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Annals of Noninvasive Electrocardiology logoLink to Annals of Noninvasive Electrocardiology
. 2018 Jan 24;23(4):e12534. doi: 10.1111/anec.12534

The analysis of the parameters of 24‐hr ECG Holter monitoring in patients with blood neoplasms undergoing high‐dose chemotherapy and stem cell transplantation

Małgorzata Poręba 1, Paweł Gać 2,✉, Lidia Usnarska‐Zubkiewicz 3, Witold Pilecki 1, Kazimierz Kuliczkowski 3, Grzegorz Mazur 4, Małgorzata Sobieszczańska 5, Rafał Poręba 4
PMCID: PMC6931497  PMID: 29363852

Abstract

Background

Hematopoietic stem cell transplantation (HSCT) is a widely used procedure in the treatment of malignant diseases, including blood neoplasms and has increased survival in hematological diseases. The aim of the study was to analyze parameters of 24‐hr ECG monitoring in patients with selected blood neoplasms in whom the procedure of hematopoietic stem cell transplantation was performed.

Methods

The study group consisted of 64 adults diagnosed with hematologic cancer qualified for HSCT with the previous high dose chemotherapy (HDC). In all patients 24‐hr Holter monitoring was carried out twice. First examination took place prior to the HSCT procedure, and the second after finishing the procedure of HSCT.

Results

The minimal and mean heart rate (HR min and HR max) from 24‐hr ECG recording was statistically significantly higher after the transplantation in comparison with the first test. The number of premature ventricular complexes (PVCs) was higher in the test after HSCT. In the second examination there was significantly higher percentage of premature ventricular complexes, incidents of tachycardia, and Mobitz type 1 second degree atrioventricular block. In regression analysis, in a group of patients with blood neoplasms after HSCT and HDC, administration of cyclophosphamide, fludarabine and total body irradiation were independent risk factors for electrocardiographic abnormalities in 24‐hr Holter monitoring, that is, the increase in HR min, HR mean and PVCs.

Conclusion

In patients with blood neoplasms undergoing HSCT more electrocardiographic abnormalities may be found after this procedure in comparison with the 24‐hr Holter monitoring before transplantation.

Keywords: blood neoplasms, electrocardiographic abnormalities, hematopoietic stem cell transplantation, high‐dose chemotherapy, Holter monitoring

1. INTRODUCTION

Hematopoietic stem cell transplantation (HSCT) is a widely used procedure in the treatment of malignant diseases, including blood neoplasms and has increased survival in hematological diseases (Roziakova et al., 2012). However, the survivors are at higher risk of developing various complications including cardiotoxicity (Roziakova et al., 2012). The early detection of abnormalities in heart function as well as its monitoring are important in such patients.

Holter 24‐hr ECG monitoring is a noninvasive and easily available test that has been used for many years mainly to detect arrhythmias and sporadically other pathologies of the heart function such as ischemic attacks or to determine the patients’ reaction to the specific treatment or medication. Its main advantage is a good availability and a fact that the analysis is not very sophisticated, simultaneously, not annoying for the patient.

Regarding the described advantages of the Holter monitoring it seems to be reasonable to adopt this technique to determine the potential changes of the specific parameters of heart rhythm from 24‐hr ECG recording in patients with hematologic malignancies in peri‐transplant period, that is, before and after HSCT transplantation.

The aim of the study was to analyze parameters of 24‐hr ECG monitoring in patients with selected blood neoplasms in whom the procedure of HSCT was performed.

2. METHODS

2.1. The study group

The study group consisted of 64 adults diagnosed with hematologic cancer qualified for the procedure of hematopoietic stem cell transplantation with the previous high dose chemotherapy (HDC) according to current medical guidelines. After analyzing medical histories of the patients eight individuals declaring co‐existence of cardio‐vascular disease were excluded from the study: three of them were diagnosed and treated for arterial hypertension, three declared type 2 diabetes mellitus, three ischemic heart disease, two had ischemic stroke in their medical past, and, eventually, 1 person was previously diagnosed with heart failure. In the final study group we had 56 patients with blood neoplasms qualified for HSCT without the diagnosed cardio‐vascular diseases. During the study no patients were on regular pharmacological treatment for any chronic disease. Out of this group 32 subjects were selected for autologous HSCT and the left 24 patients for allogeneic HSCT. The type of HDC was appropriate to the diagnosed malignancy and the doses of drugs were calculated for the patient's body weight or body surface area. Clinical characteristics of the patients from the study group were presented in Table 1. The characteristics of the high dose chemotherapy administered to the patients as well as total body irradiation which were prior to stem cell transplantation is shown also in Table 1.

Table 1.

Clinical characteristics of the study group

Age (years) 41.71 ± 12.70
Gender (%/n)
Men 57.14/32
Women 42.86/24
Blood neoplasms (%/n)
Acute Myeloid Leukemia – AML 28.57/16
Multiple Myeloma – MM 21.43/12
Hodgkin's Lymphoma – HD 16.07/9
Acute Lymphoblastic Leukemia – ALL 16.07/9
Non‐Hodgkin's Lymphoma – NHL 12.50/7
Chronic Myeloid Leukemia – CML 5.36/3
Cytostatic treatement (%/n) 100.00/56
Melphalan 64.29/36
Carmustine – BCNU 32.12/18
Etoposide 32.12/18
Cytarabine – Ara‐C 28.57/16
Busulfan 28.57/16
Cyclophosphamide 25.00/14
Fludarabine 10.71/6
Total body irradiation (%/n) 21.43/12
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2.2. 24‐hr ECG Holter monitoring

In all patients who met the criteria of entering the study 24‐hr Holter monitoring was carried out twice. First examination took place prior to the HSCT procedure (test A), and the second after finishing the procedure of HSCT, that is HDC and stem cell transplantation (test B). The precise time of the second test was dependent on the condition of the patient, and potential risk of serious infection. The mean time between two tests was 26.03 ± 8.74 days, minimal period was 13 days, and maximal ‐ 41 days.

The 24‐hr ECG Holter recording with the use of Lifecard CF (Reynolds Medical, Hertford, UK) was carried out in all participants of the study and then it was analyzed with Impresario Solo system. During the ECG monitoring patients had they normal every day activity, and they were making notes in the diary indicating the time of the specific activity. They were asked go to bed at about 10 p.m. and get up in the morning at about 6 a.m. and basing on this it has been established that the day hours were 6.00–22.00 and, simultaneously, night hours ‐ 22.00–6.00. ECG recordings were analyzed by one cardiologist. The clinical data of the patients were not known for the analyzing person, especially, data on the type of hematologic cancer and chemotherapy. Additionally, during the second analysis the physician was not informed about the previous result of ECG recording.

2.3. Statistical analysis

Statistic analysis was conducted using the STATISTICA 12 software (StatSoft Polska). For the quantitative variables arithmetic means (X) and standard deviations (SD) of estimated parameters were calculated in the study group. Distribution of variables was examined using tests of Lilliefors and W‐Shapiro‐Wilk. For the dependent quantitative variables of the normal distribution, the t test for linked variables was used. In cases of quantitative dependent variables showing the distribution distinct from normal, the pair sequence test of Wilcoxon was applied. Results for qualitative variables were expressed in a form of percentages. For dependent qualitative variables statistical analysis involved the test of McNemar or the Cochran test. In order to define a relationships between the variables, analysis of regression was performed. Results at the level of p < .05 were assumed to be of statistical significance.

3. RESULTS

In the comparative analysis of the quantitative data of the patients from 24‐hr ECG Holter monitoring it was shown that minimal heart rate (HR min), mean heart rate (HR mean) and the number of premature ventricular contractions (PVCs) was statistically higher in the test performed after HSCT (the B test) in comparison with the recordings before HSCT (the A test). There were no statistically significant differences between test A and B in maximal heart rate and the number of premature supraventricular contractions, supraventricular couplets and couplets of premature ventricular contractions. The quantitative parameters from the 24‐hr Holter recording in the study group in tests A and B are presented in Table 2.

Table 2.

24‐hr ECG Holter monitoring parameters in the study group

Test A Test B p
HR min (bpm) 54.54 ± 9.36 59.45 ± 9.52 p < .05
HR max (bpm) 120.30 ± 18.16 123.41 ± 17.64 ns
HR mean (bpm) 72.63 ± 10.95 78.29 ± 11.38 p < .05
SVPCs 167.02 ± 748.64 283.82 ± 765.77 ns
SVPCs (%/n) 92.86/52 92.86/52 ns
PVCs 41.86 ± 129.63 210.59 ± 532.71 p < .05
PVCs (%/n) 62.50/35 85.71/48 p < .05
SVPC couplets 27.70 ± 65.95 29.56 ± 71.26 ns
SVPC couplets (%/n) 48.21/27 51.78/29 ns
PVC couplets 10.22 ± 26.92 13.24 ± 29.31 ns
PVC couplets (%/n) 16.07/9 14.28/8 ns
SVT (%/n) 30.36/17 35.71/20 ns
Bradycardia (%/n) 14.28/8 10.71/6 ns
First‐degree AV block (%/n) 5.36/3 7.14/4 ns
IVR (%/n) 3.57/2 7.14/4 ns
VT (%/n) 3.57/2 3.57/2 ns
IVCD (%/n) 3.57/2 1.78/1 ns
AF (%/n) 1.78/1 5.36/3 ns
Tachycardia (%/n) 1.78/1 10.71/6 p < .05
Type 1 second‐degree AV block (%/n) 1.78/1 8.93/5 p < .05
Type 2 second‐degree AV block (%/n) 1.78/1 5.36/3 ns
Negative T waves (%/n) 1.78/1 5.36/3 ns
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AF, atrial fibrillation; AV block, atrioventricular block; IVR, idioventricular rhythm; HR max, maximal heart rate; HR mean, mean heart rate; HR min, minimal heart rate; SVPCs, supraventricular premature complexes; PVCs, premature ventricular complexes; SVT, supraventricular tachycardia; test A, before HSCT; test B, after HSCT; VT, ventricular tachycardia.

With the use of comparative analysis of qualitative parameters from 24‐hr Holter monitoring in the study group it was shown that in test B there was a statistically significant higher percentage of premature ventricular contractions, tachycardia and Mobitz type 1 second degree atrioventricular block. There were no significant differences in the incidence of the rest pathologies the in 24‐hr Holter monitoring between results from tests A and B. Qualitative parameters of the examined patients from Holter recording in tests A and B are shown also in Table 2.

The increase in the number of abnormalities in 24‐hr ECG recording in test B in comparison with test A were observed in 23 patients, which constituted 41.07% of the examined subjects.

With the use of multivariable stepwise regression analysis the independent risk factors for the increase in HR min, HR mean and PVCs were established in the test B in comparison with test A. Potential risk factors were taken under consideration such as basic clinical parameters (age, gender), the type of hematopoietic malignancy (acute myeloblastic leukemia, Hodgkin's lymphoma, multiple myeloma, acute lymphoblastic leukemia, non‐Hodgkin's lymphoma and chronic myeloblastic leukemia), the type of administered cytostatic drugs for high‐dose chemotherapy in the course of HSCT procedure (i.e., melphalan, carmustine, etoposide, cytarabine, cyclophosphamide, and busulfan), total body irradiation and the type of stem cell transplantation (auto, allo). The obtained models of regression are presented in Table 3.

Table 3.

Results of estimation for the final models obtained in the regression analysis

Model for Δ HR min (bpm)
Cyclophosphamide Age (years)
Regression coefficient 4.135 0.712
SEM of Rc 1.354 0.247
p value <0.001 <0.05
p value for the model <0.001
Model for Δ HR mean (bpm)
Fludarabine Cyclophosphamide Age (years)
Regression coefficient 3.149 3.958 0.649
SEM of Rc 1.954 2.018 0.219
p value <0.05 <0.05 <0.05
p value for the model <0.01
Model for Δ PVCs
Cyclophosphamide TBI
Regression coefficient 51.214 42.655
SEM of Rc 20.135 15.986
p value <0.01 <0.05
p value for the model <0.01
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Δ HR min, Δ HR mean, Δ PVCs, difference between test A and test B; Fludarabine, Cyclophosphamide and TBI, nominal variables, where 1: yes, 0: no; HR mean, mean heart rate; HR min, minimal heart rate; PVCs, premature ventricular complexes; SEM of Rc, standard error of regression coefficient.

The models showed that in the group of patients with hematopoietic cancers who underwent high dose chemotherapy in the course of hematopoietic stem cell transplantation, the administration of cyclophosphamide and fludarabine and higher age represented independent risk factors for the increased HR mean in 24‐hr Holter recording in test B when compared with test A. The administration of cyclophosphamide and higher age represented independent risk factors for the increased HR min in 24‐hr Holter recording in test B. However, independently of the increase in PVCs in test B when compared with test A significant factors were: the administration of cyclophosphamide and total body irradiation.

4. DISCUSSION

The literature of the problem of arrhythmia in the peri‐transplant period in patients undergoing HSCT has been growing for recent years as this type of transplantation has become popular in last decades. A lot of reports were dealing with the general issue of cardiotoxicity in the course of transplantation, mainly as a result of specific types of chemotherapy including anthracyclines, and it has been profoundly studied up till now. In last years as there was a significant increase in the number of HSCT in the world each aspect of toxicity of the procedure, including cardiotoxicity determined in different ways has been under investigation. However, in few studies arrhythmias were carefully studied, and especially rarely the 24‐Holter monitoring was used. However, in majority of studies data were based on standard ECG and general clinical evaluation. Also, the authors of various reports mainly concentrated on more severe types of arrhythmias, neglecting the simple pathologies like premature supraventricular or ventricular complexes, which are probably the most common findings in every‐day practice.

The interesting up‐to‐date study concentrating on the incidence of supraventricular arrhythmia conducted by Singla et al., (2013) and it included 983 patients with median age of 58 years, in majority mails, suffering from plasma cell disorders, lymphoma and leukemia showed that this pathology of heart rate is quite common in the course of hematopoietic cell transplantation and it was found in about 9% patients at median of 9 days after transplantation. Analyzing types of supraventricular arrhythmia in patients undergoing HSCT it has been demonstrated that the quite common arrhythmia was atrial fibrillation (in 7% of patients), then atrial flutter, and supraventricular tachycardia, noted in 1% of patients. The data are quite consistent with the other reports (Hidalgo et al., 2004; Mileshkin et al., 2005). In patients with the attacks of atrial fibrillation or flutter the rhythm in majority of cases normalized till the time of dismissal and median duration of the arrhythmia was <1 day, giving not numerous complications such as hypotention, rarely needed vasopressors, only 8% were cardioverted but 25% of patients presented recurrences (Singla et al., 2013). Additionally, arrhythmias may cause longer hospital stay and give a greater possibility of admission to intensive care unit, but also a greater probability of death within 1 year of transplant (Blaes, Konety, & Hurley, 2016; Peres et al., 2010; Tonorezos et al., 2015).

In our studies, we did not observe more severe arrhythmias in peri‐transplant period such as ventricular fibrillation or atrial fibrillation. However, in 30.3% of patients before the HSCT, and 35.71% after it we observed short nonsustained attacks of supraventricular tachycardia (SVT), which was not a significant difference. The reason for the absence of more severe changes is probably the fact we have excluded from the study the patients with previously diagnosed cardiovascular disease. It has been done intentionally in order to investigate the exact influence of the HSCT procedure itself, and exclude the other diseases or conditions that could increase the risk of arrhythmia. Also, we noted short attacks of nonsustained ventricular tachycardia in 3.57% (two patients) before HSCT and 1.78% (one patient) after it, however, that was not a significant change.

In a new retrospective study by Tonorezos et al., (2015) it has been suggested that arrhythmias after transplant may be associated with significant morbidity and mortality – 3‐fold increase in risk for death within one year of transplant. The study of Tonorezos et al., (2015) is one of the most profound ones, in which a certified cardiologist studied medical documentation and patients had the extensive heart evaluation including Holter monitoring when needed, telemetry, however obligatory tests in this study prior to transplant were: echocardiography and stress test, standard ECG, and additionally multiple gated blood pool imaging (MUGA). Authors also paid more attention to arrhythmias defined as severe, that is atrial fibrillation, supraventricular tachycardia, ventricular tachycardia or fibrillation, omitting the incidence of ventricular or atrial premature contractions, and the other ones which did not require a change in management (Tonorezos et al., 2015). One third of patients had hypertension in history, which was as abovementioned the exclusion criterion in our study. Of the defined arrhythmias 49% was atrial fibrillation (AF), 18% had supraventricular tachycardia (SVT) and 11% ‐ atrial flutter, two patients (30%) had attacks of nonsustained ventricular tachycardia (nsVT). Generally, according to the definition of arrhythmia used by the authors only 61 patients (5%) presented arrhythmia during transplant of the 1,177 patients undergoing HSCT, aged 40–76, with median age 56 years old suffering in majority from lymphoma, multiple myeloma and leukemia (Tonorezos et al., 2015). To be underlined is that 34% of patients previously had diagnosed arterial hypertension, 6% coronary artery disease, 10% diabetes, and as much as 43% were current smokers. Moreover, patients who experienced post‐HSCT arrhythmias were older, were more often women, and in their medical history the abovementioned cardiovascular pathologies together with smoking habit – coexisted more frequently. There were no differences in arrhythmia incidence between patients receiving myeloablative or reduced or nonmyeloablative chemotherapy, but patients undergoing allogeneic HSCT were more likely to experience arrhythmia than patients receiving autologous transplant, also more likely was arrhythmia when patients were treated with ATG (Tonorezos et al., 2015). Moreover, Singla, Hidalgo and other authors identified the following risk factors for arrhythmias after HSCT: the older age, presence of premature supraventricular complexes or atrio‐ventricular conduction delay (1st or 2nd degree atrioventricular block) during pretransplant period, history of prior arrhythmia, presence of valvular abnormality, increased atrial size in echocardiography, history of hypertension and/or coronary artery disease, being on beta blocker treatment or the other antiarrhythmic agent and prior anthracycline use anthracycline dose of >400 mg/m2, lower ejection fraction of the left ventricle at baseline examination in echocardiography, baseline renal dysfunction (Hidalgo et al., 2004; Peres et al., 2010; Singla et al., 2013; Sureddi et al., 2012). Fatema declared a phenomenon of weight gain of or equal to 7% accompanied by and presence of diastolic dysfunction at diagnosis in patients with multiple myeloma is also a risk factor, which is not surprising as for cardiologist weight gain is one of the marker of ongoing progression of heart failure (Fatema et al., 2009). In the abovementioned studies, the study groups included heterogenous population where some patients had prior history of cardiovascular pathology, such as hypertension, coronary artery disease and some of them even decreased ejection fraction of the left ventricle ≤45% ‐ which in practices is connected with heart failure at different stages of the disease.

According to various authors in about 10% of the study group arrhythmia existed during peri‐transplant period with the same characteristics and the most common types were atrial fibrillation and atrial flutter (Fatema et al., 2009; Tonorezos et al., 2015). Generally, cardiovascular acute complications after transplantation occur within first 100 days and out of this group arrhythmias develop according to various authors between 1% and 27% of patients, and the dispersion is a result of the differences in the populations of patients (Murdych & Weisdorf, 2001; Tonorezos et al., 2015). In comparison – our second test was carried out more or less 26 days after HSCT minimally 13 maximally 41 days) and the increase in the number of various abnormalities in 24‐hr ECG recording after HSCT in comparison with test performed previously we observed in 23 patients, which constituted 41.07% of the examined subjects.

In our study after analyzing the quantitative data of the patients from 24‐hr ECG Holter monitoring it was shown that minimal heart rate, mean heart rate, and the number of premature ventricular contractions (PVCs) was statistically higher in the test performed after HSCT in comparison with the recordings before HSCT. Actually, the number of SVPCs were also higher in the second test, however, the difference did not reach the statistical significance. Regarding qualitative parameters from 24‐hr Holter monitoring in the study group it was found that in the second test there was a statistically significant higher percentage of premature ventricular contractions, tachycardia and Mobitz type 1 second degree atrioventricular block. The abnormalities in 24‐hr ECG recording in the test after HSCT were observed in 23 patients (41.07%) of the examined subjects.

In very fresh studies conducted by Samuelson et al., (2016) it has been shown that patients with multiple myeloma with a median duration of 6 years also treated with HSCT presented different heart function abnormalities in quite high percentage in electrocardiography (up to 45%), in echocardiography (50%) and was also reflected in serum levels of N‐terminal pro‐B‐type natriuretic peptide. Only standard electrocardiograms were evaluated during and after treatment for 31 patients, and no 24‐hr monitoring, in as high as 14 of patients authors identified ECG changes such as: criteria for left ventricular hypertrophy (LVH), repolarization abnormalities consistent with LVH, evidence of left atrial hypertrophy prolonged PR interval whilst single patients had atrial fibrillation, isolated left axis deviation, and complete right bundle branch block and one patient suffered from two episodes of polymorphic ventricular tachycardia during and after active myeloma treatment (Samuelson et al., 2016). Anyway, it needs evaluation in clinical settings if the patients had the changes before, prompting the need to do heart examinations before HSCT, and the second problem is that not all of the mentioned abnormalities are serious, and sometimes may be found in almost healthy people.

According to the mentioned authors it is possible that some cytostatic drugs for example melphalan may be a predisposing factor for arrhythmias, especially for atrial fibrillation, in about 6%–11% patients of bone marrow transplantation (Feliz et al., 2011; Moreau et al., 1999; Olivieri et al., 1998; Phillips et al., 2004; Sirohi et al., 2000). In our study we have found the relationship between HDC carried out before HSCT based on cyclophosphamide, fludarabine, and total body irradiation and changes in ECG Holter monitoring which were: the increase in HR min, HR mean and PVCs.

Generally in comment to the influence of chemotherapy on ECG changes there are not many reports in the group of patients undergoing HSCT and especially using 24‐hr Holter monitoring taking the influence of a single agent into consideration. In cases when cyclophosphamide treatment was used in an early period after it there were some changes in standard ECG including low voltage of QRS, QT dispersion and systolic dysfunction of the left ventricle with ejection fraction about 30% as well as dysfunction of the right ventricle, and troponin elevation, however, the changes recovered after 1 month of treatment and only in few patients the diffuse myocardial thickening due to hemorrhagic myopericarditis was present with pericardial effusion leading to tamponade resulting in death (Atalay, Gulmez, & Ozsancak Ugurlu, 2014; Auner et al., 2002; Birchall, Lalani, Venner, & Hugh, 2000; Gottdiener, Appelbaum, Ferrans, Deisseroth, & Ziegler, 1981; Morandi et al., 2001; Nakamae, Tsumura, Hino, Hayashi, & Tatsumi, 2000; Wadia, 2015). Cardiotoxicity induced by cyclophosphamide is well‐known, with symptoms occurring usually within 1–3 weeks, resolving in some patients without late consequences, with the high mortality rate to 43%, however, no such cases were described in HSCT treatment so this is a novel finding that cyclophosphamide may increase less severe ECG changes at first that should be monitored (Goldberg, Antin, Guinan, & Rappeport, 1986; Morandi, Ruffini, Benvenuto, Raimondi, & Fosser, 2005; Slordal & Spigset, 2006; Yeh et al., 2004). Risk factors for the development of side effects after cyclophosphamide include age older than 50, previous radiation, previous or concomitant anthracycline treatment and dysfunction of the left ventricle (Appelbaum et al., 1976; Goldberg et al., 1986; Morandi et al., 2005; Slordal & Spigset, 2006; Yeh et al., 2004). Ishida et al., (2016) reported in a fresh study that Cyclophosphamide (CY) cardiotoxixity is a rare lethal complication and underlined that the minimum dose for cardiac toxicity is not known, however, there are no reports of CY toxicity < the dose of 100 mg/kg. The study dealt patients who had CY treatment as conditioning regimen before allogeneic HSCT, 12 patients that is 1.5% developed fatal cardiac failure at median 4 days after first administration of the drug and died from acute cardiac failure. The echocardiographic effects were rather seen in diastolic function of the left ventricle than in systolic, so lethal complications were rare but with high mortality. As reported by other authors at doses more than 200 or 120 mg/kg in patients undergoing total body irradiation acute, and quite often refractory congestive heart failure may occur in 1–10 days after treatment with diffuse voltage loss in ecg with echocardiographic changes of lv failure and pericardial effusion (Goldberg et al., 1986; Mills & Roberts, 1979; Santos et al., 1971; Steinherz et al., 1981).

Analysing Fludarabine toxicity there were reports when fludarabine induced sinus bradycardia of 48 bpm in patients with refractory leukemia (Chung‐Lo, Hsieh, Chiu, & Bai, 2010). Fludarabine has been quite rare associated with heart complications such as congestive heart failure especially given together with melphalane (Ritchie, Seymour, Roberts, Szer, & Grigg, 2001; Spriano et al., 1994). In cases of patients with acute heart failure tachycardia was present in ECG recording, T‐wave inversion in one case ending with recovery in about 5 months (Ritchie et al., 2001).

In our opinion we agree with Blaes who in a new report underlines the need for the close cooperation of hematology and cardiology at the time of transplantation procedure, which is especially important in pretransplantation period, however, the recent data suggest that additionally the time after transplantation is of great value, including first days and weeks (Blaes et al., 2016). For the reason HSCT becomes more available procedure for various populations of patients and the number of it will be rather growing in future the patients should be under special cardiac supervision. The best proposal would be cardiological evaluation at specific time like within 1 month, 6 months after, 1 year after HSCT, 5 years etc. including echocardiography, standard ECG recording and 24‐hr Holter monitoring.

Our study is not free of some limitations as usually at happens in a group of patients after specific types of transplantations the population is heterogeneous and not very numerous, however, this is the specificity of the patients in transplantation center, and remembering that some exclusion criteria lower the final number of patients, as well. Additionally, the patients formerly underwent different regimens of chemotherapy depending on the diagnosed disease. However, they did not present any cardiotoxic effect earlier and the cumulative doses were not exceeded.

5. CONCLUSIONS

  1. In patients with blood neoplasms undergoing high dose chemotherapy and HSCT more electrocardiographic abnormalities are found in comparison with the 24‐hr Holter monitoring before the procedure.

  2. In a group of patients with blood neoplasms after HSCT and high dose chemotherapy, administration of cyclophosphamide, fludarabine and total body irradiation were risk factors for electrocardiographic abnormalities in 24‐hr Holter monitoring, that is, the increase in HR min, HR mean, and PVCs.

CONFLICT OF INTEREST

The authors declare that they have no conflict of interest.

ETHICAL APPROVAL

All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.

INFORMED CONSENT

Informed consent was obtained from all individual participants included in the study.

Poręba M, Gać P, Usnarska‐Zubkiewicz L, et al. The analysis of the parameters of 24‐hr ECG Holter monitoring in patients with blood neoplasms undergoing high‐dose chemotherapy and stem cell transplantation. Ann Noninvasive Electrocardiol. 2018;23:e12534 10.1111/anec.12534

Funding information

This study was funded by Wroclaw Medical University.

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