Table 1.
Summary of the 19 selected publications.
| Study | Patient characteristics | Controls | HRV variables | Outcome variables | Main results |
|---|---|---|---|---|---|
| Study topic: HRV influence on prognosis | |||||
| Guo et al., 2015 |
n = 651 Group 1, n = 520, SDNN ≥ 70 ms Group 2, n = 131, SDNN < 70 ms |
None | 20- to24-h ECG monitoring (SDNN, SDANN, rMSSD, pNN50) | Survival | - Patients in group 2 had a significantly lower survival rate than patients in group 1 (25% of patients in group 2 died within 18.7 weeks vs. 78.8 weeks in group 1 patients, p < 0.0001) |
| Couck et al., 2016 |
n = 272 52.8% locally advanced pancreatic cancer; 47.2% metastatic cancer Mean age: 60.0 (±11.5) years |
None | 10 s ECG for HRV (time domain: SDNN, rMSSD), archival electronic records taken near diagnosis Cut-off: 20 ms (SDNN) - HighHRV > 20 ms - Low HRV < 20 ms |
Survival | - SDNN significantly correlated with survival, independent of all confounders. Patients with lowSDNN survived on average only 64.05 days versus those with high SDNN who survived 133.52 days |
| Giese-Davis et al., 2015 |
n = 87 One group with MRBC Mean age: 54.2 ± 9.92 years, females only |
None | 5 min ECG for HRV (time domain: HR, frequency domain: HF) | Survival | - Higher baseline HF with significantly longer survival - Visceral metastasis status and baseline heart rate related to HF - Combined HF and HR improved survival prediction |
| Wang et al., 2013 |
n = 40 One group with BM from 24 NSCLC, 6 SCLC, 4 BC, 6 others: median age: 61 (39–75) years, 21 females, 19 males; patients with no previous brain OP or RT |
None | 5 min ECG for HRV (time domain: SDNN, rMSSD), taken before WBRT, SDNN < 10 ms or ≥ 10 ms and rMSSD < 7 ms or ≥ 7 ms usedas prognostic factors in survival analysis | Overall survival (OS) | - SDNN < 10 ms as significant independent prognosticator for OS |
| Chiang et al., 2013 |
n = 138 Onegroup including LC, CRC, SC, hnC, PaC, GuC, EC, others; mean age: 67.6 ± 12.2 years, 62 females, 76 males |
None | 5 min ECG for HRV (frequency domain: HF, TP, LF/HF), data is logarithm transformed | Survival status after 7 days | - Association between InHPF and 7-day survival in patients with non-lung cancer |
| Chiang et al., 2010 | n = 33 One group with terminal HCC; mean age: 66.2 ± 13.8 years, 9 females, 24 males | None | 5 min ECG for HRV (frequency domain: HF, TP) | Time to death (TTD) | - HF power significantly associated with longer TTD - Higher TP significantly associated with longer TTD - 67% accuracy of 1-week-TTD prediction for HRVand TP -73% accuracy of 2-week TTD prediction for HF, 82% for TP |
| Fadul et al., 2010 |
n = 47 One group with LC, GITC; median age: 59 (20–79) years, males only |
None | 20 min ECG for HRV (time domain: SDNN, frequency domain: VLF, LF, HF) | Survival (interval between study entry and date of death) | - Statistically significant association between survival duration in days and presence of autonomic nervous system dysfunction (i.e., ET > 2) - Trend toward significant association between survival and lower SDNN - Strong correlation between ET and SDNN, VLF - No significant association between frequency domain parameters and survival |
| Kim et al., 2010 |
n = 68 One group with LC, SC, EC, hbC, GC, CRC; age: 26–84 years, 34 females, 34 males |
None | 5 min ECG for HRV (time domain: HR, SDNN, rMSSD, frequency domain: TP, LFP, HFP) | Survival (duration, from testing until date of death) | - SDNN of 21.3 ms or less significantly associated with longer survival duration - HR greater than 100 bpm significantly associated with longer survival duration |
| Hoffmann et al., 2001 |
n = 35 One group with metastatic carcinoid tumor (carcinoid syndrome); mean age: 56 ± 11 years, 14 females, 21 males |
None | 24-h ECG for HRV (time domain: SDNN, rMSSD, pNN50) | Survival duration with follow-up of 18 ± 7 months | - Low SDNN combined with CHD with significantly higher mortality |
| Study topic: HRV in relation to tumor burden | |||||
| Gidron et al., 2014 |
n = 185 Two groups: 72 with CRC, mean age: 63.7 ± 10.8 years, 45 females, 27 males 113 with PrC, mean age 65.1 ± 8.9 years, males only |
None | 10 s ECG for HRV (time domain: SDNN), archival electronic records taken near diagnosis Cut-off 20 ms (SDNN) - HighHRV > 20 ms - Low HRV < 20 ms |
Carcinoembryonic antigen (CEA) for CRC at 12 months Prostate specific antigen (PSA) for PrC at 6 months |
Division of patients into cancer stage 1–4: - Low HRV with significantly higher CEA levels in stage 4 than in stage1 - High HRV with no significant difference between stage 4 and stage 1 CEA levels - Significant increase of CEA levels in patients with stage 4 and low HRV after 12 months (non-significant for CEA stage1–3 and low HRV) - Low HRV with significantly higher PSA levels in stage 4 than in stage2 - High HRV with insignificant difference between stage 4 and stage 2 PSA levels - Significant increase of PSA levels in patients with stage 4 andlow HRV after 6 months (insignificant for PrCstage 2,3 and low HRV) |
| De Couck et al., 2013 |
n = 244 Two groups: 113 with PrC, mean age: 65.06 ± 8.87 years, males only 133 with NSCLC, mean age: 62.2 ± 10.2 years (no gender specification provided) |
None | 10 s ECG for HRV (time domain: SDNN, rMDSS), electronic records taken near diagnosis Cut-off 20 ms (SDNN) - HighHRV > 20 ms - Low HRV < 20 ms |
PrC: PSAlevels at 6 months and 2 years NSCLC: OS in full sample and survival time in deceased patients |
- HRV parameters significantly predicted PSA levels at 6 months independent of confounders - HRV significantly predicted PSA levels only in stage 4 (metastatic stage), not in stage 2/3 - HRV parameters with no significant correlation to OS or survival time - Higher HRV in younger (under 65 years) NSCLC patients significantly predicted longer survival time - NSCLC patients have significantly lower SDNN than PrC patients |
| Mouton et al., 2012 |
n = 38 One group with CRC; mean age: 63.7 ± 10.8 years, 24 females, 14 males |
None | 10 s ECG for HRV (time domain: SDNN, rMDSS), archival electronic records taken near diagnosis Cut-off 20 ms (SDNN) - HighHRV > 20 ms - Low HRV < 20 ms |
CEA levels at 12 months from diagnosis Examination of evolution of CEA at diagnosis, 6 and 12 months later |
- Baseline SDNN significantly, inversely predicted CEA levels at 12 months, independent of confounders - Low HRV significantly predicted higher CEA levels at 12 months - rMSSD with no predictive significance - HRV-CEA relationship significant in patients with palliative treatment, not curative treatment |
| Study topic: HRV comparison | |||||
| Bijoor et al., 2016 |
n = 184 Two groups with hnC, GITC, GyC; median age : 54 (range 40–68) Early stage Group: n = 59 Advanced stage Group: n = 128 |
n = 150 Age and gender matched healthy individuals |
1 min ECG for HRV (time domain: rMSSD) | HRV (rMSSD) of patients compared with healthy subjects HRV (rMSSD) of early stage compared to advanced stage group |
- rMSSD significantly lower in cancer group compared to healthy group - rMSSD significantly lower in advanced stage of cancer compared- to early stage |
| Palma et al., 2016 |
n = 30 Two groups with BC BCG1: <18 months since breast cancer surgery; mean age 51.1 ± 8.6 BCG2: >18 months since breast cancer surgery; mean age 56.3 ± 7.4 |
n = 15 age matched healthy women; mean age 51.2 ± 10.8 |
30 min HR recording with Polar S810i (time domain: mean RR, rMSSD, SDNN, frequency domain: LF, HF, LF/HF) | HRV of breast cancer survivors after surgery compared to cancer free women Comparison of HRVof patients according to elapsed time since the surgery |
- rMSSD, SDNN and HF are significantly reduced in post breast cancer groups compared to cancer-free group - No difference in HRV parameters regarding to the postoperative period |
| Koszewicz et al., 2016 |
n = 33 One group with pBT; mean age 53.0 ± 15.2 |
N = 43 Healthy volunteers, mean age 51.7 ± 10.1 |
HRV in% at rest (LF, HF, LF/HF) | HRV of patients compared with healthy volunteers | - HRV% significantly lower in patients group - No significant difference in LF, HF or LF/HF |
| De Couck and Gidron, 2013 |
n = 657 One group with PrC, PaC, CC, OC, NSCLC; mean age: 63.09 ± 11.07 years, 309 females, 348 males |
One group 21’438 healthy adults for HRV-control |
10 s ECG for HRV (time domain: SDNN, rMSSD), archival electronic records taken near diagnosis Cut-off 20 ms (SDNN) - HighHRV > 20 ms - Low HRV < 20 ms |
HRV (indices) of patients compared withHRV of healthy subjects | - Mean HRV of cancer patients significantly lower than HRV of healthy samples - Significantly lower HRV in advanced stages (3, 4) than early stages - Lower HRV in patients with age > 65 years - HRV with tendency to significance in group < 65 - OC and NSCLC with significantly lower HRV than other cancer types |
| Lin and Chen, 2010 |
n = 124 Two groups with hnC, LC, BC, GITC and others Group with metastasis: n = 61, mean age: 62.3± 12.7 years, 36 females, 25 males Group without metastasis: n = 63, mean age: 52.6± 10.7 years, 35 females, 28 males |
None | 5 min ECG for HRV (time domain: HR, SDANN, frequency domain: TP, LF, HF, VLF, LF/HF ratio) | Comparison of HRV of patients with and without metastasis | - HR significantly higher in patients with metastasis - SDANN, TP, LF and VLF significantly lower in patients with metastasis - No statistical significance of HF and LF/HF ratio between the two groups |
| Nevruz et al., 2007 |
n = 36 1 group with n = 14 ALL, n = 22 AML; mean age: 34 ± 16 years, 11 females, 25 males No previous treatment |
n = 32 age-matched healthy subjects; 9 female, 23 males, mean age: 33 ± 10 years | 24-h ECG for HRV (time domain: SDNN, SDANN, HRV-triangular index, rMSSD, PNN50, SNN50) within 2 weeks of diagnosis | Comparison of HRV parameters of leukemia to control group parameters Comparison of HRV parameters of ALLto HRV parameters of AML |
- SDNN, SDANN, SNN50, PNN50, HRV-triangular index values significantly lower in leukemia patients compared to control group - HRVdecreases in acute leukemias |
| Bettermann et al., 2001 |
n = 37 One Group B with BC;mean age: 56 ± 12 years, females only Subgroups: B1: with metastases, B0: non-metastases |
Two groups Group C: n = 37 healthy controls; mean age 53 ± 12 years, females only Group D: n = 40 diabetic controls; mean age: 55 ± 15 years, females only |
24-h ECGfor HRV (frequency domain: LF,HF, LF/HF, mean RR) | Comparison of HRV of B, C, D Comparison of HRV of B0, B1 |
- No significant difference of HRV parameters between B and C - No significant difference of HRV parameters between B and D - Lower HRV in B1 compared to B0 (non-significant) |
HR, heart rate; RR, time interval between R-peaks in the ECG, i.e., the inter-beat interval (IBI); NN, normal-to-normal intervals, i.e., intervals between normal R-peaks; SDANN, 24-h standard deviation of average NN intervals; SDNN, standard deviation of NN intervals; rMSSD, root mean square of successive differences; pNN50, percentages of differences between adjacent normal NN intervals > 50 ms; SNN50, R–R intervals exceeding 50 ms; HF, high-frequency power (0.15–0.4 Hz); LF/HF, low- to high-frequency power ratio; TP, total power; lnHFP, logarithm transformed high-frequency power; VLF, very low frequency (0.0033–0.04 Hz); ET, Ewing Test Score; OS, overall survival; TTD, time to death; CHD, carcinoid heart disease; WBRT, whole brain radiotherapy; CEA, carcinoembryonic antigen; PSA, prostate-specific antigen; BM, brain metastasis; NSCLC, non-small cell lung cancer; SCLC, small cell lung cancer; BC, breast cancer; LC, lung cancer; CRC, colorectal cancer; hnC, head and neck cancer; PaC, pancreatic cancer; guC, genitourinary cancer; EC, esophagus cancer (also; oesophagus cancer); HCC, hepatocellular carcinoma; GITC, gastrointestinal cancer; SC, stomach cancer; hbC, hepatobiliary cancer; GC, gastric cancer; PrC, prostate cancer; OC, ovarian cancer; CC, cervical carcinoma; ALL, acute lymphatic leukemia; AML, acute myeloid leukemia; MRBC, metastatic or recurrent breast cancer; GyC, gynecological cancer; pBT, primary brain tumor.