Friedrich M. Fruhwald

Increased Neopterin in Patients With Chronic and Acute Coronary Syndromes

OBJECTIVES The aim of our study was to determine neopterin levels in patients with chronic and acute coronary syndromes. BACKGROUND In chronic and acute coronary syndromes the release of different cytokines activates cellular defense. Infiltration of neutrophils and monocytes/macrophages is detected in the vessel wall as well as in the myocardium. Neopterin, which is a by-product of the guanosine triphosphate-biopterin pathway, is a marker for those activated macrophages. METHODS We studied 123 subjects: 1) 21 consecutive patients (17 men, 4 women; mean age +/- SD 66 +/- 15 years, range 31 to 87) with acute myocardial infarction (AMI); 2) 62 consecutive patients (50 men, 12 women; mean age 61 +/- 8 years, range 43 to 81) with signs and symptoms of clinically stable coronary artery disease (CAD); and 3) 40 healthy blood donors (28 men, 12 women; mean age 35 +/- 13 years). Neopterin levels were determined with a commercially available enzyme-linked immunosorbent assay method. RESULTS In patients with AMI before thrombolytic therapy, neopterin levels were significantly higher than levels in patients with CAD and control subjects (13.7 vs. 8.6 and vs. 6.8 nmol/liter, p < 0.0001). Values also differed significantly between patients with CAD and control subjects (p < 0.0001). Neopterin levels in patients with AMI were measured seven times during a 72-h period. Within-group comparison showed significant differences over this period (p < 0.00001). The lowest value (11.4 nmol/liter) was observed after 4 h and differed significantly from the initial value and values after 24 and 72 h (p < 0.05). After 72 h, neopterin increased to 14.9 nmol/liter, a value significantly different from all values other than the initial one. There was no correlation between neopterin and creatine kinase (CK); CK, MB isoenzyme; or lactate dehydrogenase as markers for the extent of the myocardial infarction during the observation period. CONCLUSIONS Our data support the hypothesis of an activation of monocytes and macrophages in patients with an acute or chronic coronary syndrome. Neopterin as a marker for macrophage activation is significantly increased in patients with chronic CAD and more pronounced in patients with AMI shortly after the onset of symptoms.

Changes in thyroid hormone parameters after acute myocardial infarction

Abnormalities in circulating thyroid hormone levels are very common in systemic nonthyroidal illnesses, such as acute myocardial infarction. In this study, thyroid parameters were determined in a series of 16 consecutive infarction patients treated by thrombolysis. Blood samples were taken before therapy as well as 2, 4, 6, 8, 12 and 72 h following admission. Total and free serum thyroxin and triiodothyronine decreased and reverse T3 increased significantly showing no major variations up to 72 h, whereas thyroid-stimulating hormone values remained almost unchanged during the observation period. Subjects with CK-MB levels of more than 150 ng/ml (n = 10) revealed similar changes in thyroid parameters in comparison to those with lower values (n = 6; NS). Thus, although hormone modifications very often occur following acute infarction, thyroid status may not serve as a marker for the extent of left ventricular dysfunction in the early phase of myocardial infarction.

Transient reduction of autoantibodies against oxidized ldl in patients with acute myocardial infarction

Fifteen consecutive patients (mean age 66 +/- 14, range 31-82) with an acute myocardial infarction (MI) suitable for thrombolytic therapy were included in this study. Autoantibodies against oxidized low-density lipoprotein (LDL) were determined by enzyme-linked immunosorbent assay (ELISA). Patients (n = 10) with marked elevation of the MB isoenzyme of creatinine kinase (CK-MB)-mass had significant decreases of oLDL-Ab during the acute phase, with a minimum after 8 h following the onset of thrombolytic therapy (within-group significance: p < .001; between groups: p = .01). Patients (n = 5) with CK-MB-mass values less than 70 ng/ml did not show this phenomenon. Furthermore, significant correlations existed between CK-MB-mass and oLDL-Ab after 6 and 8 h (n = 15; r = .72; p = .003) and the time of the highest CK-MB-mass values (after 12 h) and the time of the maximal decrease of oLDL-Ab (after 8 h) (r = .74; p = .003). Our observations provide further evidence for the release of free radicals and for increased lipid peroxidation during reperfusion after prolonged ischemia. The decrease of oLDL-Ab appears to be a marker for the severity of MI.

Syncope in Dilated Cardiomyopathy Is a Predictor of Sudden Cardiac Death

Fifty percent of patients with dilated cardiomyopathy die within 5 years of diagnosis. Syncope is known to be a predictor of poor outcome in patients with advanced heart failure. To assess the risk of patients with dilated cardiomyopathy with a history of syncope during standard medical treatment we compared this group to similar patients without syncope. Twenty-three patients with angiographically proven dilated cardiomyopathy and syncope were followed prospectively and compared to 201 patients without history of syncope. All patients showed a left-ventricular ejection fraction of less than 45%. Both groups did not differ in left-ventricular ejection fraction at baseline (30 +/- 7% in the syncope group, 30 +/- 8% in the no syncope group). Mean follow-up was 2.6 years in the syncope group and 2.4 years in the no syncope group. At baseline, syncope patients used more often amiodarone (p < 0.04), while there was no statistically significant difference between the two groups regarding the intake of digitalis, diuretics and angiotensin-converting enzyme inhibitors. Twenty-six percent of patients in the syncope group and 20% in the no syncope group died during follow-up (non significant). The striking difference, however, was the type of death: 5 out of 6 patients in the syncope group died suddenly compared to 13 of 41 patients in the no syncope group (p < 0.025). Patients with dilated cardiomyopathy and a history of syncope are at high risk of sudden death.

Human Paraoxonase1 Gene Polymorphisms and the Risk of Coronary Heart Disease: A Community-Based Study

Published data on the association between paraoxonase1 (PON1) polymorphisms and coronary heart disease (CHD) have yielded controversial results. The objective of this study was to determine the possible relationship between the two human PON1 amino acid variants, the Leu55Met and the Gln192Arg polymorphism, and the risk of CHD in a community-dwelling cohort of European ancestry. PON1 genotypes of 152 women and 151 men out of 1,998 randomly selected individuals aged 44–75 years were determined by polymerase chain reaction-based restriction enzyme digestion. Study participants underwent cardiological examination including a structured clinical interview, resting ECG, exercise testing and echocardiography. The diagnosis of CHD was based on history and/or appropriate findings during cardiac examination. Evidence for CHD was found in 43 (14.2%) study participants. The Leu/Leu (LL), Leu/Met (LM) and Met/Met (MM) genotypes at position 55 were noted in 131 (43.2%), 128 (42.2%) and 44 (14.5%) subjects; the Gln/Gln (QQ), Gln/Arg (QR) and Arg/Arg (RR) genotypes at codon 192 occurred in 167 (55.1%), 118 (38.9%) and 18 (5.9%) individuals, respectively. Homozygosity for the 55L-allele was significantly associated with CHD (p = 0.02), while the Gln192Arg polymorphism had no effect (p = 0.16). Logistic regression analysis demonstrated age (odds ratio 1.06/year), smoking (odds ratio 2.86), HDL cholesterol (odds ratio 0.94/mg/dl) and the paraoxonase LL genotype (odds ratio 2.25) to be significant predictors of CHD. These data suggest that the paraoxonase LL genotype at position 55 may present a risk factor for CHD.

Innovative telemonitoring system for cardiology: from science to routine operation.

OBJECTIVE Results of the Austrian MOBITEL (MOBIle phone based TELemonitoring for heart failure patients) trial indicate that home-based telemonitoring improves outcome of chronic heart failure (CHF) patients and reduces both frequency and duration of hospitalizations. Based on lessons learned, we assessed the weak points to clear the way for routine operations. METHODS We analyzed the system with respect to recommendations of the ESC Guidelines and experiences gained throughout the trial to identify potential improvements. The following components have been identified: a patient terminal with highest usability, integrated way to document drug-intake and well-being, and automated event detection for worsening of CHF. As a consequence the system was extended by Near Field Communication (NFC) technology and by an event management tool. RESULTS Usability evaluation with 30 adults (14f, median 51y. IQR[45-65]) showed that 21 (8f) were able to immediately operate the system after reading a step-by-step manual. Eight (6f) needed one time demonstration and one man (80y) failed to operate the blood pressure meter. Routine operation of the revised system started in March 2009. Within 9 months, 15 patients (4f, median 74y. IQR[71-83], all NYHA-III) transmitted 17,149 items. 43 events were detected because of body weight gain of more then 2kg within 2 days. 49 therapy adjustments were documented. Three patients stopped using the system, two (1f) because of non-compliance and one (m, 82y) because of death. Overall, the rate of adherence to daily data transfer was 78%. CONCLUSION First results confirm the applicability of the revised telemonitoring system in routine operation.

Subclinical Thyroid Disorders in Patients with Dilated Cardiomyopathy

UNLABELLED Severe thyrotoxicosis can cause irreversible congestive heart failure. To investigate the coincidence of subclinical thyroid disorders and idiopathic dilated cardiomyopathy (IDC) we investigated these patients with respect to their morphological and functional thyroid status. Thyroid sonography as well as thyroid hormone levels were measured in all patients. RESULTS Sixty-one patients (50 male, 11 female) with chronic stable IDC were included. Two out of 61 patients showed completely normal thyroid morphology and function. The other 59 patients showed either morphological or functional abnormalities or both. Of the 53 patients with morphological abnormalities 23 patients (all male) showed diffuse goiter as opposed to 29 nodular enlarged organs (24 male, 5 female). No clinically significant hypothyroidism or thyrotoxicosis was seen. A good correlation was found between the duration of IDC and thyroid volume (r = 0.44; p < 0.001). Two patients died during the study period, 1 from sudden death and 1 from progressive heart failure. CONCLUSION Subclinical thyroid disorders are frequently seen in patients with long-standing IDC when they live in an area of chronic iodine deficiency. This can be explained by chronic salt restriction as basic treatment for congestive heart failure. Therefore we conclude that examination of the thyroid gland should be done routinely in patients with IDC, especially when restriction of salt intake is recommended by the treating physician.

Comparison of effects of dalteparin and enoxaparin on hemostatic parameters and von Willebrand factor in patients with unstable angina pectoris or non--ST- segment elevation acute myocardial infarction.

The results of our study indicate that dalteparin and enoxaparin, when compared directly, have similar effects on parameters of thrombin and plasmin activation and vWF. The present study provides the first prospective, comparative results between dalteparin and enoxaparin in patients with UAP or non-ST-AMI.

Reversal of Borrelia burgdorferi Associated Dilated Cardiomyopathy by Antibiotic Treatment

SummaryIt is suggested thatBorrelia burgdorferi infection could be associated with dilated cardiomyopathy (IDC). Stanek et al. were able to cultivateBorrelia burgdorferi from myocardial biopsy tissue of a patient with longstanding dilated cardiomyopathy. Here we present a study in which we examined the effect of standard antibiotic treatment on the left ventricular ejection fraction (LVEF) in patients with dilated cardiomyopathy associated withBorrelia burgdorferi infection. In this study we assessed the serum (IgG, IgM Elisa) and history of 46 IDC patients with specific regard toBorrelia burgdorferi infection (mean LVEF 30.4±1.3%, measured by cardiac catheterization and echocardiography with the length-area-volume method). All 46 patients received standard treatment for dilated cardiomyopathy: ACE inhibitors, digitalis, and diuretics. Eleven (24%) patients showed positive serology and a history ofBorrelia burgdorferi infection; nine of these also had a typical history of tick bite and erythema chronicum migrans (ECM) and/or other organ involvement, and two had no recollection of tick bite or ECM but showed otherBorrelia burgdorferi-associated disorders (neuropathy, oligoarthritis). These 11 patients withBorrelia burgdorferi infection received standard antibiotic treatment with intravenous ceftriaxone 2 g bid for 14 days. Six (55%) recovered completely and showed a normal LVEF after 6 months, three (27%) improved their LVEF, and two (18%) did not improve at all. This amounts tonine (82%) patients with recovery/improvement in the Borrelia burgdorferi group. The 35 patients who did not show positive serology or a history ofBorrelia burgdorferi infection did not receive antibiotic treatment. In thisgroup without Borrelia burgdorferi infection 12 (26%), showed recovery/improvement following the standard treatment of dilated cardiomyopathy (see earlier). Our results indicate thatBorrelia burgdorferi infection could play a decisive role in the development of dilated cardiomyopathy, especially in a geographical region such as Graz, whereBorrelia burgdorferi is endemic. While we are aware of the small number ofBorrelia burgdorferi patients in this study, we nevertheless conclude that in a remarkable number of patients with signs ofBorrelia burgdorferi infection, dilated cardiomyopathy could be reversed and LVEF improved.

Long-term outcome and prognostic factors in dilated cardiomyopathy : preliminary results

To investigate long-term follow-up and identify prognostic factors in patients with dilated cardiomyopathy (DCM) the authors investigated 167 consecutive patients on an outpatient basis. All patients underwent left- and right-heart catheterization; follow-up comprised clinical and echocardiographic investigations. Results: After a mean follow-up period of ninety-three ± thirty-six months 82 patients (49%; 71 men, 11 women, mean age fifty-five ± eleven years) were alive. 29 of them (27 men, 2 women, mean age fifty-two ± nine) showed normal left ventricular ejection fraction (LVEF) after a mean follow-up period of one hundred four ± forty months. The remaining 53 patients (44 men, 9 women, mean age fifty-six ± eleven) revealed LVEF similar to that of the first examination. Eighty-five patients died (51%; 73 men, 12 women). Causes of death were the following: progressive heart failure, 24; sudden death, 23; stroke, 3; pulmonary embolism, 2; noncardiac death, 4; unknown causes, 29. The median period from the onset of first symptoms until definite diagnosis was two months in patients with stable conditions, three months in those with normalization of LVEF and twenty-four months in those who died, respectively (P < 0.01). At the time of diagnosis, patients with stable outcome had a mean LVEF (LVEF 1) of 37%, those who returned to normal had 40% (ns). Patients who died had a mean LVEF 1 of 32% and therefore differed significantly from both groups of survivors (P < 0.001). Left ventricular enddiastolic pressure (LVEDP) at the time of diagnosis was highest in patients who died (22 mmHg) and therefore differed significantly from both groups of survivors (normalization: 16 mmHg, stable patients: 18 mmHg, P < 0.001). Conclusions: According to their results, time until diagnosis, LVEF, and LVEDP are prognostic indicators. No difference was noted between the groups concerning etiology, medical treatment, or functional classification according to the New York Heart Association.