Monitoring calcific aortic valve disease: the role of biomarkers.

Calcific aortic valve disease is a common disease in the elderly associated with significant morbidity and mortality. It was once described as a passive degenerative process during which serum calcium attaches to the valve surface and binds to the leaflet. However, during the last decade mounting evidence demonstrated that this disease has an active biologic process with numerous signaling pathways. The histological hallmarks seem to be inflammation, oxidized lipids-also detectable in aortic valve lesions-and a remodeling of the extracellular matrix leading to bone formation. Over the years, growing evidence has indicated the risk factors for calcific aortic stenosis including lipids, hypertension, male gender, renal failure, and diabetes. Additional monitoring tools, such as molecular imaging, could improve risk stratification, while assessment of severity and prognosis of patients with chronic aortic regurgitation, is desirable. Also, several studies have investigated the role of biomarkers regarding their utility in the screening of calcific aortic valve disease and their putative clinical value, though their role still remains undetermined.

Biomarkers determining cardiovascular risk in patients with kidney disease.

Cardiovascular disease (CVD) remains the leading cause of premature death in patients with chronic kidney disease (CKD). Recent evidence suggests that the interaction of "classic" and "non-classic" cardiovascular risk factors is an important contributor in excessive and accelerated CVD in patients with CKD. Indeed, the imposing cardiovascular morbidity and mortality of CKD patients corresponds to a significant extent in endothelial dysfunction, inflammation, oxidative stress, vascular calcification and volume overload. In addition, the kidney's function decline is independently associated with CVD in patients with chronic kidney disease. Currently, there is a growing interest in the role of new biomarkers that are closely correlated with CVD in CKD population. In current review, we summarize the so far acquired knowledge of the most promising biomarkers and we discuss the major clinical correlations of novel risk factors and new biomarkers of CVD in CKD patients, their predictive value for future cardiovascular events and their use in the treatment monitoring of this population.

Prognostic clinical and angiographic characteristics for the development of a new significant lesion in remote segments after successful percutaneous coronary intervention.

BACKGROUND: The majority of cardiovascular events in patients undergoing PCI arise from the progression of NCL during the long-term follow-up period. The purpose of the study was to investigate the clinical and angiographic factors related to the progression of non-culprit lesions (NCL) of patients undergoing percutaneous coronary interventions (PCI). METHODS: One hundred and seventeen patients that underwent two coronary angiograms with a time interval greater than 3 months were enrolled. All patients underwent PCI as a treatment for the culprit lesion. In the second coronary angiography we investigated whether they had a new culprit lesion clearly differentiated from the one of the first angiogram. The demographic characteristics, the clinical syndrome responsible for the first PCI and the procedural characteristics were recorded. Quantitative coronary angiography was performed at the culprit lesion of the second angiography and in the same lesion in the first angiography. RESULTS: Multivariate analysis showed that the independent variables for the development of a significant lesion at the follow-up requiring intervention were: the presence of complex lesion (53.78% vs 36.22%, p<0.001, OR=39.42), acute myocardial infarction (AMI) at the initial diagnosis (36.3% vs 32.4%, p<0.001, OR=3.9), and smoking (46.15% vs 53.84%, p=0.03, OR=0.29). CONCLUSIONS: Patients with AMI and complex morphology of NCL have increased risk for a new intervention after successful PCI. Smoking at the time of the follow up, was associated with fewer coronary interventions.

Impact of type 2 diabetes mellitus on diffuse inflammatory activation of de novo atheromatous lesions: implications for systemic inflammation.

AIMS: Local coronary and systemic inflammation is pronounced in patients with diabetes mellitus (DM). Intracoronary thermography detects local inflammation and C-reactive protein (CRP) is a marker of systemic inflammation. We investigated whether or not, in patients with DM, thermal heterogeneity of culprit lesions (CLs) correlates with that of non-culprit lesions (NCLs) and with systemic inflammation. METHODS: We included DM patients who had two angiographically significant lesions and were undergoing percutaneous coronary intervention. We measured the temperature difference (DeltaT) between the lesion and proximal vessel wall. RESULTS: We included 104 (n=208 lesions) patients: 32 (n=64 lesions) had DM and 72 (n=144 lesions) were non-DM (control group). DeltaT was increased in DM in both CLs and NCLs (CLs: DM=0.12+/-0.06 degrees C; no DM=0.06+/-0.04 degrees C; P<0.01 versus NCLs: DM=0.13+/-0.08 degrees C versus no DM=0.06+/-0.05 degrees C; P<0.01). Patients with DM had similar DeltaT in CLs and NCLs (P=0.49). A linear correlation was detected between heat production in all lesions and CRP (R=0.45; P<0.01), which was attributed to the correlation of DeltaT in lesions of patients with DM and CRP (R=0.32; P<0.01). In lesions of patients with low CRP, a greater rate of discrepancy was found, as 100% of lesions in patients with DM versus 66.1% of lesions of patients without DM had a high DeltaT in one or both lesions (P<0.01). CONCLUSION: In patients with DM, local inflammatory activation is diffuse and correlates with systemic inflammation. However, low systemic inflammatory activation does not always predict an increase in local thermal heterogeneity.

Left atrial appendage exclusion system for stroke prevention in atrial fibrillation: a percutaneous device delivery approach.

Atrial fibrillation (AF) is a well-known predisposing factor for stroke. Most of the thrombi responsible for these ischemic events originate in the left atrial appendage. Left atrium appendage (LAA) occlusion is a potential alternative to warfarin in patients with atrial fibrillation who have contraindications to anticoagulation. The Percutaneous LAA Transcatheter Occlusion (PLAATO System, ev3 Inc., Plymouth, Minnesota) and the WATCHMAN LAA system (Atritech Inc., Plymouth, Minnesota), are currently the two devices specifically designed for LAA occlusion. Although available data are still limited, LAA occlusion is technically feasible, with good intermediate results, but its long-term safety and ability to reduce stroke incidence remains unproven. Randomized studies will clarify the usefulness of the LAA occlusion devices as an alternative treatment strategy to long-term anticoagulation.

CLimate Impacts on Myocardial infarction deaths in the Athens TErritory: the CLIMATE study.

OBJECTIVE: To evaluate the impact of meteorological variables on daily and monthly deaths caused by acute myocardial infarction (AMI). METHODS: All death certificate data from the Athens territory were analysed for AMI deaths in 2001. Daily atmospheric temperature, pressure and relative humidity data were obtained from the National Meteorological Society for Athens for the same year. RESULTS: The total annual number of deaths caused by AMI was 3126 (1953 men) from a population of 2,664,776 (0.117%). Seasonal variation in deaths was significant, with the average daily AMI deaths in winter being 31.8% higher than in summer (9.89 v 7.35, p < 0.001). Monthly variation was more pronounced for older people (mean daily AMI deaths of people older than 70 years was 3.53 in June and 7.03 in December; p < 0.001) and of only marginal significance for younger people. The best predictor of daily AMI deaths was the average temperature of the previous seven days; the relation between daily AMI deaths and seven-day average temperature (R(2) = 0.109, p < 0.001) was U-shaped. Considering monthly AMI death rates, only mean monthly humidity was independently associated with total deaths from AMI (R(2) = 0.541, p = 0.004). CONCLUSION: Ambient temperature is an important predictor of AMI mortality even in the mild climate of a Mediterranean city like Athens, its effects being predominantly evident in the elderly. Mean monthly humidity is another meteorological factor that appears to affect monthly numbers of AMI deaths. These findings may be useful for healthcare and civil protection planning.

U-shaped relationship between mortality and admission blood pressure in patients with acute stroke.

OBJECTIVE: To evaluate the relationship between systolic blood pressure (SBP) or diastolic blood pressure (DBP) on admission and early or late mortality in patients with acute stroke. DESIGN: Prospective study of hospitalized first-ever stroke patients over 8 years. SETTING: Stroke unit and medical wards in a University hospital. SUBJECTS: A total of 1121 patients admitted within 24 h from stroke onset and followed up for 12 months. MAIN OUTCOME MEASURES: Mortality at 1 and 12 months after stroke in relation to admission SBP and DBP. RESULTS: Early and late mortality in patients with acute ischaemic or haemorrhagic stroke in relation to admission SBP and DBP followed a 'U-curve pattern'. After adjusting for known outcome predictors, the relative risk of 1-month and 1-year mortality associated with a 10-mmHg SBP increase above 130 mmHg (U-point of the curve) increased by 10.2% (95% CI: 4.2-16.6%) and 7.2% (95% CI: 2.2-12.3%), respectively. For every 10 mmHg SBP decrease, below the U-point, the relative risk of 1-month and 1-year mortality rose by 28.2% (95% CI: 8.6-51.3%) and 17.5% (95% CI: 3.1-34.0%), respectively. Low admission SBP-values were associated with heart failure (P < 0.001) and coronary artery disease (P = 0.006), whilst high values were associated with history of hypertension (P < 0.001) and lacunar stroke (P < 0.001). Death due to cerebral oedema was significantly (P = 0.005) more frequent in patients with high admission SBP-values, whereas death due to cardiovascular disease was more frequent (P = 0.004) in patients with low admission SBP-values. CONCLUSION: Acute ischaemic or haemorrhagic stroke patients with high and low admission BP-values have a higher early and late mortality. Coincidence of heart disease is associated with low initial BP-values. Death due to neurological damage from brain oedema is associated with high initial BP-values.

Spatial aspects of ventricular repolarization in postinfarction patients.

QT dispersion has been proposed to reflect the heterogeneity of ventricular repolarization, but a poor reproducibility limits its clinical usefulness. Spatial vectorcardiographic descriptors constitute a novel approach to quantify ventricular repolarization. To test the ability of vectorcardiographic descriptors to discriminate among different subsets of postinfarction patients, 50 consecutively recruited patients with acute MI, 50 patients with history of an old (> 6 months) MI, and 50 healthy controls were evaluated. The maximum and minimum QT and JT intervals and QT and JT dispersion were manually measured from a digitally recorded 12-lead ECG. X, Y, and Z leads were reconstructed from the 12-lead ECG. The amplitude of the maximum spatial T vector (spatial T amplitude), the angle between the maximum spatial QRS and T vectors (spatial QRS-T angle), and the frontal plane QRS-T angle were automatically calculated. The spatial T amplitude and the spatial QRS-T angle did not differ between patients with a recent and those with an old MI (P = 1). QT dispersion was significantly lower in patients with an old MI than in patients with a recent one (P = 0.002). The spatial repolarization descriptors showed better short-term reproducibility than the dispersion indices. In conclusion, the spatial T amplitude and the spatial QRS-T angle are accurate measures of ventricular repolarization that do not differ between patients with recent and those with old MI. The different QT dispersion values observed in this study between the two post-MI groups should be considered cautiously because of the low accuracy of the manual measurements.

The spatial QRS-T angle as a marker of ventricular repolarisation in hypertension.

Ventricular repolarisation abnormalities are important in arrhythmia provocation. The dispersion of repolarisation duration is not the only aspect of repolarisation heterogeneity. Spatial vectorcardiographic descriptors constitute a novel approach to quantify ventricular repolarisation. To test the ability of vectorcardiographic descriptors to discriminate between hypertensives with high or low blood pressure (BP), 110 treated hypertensives (mean age 63.6 +/- 12.1 years) were classified in the high (systolic BP > or = 160 mm Hg or diastolic BP > or = 95 mm Hg) (n = 67), or the low (systolic BP < 160 mm Hg and diastolic BP <95 mm Hg) (n = 43) BP group. The maximum QT, JT, and T peak-T end intervals and the QT, JT, and T peak--T end dispersion were calculated from a digitally recorded 12-lead electrocardiogram (ECG). X, Y, and Z leads were reconstructed from the 12-lead ECG. The amplitude of the maximum spatial T vector (spatial T amplitude), the angle between the maximum spatial QRS and T vectors (spatial QRS-T angle) and the frontal plane QRS-T angle were calculated. The spatial QRS-T angle was higher in patients with high compared to those with low BP (P = 0.025). All conventional ECG markers of the dispersion of ventricular repolarisation duration failed to demonstrate significant differences between hypertensives with high or low BP. In conclusion, the spatial QRS-T angle was significantly increased in those treated hypertensive patients who showed repeatedly high BP values. Hence, we may suggest that the angle between the directions of ventricular depolarisation and repolarisation is a sensitive marker of the repolarisation alterations in systemic hypertension. Journal of Human Hypertension (2001) 15, 63-70

Increased variance of P wave duration on the electrocardiogram distinguishes patients with idiopathic paroxysmal atrial fibrillation.

We hypothesized that the variance of P wave duration (P variance) in the 12-lead ECG could reflect the spatial dispersion of P wave duration due to inhomogeneous and delayed propagation of sinus impulses in the atria, and moreover could present better reproducibility than maximum P wave duration and P wave dispersion that have already been used for the prediction of idiopathic paroxysmal AF. We also tested a semiautomated PC-based method to improve the accuracy and reproducibility of P wave measurements. A 12-lead ECG was obtained from 60 patients with idiopathic paroxysmal AF and from 50 healthy controls. All ECGs were analyzed manually using magnifying lens and calipers, while 20 randomly selected ones were scanned and analyzed on screen using common commercial software. P maximum, P dispersion, and P variance were all significantly higher in patients with paroxysmal AF than in controls. A P maximum value of 110 ms, a P dispersion value of 40 ms, and a P variance value of 120 ms2 separated patients from controls with a sensitivity of 88%, 83%, and 80%, respectively and a specificity of 75%, 85%, and 74%, respectively. The reproducibility of P variance was higher compared to P dispersion and P maximum. Finally, the PC-based method significantly increased accuracy and reproducibility of P wave measurements. Thus, the variance of P wave duration could be a useful ECG marker for the prediction of paroxysmal idiopathic AF and the use of PC-based methods may enhance the accurate measuring of P wave duration on the ECG.

Leukocytoclastic vasculitis: is propranolol implicated?

Drugs frequently cause cutaneous adverse reactions. The suspected agent is sometimes difficult to identify, especially in patients receiving multidrug treatment and with underlying illnesses that may contribute to the clinical picture. In our patient, propranolol-induced leukocytoclastic vasculitis was diagnosed by exclusion.