Kofflard, M.J.M.

Minor elevations in troponin i are associated with mortality and adverse cardiac events in patients with atrial fibrillation (Article)

2011-03-01T00:00:00Z

Aims In patients with atrial fibrillation, minor troponin I elevation is regularly detected; however, the prognostic significance of this finding is unknown. We therefore sought to examine the prognostic value of elevated troponin I in patients with atrial fibrillation. Methods and results A prospective study was conducted analysing all consecutive patients admitted with atrial fibrillation in a 2-year period. Patients with an ST-elevation myocardial infarction (MI) were excluded. Minor troponin elevation was defined as a troponin I level between 0.15 and 0.65 ng/mL, which is still below the 99th percentile of the upper reference limit. A positive troponin I was defined as >0.65 ng/mL. Study outcomes were all-cause mortality (death), death and myocardial infarction (death/MI), or all major adverse cardiac events (MACE: death, MI, or revascularization). A total of 407 patients were eligible for inclusion. The median duration of follow-up was 688 days. A minor elevation occurred in 81 (20) patients and 77 (19) had a positive troponin I. In a multivariate model, minor troponin I elevation and a positive troponin I were independently associated with death [hazard ratio (HR): 2.36, 95 confidence interval (CI): 1.174.73 for minor elevation and HR: 3.77, 95 CI: 1.4210.02 for positive troponin I]. Also, there was an independent correlation between the combined endpoints of death/MI and MACE and both a minor elevation and a positive troponin I. Conclusion Minor elevations in troponin I on hospital admission are associated with mortality and cardiac events in patients with atrial fibrillation and might be useful for risk stratification.

Disease penetrance and risk stratification for sudden cardiac death in asymptomatic hypertrophic cardiomyopathy mutation carriers (Article)

2009-11-01T00:00:00Z

AimsTo investigate the outcome of cardiac evaluation and the risk stratification for sudden cardiac death (SCD) in asymptomatic hypertrophic cardiomyopathy (HCM) mutation carriers.Methods and resultsSeventy-six HCM mutation carriers from 32 families identified by predictive DNA testing underwent cardiac evaluation including history, examination, electrocardiography, Doppler echocardiography, exercise testing, and 24 h Holter monitoring. The published diagnostic criteria for HCM in adult members of affected families were used to diagnose HCM. Thirty-three (43) men and 43 (57) women with a mean age of 42 years (range 16-79) were examined; in 31 (41) HCM was diagnosed. Disease penetrance was age related and men were more often affected than women (P = 0.04). Myosin Binding Protein C (MYBPC3) mutation carriers were affected at higher age than Myosin Heavy Chain (MYH7) mutation carriers (P = 0.01). Risk factors for SCD were present in affected and unaffected carriers.ConclusionHypertrophic cardiomyopathy was diagnosed in 41 of carriers. Disease penetrance was age dependent, warranting repeated cardiologic evaluation. The MYBPC3 mutation carriers were affected at higher age than MYH7 mutation carriers. Risk factors for SCD were present in carriers with and without HCM. Follow-up studies are necessary to evaluate the effectiveness of risk stratification for SCD in this population.

A microcosting study of diagnostic tests for the detection of coronary artery disease in the Netherlands (Article)

2009-10-01T00:00:00Z

Objective: The primary aim of the present study was to calculate the actual costs of four diagnostic tests for the detection of coronary artery disease in the Netherlands using a microcosting methodology. As a secondary objective, the cost effectiveness of eight diagnostic strategies was examined, using microcosting and reimbursement fees subsequently as the cost estimate. Design: A multicenter, retrospective cost analysis from a hospital perspective. Setting: The study was conducted in three general hospitals in the Netherlands for 2006. Interventions: Exercise electrocardiography (exECG), stress echocardiography (sECHO), single-photon emission computed tomography (SPECT) and coronary angiography (CA). Results: The actual costs of exECG, sECHO, SPECT and CA were €33, 216, 614 and 1300 respectively. For all diagnostic tests, labour and indirect cost components (overheads and capital) together accounted for over 75% of the total costs. Consumables played a relatively important role in SPECT (14%). Hotel and nutrition were only applicable to SPECT and CA. Diagnostic services were solely performed for CA, but their costs were negligible (2%). Using microcosting estimates, exECG-sECHO-SPECT-CA was the most and CA the least cost effective strategy (€397 and 1302 per accurately diagnosed patient). Using reimbursement fees, exECG-sECHO-CA was most and SPECT-CA least cost effective (€147 and 567 per accurately diagnosed patient). Conclusions: The use of microcosting estimates instead of reimbursement fees led to different conclusions regarding the relative cost effectiveness of alternative strategies.

Diastolic Abnormalities as the First Feature of Hypertrophic Cardiomyopathy in Dutch Myosin-Binding Protein C Founder Mutations (Article)

2009-01-01T00:00:00Z

Objectives: To test the hypothesis that carriers of Dutch founder mutations in cardiac myosin-binding protein C (MYBPC3), without left ventricular hypertrophy (LVH) or electrocardiographic abnormalities, have diastolic dysfunction on tissue Doppler imaging (TDI), which can be used for the screening of family members in the hypertrophic cardiomyopathy (HCM) population. Background: TDI is a more sensitive technique for the assessment of left ventricular contraction and relaxation abnormalities than is conventional echocardiography. Methods: Echocardiographic studies including TDI were performed in genotyped hypertrophic cardiomyopathy patients (genotype-positive, G+/LVH+; n = 27), mutation carriers without LVH (G+/LVH-; n = 27), and healthy controls (n = 55). The identified mutations in MYBPC3 in the G+/LVH+ subjects were c.2864_2865delCT (12 subjects), c.2373dupG (n = 8), and p. Arg943X (n = 7). In the G+/LVH- subjects, the following mutations were identified: c.2864_2865delCT (n = 11), c.2373dupG (n = 8), and p. Arg943X (n = 8). Results: Mean TDI-derived systolic and early and late diastolic mitral annular velocities were significantly lower in the G+/LVH+ subjects compared with the other groups. However, there was no difference between controls and G+/LVH- subjects. Mean TDI-derived late mitral annular diastolic velocities were significantly higher in the G+/LVH- subjects compared with controls and G+/LVH+ subjects. Using a cut-off value of mean ± 2 SD, an abnormal late mitral annular diastolic velocity was found in 14 (51%) of G+/LVH- patients. There was no difference among the 3 different mutations. Conclusions: In contrast to earlier reports, mean mitral annular systolic velocity and early mitral annular diastolic velocity velocities were not reduced in G+/LVH- subjects, and TDI velocities were not sufficiently sensitive for determination of the affected status of an individual subject. Our findings, however, support the theory that diastolic dysfunction is a primary component of pre-clinical HCM.

Cardiac amyloidosis mimicking fabry's disease in cardiac magnetic resonance imaging (Article)

2008-11-01T00:00:00Z

Sustained improvement after combined anterior mitral leaflet extension and myectomy in hypertrophic obstructive cardiomyopathy. (Article)

2003-10-28T00:00:00Z

BACKGROUND: Mitral leaflet extension (MLE) combined with septal myectomy is a new surgical approach to treat hypertrophic obstructive cardiomyopathy (HOCM) and an enlarged mitral leaflet area. The study presents the long-term clinical results and outcome of this technique. METHODS AND RESULTS: MLE entails grafting a glutaraldehyde-preserved autologous pericardial patch onto the center portion of the anterior mitral valve leaflet. Twenty-nine patients with HOCM were studied. Mean follow-up (+/-SD) was 3.4+/-2.1 years (range 3 months to 7.7 years). The preoperative calculated mitral leaflet area was 16.7+/-3.4 cm2. New York Heart Association functional class improved significantly from 2.8+/-0.4 to 1.3+/-0.4 (P<0.05), width of the interventricular septum decreased from 23+/-4 to 17+/-2 mm (P<0.05), left ventricular outflow tract gradient decreased from 100+/-20 to 17+/-14 mm Hg (P<0.01), severity of mitral regurgitation graded on a scale from 0 to 4+ decreased from 2.5+/-0.9 to 0.5+/-0.6 (P<0.01), and severity of the systolic anterior motion of the mitral valve graded on a scale from 0 to 3+ decreased from 2.9+/-0.3 to 0.5+/-0.7 (P<0.01) postoperatively. There were no deaths associated with surgery. CONCLUSIONS: Long-term follow-up shows sustained improvement in functional status, reduction of outflow tract obstruction, and attenuation of mitral regurgitation and systolic anterior motion of the mitral valve. In this respect, the new technique widens the surgical applications in HOCM.

Angiotensin II type 2 receptors and cardiac hypertrophy in women with hypertrophic cardiomyopathy (Article)

2001-01-01T00:00:00Z

The development of left ventricular hypertrophy in subjects with hypertrophic cardiomyopathy (HCM) is variable, suggesting a role for modifying factors such as angiotensin II. Angiotensin II mediates both trophic and antitrophic effects, via angiotensin II type 1 (AT(1)-R) and angiotensin II type 2 (AT(2)-R) receptors, respectively. Here we investigated the effect of the AT(2)-R gene A/C(3123) polymorphism, located in the 3' untranslated region of exon 3, on left ventricular mass index (LVMI) in 103 genetically independent subjects with HCM (age, 12 to 81 years). LVMI and interventricular septum thickness were determined by 2D echocardiography. Extent of hypertrophy was quantified by a point score (Wigle score). Plasma prorenin, renin, and ACE were determined by immunoradiometric or fluorometric assays, and genotyping was performed by polymerase chain reaction. In men, no associations between AT(2)-R genotype and any of the measured parameters were observed, whereas in women, LVMI decreased with the number of C alleles (211+/-19, 201+/-18, and 152+/-10 g/m(2) in women with the AA, AC, and CC genotype, respectively; P=0.015). Similar C allele-related decreases in women were observed for interventricular septum thickness (P=0.13), Wigle score (P=0.05), plasma renin (P=0.03), and plasma prorenin (P=0.26). Multiple regression analysis revealed that the AT(2)-R C allele-related effect on LVMI (beta=-30.7+/-11.1, P=0.010) occurred independently of plasma renin, the AT(1)-R gene A/C(1166) polymorphism, or the ACE gene I/D polymorphism. In conclusion, AT(2)-Rs modulate cardiac hypertrophy in women with HCM, independently of the circulating renin-angiotensin system. These data support the contention that AT(2)-Rs mediate antitrophic effects in humans.

New perspectives in Hypertrophic Cardiomyopathy (Doctoral Thesis)

1998-10-28T00:00:00Z

Hypertrophic cardiomyopathy is a primary cardiac disorder with a heterogeneous expression. Although relatively uncommon, the disease has been studied extensively as appears from the numerous studies that have explored specific facets of hypertrophic cardiomyopathy. This review will focus on the anatomic abnormalities, the prevalence, symptoms and clinical outcome, therapeutic interventions and genetic mutations responsible for the disease.

Decreased coronary flow reserve in hypertrophic cardiomyopathy is related to remodeling of the coronary microcirculation. (Article)

1998-01-01T00:00:00Z

Background—Ischemia occurs frequently in hypertrophic cardiomyopathy (HCM) without evidence of epicardial stenosis. This study evaluates the hypothesis that the occurrence of ischemia in HCM is related to remodeling of the coronary microcirculation. Methods and Results—End-diastolic septal wall thickness was significantly increased in patients with HCM (25.8±2.9 mm) in comparison with cardiac transplant recipients (control subjects: 11.4±3.0 mm; P<0.05). Although the diameter of the left anterior descending coronary artery was similar in both groups (3.0±0.8 versus 3.0±0.5 mm, P=NS), the coronary resistance reserve (CRR=CRRbasal/CRRhyperemic), corrected for extravascular compression (end-diastolic left ventricular pressure), was reduced to 1.5±0.6 in HCM (P<.05; control, 2.6±0.8). Arteriolar lumen (AL) divided by wall area was lower in HCM (21±5% versus 30±4%; P<.05), and capillary density tended to decrease (from 1824±424 to 1445±513 per mm2, P=.11) in HCM. CRR was linearly related to normalized AL according to the formula CRR=0.1 AL-0.45 (r=.57; P<.05). Further analysis revealed that CRR, AL, and capillary density were all linearly related to the degree of hypertrophy. Conclusions—Decrements in CRR were related to changes of the coronary microcirculation. Both the decrease in CRR and these changes in the coronary microcirculation were related to the degree of hypertrophy. All these factors might contribute to the well-known occurrence of ischemia in this patient group.

Decreased coronary flow reserve in hypertrophic cardiomyopathy is related to remodeling of the coronary microcirculation (Article)

1998-01-01T00:00:00Z

BACKGROUND: Ischemia occurs frequently in hypertrophic cardiomyopathy (HCM) without evidence of epicardial stenosis. This study evaluates the hypothesis that the occurrence of ischemia in HCM is related to remodeling of the coronary microcirculation. METHODS AND RESULTS: End-diastolic septal wall thickness was significantly increased in patients with HCM (25.8+/-2.9 mm) in comparison with cardiac transplant recipients (control subjects: 11.4+/-3.0 mm; P<0.05). Although the diameter of the left anterior descending coronary artery was similar in both groups (3.0+/-0.8 versus 3.0+/-0.5 mm, P=NS), the coronary resistance reserve (CRR=CRRbasal/CRRhyperemic), corrected for extravascular compression (end-diastolic left ventricular pressure), was reduced to 1.5+/-0.6 in HCM (P<.05; control, 2.6+/-0.8). Arteriolar lumen (AL) divided by wall area was lower in HCM (21+/-5% versus 30+/-4%; P<.05), and capillary density tended to decrease (from 1824+/-424 to 1445+/-513 per mm2, P=.11) in HCM. CRR was linearly related to normalized AL according to the formula CRR=O.1 AL-0.45 (r=.57; P<.05). Further analysis revealed that CRR, AL, and capillary density were all linearly related to the degree of hypertrophy. CONCLUSIONS: Decrements in CRR were related to changes of the coronary microcirculation. Both the decrease in CRR and these changes in the coronary microcirculation were related to the degree of hypertrophy. All these factors might contribute to the well-known occurrence of ischemia in this patient group.

AT1 receptor A/C1166 polymorphism contributes to cardiac hypertrophy in subjects with hypertrophic cardiomyopathy (Article)

1998-01-01T00:00:00Z

The development of left ventricular hypertrophy (LVH) in subjects with hypertrophic cardiomyopathy (HCM) is variable, suggesting a role for modifying factors such as angiotensin II. We investigated whether the angiotensin II type 1 receptor (AT1-R) A/C1166 polymorphism, the angiotensin-converting enzyme (ACE) insertion/deletion (I/D) polymorphism, and/or plasma renin influence LVH in HCM. Left ventricular mass index (LVMI) and interventricular septal thickness were determined by 2-dimensional echocardiography in 104 genetically independent subjects with HCM. Extent of hypertrophy was quantified by a point score (Wigle score). Plasma prorenin, renin, and ACE were measured by immunoradiometric or fluorometric assays, and ACE and AT1-R genotyping were performed by polymerase chain reactions. The ACE D allele did not affect any of the measured parameters except plasma ACE (P<0.04). LVMI was higher (P<0.05) in patients carrying the AT1-R C allele (190+/-8.3 g/m2) than in AA homozygotes (168+/-7.2 g/m2), and similar patterns were observed for interventricular septal thickness (23.0+/-0.7 versus 21. 6+/-0.7 mm) and Wigle score (7.0+/-0.3 versus 6.3+/-0.3). Plasma renin was higher (P=0.05) in carriers of the C allele than in AA homozygotes. Multivariate regression analysis, however, revealed no independent role for renin in the prediction of LVMI. Plasma prorenin and ACE were not affected by the AT1-R A/C1166 polymorphism, nor did the ACE and AT1-R polymorphisms interact with regard to any of the measured parameters. We conclude that the AT1-R C1166 allele modulates the phenotypic expression of hypertrophy in HCM, independently of plasma renin and the ACE I/D polymorphism.

Late Lumen Loss After Coronary Angioplasty Is Associated With the Activation Status of Circulating Phagocytes Before Treatment (Article)

1995-01-01T00:00:00Z

Background The purpose of this pilot study was to identify biological risk factors for restenosis after percutaneous transluminal coronary angioplasty (PTCA) to predict the long-term outcome of PTCA before treatment. Methods and Results To investigate whether blood granulocytes and monocytes could determine luminal renarrowing after PTCA, several characteristics of these phagocytes were assessed before angioplasty in 32 patients who underwent PTCA of one coronary artery and who had repeat angiograms at 6-month follow-up. The plasma levels of interleukin (IL)-1ß, tumor necrosis factor-, IL-6, fibrinogen, C-reactive protein, and lipoprotein(a) before angioplasty were assessed as well. We found that the expression of the membrane antigens CD64, CD66, and CD67 by granulocytes was inversely associated with the luminal renarrowing normalized for vessel size (relative loss) at 6 months after PTCA, while the production of IL-1ß by stimulated monocytes was positively associated with the relative loss. Next, these univariate predictors were corrected for the established clinical risk factors of dilation of the left anterior descending coronary artery and current smoking, which were statistically significant classic predictors in our patient group. Only the expression of CD67 did not predict late lumen loss independent of these established clinical risk factors. Multiple linear regression analysis showed that luminal renarrowing could be predicted reliably (R2=.65; P<.0001) in this patient group on the basis of the vessel dilated and only two biological risk factors that reflect the activation status of blood phagocytes, ie, the expression of CD66 by granulocytes and the production of IL-1ß by stimulated monocytes. Conclusions The results of the present study indicate that activated blood granulocytes prevent luminal renarrowing after PTCA, while activated blood monocytes promote late lumen loss. To validate this new finding, further study in an independent patient group is required.