Dabigatran in patients with atrial fibrillation: perioperative and periinterventional management.

In any type of invasive surgery, the patient's individual risk of thromboembolism has to be weighed against the risk of bleeding. Based on various everyday situations in clinical routine, the purpose of the present expert recommendations is to provide appropriate perioperative and periinterventional management for patients with atrial fibrillation undergoing long-term treatment with the thrombin inhibitor dabigatran. As we currently have no routine laboratory test to measure therapeutic levels of the substance or the risk of bleeding, general measures such as a standardized documentation of the patient's history, a sufficient time interval between the last preoperative dose and the procedure, and careful control of local hemostasis should be given special attention.

[Diagnostic accuracy of contrast-enhanced 64-row MSCT coronary angiography in patients with severe coronary calcification in the clinical routine]. / Diagnostische Wertigkeit der kontrastverstärkten MSCT-Koronarangiografie bei Patienten mit hochgradiger Koronarverkalkung im klinischen Alltag.

PURPOSE: Our aim was to evaluate the diagnostic accuracy of contrast-enhanced 64-MSCT coronary angiography (MSCT-CA) in patients with severe coronary calcification. MATERIALS AND METHODS: 110 patients with an Agatston score > 400 were included in this retrospective analysis. Each patient underwent both conventional coronary angiography and MSCT-CA. No patient was excluded from the study because of coronary artery bypass grafting or coronary stenting. The results of MSCT-CA were compared with those of conventional coronary angiography and the diagnostic accuracy for detecting a hemodynamically significant stenosis was determined for coronary segments, vessels and patients. RESULTS: The average Agatston score for the study population was 1368 ± 1105. At least one significant stenosis was detected in 97 patients (88%) during conventional coronary angiography defining the gold standard. The sensitivity, specificity, positive and negative predictive values of MSCT-CA for detecting a significant stenosis were 54%, 83%, 52% and 85% for coronary segments (n = 1384), 80%, 70%, 74% and 77% for coronary vessels (n = 440), and 100%, 31%, 92% and 100% for patients (n = 110), respectively. No significant correlation could be observed between the degree of coronary calcification and the number of misclassified coronary segments. CONCLUSION: Artifacts caused by severe coronary calcification decrease the diagnostic accuracy of MSCT-CA. Performing MSCT-CA in patients with an Agatston score > 400 with the drawbacks of contrast media application and radiation exposure should be critically questioned and this decision should be made on an individual basis.

Mobile phone-based surveillance of cardiac patients at home.

We tested the reliability, acceptability and feasibility of a home-monitoring system for cardiac patients. Each participant was equipped with a mobile phone, an automatic blood pressure device and a digital weight scale. In total, 20 patients (14 patients with chronic heart failure, six patients with hypertension; mean age 50 years, standard deviation [SD] 14) were monitored for 90 days each. They were asked to measure their blood pressure, pulse and body weight every day, and to transfer the data together with the dosage of medication to the telemonitoring server using wireless Internet technology in the mobile phone. The physician in charge received email alerts when reported data fell outside pre-defined limits. The patients' compliance with the system was high. During a cumulative monitoring period of 1,735 days, there were 2,040 data transfer sessions, a mean of 102 per patient (SD 43). The mean percentage of successful data transfers was 83% (SD 22). The stability of the telemonitoring system was 98%, meaning that patient data transfer was almost always possible. The accessibility of the secure web server for physicians was above 99%. The web-based home-monitoring system was reliable and easy to handle for both patients and health care professionals. It may be a useful tool for patients with heart failure as well as hypertensive patients.

Human paraoxonase 1 gene polymorphisms and the risk of coronary heart disease: a community-based study.

Published data on the association between paraoxonase1 (PON1) polymorphisms and coronary heart disease (CHD) have yielded controversial results. The objective of this study was to determine the possible relationship between the two human PON1 amino acid variants, the Leu55Met and the Gln192Arg polymorphism, and the risk of CHD in a community-dwelling cohort of European ancestry. PON1 genotypes of 152 women and 151 men out of 1,998 randomly selected individuals aged 44-75 years were determined by polymerase chain reaction-based restriction enzyme digestion. Study participants underwent cardiological examination including a structured clinical interview, resting ECG, exercise testing and echocardiography. The diagnosis of CHD was based on history and/or appropriate findings during cardiac examination. Evidence for CHD was found in 43 (14.2%) study participants. The Leu/Leu (LL), Leu/Met (LM) and Met/Met (MM) genotypes at position 55 were noted in 131 (43.2%), 128 (42.2%) and 44 (14.5%) subjects; the Gln/Gln (QQ), Gln/Arg (QR) and Arg/Arg (RR) genotypes at codon 192 occurred in 167 (55.1%), 118 (38.9%) and 18 (5.9%) individuals, respectively. Homozygosity for the 55L-allele was significantly associated with CHD (p = 0.02), while the Gln192Arg polymorphism had no effect (p = 0.16). Logistic regression analysis demonstrated age (odds ratio 1.06/year), smoking (odds ratio 2.86), HDL cholesterol (odds ratio 0.94/mg/dl) and the paraoxonase LL genotype (odds ratio 2.25) to be significant predictors of CHD. These data suggest that the paraoxonase LL genotype at position 55 may present a risk factor for CHD.

[Efficiency and safety of ACE-inhibiting imidapril in patients with essential hypertension]. / Effektivität und Nebenwirkungsspektrum des ACE-Hemmers Imidapril bei Patienten mit essentieller Hypertonie.

In a survey including 2224 patients with essential hypertension we investigated efficacy and tolerability of the new ACE-inhibitor Imidapril. Mean blood pressure at baseline was 172 +/- 19/98 +/- 10 mmHg. Treatment with Imidapril 5-20 mg once daily caused a decrease in BP by 21 +/- 17/11 +/- 10 mmHg (p < 0.01/0.01). Systolic BP was reduced by > 15 mmHg in 71% diastolic BP by > 10 mmHg in 64% of patients. 29% of patients achieved the treatment goal of a blood pressure < or = 140/90 within an average of 26 days. Imidapril decreased pulse-pressure (one of the most important risk markers in hypertension) by 18% (74 +/- 17 to 61 +/- 11 mmHg, p < 0.01). ACE-inhibitor related adverse effects (cough, vertigo, headache, pruritus, tachycardia, orthostatic dysregulation or nausea) were observed in 38 patients (< 2%). Efficacy of treatment was graded by the physician in charge of the patient care by means of a questionnaire. Gradings were excellent or good in 96% of patients, moderate in 3% and poor in < 1%. In summary, the effects of Imidapril on blood pressure were comparable to those of other ACE-inhibitors. However, the frequency of adverse effects was low and similar to that of angiotensin-II-antagonists.

Rescue percutaneous transluminal coronary angioplasty in a patient with a single coronary artery arising from the right Sinus Valsalvae: previously unreported scenario and review of literature.

This is the first description of treatment with coronary stenting of a patient with a single coronary artery originating from the right Sinus Valsalvae and suffering from acute inferior myocardial infarction. Angiography showed the following: the right coronary artery (RCA) had a normal course, whilst the left anterior descending (LAD) as well as the left circumflex (LCX) branches both originated separately from the proximal RCA, which served as a common mixed trunk. The LAD crossed to the left in front of the right ventricular outflow tract, whilst the LCX, taking a retroaortic course to the atrioventricular groove, had a distal occlusion. According to an anatomically based classification considering all imaginable variations, this configuration corresponds to a II-D-1 pattern, which previously has been described only in a single postmortem case. After the LCX was reopened with a guide wire, a coronary stent was successfully inserted, resulting in TIMI-3 flow. Recovery was uneventful.

[Angiotensin I receptor blockers for heart failure]. / AT-I-Rezeptor-Blocker bei Herzinsuffizienz.

Angiotensin conversion enzyme inhibitors (ACE-inhibitors) have long been the only possibility to influence the renin angiotensin system (RAS) and its often fatal influences in heart failure. In the last few years specific blockers of the angiotensin 1 receptor (AT I blockers) offered a new possibility for this therapeutic target. In contrast to ACE inhibitors AT I blockers are relatively new and, therefore, few data on heart failure are available. The first head-to-head studies that compared AT I blockers and ACE-inhibitors and their effect on mortality did not show a reduced mortality in the AT I blocker groups. Based on the available data AT I blockers should be used in heart failure patients who are intolerant of ACE-inhibitors.

Differing beta-blocking effects of carvedilol and metoprolol.

BACKGROUND: Metoprolol is a beta(1)-selective beta-adrenergic antagonist while carvedilol is a non-selective beta-blocker with additional blockades of alpha(1)-adrenoceptors. Administration of metoprolol has been shown to cause up-regulation of beta-adrenoceptor density and to decrease nocturnal melatonin release, whereas carvedilol lacks these typical effects of beta-blocking drugs. AIMS: To compare beta-blocking effects of metoprolol and carvedilol when applied orally in healthy subjects. METHODS: We investigated the effects of single oral doses of clinically recommended amounts of metoprolol (50, 100 and 200 mg) and carvedilol (25, 50 and 100 mg) to those of a placebo in a randomised, double-blind, cross-over study in 12 healthy male volunteers. Two hours after oral administration of the drugs heart rate and blood pressure were measured at rest, after 10 min of exercise, and after 15 min of recovery. RESULTS: Metoprolol tended to decrease heart rate during exercise (-21%, -25% and -24%) to a greater extent than carvedilol (-16%, -16% and -18%). At rest, increasing doses of metoprolol caused decreasing heart rates (62, 60 and 58 beats/min) whereas increasing doses of carvedilol caused increasing heart rates (62, 66 and 69 beats/min), 50 and 100 mg carvedilol failed to differ significantly from the placebo (71 beats/min). CONCLUSIONS: We conclude that clinically recommended doses of carvedilol cause a clinically relevant beta-blockade in humans predominantly during exercise where it appears to be slightly (although not significantly) less effective than metoprolol. On the other hand, the effects of carvedilol on heart rate at rest appear rather weak, particularly in subjects with a low sympathetic tone. This might be caused by a reflex increase on sympathetic drive secondary to peripheral vasodilation resulting from the alpha-blocking effects of the drug. These results might be helpful in explaining why carvedilol, in contrast to metoprolol, may fail to cause up-regulation of beta-adrenoceptor density and does not decrease nocturnal melatonin release. This, in turn, may be a reason for the weak side-effects of carvedilol resulting from the beta-blockade. In addition, our data might be of interest in the interpretation of the forthcoming results of the COMET trial, although it has to be emphasised that they were derived from healthy subjects and, therefore, cannot be directly extrapolated to patients with heart failure.

Comparison of wrist blood pressure measurement with conventional sphygmomanometry at a cardiology outpatient clinic.

OBJECTIVE: Oscillometric measurement of blood pressure at the wrist is becoming a widely used method for detection of hypertension and its control by treatment. The objective of the present study was to evaluate accuracy and suitability of wrist measurement in a clinical routine setting. PATIENTS AND METHODS: A series of 333 consecutive patients admitted to our cardiology outpatient clinic were included. Blood pressure was measured at both upper arms according to World Health Organization-International Society of Hypertension guidelines. Oscillometric measurement was performed at the contralateral wrist simultaneously. Blood pressure readings were taken by an oscillometric device applied at the wrist ('Klock'; Industrielle Entwicklung Medizintechnik, Stolberg, Germany) and a conventional mercury sphygmomanometer applied at the upper arm. RESULTS: Seventy-eight patients were excluded due to differences in blood pressure > 5 mmHg between both upper arms or due to 'error' messages of the wrist device. The data of the remaining 255 patients (149 males; mean age, 65 +/- 13 years; range, 18-95 years) are presented. Mean conventional blood pressure was significantly lower compared with the wrist device (137 +/- 20/80 +/- 11 mmHg versus 153 +/- 28/87 +/- 18 mmHg; P < 0.001 and P < 0.001). The mean difference was 16 +/- 25/6 +/- 17 mmHg. In clinical terms, differences in blood pressure exceeding +/-20/+/-10 mmHg reflecting classification of hypertension are considered important. Measurements of 101 (40%) patients were within these limits. Systolic readings of 110 (43%) and diastolic readings of 117 patients (46%) were beyond this scope. CONCLUSION: Due to low reliability of wrist blood pressure measurement, it cannot compete with the upper arm standard procedure. If ever, it should only be used if test readings in an individual comparing wrist and upper arm measurement show differences within a range of +/-20/+/-10 mmHg.

Dynamic renal function testing by compartmental analysis: assessment of renal functional reserve in essential hypertension.

BACKGROUND: In essential hypertension, acute haemodynamic changes due to dietary protein load cause patterns of acute changes in renal function that are fundamentally different from changes in normal controls. METHODS: Renal clearances of sinistrin, an inulin-like polyfructosan, and p-aminohippurate were determined before and after protein ingestion. These tests were performed in healthy controls and in patients with essential hypertension (mean arterial pressure of 112+/-2 mmHg, age, 52+/-2 years; mean+/-SEM) within a washout period, and after long-term treatment with carvedilol and fosinopril, respectively. RESULTS: In 15 healthy volunteers, protein ingestion increased glomerular filtration rate (GFR) from 110.3+/-3.6 to 120. 6+/-4.4 ml/min (P=0.0006; two-tailed pairwise t-test). In contrast, it led to an acute decrease in GFR in 16 hypertensive patients, from 111.8+/-2.9 to 103.6+/-3.3 ml/min (P=0.0010). The eight patients who were randomized to receive carvedilol improved in their renal response to protein (GFR increased from 101.4+/-6.4 to 107.1+/-5.4 ml/min; P=0.04), whereas the eight other patients randomized to receive fosinopril exhibited no change in GFR (final value 105+/-4.9 ml/min). In the patients, the acute shifts in renal plasma flows were not significant. Mean arterial blood pressure of the patients decreased from 112+/-2 to 100+/-3 mmHg (P=0.0015). CONCLUSIONS: In essential hypertension an acute protein load induces a decrease in GFR that may normalize under antihypertensive treatment. The acute changes in GFR can be reliably monitored by the here-described compartmental analysis method of renal functional reserve.

N-terminal proatrial natriuretic peptide correlates with systolic dysfunction and left ventricular filling pattern in patients with idiopathic dilated cardiomyopathy.

OBJECTIVE: To investigate the diastolic Doppler filling pattern in patients with idiopathic dilated cardiomyopathy and its relation to N-terminal pro-atrial natriuretic peptide (NT-pro-ANP). METHODS: 32 patients (26 male, six female) with idiopathic dilated cardiomyopathy were investigated. All were in sinus rhythm. Conventional M mode echocardiography and Doppler echocardiography was done in each patient. Pulsed wave Doppler inflow signals were obtained and the following variables were measured: maximum E wave, maximum A wave, E/A ratio, E wave deceleration time, A wave deceleration time. NT-pro-ANP was measured using radioimmunoassay. RESULTS: Mean (SD) left ventricular ejection fraction was 34 (7)% and mean left ventricular end diastolic diameter on M mode echocardiography was 69 (7) mm. Left ventricular filling indices were as follows: maximum E wave velocity, 0.86 (0.22) m/s; maximum A wave velocity, 0.71 (0.24) m/s; E/A ratio, 1.41 (0.65). Mean E wave deceleration time was 140 (50) ms; mean A wave deceleration time was 100 (20) ms. In a stepwise forward regression model, NT-pro-ANP correlated significantly with left atrial diameter (r = 0.603; p < 0. 001), left ventricular ejection fraction (r = -0.758; p < 0.001), and Doppler derived E/A ratio (r = 0.740; p < 0.001). CONCLUSIONS: In patients with idiopathic dilated cardiomyopathy there is a relation between NT-pro-ANP and both systolic and diastolic variables. In a multivariate model NT-pro-ANP correlated with left atrial diameter, left ventricular ejection fraction, and Doppler derived E/A ratio on transmitral inflow.

Natriuretic peptides in patients with diastolic dysfunction due to idiopathic dilated cardiomyopathy.

AIMS: The degree of systolic dysfunction does not always correlate with functional impairment in patients with congestive heart failure. In contrast, diastolic dysfunction correlates well with functional impairment. In heart failure, both elevation of N-terminal proatrial natriuretic peptide and B-type natriuretic peptide are markers of a poor prognosis. METHODS: We investigated 32 patients (26 male, 6 female; mean age 55+/-2 years) with dilated cardiomyopathy and sinus rhythm. M-mode echocardiography and 2D-echocardiography were carried out in each patient. Pulsed-wave Doppler inflow signals were obtained and the following parameters were measured: maximal E wave and maximal A wave velocity, E/A ratio, E wave deceleration time, A wave deceleration time. Immediately after echocardiography blood samples were collected from patients in the supine position. N-terminal proANP and brain natriuretic peptide were measured using a radioimmuno assay. RESULTS: The left ventricular ejection fraction was 34+/-1%, the left ventricular end-diastolic diameter on M-mode echocardiography was 68+/-1 mm, while left atrial diameter was 45+/-1 mm. Univariate analysis revealed a significant correlation between both left atrial diameter and ejection fraction and N-terminal proANP and brain natriuretic peptide. All transmitral Doppler parameters showed a significant correlation with N-terminal proANP and brain natriuretic peptide. On forward stepwise regression analysis, left atrial diameter and ejection fraction were able to predict both N-terminal proANP and brain natriuretic peptide. However, of the diastolic parameters only the E/A ratio remained significant. Mildly symptomatic patients differed significantly from severely symptomatic patients in all Doppler parameters. Mildly symptomatic patients had significantly lower levels of N-terminal proANP (0.571+/-0.079 vs 2.282+/-0.340 nmol. l(-1);P<0.001) and brain natriuretic peptide (51+/-14.8 vs 474.2+/- 86.8 pg. ml(-1);P<0. 001). CONCLUSION: There is a close relationship between natriuretic peptides and diastolic Doppler parameters of left ventricular filling in patients with dilated cardiomyopathy. There is also a significant difference between patients with mild and severe functional impairment regarding both natriuretic peptides and transmitral Doppler parameters.

Influence of beta-blockers on melatonin release.

OBJECTIVE: Melatonin is a mediator in the establishment of the circadian rhythm of biological processes. It is produced in the pineal gland mainly during the night by stimulation of adrenergic beta1- and alpha1-receptors. Sleep disturbances are common side-effects of beta-blockers. The influence of specific beta-blockade as well as that of combined alpha-and beta-blockade on melatonin production has not been investigated in humans before. METHODS: We performed a randomized, double-blind, placebo-controlled, cross-over study in 15 healthy volunteers. Subjects received single oral doses of 40 mg (R)-propranolol, 40 mg (S)-propranolol, 50 mg (R)-atenolol, 50 mg (S)-atenolol, 25 mg (R,S)-carvedilol, 120 mg (R,S)-verapamil or placebo at 1800 hours. Urine was collected between 2200 hours and 0600 hours, and 6-sulfatoxy-melatonin (aMT6s), the main metabolite of melatonin which is almost completely eliminated in urine, was determined by radioimmunoassay (RIA). RESULTS: Mean nocturnal excretion of aMT6s in urine after intake of the drugs was as follows (in microg): placebo 26; (R)-propranolol 24 (-7%, NS); (S)-propranolol 5 (-80%, P < 0.001); (R)-atenolol 27 (+7%, NS); (S)-atenolol 4 (-86%, P < 0.01); (R,S)-carvedilol 23 (-10%, NS); (R,S)-verapamil 29 (+14%, NS). These data show that only the specifically beta-blocking (S)-enantiomers of propranolol and atenolol decrease the nocturnal production of melatonin whereas the non-beta-blocking (R)-enantiomers have no effect. Unexpectedly, (R,S)-carvedilol which inhibits both alpha- and beta-adrenoceptors does not decrease melatonin production. CONCLUSION: These findings indicate that beta-blockers decrease melatonin release via specific inhibition of adrenergic beta1-receptors. Since lower nocturnal melatonin levels might be the reason for sleep disturbances, further clinical studies should investigate whether or not oral administration of melatonin might avoid this well-known side-effect of beta-blockers. The reason why (R,S)-carvedilol does not influence melatonin production remains to be determined.

Parasympathetic receptor blockade and the heart rate performance curve.

Parasympathetic receptor blockade and the heart rate performance curve. Med. Sci Sports Sci., Vol. 30. No. 2, pp. 229-233, 1998. The aim of the present study was to investigate the influence of parasympathetic receptor blockade on the heart rate performance curve (HRPC). Twenty healthy male subjects performed a first cycle ergometer test (F), showing a HRPC deflection of varying degree and direction. Subjects then in random order performed two additional cycle ergometer tests, one with atropine (A) and the other with placebo (P). Two lactate turn points (LTP1, and LTP2) were determined by means of linear regression turn point analysis. The degree and direction of the deflection of the HRPC was calculated mathematically as factor kHR (kHR>0 = downsloping of HPRC; kHR<0 = upsloping of HRPC). In comparison with that in F and P, HR in A was significantly higher at rest, LTP1, LTP2, and during recovery, but not at Power(max). An upsloping deflection of the HRPC was seen in only five cases in F and P, whereas in A 10 cases were observed (P < 0.05). In A, kHR was significantly lower than in F and P. A significant correlation for kHR was found among F, P, and A. Independent from parasympathetic receptor blockade and the HR at Power(max), the HR at LTP2 was lower in cases with negative kHR (upsloping). In A as well as in P a significant correlation was observed between kHR and HR at LTP2. The individual time course of HRPC is reproducible and may be independent of parasympathetic activity.

Bradydysrhythmia-related presyncope secondary to pheochromocytoma.

Pheochromocytoma endures as a life-threatening disorder. In the absence of systemic hypertension, diagnosis may be difficult. We present a 46-year-old normotensive male with a history of presyncope. One of these episodes could be documented, and revealed symptomatic bradycardia suspicious of sinus node arrest. Due to hints of an elevated sympathetic tone (Schellong test, circadian blood pressure pattern without diurnal rhythm) 24-h urinary catecholamine concentrations were measured and found increased. MIBG-scintigraphy and abdominal-computed tomography indicated the location of the pheochromocytoma. After removal of the tumour, no further episodes of presyncopes or bradydysrhythmias were observed.