Subclinical Systolic Dysfunction during Chemotherapy for Breast Cancer

Barroso, Geanne Maria Holanda de Menezes; Teles, Júlio César Oliveira Costa; Silva, Paulo Victor de Jesus; Fonseca, Karin Yasmin Santos; Aragão, Vinícius Antônio Santos; Aquino, Marília Marques; Melo, Enaldo Vieira de; Ferreira, Karina Oliveira; Assis, Ronnei José Feitosa de; Alves, Michel Fabiano Silva; Sousa, Antônio Carlos Sobral; Oliveira, Joselina Luzia Menezes

doi:10.36660/ijcs.20210089

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International Journal of Cardiovascular Sciences

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ORIGINAL ARTICLE • Int J Cardiovasc Sci 35 (2) • Mar-Apr 2022 • https://doi.org/10.36660/ijcs.20210089 copy

Subclinical Systolic Dysfunction during Chemotherapy for Breast Cancer

Authorship SCIMAGO INSTITUTIONS RANKINGS

Abstract

Background

Cardiotoxicity is the main complication related to cancer therapy. Studies indicate that global longitudinal strain is an early detector of subclinical dysfunction of the left ventricle, preceding the decline in ejection fraction (EF). However, the reproducibility of such methodology has not been tested outside specialized centers.

Objectives

To assess the frequency of subclinical cardiotoxicity and to compare global longitudinal strain and EF measurements during the clinical course of patients undergoing chemotherapy for breast cancer.

Methods

This was an observational prospective study of 78 adult women who underwent serial echocardiograms (baseline and 1, 3, and 6 months after the beginning of chemotherapy), to evaluate biplane and 3D EF and global longitudinal strain. Cardiotoxicity and subclinical dysfunction were defined according to American Society of Echocardiography/European Association of Cardiovascular Imaging criteria. Statistical significance was set at p < 0.05.

Results

The mean age of the patients was 50.1 ± 11.48 years. The frequency of subclinical cardiotoxicity (defined by global longitudinal strain) was 14.9% after 30 days of chemotherapy, 16.7% after 3 months, and 19.7% after 6 months, compared to 4.5%, 3%, and 6.6%, respectively, when clinical cardiotoxicity was determined according to EF. The group that developed subclinical cardiotoxicity by 30 days (group A) had a higher frequency of clinical cardiotoxicity at 3 months (p=0.028) and a lower mean biplane EF after 30 days (p= 0.036) than the group that showed no evidence of subclinical cardiotoxicity (group B).

Conclusion

Subclinical cardiotoxicity was frequent and began early, being associated with a drop in EF during the clinical course.

Breast Neoplasms; Drug Therapy; Ventricular Dysfunction; Echocardiography/ methods; Strain

Characteristic	N = 78 (%)
Age (years)	50.1 ± 11.48
Asymptomatic at the 1^st evaluation	76 (97.4)
SAH	30 (38.5)
Diabetes Mellitus	4 (5.1)
Hypercholesterolemia	22 (28.2)
Obesity	10 (12.8)
Smoking	4 (5.1)
Family history of CAD	10 (12.8)
ACEI or ARB	24 (30.8)

	Cardiotoxicity at 30 days	Cardiotoxicity at 3 months	Cardiotoxicity at 6 months
GLS	14.9% (10/67) CI: 9-22.4%	16.7% (11/66) CI: 10.1-25.8%	19.7% (12/61) CI: 11.5-27.9%
Biplane EF	4.5% (3/67) CI: 0-10.4%	3% (2/66) CI: 0-7.6%	6.6% (4/61) CI: 1.6-13.1%
3D EF	4.9% (3/61) CI: 1.6-8.2%	7% (4/57) CI: 3.5-10.5%	5.9% (3/51) CI: 0-13.7%

Characteristics	Group A: WITH subclinical cardiotoxicity at 30 days (N = 10)	Group B: WITHOUT subclinical cardiotoxicity at 30 days (N = 57)	p-value
Age (years)	53.4±11.58	49.73±11.82	0.368
Baseline BP EF	63.92±5.65	62.95±5.61	0.617
30-day BP EF	57.41±4.18	60.55±4.93	0.048
3-month BP EF	58.81±4.56	60.91±5.27	0.248
6-month BP EF	58.31±4.62	59.85±5.15	0.389
Clinical cardiotoxicity at 30 days	10% (1/10)	3.5% (2/57)	0.389
Clinical cardiotoxicity at 3 months	20% (2/10)	0% (0/47)	0.028
Clinical cardiotoxicity at 6 months	20% (2/10)	4.8% (2/42)	0.163
SAH	60% (6/10)	33.3% (19/57)	0.157
Diabetes	0% (0/10)	7% (4/57)	1
Hypercholesterolemia	40% (4/10)	26.3% (15/57)	0.452
Obesity	10% (1/10)	12.3% (7/57)	1
Smoking	10% (1/10)	3.5% (2/57)	0.389
Previous CAD	0% (0/10)	15.8% (9/57)	0.335
ACEI or ARB	20% (2/10)	31.6% (18/57)	0.711
Asymptomatic	70% (7/10)	78.9% (45/57)	0.681
Dyspnea	0% (0/10)	12.3% (7/56)	0.583
Edema	0% (0/10)	5.3% (3/57)	1
Palpitations	10% (1/10)	5.3% (3/57)	0.485
Chest pain	0% (0/10)	1.8% (1/57)	1
Asthenia	30% (3/10)	10.5% (6/57)	0.125

Characteristics	Group A: WITH subclinical cardiotoxicity in 6 months	Group B: WITHOUT subclinical cardiotoxicity in 6 months	p-value
Age (years)	55.91±9.63	47.83±10.86	0.022
Baseline BP EF	61.70±5.73	62.89±5.80	0.525
30 day BP EF	59.05±4.05	60.15±5.09	0.527
3 month BP EF	59.22±5.07	60.15±5.36	0.601
6 month BP EF	56.15±4.97	60.55±5.00	0.008
Clinical cardiotoxicity at 30 days	0% (0/10)	4.8% (2/42)	1
Clinical cardiotoxicity at 30 days	9.1% (1/11)	2.2% (1/44)	0.357
Clinical cardiotoxicity at 6 months	25% (3/12)	2% (1/49)	0.022
Asymptomatic	41.7% (5/12)	61.2% (30/49)	0.330
SAH	58.3% (7/12)	30.6% (15/49)	0.098
Diabetes	16.7% (2/12)	2% (1/49)	0.096
Hypercholesterolemia	58.3% (7/12)	24.5% (12/49)	0.036
Obesity	8.3% (1/12)	12.2% (6/49	1
Smoking	16.7% (2/12)	4.1% (2/49)	0.170
Previous CAD	8.3% (1/12)	12.2 (6/49)	1
ACEI or ARB	25% (3/12)	28.6% (14/49)	1
Asthenia at 30 days	30% (3/10)	7.1% (3/42)	0.077
Asthenia at 6 months	33.3% (4/12)	12.2% (6/49)	0.096

	WITH apparent cardiotoxicity	WITHOUT apparent cardiotoxicity	p-value
Age	48.5±5.56	49.49±11.35	0.864
Baseline GLS	-19.15±1.96 (N = 4)	-20.03±2.24 (N = 57)	0.444
30-day GLS	-16.42±2.10 (N = 4)	-18.87±2.19 (N = 48)	0.037
3-month GLS	-15.70±1.92 (N = 4)	-18.65±2.40 (N = 52)	0.020
6-month GLS	-15.45±1.04 (N = 4)	-18.38±2.75 (N = 57)	0.039
GLS reduction at 30 days	12.98±17.96 (N=4)	5.57±9.94 (N=48)	0.186
GLS reduction at 3 months	17.71±9.68 (N=4)	6.99±9.66 (N=52)	0.037
BP EF reduction at 30 days	3.91±11.88 (N=4)	4.72±8.78 (N=45)	0.864
BP EF reduction at 3 months	7.13±7.58 (N=4)	4.01±8.66 (N=45)	0.491
SAH	75% (3/4)	33.3% (19/57)	0.129
Diabetes	0% (0/0)	5.3% (3/57)	1
Hypercholesterolemia	50% (2/4)	29.8% (17/57)	0.582
Obesity	0% (0/0)	12.3% (7/57)	1
Smoking	25% (1/4)	5.3% (3/57)	0.243
Previous CAD	0% (0/4)	12.3% (7/57)	1
ACEI or ARB	0% (0/4)	29.8% (17/57)	0.322
Asymptomatic	75% (3/4)	56.1% (32/57)	0.629
Edema	25% (1/4)	24.6% (14/57)	1

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