SGLT2 inhibitors and the autonomic nervous system in diabetes: A promising challenge to better understand multiple target improvement

Sodium-glucose cotransporter 2 (SGLT2) inhibitors reduce the risk of hospitalization for heart failure in patients regardless of the presence or absence of diabetes. More evidence is needed regarding the effects of these drugs in patients across the broad spectrum of heart failure, including those with a markedly reduced ejection fraction.

Heart rate variability (HRV) is a known risk factor for mortality in both healthy and patient populations. There are currently no normative data for short-term measures of HRV. A thorough review of short-term HRV data published since 1996 was therefore performed. Data from studies published after the 1996 Task Force report (i.e., between January 1997 and September 2008) and reporting short-term measures of HRV obtained in normally healthy individuals were collated and factors underlying discrepant values were identified. Forty-four studies met the pre-set inclusion criteria involving 21,438 participants. Values for short-term HRV measures from the literature were lower than Task Force norms. A degree of homogeneity for common measures of HRV in healthy adults was shown across studies. A number of studies demonstrate large interindividual variations (up to 260,000%), particularly for spectral measures. A number of methodological discrepancies underlined disparate values. These include a systematic failure within the literature (a) to recognize the importance of RR data recognition/editing procedures and (b) to question disparate HRV values observed in normally healthy individuals. A need for large-scale population studies and a review of the Task Force recommendations for short-term HRV that covers the full-age spectrum were identified. Data presented should be used to quantify reference ranges for short-term measures of HRV in healthy adult populations but should be undertaken with reference to methodological factors underlying disparate values. Recommendations for the measurement of HRV require updating to include current technologies. ©2010, The Authors. Journal compilation ©2010 Wiley Periodicals, Inc.

A high degree of heart rate (HR) variability is found in compensated hearts with good function, whereas HR variability can be decreased with severe coronary artery disease, congestive heart failure, aging and diabetic neuropathy. To test the hypothesis that HR variability is a predictor of long-term survival after acute myocardial infarction (AMI), the Holter tapes of 808 patients who survived AMI were analyzed. Heart rate variability was defined as the standard deviation of all normal RR intervals in a 24-hour continuous electrocardiogram recording made 11 +/- 3 days after AMI. In all patients demographic, clinical and laboratory variables were measured at baseline. Mean follow-up time was 31 months. Of all Holter variables measured, HR variability had the strongest univariate correlation with mortality. The relative risk of mortality was 5.3 times higher in the group with HR variability of less than 50 ms than the group with HR variability of more than 100 ms. HR variability remained a significant predictor of mortality after adjusting for clinical, demographic, other Holter features and ejection fraction. A hypothesis to explain this finding is that decreased HR variability correlates with increased sympathetic or decreased vagal tone, which may predispose to ventricular fibrillation.