Myocardial function and effects of biologic therapy in patients with severe psoriasis: a prospective echocardiographic study.

BACKGROUND: Psoriasis is a chronic inflammatory disease and is associated with cardiovascular events. Little is known about subclinical myocardial dysfunction and potential changes in myocardial function during anti-inflammatory treatment in these patients. We prospectively studied left ventricular function in patients with severe psoriasis who initiated biologic therapy. METHODS: Between November 1 2013 and May 31 2014 the study subjects underwent physical, laboratory and comprehensive echocardiographic examination at baseline and after 3 months of treatment. Pearson correlation coefficients and Student's t-test were applied to assess changes in diastolic function (defined as the E/e' ratio) and global longitudinal strain (GLS). RESULTS: Eighteen patients with severe psoriasis treated with biologic therapy with a mean follow-up of 85.6 ± 18.2 days were included. The patients had a baseline psoriasis area and severity index (PASI) of 12.0 ± 4.1 and normal left ventricular ejection fraction [(LVEF) 56.3 ± 3.8%], diastolic dysfunction (E/e' 8.1 ± 2.1) and GLS (-16.8 ± 2.1%). At follow-up, an improvement (baseline vs. follow-up) of PASI (12.0 ± 4.1 vs. 2.7 ± 3.1, P < 0.001), E/e' (8.1 ± 2.1 vs. 6.7 ± 1.9, P ≤ 0.001) and GLS (-16.8 ± 2.1 vs. -18.3 ± 2.3%, P < 0.001) were recorded. No changes were demonstrated in LVEF (56.3 ± 3.8 vs. 56.8 ± 3.3%, P = 0.31), body mass index (30.9 ± 5.7 vs. 31.0 ± 5.8 kg/m(2) , P = 0.90), mean arterial blood pressure (103.1 ± 8.5 vs. 103.7 ± 10.8 mmHg, P = 0.74). Likewise, no changes were seen in total cholesterol, low density lipoprotein cholesterol, high density lipoprotein cholesterol, estimated glomerular filtration rate and glycosylated haemoglobin. CONCLUSION: In patients with severe psoriasis treatment with biologic therapy was associated with improved PASI and amelioration of myocardial dysfunction.

Assessment of coronary artery disease using coronary computed tomography angiography in patients with aortic valve stenosis referred for surgical aortic valve replacement.

BACKGROUND: In patients referred for aortic valve replacement (AVR) a pre-surgical assessment of coronary artery disease is mandatory to determine the possible need for additional coronary artery bypass grafting. The diagnostic accuracy of coronary computed tomography angiography (coronary CTA) was evaluated in patients with aortic valve stenosis referred for surgical AVR. METHODS: Between March 2008 and March 2010 a total of 181 consecutive patients were included. All patients underwent pre-surgical coronary CTA (64- or 320-detector CT scanner) and invasive coronary angiography (ICA). The analyses were performed blinded to each other. RESULTS: The mean ± SD age of the included patients was 71 ± 9 years and 59% were male. The prevalence of significant coronary artery stenosis >70% by ICA was 36%. Average heart rate during coronary CTA was 65 ± 16 b pm. In a patient based analysis 94% of the patients (171/181) were considered fully evaluable. Coronary CTA had a sensitivity of 68%, a specificity of 91%, a positive predictive value of 81%, and a negative predictive value of 83%. Advanced age, obstructive lung disease, NYHA function class III/IV, and high Agatston score were found to be significantly associated with disagreement between ICA and coronary CTA in univariate analysis. CONCLUSION: In patients with aortic valve stenosis referred for surgical AVR the diagnostic accuracy of coronary CTA to identify significant coronary artery disease is moderate. Coronary CTA may be used successfully in a subset of patients with low age, no chronic obstructive lung disease, NYHA function class

Survival after withdrawal of dofetilide in patients with congestive heart failure and a short baseline QTc interval; a follow-up on the Diamond-CHF QT substudy.

BACKGROUND: We have previously observed dofetilide to be associated with improved survival when the pre-treatment baseline QTc interval was below 429 ms. In this study we tested the natural extension of this observation-that the same group of patients should have a loss of survival benefit after withdrawal of dofetilide. METHODS: Patients with congestive heart failure (CHF) and reduced left ventricular function enrolled in the Diamond-CHF (Danish Investigations of Arrhythmia and Mortality on Dofetilide-CHF) study were eligible for our QT substudy provided they were in sinus rhythm and had a measurable QTc interval from a 12-lead standard ECG taken before randomization to placebo or dofetilide. An extended follow-up was performed from study closure, December 1996 until August 2001. RESULTS: Of the 418 patients entering the extended follow-up, 215 (51%) patients died during this 4.5 years of additional observation time. The baseline QTc interval made no prognostic difference to mortality in placebo treated patients. For dofetilide treated patients with a baseline QTc interval <429 ms, increased mortality was observed during the extended follow-up compared to placebo (risk ratio 1.5, 95% confidence interval 1.1-2.8)[corrected]. CONCLUSIONS: This follow-up study shows significant loss of survival benefit upon withdrawal of dofetilide in patients with CHF and a pre-treatment QTc interval below 429 ms. An independent randomized trial is warranted to validate these results.

The importance of the QT interval: a review of the literature.

OBJECTIVE: QT interval (QTi) prolongation is generally associated with increased risk of ventricular arrhythmias such as torsade de pointes (TdP) and death. METHOD: Literature review based on publications identified by means of electronic and manual search. RESULTS: It has recently become apparent that not only antiarrhythmic drugs such as sotalol and quinidine, but also a variety of non-antiarrhythmic drugs such as certain antihistamines, antimicrobial drugs, psychiatric drugs and cisapride, may have the ability to induce prolongation of the QTi and TdP. Special concern should be drawn to the coadministration of drugs that inhibit the metabolism of these drugs such as ketoconazole, itraconazol and erythomycin. Patients with congenital long QT syndrome, patients with heart disease, with hypokalemia or hypomagnesemia, and women have an increased risk. Every sign of dizziness or syncope should be regarded as a warning sign of possible arrhythmia in patients treated with drugs that potentially prolong the QTi. CONCLUSION: Measurement of the QTi before and during treatment is generally recommended in high-risk patients.

Improving the reproducibility of QT dispersion measures.

BACKGROUND: The low reproducibility of the QT dispersion (QTD) method is a major reason why it is not used in clinics. The purpose of this study was to develop QT dispersion parameters with better reproducibility and identification of patients with a high risk of ventricular arrhythmia or death. METHODS AND RESULTS: Three institutions using different methods for measuring QT intervals provided QT databases, which included more than 3500 twelve-lead surface ECGs. The data represented low and high risk subjects from the following groups: the normal population EpiSet (survivors vs dead from cardiovascular causes), acute myocardial infarction patients AmiSet (survivors vs dead) and remote myocardial infarction patients ArrSet (with vs without a history of ventricular arrhythmia). The EpiSet, AmiSet, and the ArrSet contributed with N = 122, 0, and 110 ECGs for reproducibility analysis, and 3244, 446, and 100 ECGs for the analysis of prognostic accuracy. The prognostic accuracy was measured as the area under the Receiver Operator Curve. The QT intervals were divided into six QT pairs; the longest pair consisted of the longest and the shortest QT intervals etc. The QT dispersion trend (QTDT) was defined as the slope of the linear regression of the N longest QT pairs after estimation of missing QT intervals by interpolation of measured QT intervals. The QTMAD and the QTSTD methods were defined as twice the mean absolute deviation and the standard deviation of the N longest QT pairs. The reproducibility was improved by 27% and 19% in the EpiSet and the ArrSet relative to the reproducibility of QTD. The accuracy improved for the EpiSet and the ArrSet and was maintained for the AmiSet. CONCLUSIONS: By using the three longest and the three shortest QT intervals in QTDT, QTMAD, or QTSTD, the reproducibility improved significantly while maintaining or improving the prognostic accuracy compared to QTD.

Qtc interval as a guide to select those patients with congestive heart failure and reduced left ventricular systolic function who will benefit from antiarrhythmic treatment with dofetilide.

BACKGROUND: A prolonged QTc interval is considered a contraindication for class III antiarrhythmic drugs, but the influence of a normal or a slightly increased baseline QTc interval on the risk or benefit of treatment with a class III antiarrhythmic drug is not sufficiently clarified. METHODS AND RESULTS: This prospectively defined substudy included 703 patients enrolled in the Danish Investigations of Arrhythmia and Mortality on Dofetilide-Congestive Heart Failure (DIAMOND-CHF) study. Patients included had moderate to severe CHF and reduced left ventricular systolic function. Baseline QTc interval was measured before randomization to either dofetilide, a new class III antiarrhythmic drug, or placebo. During a median follow-up of 18 months (minimum 1 year), 285 patients (41%) died. Baseline QTc interval had no prognostic value on survival in placebo-treated patients. In dofetilide-treated patients, a baseline QTc interval <429 ms was associated with a significant risk reduction (risk ratio 0.4, 95% CI 0.3 to 0.8). With increasing QTc interval, the risk increased gradually, and for QTc interval >479 ms, risk ratio was 1.3 (0.8 to 1.9). CONCLUSIONS: A baseline QTc interval within normal limits is associated with a marked reduction of mortality in patients with CHF and left ventricular systolic dysfunction treated with dofetilide. This is a potentially important indication of which patients with CHF might benefit from prophylactic treatment with an antiarrhythmic drug.

Qt dispersion has no prognostic information for patients with advanced congestive heart failure and reduced left ventricular systolic function.

BACKGROUND: QT dispersion is a potential prognostic marker of tachyarrhythmic events and death, but it is unclear whether this applies to patients with congestive heart failure (CHF). METHODS AND RESULTS: Of the 1518 patients with advanced CHF and left ventricular dysfunction enrolled in the Danish Investigations of Arrhythmia and Mortality on Dofetilide-CHF (Diamond-CHF) study, a baseline ECG was available in 1319 patients. Of these, QT dispersion could be measured in 703 patients. During a median follow-up of 18 months (minimum 1 year), 285 patients (41%) died. The median QT dispersion was 70 ms (34/155 ms [5%/95% percentiles]), with no difference between survivors and nonsurvivors. Survival analysis revealed no prognostic information derived from QT dispersion regarding all-cause mortality (risk ratio 1.00, 95% CI 1.00 to 1.00; P=0.74), cardiac mortality (risk ratio 1.00, 95% CI 1.00 to 1.01; P=0.55), or cardiac arrhythmic mortality (risk ratio 1.00, 95% CI 0.99 to 1.01; P=0.38). CONCLUSIONS: QT dispersion has no prognostic value regarding all-cause mortality, cardiac mortality, or cardiac arrhythmic mortality for patients with advanced CHF and reduced left ventricular systolic function.

Serum-ionised magnesium in patients with acute myocardial infarction. Relation to cardiac arrhythmias, left ventricular function and mortality.

Measurement of serum-ionised magnesium has recently become available, and we report the first study of the relation of this parameter to arrhythmias, left ventricular function and mortality in patients with an acute myocardial infarction. Serum-ionised magnesium was determined in 217 consecutive patients admitted to hospital with an enzyme confirmed AMI. 70 healthy subjects acted as a control group. The main study parameters were occurrence of arrhythmias, left ventricular function estimated by echocardiography, and mortality after 10 months for the AMI patients. AMI patients had significantly lower serum-ionised magnesium compared to healthy controls but the level of serum-ionised magnesium in the acute phase of a MI was neither related to arrhythmias, left ventricular function nor mortality.

Spontaneous coronary artery dissection. Case report and literature review.

Primary coronary artery dissection occurring 2 months post partum in a 33-year-old woman is described. Owing to suspected acute myocardial infarction, the patient was treated with thrombolytic therapy but her condition deteriorated. Coronary angiography showed dissection of the left anterior descending artery (LAD). Her condition stabilized during treatment with intravenous heparin, aspirin, nitrates, beta-blockers, digoxin, ACE inhibitor and anticoagulants. At discharge she had no symptoms of heart failure. One hundred and forty one cases from the literature are reviewed with special reference to patient characteristics, patient treatment, and prognosis. Primary spontaneous coronary artery dissection is a rare condition but one that must be considered when young people, especially post partum women, present an acute ischaemic syndrome. Thrombolytic therapy may be a two-edged sword and therefore early angiography should be considered in making the diagnosis and choosing the therapy.

The prognostic value of the QT interval and QT interval dispersion in all-cause and cardiac mortality and morbidity in a population of Danish citizens.

AIMS: To evaluate the prognostic value of the QT interval and QT interval dispersion in total and in cardiovascular mortality, as well as in cardiac morbidity, in a general population. METHODS AND RESULTS: The QT interval was measured in all leads from a standard 12-lead ECG in a random sample of 1658 women and 1797 men aged 30-60 years. QT interval dispersion was calculated from the maximal difference between QT intervals in any two leads. All cause mortality over 13 years, and cardiovascular mortality as well as cardiac morbidity over 11 years, were the main outcome parameters. Subjects with a prolonged QT interval (430 ms or more) or prolonged QT interval dispersion (80 ms or more) were at higher risk of cardiovascular death and cardiac morbidity than subjects whose QT interval was less than 360 ms, or whose QT interval dispersion was less than 30 ms. Cardiovascular death relative risk ratios, adjusted for age, gender, myocardial infarct, angina pectoris, diabetes mellitus, arterial hypertension, smoking habits, serum cholesterol level, and heart rate were 2.9 for the QT interval (95% confidence interval 1.1-7.8) and 4.4 for QT interval dispersion (95% confidence interval 1.0-19-1). Fatal and non-fatal cardiac morbidity relative risk ratios were similar, at 2.7 (95% confidence interval 1.4-5.5) for the QT interval and 2.2 (95% confidence interval 1.1-4.0) for QT interval dispersion. CONCLUSION: Prolongation of the QT interval and QT interval dispersion independently affected the prognosis of cardiovascular mortality and cardiac fatal and non-fatal morbidity in a general population over 11 years.

Evaluation of an ionized magnesium-pH analyzer--NOVA 8.

An ion-selective analyzer (NOVA 8 [previously NOVA CRT], NOVA Biomedical Waltham, USA) for simultaneous measurement of the concentration of ionized magnesium (cMG2+) and pH is investigated for linearity and influence of calcium ions on the Mg2+ results in different Mg2+ aqueous solutions with/without added calcium. Within the cMg2+ range 0-3.0 mmol/L, which covers most clinical values, we found cMg2+ values close to the line of identity, with a sensitivity about 94%, but 0.09 mmol/L lower in the absence of Ca2+. The analytical precision (CV) for human serum control was 1.7% in the physiological range. The accuracy and precision data for the Mg2+ electrode meet the demands for reliable results within the range for clinical use. We found a reference interval (95%) for cMg2+ of between 0.43 and 0.59 mmol/L serum, with a mean value of 0.51 mmol/L for healthy adults in the non-fasting state with no relation to sex or age. The mean cMg2+ was 61% of the mean concentration of plasma total magnesium (cTMg) ranging from (95%) 49% to 73%. No significant correlation was found between cMg2+ and total protein, albumin, phosphate, Ca2+, and total CO2. No significant difference was found between mean values for cMg2+ in whole blood, plasma, and serum. Serum samples could be stored for 24 h at 4 degrees C without significant change. Storage at -20 degrees C for 7 months caused a mean cMg2+ decrease of 8.3%. The mean slope delta lgcMg2+/delta pH measured after equilibration with different pCO2 values in each serum sample from the reference population was -0.0110, indicating a close agreement between the values for actual cMg2+ and adjusted cMg2+ (pH = 7.4).

Classification of sudden and arrhythmic death.

Since all death is (eventually) sudden and associated with cardiac arrhythmias, the concept of sudden death is only meaningful if it is unexpected, while arrhythmic death is only meaningful if life could have continued had the arrhythmia been prevented or treated. Current classifications of death as being arrhythmic or sudden are all biased by the difficulty of having to decide on the degree of unexpectedness or the likelihood that life could continue without the arrhythmia. The uncertainties are enlarged by the fact that critical data (such as knowledge of arrhythmias at the time of death or autopsy) are available in only a few percent of cases. A main problem in using classifications is the lack of validation data. This situation has, with the MADIT trial, changed in the case of the Thaler and Hinkle classification of arrhythmic death. The MADIT trial demonstrated that arrhythmic death was nearly abolished by the implantable defibrillator, indicating that arrhythmic death by this classification is meaningful, at least in the population studied. For future investigations, a call is made for committees to present data in a way that allows the reader to examine the quality of the data used for evaluation.

Use of left ventricular ejection fraction or wall-motion score index in predicting arrhythmic death in patients following an acute myocardial infarction. The TRACE Study Group.

All-cause mortality and morbidity following an acute myocardial infarction (AMI) are correlated to LV systolic dysfunction. The correlation is closest with mortality and morbidity associated with congestive heart failure (CHF). Prediction of arrhythmic death in patients with AMI relies on the correlation between arrhythmic death and "sudden unexpected death" defined as death within 1 hour of onset of new symptoms. Assessment of late potentials, heart rate variability (HRV), T wave alternans, arrhythmias seen on Holter monitoring or during exercise testing, electrophysiological testing, and baroreceptor assessment have all proven to be useful in the prediction of sudden death even when LV systolic function is known. In selected populations HRV is superior to LV systolic function assessment in predicting sudden death and/or arrhythmic events, and may even predict all-cause mortality with the same precision. Comparisons of other methods with LV function assessment should be interpreted with care because most methods have been evaluated in subgroups of infarct patients with a low risk of death. Results from a large series of high risk patients with AMI (the TRAndolapril Cardiac Evaluation study) have shown that even in patients with severe depressed LV systolic function around one-third of the patients will die suddenly. The current situation is that LV function appears to be the best method of predicting death whereas other methods appear very promising for detecting arrhythmic death in more selected populations. The optimal method for selecting patients at high risk of arrhythmic death has not yet been developed, but a combination of LV function and another method, i.e., HRV, appears promising. This may ensure that the enrolled patients have an increased risk of death and that this risk will be due to arrhythmic events. Patients with LVEF of 10% or less can be excluded as they will most likely not die suddenly.

[The yellow nail syndrome]. / De gule negles syndrom.

The yellow nail syndrome is the combination of slow growing yellow discoloured nails, lymphoedema and pleural effusion. The symptoms are supposed to be due to impaired lymphatic drainage. It is a rare clinical condition: through the last 30 years only about a hundred cases have been reported. The treatment is symptomatic (diuretics and pleuradesis). We review the literature and report four cases.

Urine protein excretion after Hymenoptera sting.

The urinary excretion of albumin was measured on 7 consecutive days after a bee or wasp sting in 20 healthy persons, using a semiquantitative immunochemical chromatographic procedure (Micral stick). The mean albumin excretion was 11.1 +/- 15.0 (SD) mg/l. This was not significantly different from the findings in a control group of 17 volunteers with no history of bee or wasp sting (mean 8.7 +/- 17.4 mg/l). Pathologic albumin excretion (50-100 mg/l) was found in three of the sting group, with mean 37.2 +/- 23.7 mg/l. After 2 more months the urinary albumin excretion had normalized in two of the three, with mean 19.3 +/- 16.0 mg/l. Nephrotic syndrome did not occur. Reactions to the sting corresponded to 1-4 on the Müller scale, but were not correlated to albumin excretion.