Siegfried Wieshammer

Dry Powder Inhalers: Which Factors Determine the Frequency of Handling Errors?

Background: Dry powder inhalers are often used ineffectively, resulting in a poor level of disease control. Objectives: To determine how often essential mistakes are made in the use of Aerolizer®, Discus®, HandiHaler® and Turbuhaler® and to study the effects of age, severity of airflow obstruction and previous training in inhalational technique by medical personnel on the error rate. Methods: Two hundred and twenty-four newly referred outpatients (age 55.1 ± 20 years) were asked how they had been acquainted with the inhaler and to demonstrate their inhalational technique. Results: The inhaler-specific error rates were as follows: Aerolizer 9.1%, Discus 26.7%, HandiHaler 53.1% and Turbuhaler 34.9%. Compared to Aerolizer, the odds ratio of an ineffective inhalation was higher for HandiHaler (9.82, p < 0.01) and Turbuhaler (4.84, p < 0.05). The error rate increased with age and with the severity of airway obstruction (p < 0.01). When training had been given as opposed to no training, the odds ratio of ineffective inhalation was 0.22 (p < 0.01). If Turbuhaler is used, the estimated risks range from 9.8% in an 18-year-old patient with normal lung function and previous training to 83.2% in an 80-year-old patient with moderate or severe obstruction who had not received any training. Conclusions: Dry powder inhalers are useful in the management of younger patients with normal lung function or mild airway obstruction. In older patients with advanced chronic obstructive pulmonary disease, the risk of ineffective inhalation remains high despite training in inhalational technique. A metered-dose inhaler with a spacer might be a valuable treatment alternative in a substantial proportion of these patients.

Left ventricular function at rest and during exercise in acute hypothyroidism.

The effect of hypothyroidism on left ventricular function at rest and during exercise was studied in nine patients without demonstrable cardiovascular disease who had had total thyroidectomy and ablative radioiodine treatment for thyroid cancer. Radionuclide ventriculography and simultaneous right heart catheterisation were performed while the patients were hypothyroid two weeks after stopping triiodothyronine treatment (to permit routine screening for metastases) and while they were euthyroid on thyroxine replacement treatment. When the patients were hypothyroid, cardiac output, stroke volume, and end diastolic volume at rest were all lower and peripheral resistance was higher than when they were euthyroid. Pulmonary capillary wedge pressure, right atrial pressure, heart rate, left ventricular ejection fraction, and the systolic pressure:volume relation of the left ventricle, which was used as an estimate of the contractile state, were not significantly different when the patients were hypothyroid or euthyroid. During exercise, heart rate, cardiac output, end diastolic volume, and stroke volume were higher when the patients were euthyroid than when they were hypothyroid. Again, pulmonary capillary wedge pressure, ejection fraction, and the systolic pressure:volume relation were similar in both thyroid states. The data suggest that the alterations in cardiac performance seen in short term hypothyroidism are primarily related to changes in loading conditions and exercise heart rate; they do not suggest that acute thyroid hormone deficiency has a major effect on the contractile properties of the myocardium.

Doppler echocardiographic evaluation of left ventricular diastolic function in acute hypothyroidism

OBJECTIVE Left ventricular diastolic dysfunction Is an important cause of symptomatic heart failure. Previous studies suggest that thyroid dysfunction affects left ventricular diastolic function but the underlying mechanisms remain controversial. The study was undertaken to assess the influence of acute hypothyroidism on left ventricular diastolic function and to elucidate possible underlying mechanisms by means of Doppler echocardiography in a group of athyreotic patients, whose thyroid state depended only on external thyroid hormone supply and could therefore easily be controlled.

NT-proBNP for pulmonologists: not only a rule-out test for systolic heart failure but also a global marker of heart disease.

Background: Recognizing heart disease is relevant to pulmonologists because many patients suspected to have dyspnea of pulmonary origin harbor heart disease. Objectives: To investigate the role of N-terminal pro-brain natriuretric peptide (NT-proBNP) in identifying heart disease and cardiac causes of dyspnea among patients referred for evaluation by a pulmonologist. Methods: 697 consecutive outpatients (aged 57.5 ± 16.4 years) with chronic dyspnea prospectively underwent a diagnostic work-up for heart and lung diseases. Results: The prevalence of patients with heart disease was 25.3%. The cardiac findings were placed into 6 groups which were associated with an increase in NT-proBNP in the following order: (1) left ventricular hypertrophy [regression coefficient (β) = 0.33, p = 0.03]; (2) exercise-induced myocardial ischemia (β = 0.73, p = 0.02);(3) valvular or congenital heart disease or pericardial effusion (β = 0.93, p < 0.0001); (4) pulmonary hypertension (β = 1.14, p < 0.0001); (5) atrial fibrillation or left bundle branch block (β = 1.22, p < 0.0001), and (6) left ventricular systolic dysfunction (β = 1.94, p < 0.0001). Using predefined cut-off values of 93 pg/ml (men) and 144 pg/ml (women), sensitivity was 0.75 and specificity was 0.79 for identifying heart disease. The negative predictive value was 0.90. If heart disease had to be considered as a cause of the dyspnea, sensitivity and the negative predictive value went up to 0.90 and 0.97, respectively. Conclusions: NT-proBNP performs well as a test for ruling out cardiac dyspnea. It is also useful as a rule-in test for heart disease, which enables the pulmonologist to appropriately select candidates for in-depth evaluation by cardiology.

A Link between Impaired Lung Function and Increased Cardiac Stress

Background: Patients with impaired lung function often have systemic inflammation. C-reactive protein (CRP) and N-terminal pro-brain natriuretic peptide (NT-proBNP) are markers for inflammation and cardiac stress, respectively. Objectives: To evaluate the association between both markers and the potential impacts of lung disease on this relationship. Methods: CRP and NT-proBNP were prospectively measured in 697 consecutive outpatients (57.5 ± 16.4 years) with chronic dyspnea. The patients were stratified into quartiles according to CRP levels (quartile 1: median CRP 0.35 mg/l; quartile 2: 1.50 mg/l; quartile 3: 3.62 mg/l; quartile 4: 10.90 mg/l) and classified into 2 categories based on the presence (n = 176) or absence (n = 521) of heart disease. Results: Patients with at least moderately severe airway obstruction and those with interstitial lung disease had higher CRP values than patients without lung disease (median 3.50 vs. 4.34 vs. 1.80 mg/l, respectively; p < 0.01). In patients without heart disease, NT-proBNP values increased from CRP quartiles 1–3 to quartile 4 (median 47.4 vs. 82.1 pg/ml; p < 0.01) after adjusting for important covariates such as age, sex, body mass index, renal function and arterial hypertension. Likewise, the values for NT-proBNP were lower in CRP quartiles 1–3 than in quartile 4 (median 212.0 vs. 647.7 pg/ml; p < 0.01) in patients with heart disease after additional adjustment for the type of cardiac disorder. Lung disease had no direct effect on the relationship between CRP and NT-proBNP. Conclusion: Systemic inflammation that originates in the lung places an excess burden on the heart, which may contribute to the functional impairment of patients with advanced pulmonary disease.

Cardiotoxicity and Cancer Therapy: Treatment-Related Cardiac Morbidity in Patients Presenting with Symptoms Suggestive of Heart or Lung Disease

Objectives: Cardiac injury is one of the complications of cancer treatment. This study aimed to investigate the relationships between the types of radiotherapy of the chest (RT), chemotherapy (CT), cancer surgery (CS) and endocrine therapy (ET), and the presence of heart disease, and their associations with the serum level of N-terminal pro-B-type natriuretic peptide (NT-proBNP). Methods: A consecutive series of 374 patients with cancer who were referred because of symptoms suggestive of heart or lung disease prospectively underwent a diagnostic workup. Results: The prevalence of heart disease was 36.9%. RT administered before 1995 (n = 19) was associated with both increased odds of heart disease [adjusted odds ratio 10.3, 95% confidence interval 3.1-34.0] and higher ln-transformed NT-proBNP values (p < 0.01) compared to the control group (no RT or RT for right-sided breast cancer from 1995 onwards; n = 311). Anthracycline-treated patients (n = 54) had higher adjusted values for ln(NT-proBNP) compared to the control group (no CT; n = 243; p < 0.01) but no increased odds of heart disease. Conclusions: While pre-1995 RT and anthracycline-containing CT were associated with cardiac effects, there was no evidence that RT using modern cardioprotective techniques, CT in the absence of anthracyclines, CS or ET had detrimental effects on the heart.

Hemodynamic profile of carvedilol.

SummarySeveral so-called multiple-action compounds have been developed, such as medroxalol (alpha and beta blockade, and beta-2 stimulation), celiprolol (alpha-2 and beta-1 blockade, and beta-2 stimulation) and carvedilol (beta blockade and vasodilatation) for the treatment of patients with arterial hypertension and with coronary heart disease. Carvedilol exerts relatively uniform peripheral effects, i. e. a reduction of both systolic and diastolic blood pressure at rest and during exercise, and a decrease in the resting and exercise heart rate. Blood pressure fall due to carvedilol may be induced by its vasodilating effect, as documented by measurements of forearm blood flow and peripheral vascular resistance. Moreover, renal hemodynamics does not seem to be significantly altered by carvedilol. Carvedilol may also produce an improvement of the LV contractile status in patients with CHD and impaired LV function, mainly due to afterload reduction, in addition to its antianginal effect, which is due mainly to the beta-blocking properties of this substance. From the studies mentioned it may be concluded that carvedilol is a useful and promising drug for treating patients with both arterial hypertension and with coronary artery disease.

Limitations of radionuclide ventriculography in the non-invasive diagnosis of coronary artery disease. A correlation with right heart haemodynamic values during exercise.

A consecutive series of 56 patients with chest pain but no evidence of previous myocardial infarction was prospectively studied by radionuclide ventriculography to determine the value of global and regional radionuclide indices in detecting coronary artery disease. The results were correlated with the clinical judgment of chest pain, the results of the exercise electrocardiogram, and the right heart haemodynamic measurements during exercise. As a result of the criteria for entry, the study group was representative of the population seen in such a clinical setting. Only 25% of patients had coronary artery disease. The predictive power of radionuclide ventriculography was limited. The conventionally used criterion that normal subjects have an increase in left ventricular ejection fraction of at least 5% with exercise provided only 78% sensitivity and 57% specificity. Fourier analysis and visual interpretation of radionuclide studies wrongly diagnosed three out of 10 patients with extensive disease requiring surgery. These results suggest that radionuclide ventriculography is of limited value in the non-invasive diagnosis of coronary artery disease.

Elevated Levels of N-Terminal Pro-Brain Natriuretic Peptide in Patients with Chronic Dyspnea and Moderate Renal Dysfunction: Decreased Clearance or Increased Cardiac Stress

Background/Aims: Serum levels of N-terminal pro-brain natriuretic peptide (NT-proBNP) are often increased in patients with impaired renal function. The objective of this study was to investigate whether the increase in NT-proBNP is predominantly due to a reduced renal clearance or an increased cardiac secretion. Methods: A series of 697 outpatients (age: 57.5 ± 16.4 years) referred for evaluation of dyspnea were assigned to 4 groups according to their estimated glomerular filtration rate [eGFR (ml/min per 1.73 m2)]: group 1, eGFR <60 (n = 77); group 2, eGFR ≧60 to <75 (n = 139); group 3, eGFR ≧75 to <90 (n = 191), and group 4, eGFR ≧90 (n = 289). The patients were also grouped into 2 categories based on the presence (n = 176) or absence (n = 521) of heart disease. Results: In patients with heart disease, the adjusted values for NT-proBNP were higher in eGFR group 1 than in eGFR groups 2–4 (p ≤ 0.01). In patients without heart disease, eGFR group 1 membership had no effect on NT-proBNP. Conclusion: A reduced renal clearance does not explain increased NT-proBNP levels in patients with moderate renal impairment and dyspnea. Our data suggest that a moderate reduction in renal function places additional stress on the heart in patients with established cardiac disease.

Quantification of mitral regurgitation by colour flow Doppler imaging--value of the 'proximal isovelocity surface area' method.

In this study 97 patients with mitral regurgitation (age 62 +/- 11 years, 55 men, 42 women) quantified by angiography were studied using colour flow Doppler imaging of isovelocity surface areas in the flow convergence region proximal to the regurgitant orifice. The radii of the proximal isovelocity surface areas for the flow velocities of 28 and 41 cm/s were measured. A flow convergence region was imaged in 100% (96%) of the patients with Grade I/II or more and in 92% (64%) of the patients with Grade I mitral regurgitation for a flow velocity of 28 (41) cm/s. The radii of the proximal isovelocity surface areas correlated significantly with the angiographic grade in patients with sinus rhythm as well as atrial fibrillation. A correct differentiation of Grade I to II from Grade III to IV mitral regurgitation was provided in more than 90% of all patients for both flow velocities investigated. Assuming hemispheric proximal isovelocity surface areas, in 11 patients the regurgitant volumes from echocardiography (range: 2.6-241 (0.9-198) ml for a flow velocity = 28 (41) cm/s) correlated with, but considerably overestimated the values from cardiac catheterization (range: 1.4-72.5 ml) with r = 0.79 (0.82) (P < 0.01) and SEE = 57.9 (42.4) ml for a flow velocity of 28 (41) cm/s. It was concluded that colour flow Doppler imaging of the flow convergence region enables the diagnosis of mitral regurgitation and the differentiation between Grade I to II and Grade III to IV mitral regurgitation, but may be of little value in estimating the regurgitant volume, assuming a hemispheric symmetry of the proximal flow convergence region.