Incidence of cervical intraepithelial neoplasia in Estonia.

OBJECTIVE: This study aimed to assess the incidence of cervical intraepithelial neoplasia (CIN) by grade (CIN 1, CIN 2, CIN 3) and age in Estonia (a country with less developed cervical cancer screening program and high cervical cancer incidence). MATERIALS AND METHODS: This descriptive study uses data from a health insurance fund covering the whole country to estimate the incidence of CIN by grade. CIN case definition was based on specific diagnostic procedures (biopsy, pathological diagnosis, and colposcopy) and/or treatment procedures (excision, local destructive therapy, conization, and hysterectomy) with the CIN-specific diagnosis code (International Statistical Classification of Diseases, 10 Revision) reported on health care claims. Age-specific incidence rates were calculated together with the 95% CIs. Main outcome measure includes CIN grade-specific incidence rate per 1,000 women. RESULTS: The estimates for CIN incidence per 1,000 women range from 0.68 to 2.83 for CIN 1, 0.63 to 1.24 for CIN 2, and 0.13 to 0.53 for CIN 3 for narrow (biopsy/pathological diagnosis based) and broad (any CIN-specific diagnostic procedure/treatment based) case definition criteria, respectively. CONCLUSIONS: Our estimates for cervical dysplasia disease frequency and age distribution are in line with those from other developed countries. Administrative health care resources (such as health insurance fund data) are a valuable source for health research.

Benefit of atrial septal defect closure in adults: impact of age.

AIMS: To evaluate the effect of age on the clinical benefit of atrial septal defect (ASD) closure in adults. METHODS AND RESULTS: Functional status, the presence of arrhythmias, right ventricular (RV) remodelling, and pulmonary artery pressure (PAP) were studied in 236 consecutive patients undergoing transcatheter ASD closure [164 females, mean age of 49 ± 18 years, 78 younger than 40 years (Group A), 84 between 40 and 60 years (Group B) and 74 older than 60 years (Group C)]. Defect size [median 22 mm (inter-quartile range, 19, 26 mm)] and shunt ratio [Qp:Qs 2.2 (1.7, 2.9)] did not differ among age groups. Older patients had, however, more advanced symptoms and both, PAP (r = 0.65, P < 0.0001) and RV size (r = 0.28, P < 0.0001), were significantly related to age. Post-interventionally, RV size decreased from 41 ± 7, 43 ± 7, and 45 ± 6 mm to 32 ± 5, 34 ± 5, and 37 ± 5 mm for Groups A, B, and C, respectively (P < 0.0001), and PAP decreased from 31 ± 7, 37 ± 10, and 53 ± 17 mmHg to 26 ± 5, 30 ± 6, and 43 ± 14 mmHg (P < 0.0001), respectively. Absolute changes in RV size (P = 0.80) and PAP (P = 0.24) did not significantly differ among groups. Symptoms were present in 13, 49, and 83% of the patients before and in 3, 11, and 34% after intervention in Groups A, B, and C. Functional status was related to PAP. CONCLUSIONS: At any age, ASD closure is followed by symptomatic improvement and regression of PAP and RV size. However, the best outcome is achieved in patients with less functional impairment and less elevated PAP. Considering the continuous increase in symptoms, RV remodelling, and PAP with age, ASD closure must be recommended irrespective of symptoms early after diagnosis even in adults of advanced age.

Prognostic value of serial B-type natriuretic peptide measurement in asymptomatic organic mitral regurgitation.

AIMS: Optimal timing of surgery is crucial in mitral regurgitation (MR) to avoid excess mortality and morbidity. The role of brain-type natriuretic peptide (BNP) in this setting remains controversial. We evaluated the value of serial BNP measurements for early prediction of deterioration in asymptomatic MR. METHODS AND RESULTS: Eighty-seven consecutive asymptomatic patients with severe organic MR, normal left ventricular (LV) function (ejection fraction ≥ 60%, end-systolic diameter index < 26 mm/m²), systolic pulmonary artery pressure (sPAP) <50 mmHg, and no atrial fibrillation underwent clinical assessment, echocardiography, and measurement of BNP and N-terminal pro-BNP (NT-proBNP) at 6-month intervals. The primary endpoint was the development of symptoms and/or LV dysfunction. The secondary endpoint was the occurrence of atrial fibrillation or sPAP ≥ 50 mmHg. Over a mean follow-up of 786 ± 454 days, 20 patients reached the primary endpoint and 5, the secondary endpoint. By univariate analysis, age, BNP, NT-proBNP, and sPAP were significant predictors of reaching the primary endpoint during the 6 months following testing, whereas LV function and dimensions were not. By multivariate analysis, only BNP (P = 0.03) and sPAP (P = 0.04) remained independent predictors. When secondary endpoints were additionally considered, results remained unchanged. Receiver operator curve analysis yielded AUC-values of 0.90, 0.84, and 0.80 for BNP, NT-proBNP, and sPAP, but 0.60 and 0.57 for left ventricular ejection fraction and end-systolic diameter. The negative predictive value for normal neurohormone levels and sPAP was high (98-100%). A BNP of 145 pg/mL had a positive predictive value of 36%. CONCLUSION: Brain natriuretic peptide and NT-proBNP independently predict outcome in asymptomatic MR. Serial measurements may help to improve timing of surgery. Low plasma levels with their high negative predictive values appear to be particularly helpful by identifying low-risk individuals.

Gender differences in clinical presentation and surgical outcome of aortic stenosis.

BACKGROUND: Little is known about the gender differences of patients undergoing aortic valve replacement (AVR) for isolated severe aortic stenosis. METHODS AND RESULTS: 408 consecutive patients (215 women and 193 men; p=0.9) were analysed. At presentation, women were older (73.7+/-9.3 years vs men 66.5+/-11.5 years; p<0.001), more symptomatic (New York Heart Association (NYHA) class: women 2.3+/-0.7 vs men 2.0+/-0.65; p<0.001), and presented with smaller valve areas (women 0.6+/-0.2 cm(2) vs men 0.7+/-0.2 cm(2); p<0.001) and higher mean pressure gradients (women 67.3+/-19.2 mm Hg vs men 62.2+/-20.0 mm Hg, p=0.001). Despite older age and more advanced disease in women, operative mortality did not differ. Survival after AVR by Kaplan-Meier analysis tended to be even better in women (92.8%, 89.8%, 81.4% vs men 89.1%, 86.6%, 76.3% at 1, 2 and 5 years, p=0.31). After division into age quintiles, the outcome of women was significantly better in patients older than 79 years (p=0.005). After adjustment for clinical characteristics, gender did not predict operative mortality and late outcome. Despite physical improvement in both groups after surgery, women remained more symptomatic (NYHA class: women 1.6+/-0.7 vs men 1.3+/-0.4; p=0.001). CONCLUSION: Although women referred to AVR are older and more symptomatic, operative and long-term mortality are not increased. In the oldest age group of 79 years and older, women even have a better outcome, presumably due to a longer mean life expectancy.

Heterogeneity of traumatic injury of the tricuspid valve: a report of four cases.

Tricuspid valve injury causing severe tricuspid regurgitation is the most common cardiac complication following blunt chest trauma. We present four cases with different clinical presentations that included pleural effusion, arrhythmias, cyanosis, peripheral edema and dyspnea, with varying onset of symptoms. Echocardiographic evaluation and intraoperative findings in these patients revealed a broad spectrum of injury to the tricuspid valve including papillary muscle and chordal rupture, chordal elongation and leaflet perforation. Because surgical treatment is required in most patients and since the diagnosis is often delayed, we believe that early echocardiographic evaluation is required in all patients with blunt chest trauma, in particular if clinical symptoms of right heart failure are present.

Diastolic function assessment in clinical practice: the value of 2-dimensional echocardiography.

BACKGROUND: The aim of this study was to test the hypothesis that diastolic dysfunction associated with increased filling pressures is unlikely in a structurally normal heart and to assess whether 2-dimensional echocardiography can facilitate diastolic function grading in a clinical setting. METHODS: Consecutive patients referred for transthoracic echocardiography received a comprehensive Doppler echocardiographic evaluation of diastolic function and measurements of left ventricular ejection fraction (EF) by biplane Simpson's method, left atrial volume index (LAVI) by area-length method, and interventricular septal thickness (IVS) from 2-dimensional images. Patients with atrial fibrillation, cardiac pacemaker, severe mitral regurgitation, or mitral prosthesis were excluded. RESULTS: Of 187 patients, 38 had normal diastolic function and 77 had grade I; 54, grade II; and 18, grade III diastolic dysfunction. The presence of any 2-dimensional abnormality (EF < 55%, IVS > or = 14 mm, LAVI > or = 40 mL/m2) identified any diastolic dysfunction (grade I-III) with 92.6% sensitivity and 92.1% specificity. In a receiver operating characteristic analysis to predict any diastolic dysfunction, the areas under the receiver operating characteristic curve for EF, IVS, and LAVI and the sum of all 3 abnormalities were 0.69, 0.81, 0.87, and 0.95 (all P < .0001), respectively. Among all patients with at least one abnormality, the probability of diastolic dysfunction was 97.9% (138/141). Interpretation of 2-dimensional abnormalities together with the mitral inflow pattern resulted in correct diastolic function grading in 98.4% (184/187). CONCLUSIONS: Structural abnormalities on 2-dimensional echocardiography are not only statistically associated with diastolic dysfunction, but the combination of LAVI, EF, and IVS is of practical value for diastolic function grading. The presence of any such 2-dimensional abnormality should be considered indicative of diastolic dysfunction.

Outcome of watchful waiting in asymptomatic severe mitral regurgitation.

BACKGROUND: The management of asymptomatic severe mitral regurgitation remains controversial. The aim of this study was to evaluate the outcome of a watchful waiting strategy in which patients are referred to surgery when symptoms occur or when asymptomatic patients develop left ventricular (LV) enlargement, LV dysfunction, pulmonary hypertension, or recurrent atrial fibrillation. METHODS AND RESULTS: A total of 132 consecutive asymptomatic patients (age 55+/-15 years, 49 female) with severe degenerative mitral regurgitation (flail leaflet or valve prolapse) were prospectively followed up for 62+/-26 months. Patients underwent serial clinical and echocardiographic examinations and were referred for surgery when the criteria mentioned above were fulfilled. Overall survival was not statistically different from expected survival either in the total group or in the subgroup of patients with flail leaflet. Eight deaths were observed. Thirty-eight patients developed criteria for surgery (symptoms, 24; LV criteria, 9; pulmonary hypertension or atrial fibrillation, 5). Survival free of any indication for surgery was 92+/-2% at 2 years, 78+/-4% at 4 years, 65+/-5% at 6 years, and 55+/-6% at 8 years. Patients with flail leaflet tended to develop criteria for surgery slightly but not significantly earlier. There was no operative mortality. Postoperative outcome was good with regard to survival, symptomatic status, and postoperative LV function. CONCLUSIONS: Asymptomatic patients with severe degenerative mitral regurgitation can be safely followed up until either symptoms occur or currently recommended cutoff values for LV size, LV function, or pulmonary hypertension are reached. This management strategy is associated with good perioperative and postoperative outcome but requires careful follow-up.

Big endothelin-1 is not a predictor in aortic stenosis, but is related to arterial blood pressure.

BACKGROUND: In aortic stenosis, natriuretic peptides have recently been shown to correlate with ventricular function and to predict symptom-free survival and outcome. Elevated big endothelin-1 (bigET) is associated with poor prognosis in chronic heart failure, but little is known about its role in severe aortic stenosis. METHODS: In 61 patients with aortic stenosis (71+/-10 years, mean gradient 65+/-20 mm Hg, valve area 0.63+/-0.15 cm2), plasma bigET was determined by radioimmunoassay and related to echocardiographic parameters, symptoms and survival. Patients were followed for 1 year. RESULTS: BigET (mean 2.3+/-1.5, range 0.1-7.5 fmol/ml) was elevated > or = 1.9 fmol/ml in 54% of patients, but was not correlated to the transvalvular gradients or valve area. BigET did not differ significantly between 14 asymptomatic (2.4+/-1.0 fmol/ml) and 47 symptomatic patients (2.3+/-1.6 fmol/ml), although the highest levels were observed in 5 patients in NYHA class III-IV (4.2+/-2.2 fmol/ml, p=0.035). No significant difference in bigET was observed between 51 survivors and 10 patients who died during follow-up (2.2+/-1.4 vs 2.7+/-1.6 fmol/ml). BigET did not differ between 7 asymptomatic patients developing symptoms and those remaining asymptomatic during follow-up. BigET was significantly related to the systolic blood pressure and left ventricular systolic pressure (r=0.389, p=0.0025 and r=0.401, p=0.0018, respectively), but not to the diastolic blood pressure or interventricular septal wall thickness. BigET was inversely related to the left ventricular ejection fraction (r=0.327, p=0.01) and fractional shortening (r=0.391, p=0.044). CONCLUSION: Although frequently elevated, bigET-1 is not a useful predictor of symptoms or outcome in patients with severe aortic stenosis. BigET increases inversely with left ventricular function and directly with systolic left ventricular and blood pressure, but is not related to transvalvular gradients or valve area.

Statins but not angiotensin-converting enzyme inhibitors delay progression of aortic stenosis.

BACKGROUND: Recently, statins and angiotensin-converting enzyme inhibitors (ACEIs) have been shown to slow aortic valve calcium accumulation. Although several studies also suggest that statins may reduce the hemodynamic progression of aortic stenosis (AS), no data are available for ACEIs or the combination of both. METHODS AND RESULTS: A total of 211 consecutive patients (aged 70+/-10 years, 104 females) with native AS, defined by a peak velocity >2.5 m/s (valve area 0.84+/-0.23 cm(2), mean gradient 42+/-19 mm Hg), with normal left ventricular function and no other significant valvular lesion who were examined between 2000 and 2002 and who had 2 echocardiograms separated by at least 6 months were included. Of these, 102 patients were treated with ACEIs, 50 patients received statins, and 32 patients received both. Hemodynamic progression of AS was assessed and related to medical treatment. Annualized increase in peak aortic jet velocity for the entire study group was 0.32+/-0.44 m x s(-1) x y(-1). Progression was significantly lower in patients treated with statins (0.10+/-0.41 m x s(-1) x y(-1)) than in those who were not (0.39+/-0.42 m x s(-1) x y(-1); P<0.0001). This effect was observed both in mild-to-moderate and severe AS. ACEI use, however, did not significantly affect hemodynamic progression (P=0.29). Furthermore, ACEIs had no additional effect on AS progression when given in combination with statins (0.11+/-0.42 versus 0.08+/-0.43 m x s(-1) x y(-1) for combination versus statin only; P=0.81). Cholesterol levels did not correlate with hemodynamic progression either in the group receiving statins or in the group that did not. CONCLUSIONS: ACEIs do not appear to slow AS progression. However, statins significantly reduce the hemodynamic progression of both mild-to-moderate and severe AS, an effect that may not be related to cholesterol lowering.

Ferrous iron administration during pregnancy and adaptational oxidative stress (Pilot study).

UNLABELLED: The purpose of this investigation was to measure the effect of ferrous iron therapy on indices of oxidative stress in pregnant women. MATERIAL AND METHODS: Nineteen healthy pregnant women with borderline anemia were subjected to per oral ferrous iron in prophylactic doses (36 mg daily, +Fe group, n=13) or did not get any treatment (-Fe group, n=6). The indices measured in two time-points were: conjugated dienes, lag phase of low-density lipoproteins, total antioxidant activity of the serum, total glutathione and its fractions, protein carbonyls, catalase, ferritin, serum iron and unsaturated iron binding capacity. RESULTS: All women had high values of conjugated dienes, total antioxidant activity and short lag phases of low-density lipoproteins in both time points. Elevated values of oxidized glutathione in both groups increased about 2-fold and reached a significant difference level (p=0.02) by the end of the test period. CONCLUSION: Low doses of per oral ferrous iron did not change deleteriously the physiological pattern of parameters of oxidative stress in our small group of healthy pregnant non-smokers but the elevation of oxidized glutathione might imply on the elevation of risk.

Natriuretic peptides predict symptom-free survival and postoperative outcome in severe aortic stenosis.

BACKGROUND: The prognostic value of natriuretic peptides in aortic stenosis (AS) remains unknown. METHODS AND RESULTS: B-type natriuretic peptide (BNP), N-terminal BNP (NtBNP), and N-terminal atrial natriuretic peptide (NtANP) were determined in 130 patients with severe AS (mean age, 70+/-12 years; mean gradient, 64+/-21 mm Hg; valve area, 0.64+/-0.15 cm2) who were followed up for 377+/-150 days. Natriuretic peptides increased with NYHA class and with decreasing ejection fraction (EF). Even asymptomatic patients frequently had elevated neurohormones. Asymptomatic patients who developed symptoms during follow-up had higher BNP and NtBNP levels at entry compared with those remaining asymptomatic (median for NtBNP, 131 pmol/L [interquartile range, 50 to 202 pmol/L] versus 31 pmol/L [range, 19 to 56 pmol/L]; P<0.001). Symptom-free survival at 3, 6, 9, and 12 months for patients with NtBNP <80 versus > or =80 pmol/L was 100%, 88+/-7%, 88+/-7%, and 69+/-13% compared with 92+/-8%, 58+/-14%, 35+/-15%, and 18+/-15%, respectively (P<0.001). Seventy-nine patients eventually underwent surgery because of symptoms. Considering preoperative neurohormone levels, age, NYHA class, aortic valve area, EF, and presence of coronary artery disease, we found that neurohormones, EF, and NYHA class predicted survival; neurohormones predicted postoperative symptomatic status; and neurohormones and preoperative EF predicted postoperative EF. However, by multivariate analysis, NtBNP was the only independent predictor of outcome. CONCLUSIONS: In severe AS, natriuretic peptides provide important prognostic information beyond clinical and echocardiographic evaluation. NtBNP independently predicts symptom-free survival, and preoperative NtBNP independently predicts postoperative outcome with regard to survival, symptomatic status, and left ventricular function. Thus, neurohormones may gain particular importance for timing of surgery in asymptomatic severe AS.

Mild and moderate aortic stenosis. Natural history and risk stratification by echocardiography.

AIMS: To define the natural history and predictors of outcome in mild and moderate aortic stenosis (AS). METHODS AND RESULTS: One hundred and seventy-six consecutive asymptomatic patients (73 women, age 58+/-19 years) with mild to moderate AS (jet velocity 2.5 to 3.9m/s) were followed for 48+/-19 months. Haemodynamic progression and clinical outcome was analysed. Event-free survival with end-points defined as death (n=34) or aortic valve surgery (n=33), was 95+/-2%, 75+/-3% and 60+/-5% at 1, 3 and 5 years, respectively. Both, cardiac and non-cardiac mortality were significantly increased, resulting in a 1.8 times higher mortality than expected (P<0.005). By multivariate analysis, moderate to severe aortic valve calcification, coronary artery disease (CAD) and peak jet velocity were independent predictors of outcome. Event-free survival for patients with moderate or severe valve calcification was 92+/-4%, 61+/-7% and 42+/-7% at 1, 3 and 5 years versus 100%, 90+/-4% and 82+/-5% for patients with no or mild calcification. Patients with calcified aortic valves, CAD or with an event had a significantly faster haemodynamic progression. Of 129 patients with a follow-up echocardiographic exam, 59 (46%) developed severe stenosis during follow-up. CONCLUSION: Outcome of mild and moderate AS is worse than commonly assumed. Rapid progression and excess mortality have to be considered. Significant valve calcification, CAD and rapid progression of aortic jet velocity indicate poor outcome. Patients with these characteristics may require closer follow-up than generally assumed.

Relationship between dobutamine response of dyssynergic myocardium and angiographically documented blood supply.

OBJECTIVE: Because hibernation is considered a down-regulation of contractile function in response to reduced regional myocardial perfusion, hibernating myocardium is expected to be supplied by a critically stenosed or even occluded coronary artery. Thus, high-dose dobutamine has been postulated to cause ischemia and reworsening of myocardial function (biphasic response), whereas myocardium that demonstrates sustained improvement with high-dose dobutamine should not be supplied by a significantly stenosed vessel. This study evaluates the type of dobutamine response-biphasic versus sustained improvement-of dyssynergic myocardium in relation to its angiographically documented blood supply. METHODS: In 38 patients (5 women; mean age 60 +/- 9 years) with chronic coronary artery disease and impaired left ventricular ejection fraction (

Elimination of errors caused by first-order aliasing in velocity encoded cine-MR measurements of postoperative jets after aortic coarctation: in vitro and in vivo validation.

The aim of this study was to evaluate a velocity-encoded cine-MR (VEC-MR) sequence in measuring flow velocities up to two times the velocity encoding value (VENC) in a flow phantom and to validate the method for assessing poststenotic jet velocities in postoperative patients after aortic coarctation. In vitro, a flow phantom was used (0.5T; TR/TE: 51/8 ms, flip angle=30 degrees, FOV=280 mm, 128x256 matrix VENC 40 or 80 cm/s). On binary images, maximum flow velocities (V(max)) were calculated with a region of interest (ROI, 8 pixels). With aliasing, V(max) was calculated by VENC+(V(aliasing)). In vivo, 16 postoperative patients after aortic coarctation underwent double-oblique VEC-MR imaging through the aortic arch (ECG triggering, 16 phases/RR, TR=600-800 ms, flow-encoding cranio-caudal, VENC=2 m/s). Peak systolic velocities were measured and transthoracic Doppler echocardiography (TTDE) was performed. In vitro, there were excellent correlations for MR velocity measurements with and without aliasing ( r=0.99) and for true and MR-derived flow velocities ( r=0.99). In vivo, there was good correlation between VEC-MR and TTDE-assessed V(max) values in the aorta at the former coarctation site ( r=0.90, n=16). Aliasing occurred in 13 patients. VEC-MR is a useful modality for assessing jet velocities in the follow-up of patients after aortic coarctation. Despite of aliasing, accurate velocity measurements up to two times VENC are possible using binary images.