Lack of diagnostic utility of the ECG-derived ventricular gradient in patients with suspected acute pulmonary embolism.

INTRODUCTION: The YEARS algorithm was successfully developed to reduce the number of computed tomography pulmonary angiography (CTPA) investigations in the diagnostic management of patients with suspected pulmonary embolism (PE), although half of patients still needed to be referred for CTPA. We hypothesized that ECG derived ventricular gradient optimized for right ventricular pressure overload (VG-RVPO), an easy to use tool for detecting PE-induced pulmonary hypertension (PH), may further improve the efficiency of the YEARS algorithm. METHODS: In this post-hoc analysis of the Years study, ECGs of 479 patients with suspected PE managed according to the YEARS algorithm were available for analysis. The diagnostic performance of VG-RVPO was assessed and likelihood ratios were calculated. RESULTS: PE was diagnosed in 88 patients (18%). In patients with confirmed PE, 34% had an abnormal VG-RVPO versus 24% of those without PE (odds ratio 1.6; 95%CI 0.94-2.6). The mean VG-RVPO was -22 ± 13 and did not differ between the two patient groups (-22 versus -20; mean difference - 2, 95% CI -4.8 to 1.3). The sensitivity of VG-RVPO for PE was 24% (95%CI 34-45), the specificity 76% (95%CI 71-80) and the c-statistic 0.45 (95% CI 0.38-0.51). When combined with the YEARS algorithm, the likelihood ratios of VG-RVPO remained close to 1.0. Ruling out PE in patients with an indication for CTPA based on a normal VG-RVPO would have resulted in 58 missed cases. CONCLUSIONS: The VG-RVPO has no diagnostic value for suspected acute PE, either as stand-alone diagnostic test or combined with the YEARS algorithm. CONDENSED ABSTRACT: This post-hoc analysis of the YEARS study failed to demonstrate incremental diagnostic value of VG-RVPO for acute PE, either as stand-alone diagnostic test or combined with the YEARS algorithm. Nevertheless, the role of VG-RVPO recorded on admission could potentially be valuable in the risk stratification of PE during hospitalization, although this remains to be studied.

Electrocardiographic detection of pulmonary hypertension in patients with systemic sclerosis using the ventricular gradient.

BACKGROUND: Pulmonary hypertension (PH) is a leading cause of death in systemic sclerosis (SSc) patients. The current study assessed the ability of the ECG-derived ventricular gradient (VG-RVPO) to detect PH and predict all-cause mortality in PH patients with subtypes of SSc differing in the extent of multi-organ involvement. METHODS: ECGs were obtained from 196 patients with limited and 77 patients with diffuse SSc included from our screening programme on cardiac complications. The association of the VG-RVPO with (1) the presence of PH, (2) conventional screening parameters and (3) survival in PH patients was assessed. RESULTS: In limited SSc patients an elevated VG-RVPO corresponded with the presence of PH (-5±12 mV.ms vs -22±16 mV.ms, P<0.01), correlated significantly with conventional screening parameters and had a better diagnostic performance than the presence of a right heart axis (AUC 0.81 vs 0.60; P=0.04). These differences were not observed in patients with diffuse SSc. An elevated VG-RVPO was associated with decreased survival in all SSc patients with PH (3 year survival 30% vs 64%, P=0.02). CONCLUSION: An elevated VG-RVPO is associated with PH in limited SSc patients and with decreased survival in all SSc patients with PH.

The role of insulin resistance in the association between body fat and autonomic function.

BACKGROUND AND AIM: Excess body fat is associated with altered autonomic function. We investigated whether this association is mediated by insulin resistance. METHODS AND RESULTS: Cross-sectional analysis of a subgroup of the Netherlands Epidemiology of Obesity study with measurements of autonomic function (heart rate variability calculated as mean interbeat interval, standard deviation of all normal intervals (SDNN), low frequency (LF) power and high frequency (HF) power). We measured BMI(kg/m²), total body fat(%) and waist circumference(cm), and calculated the HOMA-index of insulin resistance (HOMA-IR). We examined the association between body fat and heart rate variability with multivariate linear regression analysis. To investigate whether the association was mediated by insulin resistance, we additionally adjusted for HOMA-IR. After exclusion of participants with glucose lowering medication (n = 19), 466 participants were included. Per SD of BMI, the difference in SDNN was -2.7% (95%CI: -5.5, 0.1) in the multivariate model. Additional adjustment for HOMA-IR attenuated this association to -1.2% (95%CI: -4.2, 1.7), suggesting that 55% of the association between BMI and SDNN was mediated by HOMA-IR. All measures of body fat were associated with mean interbeat interval, SDNN and LF power. Depending on the parameter of body fat or heart rate variability, 29-81% of the association was mediated by HOMA-IR. CONCLUSION: In this cross-sectional study, body fat was associated with heart rate variability. This association may at least partially be mediated by insulin resistance. Future studies should investigate whether a reduction in obesity and insulin resistance may prevent the adverse cardiovascular consequences of altered autonomic function.

Role of the ECG in initial acute coronary syndrome triage: primary PCI regardless presence of ST elevation or of non-ST elevation.

The major initial triaging decision in acute coronary syndrome (ACS) is whether or not percutaneous coronary intervention (PCI) is the primary treatment. Current guidelines recommend primary PCI in ST-elevation ACS (STEACS) and initial antithrombotic therapy in non-ST-elevation ACS (NSTEACS). This review probes the question whether this decision can indeed be based on the ECG. Genesis of STE/NSTE ECGs depends on the coronary anatomy, collateral circulation and site of the culprit lesion. Other causes than ischaemia may also result in ST-segment changes. It has been demonstrated that the area at risk cannot reliably be estimated by the magnitude of the ST change, that complete as well as incomplete occlusions can cause STE as well as NSTE ECGs, and that STE and NSTE patterns cannot differentiate between transmural and non-transmural ischaemia. Furthermore, unstable angina can occur with STE and NSTE ECGs. We conclude that the ECG can be used to assist in detecting ischaemia, but that electrocardiographic STE and NSTE patterns are not uniquely related to distinctly different pathophysiological mechanisms. Hence, in ACS, primary PCI might be considered regardless of the nature of the ST deviation, and it should be done with the shortest possible delay, because 'time is muscle'.

Baroreflex sensitivity: mechanisms and measurement.

This article is a brief review of baroreflex physiology, the definition and functional meaning of baroreflex sensitivity, and the methods used to measure baroreflex sensitivity. The arterial baroreflex is important for haemodynamic stability and for cardioprotection, and it has convincingly been demonstrated that baroreflex sensitivity, even when assessed with different methods, has a strong prognostic value. Development of new baroreflex assessing procedures is still ongoing, with a focus on increased reliability in difficult measuring circumstances, e.g., in patients with a weak baroreflex and in patients with frequent arrhythmias.

Neurocardiological differences between musicians and control subjects.

BACKGROUND: Exercise training is beneficial in health and disease. Part of the training effect materialises in the brainstem due to the exercise-associated somatosensory nerve traffic. Because active music making also involves somatosensory nerve traffic, we hypothesised that this will have training effects resembling those of physical exercise. METHODS: We compared two groups of healthy, young subjects between 18 and 30 years: 25 music students (13/12 male/female, group M) and 28 controls (12/16 male/female, group C), peers, who were non-musicians. Measurement sessions to determine resting heart rate, resting blood pressure and baroreflex sensitivity (BRS) were held during morning hours. RESULTS: Groups M and C did not differ significantly in age (21.4 ± 3.0 vs 21.2 ± 3.1 years), height (1.79 ± 0.11 vs 1.77 ± 0.10 m), weight (68.0 ± 9.1 vs 66.8 ± 10.4 kg), body mass index (21.2 ± 2.5 vs 21.3 ± 2.4 kg∙m(-2)) and physical exercise volume (39.3 ± 38.8 vs 36.6 ± 23.6 metabolic equivalent hours/week). Group M practised music daily for 1.8 ± 0.7 h. In group M heart rate (65.1 ± 10.6 vs 68.8 ± 8.3 beats/min, trend P =0.08), systolic blood pressure (114.2 ± 8.7 vs 120.3 ± 10.0 mmHg, P = 0.01), diastolic blood pressure (65.0 ± 6.1 vs 71.0 ± 6.2 mmHg, P < 0.01) and mean blood pressure (83.7 ± 6.4 vs 89.4 ± 7.1, P < 0.01) were lower than in group C. BRS in groups M and C was 12.9 ± 6.7 and 11.3 ± 5.8 ms/mmHg, respectively (P = 0.17). CONCLUSIONS: The results of our study suggest that active music making has training effects resembling those of physical exercise training. Our study opens a new perspective, in which active music making, additionally to being an artistic activity, renders concrete health benefits for the musician.

ECG derived ventricular gradient exceeds echocardiography in the early detection of pulmonary hypertension in scleroderma patients.

BACKGROUND: Patients with systemic sclerosis (SSc) are at risk for developing pulmonary hypertension (PH) which is a major cause of death in this population. Echocardiographic (TTE) derived pulmonary arterial pressure (PAP) can be unreliable for the early detection of PH. Previous studies demonstrate that the ECG derived ventricular gradient optimized for right ventricular pressure overload (VG-RVPO) can detect PH in a heterogeneous population suspected of PH. The aim of this study is to assess the use of the VG-RVPO as a screening and monitoring instrument of early PH in SSc patients. METHODS: Serial ECGs and TTEs from twenty-seven SSc patients who underwent right heart catheterization (RHC) were retrospectively analyzed. The changes in PAP and VG-RVPO over time were studied in patients with and without diagnosed PH. RESULTS: Twenty-four patients (52.5% female, mean age 58.4 years SD 14.3) were studied. In eleven patients PH was confirmed with RHC. In these patients VG-RVPO was significantly higher -8 ±â€¯19 than in patients without PH -23 ±â€¯10 mV·ms, (P < 0.05). In addition, in PH patients the VG-RVPO increased over time in contrast to patients without PH (P < 0.01). The VG was more sensitive to detect disease progression in earlier stages of disease as compared to echocardiographic derived PAP. CONCLUSIONS: The VG-RVPO is a sensitive, non-invasive and cost effective tool for early detection of PH in SSc patients. Serial measurements indicate that the VG-RVPO can be used as a follow-up instrument and outperforms TTE to detect early changes in right ventricular pressure over time.

Low heart rate variability in a 2-minute rhythm strip predicts risk of coronary heart disease and mortality from several causes: the ARIC Study. Atherosclerosis Risk In Communities.

BACKGROUND: Low heart rate variability (HRV) is associated with a higher risk of death in patients with heart disease and in elderly subjects and with a higher incidence of coronary heart disease (CHD) in the general population. METHODS AND RESULTS: We studied the predictive value of HRV for CHD and death from several causes in a population study of 14 672 men and women without CHD, aged 45 to 65, by using the case-cohort design. At baseline, in 1987 to 1989, 2-minute rhythm strips were recorded. Time-domain measures of HRV were determined in a random sample of 900 subjects, for all subjects with incident CHD (395 subjects), and for all deaths (443 subjects) that occurred through 1993. Relative rates of incident CHD and cause-specific death in tertiles of HRV were computed with Poisson regression for the case-cohort design. Subjects with low HRV had an adverse cardiovascular risk profile and an elevated risk of incident CHD and death. The increased risk of death could not be attributed to a specific cause and could not be explained by other risk factors. CONCLUSIONS: Low HRV was associated with increased risk of CHD and death from several causes. It is hypothesized that low HRV is a marker of less favorable health.

The importance of high-frequency paced breathing in spectral baroreflex sensitivity assessment.

OBJECTIVE: Computation of the low-frequency (LF) blood pressure variability (BPV) to heart rate variability (HRV) transfer-index is a common method to assess baroreflex sensitivity (BRS), tacitly assuming that all LF-HRV is caused by baroreflex feedback of LF-BPV. However, respiration may also cause HRV by mechanisms not involving the baroreflex. Application of narrow-band (controlled) high-frequency breathing would keep such non-baroreflex-mediated HRV best out of the LF band. Spontaneous breathing, because of its broad-band character, might cause extra, non-baroreflex-mediated, HRV in the LF band, while paced LF breathing would even concentrate most non-baroreflex-mediated HRV in the LF band. Our study addresses the likely resulting BRS overestimation. DESIGN: We recorded HRV and BPV in 20 healthy young subjects in the sitting position. We varied the sympathovagal balance by gradual leg-lowering from horizontal till 60 degrees . At each angle the subjects performed controlled 0.10 Hz, spontaneous, and controlled 0.25 Hz respiration. RESULTS: Resting BRS values were 15.5(7.2), 13.1 (3.7), and 11.6(6.2) ms/mmHg, respectively. Both the 15/min and the free breathing values differed significantly, P< 0.01 and P= 0.04, from the 6/min breathing value. With lowered legs, the BRS values were 8.2(3.4), 8.3(2.9), and 8.3(3.4) ms/mmHg, respectively. CONCLUSION: Controlled 6/min breathing caused significant BRS overestimation under resting conditions. For the group, spontaneous respiration yielded acceptable BRS values, but individual BRS values deviated sometimes considerably. Conversely, with gravitational load, the respiratory pattern had only minor impact on BRS. Our results demonstrate that the risk of an overestimated BRS value is realistic as long as respiration is not controlled and of high-frequency.

Similar orthostatic defense in active, healthy young adult and late middle-aged men.

Orthostatic defense is commonly validated with a 60 degrees to 80 degrees head-up tilt test, addressing the step response rather than the response to permanent orthostatis. During the initial phase of tilt, neural factors predominate, while later, the slower humoral factors fade in. It has been demonstrated that, during adaptation of the circulatory system to the standing conditions, overshoot and undershoot occur. These oscillations hamper straight-forward interpretation of a tilt test, and may contribute to the inconclusiveness of current studies regarding the aging of orthostatic defense. Gradual, progressive, orthostatic load testing seems a valuable alternative. We used a novel, incremental, head-up tilt protocol (0 degrees to 80 degrees, 13 increments) to impose graded orthostatic stress on 46 healthy young adult men (mean age +/- SD 25 +/- 3 years), and on 16 healthy late middle-aged men (60 +/- 4 years), while recording the electrocardiogram and the blood pressure. A first-order estimate of the heart rate range associated with the sympathovagal transition was made by combined analysis of heart rate and heart rate variability trends. We observed similar responses in heart rate, heart rate variability, and blood pressure.(ABSTRACT TRUNCATED AT 250 WORDS)

Correlation of heart rate variability with cardiac functional and metabolic variables in cyclists with training induced left ventricular hypertrophy.

OBJECTIVE: To examine the correlation between heart rate variability and left ventricular mass in cyclists with an athlete's heart. METHODS: Left ventricular mass and diastolic function were determined at rest and myocardial high energy phosphates were quantified at rest and during atropine-dobutamine stress in 12 male cyclists and 10 control subjects, using magnetic resonance techniques. Ambulatory 24 hour ECG recordings were obtained, and time and frequency domain heart rate variability indices were computed. RESULTS: In the cyclists, the mean of all RR intervals between normal beats (meanNN), the SD of the RR intervals, and their coefficient of variation were significantly greater than in control subjects (p < 0.01, p < 0.01, and p < 0.05, respectively). For cyclists and control subjects, only meanNN correlated with left ventricular mass (r = 0.48, p = 0.038). The heart rate variability indices that correlated with functional or metabolic variables were: meanNN v E/A peak (the ratio of peak early and peak atrial filling rate) (r = 0.48, p = 0.039); the root mean square of successive differences in RR intervals among successive normal beats v E/A area (ratio of peak early and peak atrial filling volume) (r = 0.48, p = 0.040); percentage of successive RR intervals differing by more than 50 ms v the phosphocreatine to ATP ratio at rest (r = 0.54, p = 0. 017); and the SD of the average RR intervals during all five minute periods v the phosphocreatine to ATP ratio during stress (r = 0.60, p = 0.007). CONCLUSIONS: Highly trained cyclists have increased heart rate variability indices, reflecting increased cardiac vagal control compared with control subjects. Left ventricular mass has no major influence on heart rate variability, but heart rate variability is significantly correlated with high energy phosphate metabolism and diastolic function.

Exercise training and heart rate variability in older people.

PURPOSE: Heart rate variability (HRV), a characteristic that is potentially increased by physical activity, has been associated with incidence of cardiac events and total mortality. Since the incidence of cardiac events among older people is high and their physical activity levels and HRV are generally low, it is important to investigate whether regular physical activity can modify HRV in this age group. The purpose of the study was to investigate the effect of regular physical activity on HRV in older men and women. METHODS: In a randomized controlled trial, the effect of six months' training on HRV was investigated in a group of 51 older men and women (67.0 +/- 5.1 yr). The training group gathered three times per week for 45 min supervised training. RESULTS: At the end of the intervention period, HRV was higher primarily during the day. During daytime, the SD of all normal intervals (+6%) as well as the low frequency component (+ 15%) and the very low frequency component (+ 10%) of HRV were significantly increased (P < 0.05) as compared with the control group. Effects of training were most pronounced in subjects inactive in sports at baseline. CONCLUSION: This study demonstrates that regular physical activity increases HRV (specifically in the very low and low frequency components) in older subjects. Hence, in older subjects, physical training may be an effective means to modify positively a factor that is associated with increased incidence of cardiac events.

Correlated neurocardiologic and fitness changes in athletes interrupting training.

PURPOSE: We studied nine male Dutch top marathon skaters during a 1-month interruption of their training schedules after their last contest in the winter to investigate a possible decline in baroreflex sensitivity. METHODS: Before and after this period, a maximal exercise test was done, and at days 0, 4, 7, 14, and 28 neurocardiologic measurement sessions--heart rate and noninvasive baroreflex sensitivity, recumbent and tilt--were performed. RESULTS: Interruption of training resulted in a significant and relevant decrease in the maximal oxygen uptake (from 65.7 +/- 5.8 to 61.6 +/- 4.7 mL O2 x kg(-1) x min(-1); P = 0.03), most likely associated with decreased competitive possibilities. Resting heart rate modestly increased (from 54.6 +/- 7.2 to 58.8 +/- 7.5 bpm), however, not significantly. Heart rate during 60 degrees tilt increased considerably (from 70.1 +/- 6.1 to 80.1 +/- 9.1 bpm; P = 0.01), possibly due to a decrease in blood volume and an increase in cardiopulmonary baroreflex gain. Arterial baroreflex sensitivity decreased significantly in the recumbent (from 13.3 +/- 5.4 to 9.8 +/- 3.8 ms x mm Hg(-1), P = 0.04), but not in the 60 degrees tilt position (from 6.7 +/- 2.0 to 6.0 +/- 2.5 ms x mm Hg(-1)). The relative decrease in baroreflex sensitivity and maximal oxygen uptake correlated significantly (r = 0.71, P = 0.02). CONCLUSIONS: In summary, our data show that correlated detrimental changes in fitness and baroreflex sensitivity are measurable in these athletes after a month of interruption of training.

Heart rate variability during repeated incremental head-up tilt discloses time dependence of individual autonomic dynamics.

According to the Rosenblueth-Simeone model, the heart rate (HR) is proportional to the sympathovagal balance. The individual proportionality constant is the intrinsic HR, which can be determined only invasively. The percentage low-frequency spectral HR variability power, relative to the low- plus high-frequency spectral power (%LF) has been raised as a noninvasive alternative. We previously studied young healthy male subjects, in whom gradual autonomic changes were induced by incremental head-up tilt (0-10-20-30-40-45-50-55-60-65-70-75-80 degrees). At each tilt angle we computed HR and %LF. Linear regressions of %LF on HR, characterizing individual autonomic dynamics, confirmed that, within a subject, changes in %LF were proportional to changes in HR. For the current study, we made repeated measurements in 19 subjects after 1 to 8 months. In six subjects, the session 1 and session 2 regression lines differed significantly (t-test, p < 0.05), demonstrating the time dependence of the autonomic dynamics. In such cases, similar HR values on different days are to be associated with different %LF values. We also determined the reproducibility of the supine HR and %LF values. For all 19 subjects, the coefficients of variation were 7 and 22%, respectively: HR reproduces better than %LF. Hence, time-dependent autonomic dynamics contribute systematically to the inferior reproducibility of %LF.

Methods in heart rate variability analysis: which tachogram should we choose?

We investigated the practical impact of the representation of the cardiac rhythm--the cardiotachogram--on two elementary spectral indexes in heart rate variability analysis: the low-frequency (0.07-0.14 Hz) and high-frequency (0.14-0.40 Hz) powers. Five commonly used tachograms (inter-beat interval function/series, counts, instantaneous heart rate function/series) were compared. Measurements were done on seven volunteers in the supine and standing positions. Ratios, and their deviations from 100%, of alternative power values were calculated. Mean low-frequency and high-frequency ratio deviations ranged from 0 to 5% and from 6 to 37%. The spectrum of counts yielded on average more (15-37%) high-frequency power. Spectra were incomparable without normalization of the tachogram with respect to heart rate. In conclusion, (i) the choice of a particular spectrum may lead to differing conclusions on the vagal contribution to heart rate variability and (ii) inconclusive results from studies using different tachogram variants can partly be due to the omission of normalization.