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Cardio-Oncology: Novel Concepts in Diagnosis, Prevention and Treatment of Cardiotoxicity, from Gender Differences and Beyond

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A special issue of Journal of Clinical Medicine (ISSN 2077-0383). This special issue belongs to the section "Cardiovascular Medicine".

Deadline for manuscript submissions: closed (10 June 2023) | Viewed by 26606

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Prof. Dr. Sabina Gallina

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Department of Neuroscience, Imaging and Clinical Sciences, University of Chieti-Pescara, Chieti, Italy
Interests: echocardiography; heart failure; blood pressure; clinical cardiology; cardiac function; cardiomyopathies; atherosclerosis; cardiovascular medicine; cardiovascular physiology; chronic heart failure
Special Issues, Collections and Topics in MDPI journals

Dr. Valentina Bucciarelli

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Department of Pediatric and Congenital Cardiology and Cardiac Surgery, Azienda Ospedaliero-Universitaria “Ospedali Riuniti”, Ancona, Italy
Interests: congenital heart disease; pediatric cardiology; gender medicine; physical exercise; speckle-tracking echocardiography; heart failure
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Significant improvements in recent decades in the diagnosis and therapy of a variety of cancers have profoundly transformed several neoplasms, from incurable conditions to chronic diseases. On the other hand, therapeutic advances have led to increased morbidity and mortality due to treatment side effects. In this clinical scenario, cardiovascular (CV) disease is evolving as a crucial cause of morbidity and death in many cancer survivors. The latter may be the result of cardiotoxicity as well as the enhanced development of CV disease, especially in the presence of traditional CV risk factors. Moreover, CVD and cancer share several overlapping risk factors such as age, tobacco habit, obesity and sedentary behavior. Cardio-oncology represents a relatively new subspecialty focusing on the diagnosis, prevention and treatment of CV complications related to cancer and its therapy. Gender differences are well known in oncological and CV diseases, but to date, they are still less enlightened in cardio-oncological scenarios. The aim of this Special Issue is to highlight recent advances in gender differences, prevention, diagnosis, treatment and prognosis in cardio-oncology.

Prof. Dr. Sabina Gallina
Dr. Valentina Bucciarelli
Guest Editors

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Keywords

cardio-oncology
cardiotoxicity
gender medicine
chemotherapy
radiotherapy
immune and targeted therapeutics
physical activity
quality of life

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Related Special Issue

Cardio-Oncology: Novel Concepts in Diagnosis, Prevention and Treatment of Cardiotoxicity, from Gender Differences and Beyond (Second Edition) in Journal of Clinical Medicine (1 article)

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Research

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10 pages, 1137 KB

Open AccessArticle

Left Ventricular Twist and the “Rigid Body Rotation” Pattern in Patients Treated with Anthracyclines or Anti-HER2

by Federico Guerra, Giulia Stronati, Alice Frangione, Edlira Rrapaj, Marco Flori, Michele Alfieri, Samuele Principi, Alessandro Barbarossa, Giuseppe Ciliberti and Antonio Dello Russo

J. Clin. Med. 2024, 13(11), 3352; https://doi.org/10.3390/jcm13113352 - 6 Jun 2024

Viewed by 1648

Abstract

Background: During the physiological cardiac cycle, the helix orientation of the muscle fibres induces the rotation of the apex relative to the base of the left ventricular (LV). In heart failure, LV torsion is impaired, and rotation at basal and apical levels occurs in the same direction, a phenomenon called rigid body rotation (RBR). We aimed to evaluate whether the RBR pattern and GLS together could improve the diagnosis of cardiotoxicity in patients treated with anthracyclines and/or anti-HER2. Methods: With an observational, retrospective study involving 175 patients (mean age 55 ± 12 years, 94% females), we evaluated the development of cancer therapeutic–related cardiac dysfunction (CTRCD) defined according to ESC guidelines. We characterised LV dysfunction by echocardiographic standard and speckle-tracking (GLS and RBR pattern) measurements. Patients with a previous diagnosis of structural heart disease or atrial fibrillation were excluded. Results: At the time of enrolment, the chemotherapy regimen included trastuzumab (96%), pertuzumab (21%), and anthracyclines (13%). Twenty-two patients (12.5%) developed cardiotoxicity, and thirteen patients developed an RBR within 6 months of follow-up. In all cases, the RBR pattern was associated with cardiotoxicity (p < 0.001), reporting an optimal specificity but poor sensitivity at three and six months. However, the addition of the RBR pattern to the global longitudinal strain (GLS) ≥ −16% increased the odds ratio (OR) from 25.6 to 32.6 at three months and from 32.5 to 49.6 at six months rather than GLS alone. Conclusions: The RBR pattern improves the diagnostic accuracy of GLS for the detection of cardiotoxicity secondary to anthracyclines and anti-HER2-based treatments. Full article

(This article belongs to the Special Issue Cardio-Oncology: Novel Concepts in Diagnosis, Prevention and Treatment of Cardiotoxicity, from Gender Differences and Beyond)

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18 pages, 713 KB

Open AccessArticle

Cardiometabolic Profile, Physical Activity, and Quality of Life in Breast Cancer Survivors after Different Physical Exercise Protocols: A 34-Month Follow-Up Study

by Valentina Bucciarelli, Francesco Bianco, Andrea Di Blasio, Teresa Morano, Desiree Tuosto, Francesco Mucedola, Serena Di Santo, Alessandra Cimini, Giorgio Napolitano, Ines Bucci, Angela Di Baldassarre, Ettore Cianchetti and Sabina Gallina

J. Clin. Med. 2023, 12(14), 4795; https://doi.org/10.3390/jcm12144795 - 20 Jul 2023

Cited by 7 | Viewed by 2595

Abstract

Background: Breast cancer (BC) and cardiovascular (CV) disease share many risk factors associated with worse outcomes, in terms of cancer relapse, CV events, and quality of life (QoL), that could be counteracted by physical exercise (PE). We aimed to assess the impact of a 12-week differential PE protocol on cardiometabolic profile, QoL, CV- and BC-related long-term outcomes, and physical activity (PA) in a cohort of BC survivors (BCS) not treated with chemotherapy. Methods: 57 BCS participated in a 12-week PE protocol [aerobic exercise training (AET) or resistance exercise training (RET)]. Anthropometric and CV evaluation, health-related (HR)-QoL, daily PA, cortisol, and dehydroepiandrosterone sulfate (DHEA-S) levels were assessed before (T0) and after (T1) PE. We assessed BC and CV outcomes, HR-QoL, CV-QoL, and PA at the follow-up. Results: RET improved waist circumference, DHEA-S, cortisol/DHEA-S, systolic and mean blood pressure, and ventricular/arterial coupling; AET ameliorated sagittal abdomen diameter and pulse wave velocity. Regarding HR-QoL, physical function improved only in AET group. At a mean 34 ± 3.6-month follow-up, we documented no significant differences in CV-QoL, HR-QoL, and PA or CV and BC outcomes. Conclusions: AET and RET determine specific, positive adaptations on many parameters strongly related to CV risk, CV and BC outcomes, and QoL, and should be included in any cardio-oncology rehabilitation program. Full article

(This article belongs to the Special Issue Cardio-Oncology: Novel Concepts in Diagnosis, Prevention and Treatment of Cardiotoxicity, from Gender Differences and Beyond)

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10 pages, 1153 KB

Open AccessArticle

Predicting Long-Term Ventricular Arrhythmia Risk in Children with Acute Lymphoblastic Leukemia Using Normal Values of Ventricular Repolarization Markers Established from Japanese Cohort Study

by Masahiro Takeguchi, Satoshi Kusumoto, Kazuhito Sekiguchi, Souichi Suenobu and Kenji Ihara

J. Clin. Med. 2023, 12(14), 4723; https://doi.org/10.3390/jcm12144723 - 17 Jul 2023

Cited by 2 | Viewed by 1835

Abstract

Background: Cardiac complications due to anthracycline treatment may become evident several years after chemotherapy and are recognized as a serious cause of morbidity and mortality in cancer patients or childhood cancer survivors. Objectives: We analyzed ventricular repolarization parameters in electrocardiography for pediatric acute lymphoblastic leukemia patients during chemotherapy and in long-term follow-up. To establish the reference values of ventricular repolarization parameters in children, we retrospectively summarized the Tpe interval, QT interval, QTc interval, and Tpe/QT ratio in healthy Japanese children. Methods: Electrocardiography data recorded from students in 1st and 7th grades were randomly selected from a database maintained by the school-based screening system in the Oita city cohort, Japan. Subsequently, chronological data of the Tpe/QT ratio in 17 pediatric patients with acute lymphoblastic leukemia were analyzed over time. Results: The mean ± standard deviation of the Tpe interval in 1st and 7th graders was 70 ± 7 and 78 ± 17 ms, respectively, while the mean ± standard deviation of the Tpe/QT ratio was 0.21 ± 0.02 and 0.22 ± 0.02 ms, respectively. During the intensive phase of treatment, the Tpe/QT ratios of 3 high-risk patients among the 17 patients with acute lymphoblastic leukemia exceeded the upper limit. Conclusion: The Tpe/QT ratio has a potential clinical application in predicting the risk of long-term ventricular arrhythmia of cancer patients or childhood cancer survivors from childhood to adulthood. Full article

(This article belongs to the Special Issue Cardio-Oncology: Novel Concepts in Diagnosis, Prevention and Treatment of Cardiotoxicity, from Gender Differences and Beyond)

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12 pages, 267 KB

Open AccessArticle

Echocardiographic Findings in Asymptomatic Mediastinal Lymphoma Survivors Years after Treatment Termination

by Izabela Nabiałek-Trojanowska, Hanna Jankowska, Grzegorz Sławiński, Alicja Dąbrowska-Kugacka and Ewa Lewicka

J. Clin. Med. 2023, 12(10), 3427; https://doi.org/10.3390/jcm12103427 - 12 May 2023

Cited by 1 | Viewed by 2300

Abstract

Patients treated due to mediastinal lymphomas are at risk of cardiovascular complications, as they receive chemotherapy, usually containing anthracyclines, often combined with thoracic radiotherapy. The aim of this prospective study was to assess early asymptomatic cardiac dysfunction using resting and dobutamine stress echocardiography (DSE) at least 3 years after the end of mediastinal lymphoma treatment. Two groups of patients were compared: those treated with chemoradiotherapy and those exclusively treated with chemotherapy. Left ventricular contractile reserve (LVCR) during DSE was assessed using changes in LV ejection fraction (LVEF), LV global longitudinal strain (LV GLS), and a novel parameter—Force, which is the ratio of the systolic blood pressure to the LV end-systolic volume. The study included 60 patients examined at a median of 89 months after the end of treatment. Resting echocardiography showed normal LVEF of 58.9 ± 9.6%, borderline LV GLS of −17.7 ± 3%, decreased mean stroke volume (SV) of 51.4 ± 17 mL, and indexed SV of 27.3 ± 8 mL/m², and the right ventricular free wall longitudinal strain (LS) was impaired in some patients but not in all. There were no significant differences between the groups, with the exception of arterial hypertension, which was more common in the chemotherapy group (32% vs. 62.5%, p = 0.04). In resting echocardiography, only LV posterior wall LS differed significantly and was impaired in patients treated with chemotherapy (−19.1 ± 3.1% vs. −16.5 ± 5.1%, p = 0.04). DSE, performed in 21 patients after a median of 166 months from the end of cancer treatment, detected new contractility disorders in 1 patient (4.8%) and decreased LVCR in the majority of patients when determined using changes in LVEF or LV GLS, and in all patients when assessed with changes in Force. Conclusions: Most asymptomatic mediastinal lymphoma survivors showed preserved ventricular function on resting echocardiography. However, all of them showed impaired LV contractile reserve on DSE, as assessed with a simple parameter—Force. This may indicate subtle LV dysfunction and confirms the need for long-term monitoring of patients with potentially cardiotoxic cancer treatment. Full article

(This article belongs to the Special Issue Cardio-Oncology: Novel Concepts in Diagnosis, Prevention and Treatment of Cardiotoxicity, from Gender Differences and Beyond)

13 pages, 633 KB

Open AccessArticle

Sex-Related Disparities in Cardiac Masses: Clinical Features and Outcomes

by Francesco Angeli, Luca Bergamaschi, Andrea Rinaldi, Pasquale Paolisso, Matteo Armillotta, Andrea Stefanizzi, Angelo Sansonetti, Sara Amicone, Andrea Impellizzeri, Francesca Bodega, Lisa Canton, Nicole Suma, Damiano Fedele, Davide Bertolini, Francesco Pio Tattilo, Daniele Cavallo, Ornella Di Iuorio, Khrystyna Ryabenko, Marcello Casuso Alvarez, Nazzareno Galiè, Alberto Foà and Carmine Pizzi Show full author list Hide full author list

J. Clin. Med. 2023, 12(8), 2958; https://doi.org/10.3390/jcm12082958 - 19 Apr 2023

Cited by 7 | Viewed by 3168

Abstract

Background. Cardiac masses (CM) represent a heterogeneous clinical scenario, and sex-related differences of these patients remain to be established. Purpose: To evaluate sex-related disparities in CMs regarding clinical presentation and outcomes. Material and Methods. The study cohort included 321 consecutive patients with CM enrolled in our Centre between 2004 and 2022. A definitive diagnosis was achieved by histological examination or, in the case of cardiac thrombi, with radiological evidence of thrombus resolution after anticoagulant treatment. All-cause mortality at follow-up was evaluated. Multivariable regression analysis assessed the potential prognostic disparities between men and women. Results. Out of 321 patients with CM, 172 (54%) were female. Women were more frequently younger (p = 0.02) than men. Regarding CM histotypes, females were affected by benign masses more frequently (with cardiac myxoma above all), while metastatic tumours were more common in men (p < 0.001). At presentation, peripheral embolism occurred predominantly in women (p = 0.03). Echocardiographic features such as greater dimension, irregular margin, infiltration, sessile mass and immobility were far more common in men. Despite a better overall survival in women, no sex-related differences were observed in the prognosis of benign or malignant masses. In fact, in multivariate analyses, sex was not independently associated with all-cause death. Conversely, age, smoking habit, malignant tumours and peripheral embolism were independent predictors of mortality. Conclusions. In a large cohort of cardiac masses, a significant sex-related difference in histotype prevalence was found: Benign CMs affected female patients more frequently, while malignant tumours affected predominantly men. Despite better overall survival in women, sex did not influence prognosis in benign and malignant masses. Full article

(This article belongs to the Special Issue Cardio-Oncology: Novel Concepts in Diagnosis, Prevention and Treatment of Cardiotoxicity, from Gender Differences and Beyond)

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14 pages, 303 KB

Open AccessArticle

Childhood Cancer Survivors Have Impaired Strain-Derived Myocardial Contractile Reserve by Dobutamine Stress Echocardiography

by Olof Broberg, Ingrid Øra, Constance G. Weismann, Thomas Wiebe and Petru Liuba

J. Clin. Med. 2023, 12(8), 2782; https://doi.org/10.3390/jcm12082782 - 9 Apr 2023

Cited by 3 | Viewed by 2264

Abstract

Abnormal left ventricular contractile reserve (LVCR) is associated with adverse cardiac outcomes in different patient cohorts and might be useful in the detection of cardiomyopathy in childhood cancer survivors (CCS) after cardiotoxic treatment. The aim of this study was to evaluate LVCR by dobutamine stress echocardiography (DSE) combined with measures of myocardial strain in CCS previously treated with anthracyclines (AC). Fifty-three CCS (age 25.34 ± 2.44 years, 35 male) and 53 healthy controls (age 24.40 ± 2.40 years, 32 male) were included. Subjects were examined with echocardiography at rest, at low-dose (5 micrograms/kg/min), and at high-dose (40 micrograms/kg/min) dobutamine infusion. Left ventricular ejection fraction (LVEF) and global longitudinal strain (GLS), strain rate (GSR), and early diastolic strain rate (GEDSR) at different DSE phases were used as measures of LVCR. The mean follow-up time among CCS was 15.8 ± 5.8 years. GLS, GSR, and LVEF were lower at rest in CCS compared to controls (p ≤ 0.03). LVEF was within the normal range in CCS. ΔGLS, ΔGSR, and ΔGEDSR but not ΔLVEF were lower in CCS compared to controls after both low- (p ≤ 0.048) and high-dose dobutamine infusion (p ≤ 0.023). We conclude that strain measures during low-dose DSE detect impaired myocardial contractile reserve in young CCS treated with AC at 15-year follow-up. Thus, DSE may help identify asymptomatic CCS at risk for heart failure and allows for tailored follow-up accordingly. Full article

(This article belongs to the Special Issue Cardio-Oncology: Novel Concepts in Diagnosis, Prevention and Treatment of Cardiotoxicity, from Gender Differences and Beyond)

13 pages, 1005 KB

Open AccessArticle

Incidence and Predictors of Cardiac Implantable Electronic Devices Malfunction with Radiotherapy Treatment

by Meor Azraai, Daisuke Miura, Yuan-Hong Lin, Thalys Sampaio Rodrigues and Voltaire Nadurata

J. Clin. Med. 2022, 11(21), 6329; https://doi.org/10.3390/jcm11216329 - 27 Oct 2022

Cited by 2 | Viewed by 3095

Abstract

Aims: To investigate the incidence of cardiac implantable electronic devices (CIED) malfunction with radiotherapy (RT) treatment and assess predictors of CIED malfunction. Methods: A 6-year retrospective analysis of patients who underwent RT with CIED identified through the radiation oncology electronic database. Clinical, RT (cumulative dose, dose per fraction, beam energy, beam energy dose, and anatomical area of RT) and CIED details (type, manufacturer, and device malfunction) were collected from electronic medical records. Results: We identified 441 patients with CIED who underwent RT. CIED encountered a permanent pacemaker (PPM) (78%), cardiac resynchronization therapy—pacing (CRT-P) (2%), an implantable cardioverter defibrillator (ICD) (10%), and a CRT-defibrillator (CRT-D) (10%). The mean cumulative dose of RT was 36 gray (Gy) (IQR 1.8–80 Gy) and the most common beam energy used was photon ≥10 megavolt (MV) with a median dose of 7 MV (IQR 5–18 MV). We further identified 17 patients who had CIED malfunction with RT. This group had a higher cumulative RT dose of 42.5 Gy (20–77 Gy) and a photon dose of 14 MV (12–18 MV). None of the malfunctions resulted in clinical symptoms. Using logistic regression, the predictors of CIED malfunction were photon beam energy use ≥10 MV (OR 5.73; 95% CI, 1.58–10.76), anatomical location of RT above the diaphragm (OR 5.2, 95% CI, 1.82–15.2), and having a CIED from the ICD group (OR 4.6, 95% CI, 0.75–10.2). Conclusion: Clinicians should be aware of predictors of CIED malfunction with RT to ensure the safety of patients. Full article

(This article belongs to the Special Issue Cardio-Oncology: Novel Concepts in Diagnosis, Prevention and Treatment of Cardiotoxicity, from Gender Differences and Beyond)

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Review

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12 pages, 621 KB

Open AccessReview

Metabolomic Profiles on Antiblastic Cardiotoxicity: New Perspectives for Early Diagnosis and Cardioprotection

by Luca Fazzini, Ludovica Caggiari, Martino Deidda, Carlotta Onnis, Luca Saba, Giuseppe Mercuro and Christian Cadeddu Dessalvi

J. Clin. Med. 2022, 11(22), 6745; https://doi.org/10.3390/jcm11226745 - 15 Nov 2022

Cited by 5 | Viewed by 2137

Abstract

Antiblastic drugs-induced cardiomyopathy remains a relevant cause of morbidity and mortality, during and after chemotherapy, despite the progression in protective therapy against cardiovascular diseases and myocardial function. In the last few decades, many groups of researchers have focused their attention on studying the metabolic profile, first in animals, and, subsequently, in humans, looking for profiles which could be able to predict drug-induced cardiotoxicity and cardiovascular damage. In clinical practice, patients identified as being at risk of developing cardiotoxicity undergo a close follow-up and more tailored therapies. Injury to the heart can be a consequence of both new targeted therapies, such as tyrosine kinase inhibitors, and conventional chemotherapeutic agents, such as anthracyclines. This review aims to describe all of the studies carried on this topic of growing interest. Full article

(This article belongs to the Special Issue Cardio-Oncology: Novel Concepts in Diagnosis, Prevention and Treatment of Cardiotoxicity, from Gender Differences and Beyond)

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10 pages, 248 KB

Open AccessReview

Gender Differences in Diagnosis, Prevention, and Treatment of Cardiotoxicity in Cardio-Oncology

by Shawn Simek, Brian Lue, Anjali Rao, Goutham Ravipati, Srilakshmi Vallabhaneni, Kathleen Zhang, Vlad G. Zaha and Alvin Chandra

J. Clin. Med. 2022, 11(17), 5167; https://doi.org/10.3390/jcm11175167 - 1 Sep 2022

Cited by 8 | Viewed by 2826

Abstract

Gender differences exist throughout the medical field and significant progress has been made in understanding the effects of gender in many aspects of healthcare. The field of cardio-oncology is diverse and dynamic with new oncologic and cardiovascular therapies approved each year; however, there is limited knowledge regarding the effects of gender within cardio-oncology, particularly the impact of gender on cardiotoxicities. The relationship between gender and cardio-oncology is unique in that gender likely affects not only the biological underpinnings of cancer susceptibility, but also the response to both oncologic and cardiovascular therapies. Furthermore, gender has significant socioeconomic and psychosocial implications which may impact cancer and cardiovascular risk factor profiles, cancer susceptibility, and the delivery of healthcare. In this review, we summarize the effects of gender on susceptibility of cancer, response to cardiovascular and cancer therapies, delivery of healthcare, and highlight the need for further gender specific studies regarding the cardiovascular effects of current and future oncological treatments. Full article

(This article belongs to the Special Issue Cardio-Oncology: Novel Concepts in Diagnosis, Prevention and Treatment of Cardiotoxicity, from Gender Differences and Beyond)

Other

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11 pages, 753 KB

Open AccessStudy Protocol

Distance Monitoring of Advanced Cancer Patients with Impaired Cardiac and Respiratory Function Assisted at Home: A Study Protocol in Italy

by Rita Ostan, Silvia Varani, Andrea Giannelli, Italo Malavasi, Francesco Pannuti, Raffaella Pannuti, Guido Biasco, Anna Vittoria Mattioli and on behalf of the ANT Collaborative Group

J. Clin. Med. 2023, 12(5), 1922; https://doi.org/10.3390/jcm12051922 - 28 Feb 2023

Cited by 1 | Viewed by 2950

Abstract

During the pandemic, telemedicine and telehealth interventions have been leading in maintaining the continuity of care independently of patients’ physical location. However, the evidence available about the effectiveness of the telehealth approach for advanced cancer patients with chronic disease is limited. This interventional randomized pilot study aims to evaluate the acceptability of a daily telemonitoring of five vital parameters (heart rate, respiratory rate, blood oxygenation, blood pressure, and body temperature) using a medical device in advanced cancer patients with relevant cardiovascular and respiratory comorbidities assisted at home. The purpose of the current paper is to describe the design of the telemonitoring intervention in a home palliative and supportive care setting with the objective of optimizing the management of patients, improving both their quality of life and psychological status and the caregiver’s perceived care burden. This study may improve scientific knowledge regarding the impact of telemonitoring. Moreover, this intervention could foster continuous healthcare delivery and closer communication among the physician, patient and family, enabling the physician to have an updated overview of the clinical trajectory of the disease. Finally, the study may help family caregivers to maintain their habits and professional position and to limit financial consequences. Full article

(This article belongs to the Special Issue Cardio-Oncology: Novel Concepts in Diagnosis, Prevention and Treatment of Cardiotoxicity, from Gender Differences and Beyond)

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