Twenty-four-month alpha-galactosidase A replacement therapy in Fabry disease has only minimal effects on symptoms and cardiovascular parameters.

Fabry disease is an X-linked lysosomal storage disease caused by deficiency of alpha-galactosidase A enzyme activity. Decreased enzyme activity leads to accumulation of glycosphingolipids in different tissues including endothelial cells and smooth-muscle cells and cardiomyocytes, and cardiovascular complications are common in the disease. Since 2001, specific enzyme replacement therapy (ERT) with alpha-galactosidase A has been available. It has been reported to improve clinical symptoms and quality of life. However, limited and controversial data on its efficacy to cardiac involvement have been published. Nine patients (5 male) with Fabry disease were included in an open-label prospective follow-up study of 24-month ERT. Comprehensive cardiovascular evaluation was performed by MRI, stress echocardiography and quality of life assessment. Plasma globotriaosylceramide decreased from 6.2 to 1.4 microg/ml during ERT (p<0.05). The only other measured parameters that changed significantly were resting heart rate that decreased from 79 to 67 bpm (p<0.01) and end-systolic volume that decreased by 12.4 ml (p<0.05). The other parameters consisting of quality of life, self-estimated cardiovascular condition, diastolic function, exercise capacity, ECG parameters, ejection fraction and ventricular mass did not change. ERT has only minimal effect on symptoms and cardiovascular morphology and function in Fabry disease. Therefore, effective conventional medical therapy is still of major importance in Fabry disease. Larger ERT studies are warranted, especially in women, to solve current open questions, such as the age at which ERT should be started, optimal dosage and intervals between infusions. Furthermore, longer follow-up studies are needed to assess the effects of ERT on prognosis.

Neurologic manifestations of infective endocarditis: a 17-year experience in a teaching hospital in Finland.

BACKGROUND: Many previous studies have endeavored to find appropriate means to reduce the occurrence of neurologic manifestations in patients with infective endocarditis (IE). We evaluated patients with IE-associated neurologic complications and compared them with patients with IE who did not have neurologic symptoms. Particular attention was focused on assessing the impact of cardiac surgery and the presence of potential risk factors for complications on the outcome of the patients. METHODS: A total of 218 episodes designated as definite or possible IE according to Duke criteria and treated during the years 1980 through 1996 in a Finnish teaching hospital were retrospectively evaluated for neurologic manifestations. RESULTS: Neurologic complications were identified in 55 episodes (25%), with an embolic event as the most frequent manifestation (23/55; 42%). In the majority (76%) of episodes, the neurologic manifestation was evident before antimicrobial treatment was started, being the first sign of IE in 47% of episodes. Only 1 recurrent cerebral embolization was observed. Neurologic complications were significantly associated with Staphylococcus aureus infection (29% vs 10%; P =.001) and with IE affecting both the aortic and the mitral valves (56% vs 23%; P<.01), but not with echocardiographic detection of vegetations or anticoagulant therapy. Death during the acute phase of IE occurred in 13 episodes (24%) with neurologic complications and in 17 episodes (10%) without neurologic complications (P<.03). In episodes with neurologic complications, the IE-associated mortality rate was 25% (10/40) in the medical treatment group and 20% (3/15) in the surgical group. No neurologic deterioration was observed in these surgically treated patients postoperatively. CONCLUSIONS: Our results reinforce the belief that rapid diagnosis and initiation of antimicrobial therapy may still be the most effective means to prevent neurologic complications. These data underscore the importance of diagnostic alertness to the prognosis of patients with IE.

Effects of five years of cardiac rehabilitation after coronary artery bypass grafting on coronary risk factors.

Coronary risk factors were studied in 119 patients randomly assigned to cardiac rehabilitation and compared with 109 patients receiving standard care alone after coronary artery bypass grafting. The long-term impact of rehabilitation on risk factors was modest in patients undergoing elective coronary surgery.

Combined cardioplegia delivery offers no advantage over antegrade cardioplegia administration in coronary surgical patients with a preserved left ventricular function.

The effects of antegrade and of combined antegrade and retrograde cardioplegia were compared in 101 patients undergoing elective coronary artery surgery. The patients were randomly allocated to two groups: antegrade cardioplegia was administered in 53 patients and combined cardioplegia in 43 patients. The patients of the two groups were similar in age, sex and left ventricular ejection fraction. Aortic clamping time and the number of coronary bypasses were equal in the groups. The ventricular septal temperature was measured continuously during cardioplegia administration, after each distal anastomosis accomplished, and continuously after aortic declamping. Serum CK-MB activities were serially measured for up to 3 days postoperatively. Electrocardiograms (ECG) were taken preoperatively, as well as on the first, second and eighth postoperative days. The left ventricular function was evaluated with a volume load test preoperatively and on the first postoperative morning. The two groups were similar with respect to myocardial cooling, response to volume loading, the number of patients with perioperative myocardial infarctions, cardiac arrhythmias or atrioventricular conduction blocks and clinical outcome. However, the CK-MB activities were lower in the antegrade group suggesting better myocardial protection in an unselected group of patients undergoing coronary artery bypass grafting.

Infective endocarditis in a Finnish teaching hospital: a study on 326 episodes treated during 1980-2004.

OBJECTIVES: To evaluate potential changes of infective endocarditis (IE) in patients treated in a Finnish teaching hospital during the past 25 years. PATIENTS: 326 episodes of IE in 303 patients treated during 1980-2004 were evaluated for clinical characteristics and their changes over time. RESULTS: The mean age of the patients increased with time (from 47.2 to 54.5 years, p = 0.003). Twenty-five (7.7%) episodes were associated with intravenous drug use (IVDU), with a significant increase of these episodes after 1996 (from 0 to 19 (20%), p < 0.001). Viridans streptococci were the most common causative agents of IE during 1980-1994, but after that Staphylococcus aureus was the most common pathogen (p = 0.015). The proportion of IE of the aortic valve decreased during the study (from 30 (49%) to 26 (27%), whereas the proportions of mitral (11 (18%) to 33 (35%) and tricuspid valve IE (0 to 13 (14%) increased correspondingly (p = 0.001). This was mainly due to more patients with IVDU. Chronic dialysis for renal failure as an underlying condition increased over time (from 0 to 7 (7.4%), p = 0.015) but no other predisposing conditions changed. Complications such as neurological manifestations and heart failure did not change in frequency, but the incidence of lung emboli increased (from 0% to 10.5%, p < 0.001); 83% of these emboli occurred in patients with IVDU. The proportion of patients requiring surgical treatment and mortality due to IE did not change. CONCLUSIONS: During these 25 years, the causative agents, affected valves and complications of IE changed to some degree. These changes were mainly attributed to the increase of IVDU-associated IE. Except for the increase in age, the clinical presentation and outcome in non-addicts remained substantially unchanged.

The effect of 12-month enzyme replacement therapy on myocardial perfusion in patients with Fabry disease.

Fabry disease (McKusick 301500) is an X-linked lysosomal storage disorder secondary to deficient alpha-galactosidase A activity which leads to the widespread accumulation of globotriaosylceramide (Gb(3)) and related glycosphingolipids, especially in vascular smooth-muscle and endothelial cells. We have recently shown that the myocardial perfusion reserve of Fabry patients is significantly decreased. Thus, in the present study we investigated, whether it can be improved with enzyme replacement therapy (ERT). Ten patients (7 male, 3 female; mean age 34, range 19-49 years) with confirmed Fabry disease were approved for this uncontrolled, open-label study. Myocardial perfusion was measured at rest and during dipyridamole-induced hyperaemia by positron emission tomography and radiowater. Myocardial perfusion reserve was calculated as the ratio between maximal and resting perfusion. Perfusion measurements were performed before and after 6 and 12 months of ERT by recombinant human alpha-galactosidase A (Fabrazyme, Genzyme). Plasma Gb(3) concentration decreased significantly and the patients reported that they felt better and suffered less pain after the ERT. However, neither resting or dipyridamole-stimulated myocardial perfusion nor myocardial perfusion reserve changed during the ERT. Pretreatment relative wall thickness correlated negatively with posttreatment changes in flow reserve (r = -0.76, p = 0.05) and positively with posttreatment changes in minimal coronary resistance (r = 0.80, p = 0.03). This study shows that 12 months of ERT does not improve myocardial perfusion reserve, although the plasma Gb(3) concentration decreases. However, individual variation in the response to therapy was large and the results suggest that the success of the therapy may depend on the degree of cardiac hypertrophy.

Impaired myocardial perfusion reserve but preserved peripheral endothelial function in patients with Fabry disease.

Fabry disease (McKusick 301500) is an X-linked lysosomal storage disorder due to deficient alpha-galactosidase A activity, which leads to accumulation of glycosphingolipids, especially in vascular smooth-muscle and endothelial cells. The effect of this accumulation on peripheral and cardiac vascular function is poorly known. We studied 15 Fabry patients (mean age 35 years and mean BMI 24.8 kg/m2) and 30 age- and BMI-matched healthy controls to examine whether myocardial perfusion reserve and peripheral artery endothelial function are altered. Myocardial perfusion was measured at rest and during dipyridamole-induced hyperaemia by positron emission tomography and H2(15)O. Myocardial blood flow reserve was calculated as the ratio between the dipyridamole-induced maximal blood flow and resting blood flow. Peripheral artery endothelial function was assessed by measuring the brachial artery flow-mediated dilatation using ultrasound at rest and during reactive hyperaemia. The myocardial perfusion reserve was significantly lower in Fabry patients than in controls (3.3+/-1.2 vs 4.4+/-1.6, p=0.02), while the brachial artery flow-mediated dilatation was similar (5.9%+/-3.9% vs 4.5%+/-3.6%, p=0.27). Thus, inFabry disease, myocardial perfusion reserve is reduced while the peripheral artery endothelial function is preserved.

Eikenella corrodens prosthetic valve endocarditis in a patient with ulcerative colitis.

A 33-y-old male with ulcerative colitis developed prosthetic valve endocarditis (PVE) caused by Eikenella corrodens. The outcome of conservative treatment was successful. Only 2 cases of E. corrodens PVE were found in a survey of the English-language medical literature. In contrast to previous data indicating that eikenella infections usually derive from the oral cavity, our patient most likely acquired the infection by colonoscopy and mucosal biopsies, which were performed a few days before onset of the disease.

Fatal influenza A myocarditis with isolation of virus from the myocardium.

A previously healthy 27-year-old woman developed an acute cardiac failure one week after onset of influenza-like respiratory infection, and died on her fourth day in hospital. Intravital differential diagnosis included myocardial infarction because of ECG changes and massive elevation of myocardial enzymes. Autopsy revealed severe myocarditis and intact coronary arteries. At microscopic examination the myocardium was heavily infiltrated with lymphocytes, and there was a marked myocytolysis. Influenza A virus was isolated from the myocardial tissue. An immunological mechanism of myocardial damage is suggested.

Early results and complications of coronary artery bypass surgery. A consecutive series of 441 patients.

The mortality rate and early complications of coronary artery bypass surgery were assessed for the first 441 consecutive patients operated on at Turku University Hospital. The overall hospital mortality rate was 2.5%. Perioperative myocardial infarction (PMI) accounted for more than half of the deaths, cerebral thromboembolism and sudden coronary death each for one-fifth and left ventricular failure for one-tenth. Postoperative complications occurred in 17.7% of the patients. Bleeding and postpericardiotomy syndrome were the most common complications (in 5.2 and 3.6% of the patients). Sternal resuture was needed in 3.2% of the patients, and PMI occurred in 2.9%. PMI had a 46% mortality rate, with two-thirds of the deaths occurring in the operating theatre. Only PMI reached statistical significance as sole cause of death. Mode of myocardial protection, completeness of revascularization and severity of coronary disease did not influence the PMI rate. Graft patency overall was 92.8% on average 3 months after surgery. The respective patency rates for internal mammary artery grafts and vein grafts were 90.3 and 92.9%.

Coronary heart disease risk factors before and after bypass surgery: results of a controlled trial on multifactorial rehabilitation.

The effect of a three-phase multifactorial institution-based rehabilitation programme on coronary heart disease (CHD) risk factors was studied in an open randomised trial comprising 228 patients undergoing coronary artery bypass surgery allocated into a rehabilitation (R) group (n = 119) and a hospital (H = control) group (n = 109). Follow-up examinations were performed at 6 and 12 months. Serum total cholesterol and triglyceride levels decreased significantly in both groups during follow-up. These decreases were not significantly different between the R and H groups. Serum high density lipoprotein (HDL) cholesterol level increased significantly at 6 and 12 months in the R group, but not in the H group. The differences in the changes between the groups were not significant. The ratio of serum HDL cholesterol to total cholesterol increased significantly in the R group from the preoperative value of 0.154 to 0.179 (P less than 0.001) at 6 months and to 0.180 (P less than 0.001) at 12 months. In the H group these values were 0.152, 0.166 (P less than 0.001) and 0.168 (P less than 0.001), respectively. The significance of the differences in the changes between the groups were P = 0.01 at 6 months and 0.06 at 12 months. These differences were more obvious in patients aged 55 years or under. There was a significant decrease (P = 0.005) in the proportion of smokers in the R group and a significant increase in the proportion of patients taking regular exercise in both groups as assessed by questionnaire.(ABSTRACT TRUNCATED AT 250 WORDS)

Exercise habits and physical performance during comprehensive rehabilitation after coronary artery bypass surgery.

The effects of training as part of a comprehensive rehabilitation programme on exercise capacity and habits was studied in 171 male coronary artery bypass surgery patients randomized into a rehabilitation (R) (n = 93) and a reference, hospital-based treatment (H), group (n = 78). The rehabilitation programme started with a 2-day informative course before surgery and continued with a 3-week exercise-based course 2 months after surgery followed by a 2-day refresher 8 months post-operatively. The percentages of subjects having regular exercise were 22% and 10% pre-operatively, 42% and 38% 6 months and 46% and 38% 12 months after surgery in the R and H groups, respectively. The changes in the proportions observed in R and H groups were not significantly different. Total work during a bicycle exercise test increased from 38.9 +/- 24.3 kJ pre-operatively to 64.0 +/- 31.4 kJ 6 months (P less than 0.001) and to 70.0 +/- 35.7 kJ 12 months (P less than 0.001) post-operatively in group R and from 40.8 +/- 25.6 kJ to 57.3 +/- 26.6 kJ (P less than 0.001) and to 60.4 +/- 30.8 kJ (P less than 0.001) in group H, respectively. The increase from the pre-operative value was greater in group R than in group H both 6 (P = 0.03) and 12 months (P = 0.02) after surgery. Respective changes occurred in maximal work load, but the increase was significantly greater in group R than in group H only 12 months post-operatively.(ABSTRACT TRUNCATED AT 250 WORDS)

The proportion of patients with cognitive impairment after coronary artery bypass surgery: an 8-month follow-up study.

The aim of this study was to investigate cognitive function after coronary artery bypass surgery and the association of this with surgical variables. All male patients scheduled for elective surgery, aged 40-64 years, mean age 54 +/- 6 (n = 104), and participating in a randomized rehabilitation study, were included. A comprehensive psychodiagnostic examination was conducted preoperatively, 2, and 8 months postoperatively. The assessment of change was conducted using tertiles, defined according to population norms. More patients revealed improvement than impairment, and practically no significant associations with surgical variables were found.

Quality of life and return to work 5 years after coronary artery bypass surgery. Long-term results of cardiac rehabilitation.

BACKGROUND: Rehabilitation is an important part of the treatment of patients with ischemic heart disease. Therefore, many patients undergoing coronary artery bypass surgery (CABS) also participate in cardiac rehabilitation programs. This study was conducted to investigate whether rehabilitation influences quality of life and work status after CABS. METHODS: Consecutive patients undergoing elective CABS were randomly assigned to a rehabilitation group (R, N = 119) and a hospital-treatment group (H N = 109). All patients received usual medical care. Group R participated in a rehabilitation program based on exercise and counseling. The follow-up time was 5 years. The measured domains of health-related quality of life were heart symptoms, functional class, exercise capacity, use of medication, depression, the patients' perception of health, and overall life situation. The Nottingham Health Profile as a measure of perceived distress was used. RESULTS: Symptoms, use of medication, exercise capacity, and depression scores did not differ between groups R and H. Five years after the CABS, the patients in group R reported less restriction in physical mobility on the Nottingham Health Profile than patients in group H (P = 0.005), and more patients in group R than in group H perceived their health (P = 0.03) and overall life situation (P = 0.02) as good. The increase in the proportion of subjects working was higher in group R than group H at 3 years after the CABS (P = 0.02), but not at other follow-up times. CONCLUSION: A cardiac rehabilitation program in conjunction with usual medical care after CABS may induce a perception of improved health. The influence on return to work is limited.

Components of the insulin resistance syndrome are associated with progression of atherosclerosis in non-grafted arteries 5 years after coronary artery bypass surgery.

AIMS: Risk factors for progression of atherosclerosis in non-grafted coronary arteries were examined in a prospective 5-year follow-up study of 228 consecutive coronary artery bypass surgery patients, with the main emphasis on insulin resistance syndrome. METHODS AND RESULTS: Serum lipids and lipoproteins were measured pre-operatively and 1, 2, 3 and 5 years after surgery; and a baseline oral glucose tolerance test with plasma insulin determinations was performed pre-operatively. Progression of atherosclerosis was assessed by means of computer-based quantitative coronary angiography. Compared to subjects without progression, the patients with progression of atherosclerotic lesions had a higher body mass index both at baseline (P = 0.022) and at 5 years (P = 0.007), were more often treated for hypertension at baseline (P = 0.008) and at 5 years (P = 0.012), used diuretics more often during the follow-up period (P = 0.002), had a larger blood glucose area under the curve (P = 0.015) and a lower insulin sensitivity index (P = 0.006) in the baseline oral glucose tolerance test, had a higher serum total cholesterol concentration at baseline (P = 0.044), and a higher serum triglyceride concentration (P = 0.005) during the whole follow-up period. Clustering of the components of insulin resistance syndrome at baseline was more frequently found in patients with progression of atherosclerotic lesions than in patients without progression (P = 0.025). For example, for patients with < or = 1 component, the risk of progression was 17%, while for patients with > or = 5 components the risk was 67%. As compared to the other patients, those with new atherosclerotic lesions had a lower insulin sensitivity index at baseline (P = 0.033), and a lower serum high density lipoprotein cholesterol concentration during the follow-up period (P = 0.033). CONCLUSION: In addition to high serum cholesterol, the components of the insulin resistance syndrome are associated with progression of atherosclerosis in non-grafted coronary arteries 5 years after coronary artery bypass surgery.

Angiographic changes in saphenous vein grafts and atherosclerosis risk factors. A 5-year study with serial measurements of serum lipids and lipoproteins.

The association between cardiovascular risk factors and stenosis or occlusion of saphenous vein grafts was analysed in a prospective 5-year study of 176 unselected patients with coronary artery bypass grafting (CABG). Methods included serial measurements of serum lipids and lipoproteins, determination of apolipoprotein E phenotype, lipoprotein (a) levels 5 years postoperatively, and subcutaneous fat biopsy to determine the fatty acid composition before and one year after CABG. Graft angiography with quantitative analysis of angiograms was performed at the end of follow-up. A coronary artery with diameter < or = 1.5 mm was associated with occlusion of vein grafts (p < 0.01). The mean levels of serum lipids and lipoproteins, other traditional risk factors for atherosclerosis, and subcutaneous fatty acid composition were similar in patients with and without graft occlusion, and similar when the maximum diameter of non-occluded grafts was < 50% vs > or = 50%, and < 25% vs > or = 25%. High lipoprotein (a) concentration tended to be associated with obstructive changes in vein grafts. Our data indicate that, because lipids, lipoproteins and other traditional cardiovascular risk factors do not predict occlusion or stenosis of saphenous vein grafts five years after CABG, it is not currently possible to predict directly from the levels of these risk factors which patients are likely to benefit from pharmacological or other interventions.