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Impact of cancer and chemotherapy on autonomic nervous system function and cardiovascular reactivity in young adults with cancer: a case-controlled feasibility study.

Adams SC, Schondorf R, Benoit J, Kilgour RD - BMC Cancer (2015)

Bottom Line: Their results were compared to 12 sex- and age-matched controls.Our feasibility criteria addressed: i) recruitment potential, ii) retention rates, iii) pre-chemotherapy assessment potential, iv) test performance/tolerability, and v) identification and minimizing the influence of potentially confounding medication.According to the CASS, there was evidence of ANS impairment at baseline in 30.8 % of patients, which persisted in 18.2 % of patients at follow-up, compared to 0 % of controls at baseline or follow-up.

View Article: PubMed Central - PubMed

Affiliation: Department of Exercise Science, Concordia University, Montreal, QC, Canada. scott.adams@ualberta.ca.

ABSTRACT

Background: Preliminary evidence suggests cancer- and chemotherapy-related autonomic nervous system (ANS) dysfunction may contribute to the increased cardiovascular (CV) morbidity- and mortality-risks in cancer survivors. However, the reliability of these findings may have been jeopardized by inconsistent participant screening and assessment methods. Therefore, good laboratory practices must be established before the presence and nature of cancer-related autonomic dysfunction can be characterized. The purpose of this study was to assess the feasibility of conducting concurrent ANS and cardiovascular evaluations in young adult cancer patients, according to the following criteria: i) identifying methodological pitfalls and proposing good laboratory practice criteria for ANS testing in cancer, and ii) providing initial physiologic evidence of autonomic perturbations in cancer patients using the composite autonomic scoring scale (CASS).

Methods: Thirteen patients (mixed diagnoses) were assessed immediately before and after 4 cycles of chemotherapy. Their results were compared to 12 sex- and age-matched controls. ANS function was assessed using standardized tests of resting CV (tilt-table, respiratory sinus arrhythmia and Valsalva maneuver) and sudomotor (quantitative sudomotor axon reflex test) reactivity. Cardiovascular reactivity during exercise was assessed using a modified Astrand-Ryhming cycle ergometer protocol. Our feasibility criteria addressed: i) recruitment potential, ii) retention rates, iii) pre-chemotherapy assessment potential, iv) test performance/tolerability, and v) identification and minimizing the influence of potentially confounding medication. T-tests and repeated measures ANOVAs were used to assess between- and within-group differences at baseline and follow-up.

Results: The overall success rate in achieving our feasibility criteria was 98.4 %. According to the CASS, there was evidence of ANS impairment at baseline in 30.8 % of patients, which persisted in 18.2 % of patients at follow-up, compared to 0 % of controls at baseline or follow-up.

Conclusions: Results from our feasibility assessment suggest that the investigation of ANS function in young adult cancer patients undergoing chemotherapy is possible. To the best of our knowledge, this is the first study to report CASS-based evidence of ANS impairment and sudomotor dysfunction in any cancer population. Moreover, we provide evidence of cancer- and chemotherapy-related parasympathetic dysfunction - as a possible contributor to the pathogenesis of CV disease in cancer survivors.

No MeSH data available.


Related in: MedlinePlus

Individual QSART scores at the forearm (top left), proximal leg (top right), distal leg (bottom left) and foot (bottom right) for patients and controls at baseline and follow-up. Note Data points have been color-coded within each group and according to subject. Circular data points reflect scores or measurements falling within normal age- and gender-related ranges. Whereas triangular and square data points reflect scores or measurements > 50 % and < 50 %, respectively, of the lower normal age- and gender-related limits. Black vertical bars and corresponding values represent group means for each time point
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Fig4: Individual QSART scores at the forearm (top left), proximal leg (top right), distal leg (bottom left) and foot (bottom right) for patients and controls at baseline and follow-up. Note Data points have been color-coded within each group and according to subject. Circular data points reflect scores or measurements falling within normal age- and gender-related ranges. Whereas triangular and square data points reflect scores or measurements > 50 % and < 50 %, respectively, of the lower normal age- and gender-related limits. Black vertical bars and corresponding values represent group means for each time point

Mentions: T2 measurements were collected a mean of 14.3 weeks and 19.0 weeks after T1 for patients and controls, respectively. 2x2 repeated measures ANOVAs revealed significant, or near significant, between-group differences for all dependent variables found in Table 5. Autonomic dysfunction is defined as a minimum score of two in any of the three CASS domains (i.e., cardiovagal, adrenergic and sudomotor), or a minimum score of one in at least two domains – out of a total possible score of 10 [42]. After applying the CASS criteria, the individual (Figs. 3 and 4) and group results (Tables 6 and 7) demonstrate mild to moderate ANS dysfunction at T1 (1.23 ± 1.59; mean ± SD), with slight improvement in ANS function at T2 (0.67 ± 0.99). The observed group main effects were the patients’ cardiovagal [F(1,21) = 4.575, p = 0.044] and total [F(1,21) = 5.975, p = 0.023] CASS scores were significantly higher than controls. Although the difference between patients’ and controls’ sudomotor CASS scores did not reach significance [F(1,21) = 3.702, p = 0.068], the number of patients who had abnormal or borderline abnormal QSART scores was significantly higher than controls [F(1,21) = 4.830, p = 0.039]. Neither group displayed evidence of severe ANS or CV dysfunction at either testing time point. Unmanaged, disease- and treatment-related complications prevented one patient from attempting the VM at T1, and a different patient from attempting the VM and tilt-table test at T2. Two patients and two controls demonstrated orthostatic intolerance during the tilt-table test at T1 and T2 (one subject from each group at each time point).Table 5


Impact of cancer and chemotherapy on autonomic nervous system function and cardiovascular reactivity in young adults with cancer: a case-controlled feasibility study.

Adams SC, Schondorf R, Benoit J, Kilgour RD - BMC Cancer (2015)

Individual QSART scores at the forearm (top left), proximal leg (top right), distal leg (bottom left) and foot (bottom right) for patients and controls at baseline and follow-up. Note Data points have been color-coded within each group and according to subject. Circular data points reflect scores or measurements falling within normal age- and gender-related ranges. Whereas triangular and square data points reflect scores or measurements > 50 % and < 50 %, respectively, of the lower normal age- and gender-related limits. Black vertical bars and corresponding values represent group means for each time point
© Copyright Policy - open-access
Related In: Results  -  Collection

License 1 - License 2
Show All Figures
getmorefigures.php?uid=PMC4522971&req=5

Fig4: Individual QSART scores at the forearm (top left), proximal leg (top right), distal leg (bottom left) and foot (bottom right) for patients and controls at baseline and follow-up. Note Data points have been color-coded within each group and according to subject. Circular data points reflect scores or measurements falling within normal age- and gender-related ranges. Whereas triangular and square data points reflect scores or measurements > 50 % and < 50 %, respectively, of the lower normal age- and gender-related limits. Black vertical bars and corresponding values represent group means for each time point
Mentions: T2 measurements were collected a mean of 14.3 weeks and 19.0 weeks after T1 for patients and controls, respectively. 2x2 repeated measures ANOVAs revealed significant, or near significant, between-group differences for all dependent variables found in Table 5. Autonomic dysfunction is defined as a minimum score of two in any of the three CASS domains (i.e., cardiovagal, adrenergic and sudomotor), or a minimum score of one in at least two domains – out of a total possible score of 10 [42]. After applying the CASS criteria, the individual (Figs. 3 and 4) and group results (Tables 6 and 7) demonstrate mild to moderate ANS dysfunction at T1 (1.23 ± 1.59; mean ± SD), with slight improvement in ANS function at T2 (0.67 ± 0.99). The observed group main effects were the patients’ cardiovagal [F(1,21) = 4.575, p = 0.044] and total [F(1,21) = 5.975, p = 0.023] CASS scores were significantly higher than controls. Although the difference between patients’ and controls’ sudomotor CASS scores did not reach significance [F(1,21) = 3.702, p = 0.068], the number of patients who had abnormal or borderline abnormal QSART scores was significantly higher than controls [F(1,21) = 4.830, p = 0.039]. Neither group displayed evidence of severe ANS or CV dysfunction at either testing time point. Unmanaged, disease- and treatment-related complications prevented one patient from attempting the VM at T1, and a different patient from attempting the VM and tilt-table test at T2. Two patients and two controls demonstrated orthostatic intolerance during the tilt-table test at T1 and T2 (one subject from each group at each time point).Table 5

Bottom Line: Their results were compared to 12 sex- and age-matched controls.Our feasibility criteria addressed: i) recruitment potential, ii) retention rates, iii) pre-chemotherapy assessment potential, iv) test performance/tolerability, and v) identification and minimizing the influence of potentially confounding medication.According to the CASS, there was evidence of ANS impairment at baseline in 30.8 % of patients, which persisted in 18.2 % of patients at follow-up, compared to 0 % of controls at baseline or follow-up.

View Article: PubMed Central - PubMed

Affiliation: Department of Exercise Science, Concordia University, Montreal, QC, Canada. scott.adams@ualberta.ca.

ABSTRACT

Background: Preliminary evidence suggests cancer- and chemotherapy-related autonomic nervous system (ANS) dysfunction may contribute to the increased cardiovascular (CV) morbidity- and mortality-risks in cancer survivors. However, the reliability of these findings may have been jeopardized by inconsistent participant screening and assessment methods. Therefore, good laboratory practices must be established before the presence and nature of cancer-related autonomic dysfunction can be characterized. The purpose of this study was to assess the feasibility of conducting concurrent ANS and cardiovascular evaluations in young adult cancer patients, according to the following criteria: i) identifying methodological pitfalls and proposing good laboratory practice criteria for ANS testing in cancer, and ii) providing initial physiologic evidence of autonomic perturbations in cancer patients using the composite autonomic scoring scale (CASS).

Methods: Thirteen patients (mixed diagnoses) were assessed immediately before and after 4 cycles of chemotherapy. Their results were compared to 12 sex- and age-matched controls. ANS function was assessed using standardized tests of resting CV (tilt-table, respiratory sinus arrhythmia and Valsalva maneuver) and sudomotor (quantitative sudomotor axon reflex test) reactivity. Cardiovascular reactivity during exercise was assessed using a modified Astrand-Ryhming cycle ergometer protocol. Our feasibility criteria addressed: i) recruitment potential, ii) retention rates, iii) pre-chemotherapy assessment potential, iv) test performance/tolerability, and v) identification and minimizing the influence of potentially confounding medication. T-tests and repeated measures ANOVAs were used to assess between- and within-group differences at baseline and follow-up.

Results: The overall success rate in achieving our feasibility criteria was 98.4 %. According to the CASS, there was evidence of ANS impairment at baseline in 30.8 % of patients, which persisted in 18.2 % of patients at follow-up, compared to 0 % of controls at baseline or follow-up.

Conclusions: Results from our feasibility assessment suggest that the investigation of ANS function in young adult cancer patients undergoing chemotherapy is possible. To the best of our knowledge, this is the first study to report CASS-based evidence of ANS impairment and sudomotor dysfunction in any cancer population. Moreover, we provide evidence of cancer- and chemotherapy-related parasympathetic dysfunction - as a possible contributor to the pathogenesis of CV disease in cancer survivors.

No MeSH data available.


Related in: MedlinePlus