Pharmacogenetics of therapy effectiveness for anthracycline-induced cardiotoxicity

Abstract Objective To evaluate role of genetic factors (polymorphisms of ADRB1 gene (Arg389Gly, rs1801253) and ACE gene (I/D, rs4343) for effectiveness assessment of β-blocker (carvedilol) and angiotensin-converting enzyme inhibitor (enalapril) therapy in women with anthracycline- induced cardiotoxicity during 12-month follow-up period. Methods A total of 82 women, median age of 45.0 (42.0; 50.0) years with anthracycline-induced cardiotoxicity and without prior cardiovascular diseases were enrolled in the study. All patients received chemotherapy for the treatment of breast cancer included a combination of doxorubicin and cyclophosphamide, or combination of doxorubicin, cyclophosphamide and docetaxel. The cumulative dose of doxorubicin was 300–360 mg/m2. Criteria for the development of cardiotoxicity were a decrease in the left ventricle ejection fraction (LVEF) at the 12 months after chemotherapy completion by >10%, the development of heart failure (HF) with symptoms and clinical signs, and NT-proBNP levels ≥125 pg/mL. Echocardiography and serum levels of NT-proBNP were performed at baseline and at 12 months after enrollment. Average up-titrated dosage of carvedilol was 50 (25; 50) mg per day and enalapril was 10 (10; 20) mg per day. Evaluation of gene polymorphisms of ADRB1 gene and ACE gene were carried out by polymerase chain reaction at baseline before treatment initiation. Results The baseline LVEF, end-systolic and end-diastolic dimension indexes, NT-proBNP levels, 6-minute walk test distance did not differ among patients with different genotypes of ADRB1 and ACE genes. However, carriers of T/T genotype of ADRB1 gene had a significant increasing in LVEF (<0.001) by 11% from 50.0 (48.0; 51.0) to 56.0 (53.0; 57.0)% and decreasing in end-systolic dimension index (p<0.001) by 27.7% and end-systolic dimension index (p<0.001) by 6% within 12 months of follow-up period. The levels of NT-proBNP decreased (p=0.001) by 34.2% from 327.5 (260.1; 381.8) to 213.5 (195.3; 256.7) pg/mL and 6-minute walk test distance increased (0.008) by 10%. Carriers of G/G genotype of ACE gene had the same benefits from this therapy: LVEF (<0.001) increased by 6.5% from 50.5 (47.0; 51.0) to 54.0 (50.0; 57.0)%, end-systolic dimension index (p<0.001) decreased by 5.3% and end-systolic dimension index (p<0.001) by 3% within 12 months of follow-up period. The levels of NT-proBNP decreased (p=0.005) by 20.3 from 314.1 (279.6; 372.9) to 249.9 (197.3; 267.8) pg/mL and 6-minute walk test distance increased (0.008) by 5%. Carriers of other genotypes had decreasing in LVEF, increasing in LV dimensions and NT-proBNP, and further progression of HF. Conclusion Our data suggest that evaluation of gene polymorphisms of ADRB1 (Arg389Gly, rs1801253) and ACE gene (I/D, rs4343) can be recommended before treatment initiation of anthracycline- induced cardiotoxicity in women without prior cardiovascular diseases to determine who will benefit of carvedilol and enalapril therapy. FUNDunding Acknowledgement Type of funding sources: None.

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HIV infection is an independent risk factor for decreased 6-minute walk test distance

PLoS ONE ◽

10.1371/journal.pone.0212975 ◽

2019 ◽

Vol 14 (4) ◽

pp. e0212975 ◽

Cited By ~ 3

Author(s):

Tom E. Robertson ◽

Mehdi Nouraie ◽

Shulin Qin ◽

Kristina A. Crothers ◽

Cathy J. Kessinger ◽

...

Keyword(s):

Risk Factor ◽

Hiv Infection ◽

Independent Risk Factor ◽

Walk Test ◽

Test Distance ◽

6 Minute Walk Test ◽

Minute Walk

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Prediction Of Maximal Mets And Ventilatory Threshold Using 6-minute Walk Test Distance And The Rating Of Perceived Exertion

Medicine & Science in Sports & Exercise ◽

10.1249/01.mss.0000476859.91958.3d ◽

2015 ◽

Vol 47 ◽

pp. 163

Author(s):

John P. Porcari ◽

Hannah Brown ◽

Carl Foster ◽

Scott Doberstein ◽

John Greany ◽

...

Keyword(s):

Perceived Exertion ◽

Ventilatory Threshold ◽

Rating Of Perceived Exertion ◽

Walk Test ◽

Test Distance ◽

6 Minute Walk Test ◽

Minute Walk

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Feasibility and Acceptability of a Physical Activity Tracker and Text Messages to Promote Physical Activity During Chemotherapy for Colorectal Cancer: Pilot Randomized Controlled Trial (Smart Pace II)

JMIR Cancer ◽

10.2196/31576 ◽

2022 ◽

Vol 8 (1) ◽

pp. e31576

Author(s):

Erin L Van Blarigan ◽

Anand Dhruva ◽

Chloe E Atreya ◽

Stacey A Kenfield ◽

June M Chan ◽

...

Keyword(s):

Physical Activity ◽

Digital Health ◽

Controlled Trial ◽

Text Message ◽

Text Messages ◽

Walk Test ◽

Randomized Controlled ◽

6 Minute Walk Test ◽

Minute Walk

Background We conducted a pilot 2-arm randomized controlled trial to assess the feasibility of a digital health intervention to increase moderate-to-vigorous physical activity in patients with colorectal cancer (CRC) during chemotherapy. Objective This study aimed to determine whether a digital health physical activity intervention is feasible and acceptable during chemotherapy for CRC. Methods Potentially eligible patients with CRC expected to receive at least 12 weeks of chemotherapy were identified in person at the University of California, San Francisco, and on the web through advertising. Eligible patients were randomized 1:1 to a 12-week intervention (Fitbit Flex, automated SMS text messages) versus usual care. At 0 and 12 weeks, patients wore an Actigraph GT3X+ accelerometer for 7 days and completed surveys, body size measurements, and an optional 6-minute walk test. Participants could not be masked to their intervention arm, but people assessing the body size and 6-minute walk test outcomes were masked. The primary outcomes were adherence (eg, Fitbit wear and text response rate) and self-assessed acceptability of the intervention. The intervention would be considered feasible if we observed at least 80% complete follow-up and 70% adherence and satisfaction, a priori. Results From 2018 to 2020, we screened 240 patients; 53.3% (128/240) of patients were ineligible and 26.7% (64/240) declined to participate. A total of 44 patients (44/240, 18%) were randomized to the intervention (n=22) or control (n=22) groups. Of these, 57% (25/44) were women; 68% (30/44) identified as White and 25% (11/44) identified as Asian American or Pacific Islander; and 77% (34/44) had a 4-year college degree. The median age at enrollment was 54 years (IQR 45-62 years). Follow-up at 12 weeks was 91% (40/44) complete. In the intervention arm, patients wore Fitbit devices on a median of 67 out of 84 (80%) study days and responded to a median of 17 out of 27 (63%) questions sent via SMS text message. Among 19 out of 22 (86%) intervention patients who completed the feedback survey, 89% (17/19) were satisfied with the Fitbit device; 63% (12/19) were satisfied with the SMS text messages; 68% (13/19) said the SMS text messages motivated them to exercise; 74% (14/19) said the frequency of SMS text messages (1-3 days) was ideal; and 79% (15/19) said that receiving SMS text messages in the morning and evening was ideal. Conclusions This pilot study demonstrated that many people receiving chemotherapy for CRC are interested in participating in digital health physical activity interventions. Fitbit adherence was high; however, participants indicated a desire for more tailored SMS text message content. Studies with more socioeconomically diverse patients with CRC are required. Trial Registration ClinicalTrials.gov NCT03524716; https://clinicaltrials.gov/ct2/show/NCT03524716

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ESTIMATION OF VO2MAX FROM 6 MINUTE WALK TEST DISTANCE IN PATIENTS WITH DIASTOLIC AND SYSTOLIC HEART FAILURE 11:15 AM

Journal of Cardiopulmonary Rehabilitation ◽

10.1097/00008483-199909000-00005 ◽

1999 ◽

Vol 19 (5) ◽

pp. 288

Author(s):

L. A. Kaminsky ◽

P. H. Brubaker ◽

K. P. Stewart ◽

D. W. Kitzman

Keyword(s):

Heart Failure ◽

Systolic Heart Failure ◽

Walk Test ◽

Test Distance ◽

6 Minute Walk Test ◽

Minute Walk

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Effects of Home‐Based Cardiac Rehabilitation on Time to Enrollment and Functional Status in Patients With Ischemic Heart Disease

Journal of the American Heart Association ◽

10.1161/jaha.120.016456 ◽

2020 ◽

Vol 9 (19) ◽

Author(s):

David W. Schopfer ◽

Mary A. Whooley ◽

Kelly Allsup ◽

Mark Pabst ◽

Hui Shen ◽

...

Keyword(s):

Heart Disease ◽

Ischemic Heart Disease ◽

Cardiac Rehabilitation ◽

Ischemic Heart ◽

Walk Test ◽

Home Based ◽

Test Distance ◽

6 Minute Walk Test ◽

Minute Walk

Background Cardiac rehabilitation is an established performance measure for adults with ischemic heart disease, but patient participation is remarkably low. Home‐based cardiac rehabilitation (HBCR) may be more practical and feasible, but evidence regarding its efficacy is limited. We sought to compare the effects of HBCR versus facility‐based cardiac rehabilitation (FBCR) on functional status in patients with ischemic heart disease. Methods and Results This was a pragmatic trial of 237 selected patients with a recent ischemic heart disease event, who enrolled in HBCR or FBCR between August 2015 and September 2017. The primary outcome was 3‐month change in distance completed on a 6‐minute walk test. Secondary outcomes included rehospitalization as well as patient‐reported physical activity, quality of life, and self‐efficacy. Characteristics of the 116 patients enrolled in FBCR and 121 enrolled in HBCR were similar, except the mean time from index event to enrollment was shorter for HBCR (25 versus 77 days; P <0.001). As compared with patients undergoing FBCR, those in HBCR achieved greater 3‐month gains in 6‐minute walk test distance (+95 versus +41 m; P <0.001). After adjusting for demographics, comorbid conditions, and indication, the mean change in 6‐minute walk test distance remained significantly greater for patients enrolled in HBCR (+101 versus +40 m; P <0.001). HBCR participants reported greater improvements in quality of life and physical activity but less improvement in exercise self‐efficacy. There were no deaths or cardiovascular hospitalizations. Conclusions Patients enrolled in HBCR achieved greater 3‐month functional gains than those enrolled in FBCR. Our data suggest that HBCR may safely derive equivalent benefits in exercise capacity and overall program efficacy in selected patients. Registration URL: https://www.clinicaltrials.gov ; Unique identifier: NCT02105246.

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