Preben Bjerregaard

Idiopathic Short QT Interval:A New Clinical Syndrome?

In this first clinical report of an idiopathic familial persistently short QT interval (QTI), we describe three members of one family (a 17-year-old female, her 21-year-old brother, and their 51-year-old mother) demonstrating this ECG phenomenon, associated in the 17-year-old with several episodes of paroxysmal atrial fibrillation requiring electrical cardioversion. Similar ECG changes seen in an unrelated 37-year-old patient were associated with sudden cardiac death. Our report also describes other manifestations of abnormal shortening of the QTI and considers the possible arrhythmogenic potential of the short QTI.

The Brugada syndrome: clinical, electrophysiologic and genetic aspects ☆

This review deals with the clinical, basic and genetic aspects of a recently highlighted form of idiopathic ventricular fibrillation known as the Brugada syndrome. Our primary objective in this review is to identify the full scope of the syndrome and attempt to correlate the electrocardiographic manifestations of the Brugada syndrome with cellular and ionic heterogeneity known to exist within the heart under normal and pathophysiologic conditions so as to identify the cellular basis and thus potential diagnostic and therapeutic approaches. The available data suggest that the Brugada syndrome is a primary electrical disease resulting in abnormal electrophysiologic activity in right ventricular epicardium. Recent genetic data linking the Brugada syndrome to an ion channel gene mutation (SCN5A) provides further support for the hypothesis. The electrocardiographic manifestations of the Brugada syndrome show transient normalization in many patients, but can be unmasked using sodium channel blockers such as flecainide, ajmaline or procainamide, thus identifying patients at risk. The available data suggest that loss of the action potential dome in right ventricular epicardium but not endocardium underlies the ST segment elevation seen in the Brugada syndrome and that electrical heterogeneity within right ventricular epicardium leads to the development of closely coupled premature ventricular contractions via a phase 2 reentrant mechanism that then precipitates ventricular tachycardia/ventricular fibrillation (VT/VF). Currently, implantable cardiac defibrillator implantation is the only proven effective therapy in preventing sudden death in patients with the Brugada syndrome and is indicated in symptomatic patients and should be considered in asymptomatic patients in whom VT/VF is inducible at time of electrophysiologic study.

Short QT Syndrome and Atrial Fibrillation Caused by Mutation in KCNH2

Background: The short QT syndrome is a newly described clinical entity characterized by the presence of a short QT interval associated with cardiac tachyarrhythmias including sudden cardiac death at a young age in otherwise healthy individuals. A genetic basis has been identified linking the disease to mutations in KCNH2 in the familial forms and a mutation in KCNQ1 in a sporadic form of the disease.

Attenuated 24-h heart rate variability in apparently healthy subjects, subsequently suffering sudden cardiac death

Attenuated cardiac parasympathetic activity appear to be an important risk factor contributing to sudden cardiac death in subjects with overt coronary disease but its predictive value in otherwise healthy normal subjects is not known. We have for 8 years followed 260 apparently healthy adult subjects who underwent Hotler monitoring. Twelve died, 14 developed ischaemic heart disease and four suffered sudden cardiac death. A healthy control subject was matched, along with other risk factors, for each case. In each subject 24-h heart rate variability was calculated as the deviation of all normal R—R intervals from mean R—R (SD) and the percentage of successive R—R interval differences exceeding 6% (%DIF6%)—this was used as an index of cardiac parasympathetic activity. There were no significant differences in heart rate variability between the cases developing problems and controls. In the sudden cardiac death victims, however, there was a clear trend towards lower heart rate variability. In them waketime mean SD was 73 ms versus 85 ms for cases and controls respectively (p = 0.08), and for sleeptime 61 ms versus 76 ms (p = 0.07). Compared to normal limits for heart rate variability obtained in 140 subjects that remained healthy for 8 years, figures for both SD and %DIF6% in sudden cardiac death subjects were at or below 95% confidence limits. The results indicate that altered autonomic balance may contribute to sudden cardiac death even in apparently healthy subjects. Subjects with a low 24-h heart rate variability on Holter monitoring may be predicted at an early stage of being at greater risk. This has considerable implications not only for predicting subjects at risk but for assessing physiological (such as exercise) and pharmacological interventions which may reduce such risk.

Circadian variation and influence of risk factors on heart rate variability in healthy subjects

Quantification of variations in instantaneous heart rate (HR) can be used to evaluate cardiac autonomic function. A 24-hour standard deviation of all normal RR intervals less than 50 ms in survivors of myocardial infarction has been shown to be an independent marker of adverse prognosis. Twenty-four-hour HR variability in 140 healthy subjects aged 40 to 77 years was determined as (1) standard deviation, and (2) percentage of successive RR interval differences greater than 6%--an index of parasympathetic activity. The 24-hour standard deviation varied between 68 and 261 ms (median 139). Range for index of parasympathetic activity was 0.1 to 29.6% (median 4.4). Twenty percent of the interindividual variation in HR variability was explained by impact of risk factors. Standard deviation was uninfluenced by age, whereas parasympathetic activity decreased by increasing age. High physical training level was independently associated with significantly higher standard deviation (and parasympathetic activity) values during both day and night. Hourly figures of standard deviation decreased during the night, whereas parasympathetic activity increased and peaked early morning. Standard deviation values as low as those reported in high-risk patients were not observed, but comparable low values for, and lack of diurnal variation in, parasympathetic activity were seen in healthy subjects also. In conclusion, risk factors and, in particular, the physical training level have impact on 24-hour HR variability in healthy subjects. This may prove valuable for modification of cardiac autonomic activity in patients.

Nationwide and Long-Term Survey of Primary Glomerulonephritis in Japan as Observed in 1,850 Biopsied Cases

Primary chronic glomerulonephritis is the most common cause of end-stage renal failure in Japan. The incidence in dialysis patients in Japan is about four times higher than in the United States for reason which are unclear. We conducted a nationwide survey on the natural history and treatment of primary glomerulonephritis under a program project from the Ministry of Health and Welfare of Japan entitled ‘Progressive Chronic Renal Disease’. We analyzed patient characteristics, disease onset, clinical data, and histological findings in 1,850 patients with primary glomerulonephritis from 53 institutions in 1985 who underwent renal biopsy at least 5 years ago, and the follow-up study was carried out 8 years after registration. The incidence of diffuse-mesangial proliferative glomerulonephritis is 41.9%, that of minor glomerular abnormalities 17.5%, and that of focal-mesangial proliferative glomerulonephritis 13.0%. Of 1,045 biopsy specimens that were examined by immunofluorescence microscopy, 47.4% showed IgA nephropathy. Half of all cases with primary chronic glomerulonephritis were asymptomatic and were detected on routine health examination. The survival rates at 20 years from the apparent onset or earliest known renal abnormality are: focal glomerular sclerosis 49%, membranoproliferative glomerulonephritis 58%, diffuse-mesangial proliferative glomerulonephritis 66%, focal-proliferative glomerulonephritis 81%, membranous nephropathy 82%, minor glomerular abnormalities 94%, and IgA nephropathy 61%. In conclusion, a high incidence of IgA nephropathy and a better renal survival of membranous nephropathy are the features of primary chronic glomerulonephritis in Japan. This high incidence of IgA nephropathy together with its poor prognosis is probably the reason for the increased incidence of primary chronic glomerulonephritis in dialysis patients in Japan. In addition, the importance of routine health examination including urinalysis is demonstrated.

Effects of metoprolol on heart rate variability in survivors of acute myocardial infarction

Abstract In survivors of acute myocardial infarction (AMI), reduced 24-hour heart rate (HR) variability is an independent predictor of mortality 1 and sudden cardiac death. 2 The attenuated overall variability is supposed to be due to an autonomic imbalance caused by high sympathetic and concomitant low vagal activity, 3,4 which in experimental studies is associated with lowered threshold for ventricular tachyarrhythmias. 5 Beta blockade in patients surviving AMI has proven to be of beneficial effect particularly in the sudden cardiac death rate. 6 The exact mechanism is not clear. 7 This study investigates the effects of β blockade on 24-hour HR variability in patients who have survived AMI.

A Detailed Angiographic Analysis of Patients With Ambulatory Electrocardiographic Ischemia: Results From the Asymptomatic Cardiac Ischemia Pilot (ACIP) Study Angiographic Core Laboratory

OBJECTIVES The purpose of this Asymptomatic Cardiac Ischemia Pilot (ACIP) data bank study was to characterize angiographic features of coronary pathology of patients enrolled in the ACIP study. BACKGROUND Ischemia during ambulatory electrocardiographic (AECG) monitoring is associated with increased morbidity and mortality. Reports relating AECG ischemia to severity or complexity of coronary artery disease are few in number and small in size and have produced conflicting results. METHODS Coronary angiograms from patients with asymptomatic AECG ischemia enrolled in the ACIP study were reviewed at a central core laboratory. Quantitative measurement of percent stenosis and Thrombolysis in Myocardial Infarction flow grades were used to assess the severity of coronary artery disease. Lesions were also evaluated for the presence of intracoronary thrombus, ulceration and lumen contour as indicators of stenosis complexity. In addition, comparisons were made with 27 patients screened for the ACIP study, but who were found ineligible because they did not have AECG ischemia on 48-h Holter monitoring. RESULTS A total of 329 (75%) of 439 patients with AECG ischemia had multivessel coronary artery disease. Proximal stenoses > or = 50% diameter reduction were common in patients with AECG ischemia (62.2%), as were proximal stenoses > or = 70% (38.7%). Features suggesting complex plaque were found in 50.1% of patients with AECG ischemia. CONCLUSIONS Multivessel coronary artery disease, severe proximal stenoses and features of complex plaque were observed frequently in patients who exhibited AECG ischemia. The presence of severe and complex coronary artery disease may explain, in part, the increased risk for adverse outcome associated with ischemia during activities of daily life.

Clinical diagnosis and risk stratification in patients with Brugada syndrome

In patients with Brugada syndrome (BRS), especially those who are asymptomatic, preclinical diagnosis and risk stratification are vital to the prevention of the fatal ventricular arrhythmias. The initial optimism that a diagnosis of BRS could be made simply on the basis of distinct

Short QT Syndrome

Short QT syndrome (SQTS) is an inheritable primary electrical disease of the heart, discovered in 1999. It is characterized by an abnormally short QT interval (<300 ms) and a propensity to atrial fibrillation and sudden cardiac death (SCD). Like in the case of long QT syndrome there is more than one genetic mutation that can lead to a short QT interval in the ECG and so far two have been identified. Shortening of the effective refractory period combined with increased dispersion of repolarization is the likely substrate for reentry and life threatening tachyarrhythmias. Only 22 people have been classified as having SQTS: 15 from the actual measurement of a short QT interval in their ECG and 7 by history, all having died from SCD. It is very likely that several cases, especially among children, have been overlooked, since the shortness of the QT interval only becomes apparent at heart rates <80 beats/min. The best form of treatment is still not known, but prevention of atrial fibrillation has been accomplished by propafenone, and an implantable cardioverter defibrillator is recommended for prevention of SCD.