Steen Juul-Möller

A dedicated investigation unit improves management of syncopal attacks (Syncope Study of Unselected Population in Malmö—SYSTEMA I)

Aims To investigate whether a systematic approach to unexplained syncopal attacks based on the European Society of Cardiology guidelines would improve the diagnostic and therapeutic outcomes. Methods and results Patients presenting with transient loss of consciousness to the Emergency Department of Skåne University Hospital in Malmö were registered by triage staff. Those with established cardiac, neurological, or other definite aetiology and those with advanced dementia were excluded. The remaining patients were offered evaluation based on an expanded head-up tilt test protocol, which included carotid sinus massage, and nitroglycerine challenge if needed. Out of 201 patients registered over a period of 6 months, 129 (64.2%) were found to be eligible; of these, 101 (38.6% men, mean age 66.3 ± 18.4 years) decided to participate in the study. Head-up tilt test allowed diagnoses in 91 cases (90.1%). Vasovagal syncope (VVS) was detected in 45, carotid sinus hypersensitivity (CSH) in 27, and orthostatic hypotension (OH) in 51 patients. Twelve patients with VVS and 15 with CSH also had OH, whereas 25 were diagnosed with OH only. In a multivariate logistic regression, OH was independently associated with age [OR (per year): 1.05, 95% CI 1.02–1.08, P = 0.001], history of hypertension (2.73, 1.05–7.09, P = 0.039), lowered estimated glomerular filtration rate (per 10 mL/min/1.73 m2: 1.17, 1.01–1.33, P = 0.032), use of loop diuretics (10.44, 1.22–89.08, P = 0.032), and calcium-channel blockers (5.29, 1.03–27.14, P = 0.046), while CSH with age [(per year) 1.12, 1.05–1.19, P < 0.001), use of angiotensin-converting enzyme inhibitor/angiotensin receptor blocker (4.46, 1.22–16.24, P = 0.023), and nitrates (27.88, 1.99–389.81, P = 0.013). Conclusion A systematic approach to patients presenting with unexplained syncopal attacks considerably increased diagnostic efficacy and accuracy. Potential syncope diagnoses have a tendency to overlap and show diversity in demographic, anamnestic, and pharmacological determinants.

Novel cardiovascular biomarkers in unexplained syncopal attacks: the SYSTEMA cohort

The aim of the study was to investigate the resting levels of novel cardiovascular biomarkers in common types of noncardiac syncope.

Prospective Study of Autonomic Nerve Function in Type 1 and Type 2 Diabetic Patients: 24 Hour Heart Rate Variation and Plasma Motilin Levels Disturbed in Parasympathetic Neuropathy

To clarify the impact of autonomic neuropathy in diabetic patients, we have conducted a prospective study of 58 Type 1 and 51 Type 2 diabetic patients (investigated at baseline, after 4, and after 7 years). In Type 1 diabetic patients, the sympathetic nerve function (orthostatic acceleration and brake indices) and in Type 2 patients, parasympathetic nerve function (R‐R interval variation; E/I ratio) deteriorated during 7 years of prospective observation. Symptoms of autonomic neuropathy were associated with signs of autonomic neuropathy (low brake indices) in Type 1 but not in Type 2 diabetic patients. In the latest assessment 24 h ECG recording was performed and blood samples assayed for neuropeptide Y (NPY) and motilin were obtained. Type 1 diabetic patients with parasympathetic neuropathy (abnormal E/I ratio) showed significantly lower SD value (less variation in the R‐R intervals; 29 [17] vs 50 [16], [mean {interquartile range}]; p = 0.001) and higher postprandial plasma motilin values (70 [20] pmol I−1 vs 50 [15] pmol I−1; p< 0.01) than patients with normal parasympathetic nerve function. In Type 2 diabetic patients, sympathetic neuropathy (low brake indices) was associated with an increased frequency of ventricular extra systolic beats during 24 h ECG recording (rs = 0.65; p<0.01). Postprandial plasma NPY levels were not associated with disturbed autonomic nerve function.

Parasympathetic Neuropathy Associated with Left Ventricular Diastolic Dysfunction in Patients with Insulin-Dependent Diabetes Mellitus

Patients with insulin-dependent diabetes mellitus (IDDM) may develop autonomic neuropathy (AN) and cardiac complications. The association between AN and cardiac dysfunction was assessed in 34 IDDM patients (age 40 years, diabetes duration 21 years, 15 women) by echocardiography/Doppler and autonomic nerve function tests. The expiration/inspiration ratio (E/I) was used to assess parasympathetic damage, and the acceleration and brake indices for assessment of sympathetic impairment. AN was present in 21 patients. Patients with abnormal E/I (n = 11) had lower E/A ratios than patients without AN; early to atrial peak filling ratio (E/Amax) was median 1.1 (inter-quartile range 0.2) vs 1.4 (0.7), p = 0.022; early to atrial integral filling ratio (E/Aintegral) was 1.7 (0.3) vs 2.3 (1.2), p = 0.006. Patients with AN and normal E/I (sympathetic neuropathy, n = 10) and patients without AN had similar E/A ratios. E/Aintegral was also lower in patients with abnormal E/I compared with patients with AN and normal E/I; 1.7 (0.3) vs 2.2 (0.7), p = 0.008. Systolic function and cardiac dimensions were generally unaffected and similar in the three groups. In conclusion, diastolic dysfunction and parasympathetic neuropathy are related in IDDM patients.

A prospective study of supraventricular activity and incidence of atrial fibrillation

BACKGROUND Atrial fibrillation (AF) episodes are thought to be started by an electrical trigger reaching susceptible atria. Such a trigger could be present long before the occurrence of sustained symptomatic arrhythmia. OBJECTIVE We sought to determine whether supraventricular extrasystoles (SVESs) and supraventricular tachycardias (SVTs) measured at 24-hour Holter electrocardiogram were associated with an increased incidence of AF. METHODS In 1998-2000, 389 individuals (44% men; mean age 65 years) were examined using 24-hour Holter electrocardiogram. Six individuals with known prevalent AF were excluded. After a mean follow-up of 10.3 years, there were 45 cases of incident AF. Hazard ratios (HRs) were computed using multivariable Cox regression adjusting for age, sex, systolic blood pressure, height, weight, smoking, and homeostatic model assessment of insulin resistance. RESULTS Frequency of SVESs as well as SVT episodes per hour were independent predictors of incident AF (HR per log unit 1.38; 95% confidence interval 1.14-1.68; P = .001 and HR 1.95; 95% confidence interval 1.21-3.13; P = .006, respectively). Further adjustment for education level, alcohol use, use of medication, and physical activity did not substantially alter the results, nor did analysis using competing risks regression accounting for a competing risk of death. The maximum duration of SVT or the heart rate at SVT was not significantly associated with the incidence of AF. CONCLUSION SVESs and SVTs independently predict AF. The prognostic significance was similar for SVESs, SVTs, and a combination of the two. Repeated efforts to detect AF could be of merit in individuals with frequent supraventricular activity.

Increased occurrence of arrhythmias in men with ischaemic type ST-segment depression during long-term ECG recording. Prognostic impact on ischaemic heart disease : results from the prospective population study Men born in 1914 Malmö, Sweden

Abstract. The objective of this long‐term ECG (LTER) study in 394 68‐year‐old men, selected at random from the general population of Malmö, Sweden, was to determine the prevalence and occurrence of cardiac arrhythmias and their impact on morbidity and mortality from IHD. According to Lown classification, 29.4% (116 men) had ventricular arrhythmia (VA) group 4–5. Serious ventricular arrhythmia (Lown group 4–5) was more common in men with asymptomatic ischaemic type ST‐segment depression (STD) than in those without it (37.8% vs. 26.7%; P < 0.05). During the mean follow‐up period of 53.1 months there were seven IHD deaths (6%) among the 116 patients with VA, Lown 4–5, and nine IHD deaths (3.2%) among the 278 patients without serious VA, Lown 0–3, (P = 0.26). Six and three of these deaths, respectively, were considered to be sudden (P = 0.022). The increased cardiac event rate (fatal or non‐fatal MI or deaths due to chronic IHD) associated with a serious ventricular arrhythmia disappeared when history of IHD at baseline and occurrence of STD during LTER were taken into account. The study did not provide any evidence to suggest that ventricular arrhythmia was triggered by myocardial ischaemia. Five of 9 (56%) deaths due to IHD in men with STD occurred among the 38% (37/98) of patients who belonged to Lown class 4–5. It is concluded that the prognostic information derived from LTER can be improved by combined monitoring of STD and ventricular arrhythmias.

Adrenergic and cardiac dysfunction in primary hyperparathyroidism.

Objective  Primary hyperparathyroidism (PHPT) is associated with cardiovascular morbidity and premature death, but the underlying mechanisms are incompletely understood. The aim of this study was to investigate whether adrenergic dysfunction may be a contributing factor.

ECG Diagnosis of Coronary Artery Disease

Objective: In order to assess the diagnostic accuracy of ST depression in the diagnosis of coronary artery disease (CAD) in patients with suspected myocardial ischemia we compared ST depression in 3‐lead ambulatory ECG (AECG) with that of exercise tolerance testing (ETT).

SYNCOPE -a complex syndrome of several causes.

A patient presenting with a transient loss of consciousness (TLOC) can be a real challenge for the clinician with shortand long-term outcomes ranging from an isolated and benign event to a potentially lethal arrhythmia and sudden cardiac death.[1] The problem is not uncommon: between 1% and 2% of all admissions at the Emergency Departments are related to TLOC, and one of three patients will finally be hospitalized [2–4]. In the primary care, we may expect two TLOC incidences per 1000 person-years[5] but this number is probably underestimated as other sources report 4–5 times higher occurrence[6, 7]. Syncope, a temporary impairment of circulation leading to sudden brain hypoperfusion, is the absolutely dominant cause of TLOC.[8, 9] The main etiology of syncope consists of neurocardiogenic reflexes, autonomic disorders (such as orthostatic hypotension), primary cardiovascular disease (arrhythmic and/or structural heart disease), or combination of these [1]. Accordingly, syncope excludes by definition neurological diseases such as epilepsy, and syncope mimics such as psychogenic pseudo syncopal attacks. Today, handling of patients with syncopal attacks often results in long term rotation within the health care system between various specialists, general practitioners, cardiologists, neurologists, internists, geriatricians, otolaryngologists, paediatricians, and even psychiatrists without receiving the proper diagnosis and treatment. A solution proposed by various consensus groups would be to follow specially designed diagnostic algorithms, or to create dedicated ‘syncope units’.[1, 10, 11] However, patients with syncope constitute not only a clinical problem but an economical one as well. In Southern Sweden, in Region Sk ane, 3 312 patients (2 760 per million inhabitants) were diagnosed with syncope (ICD-10 code R55.9) during the year 2009 according to the official statistic reports. The total annual costs for the health care system were large: 1,9 million € directly at the ED; 8,3 million € in patients with fractures; 10,7 million € in patients with arrhythmias; and 17,0 million € in patients with valve disease. Consequently, there is a distinct need to improve the management of syncope, when we consider both clinical and economic aspects.

Use of the ambulatory ECG for identifying individuals at risk for subsequent coronary events

While the ECG is an accepted method for diagnosing myocardial ischemia, the diagnostic accuracy is highly dependent on the pretest prevalence of coronary artery disease (CAD) in the individual patient. The accepted criteria for this diagnosis are reversible ST-segment depression and horizontal or downsloping of at least 0.1 mV (in the case of the ambulatory ECG [Amb-ECG], for at least 1 minute).’ In order to properly diagnose reversible myocardial ischemia, a pretest likelihood of 75% of the disease is needed to reach >90% accuracy of CAD.2 The ECG method generally used for diagnosing reversible myocardial ischemia has, by tradition, been the exercise tolerance test (ETT). For some years, the Amb-ECG has also been used as a practical alternative to the ETT in screening patients for myocardial ischemia. The question that arises today is whether AmbECG may be used as a screening tool to identify apparently healthy subjects who are at high risk for future myocardial infarction ( ~ 1 ) . If this is possible, pharmacological risk factor treatment may reduce the m o r b i d i ~ and mortality within this high risk group. Also, as a consequence, a low risk group may be identified, with less need for aggressive intervention.