuremic patients with symptomatic chronic lower limb ischemia. These data support a putative protective role for fetuin-A in the development of arterial calcification.

Generalized alterations in the biomechanical properties of large veins in non-thrombotic thrombophilic young patients.

AIM: In young, post-thrombotic patients, venous distensibility is decreased not only in the affected lower limb, but also in the contralateral limb and in the jugular vein when compared to age-matched control subjects. In the present study, we investigated venous wall mechanical properties in young, asymptomatic thrombophilic patients. METHODS: Eleven young (24+/-0.4 years) control subjects and 9 age-matched patients (21.1+/-1.8 years) with proven thrombophilic molecular defects, but without any signs or history of previous deep vein thrombosis, were compared. Anterolateral and mediolateral diameters of the common femoral, axillary and internal jugular veins were measured by ultrasonography in situ. Pressure alterations were induced by altering body positions and by pressure-controlled Valsalva tests. Distensibility was calculated from diameter and pressure changes. RESULTS: In thrombophilic patients, resting diameter of both the common femoral and of internal jugular veins at low transmural pressure was larger than those for the control subjects. Distensibility, however, was significantly less when high pressures were applied. Alterations in diameter of the axillary vein were minimal. CONCLUSION: Our measurements suggest that there are generalized changes in venous mechanical properties in thrombophilic patients even before the appearance of thrombotic processes. These biomechanical alterations of the venous wall and/or surrounding connective tissue are similar to those found in connection with aging and in post-thrombotic patients. The pathological mechanisms behind these processes are unknown.

Changes in the plasma concentration of soluble thrombomodulin in patients with severe carotid artery stenosis after eversion endarterectomy.

OBJECTIVE AND DESIGN: The purpose of the study was to investigate the putative role of soluble thrombomodulin (sTM) in severe carotid artery stenosis. MATERIALS AND METHODS: We prospectively studied 64 patients who were undergoing carotid endarterectomy (2001-2003). Plasma sTM concentration was determined in each patient before surgery and at 14 months postsurgery. -308 TNF-alpha promoter polymorphism was also determined. RESULTS: Strong negative correlation was found between the preoperative duplex scan values and the plasma sTM concentrations (R = -0.418, p = 0.0006). Patients with 308 A TNF-alpha genotype had significantly lower (p = 0.0415) preoperative sTM values than their counterparts with no such polymorphism. Soluble TM concentrations measured in plasma samples taken at the end of the postsurgical follow-up period of 14 months duration were significantly higher compared to the preoperative values (p < 0.0001). CONCLUSIONS: Our present findings indicate that sTM may be adsorbed to the atherosclerotic plaques or inflamed endothelium in carotid arteries. The pathological significance of this adsorption remains to be determined.

Long-term restenosis rate of eversion endarterectomy on the internal carotid artery.

OBJECTIVES: The eversion endarterectomy of the internal carotid artery was introduced in Hungary in 1991. The aim of this study was to define the long-term restenosis rate of this procedure. PATIENTS AND METHODS: Between 1991 and 1993, 171 operations, on 151 patients, were performed by single surgeon: with long-term follow up of 109 patients, which included annual physical and ultrasound examinations. Restenosis rate and plaque morphology were defined. Survival and patency rate were analysed by life-tables. RESULTS: The combined perioperative stroke morbidity and mortality rate was 0.8%. The 5-year patient survival rate was 85%, the recurrent stenosis free rate was 88% at 5 years. Only 9% of the patients had carotid restenosis of more than 70% during this period. Ultrasound plaque morphology showed calcification in one case. Two patients had re-operations, with plaque histology showed myointimal hyperplasia in each case. CONCLUSIONS: Our results for restenosis are compare favourably with the 2-34% restenosis rate reported in the literature. Ultrasound and histological findings suggest that atherosclerosis does not play a significant role in the development of restenosis after the eversion carotid endarterectomy.

[Late results after eversion endarterectomy of the internal carotid artery]. / Késói eredmények az arteria carotis interna everziós endarteriektómiája után.

OBJECTIVES: The eversion endarterectomy of the internal carotid artery was introduced in Hungary in 1991. The aim of this study was to define the long-term restenosis rate of this new method. MATERIALS AND METHODS: Between 1991 and 1993, 171 operations were performed by one surgeon on 151 patients: 109 patients had enough compliance to take part in long-term follow-up, which included annual physical and ultrasound (Ultramark 9) investigations. Restenosis rate and plaque morphology was defined. Survival and patency rates were calculated by life-table method. RESULTS: The perioperative combined stroke morbidity and mortality rate was 0.8%. The 5-year patient survival rate was 85%, the recurrent stenosis free rate was 88%/5 years, and 9% of the patients had restenosis greater than 70% in this period. The plaque morphology showed calcification in 1 case. Two patients needed 3 reoperations (2.4%). Plaque histology showed myointimal hyperplasia in every 3 cases. CONCLUSIONS: Comparing our results to the literature (2-34% restenosis rate) it seems to be acceptable and encouraging for the future. The ultrasound and histological findings suggest that arteriosclerosis does not play significant role in development of restenosis after the eversion method.