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Background and Aims: Cardiovascular complications are common in hip fracture patients but the role of fracture type and operative method in these is unclear. This prospective cohort study aimed to evaluate the impact of fracture- and operative characteristics on perioperative cardiovascular complications and prognosis in unselected hip fracture patients. Material and Methods: During a 7-month trial registration period, a population of 197 consecutive hip fracture patients (median age 84 years) diagnosed with femoral neck or pertrochanteric fracture was formed. The exclusion criteria were patient refusal, subtrochanteric fracture, or death preoperatively. Pre- and postoperative troponin T (TnT) elevation, perioperative N-terminal fragment of pro-B-type natriuretic peptide (NT-proBNP) level, perioperative cardiovascular adverse events, and all-cause 30-day and 2- and 5-year mortalities were studied. Results: Femoral neck fracture was independently associated with preoperative myocardial injury witnessed by TnT elevation (HR 2.95, 95% confidence interval 1.21–7.19, p = 0.018). The fracture type, surgery delay, or operative method were not significantly associated with NT-proBNP levels, cardiovascular adverse event diagnoses, or prognosis. Cardiovascular adverse events were clinically diagnosed in 28 (14%) participants, and these had a higher mortality compared to participants without such diagnosis (at 30 days, 32% vs 5%; 2 years, 71% vs 31%; and 5 years, 86% vs 59%; p Conclusion: While the femoral neck fracture independently predicts preoperative cardiovascular morbidity, the operative method does not affect perioperative cardiovascular complications or the prognosis, and it may be selected by the treating clinician based on other criteria.

Aim To evaluate the quantity and mechanism of sudomotor function during euglycaemia and hypoglycaemia using sympathetic skin responses in patients with Type 1 diabetes and control subjects. Methods Sympathetic skin responses were measured in 16 patients with diabetes without neuropathy and in eight control subjects during euglycaemic and hypoglycaemic clamp. Results During hypoglycaemia, the number of repetitive synchronous sympathetic skin responses significantly increased in both groups (P

Vikman S, Airaksinen KEJ, Tierala I, Peuhkurinen K, Majamaa-Voltti K, Niemela M, Tuunanen H, Nieminen MS, Niemela K (Tampere University Hospital, Tampere; University of Turku, Turku; University of Helsinki, Helsinki; University of Kuopio, Kuopio; and University of Oulu, Oulu; Finland). Improved adherence to practice guidelines yields better outcome in high-risk patients with acute coronary syndrome without ST elevation: findings from nationwide FINACS studies. J Intern Med 2004; 256: 316–323. Objectives. Treatment options for acute coronary syndrome (ACS) without ST elevation have evolved rapidly during the recent years, but the successful implementation of practice guidelines incorporating new treatments into practice has been challenging. In this study, we evaluate whether targeted educational intervention could improve adherence to treatment guidelines of ACS without ST elevation. Design, setting and subjects. A previous study, FINACS I, evaluated the treatment and outcome of 501 consecutive non-ST elevation ACS patients that were referred in early 2001 to nine hospitals, covering nearly half of the Finnish population. That study revealed poor adherence to ESC guidelines, so targeted educational intervention on optimal practice was arranged before the second study (FINACS II), which was performed in the same hospitals using the same protocol as FINACS I. FINACS II, undertaken in early 2003, evaluated 540 consecutive patients. Interventions. Targeted educational programmes on optimal practice. Main outcome measures. The use of evidence-based therapies in non-ST elevation ACS patients. In-hospital event-free (death, new myocardial infarction, refractory angina, readmission with unstable angina and transient cerebral ischaemia/stroke) survival, and event-free survival at 6 months. Results. Baseline characteristics and risk markers were similar in both studies, and no significant changes in resources were seen. In 2003, the in-hospital use of statins, ACE-inhibitors, clopidogrel and glycoprotein (GP) IIb/IIIa receptor antagonists increased significantly, and in-hospital angiography was performed more often, especially in high-risk patients (59% vs. 45%, P

Objectives. We investigated the prognostic significance of orthostatic hypotension on the risk of myocardial infarction (MI) amongst the elderly. Design. Prospective population-based study. Setting. Home-dwelling population. Subjects. Orthostatic testing was performed between 8 a.m. and 2 p.m., irrespective of having had meals, on 792 persons, representing 82% of all home-dwelling persons aged ≥70 years living in five municipalities around the city of Oulu. Main outcome measures. Occurrence of cases of MI were recorded during mean 3.58 (SD 1.09) years follow-up period, from national mortality statistics and local hospital discharge registers. Results. Ninety cases of MI, of which 40 were fatal after initial hospitalization, occurred during the follow-up period. Orthostatic diastolic blood pressure (BP) drop 1 min after standing up was associated with subsequent MI, but systolic BP reactions had no predictive value. According to the Cox regression model, the strongest predictor of the occurrence of subsequent MI was found in regard to ≥8 mmHg drop in diastolic BP 1 min after standing up; adjusted for history of MI, diabetes mellitus, chest pain, use of calcium antagonist, β-blocker, nitrate and diuretic medication, hazard ratio of MI being 2.00 (1.11–3.59). Conclusions. Orthostatic testing offers a novel means to assess the risk of MI amongst elderly persons. Diastolic BP drop immediately after standing up identifies elderly subjects at a high risk of subsequent MI.

Asymptomatic coronary artery disease and myocardial infarctions are common in diabetic subjects. The available clinical and epidemiological data suggest that the increased incidence of asymptomatic myocardial infarctions and coronary artery disease in diabetic patients mainly reflects accelerated coronary atherosclerosis and the proportion of silent disease relative to symptomatic disease or episodes is not increased in diabetes. In spite of the theoretical background, there is no convincing clinical or epidemiological evidence that diabetic autonomic neuropathy plays a major part in the lack of ischaemic pain. This is not surprising because the mechanisms of silent myocardial ischaemia are complex and controversial even without diabetes.

In spite of recent advances in secondary prevention, sudden cardiac death has remained a major public health problem as the majority of fatalities occur in subjects without a history of severe heart disease. Abrupt rupture of a vulnerable plaque resulting in thrombotic occlusion of a coronary artery is a common cause of sudden death in this population. Coronary occlusion does not, however, invariably lead to sudden death but may cause acute myocardial infarction or exacerbation of chest pain. Extensive studies in experimental animals and increasing clinical evidence indicate that autonomic nervous activity has a significant role in modifying the clinical outcome. Sympathetic hyperactivity favours the genesis of life-threatening ventricular tachyarrhythmias while vagal activation exerts an antifibrillatory effect. Strong afferent stimuli from the ischaemic myocardium impair arterial baroreflex and may lead to dangerous haemodynamic instability. Studies with a human angioplasty model have shown that there is wide interindividual variation in the type and severity of autonomic reactions during the early phase of abrupt coronary occlusion, a critical period for out-of-hospital cardiac arrest. The site of the occlusion is not a significant determinant of the reactions, whereas the severity of a coronary stenosis, adaptation or ischaemic preconditioning, beta-blockade and gender seem to affect the autonomic reactions and occurrence of complex ventricular arrhythmias. Clinical and angiographic factors are, however, poor predictors of autonomic reactions in an individual patient. Recent studies have documented a hereditary component for autonomic function, and genetic factors may also modify the clinical manifestations of acute coronary occlusion.

Cardiovascular parasympathetic activity is attenuated in essential hypertension. Both β-adrenoceptor antagonists and angiotensin converting enzyme inhibitors have been reported to increase vagal modulation of heart rate and baroreflex sensitivity, but the relations between the antihypertensive and vagal cardiac effects of these drugs have remained unclear in essential hypertension. In the present study we evaluated the effects of a 4-week crossover monotherapy with metoprolol and ramipril on spectrum analysis indices of heart rate variability in the supine rest and head-up tilted positions, baroreflex sensitivity (phenylephrine method), and 24-h ambulatory blood pressure (BP) in 12 formerly untreated stage 1–2 essential hypertensive patients. Compared to the pretreatment values, both drugs decreased BP similarly and significantly. However, the drugs showed different effects on cardiac vagal activity: metoprolol increased significantly mean R-R interval, R-R interval total, and high-frequency variability at supine rest and baroreflex sensitivity, but ramipril did not significantly affect these variables. The metoprolol-induced decrease in ambulatory BP correlated with the prolongation of the R-R interval and the increase of high-frequency variability at supine rest. The present data show that 4-week treatment with metoprolol increases tonic and reflex vagal cardiac activity, whereas ramipril does not affect vagal cardiac control in essential hypertension. Increase in vagal activity may contribute to the BP-lowering effect of metoprolol in hypertensive patients.

Background —The prognostic role of heart rate (HR) variability analyzed from 24-hour ECG recordings in the general population is not well known. We studied whether analysis of 24-hour HR behavior is able to predict mortality in a random population of elderly subjects. Methods and Results —A random sample of 347 subjects of ≥65 years of age (mean, 73±6 years) underwent a comprehensive clinical evaluation, laboratory tests, and 24-hour ECG recordings and were subsequently followed up for 10 years. Various spectral and nonspectral measures of HR variability were analyzed from the baseline 24-hour ECG recordings. Risk factors for all-cause, cardiac, cerebrovascular, cancer, and other causes of death were assessed. By the end of 10-year follow-up, 184 subjects (53%) had died and 163 (47%) were still alive. Seventy-four subjects (21%) had died of cardiac disease, 37 of cancer (11%), 25 of cerebrovascular disease (7%), and 48 (14%) of various other causes. Among all analyzed variables, a steep slope of the power-law regression line of HR variability (P P P =.0002). The slope of HR variability predicted both cardiac (adjusted relative risk, 2.05; P =.0002) and cerebrovascular death (adjusted relative risk, 2.84; P =.0001) but not cancer or other causes of death. Conclusions —Power-law relationship of 24-hour HR variability is a more powerful predictor of death than the traditional risk markers in elderly subjects. Altered long-term behavior of HR implies an increased risk of vascular causes of death rather than being a marker of any disease or frailty leading to death.

OBJECTIVE To test the hypothesis that diabetic autonomic neuropathy interfering with sensory impulses from the heart by sympathetic denervation is the major cause of the high prevalence of asymptomatic coronary artery disease (CAD) in diabetic patients. RESEARCH DESIGN AND METHODS We evaluated cardiac sympathetic innervation in a population-based group of 10 asymptomatic diabetic patients with angiographically proven CAD and in an age- and sex-matched group of 10 diabetic patients with symptomatic CAD using [123I]metaiodobenzylguanide (MIBG) scintigraphy. Exercise electrocardiography and myocardial perfusion imaging by 201Tl were used to detect myocardial ischemia, and standard cardiovascular tests were used to diagnose autonomic nervous dysfunction. RESULTS Thallium scintigraphy revealed perfusion defects in all 10 symptomatic patients and in 9 of the asymptomatic patients. MIBG accumulation defects were found in all cases with painless and with painful disease. In the asymptomatic group, the denervation area exceeded the ischemic area in six cases and areas with total MIBG accumulation defects were seen in four cases. In one case, the MIBG defect was not in the ischemic region. In the symptomatic group, the denervation area exceeded the area of the ischemic region in all cases and areas of total denervation were seen in six cases. The autonomic nervous function tests were abnormal in two asymptomatic and three symptomatic patients with CAD. CONCLUSIONS Cardiac sympathetic denervation is common in both patients with painful CAD and patients with asymptomatic CAD regardless of diabetic autonomic neuropathy. This finding supports the view that sympathetic innervation of the heart is highly sensitive to ischemia and this profound effect of ischemia masks the potential effects of autonomic neuropathy on sympathetic innervation. Mechanisms leading to the lack of ischemic pain in diabetic patients with CAD are complex and are not solely explained by autonomic neuropathy.

We determined changes in serum concentrations of thyroid hormones during carbamazepine (CBZ) therapy during a 5-year prospective follow-up study of 20 patients with newly diagnosed epilepsy. In addition, we evaluated the effects of replacing CBZ with oxcarbazepine (OCBZ) in 12 male patients with epilepsy in a 6-month prospective follow-up study. Circulating thyroxine and free thyroxine levels decreased after 2-month CBZ treatment and remained at a low level during the 5-year follow-up. There were no associated changes in serum thyrotropin (TSH) concentrations. When CBZ was replaced by OCBZ, the function of the liver's P450 enzyme system normalized, as shown by an increase in antipyrineT1/2, and a decrease in antipyrineCL. Serum total and free thyroxine levels increased, and thereafter serum TSH levels decreased. Indexes of diastolic heart function improved concomitantly, which may reflect subclinical hypothyroidism at the cellular level during CBZ treatment. We conclude that normal thyroid function can be restored in patients with epilepsy by replacing CBZ with OCBZ.

The inter-relationships between ischaemia-induced metabolic changes and atrial natriuretic peptide (ANP) release were studied in 18 patients undergoing elective percutaneous transluminal coronary angioplasty (PTCA). Transcardiac differences in ANP, lactate, pH, pCO2 and O2 saturation were analysed before and after balloon inflation. The patients were divided into ischaemia and non-ischaemia groups on the basis of the change in lactate extraction ratio during balloon inflation. The ischaemia group (patients with a decrease in lactate extraction ratio) showed an increase of 27 +/- 15 pg.ml-1 in the transcardiac ANP difference, whereas a decrease of 27 +/- 17 pg.ml-1 occurred in the non-ischaemia group (no decrease in lactate extraction ratio). The change between the two patient groups was statistically significant (P0.05). Metabolic 'pre-conditioning' was not observed in patients with successive dilatations, therefore data from all the dilatations were combined and evaluated by regression analysis. A correlation coefficient of 0.40 (P0.05) was obtained between the PTCA-induced changes in transcardiac ANP and lactate differences. We conclude that transient myocardial ischaemia induced by PTCA increases circulating ANP concentrations in patients with signs of metabolic ischaemia, but not in those without.

The imbalance of the autonomic nervous function has been shown to contribute to the genesis of ventricular arrhythmias. Power spectral analysis of components of heart rate variability has the potential to quantify the cardiac autonomic tone during ambulatory electrocardiographic recording. We analysed the power spectral components of total power, very low frequency power (0.0033-0.04 Hz), low frequency (0.04-0.15 Hz) and high frequency (0.15-0.40 Hz) power in 12 consecutive patients accompanied with 27 episodes of ventricular tachycardia in acute myocardial infarction. The spectral areas were measured in 5-min periods preceding the onset of ventricular tachycardias. The total power of heart rate variability increased progressively before the onset of ventricular tachycardia episodes (P0.05). The increase of total power was mainly due to higher, very low frequency power at the onset rather than before the onset of ventricular tachycardia (P0.05). The trend towards adrenergic predominance at the onset of ventricular tachycardia was observed by an increase of average heart rate (P0.05) without concomitant increase in high frequency power. Thus, the occurrence of ventricular tachycardia is associated with changes in the power spectrum of heart rate variability suggesting alterations in autonomic tone at the onset of ventricular tachycardia in acute myocardial infarction.

Oral anticoagulant therapy with warfarin commenced pre-operatively (n = 102) to prevent coronary artery vein graft occlusions was compared in terms of efficacy and safety with dipyridamole and aspirin (n = 130) in a randomized consecutive series of patients. Anticoagulant therapy was started at least 2 weeks before coronary artery bypass surgery (CABG) and antiplatelet therapy was started at least 3 days before CABG with dipyridamole followed by a combination of 250 mg aspirin once a day via a nasogastric tube 6 h after CABG. Overall, vein graft patency at 3 months after surgery did not differ significantly between the anticoagulant group (203/275, 74%) and dipyridamole-aspirin group (238/311, 77%), but the occlusion rate for grafts with endarterectomy was higher in the anticoagulant (46%) than in the dipyridamole and aspirin group (16%), (P less than 0.05). The rate of peri-operative complications including deaths, re-operation and myocardial infarction was higher in the anticoagulant than antiplatelet group (26.5% vs 13.8%, P less than 0.05). The occurrence of postoperative bleeding complications did not differ significantly between the groups. Thus, oral anticoagulant therapy commenced pre-operatively has no advantages over conventional antiplatelet therapy in patients who undergo CABG. Neither antithrombotic regimens proved to be satisfactory for preventing acute bypass vein graft occlusions in this patient population with advanced coronary artery disease.

OBJECTIVES--To study the risk factors for cardiac mortality after coronary artery bypass graft surgery. DESIGN AND SETTING--Follow up study of patients who had undergone coronary artery bypass graft surgery at the University Hospital of Oulu, Finland. PATIENTS AND INTERVENTIONS--339 consecutive patients who underwent cardiac catheterisation three months after bypass surgery. MAIN OUTCOME MEASURES--Incidence of cardiac deaths during the follow up period of five years and predictive value of clinical and angiographic variables for subsequent cardiac mortality. RESULTS--The incidence of cardiac deaths was 5.1%, and 81% of these were sudden deaths. The postoperative ejection fraction was significantly lower in the patients with subsequent cardiac death than in the survivors (p less than 0.001), and their left ventricular end systolic and end diastolic volumes were higher (p less than 0.001 and p less than 0.05 respectively). The incidence of cardiac deaths was 43% in the patients with a postoperative ejection fraction of less than 40%. The myocardial jeopardy index after surgery and the rate of graft patency were not significantly different in the survivors and patients who died. The only clinical factors that were different between the groups were postoperative use of diuretics (p less than 0.001) or digitalis (p = 0.02). After adjustment for other prognostic variables by the proportional hazards method, a low postoperative ejection fraction remained significant as a predictor of the relative risk of cardiac mortality five years after operation (p less than 0.01). CONCLUSIONS--Patients with angiographic evidence of impaired left ventricular function after bypass surgery are still at relatively high risk of dying suddenly, but myocardial ischaemia due to incomplete revascularisation is not strongly associated with an increased risk of cardiac mortality. Conventional clinical methods do not seem to be helpful for identifying patients with an increased risk of cardiac death after bypass surgery.

We evaluated the autonomic influence on pregnancy outcome with prospective study of 100 consecutive pregnancies in women with insulin-dependent diabetes mellitus (IDDM). Tests of cardiovascular autonomic nervous function were performed at the beginning of each pregnancy, and two groups were formed. Group 1 was comprised of 23 pregnancies with autonomic dysfunction, and group 2 was comprised of 77 pregnancies with no abnormalities in cardiovascular tests. Elective abortion was later induced for medical reasons in two cases in group 1, and these women were excluded from the study. The groups were comparable with respect to age, duration of diabetes, and presence of nephropathy. Both groups also achieved comparable glycemic control during pregnancy. There were no significant differences between groups 1 and 2 in any specific pregnancy complication (spontaneous abortions, 5 vs. 3%; perinatal mortality, 10 vs. 1%; congenital malformations, 10 vs. 4%; respiratory distress syndrome, 5 vs. 8%; preeclampsia, 20 vs. 10%; maternal ketoacidosis, 4 vs. 0%; and maternal hypoglycemic accidents, 10 vs. 4%, respectively), but the frequency of pregnancies with at least one of the above complications was greater in group 1 (52 vs. 23%, P = 0.01). Stepwise logistic regression analysis showed the association between autonomic dysfunction and pregnancy outcome to be independent of high initial glycosylated hemoglobin levels, long duration of diabetes, and nephropathy. Maternal autonomic dysfunction seems to be associated with an increased frequency of overall pregnancy complications but does not significantly interfere with the achievement of tight metabolic control during pregnancy.

Diabetic patients may have various abnormalities in left ventricular systolic and diastolic function not attributable to coronary heart disease, hypertension or other known cardiac disease. Although the exact causes of this diabetic heart muscle disease or "diabetic cardiomyopathy" are still incompletely understood, several mechanisms may contribute to it including disturbed myocardial energy metabolism, microvascular changes, structural changes in collagen, increased myocardial fibrosis, and cardiac autonomic neuropathy. Perhaps the most typical feature of diabetic heart muscle disease is an abnormal filling pattern of the left ventricle, suggesting reduced compliance or prolonged relaxation. Left ventricular systolic function is commonly normal at rest in asymptomatic diabetic patients, but it frequently becomes abnormal during exercise. The abnormalities in left ventricular systolic function may be partly reversible along with an improvement of metabolic control of diabetes. It is not known how frequently subclinical abnormalities in left ventricular function in diabetic patients result in clinically manifest heart failure.

A 32-year-old man called an ambulance because of rapidly worsening nausea and dyspnoea. When contacted he was precomatous and no clear history could be taken. Patient records showed that he was taking flecainide 200 …

Serum thyroid hormone and thyrotropin levels were assayed and the myocardial function was evaluated by measuring systolic time intervals both in 30 patients with epilepsy on long-term carbamazepine monotherapy and in 19 healthy volunteers. Serum thyroxine, free thyroxine and triiodothyronine levels were significantly lower (p < 0.001) in the patient group than in the control group and systolic time intervals were similar in both groups.

Background —Trigger mechanisms for the onset of paroxysmal atrial fibrillation (AF) in patients without structural heart disease are not well established. New analysis methods of heart rate (HR) variability based on nonlinear system theory may reveal features and abnormalities in R-R interval behavior that are not detectable by traditional analysis methods. The purpose of this study was to reveal possible alterations in the dynamics of R-R intervals before the spontaneous onset of paroxysmal AF. Methods and Results —Traditional time and frequency domain HR variability indices, along with the short-term scaling exponent α 1 and approximate entropy (ApEn), were analyzed in 20-minute intervals before 92 episodes of spontaneous, paroxysmal AF in 22 patients without structural heart disease. Traditional HR variability measures showed no significant changes before the onset of AF. A progressive decrease occurred both in ApEn (1.09±0.26 120 to 100 minutes before AF; 0.88±0.24 20 to 0 minutes before AF; P 1 (1.01±0.28 120 to 100 minutes before AF, 0.89±0.28 20 to 0 minutes before AF; P P 1 (0.91±0.28 versus 1.27±0.21; P Conclusions —A decrease in the complexity of R-R intervals and altered fractal properties in short-term R-R interval dynamics precede the spontaneous onset of AF in patients with no structural heart disease. Further studies are needed to determine the physiological correlates of these new, nonlinear HR variability measures.

Dynamics analysis of RR interval behavior and traditional measures of heart rate variability were compared between postinfarction patients with and without vulnerability to ventricular tachyarrhythmias in a case-control study. Short-term fractal correlation of heart rate dynamics was better than traditional measures of heart rate variability in differentiating patients with and without life-threatening arrhythmias.

Background Women have worse outcomes when they experience acute myocardial infarction (MI), but the reasons for this sex-related difference are not well understood. Because cardiovascular neural regulation plays an important role in cardiac mortality, we studied possible sex-related differences in the autonomic modulation of heart rate (HR) in middle-aged subjects without known heart disease. Methods and Results Baroreflex sensitivity (BRS) and HR variability were studied in randomly selected, age-matched populations of middle-aged women (n=186; mean age, 50±6 years) and men (n=188; mean age, 50±6 years) without hypertension, diabetes, or clinical or echocardiographic evidence of heart disease. BRS measured from the overshoot phase of the Valsalva maneuver was significantly lower in women (8.0±4.6 ms/mm Hg, n=152) than in men (10.5±4.6 ms/mm Hg, n=151) ( P P P P P P P Conclusions Baroreflex responsiveness is attenuated in middle-aged women compared with men, but the tonic vagal modulation of HR is augmented. Hormone replacement therapy appears to have favorable effects on the cardiovascular autonomic regulation in postmenopausal women.

OBJECTIVE--To study the significance of perfusion of the infarct related coronary artery for susceptibility to ventricular tachyarrhythmias in patients with a remote myocardial infarction. SETTING--Tertiary referral cardiac centre. METHODS--Angiographic filling of the infarct related artery was assessed in a consecutive series of 85 patients with different susceptibilities to ventricular tachyarrhythmias after previous (> 3 months) Q wave myocardial infarction: 30 patients had a history of cardiac arrest (n = 16) or sustained ventricular tachycardia (n = 14), and sustained ventricular tachyarrhythmia was inducible in these by programmed electrical stimulation (arrhythmia group); 47 patients had no clinical arrhythmic events and no inducible ventricular tachyarrhythmias during programmed ventricular stimulation (control group). Eight patients without a history of any arrhythmic events were inducible into ventricular tachycardia. RESULTS--The patients in the arrhythmia group were older (63 (SD 8) years) than the control patients (59 (6) years, P < 0.05), and had larger left ventricular volumes in cineangiography (P < 0.01), but ejection fraction, severity of left ventricular wall motion abnormalities, previous thrombolytic therapy, and time from previous infarction did not differ between the groups. Patients with susceptibility to ventricular tachyarrhythmias more often had a totally occluded infarct related artery on angiography (77%) than patients without arrhythmia susceptibility (21%) (P < 0.001), and complete collateral filling of the infarct artery in cases without complete anterograde filling was less common in the arrhythmia group than in the control group (P < 0.001). Patients without a history of malignant arrhythmia but with inducible ventricular tachyarrhythmia also had no or poor perfusion of the infarct artery more often than the patients without inducible arrhythmia (P < 0.001). Logistic multiple regression showed that no or poor anterograde or collateral filling of the infarct related artery was the most powerful predictor of susceptibility to ventricular tachyarrhythmias (P < 0.001). Left ventricular size and function were not independently related to arrhythmic susceptibility. CONCLUSIONS--No or poor angiographic filling of the infarct related artery is closely associated with susceptibility to ventricular tachyarrhythmias late after acute myocardial infarction, suggesting that perfusion of the infarct artery will modify favourably the electrophysiological substrate of the infarct scar independently of the myocardial salvage achieved by early reperfusion.

We wished to assess the effects of beta-blockade on baroreflex sensitivity and standard tests of integrity of autonomic nervous function in patients with coronary artery disease, and to determine whether the effects of lipophilic (metoprolol) and hydrophilic (atenolol) beta-blockers differ. Beta-blocking drugs increase spontaneous heart rate variability in healthy subjects and in patients with coronary heart disease, but little is known about their effects on baroreflex sensitivity and heart-rate based tests of autonomic integrity. In a randomly allocated double-blind crossover study with three 2-week treatment periods, metoprolol CR 200 mg once a day, or atenolol 100 mg once a day, or placebo once a day, were administered to 18 male patients with stable coronary artery disease. Baroreflex sensitivity was determined from the natural baroreflex challenge of Valsalva strain. Heart rate reactions to standard stimuli were measured. No significant differences were found between the effects of atenolol and metoprolol. Beta-blockade did not significantly affect the baroreflex sensitivity, but it diminished the Valsalva ratio significantly (P < 0.001). The difference between maximum and minimum heart rate during hyperventilation was also significantly lower during beta-blockade. The heart rate response to standing up and the ratio of maximum to minimum heart rate during deep breathing were not influenced by beta-blockade. Discontinuation of beta-blockade seems to be unnecessary for reliable determination of baroreflex sensitivity in patients with coronary artery disease, when the natural pressure challenge of Valsalva strain is sued. Both hydrophilic and lipophilic bet-blockers interfere with certain diagnostic tests of autonomic nervous function.(ABSTRACT TRUNCATED AT 250 WORDS)

BACKGROUND Altered neural regulation of the cardiovascular system may be an important factor for various manifestations of ischemic heart disease. This research was designed to compare the circadian rhythm of cardiac neural regulation and autonomic responses to arousal and upright posture between patients with uncomplicated coronary artery disease (CAD) and age-matched subjects with no evidence of heart disease. METHODS AND RESULTS Twenty-four-hour heart rate variability (HRV) in the frequency domain was analyzed in 20 male patients (mean age, 52 +/- 7 years) with angiographic evidence of CAD without prior myocardial infarction and in 20 healthy men (mean age, 51 +/- 8 years) with no clinical, echocardiographic, or exercise ECG evidence of heart disease. None of the 24-hour average frequency-domain components of HRV differed significantly between the two groups. Healthy subjects had a significant circadian rhythm of normalized units of high-frequency (HF) power of HRV with higher values during sleep. Normalized units of low-frequency (LF) power and the LF/HF ratio also showed a significant circadian rhythm in healthy subjects, with higher values during the daytime. No significant circadian rhythms in any of the normalized spectral components of HRV were observed in patients with CAD, and the night-day difference in LF/HF ratio was smaller in the patients with CAD than in the healthy subjects (0.5 +/- 1.4 versus 1.8 +/- 0.7, P < .001). Awakening when in the supine position resulted in a significant increase in the LF/HF ratio (P < .01) in the healthy subjects, but no significant changes in HRV were observed after awakening in patients with CAD. Assumption of upright position resulted in a comparable decrease in the components of HRV between the groups. CONCLUSIONS The circadian rhythm of cardiac neural regulation is altered in patients with uncomplicated CAD. Reduced autonomic responses to sleep-wake rhythm suggest that the modulation of cardiac autonomic function by stimuli from the central nervous system is impaired in CAD.

The overshoot rise in arterial pressure after release of Valsalva strain is a natural challenge for baroreflex regulation of heart rate. To assess the feasibility of the Valsalva manoeuvre in the determination of baroreflex sensitivity (BRS), we measured the slope of the linear relationship between the length of the RR interval and preceding systolic blood pressure value during the overshoot phase after the strain and compared this index of BRS to a standard phenylephrine test in 64 subjects, of whom 58 had coronary artery disease. The BRS slopes obtained with the Valsalva manoeuvre showed a good linear correlation with the phenylephrine test (r = 0.77 in the 27 patients with two Valsalva and phenylephrine tests and r = 0.56 in the whole cohort). The correlation coefficients of the BRS slopes were better than in the phenylephrine test (r = 0.89 vs r = 0.85, P < 0.05). The rise in systolic blood pressure in the slope calculation area was higher than with phenylephrine (41 +/- 18 vs 30 +/- 10 mmHg, P < 0.01). The reproducibility of BRS slopes in successive tests was comparable with both methods. These results suggest that non-invasive assessment of BRS using Valsalva strain to induce blood pressure rise is possible in patients with coronary artery disease.

Low heart rate variability (HRV) is a predictor of a poor outcome after myocardial infarction. To determine whether coronary artery bypass grafting (CABG) has any effect on HRV, the power spectrum components of HRV were measured in 35 patients before, and 1 week after, CABG. Significant attenuation of all spectral components of HRV were found after CABG (P less than 0.001). High frequency (HF) power decreased to one third of the preoperative level, mid-frequency (MF) power to as little as one fifteenth and low frequency (LF) power to one seventh of the preoperative level. No significant restoration in MF or HF powers occurred during the 6-week follow-up period. The results suggest that CABG causes a marked attenuation of HRV. The prognostic significance of this attenuation is not known.

To evaluate the effect of coronary artery disease on parasympathetic cardiac reflexes in patients with non-insulin-dependent diabetes mellitus (NIDDM), we studied standard cardiovascular reflexes in 27 NIDDM patients with coronary artery disease (group 1) and in 21 NIDDM patients with no signs of coronary artery disease (group 2). Groups did not differ with respect to age, duration of diabetes, or presence of retinopathy. The mean +/- SD heart-rate variation in deep breathing was lower in group 1 than in group 2 (11.6 +/- 6.5 vs. 17.1 +/- 9.0 beats/min, P less than 0.05). Heart-rate variation was more often abnormally low (less than or equal to 10 beats/min) in group 1 than in group 2 (48 vs. 19%, P less than 0.05). Thus, the presence of coronary artery disease appears to modify cardiac parasympathetic reflexes in patients with diabetes mellitus and must be kept in mind when interpreting test results.

We evaluated autonomic nervous function in 14 subjects with severe pre-eclampsia and 11 subjects with normal third-trimester pregnancies using standard cardiovascular tests, i.e. heart rate responses to deep breathing and standing up, and blood pressure response to standing up. Both of the heart rate responses were lower in subjects with severe pre-eclampsia than in the control group (P less than 0.01 and P less than 0.001, respectively). Four subjects with severe pre-eclampsia had postural hypotension, defined as a systolic blood pressure fall of at least 30 mmHg on standing. Our results show that severe pre-eclampsia may be associated with autonomic nervous dysfunction. The inability to regulate heart rate and blood pressure in response to postural alterations may compromise the placental and renal blood flow in certain conditions, emphasising the importance of bed rest in severe pre-eclampsia.

Airaksinen KEJ, Ikaheimo MJ, Huikuri HV, Koistinen MJ, Linnaluoto M, Takkunen JT (Cardiovascular Division, Department of Medicine, Oulu University Central Hospital, Oulu, Finland). Effects of isometric exercise and heart rate on left ventricular filling pattern assessed by pulsed Doppler echocardiography. Left ventricular filling pattern was assessed by pulsed Doppler echocardiography at rest and during handgrip exercise in 33 healthy middle-aged subjects. The peak mitral flow-velocities during the early rapid filling phase (E) and during late (atrial) filling (A) were measured and the ratio of these peak flow-velocities (E:A ratio) was calculated. The E:A ratio was inversely related to age (r = −0.50), heart rate (r = −0.47) and septal thickness (r = −0.36) at rest. Exercise caused a significant (P < 0.001) decrease in E:A ratio as a result of an increase in the peak A velocity. No significant change in the peak E velocity was observed during exercise. The exercise E:A ratio was related to heart rate (r = −0.53), but not to resting E:A ratio or age, since the decrease in E:A ratio tended to be less in the older subjects. Our study shows that isometric exercise augments the relative contribution of atrial contraction to left ventricular filling and this increase may ‘mask’ minor changes in resting transmitral flow pattern associated with, e.g. ageing. Secondly, in addition to age, heart rate must be taken into account when studying populations with different heart-rate levels or interventions associated with simultaneous heart rate changes.

Supine and standing heart rate and heart rate responses to deep breathing and standing up (the 30-to-15 ratio), indices of autonomic nervous function, were measured during each trimester and postpartum in 25 women with insulin-dependent diabetes and 10 nondiabetic women. The groups did not differ with respect to autonomic function in the basal state (postpartum), and the heart rate response to deep breathing diminished progressively in both groups during pregnancy, although the change tended to be less pronounced in the diabetic women. The 30-to-15 ratio did not alter significantly during pregnancy. The diabetic women had a higher supine heart rate than the healthy women in the basal state, but the pregnancy-induced increase in heart rate was less in the diabetic women. Thus, the reversible diminution of heart rate response to deep breathing during pregnancy is a physiological finding and does not denote development of autonomic nervous dysfunction. Second, the increase in heart rate, a primary cardiovascular adjustment to pregnancy, seems to be blunted in diabetic women.

Impaired reflex control of heart rate seems to be associated with increased risk of sudden cardiac death. To assess the effect of aortic valve stenosis on parasympathetic heart rate control we measured the heart rate responses to deep breathing and to standing up, non-invasive measures of cardiac parasympathetic activity, in 24 patients with valvular aortic stenosis and in 24 healthy asymptomatic subjects of the same age group. All but one of the patients were symptomatic and the mean aortic valve pressure gradients ranged from 32 to 114 mmHg. The heart rate response to deep breathing was significantly (P less than 0.05) lower in valve patients than in the healthy subjects. The heart rate changes evoked by standing up, however, did not differ significantly between the groups. The heart rate response to deep breathing was inversely weakly related to the left ventricular end-diastolic pressure (r = -0.41, P less than 0.05), but not significantly to the aortic valve pressure gradient, valve area, left ventricular ejection fraction or presence of coronary artery disease. Our results suggest that the impairment of reflex heart rate control is common in patients with significant aortic valve stenosis.

To assess the adaptation of the heart of diabetic subjects in the natural volume overload state of pregnancy, echocardiography was performed during each trimester and postpartum in 17 women with insulindependent diabetes mellitus (IDDM) and in 11 healthy women. The mean duration of diabetes was 14 yr and signs of microvascular complications were detected in 6 patients. The diabetic women had slightly smaller left ventricles than the control women already in the basal state (postpartum), and the pregnancy-induced increase in left ventricular size and stroke volume was less in the diabetic than in the control women. The heart rate rise also tended to be less in the diabetic women, resulting in a markedly smaller increase in cardiac output in this group (1.3 vs. 3.4 L/min, P < .01). Left ventricular systolic function, wall thicknesses, or left atrial size did not differ between the groups at any point in the study. Minor collections of pericardial fluid were observed in 14 (76%) diabetic women and in 5 (45%) control women during the second and/or third trimester, but only 2 diabetic women had classic pericardial effusions. In conclusion, the normal hemodynamic adjustments to pregnancy seem to be impaired in women with IDDM. Preclinical diabetic cardiomyopathy and autonomic neuropathy may be involved in the observed alterations.

We measured the variation in heart rate during deep breathing, a sensitive non-invasive measure of cardiac parasympathetic activity, in 95 patients 3 weeks after myocardial infarction and in 40 asymptomatic healthy controls. The variation in rate was significantly lower (11.6 +/- 6.1 vs 17.6 +/- 7.3 beats/min, P less than 0.001) in patients with myocardial infarction than in controls. Forty-nine patients (52%) and 5 controls (13%) were considered to have diminished (less than or equal to 10 beats/min) variation of rate. The diminution in this variation was not related to the type or location of myocardial infarction, to maximum release of CK-MB or to cardiovascular medication. Our results suggest that impairment of vagal control of heart rate is common after myocardial infarction. The impairment cannot be predicted by any specific feature of the disease.

Left ventricular diastolic function was assessed by pulsed Doppler echocardiography in 21 subjects (mean age 48 yr) with insulin-dependent diabetes mellitus (IDDM) and without evidence of ischemic heart disease and in 21 healthy control subjects of similar age and sex distribution. The peak mitral valve flow velocities during the early rapid filling phase (E) and during late atrial filling (A) were measured, and the ratio of these peak flow velocities (E:A) was calculated. E was similar in both groups, but A was higher (P < .01) in the diabetic group. Thus, E A was lower (1.19 ± 0.24 vs. 1.65 ± 0.67; P

Heart rate variation in deep breathing, a sensitive non-invasive measure of cardiac parasympathetic activity, was measured in 63 patients with coronary artery disease, in 22 patients with atypical chest pain, and in 20 healthy symptom free volunteers. There was significantly less heart rate variation in deep breathing in the patients with coronary artery disease than in the healthy subjects. Twenty patients (32%) with coronary artery disease had lower than normal variation in heart rate. The patients with chest pain showed an intermediate heart rate response to deep breathing. Sinus arrhythmia in the patients with coronary artery disease was not related to the functional class, medication, number or location of narrowed vessels, or to the left ventricular ejection fraction, and end diastolic pressure. These results suggest that impairment of the parasympathetic nervous function is common in coronary artery disease.

Objective: Low heart rate variability after acute myocardial infarction is associated with an increased risk of cardiac mortality. The aim of this study was to investigate the determinants of frequency domain measures of heart rate variability in acute myocardial infarction. Methods: Heart rate variability in the frequency domain was compared in 43 patients in the early (0-12 h from the onset of pain) and convalescent (1 week after) phases of myocardial infarction and related to location (22 patients with anterior infarction and 21 patients with inferior infarction) and size of the infarct, occurrence of ventricular ectopic activity, and thrombolytic therapy. Results: In the early phase of infarction all the power spectral components of heart variability were significantly lower in the patients with anterior infarcts than in those with inferior infarcts (p < 0.05 for all), but heart rate variability did not differ significantly between anterior and inferior infarct groups in the convalescent phase. High frequency power of heart rate variability was significantly lower in the convalescent phase than in the early phase in both the anterior and inferior infarction groups (p < 0.05 and p = 0.001, respectively), but other measures of variability did not change significantly. The ejection fraction was correlated with total power (p < 0.05), low frequency power (p < 0.01), and very low frequency power of heart rate variability (p < 0.05), and the low frequency and high frequency power components were significantly lower in the patients with non-sustained ventricular tachycardia than in those without repetitive ventricular activity in the convalescent phase of myocardial infarction (p < 0.05). Thrombolytic therapy had no influence on the measures of heart rate variability. Conclusions: The frequency domain measures of heart rate variability are mostly determined by the location of myocardial infarction in the early phase, whereas a correlation between heart rate variability and left ventricular function and arrhythmic propensity is more obvious in the convalescent phase. Cardiovascular Research 1994; 28 :1273-1276

Objective To measure plasma atrial natriuretic peptide (ANP) in relation to maternal haemodynamics and body fluid balance in the early puerperium following uncomplicated pregnancy and pre-eclampsia. Design A longitudinal study from late pregnancy and into the early postpartum period (days 1 to 3 and days 4 to 6) compared with nonpregnant controls. Subjects Eleven women with uncomplicated pregnancies, 12 women with pre-eclampsia and 12 healthy, nonpregnant women. Main outcome measures Maternal heart dimensions determined by M-mode echocardiography, concentrations of ANP, and daily urine output and sodium excretion. Results After delivery increases in left atrial dimensions, represented as mean (SEM), from 33.2 (1–6) to 37.7 (1.7) mm and ANP levels from 7.9 (1.1) to 19.0 (2.7) pmol/L were observed at 1–3 days postpartum in normal pregnant women, but we were not able to demonstrate a significant increase in diuresis and natriuresis. In the third trimester left atrial dimensions (38.4 (1.2) mm) and ANP levels (15.4 (2.2) pmol/L) were greater in pre-eclampsia. ANP levels rose further in pre-eclamptic women in the early puerperium (27.4 (7.4) pmol/L) with an increase in diuresis and natriuresis, while left atrial dimensions did not change significantly (39.4 (1.7) mm). A pericardial effusion was found in 11 pre-eclamptic but in only three healthy pregnant women. Conclusions A concommitant increase in left atrial dimensions and ANP in the early puerperium following uncomplicated pregnancies is consistent with the mechanism of atrial stretch as a stimulus for ANP release, although the biological significance of this finding remained unclear. A significantly higher release of ANP in the early puerperium after pregnancies complicated by pre-eclampsia may be a mechanism which promotes the renal elimination of excessive body fluids and sodium.

Impairment of vagal heart rate control is common in coronary artery disease. To evaluate whether percutaneous transluminal coronary angioplasty (PTCA) has any beneficial effect on this impairment we measured heart rate responses to deep breathing and to standing up, standard tests of cardiac parasympathetic activity, in 28 patients before and 4 weeks after successful PTC A. Before PTC A, 10 patients (36%) had an abnormal heart rate response to deep breathing and one patient (4%) an abnormal response to standing up. The heart rate responses did not change significantly from thepreoperative values after PTC A. Thus, the relief of critical coronary obstruction by PTC A seems to have no beneficial effect on vagal heart rate control