RELATIONSHIP BETWEEN QUALITY OF LIFE INDICATORS  
AND CARDIAC STATUS INDICATORS IN CHEMOTHERAPY PATIENTS
Blaž Matija GERŠAK1*, Andreja KUKEC1, Henning STEEN2,3,4,5, Moritz MONTENBRUCK2, 
Maja ŠOŠTARIČ1,6, Arne Kristian SCHWARZ2, Sebastian ESCH2, Sebastian KELLE7,8,9, Sorin 
GIUSCA10, Grigorios KOROSOGLOU10, Pia WÜLFING11, Susan DENT12, Daniel LENIHAN13
1University of Ljubljana, Faculty of Medicine, Vrazov trg 2, 1000 Ljubljana, Slovenia
2Center for Preventive Medicine, Marien Hospital, Hamburg, Germany
3Faculty of Medicine, University of Hamburg, Hamburg, Germany
4Medical Faculty, Heidelberg University, Heidelberg, Germany
5Medneo GmbH Hospital & Health Care, Berlin, Germany
6University Medical Centre Ljubljana, Department of Anaesthesiology and Surgical Intensive Therapy, Ljubljana, Slovenia
    7Department of Internal Medicine and Cardiology, German Heart Centre Berlin, Berlin, Germany 
8Department of Internal Medicine and Cardiology, Charité University Hospital Berlin, Berlin, Germany
9German Centre for Cardiovascular Research, Berlin, Germany
10GRN Academic Teaching Hospital Weinheim, Weinheim, Germany
11Breast Center, Jerusalem Hospital, Hamburg, Germany
12Duke Cancer Institute, School of Medicine, Duke University, Durham, North Carolina, USA
13Cardio-Oncology Center of Excellence, School of Medicine, Washington University in St. Louis, St Louis, Missouri, USA 
Received: Mar 9, 2021
Accepted: Mar 31, 2021
Original scientific article
*Corresponding author: E-mail: blaz.gersak@maat.si
10.2478/sjph-2021-0028 Zdr Varst. 2021;60(4):199-209
199
POVEZANOST MED KAZALNIKI KAKOVOSTI ŽIVLJENJA TER KAZALNIKI 
SRČNEGA STATUSA PRI BOLNIKIH, KI PREJEMAJO KEMOTERAPIJO 
© National Institute of Public Health, Slovenia. 
Gersak BM et al. Relationship between quality of life indicators and cardiac status indicators in chemotherapy patients.  
Zdr Varst. 2021;60(4):199-209. doi: 10.2478/sjph-2021-0028.
ABSTRACT
Keywords: 
antineoplastic 
agents, 
cardiotoxicity, 
ventricular function 
– left, ventricular 
function – right, 
quality of life, 
magnetic resonance 
imaging, cine, 
echocardiography, 
lymphoma, Hodgkin 
disease, breast 
neoplasms
IZVLEČEK
Ključne besede: 
antineoplastični 
agensi, 
kardiotoksičnost, 
ventrikularna 
funkcija – levi, 
ventrikularna 
funkcija – desni, 
kakovost življenja, 
magnetno-
resonančno 
slikanje, video, 
ehokardiografija, 
limfomi, hodgkinova 
bolezen, 
neoplazme dojk
Aim: With the aim of improving personalized treatment of patients on chemotherapy, the objective of the study was to 
assess the degree of association between selected Quality of life (QoL) indicators and both clinical and imaging cardiac 
status indicators when detecting deterioration in QoL of these patients. 
Methods: In a cohort clinical study in Hamburg, from August 2017 through October 2020, 59 cancer patients, aged 18-80 
years, were evaluated before chemotherapy, and at several follow-ups, using EQ-5D and SF-36 QoL questionnaires, fast 
strain-encoded (fast-SENC) cardiac magnetic resonance (CMR), conventional CMR, and echocardiography, and further 
received a clinical and biomarker examination. Data was analyzed using survival analyses. A decline of more than 5% in 
each observed QoL metric value was defined as the observed event. Patient were separated into groups according to 
the presentation of cardiotoxicity as per its clinical definition, the establishment of the indication for cardioprotective 
therapy initiation, and by a worsening in the value of each observed imaging metric by more than 5% in the previous 
follow-up compared to the corresponding pre-chemotherapy baseline value. 
Results: Among clinical cardiac status indicators, the indication for cardioprotective therapy showed statistically good 
association with QoL scores (EQ-5D p=0.028; SF-36 physical component p=0.016; SF-36 mental component p=0.012). In 
terms of imaging metrics, the MyoHealth segmental myocardial strain score was the only one demonstrating consistently 
good QoL score association (EQ-5D p=0.005; SF-36 physical component p=0.056; SF-36 mental component p=0.002). 
Conclusions: Established fast-SENC CMR scores are capable of highlighting patients with reduced QoL, who require 
more frequent/optimal management.
Namen: Z namenom izboljšati personalizirano zdravljenje bolnikov, ki prejemajo kemoterapijo, je bil cilj naše raziskave 
oceniti stopnjo povezanosti med izbranimi kazalniki kakovosti življenja (QoL) ter kliničnimi in slikovnimi kazalniki 
srčnega statusa v kontekstu zaznave poslabšanja QoL teh bolnikov. 
Metode: V kohortni klinični študiji v Hamburgu smo od avgusta 2017 do oktobra 2020 59 bolnikom z rakom, starim 
18–80 let, pred kemoterapijo in več kontrolnimi pregledi, napravili oceno QoL z vprašalnikoma EQ-5D in SF-36, hitro z 
deformacijo miokarda kodirano (fast-SENC) magnetnoresonančno slikanje srca (CMR), konvencionalno CMR, ultrazvočni 
pregled srca ter klinični pregled z določitvijo biomarkerjev. Podatke smo analizirali z analizo preživetja. Upad za več 
kot 5 % v vrednosti posameznega opazovanega kazalnika QoL je bil izbran kot opazovani dogodek. Razdelitev bolnikov v 
skupine je bila definirana glede na pojav kardiotoksičnosti po njeni klinični definiciji, postavitev indikacije za zdravljenje 
z zdravili za zaščito srčne mišice ter na osnovi poslabšanja vrednosti posameznega opazovanega slikovnega kazalnika za 
več kot 5 % ob zadnjem kontrolnem pregledu v primerjavi z njegovo vrednostjo pred pričetkom kemoterapije. 
Rezultati: Med kliničnimi kazalniki srčnega statusa je postavitev indikacije za zdravljenje z zdravili za zaščito srčne 
mišice pokazala statistično dobro povezanost s kazalniki QoL (EQ-5Dp = 0,028; SF-36 telesna komponenta p = 0,016; SF-
36 mentalna komponenta p = 0,012). Med slikovnimi kazalniki je bila MyoHealth ocena segmentne krčljivosti miokarda 
edina, ki je pokazala konsistentno dobro povezanost s kazalniki QoL (EQ-5D p = 0,005; SF-36 telesna komponenta p = 
0,056; SF-36 mentalna komponenta p = 0,002).
Zaključek: Uveljavljeni fast-SENC kazalniki CMR so se pokazali za sposobne izpostaviti bolnike z zmanjšano QoL, ki 
potrebujejo pogostejšo/optimalnejšo obravnavo.
1 INTRODUCTION
In the past 20 years, systemic cancer therapy has 
advanced considerably, lowering mortality and increasing 
life expectancy. With a substantially increased proportion 
of cancer survivors treated with chemotherapy, long 
term consequences of systemic chemotherapeutics 
have become a very important factor in the context 
of public health. A very prominent one among those is 
cardiovascular dysfunction due to cardiotoxic effects of 
chemotherapeutic regimes (1). Moreover, it is important 
to recognize that cancer patient quality of life (QoL) 
is also influenced by cardiovascular health (2), whose 
management is an important part of personalized patient 
management, which has been shown to improve survival 
and QoL in cancer patients (3), and has expanded to form 
its own clinical sub-field of cardio-oncology.
Chemotherapy drugs such as anthracyclines, taxanes, 
targeted biological therapies (trastuzumab, etc.), and 
drug combinations, with or without concomitant radiation 
therapy, have been shown to cause cardiotoxicity leading 
to heart failure (4, 5). In patients receiving anthracycline 
therapy, the incidence of chemotherapy-induced 
cardiotoxicity is approximately 30%, and can surpass many 
malignancies as the leading cause of mortality (6).
In the context of patient QoL, the clinical status as observed 
by the clinician is not reliable. It has been shown that 
attending physicians often underestimate chemotherapy-
related symptom severity and frequency, with low 
sensitivity and specificity for detecting side effects of 
chemotherapy with or without concomitant radiation 
therapy, resulting in less than optimal treatment course 
decisions regarding chemotherapy continuation, halting, or 
dose alteration, as well as worse patient QoL (7).
It has also been shown that regular patient self-evaluation 
and reporting of QoL status can significantly improve 
physical and mental QoL metrics, reduce emergency room 
admittance, and even extend mean survival in patients 
with solid tumors by as much as 5 months, without 
increasing the cost in health resources (8).
Cardiac magnetic resonance (CMR) strain testing (strain-
encoded, harmonic phase analysis) has been shown to 
detect cardiotoxicity before systemic changes occur. CMR 
strain has been shown to detect abnormal myocardial 
function in cancer patients treated with high-dose 
anthracycline chemotherapy despite normal systolic 
function by traditional metrics, namely traditional CMR 
and echocardiographic (ECHO) left ventricular ejection 
fraction (LVEF) (9).
With the aim of improving personalized treatment of patients 
on chemotherapy, the study’s objective was to assess the 
degree of association between selected QoL indicators and 
both clinical and imaging cardiac status indicators when 
detecting deterioration in these patients’ QoL.
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2 METHODS
2.1 Study design
This study was part of the PREFECT research project 
(ClinicalTrials.gov identifier NCT03543228) (10), and was 
designed as a prospective cohort clinical study, performed 
in its entirety at the Katholisches Marienkrankenhaus 
GmbH.
2.2 Study population
In the period between August 2017 and July 2019, 63 patients 
were screened for their consent to study participation. 
The inclusion criteria were: age 18 to 80 years, any 
gender, in the case of women the absence of pregnancy, 
no contraindications for magnetic resonance imaging, 
breast cancer, non-Hodgkin’s or Hodgkin’s lymphoma, no 
history of prior chemotherapy or renal failure, a glomerular 
filtration rate of higher than 30ml/kg/m2, and an indication 
to undergo chemotherapy for cancer treatment with or 
without concomitant radiation therapy. Those who agreed 
to participate, having provided written informed consent, 
were subsequently enrolled in the study.
2.3 Data collection procedure
Anti-cancer medications were prescribed at the attending 
oncologist’s discretion, as per current European Society 
for Medical Oncology clinical practice guidelines (11). 
Patients with breast cancer were treated with epirubicin 
and cyclophosphamide every 3 weeks for a total of 4 
cycles, followed by 12 weekly cycles of paclitaxel (EC-P); 
a few patients received dose-dense EC-P. Patients with 
HER2+ breast cancer were treated with trastuzumab and 
radiation therapy. Patients with non-Hodgkin’s lymphoma 
were treated with cyclophosphamide, doxorubicin, 
vincristine, and prednisone with rituximab (R-CHOP), 
while patients with Hodgkin’s lymphoma were treated 
with a combination therapy including anthracyclines with 
or without radiation therapy.
Subjects were evaluated at baseline, 3-months, 6-months 
and 1-year follow-ups, and additionally as needed in 
between designated follow-up time points, using fast 
strain-encoded (fast-SENC) CMR, conventional CMR, and 
ECHO. They also had blood drawn for routine biochemical 
testing, including cardiac biomarker evaluation (troponin, 
brain natriuretic peptide, N-terminal pro b-type natriuretic 
peptide). At same time points as the above mentioned 
tests, all subjects were evaluated at the study location, 
with appropriate guidance, using EQ-5D and SF-36 QoL 
questionnaires.
2.4 Data collection instruments
2.4.1 QoL status measurement instruments
EQ-5D is a questionnaire-based tool for patient self-reported 
generic QoL measurement, developed and maintained by 
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the EuroQol Research Foundation. It combines a measure 
with five preference-based questions, and a visual analog 
scale (VAS). The five questions each describe one generic 
QoL aspect: mobility, self-care, usual activities, pain/
discomfort, and anxiety/depression, with two possible 
responses (absence of problems, presence of problems) in 
each. The responses were converted into index and utility 
scores anchored at 0 for death and 1 for perfect health. 
The VAS provides a measure of perceived health status 
with a grade ranging from 0 (the worst possible health 
status) to 100 (the best possible health status) (12, 13). For 
the purpose of our study, we observed changes in the VAS 
score. The questionnaire has been in regular use in the 
clinical setting in the Germanophone world since 1998, 
after its German translation was validated (14). A newer 
version of the questionnaire, the EQ-5D-5L, providing 5 
possible responses ranging from the worst possible health 
status to the best possible health status, was thereupon 
validated on the German population in 2014 (15). In our 
study, we used the original 2-level version, whose VAS 
component is the same as in the 5-level version.
SF-36 is a 36-item questionnaire-based tool for patient self-
reported health-related QoL measurement, developed and 
maintained by the RAND Corporation. It has eight basic 
scores, describing different aspects of health-related QoL: 
physical functioning, role-physical, bodily pain, general 
health, vitality, social functioning, role-emotional, and 
mental health. Each score is calculated (with weighting) 
from several preference-based questions with possible 
responses ranging from the worst possible health status 
to the best possible health status in either 2, 3, 5, or 6 
increments, depending on the question. From the noted 
basic scores, two combined scores are derived: a physical 
health component score and a mental health component 
score. SF-36 also includes a single combined overview 
score, also derived from the eight basic scores, describing 
perceived change in patient’s health status over the past 
year. Calculating each of the noted basic and combined 
scores gives a score ranging from 0 to 100. Higher scores 
indicate a better health status, and a mean score of 50 has 
been articulated as a normative value for all scores (16, 
17). For the purpose of our study, we observed changes 
in the physical and mental component scores. The 
questionnaire has been in regular use in the clinical setting 
in the Germanophone world since 1994, since its German 
translation was validated (18). It was validated again in 
1999 on a larger population of 6964 survey participants, 
resulting in a description of an updated German normative 
population sample (18).
2.4.2 Cardiac status measurement instruments
All traditional CMR and fast-SENC CMR measurements 
were performed with electrocardiogram triggering on the 
R-wave on a 1.5 Tesla Achieva magnetic resonance imaging 
scanner, Philips Medical Systems International BV. Each 
patient received a comprehensive baseline CMR exam 
before initiating chemotherapy, which included steady-
state free precession with global calculations (LVEF, 
volumes, mass), strain-encoded CMR, fast-SENC CMR, T1 
and T2-weighted mapping, and adenosine perfusion stress 
testing. Conventional CMR acquisitions, including T1 and 
T2-weighted mapping images and strain-encoded CMR, 
were analyzed using the CVI 42 software package, Circle 
Cardiovascular Imaging, as per the manufacturer’s training 
and recommendations. Fast-SENC CMR circumferential 
and longitudinal left ventricle and right ventricle strain 
were calculated and analyzed using the MyoStrain 5.0 
software package Myocardial Solutions, Inc., as per the 
manufacturer’s training and recommendations, to provide 
a validated, standardized left ventricle and right ventricle 
end-systolic segmental and global longitudinal and 
circumferential strain metrics (19).
ECHO LVEF was measured by the Simpson’s method 
from biplane planes from the 2-chamber and 4-chamber 
views according to the manufacturer’s training and 
recommendations. ECHO global longitudinal strain 
(GLS) was measured using speckle tracking algorithms 
incorporated into the Affiniti 50 G ultrasound machine, 
Philips Medical Systems International BV, according to 
manufacturer training and recommendations.
All laboratory analyses were performed as per standard 
operating procedures at the study institution’s laboratories 
as well as an outsourced laboratory, Hämatologisch-
Onkologische Praxis Altona.
2.5 Data analysis
2.5.1 QoL status indicators
An event was deemed to have occurred if a drop of more 
than 5% in each respective QoL status indicator score (EQ-
5D score, SF-36 physical component score, SF-36 mental 
component score) was recorded as compared to its 
associated pre-chemotherapy value. The timepoint at the 
described event was thus recorded. If no event occurred, 
the last timepoint and QoL value was recorded. The 
observed outcome was the time (in days) from the baseline 
pre-chemotherapy examination to the target event.
In the analysis, three outcomes were observed: time to a 
drop of more than 5% in the EQ-5D score, time to a drop 
of more than 5% in the SF-36 physical component score, 
and time to a drop of more than 5% in the SF-36 mental 
component score.
2.5.2 Cardiac status indicators
The development of symptomatic heart failure, a 
significant reduction in LVEF, or cardiac biomarker 
indicators of myocardial injury were used to classify 
patients with subclinical cardiotoxicity and clinical 
Figure 1. EQ-5D questionnaire events – (A) clinical definition 
of cardiotoxicity; (B) clinical indication for 
cardioprotective therapy initiation; Germany,  
single-center study, August 2017 through October 
2020, chemotherapy for cancer treatment.
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cardiotoxicity based on the American Society of 
Echocardiography Expert Consensus Position Paper, the 
European Society of Cardiology Position Paper, and the 
European Society for Medical Oncology clinical practice 
guidelines (11, 20, 21). Fast-SENC CMR was not used in 
categorizing cardiotoxicity status. Clinical cardiotoxicity 
was defined as an absolute change in LVEF from greater 
than 10% from baseline to below 53%, combined with 
heart failure symptoms or abnormal cardiac biomarker 
values (troponin, brain natriuretic peptide, or N-terminal 
pro b-type natriuretic peptide). Subclinical cardiotoxicity 
was defined as an asymptomatic patient with a greater 
than 15% decrease in LVEF that remains greater or equal 
to 53%, worsening in GLS of more than 15% from baseline, 
or abnormal cardiac biomarker values (troponin, brain 
natriuretic peptide, or N-terminal pro b-type natriuretic 
peptide). Patients with clinical cardiotoxicity and those 
with subclinical cardiotoxicity were combined into the 
“Cardiotoxicity” group, while the rest fell into the “No 
Cardiotoxicity” group.
The indication to initiate cardioprotective therapy was 
made at the discretion of the treating oncologist in 
consultation with a cardiologist. Establishment of the 
indication to initiate cardioprotective therapy was used to 
separate patients into the “Cardioprotection Indicated” 
and “No Cardioprotection Indicated” groups. Every patient 
who was indicated to receive cardioprotective therapy did 
do so.
Whether or not the value of each respective cardiac 
imaging indicator (traditional CMR LVEF, traditional CMR 
GLS, ECHO LVEF, ECHO GLS, fast-SENC CMR LVEF, fast-
SENC CMR standard parameters) worsened by more than 
5% in the last follow-up compared to the corresponding 
pre-chemotherapy baseline value, was used to separate 
patients into the “Did Not Maintain Baseline” and 
“Maintained Baseline” groups for each respective cardiac 
imaging indicator. If a specific cardiac imaging indicator 
value worsened by more than 5%, the patient was grouped 
under “Did Not Maintain Baseline” for that specific cardiac 
imaging indicator Otherwise, it was grouped under 
“Maintained Baseline” for that specific cardiac imaging 
indicator. An indicator’s worsening was indicated by a 
value decrease in LVEF measurements and fast-SENC 
CMR standard parameters, and a value increase in raw 
myocardial strain measurements (GLS).
2.5.3 Statistical analysis
Kaplan-Meier product limit statistic, along with the log-
rank test, was used to assess the relationship between the 
observed QoL indicators and cardiac status indicators. The 
curves and statistics were graphed and calculated using 
Python 3.x, Python Software Foundation, with the lifelines 
0.25.x package, https://github.com/CamDavidsonPilon/
lifelines. P-values of <0.05 were considered statistically 
significant.
3 RESULTS
3.1 Observed patient group
All 63 patients who met the inclusion criteria agreed to 
participate and were enrolled into the study.
Of the 63 enrolled patients, 3 were excluded due to a 
change in therapy plan (non-chemotherapy cancer 
treatment), while another 1 patient was lost to follow-
ups beyond the first visit. Results using the outcomes for 
the remaining 59 patients were subsequently used in all 
analyses.
Our population included 50 female and 9 male patients, 
with a median age of 51 years and mean of 53.9±14.5 
years, respectively. Baseline QoL score values in the 
population were: EQ-5D median 75, mean 69.4±24.0; SF-
36 physical component median 54.4, mean 51.1±8.6; SF-36 
mental component median 44.8, mean 45.5±9.6.
3.2 Survival analyses
3.2.1 EQ-5D
Results of the association analysis for the observed EQ-5D 
outcomes are shown in Figures 1-3.
A B
Clinical cardiotoxicity definition (Figure 1A) and the 
indication for cardioprotective therapy initiation (Figure 
1B) both show statistically good association with EQ-5D 
scores.
Figure 2 shows that a worsening of more than 5% in 
the last follow-up compared to the corresponding pre-
chemotherapy baseline value in LVEF measurement values 
shows no association with EQ-5D scores, irrespective of 
the method used to obtain those values.
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Figure 2.
Figure 3.
EQ-5D questionnaire events – traditional cardiac imaging modality metrics: (A) ECHO LVEF – echocardiographic left 
ventricular ejection fraction; (B) CMR LVEF – traditional cardiac magnetic resonance left ventricular ejection fraction; (C) 
MYOSTRAIN LVEF – fast strain-encoded cardiac magnetic resonance left ventricular ejection fraction; Germany, single-center 
study, August 2017 through October 2020, chemotherapy for cancer treatment.
EQ-5D questionnaire events – myocardial strain imaging modality metrics: (A) ECHO GLS – echocardiographic global 
longitudinal strain; (B) CMR GLS – traditional cardiac magnetic resonance global longitudinal strain; (C) MYOHEALTH, 
(D) FUNCTIONAL MYOSTRAIN, (E) MYOSTRAIN ≤-11 and (F) MYOSTRAIN ≤-12 – percent of left ventricle longitudinal and 
circumferential fast strain-encoded cardiac magnetic resonance segments with normal, functional, ≤-11% or ≤-12% strain, 
respectively; Germany, single-center study, August 2017 through October 2020, chemotherapy for cancer treatment.
A B C
A
D
B
E
C
F
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A worsening of more than 5% in the last follow-up 
compared to the corresponding pre-chemotherapy 
baseline value in segmental myocardial strain scores all 
show either statistically good association (Figure 3C, D 
and E) or borderline association (Figure 3F) with EQ-5D 
scores, while there is no association between a worsening 
of more than 5% in the last follow-up compared to the 
corresponding pre-chemotherapy baseline value in any 
of the observed global myocardial strain measurement 
values and EQ-5D scores, irrespective of the method used 
to obtain those values.
3.2.2 SF-36 physical component
Results of the association analysis for the observed SF-36 
physical component outcomes are shown in Figures 4-6.
The clinical cardiotoxicity definition (Figure 4A) and the 
indication for cardioprotective therapy initiation (Figure 
4B) both show a statistically good association with SF-36 
physical component scores.
Figure 4. SF-36 physical component questionnaire events – 
(A) clinical definition of cardiotoxicity; (B) clinical 
indication for cardioprotective therapy initiation; 
Germany, single-center study, August 2017 through 
October 2020, chemotherapy for cancer treatment.
A B
Figure 5. SF-36 physical component questionnaire events – traditional cardiac imaging modality metrics: (A) ECHO LVEF – 
echocardiographic left ventricular ejection fraction; (B) CMR LVEF – traditional cardiac magnetic resonance left ventricular 
ejection fraction; (C) MYOSTRAIN LVEF – fast strain-encoded cardiac magnetic resonance left ventricular ejection fraction; 
Germany, single-center study, August 2017 through October 2020, chemotherapy for cancer treatment.
A B C
Figure 5 shows that a worsening of more than 5% in 
the last follow-up compared to the corresponding pre-
chemotherapy baseline value in LVEF measurement values 
shows no association with SF-36 physical component 
scores, irrespective of the method used to obtain those 
values.
A worsening of more than 5% in the last follow-up compared 
to the corresponding pre-chemotherapy baseline value 
in the MyoHealth score (Figure 6C) shows borderline 
association with SF-36 physical component scores, while a 
worsening of more than 5% in the last follow-up compared 
to the corresponding pre-chemotherapy baseline value in 
all other observed myocardial strain indicators show no 
association with SF-36 physical component scores.
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Figure 7. SF-36 mental component questionnaire events – (A) 
clinical definition of cardiotoxicity; (B) clinical 
indication for cardioprotective therapy initiation; 
Germany, single-center study, August 2017 through 
October 2020, chemotherapy for cancer treatment.
A B
Figure 6. SF-36 physical component questionnaire events – myocardial strain imaging modality metrics: (A) ECHO GLS – 
echocardiographic global longitudinal strain; (B) CMR GLS – traditional cardiac magnetic resonance global longitudinal 
strain; (C) MYOHEALTH, (D) FUNCTIONAL MYOSTRAIN, (E) MYOSTRAIN ≤-11 and (F) MYOSTRAIN ≤-12 – percent of left ventricle 
longitudinal and circumferential fast strain-encoded cardiac magnetic resonance segments with normal, functional, ≤-11% 
or ≤-12% strain, respectively; Germany, single-center study, August 2017 through October 2020, chemotherapy for cancer 
treatment.
A
D
B
E
C
F
3.2.3 SF-36 mental component
Results of the association analysis for the observed SF-36 
mental component outcomes are shown in Figures 7-9.
The indication for cardioprotective therapy initiation 
(Figure 7B) shows a statistically good association with SF-36 
mental component scores, while the clinical cardiotoxicity 
definition (Figure 7A) shows borderline association with 
SF-36 mental component scores.
Figure 8 shows that a worsening of more than 5% in 
the last follow-up compared to the corresponding pre-
chemotherapy baseline value in LVEF measurement values 
shows no association with SF-36 mental component scores, 
irrespective of the method used to obtain those values.
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Figure 8. SF-36 mental component questionnaire events – traditional cardiac imaging modality metrics: (A) ECHO LVEF – 
echocardiographic left ventricular ejection fraction; (B) CMR LVEF – traditional cardiac magnetic resonance left ventricular 
ejection fraction; (C) MYOSTRAIN LVEF – fast strain-encoded cardiac magnetic resonance left ventricular ejection fraction; 
Germany, single-center study, August 2017 through October 2020, chemotherapy for cancer treatment.
A B C
Figure 9. SF-36 mental component questionnaire events – myocardial strain imaging modality metrics: (A) ECHO GLS – 
echocardiographic global longitudinal strain; (B) CMR GLS – traditional cardiac magnetic resonance global longitudinal 
strain; (C) MYOHEALTH, (D) FUNCTIONAL MYOSTRAIN, (E) MYOSTRAIN ≤-11 and (F) MYOSTRAIN ≤-12 – percent of left ventricle 
longitudinal and circumferential fast strain-encoded cardiac magnetic resonance segments with normal, functional, ≤-11% 
or ≤-12% strain, respectively; Germany, single-center study, August 2017 through October 2020, chemotherapy for cancer 
treatment.
A
D
B
E
C
F
extensive array of comorbidities are much more likely to 
receive cardioprotection, which is bound to positively 
affect their QoL status both through the actual as well 
as placebo effects of cardioprotective medication, as 
opposed to their not cardioprotected counterparts. 
Lastly, age is also an important confounder in patient 
QoL self-estimation. To get around the noted limitations, 
multivariate models would need to be developed. Due 
to the small sample size however, this was not possible. 
The next limitation was the effect of differing patient-
perceived QoL starting points at the baseline on observed 
data. The starting baseline QoL status after a confirmed 
diagnosis of cancer was bound to be higher in younger 
patients and those with fewer or no prior comorbidities, 
compared to older ones and those with more significant 
concomitant diseases. In our study, this was merited by 
observing the relative drop in QoL status, and thus the 
noted observation does not affect our conclusions. Finally, 
the log-rank test may not have been the best test choice 
in all cases, but we considered it good enough to roughly 
estimate the statistical significance of the differences.
On the other hand, our study also has some important 
strengths. The primary one is the fact that it is the first 
to investigate fast-SENC CMR in respect to patient QoL in 
any clinical scenario, both within and without the field of 
cardio-oncology. Also, using the Kaplan-Meier product limit 
statistic as the analysis tool, while not standard for this type 
of study, gives our results an additional time component, 
adding deeper insight into our observed population.
Our findings contribute in a meaningful way to both 
the cardio-oncology and public health fields. Fast-SENC 
CMR could, in addition to its original intended use for 
early cardiotoxicity detection and prediction, give 
regular follow-up imaging examinations an additional 
screening and diagnostic quality, both if used alongside 
questionnaire-based QoL analysis tools or without. In this 
context, fast-SENC CMR would serve as an indicator of 
the effect of anti-cancer therapy on the cardiovascular 
component of a patient’s QoL, not influenced by other 
unwanted side effects of cancer treatment and elements 
from personal life that can influence various dedicated 
QoL tool scores. This would give the clinician valuable 
objective insight into this very important component of 
the overall patient QoL, which, if managed early with 
cardioprotective therapy, could greatly aid in quality 
personalized management of cancer patients, resulting in 
higher survival rates (3), better quality adjusted life years, 
and a lower burden on the healthcare system.
Numerous questions remain unanswered within the 
general topic our study. Firstly, a study on a larger 
patient population is merited. Furthermore, based on 
our findings, higher-risk patients could benefit from 
cardioprotective therapy that is instigated preemptively, 
even before subclinical changes in cardiac function can be 
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A worsening of more than 5% in the last follow-up compared 
to the corresponding pre-chemotherapy baseline value 
in the MyoHealth score (Figure 9C) shows a statistically 
good association with SF-36 mental component scores, a 
worsening of more than 5% in the last follow-up compared 
to the corresponding pre-chemotherapy baseline value 
in the percent of MyoStrain segments with contraction 
values of ≤-11% (Figure 9E) shows a borderline association 
with SF-36 mental component scores, while a worsening 
of more than 5% in the last follow-up compared to the 
corresponding pre-chemotherapy baseline value in all 
other observed myocardial strain indicators show no 
association with SF-36 mental component scores.
4 DISCUSSION
The differentiation in EQ-5D, SF-36 physical component 
and SF-36 mental component, observed in MyoHealth 
and Functional MyoStrain, successfully highlights the 
injury occurring from chemotherapy, which manifests in 
reduced QoL. Moreover, across each of the QoL metrics, 
MyoHealth was the single imaging parameter that 
consistently demonstrated the best delineation. Since 
MyoHealth correctly identified several events, the validity 
of associated statistical analyses, which showed that QoL 
results are best delineated by injury based on MyoStrain, 
is reinforced, suggesting that early identification of 
subclinical cardiotoxicity using fast-SENC CMR, with 
associated cardioprotection, may be able to impact QoL. 
Studies investigating QoL in cancer patients, more so 
cardiac patients in general, are numerous, both in the 
local (8, 22-24) and worldwide setting, as are those that 
investigate ECHO and traditional CMR measurements in 
relation to patient QoL. Comparison with similar studies 
to ours however is practically impossible due to the fact 
that fast-SENC CMR, as confirmed by the manufacturer, 
has never been analyzed in respect to patient QoL in 
any clinical scenario, including oncology. The only study 
done with fast-SENC CMR in vague relation to QoL was 
an economic evaluation of fast-SENC CMR in the diagnosis 
and management of early heart failure by Schneider and 
Stojanovic, published in 2019 (25).
Our study is limited by a few factors. The most important 
one is that the findings could be confounded by the impact 
of chemotherapy, cardioprotective medications, radiation 
therapy, comorbidities, age, and human psychology on 
perceived QoL. Chemotherapy and cardioprotective 
medications are known to have side effects that patients 
can perceive as reducing physical or mental conditions and 
therefore can impact EQ-5D, SF-36 physical component, 
and SF-36 mental component calculations. Radiation 
therapy is known to have a negative effect on regional 
myocardial performance, which is especially important 
in patients with breast cancer (26). Patients with a more 
detected. In light of this, it could be beneficial to expand 
upon the scope of the research project this study is a part 
of by performing a randomized controlled trial on a select 
high-risk patient-group that could potentially benefit 
from initiation of cardioprotective therapy at the very 
beginning of their chemotherapy regimen. Moreover, for 
determining the optimal type, combination and regimen 
of cardioprotective therapy in cancer patients in general, 
another randomized controlled trial using fast-SENC CMR 
to follow patients’ cardiac status would also be extremely 
beneficial, especially in the context of alleviating the 
public health burden imposed by the cardiotoxicity of 
chemotherapy and radiation therapy.
5 CONCLUSIONS
Established fast-SENC CMR scores including MyoHealth 
and Functional MyoStrain delineated patients who 
were predisposed to reduced QoL. The importance of 
appropriately classifying patients at risk of developing 
cardiotoxicity before and during cancer treatment has 
valuable potential clinical implications of highlighting 
patients who need to be monitored more frequently and 
managed more optimally.
CONFLICTS OF INTEREST
Henning Steen, Arne Kristian Schwarz, Sebastian Kelle, 
Grigorios Korosoglou and Daniel Lenihan hold a consulting 
position at and/or are in research collaboration with 
Myocardial Solutions, Inc. Other authors declare that no 
conflicts of interest exist.
FUNDING
The study was financed by the study institution, 
Katholisches Marienkrankenhaus GmbH, save for the 
statistical analysis, which was paid for by Myocardial 
Solutions, Inc., and performed by an independent 
contractor. Fast-SENC CMR analysis software and the 
associated training was provided by the manufacturer, 
Myocardial Solutions, Inc., free of charge.
ETHICAL APPROVAL
The study was registered at ClinicalTrials.gov on 1 June 
2018. The ethical approval was received from the ethical 
review board of the Hamburg Medical Association KdöR. 
The study complied with the Declaration of Helsinki, 
World Medical Association.
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