Despite its extensive use in physiological and clinical research, the analysis of HRV (heart rate variability) is still poorly supported by rigorous reliability studies. The main aim of the present study was to perform an in-depth assessment of absolute and relative reliability of standard indexes of HRV from short-term laboratory recordings. In 39 healthy subjects [mean age (min–max): 38 (26–56) years; 18 men and 21 women] we recorded 5 min of supine ECG during spontaneous and paced (15 breaths/min) breathing. The test was repeated on the next day under the same conditions. From the RR intervals we computed standard indexes of HRV: SDNN (S.D. of RR interval values), RMSSD (root-mean-square of successive RR interval differences), LF (low frequency) and HF (high frequency) power (absolute and normalized units) and LF/HF. Absolute reliability was assessed by 95% limits of random variation; relative reliability was assessed by the ICC (intraclass correlation coefficient). The sample size needed to detect a mean difference ≥30% of the between-subject S.D. was also estimated. Although there was no significant mean change between the two tests, we found that in individual subjects the second measurement was as high/low as 1.9/0.5 times (SDNN, best case) and 3.5/0.3 times (LF/HF, worst case) the first measurement, due to pure random variation. For most parameters the ICC was >0.8 (range 0.65–0.88). The estimated sample size ranged from 24–98 subjects. Reliability indexes tended to improve during paced breathing. We conclude that short-term HRV parameters are subject to large day-to-day random variations. Random error, however, represents a limited part of the between-subject variability; therefore observed differences between individuals mostly reflect differences in the subjects' error-free value rather than random error. Overall, paced breathing improves reliability.

Background: Using data from the GARFIELD ‐ AF (Global Anticoagulant Registry in the FIELD –Atrial Fibrillation), we evaluated the impact of chronic kidney disease ( CKD ) stage on clinical outcomes in patients with newly diagnosed atrial fibrillation ( AF ). Methods and Results: GARFIELD ‐ AF is a prospective registry of patients from 35 countries, including patients from Asia (China, India, Japan, Singapore, South Korea, and Thailand). Consecutive patients enrolled (2013–2016) were classified with no, mild, or moderate‐to‐severe CKD , based on the National Kidney Foundation's Kidney Disease Outcomes Quality Initiative guidelines. Data on CKD status and outcomes were available for 33 024 of 34 854 patients (including 9491 patients from Asia); 10.9% (n=3613) had moderate‐to‐severe CKD , 16.9% (n=5595) mild CKD , and 72.1% (n=23 816) no CKD . The use of oral anticoagulants was influenced by stroke risk (ie, post hoc assessment of CHA ₂ DS ₂ ‐ VAS c score), but not by CKD stage. The quality of anticoagulant control with vitamin K antagonists did not differ with CKD stage. After adjusting for baseline characteristics and antithrombotic use, both mild and moderate‐to‐severe CKD were independent risk factors for all‐cause mortality. Moderate‐to‐severe CKD was independently associated with a higher risk of stroke/systemic embolism, major bleeding, new‐onset acute coronary syndrome, and new or worsening heart failure. The impact of moderate‐to‐severe CKD on mortality was significantly greater in patients from Asia than the rest of the world ( P =0.001). Conclusions: In GARFIELD ‐ AF , moderate‐to‐severe CKD was independently associated with stroke/systemic embolism, major bleeding, and mortality. The effect of moderate‐to‐severe CKD on mortality was even greater in patients from Asia than the rest of the world. Clinical Trial Registration: URL : http://www.clinicaltrials.gov . Unique identifier: NCT 01090362.

Background The aim of the present study was to investigate the effect of a single bout of mild exercise on autonomic nervous system activity in healthy subjects. Methods and Results The study group comprised 18 healthy males, aged between 20 and 24 years, who had not been training regularly for the last 3 months. A supine recording of systolic arterial pressure (SAP) and RR interval and the administration of the phenylephrine test were performed at baseline and repeated after a 60-min recovery period following treadmill exercise training for 30 min at 65% of maximal heart rate. Mean SAP and RR interval, heart rate variability (HRV) indices (the standard deviation of normal-to-normal RR intervals (SDNN), the square root of the mean of squared differences between successive intervals and the percentage of adjacent RR intervals differing more than 50 ms), noninvasive spectral baroreflex sensitivity (Spe-BRS) and phenylephrine baroreflex sensitivity (Phe-BRS) were assessed before and after training. Mean SAP measured after exercise was lower than baseline (120±12 mmHg vs 128±12 mmHg, p=0.05). Spe-BRS and Phe-BRS increased significantly after exercise, from 11.8±6.1 ms/mmHg to 16.0±7.8 ms/mmHg (p=0.034), and from 16.0±8.8 ms/mmHg to 21.9±9.3 ms/mmHg (p=0.022), respectively. A parallel increase was also observed in SDNN (from 81±44 ms to 96±53 ms, p=0.02), but the other HRV indices showed no significant differences between pre- and post-exercise. Conclusions A single session of mild exercise performed by sedentary young men leads to significant autonomic nervous system improvement, which suggests that even mild physical activity is beneficial for neural cardiac regulation and should be recommended to sedentary healthy subjects. (Circ J 2005; 69: 976 - 980)

Aims: Transoesophageal echocardiography (TOE) is often performed before catheter ablation or cardioversion to rule out the presence of left atrial appendage thrombus (LAT) in patients on chronic oral anticoagulation (OAC), despite associated discomfort. A machine learning model [LAT-artificial intelligence (AI)] was developed to predict the presence of LAT based on clinical and transthoracic echocardiography (TTE) features. Methods and results: Data from a 13-site prospective registry of patients who underwent TOE before cardioversion or catheter ablation were used. LAT-AI was trained to predict LAT using data from 12 sites (n = 2827) and tested externally in patients on chronic OAC from two sites (n = 1284). Areas under the receiver operating characteristic curve (AUC) of LAT-AI were compared with that of left ventricular ejection fraction (LVEF) and CHA2DS2-VASc score. A decision threshold allowing for a 99% negative predictive value was defined in the development cohort. A protocol where TOE in patients on chronic OAC is performed depending on the LAT-AI score was validated in the external cohort. In the external testing cohort, LAT was found in 5.5% of patients. LAT-AI achieved an AUC of 0.85 [95% confidence interval (CI): 0.82–0.89], outperforming LVEF (0.81, 95% CI 0.76–0.86, P < .0001) and CHA2DS2-VASc score (0.69, 95% CI: 0.63–0.7, P < .0001) in the entire external cohort. Based on the proposed protocol, 40% of patients on chronic OAC from the external cohort would safely avoid TOE. Conclusion: LAT-AI allows accurate prediction of LAT. A LAT-AI-based protocol could be used to guide the decision to perform TOE despite chronic OAC.

Despite a well-established prognostic value in cardiac patients, HRV (heart rate variability) indexes have been used little in the clinical setting. Poor reliability of the measurements might be a possible explanation for this. In the present study, we assessed the reliability of short-term HRV indexes in post-MI (myocardial infarction) patients. We studied 61 MI patients [50 males; age, 59±8 years; and LVEF (left ventricular ejection fraction), 46±6%; values are means±S.D.], who underwent a 5+5 min ECG recording during spontaneous and paced breathing on two consecutive days. Standard time-domain [SDNN (S.D. of RR interval values) and RMSSD (root-mean-square of successive RR interval differences)] and frequency-domain [LF (low-frequency) and HF (high-frequency) power, and LF/HF] indexes of HRV were computed. Absolute and relative reliability were assessed by the 95% limits of random variation and by the ICC (intra-class correlation coefficient). The agreement between the two measurements in classifying patients at low or high risk, according to different cut-points, and the sample size needed to detect a clinically relevant change, were also assessed. During spontaneous breathing, individual changes in test–retest measurements ranged from −41 to +61% (SDNN; best case) and from −76 to +316% (LF/HF; worst case). The ICC ranged from 0.72 to 0.81. Most patients (79–90%) were assigned to the same class by the two measurements. Paced breathing did not improve reliability. In conclusion, short-term HRV parameters in MI patients may have large day-to-day variations, making the detection of treatment effects in individual patients difficult; however, the ICC values and the analysis of the consistency of classification between repeated tests indicate that HRV measurements fulfil the criteria required to be used for diagnostic or classification purposes.

Hereditary hemochromatosis (HH) is a genetic disease leading to excessive iron absorption, its accumulation, and oxidative stress induction causing different organ damage, including the heart. The process of cardiac involvement is slow and lasts for years. Cardiac pathology manifests as an impaired diastolic function and cardiac hypertrophy at first and as dilatative cardiomyopathy and heart failure with time. From the moment of heart failure appearance, the prognosis is poor. Therefore, it is crucial to prevent those lesions by upfront therapy at the preclinical phase of the disease. The most useful diagnostic tool for detecting cardiac involvement is echocardiography. However, during an early phase of the disease, when patients do not present severe abnormalities in serum iron parameters and severe symptoms of other organ involvement, heart damage may be overlooked due to the lack of evident signs of cardiac dysfunction. Considerable advancement in echocardiography, with particular attention to speckle tracking echocardiography, allows detecting discrete myocardial abnormalities and planning strategy for further clinical management before the occurrence of substantial heart damage. The review aims to present the current state of knowledge concerning cardiac involvement in HH. In addition, it could help cardiologists and other physicians in their everyday practice with HH patients.