Lower hemoglobin levels associate with higher baroreflex sensitivity and heart rate variability.

The aim of this study was to cross-sectionally examine whether hemoglobin (Hb) levels within the normal variation associate with heart rate variability (HRV) measures and baroreflex sensitivity (BRS). The study population included 733 Finnish subjects of the OPERA cohort (aged 41-59 yr, 53% males, 51.7% treated for hypertension) of whom HRV was measured from a standardized 45-min period and whose Hb levels were within the Finnish reference intervals. The low Hb tertile (mean Hb, 135 g/L) had an overall healthier metabolic profile compared with the high Hb tertile (mean Hb, 152 g/L). BRS was higher in the low Hb tertile compared with the high Hb tertile (P < 0.05). R-R interval (RRi) and standard deviation (SD) of the RRi (SDNN)index were the longest in the low Hb tertile regardless of posture. Of the spectral components of HRV, HF power was the highest in the low Hb tertile regardless of posture (P < 0.05). In a stepwise logistic regression model, BRS associated negatively with Hb levels after adjusting for covariates (B = -0.160 [-0.285; -0.035]). Similar associations were observed for SDNNindex when lying down (B = -0.105 [-0.207; -0.003]) and walking (B = -0.154 [-0.224; -0.083]). For HF power negative associations with Hb levels were observed when lying down (B = -0.110 [-0.180; -0.040]), sitting (B = -0.150 [-0.221; -0.079]), and in total analysis (B = -0.124 [-0.196; -0.053]). Overall, lower Hb levels associated independently with healthier cardiac autonomic function.NEW & NOTEWORTHY Heart rate variability (HRV) and baroreflex sensitivity (BRS), which can be measured noninvasively, can predict cardiac and metabolic diseases. Our findings show that within normal variation subjects with lower hemoglobin (Hb) levels have an overall healthier HRV profile and increased cardiac parasympathetic activity in middle age, independent of age, sex, smoking status, and key metabolic covariates. These findings support our previous findings that Hb levels can be used in assessing long-term risks for cardiometabolic diseases.

MiR-185-5p regulates the development of myocardial fibrosis.

BACKGROUND: Cardiac fibrosis stiffens the ventricular wall, predisposes to cardiac arrhythmias and contributes to the development of heart failure. In the present study, our aim was to identify novel miRNAs that regulate the development of cardiac fibrosis and could serve as potential therapeutic targets for myocardial fibrosis. METHODS AND RESULTS: Analysis for cardiac samples from sudden cardiac death victims with extensive myocardial fibrosis as the primary cause of death identified dysregulation of miR-185-5p. Analysis of resident cardiac cells from mice subjected to experimental cardiac fibrosis model showed induction of miR-185-5p expression specifically in cardiac fibroblasts. In vitro, augmenting miR-185-5p induced collagen production and profibrotic activation in cardiac fibroblasts, whereas inhibition of miR-185-5p attenuated collagen production. In vivo, targeting miR-185-5p in mice abolished pressure overload induced cardiac interstitial fibrosis. Mechanistically, miR-185-5p targets apelin receptor and inhibits the anti-fibrotic effects of apelin. Finally, analysis of left ventricular tissue from patients with severe cardiomyopathy showed an increase in miR-185-5p expression together with pro-fibrotic TGF-ß1 and collagen I. CONCLUSIONS: Our data show that miR-185-5p targets apelin receptor and promotes myocardial fibrosis.

Association of atrial depolarization variability and cardiac autonomic regulation with sudden cardiac death in coronary artery disease.

AIMS: To evaluate the prognostic significance of the temporal variability of P-wave morphology, specifically in relation to cardiac autonomic regulation. METHODS AND RESULTS: We analyzed the standard deviation of P-wave residuum (PWRSD) from five consecutive beats of the standard 12-lead ECG in 1236 patients with angiographically verified coronary artery disease (CAD). We evaluated the prognostic value of PWRSD, of PWRSD and PWR in relation to the 24 h standard deviation of normal-to-normal intervals (PWRSD/SDNN and PWR/SDNN). After 8.7 ± 2.2 years of follow-up on average, 43 patients (3.5%) experienced sudden cardiac death (SCD) or were resuscitated from sudden cardiac arrest (SCA), 34 (2.8%) succumbed to non-sudden cardiac death (NSCD) and 113 (9.1%) to non-cardiac death (NCD). In the Cox regression analysis, PWRSD (≥0.002727) had a significant univariate (uv) [hazard ratio (HR): 4.27, 95% confidence interval (CI): 2.26-8.08, P = 0.000008] and multivariate (mv) (HR: 2.58, 95% CI: 1.31-5.08, P = 0.006) association with SCD/SCA but not with NSCD (uv P = 0.76, mv P = 0.33) or NCD (uv P = 0.57, mv P = 0.66). All the studied P-morphology parameters retained a significant association with the risk of SCD/SCA after relevant adjustment (mv P-values from 0.00003 to <0.05) but not with NSCD or NCD. When dichotomized PWRSD, PWR, PWRSD/SDNN, and PWR/SDNN were added to the clinical risk model for SCD/SCD, the C-index increased from 0.799 to 0.834 and integrated discrimination index and net reclassification index improved significantly (P < 0.001). CONCLUSION: Variability of P-morphology representing temporo-spatial heterogeneity of atrial depolarization, specifically when combined with cardiac autonomic regulation, independently predicts the risk of SCD in patients with CAD.

Temporal variability of T-wave morphology and risk of sudden cardiac death in patients with coronary artery disease.

BACKGROUND: The possible relationship between temporal variability of electrocardiographic spatial heterogeneity of repolarization and the risk of sudden cardiac death (SCD) in patients with coronary artery disease (CAD) is not completely understood. METHODS: The standard deviation of T-wave morphology dispersion (TMD-SD), of QRST angle (QRSTA-SD), and of T-wave area dispersion (TW-Ad-SD) were analyzed on beat-to-beat basis from 10 min period of the baseline electrocardiographic recording in ARTEMIS study patients with angiographically verified CAD. RESULTS: After on average of 8.6 ± 2.3 years of follow-up, a total of 66 of the 1,678 present study subjects (3.9%) had experienced SCD or were resuscitated from sudden cardiac arrest (SCA). TMD-SD was most closely associated with the risk for SCD and was significantly higher in patients who had experienced SCD/SCA compared with those who remained alive (3.61 ± 2.83 vs. 2.64 ± 2.52, p = .008, respectively), but did not differ significantly between the patients who had experienced non-SCD (n = 71, 4.2%) and those who remained alive (3.20 ± 2.73 vs. 2.65 ± 2.53, p = .077, respectively) or between the patients who succumbed to non-cardiac death (n = 164, 9.8%) and those who stayed alive (2.64 ± 2.17 vs. 2.68 ± 2.58, p = .853). After adjustments with relevant clinical risk indicators of SCD/SCA, TMD-SD still predicted SCD/SCA (HR 1.107, 95% CIs 1.035-1.185, p = .003). CONCLUSIONS: Temporal variability of electrocardiographic spatial heterogeneity of repolarization represented by TMD-SD independently predicts long-term risk of SCD/SCA in patients with CAD.

Early Growth Patterns and Cardiac Structure and Function at Midlife: Northern Finland 1966 Birth Cohort Study.

OBJECTIVES: To evaluate the influence of early growth patterns that have previously been associated with later cardiometabolic risk on cardiac left ventricular (LV) structure and function in midlife. STUDY DESIGN: A subpopulation of the Northern Finland Birth Cohort 1966 took part in follow-up, including echocardiography (n = 1155) at the age of 46 years. Body mass index (BMI) growth curves were modeled based on frequent anthropometric measurements in childhood. Age and BMI at adiposity peak (n = 482, mean age 9.0 months) and at adiposity rebound (n = 586, mean age 5.8 years) were determined. Results are reported as unstandardized beta (ß) or OR with 95% CIs for 1 SD increase in early growth variable. RESULTS: Earlier adiposity rebound was associated with increased LV mass index (ß = -4.10 g/m2 (-6.9, -1.3); P = .004) and LV end-diastolic volume index (ß = -2.36 mL/m2 (-3.9, -0.84); P = .002) as well as with eccentric LV hypertrophy (OR 0.54 [0.38, 0.77]; P = .001) in adulthood in males. BMI at adiposity rebound was directly associated with LV mass index (ß = 2.33 g/m2 [0.80, 3.9]; P = .003). Higher BMI at both adiposity peak and at adiposity rebound were associated with greater LV end-diastolic volume index (ß = 1.47 mL/m2; [0.51, 2.4], ß = 1.28 mL/m2 [0.41, 2.2], respectively) and also with eccentric LV hypertrophy (OR 1.41 [1.10, 1.82], OR 1.53 [1.23, 1.91], respectively) and LV concentric remodeling (OR 1.38 [1.02, 1.87], OR 1.40 [1.06, 1.83], respectively) in adulthood (P < .05 for all). These relationships were only partly mediated by adult BMI. CONCLUSIONS: Early growth patterns in infancy and childhood contribute to cardiac structure at midlife.

Gender differences in prevalence and prognostic value of fragmented QRS complex.

BACKGROUND: Fragmented QRS (fQRS) on 12-lead electrocardiogram (ECG) is associated with scarred myocardium and adverse outcome. However, the data on gender differences in terms of its prevalence and prognostic value is sparse. The aim of this study was to evaluate whether gender differences in fQRS exist among subjects drawn from populations with different risk profiles. METHODS: We analyzed fQRS from 12-lead ECG in 953 autopsy-confirmed victims of sudden cardiac death (SCD) (78% men; 67.0 ± 11.4 yrs), 1900 coronary artery disease (CAD) patients with angiographically confirmed stenosis of ≥50% (70% men; 66.6 ± 9.0 yrs, 43% with previous myocardial infarction [MI]), and in 10,904 adults drawn from the Finnish adult general population (52% men; 44.0 ± 8.5 yrs). RESULTS: Prevalence of fQRS was associated with older age, male sex and the history and severity of prior cardiac disease of subjects. Among the general population fQRS was more commonly found among men in comparison to women (20.5% vs. 14.8%, p < 0.001). The prevalence of fQRS rose gradually along with the severity of prior cardiac disease in both genders, yet remained significantly higher in the male population: subjects with suspected or known cardiac disease (25.4% vs. 15.8% p < 0.001), CAD patients without prior MI (39.9% vs. 26.4%, p < 0.001), CAD patients with prior MI (42.9% vs. 31.2%, p < 0.001), and victims of SCD (56.4% vs. 44.4%, p < 0.001). CONCLUSIONS: The prevalence of QRS fragmentation varies in different populations. The fragmentation is clearly related to the underlying cardiac disease in both genders, however women seem to have significantly lower prevalence of fQRS in each patient population in comparison to men.

Childhood growth patterns and cardiovascular autonomic modulation in midlife: Northern Finland 1966 Birth Cohort Study.

OBJECTIVES: To test the hypothesis that age and body mass index (BMI) at BMI peak during infancy and at BMI rebound in childhood are related to cardiovascular autonomic modulation in adulthood. METHODS: At the age of 46 years, a sample (n = 5861) of the participants of the Northern Finland Birth Cohort 1966 took part in follow-up examinations. Heart rate variability (HRV), baroreflex sensitivity (BRS) and low-frequency oscillations of systolic blood pressure (LFSBP) were measured during sympathetic stimulus by standing. BMI at various ages was calculated from frequent anthropometric measurements collected from child welfare clinical records. BRS and LFSBP were available for 1243 participants with BMI peak data and 1524 participants with BMI rebound data, and HRV for 2137 participants with BMI peak data and 2688 participants with BMI rebound data. RESULTS: Age at BMI rebound had a significant inverse association with LFSBP (beta = -0.071, p = 0.006) after all adjustments (p < 0.001) and was also directly associated with BRS (beta = 0.082, p = 0.001) independently of birth and maternal factors (p = 0.023). BMI at BMI peak and at BMI rebound was inversely associated with high-frequency component of HRV (HF) (beta = -0.045, p = 0.036 for BMI at peak; beta = -0.043, p = 0.024 for BMI at rebound) and directly associated with the ratio of low- and high-frequency components of HRV (LF/HF ratio) (beta = 0.084, p = < 0.001 for BMI at peak; beta = 0.069, p < 0.001 for BMI at rebound). These associations remained significant after all adjustments (p < 0.05 for all). CONCLUSIONS: This novel study shows that younger age at BMI rebound and higher BMI at BMI peak and at BMI rebound are associated with higher levels in markers suggestive of augmented sympathetic and reduced vagal cardiovascular modulation in midlife.

Postexercise Heart Rate Recovery in Adults Born Preterm.

OBJECTIVE: To evaluate postexercise heart rate recovery (HRR) in adults born preterm. STUDY DESIGN: We studied the association between preterm birth and postexercise HRR in 545 adults (267 women) at 23.3 years of age (range 19.9-26.3 years). One hundred three participants were born early preterm (<34 completed weeks), 178 late preterm (34-36), and 264 were full term (control group). HRR was calculated as change in heart rate (HR) 30 seconds and 60 seconds after cessation of submaximal step test and maximum HR slope during the first minute after. RESULTS: Mean peak HR was 159.5 bpm in the early preterm (P = .16 with controls), 157.8 bpm in the late preterm (P = .56), and 157.0 bpm in the control group. Mean HRR 30 seconds after exercise was 3.2 bpm (95% CI 1.1-5.2) lower in the early preterm group and 2.1 bpm (0.3-3.8) lower in the late preterm group than the full term controls. Mean 60s HRR was 2.5 (-0.1 to 5.1) lower in the early preterm group and 2.8 bpm (0.6-4.9) lower in the late preterm group. Mean maximum slope after exercise was 0.10 beats/s (0.02-0.17) lower in the early preterm group and 0.06 beats/s (0.00-0.12) lower in the late preterm group. CONCLUSIONS: Our results suggest reduced HRR after exercise in adults born preterm, including those born late preterm. This suggests altered reactivation of the parasympathetic nervous system, which may contribute to cardiovascular risk among adults born preterm.

Prognostic significance of P-wave morphology in patients with coronary artery disease.

INTRODUCTION: The prognostic significance of P-wave morphology in patients with coronary artery disease (CAD) is not well-known. METHODS: A total of 1946 patients with angiographically verified CAD were included in the Innovation to reduce Cardiovascular Complications of Diabetes at the Intersection (ARTEMIS) study. The P-wave morphology could be analyzed in 1797 patients. RESULTS: During 7.4 ± 2.0 years, a total of 168 (9.3%) patients died or experienced resuscitation from sudden cardiac arrest (SCA), 43 (2.4%) patients experienced sudden cardiac death (SCD) or were resuscitated from SCA, 37 (2.1%) patients succumbed to non-SCD (NSCD), and 88 (4.9%) patients to noncardiac death (NCD). Of the P-wave parameters, the absolute P-wave residuum (PWR), the heterogeneity of the P-wave morphology (PWH), and the P-wave duration (Pdur) had the closest univariate association with the risk of SCD/SCA (0.0038 ± 0.0026 vs 0.0022 ± 0.0017, P < .001; 11.0 ± 5.2 vs 8.6 ± 3.6, P < .01; 142.7 ± 16.9 vs 134.8 ± 14.3 milliseconds, P < .01; SCD/SCA vs no SCD/SCA, respectively). After adjustments with factors that were associated with the risk of SCD/SCA, such as diabetes, smoking, left bundle branch block, high-sensitivity C-reactive protein, and high-sensitivity troponin T, PWR (P < .001), PWH (P < .05), and Pdur (P < 0.01) still predicted SCD/SCA but not non-sudden cardiac death. When these parameters were added to the SCD/SCA clinical risk model, the discrimination and reclassification accuracy of the risk model increased significantly (P < .05, P < .001) and the C-index increased from 0.745 to 0.787. CONCLUSION: The P-wave morphology parameters independently predict SCD/SCA in patients with CAD.

Associations of fitness and physical activity with orthostatic responses of heart rate and blood pressure at midlife.

Cardiorespiratory fitness (CRF) and physical activity (PA) are associated with autonomic function, but their associations to orthostatic autonomic responses are unclear in epidemiological setting. We hypothesized that higher CRF and PA would associate with higher immediate vagal responses and lower incidence of adverse findings during orthostatic test. At age of 46, 787 men and 938 women without cardiorespiratory diseases and diabetes underwent an orthostatic test (3-minutes sitting, 3-minutes standing) with recording of RR intervals (RRi) and blood pressure (BP) by finger plethysmography. Acute responses of RRi (30:15 ratio) and BP were calculated. CRF was measured by a submaximal step test and daily amount of moderate-to-vigorous PA (MVPA) for 2 weeks by wrist-worn accelerometer. Lifelong PA was based on questionnaires at ages of 14, 31, and 46. High CRF was significantly associated with higher RRi 30:15 ratio (adjusted standardized ß = 0.17, P < 0.001) and milder acute decrease of systolic BP while standing (ß = 0.10, P = 0.001), while MVPA was not (ß = 0.04 for RRi 30:15 ratio and ß = 0.05 for systolic BP acute response). High lifelong PA was significantly associated with higher RRi 30:15 ratio (ß = 0.08, P = 0.002) but not with acute systolic BP response. Those in the lowest tertile of CRF had 9.2-fold risk (P = 0.002) of having postural orthostatic tachycardia syndrome compared to more fit. Cardiorespiratory fitness and lifelong physical activity, but not current physical activity, were independently associated with higher cardiac vagal response to orthostasis. The present results underscore the importance fitness and lifelong physical activity in prevention of abnormal autonomic function and related cardiovascular risk.

Effect of passive heat exposure on cardiac autonomic function in healthy children.

PURPOSE: The aim of this study was to examine the effect of passive heat stress on heart rate variability parameters in healthy children. METHOD: Fifteen children (9.3 ± 1.6 years) of both sexes (eight male) participated in two randomized experimental conditions separated by 5-12 days. Children were seated for 2 h in an environmental chamber for two sessions: neutral (22.4 ± 0.1 °C, 40.4 ± 6.5% RH) and hot (34.9 ± 0.3 °C, 36.6 ± 6.2% RH) conditions. Electrocardiogram, mean skin temperature, tympanic temperature, and blood pressure were recorded. Five min epochs were averaged for analysis of cardiac autonomic function over the 2-h protocol. RESULT: Mean skin and tympanic temperatures and heart rate increased during the hot condition (all p < 0.01) while mean arterial pressure decreased (p < 0.01). During the hot condition, root-mean-square difference of successive normal RR intervals (45 ± 9 to 38 ± 7 ms), and low- (LF, 1536 ± 464 vs. 935 ± 154 ms2) and high-frequency power (HF, 1544 ± 693 vs. 866 ± 355 ms2) decreased, whereas LF/HF ratio increased (1.64 ± 0.24 vs. 2.40 ± 0.23 au); all indices were different from neutral (all p < 0.05). These were all unchanged throughout the neutral condition (all p > 0.05), except for LF/HF ratio which decreased during the neutral condition (p < 0.05). CONCLUSION: Mild hyperthermia elicited marked changes in cardiac autonomic control in young children. These data suggest that, in healthy children, vagal withdrawal is responsible for the cardiac autonomic response to hyperthermia.

Exercise capacity is associated with endothelin-1 release during emotional excitement in coronary artery disease patients.

Endothelin-1 (ET-1), a potent vasoconstrictor, IL-6, and catecholamines are increased and heart rate variability [SD of normal to normal R-R intervals (SDNN)] decreased during emotional excitement, but individual responses vary. We tested the hypothesis that exercise capacity is associated with physiological responses caused by real-life emotional excitement. We measured the plasma levels of ET-1, IL-6, catecholamines, heart rate, and SDNN in enthusiastic male ice hockey spectators (n = 51; age, 59 ± 9 years) with stable coronary artery disease (CAD) at baseline and during the Finnish National Ice Hockey League's final play-off matches. Maximal exercise capacity (METs) by bicycle exercise test and left ventricular ejection fraction (LVEF) were measured on a separate day. ET-1 response from baseline to emotional excitement correlated with maximal METs (r = -0.30; P = 0.040). In a linear stepwise regression analysis age, body mass index (BMI), METs, LVEF, basal ET-1, and subjective experience of excitement were entered the model as independent variables to explain ET-1 response. This model explained 27% of ET-1 response (P = 0.003). Maximal METs were most strongly correlated with ET-1 response (ß = -0.45; partial correlation r = -0.43; P = 0.002), followed by BMI (ß = -0.31; partial correlation r = -0.31; P = 0.033) and LVEF (ß = -0.30; partial correlation r = -0.33; P = 0.023). Exercise capacity may protect against further cardiovascular events in CAD patients, because it is associated with reduced ET-1 release during emotional excitement.

Heart rate variability and the metabolic syndrome: a systematic review of the literature.

BACKGROUND: A number of cross-sectional studies have examined associations between heart rate variability and metabolic syndrome, but differences in study populations, data collection and analysis methodologies make synthesis difficult. The purpose of this study was to systematically review published primary research examining associations between heart rate variability and metabolic syndrome or its individual risk factors. METHODS: A systematic literature search of PubMed and EMBASE was conducted to identify relevant articles published from January 1999 to December 2012. Studies were included if they examined associations between heart rate variability analysed by standard protocols and metabolic syndrome risk factors according to published definitions. All papers were scored with a modified Downs and Black instrument, and data were extracted. RESULTS: Fourteen studies were included. Heart rate variability generally was reduced in women with metabolic syndrome compared to those without, while results in men were inconsistent. Time and frequency domain heart rate variability parameters were associated with individual metabolic syndrome risk factors, though sex differences exist. Only two studies considered nonlinear and Poincaré plot heart rate variability parameters, which were reduced in metabolic syndrome. CONCLUSIONS: Heart rate variability is altered differently in men and women with metabolic syndrome. Future studies should follow consistent heart rate variability analysis protocols and metabolic syndrome definitions and include more comprehensive analyses to investigate potential mechanisms.

Lifestyle and Cardiac Structure and Function in Healthy Midlife Population.

The association between lifestyle and cardiac structure and function measures, such as global longitudinal strain and diastolic function in a healthy midlife general population, is not well known. A subpopulation of the Northern Finland Birth Cohort 1966 took part in follow-up, including echocardiography (n = 1,155) at the age of 46. All antihypertensive medication users (n = 164), patients with diabetes (n = 70), subjects with any cardiac diseases (n = 24), and subjects with echocardiography abnormalities (n = 21) were excluded. Moderate to vigorous physical activity (MVPA) was recorded with a wrist-worn accelerometer over 14 days and categorized into high, moderate, and low MVPA groups. Similarly, alcohol consumption was categorized as low, moderate, and high-dose users of alcohol and smoking as nonsmokers, former, and current smokers. The total number of healthy subjects included in the study was 715 (44% males). Left ventricular mass index and left atrial end-systolic volume index were significantly higher in the high MVPA group compared with the low MVPA group (adjusted main effect p = 0.002 and p <0.001, respectively). Cardiac function did not differ among the physical activity groups. High alcohol consumption was associated with impaired global longitudinal strain and diastolic function (adjusted main effect p = 0.002 and p = 0.004, respectively) but not with any cardiac structure variables. Smoking was not associated with cardiac structure or function. In healthy middle-aged adults, MVPA was independently associated with structural changes in the heart but not with cardiac function. High alcohol consumption was associated with impaired modern cardiac function measures but not with cardiac structure.

Adherence to exercise after an acute coronary syndrome: a 6-month randomized controlled trial.

Introduction: Exercise training with well-known health benefits is a key element in the self-management of coronary artery disease (CAD). Although current guidelines for patients with CAD recommend daily exercise training, most of the patients do not follow the guidelines. We tested the hypothesis that an exercise training program guided by a novel technology used at home will improve adherence to exercise training. Methods: One to three weeks after percutaneous coronary intervention (PCI), acute coronary syndrome patients (n = 50) were randomized into traditional (age 65 ± 8 years) and novel technology-guided (age 60 ± 8 years) exercise rehabilitation groups. The novel technology included a tablet computer with a virtual autonomous physiotherapy agent (VAPA group) for every patient at home; it was used to guide exercise training time, volume, and intensity. Traditional rehabilitation was performed by exercise training prescriptions, phone calls, and diaries (control group). The duration of the rehabilitation program was 6 months for both groups. Exercise capacity and 24-h heart rate variability were measured at baseline and at the end of the program. Adherence to exercise was measured over 6 months as the percentage of realized training. Results: None of the patients dropped out from the VAPA group, while three patients dropped out from the control group. Adherence to exercise was higher in the VAPA group than in the control group for resistance training (141% ± 56% vs. 50% ± 20%, p < 0.0001), and there were no differences between the groups for aerobic training (144% ± 45% vs. 119% ± 65%, p = 0.22). Exercise capacity increased in both the groups (time p < 0.001, time × group interaction p = ns). High-frequency power of R-R intervals (lnHF) increased in the VAPA group but remained unchanged in the control group (natural logarithm of lnHF power from 5.5 ± 0.7 to 5.8 ± 0.9 ms2 and from 5.3 ± 0.8 to 5.2 ± 0.7 ms2, respectively, time × group interaction p = 0.014). Conclusion: Compared with the use of traditional methods, the use of novel technology at home results in better adherence to exercise, particularly in resistance training, in acute coronary syndrome patients. Second, the VAPA group showed improved cardiac vagal regulation, documented by increased vagally mediated R-R interval fluctuation, compared with the traditional training group (ClinicalTrials.gov identifier: NCT03704025).

Prognostic significance of beat-to-beat variability of spatial heterogeneity of repolarization analyzed from a 5-minute resting electrocardiogram in coronary artery disease.

BACKGROUND: Data on the prognostic significance of temporal variability of spatial heterogeneity of electrocardiographic repolarization in coronary artery disease (CAD) are limited. OBJECTIVE: The purpose of this study was to evaluate the prognostic value of temporal variability of T-wave morphology analyzed from a 5-minute resting electrocardiogram in CAD. METHODS: The standard deviation (SD) of T-wave morphology dispersion (TMD-SD) and the SD of total cosine R-to-T were analyzed on a beat-to-beat basis from a 5-minute period of the standard resting 12-lead electrocardiogram obtained before the clinical stress test in 1702 patients with angiographically verified CAD and well-preserved left ventricular function. RESULTS: During an average of 8.7 ± 2.2 years of follow-up, 60 patients experienced sudden cardiac death/arrest (SCD/SCA) (3.5%), 69 patients nonsudden cardiac death (NSCD) (4.1%), and 161 patients noncardiac death (9.5%). TMD-SD was significantly higher in patients who experienced SCD/SCA than in other patients (1.72 ± 2.00 vs 1.12 ± 1.75; P = .01) and higher in patients who succumbed to NSCD than in other patients (1.57 ± 1.74 vs 1.12 ± 1.76; P = .04), but it did not differ significantly between patients who experienced noncardiac death and those without such an event (1.16 ± 1.42 vs 1.14 ± 1.79; P = .86). In the Cox multivariable hazards model, TMD-SD retained its significant association with the risk of SCD/SCA (hazard ratio 1.119; 95% confidence interval 1.015-1.233; P = .024) but not with the risk of NSCD (hazard ratio 1.089; 95% confidence interval 0.983-1.206; P = .103). CONCLUSION: TMD-SD is independently associated with the long-term risk of SCD/SCA in patients with CAD.

Heart rate variability in sciatica patients referred to spine surgery: a case control study.

BACKGROUND: A chronic pain condition may result in altered autonomic nervous system regulation in various patient populations. We evaluated whether autonomic regulation differs between sciatica patients referred to spine surgery and age-matched healthy controls analyzed with heart rate variability techniques (HRV). METHODS: HRV of patients (n = 201) and healthy controls (n = 138) were measured in standing conditions (5 min). High frequency (HF) power as an index of cardiac vagal modulation and the low-to-high-frequency (LF/HF) ratio and short-term fractal scaling exponent α1 as indices of sympathovagal balance were analyzed. Pain intensity was assessed on a Visual Analog Scale (VAS) and perceived disability with Oswestry Disability Index. RESULTS: The Oswestry and VAS scores were higher in the patients than in the controls (p < 0.0001 for both). HF power was markedly lower for the patients compared to the controls (p < 0.0001). The LF/HF ratio and α1 were higher in the patients than in the controls (p < 0.01 for both). After adjusting for sex, smoking, BMI, and leisure-time physical activity, HF power (p = 0.011) and α1 (p = 0.012) still differed between the groups. Among the patients, HF power was slightly associated with the duration of chronic pain (r = -.232, p = 0.003). CONCLUSIONS: Sciatica patients referred to spine surgery had altered cardiac autonomic regulation expressed as decreased vagal activity and an increased sympathovagal balance toward sympathetic dominance when compared with age-matched healthy controls.

Endothelin-1 is associated with mortality that can be attenuated with high intensity statin therapy in patients with stable coronary artery disease.

BACKGROUND: All coronary artery disease (CAD) patients do not benefit equally of secondary prevention. Individualized intensity of drug therapy is currently implemented in guidelines for CAD and diabetes. Novel biomarkers are needed to identify patient subgroups potentially benefitting from individual therapy. This study aimed to investigate endothelin-1 (ET-1) as a biomarker for increased risk of adverse events and to evaluate if medication could alleviate the risks in patients with high ET-1. METHODS: A prospective observational cohort study ARTEMIS included 1946 patients with angiographically documented CAD. Blood samples and baseline data were collected at enrollment and the patients were followed for 11 years. Multivariable Cox regression was used to assess the association between circulating ET-1 level and all-cause mortality, cardiovascular (CV) death, non-CV death and sudden cardiac death (SCD). RESULTS: Here we show an association of circulating ET-1 level with higher risk for all-cause mortality (HR: 2.06; 95% CI 1.5-2.83), CV death, non-CV death and SCD in patients with CAD. Importantly, high intensity statin therapy reduces the risk for all-cause mortality (adjusted HR: 0.05; 95% CI 0.01-0.38) and CV death (adjusted HR: 0.06; 95% CI 0.01-0.44) in patients with high ET-1, but not in patients with low ET-1. High intensity statin therapy does not associate with reduction of risk for non-CV death or SCD. CONCLUSIONS: Our data suggests a prognostic value for high circulating ET-1 in patients with stable CAD. High intensity statin therapy associates with reduction of risk for all-cause mortality and CV death in CAD patients with high ET-1.

Patients with coronary artery disease (CAD) ­ in which the blood vessels supplying the heart become blocked - need careful management to prevent adverse outcomes related to their disease, such as a heart attack or sudden cardiac death. Identification of markers in the blood to predict adverse outcomes would help to improve the care of patients with CAD. Here, we find that higher circulating levels of endothelin-1 (ET-1), a protein secreted normally to maintain blood pressure, associate with greater risk of death in CAD patients. Cholesterol-lowering statin therapy used at high intensity (high dosage) can counteract the increased risk of death observed in CAD patients with high ET-1. Therefore, circulating ET-1 level could be used as a marker to predict the risk of death in CAD patients, and an indication for high intensity statin therapy. Our findings could help clinicians to improve the management of patients with CAD.

α-Adrenergic effects on low-frequency oscillations in blood pressure and R-R intervals during sympathetic activation.

The present study was designed to address the contribution of α-adrenergic modulation to the genesis of low-frequency (LF; 0.04-0.15 Hz) oscillations in R-R interval (RRi), blood pressure (BP) and muscle sympathetic nerve activity (MSNA) during different sympathetic stimuli. Blood pressure and RRi were measured continuously in 12 healthy subjects during 5 min periods each of lower body negative pressure (LBNP; -40 mmHg), static handgrip exercise (HG; 20% of maximal force) and postexercise forearm circulatory occlusion (PECO) with and without α-adrenergic blockade by phentolamine. Muscle sympathetic nerve activity was recorded in five subjects during LBNP and in six subjects during HG and PECO. Low-frequency powers and median frequencies of BP, RRi and MSNA were calculated from power spectra. Low-frequency power during LBNP was lower with phentolamine versus without for both BP and RRi oscillations (1.6 ± 0.6 versus 1.2 ± 0.7 ln mmHg(2), P = 0.049; and 6.9 ± 0.8 versus 5.4 ± 0.9 ln ms(2), P = 0.001, respectively). In contrast, the LBNP with phentolamine increased the power of high-frequency oscillations (0.15-0.4 Hz) in BP and MSNA (P < 0.01 for both), which was not observed during saline infusion. Phentolamine also blunted the increases in the LBNP-induced increase in frequency of LF oscillations in BP and RRi. Phentolamine decreased the LF power of RRi during HG (P = 0.015) but induced no other changes in LF powers or frequencies during HG. Phentolamine resulted in decreased frequency of LF oscillations in RRi (P = 0.004) during PECO, and a similar tendency was observed in BP and MSNA. The power of LF oscillation in MSNA did not change during any intervention. We conclude that α-adrenergic modulation contributes to LF oscillations in BP and RRi during baroreceptor unloading (LBNP) but not during static exercise. Also, α-adrenergic modulation partly explains the shift to a higher frequency of LF oscillations during baroreceptor unloading and muscle metaboreflex activation.

Risk factors of self-terminating and perpetuating ventricular tachyarrhythmias in post-infarction patients with moderately depressed left ventricular function, a CARISMA sub-analysis.

AIMS: The present study aimed to assess whether there are differences in risk indicators for perpetuating ventricular tachyarrhythmias (pVT) and self-terminating ventricular tachyarrhythmias (stVT). METHODS AND RESULTS: Patients with acute myocardial infarction (AMI) and baseline left ventricular ejection fraction ≤ 40% (n = 292) received an implantable electrocardiogram loop recorder from 5 to 21 days after AMI and were followed up for 24 months to document arrhythmic events in the Cardiac Arrhythmias and Risk Stratification after Acute Myocardial Infarction (CARISMA) study. Several risk markers, such as the inducibility to sustained ventricular tachycardia during programmed electrical stimulation (PES), the signal-averaged ECG QRS duration (SAECG-QRS), heart rate variability (HRV) and turbulence (HRT), T-wave alternans, and non-sustained ventricular tachycardia on Holter were analysed at 6 weeks after the AMI. During the follow-up, 26 patients (9%) experienced an stVT (≥ 16 beats and < 30 s), and 21 patients (7%) a pVT. The occurrence of non-sustained ventricular tachycardia on Holter significantly predicted stVT [hazard ratio (HR) = 2.90, 1.26-6.67, 95% confidence interval (CI), P = 0.01], but not pVT during the follow-up. The inducibility during PES (HR = 5.02, 1.85-13.60, 95% CI, P = 0.001), SAECG-QRS ≥ 130 ms (HR = 8.73, 3.38-22.56, 95% CI, P < 0.001), the short-term scaling exponent HRV parameter ≤ 0.77 (HR = 5.65, 2.12-15.10, 95% CI, P = 0.001), and HRT slope ≤ 1.75 ms/NN (HR = 4.57, 1.80-11.59, 95% CI, P = 0.001) were significant predictors of pVT, even after adjustments with relevant clinical parameters (P from < 0.01 to < 0.001), but did not significantly predict the occurrence of stVT (P from 0.35 to 0.75). CONCLUSION: Self-terminating ventricular tachyarrhythmia and pVT have differences in electrophysiological substrate and arrhythmia modifiers in post-AMI patients with moderate left ventricular dysfunction.