Heart rate variability measurement and clinical depression in acute coronary syndrome patients: narrative review of recent literature

Figures & data

Table 1 Definitions of frequently used heart rate variability (HRV) measurements

Variable abbreviation	HRV definitions (unit of measurement)
Time domain variables: measured using descriptive statistics^Citation5,Citation27
Long-term time domain measures
SDNN	Standard deviation (SD) of all normal RR intervals (Normal-Normal [NN]) usually measured over ~24 hours (milliseconds [ms]) (estimates global heart rate variability power; corresponds to total power)
SDANN	Standard deviation of the average normal RR (NN) intervals in all 5-minute segments, usually measured over ∼24 hours (ms) (corresponds to ULF)
SDNN index	Mean of the standard deviations of normal RR (NN) intervals in all 5-minute segments over ∼24 hours (ms) (corresponds to the mean of 5-minute segments of total power)
Short-term time domain measures
rMSSD (rMSNN)	Square root of the mean of squares of the differences between successive normal RR (NN) intervals (ms); referred to as rMSNN in the study by Guinjoan et al^Citation13 (corresponds to HF)
pNN50*	Percentage of normal RR intervals that are >50 ms different from previous normal RR during recording time (%) (corresponds to HF)
Frequency domain variables: measured using spectral analysis^Citation5,Citation27
TP*	Total power, estimates global power, ie, HF, LF, VLF, and ULF, measured over ~24 hours (ms^Citation2)
HF*	Average of 5-min segments of high frequency power for total recording time (ms^Citation2); HF reference range =0.15–0.4 Hz
LF*	Average of 5-min segments of low frequency power for the total recording time (ms^Citation2); LF reference range =0.04–0.15 Hz
VLF*	Very low frequency power, averages of 5-minute segments measured over the total recording time (ms^Citation2); VLF reference range =0.003–0.04 Hz
ULF*	Ultra low frequency power measured over ~24 hours (ms^Citation2); ULF reference range ≤0.003 Hz
LF/HF*	Average of 5-min segments of normalized low/high frequency ratio: (LF/[total power – VLF] ×100) divided by (HF/[total power – VLF] ×100)
Nonlinear measures^Citation9,Citation29,Citation33^–^Citation36
ApEn	Approximate entropy: measure of randomness or disorder within a system; calculation of the logarithmic likelihood that patterns that are similar remain similar in the next incremental comparisons
DFA1	Detrended fractal analysis: short-term fractal scaling exponent calculated over 3–11 beats, averaged over 1,000 beats for 24 hours (also known as alpha-1, reported as an exponent value)
SD12 SD1, SD2	SD12, SD1, and SD2 are derived from the Poincare plot (a scatter plot in which each R–R interval is plotted against the next R–R interval). SD12 is the ratio of the dispersion, or standard deviation, of the plot’s perpendicular axis, indicating short-term, instantaneous beat-to-beat variance (known as SD1), versus the standard deviation of the plot’s diagonal axis, indicating long-term, continuous variance (known as SD2) Note: While the SD1/SD2 ratio is a nonlinear measurement, SD1 and SD2, calculated individually, are linear measurements; SD1 correlates precisely with rMSSD

Notes: The terms “variables,” “measures,” “measurements,” and “indices” are often used interchangeably in referring to HRV.

* Natural log transformations are often performed for these variables, which usually are not normally distributed. Time domain HRV measurements are based upon the intervals between the “R” waves in the QRS complexes (referred to as the RR interval). The QRS complex in the ECG corresponds to depolarization of the ventricles.

Figure 1 Representation of potential coronary outcome pathways related to mood and heart rate variability after an episode of acute coronary syndrome, ie, unstable angina, non-ST elevation myocardial infarction, or ST elevation myocardial infarction.

Table 2 Study summaries of heart rate variability and depression in acute coronary syndrome

Author	Sample	Measurements: HRV depression	Design/outcome measure	Significant results
Differences in heart rate variability and depression between acute coronary syndrome patients
Guinjoan et al^Citation13	n=56 ACS patients ≥60 years, in CCU	Derived from 550 heartbeats during ACS hospitalization: pNN50, SDNN, rMSNN, TP, HF, LF, and LF/HF_______________ • Patient interviews • Hamilton Depression Score	• Cross-sectional • Differences in HRV and depression scores between depressed and nondepressed patients ≤72 hours after ACS admission	• n=19 depressed • pNN50 (P=0.006), rMSNN (P=0.009) and HF (P=0.024) lower in depressed patients compared with nondepressed patients
Vigo et al^Citation14	n=52 ACS patients ≥60 years, in CCU	Recorded over ~10 minutes during ACS hospitalization: pEn, DFA1, and SD1____________ • Patient interviews • Hamilton Depression Score	• Cross-sectional • Differences in nonlinear HRV measures in depressed patients ≤72 hours of ACS admission	• n=19 depressed • Depression associated with altered patterns of SD1 (P=0.001), DFA1 (P=0.023), and ApEn (P=0.046)
Catipović-Veselica et al^Citation15	n=297 ACS patients in CCU	Recorded over 24 hours during ACS hospitalization: ANN, SDNN, and SDNN index_________________ • Patient interviews	• Cross-sectional • Differences in HRV and clinical variables between those with and without depression during hospitalization, at time of discharge	• n=79 major depression • n=87 minor depression • SDNN, SDANN, SDNN index lower (P<0.05) in minor or major depression in univariate analyses
Martens et al^Citation16	n=82 Hospitalized MI patients	Recorded over 24 hours, ~2 months post-ACS hospitalization: SDNN, SDANN, rMSSD, VLF, LF, HF, and LF/HF________________ • Beck Depression Inventory • State Trait Anxiety Inventory (anxiety screening measure)	• Cross-sectional • Extent to which depression and anxiety scores or depression and anxiety symptoms can estimate variance in HRV, 2 months post-ACS hospitalization	• n=19 depressed • Depressive disorder was associated with lower SDNN (P=0.022) and SDANN (P=0.023) in univariate analysis. Only anxiety was associated with HRV in multivariable analysis
Heart rate variability and depression in association with acute coronary syndrome outcomes
de Guevara et al^Citation17	n=38 ACS patients ≥60 years, in CCU	Derived from 550 heartbeats, during ACS hospitalization: pNN50, SDNN, rMSSN, TP, HF, LF, and LF/HF ratio__________ • Patient interviews • Hamilton Depression Score	• Longitudinal • Differences in nonlinear HRV measures and depression scores for patients ≤72 hours of ACS admission (baseline) and after 6 months	• n=30 survivors • I ncrease in Hamilton Depression Score correlated with decrease HRV 6 months post-ACS, specifically, TP (P=0.014), LF (P=0.014), and HF (P=0.007)
Carney et al^Citation18	n=678 MI patients in CCU	Recorded over 24 hours, baseline assessment within 28 days of ACS: VLF (log)_______________ • Patient interviews • Beck Depression Inventory	• Longitudinal • Changes in HRV and depression associated with all-cause mortality at 28 days (baseline), 6 months and 30 months after ACS discharge	• n=311 depressed • Depression associated with decreased VLF and mortality after adjusting for potential confounders (P<0.001)
Drago et al^Citation19	n=100 consecutive acute MI patients in CCU	Recorded over 24 hours, baseline assessment during ACS hospitalization: SDNN_______________ • Patient interviews • Beck Depression Inventory	• Longitudinal • Association of HRV with recurrent MI or all-cause mortality starting at time of ACS hospitalization (baseline measurement 7–14 days after admission) over 5-year follow-up	• n=15 major depression • n=35 mild-to-moderate depression • HRV lower in major (P<0.01) and mild-to-moderate depression (P=0.01)
Glassman et al^Citation20	n=258 ACS patients with major depressive disorder	Recorded over 24 hours, baseline assessment within 30 days of ACS: HF, LF, VLF, and ULF____________ • Patient interviews • Hamilton Depression Score	• Longitudinal • Differences in HRV and depression between groups • Changes in HRV and depression between baseline assessment within 30 days of ACS and 16-week follow-up	• n=258 depressed at follow-up • All HRV measures were low • ULF significantly higher in sertraline group compared with placebo group (P=0.02) • LF higher with improved mood (P=0.05)
Heart rate variability and depression in relation to inflammation in acute coronary syndrome patients
Frasure-Smith et al^Citation21	n=682 ACS patients with follow-up visit	Recorded over 30 minutes, ~2 months post-ACS hospitalization: Mean RR, SDNN, HF, and LF_______ • Patient interviews • Beck Depression Inventory	• Cross-sectional • Differences in HRV and two inflammatory markers (IL-6 and C-reactive protein) in relation to depression, measured 2 months after ACS episode	• n=191 depressed • SDNN, LF, and HF (all P<0.001), inversely related to IL-6 and C-reactive protein (P<0.05) in univariate analyses • Correlation between HRV and C-reactive protein stronger with severe depression (P<0.05)

Note: *See Table 1 for HRV definitions.

Abbreviations: ACS, acute coronary syndrome; CCU, coronary care unit; HRV, heart rate variability; IL, interleukin; log, natural logarithm transformation; MI, myocardial infarction.

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