Markku K. Linnaluoto

Reproducibility and circadian rhythm of heart rate variability in healthy subjects

Low heart rate (HR) variability, expressed as the standard deviation of cardiac cycle lengths, has been shown to be associated with increased mortality in patients with coronary artery disease.1,2 HR variability can be easily measured from 24-hour electrocardiographic recordings using recently developed software.1,2 However, reference values for HR variability and their reproducibility in normal persons are not well studied. We estimated the reproducibility and circadian rhythm of HR variability, measured from repeated 24-hour electrocardiographic recordings, in young healthy adults to establish normal values and determine patterns of reproducibility.

Remote monitoring of implantable cardioverter defibrillator patients: a safe, time-saving, and cost-effective means for follow-up

Aims The purpose of this prospective study was to investigate whether internet-based remote monitoring offers a safe, practical, and cost-effective alternative to the in-office follow-up visits of patients with an implantable cardioverter defibrillator (ICD). Methods and results Forty-one patients (62 ± 10 years, range 41–76, 83% male) with previously implanted ICD were followed for 9 months. One-hundred and nineteen scheduled and 18 unscheduled data transmissions were performed. There were no device-related adverse events. Over 90% of the patients found the system easy to use. Physicians reported the system as being ‘very easy’ or ‘easy’ to use and found the data comparable to traditional device interrogation in 99% of the cases. They were able to address all unscheduled data transmissions remotely. Compared with the in-office visits, remote monitoring required less time from patients (6.9 ± 5.0 vs. 182 ± 148 min, P < 0.001) and physicians (8.4 ± 4.5 vs. 25.8 ± 17.0 min, P < 0.001) to complete the follow-up. Substitution of two routine in-office visits during the study by remote monitoring reduced the overall cost of routine ICD follow-up by 524€ per patient (41%). Conclusion Remote monitoring offers a safe, feasible, time-saving, and cost-effective solution to ICD follow-up.

Circadian rhythm of heart rate variability in survivors of cardiac arrest

Reduced heart rate (HR) variability is associated with increased risk of cardiac arrest in patients with coronary artery disease. In this study, the power spectral components of HR variability and their circadian pattern in 22 survivors of out-of-hospital cardiac arrest not associated with acute myocardial infarction were compared with those of 22 control patients matched with respect to age, sex, previous myocardial infarction, ejection fraction and number of diseased coronary arteries. Survivors of cardiac arrest had significantly lower 24-hour average standard deviation of RR intervals than control patients (29 +/- 10 vs 51 +/- 15 ms, p less than 0.001), and the 24-hour mean high frequency spectral area was also lower in survivors of cardiac arrest than in control patients (13 +/- 7 ms2 x 10 vs 28 +/- 14 ms2 x 10, p less than 0.01). In a single cosinor analysis, a significant circadian rhythm of HR variability was observed in both groups with the acrophase of standard deviation of RR intervals and high-frequency spectral area occurring between 3 and 6 A.M. which was followed by an abrupt decrease in HR variability after arousal. The amplitude of the circadian rhythm of HR variability did not differ between the groups. Thus, HR variability is reduced in survivors of cardiac arrest but its circadian rhythm is maintained so that a very low HR variability is observed in the morning after awakening, corresponding to the time period at which the incidence of sudden cardiac death is highest.

Gender difference in autonomic and hemodynamic reactions to abrupt coronary occlusion.

OBJECTIVES We sought to determine whether there are gender-related differences in autonomic and hemodynamic responses to abrupt coronary occlusion. BACKGROUND The risk of sudden death before hospital admission is higher in men with an acute myocardial infarction. The reasons for this gender-related difference are not well understood. Cardiovascular autonomic regulation modifies the outcome of acute coronary events, and there are gender differences in the autonomic regulation of heart rate (HR) in normal physiologic circumstances. METHODS We analyzed the changes in HR, HR variability and blood pressure and the occurrence of ventricular ectopic beats during a 2-min coronary occlusion in 140 men and 65 women referred for single-vessel coronary angioplasty. The ranges of nonspecific responses were determined by analyzing a control group of 19 patients with no ischemia during a 2-min balloon inflation in a totally occluded coronary artery. RESULTS Women more often had ST segment changes (p < 0.01) and chest pain (p < 0.05) during the occlusion. Significant bradycardia or increase in HR variability as a sign of vagal activation occurred more often in women than in men (31% vs. 13%, p < 0.01 and 25% vs. 11%, p < 0.05, respectively). Coronary occlusion also more often caused (28% vs. 11%, p < 0.01) a decrease in blood pressure in women. The most pronounced female preponderance was in the incidence of Bezold-Jarisch-type reaction (i.e., simultaneous bradycardia and decrease in blood pressure [16% vs. 0.7%, p < 0.0001]). Logistic regression models developed to analyze the significance of gender while controlling for baseline variables and signs of ischemia identified female gender to be an independent predictor of bradycardic reactions (odds ratio [OR] 3.2, 95% confidence interval [CI] 1.4 to 7.7, p < 0.01), hypotensive reactions (OR 2.6, 95% CI 1.1 to 6.0, p < 0.05) and Bezold-Jarisch-type response (OR 22.2, 95% CI 2.5 to 200, p < 0.01). Significance of female gender as a protector against early coronary occlusion-induced ventricular ectopic beats emerged as having borderline significance (OR 0.4, CI 0.1 to 1.1, p = 0.07). CONCLUSIONS Vagal activation is more common in women than in men during abrupt coronary occlusion and may have beneficial antiarrhythmic effects, modifying the outcome of acute coronary events.

Pericardial effusion after cardiac surgery: incidence, relation to the type of surgery, antithrombotic therapy, and early coronary bypass graft patency.

To investigate the incidence and clinical significance of postoperative pericardial effusion (PE), the presence of PE was evaluated by echocardiography, 1 and 2 weeks postoperatively, in 50 patients after insertion of a valve prosthesis and in 100 patients after coronary bypass surgery (50 patients receiving a combination of aspirin and dipyridamole and 50 receiving warfarin). PE was found during either procedure in 77% of patients and was marked in 29%. Symptoms of postpericardiotomy syndrome (p less than 0.05), pericardial friction rub (p less than 0.01), atrial arrhythmias (p less than 0.05), cardiac enlargement (p less than 0.01), and pleural effusion (p less than 0.05) were detected more frequently in patients with PE than in those without PE. PE was not related to the type of antithrombotic therapy, the rate of coronary bypass graft occlusion, or the type of cardiac surgery. However, the use of the left internal mammary artery as a coronary bypass graft was associated with a slightly higher incidence of PE (p less than 0.05). One patient (0.7%) required surgical drainage of PE. It was concluded that PE is a common and benign finding after cardiac surgery and usually disappears without specific therapy.

Association of lipoprotein cholesterol and triglycerides with the severity of coronary artery disease in men and women.

The differences between the lipid profiles of male and female patients and the effect of plasma lipids on the extent of coronary artery disease were evaluated in 122 angiographically assessed coronary artery disease patients (95 males and 27 females) and 60 controls. Both male and female patients had lower HDL-cholesterol and higher total cholesterol, LDL-cholesterol, triglyceride, VLDL-cholesterol and VLDL-triglyceride concentrations than the controls. The VLDL lipid values did not differ significantly between the male patients with different extent of CAD, whereas the VLDL lipid values of female patients tended to increase with an increasing severity of CAD. High Lp(a) (> or = 35 mg/dl) values were more prevalent in patients with > 50% coronary stenosis compared to patients with < 50% stenosis and the controls (29%, 17% and 12%, respectively). The apolipoprotein E phenotypes and epsilon allele frequencies were similar in the patients and the controls. Low HDL-cholesterol and high LDL-cholesterol are CAD risk factors for both sexes. For women, elevated VLDL-triglycerides seem to be an additional risk factor for CAD.

Responses of heart rate variability to coronary occlusion during coronary angioplasty

Signs of sympathetic activation are frequent during the early hours of anterior wall acute myocardial infarction, whereas parasympathetic reflexes predominate in inferior wall acute myocardial infarction. To assess the immediate autonomic responses to acute coronary occlusion, the high-frequency power and root-mean-square successive difference, frequency and time domain measures of heart rate (HR) variability were analyzed in 73 cases of significant (50 to 95%) coronary artery stenosis immediately before and during balloon occlusion (mean 99 seconds). The range of nonspecific changes was formed on the basis of a control group with no ischemia during dilatations of 16 totally occluded coronary arteries. Balloon occlusion of the left anterior descending artery (n = 35) caused an abnormal increase in the measures of HR variability as a sign of vagal activation in 8 patients (23%), and a significant decrease in HR variability in 4 (11%). Occlusion of the left circumflex artery (n = 19) caused an increase in HR variability in 5 patients (26%), and a decrease in 2 (11%). Right coronary artery occlusion (n = 19) caused an increase in HR variability in 5 patients (26%) and a decrease in 4 (21%). Thus, coronary occlusion causes immediate changes in HR variability in greater than one third of patients with coronary artery disease. The direction of these initial HR variability changes cannot be predicted by the site of coronary occlusion.

Prevalence and prognostic significance of complex ventricular arrhythmias after coronary arterial bypass graft surgery

To assess the prevalence and long-term prognostic significance of complex ventricular arrhythmias after coronary arterial bypass graft surgery, 126 patients were studied by 24-hour ambulatory electrocardiographic recordings and cardiac catheterizations (including left ventricular, coronary arterial and bypass graft angiograms) before and 3 months after surgery, and then prospectively followed-up for a mean of 50 months. Complex ventricular arrhythmias (ventricular premature complexes greater than 30/hour, multiform and/or repetitive complexes) occurred more commonly after than before surgery (in 49/126 vs. 30/126 patients, P less than 0.05). In 18 patients (14%) who had significant worsening of ventricular arrhythmias, the ejection fraction decreased significantly (from 56 +/- 13% to 50 +/- 15%, P less than 0.05) after operation. During the period of follow-up, there were 4 witnessed sudden cardiac deaths. Complex ventricular arrhythmias tended to be more prevalent in patients who died suddenly (in 100%) compared to survivors (in 37%), but their presence did not predict the subsequent sudden death when ejection fraction was included in the stepwise regression model. None of the patients with an ejection fraction over 40% suffered sudden death despite the prevalence of complex arrhythmias in 32% of these patients. Thus, complex ventricular arrhythmias tend to occur more frequently after than before bypass surgery and their occurrence appears to be related to impairment of left ventricular function. Patients with well preserved ventricular function are at low risk of dying suddenly despite presence of complex ventricular arrhythmias after surgery.

Left ventricular response to isometric exercise and its value in predicting the change in ventricular function after mitral valve replacement for mitral regurgitation

Reduced left ventricular (LV) afterload and its effect on the resting ejection fraction may lead to overestimation of LV function in mitral regurgitation (MR). To evaluate LV function during increased afterload of the heart, an isometric handgrip test was performed during cardiac catheterization in 15 patients with mitral regurgitation (MR group) and in 9 normal subjects (normal group). Twelve months after successful mitral valve replacement (MVR) the patients were recatheterized, and the value of preoperative stress testing in predicting the change in resting ventricular function after surgery was estimated. Isometric exercise caused an increase in endsystolic wall stress, a measure of ventricular afterload, in both the MR group and the control group (p less than 0.001). The ejection fraction remained unchanged in the control group, but decreased from 0.58 +/- 0.08 to 0.53 +/- 0.08 in the MR group (p less than 0.001). After MVR, end-systolic wall stress increased significant (p less than 0.001) and the ejection fraction decreased from 0.58 +/- 0.05 to 0.51 +/- 0.1 (p less than 0.05). A positive correlation existed between the change in the ejection fraction during preoperative stress testing and the change in the resting ejection fraction after MVR (r = 0.65, p less than 0.01). In 8 patients whose resting ejection fraction was within normal limits (greater than 0.55) preoperatively, the ejection fraction was depressed (less than 0.55) 1 year after surgery. In all but 1 of these patients the isometric exercise revealed the reduced ventricular response to afterload stress preoperatively (decrease of the ejection fraction greater than 0.03 during exercise). Therefore, the isometric exercise-induced change in LV function appears to predict the influence of MVR on LV function.

Changes in frequency domain measures of heart rate variability in relation to the onset of ventricular tachycardia in acute myocardial infarction

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 (P < 0.05). 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 (P < 0.05). The trend towards adrenergic predominance at the onset of ventricular tachycardia was observed by an increase of average heart rate (P < 0.05) 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.