Early Effects of Modern Radiotherapy for Lung Cancer on Endothelial Damage and Myocardial Fibrosis: A Prospective Single-Center Study.

Radiotherapy (RT) may have a cardiotoxic effect on the heart and cardiovascular system. Postulated mechanisms mediating these complications include vascular endothelium damage and myocardial fibrosis. The aim of our study was to assess endothelial damage and myocardial fibrosis in the early period after RT on the basis of cardiac biomarkers and in relation to the radiation dose applied to individual heart structures in patients treated for non-small-cell lung cancer. This single-center prospective study included consecutive patients with lung cancer (LC) who were referred for treatment with radiochemotherapy (study group) or chemotherapy (control group). The study protocol included performing an echocardiographic examination, a standard ECG examination, and collecting blood samples for laboratory tests before starting treatment for lung cancer in the first week after completing RT (after four cycles of chemotherapy in the control group) and after 12 weeks from the end of treatment. The study included 23 patients in the study group and 20 patients in the control group. Compared to the baseline values, there was a significant increase in total cholesterol concentration in the study group immediately after the end of RT, which persisted for three months after the end of therapy. After taking into account the use of statins in the analysis, it was found that an increase in total cholesterol concentration after oncological treatment was observed only among patients who did not use statins. Taking into account the assessment of myocardial fibrosis markers, there were no significant changes in the concentration of matrix metallopeptidase 9 (MMP-9) and tissue inhibitors of metalloproteinases 1 (TIMP-1) in the study group. In patients treated with radiochemotherapy, there was a significant increase in the concentration of intercellular adhesion molecule 1 (ICAM-1) immediately after RT, when compared to the baseline. After taking into account the use of statins, an increase in ICAM-1 concentration immediately after RT was observed only in patients who did not use statins. There was also a significant correlation between the radiation dose received by the left anterior descending coronary artery (LAD) and left circumferential coronary artery, and vascular cell adhesion protein 1 (VCAM-1) concentration measured at three months after the end of RT. Immediately after completion of radiotherapy, a significant increase in the level of ICAM-1 is observed indicating endothelial damage. The radiation dose to coronary arteries should be minimized, as it correlates with the concentration of VCAM-1. The use of statins may prevent the increase in total cholesterol and ICAM-1 concentration after irradiation for lung cancer; however, further studies designed for this specific purpose are necessary to confirm the effectiveness of statins in this area.

Effect of Radiotherapy on the Right Ventricular Function in Lung Cancer Patients.

BACKGROUND: Anticancer treatment is associated with many side effects, including those involving the cardiovascular system. While many studies are available on the effects of radiotherapy (RT) on the left ventricle (LV), studies are lacking on the early effects of RT on the structure and function of the right ventricle (RV). Our study aims to assess, using modern echocardiographic techniques, the effect of irradiation on RV systolic function in the mid-term follow-up of patients undergoing RT for lung cancer (LC). METHODS: This single-center, prospective study included consecutive patients with LC who were referred for treatment with definite radiotherapy and chemotherapy (study group) or chemotherapy only (control group). RESULTS: The study included 43 patients with a mean age of 64.9 ± 8.1 years. Cancer treatment-related RV toxicity (CTR-RVT) was found in 17 patients (40%). Early reductions in TAPSE values were observed among patients in the study group (20.3 mm vs. 22.1 mm, p = 0.021). Compared to baseline, there was a significant reduction in RV global longitudinal strain (RV GLS) in the study group immediately after the treatment (-21.1% vs. -18.4%, p = 0.02) and also at 3 months after RT (-21.1% vs. -19.1%, p = 0.021). A significant reduction in the RV FWLS value was also observed at 3 months after the end of the treatment (-23.8% vs. -21.8, p = 0.046). There were no significant changes in the three-dimensional right ventricular ejection fraction (3DRVEF) during the follow-up. We found a correlation (p = 0.003) between the mean dose of radiation to the RV and 3DRVEF when assessed immediately after RT. The mean dose of radiation to the heart correlated with RV free-wall longitudinal strain (RV FWLS) immediately after RT (p = 0.03). CONCLUSIONS: RV cardiotoxicity occurs in nearly half of patients treated for lung cancer. TAPSE is an important marker of deterioration of RV function under LC treatment. Compared to 3DRVEF, speckle tracking echocardiography is more useful in revealing deterioration of RV systolic function after radiotherapy.

Differences in cardiac adaptation to exercise in male and female athletes assessed by noninvasive techniques: a state-of-the-art review.

Athlete's heart is generally regarded as a physiological adaptation to regular training, with specific morphological and functional alterations in the cardiovascular system. Development of the noninvasive imaging techniques over the past several years enabled better assessment of cardiac remodeling in athletes, which may eventually mimic certain pathological conditions with the potential for sudden cardiac death, or disease progression. The current literature provides a compelling overview of the available methods that target the interrelation of prolonged exercise with cardiac structure and function. However, this data stems from scientific studies that included mostly male athletes. Despite the growing participation of females in competitive sport meetings, little is known about the long-term cardiac effects of repetitive training in this population. There are several factors-biochemical, physiological and psychological, that determine sex-dependent cardiac response. Herein, the aim of this review was to compare cardiac adaptation to endurance exercise in male and female athletes with the use of electrocardiographic, echocardiographic, and biochemical examination, to determine the sex-specific phenotypes, and to improve the healthcare providers' awareness of cardiac remodeling in athletes. Finally, we discuss the possible exercise-induced alternations that should arouse suspicion of pathology and be further evaluated.

Clinical and Laboratory Predictors of Long-Term Outcomes after Catheter Ablation for a Ventricular Electrical Storm.

Background: Ventricular electrical storm (VES) is characterized by the occurrence of multiple episodes of sustained ventricular arrhythmias (VA) over a short period of time. Radiofrequency ablation (RFA) has been reported as an effective treatment in patients with ventricular tachycardia (VT). Objective: The aim of the present study was to indicate the short-term and long-term predictors of recurrent VA after RFA was performed due to VES. Methods: A retrospective, single-centre study included patients, who had undergone RFA due to VT between 2012 and 2021. In terms of the short-term (at the end of RFA) effectiveness of RFA, the following scenarios were distinguished: complete success: inability to induce any VT; partial success: absence of clinical VT; failure: inducible clinical VT. In terms of the long-term (12 months) effectiveness of RFA, the following scenarios were distinguished: effective ablation: no recurrence of any VT; partially successful ablation: VT recurrence; ineffective ablation: VES recurrence. Results: The study included 62 patients. Complete short-term RFA success was obtained in 77.4% of patients. The estimated cumulative VT-free survival and VES-free survival were, respectively, 28% and 33% at the 12-month follow-up. Ischemic cardiomyopathy and complete short-term RFA success were predictors of long-term RFA efficacy. Neutrophil to lymphocyte ratio (NLR) and GFR <60 mL/min/1.73 m2 were associated with VES recurrence. NLR ≥2.95 predicted VT and/or VES recurrence with a sensitivity of 66.7% and specificity of 72.2%. Conclusion: Ischemic cardiomyopathy and short-term complete success of RFA were predictors of no VES recurrence during the 12-month follow-up, while NLR and GFR <60 ml/min/1.73 m2 were associated with VES relapse.

Coexistence of Left Atrial Tumor and Lung Cancer-The Key Role of an Individualized Approach.

During the diagnostic work-up in oncology, it is exceedingly rare to assume a concomitant presence of two cancers, a benign one and a malignant one, in a single patient. A 61-year-old man was admitted to the cardiology department for cardiac evaluation prior to planned radical treatment of non-small cell (NSCLC) left lung cancer (cT3N1M0). Echocardiography revealed a prominent, unpedunculated structure, measuring 17 × 14 mm, located in the left atrium (LA) near the fossa ovalis. The tumor was confirmed via cardiac magnetic resonance (CMR) imaging, which showed the radiological features of an atrial myxoma. The patient consulted with the Cardiac Surgery Department and was deemed ineligible for surgical treatment of a lesion with mucinous features; thus, no definitive histopathologic confirmation of the tumor present was possible. He was then successfully treated with radical radiochemotherapy and immunotherapy. During the 2-year follow-up, regular echocardiography and CMR were performed, which documented a stable LA tumor size.

Cardiac Arrhythmias in Patients Treated for Lung Cancer: A Review.

Cardio-oncology currently faces one of the greatest challenges in the field of health care. The main goal of this discipline is to ensure that patients treated for cancer do not suffer or die from cardiovascular disease. The number of studies on the mechanisms of heart injury during cancer treatment is constantly increasing. However, there is insufficient data on heart rhythm disorders that may result from this treatment. This issue seems to be particularly important in patients with lung cancer, in whom anticancer therapy, especially radiotherapy, may contribute to the onset of cardiac arrhythmias. The observed relationship between cardiac dosimetry and radiotherapy-induced cardiotoxicity in lung cancer treatment may explain the increased mortality from cardiovascular causes in patients after chest irradiation. Further research is essential to elucidate the role of cardiac arrhythmias in this context. Conversely, recent reports have highlighted the application of stereotactic arrhythmia radioablation (STAR) in the treatment of ventricular tachycardia. This review of available studies on the epidemiology, pathogenesis, diagnosis, and treatment of arrhythmias in patients treated for lung cancer aims to draw attention to the need for regular cardiological monitoring in this group of patients. Improving cardiac care for patients with lung cancer has the potential to enhance their overall therapeutic outcomes.

Metabolomics Meets Clinics: A Multivariate Analysis of Plasma and Urine Metabolic Signatures in Pulmonary Arterial Hypertension.

Pulmonary arterial hypertension (PAH) is a severe, multifactorial, and frequently misdiagnosed disorder. The aim of this observational study was to compare the plasma and urine metabolomic profiles of PAH patients and healthy control subjects. Plasma and urine metabolomic profiles were analyzed using the GC-MS technique. Correlations between metabolite levels and clinical parameters among PAH patients, as well as the between-group differences, were evaluated. The linear discriminant analysis model, which allows for subject classification in terms of PAH with the highest possible precision, was developed and proposed. Plasma pyruvic acid, cholesterol, threonine, urine 3-(3-hydroxyphenyl)-3-hydroxypropanoic acid, butyric acid, 1,2-benzenediol, glucoheptonic acid, and 2-oxo-glutaric acid were found to build a relatively accurate classification model for PAH patients. The model reached an accuracy of 91% and significantly improved subject classification (OR = 119 [95% CI: 20.3-698.3], p < 0.0001). Five metabolites were detected in urine that provide easily available and noninvasive tests as compared to right heart catheterization. The selected panel of metabolites has potential for early recognition of patients with dyspnea and faster referral to a reference center.

Plasma untargeted metabolomics with proteinase K discloses phospholipid signature associated with pulmonary arterial hypertension.

Pulmonary arterial hypertension is a rare but life-threatening and clinically heterogeneous disease. The diagnostic schedule of this disorder is complex, and no specific indicator of the arterial etiology has been explored. In this study, untargeted plasma metabolomics was applied to evaluate the metabolic fingerprints of pulmonary arterial hypertension patients. Plasma samples were prepared using a new approach, which applies proteinase K during the sample preparation procedure to increase the metabolite coverage. The metabolic fingerprints were determined via LC-MS and subsequently analyzed with the use of both uni- and multivariate statistics. A total of 21 metabolites were discovered to be significantly altered in pulmonary arterial hypertensive patients. The metabolites were mainly related to the phospholipid metabolic pathways. In this study, decreases were found in the phosphatidylcholines (PCs) [PC(32:0), PC(40:7), PC(42:7)], phosphatidylethanolamine PE(18:0/18:2), lysophosphatidylethanolamines (LPEs) [LPE(22:6), LPE(18:2), LPE(18:0), LPE(20:4), LPE(20:1), LPE(20:0)], lysophosphatidylcholine LPC(20:4) and lysophosphatidylserine LPS(19:0), as well as increase of sphingomyelin SM(36:2), in the plasma samples of pulmonary arterial hypertensive patients in comparison to the control group. Besides their function as components of the biological membranes, these metabolites are also involved in the intracellular signaling pathways that are related to cell proliferation and apoptosis. The results obtained during this study confirm the potential of (untargeted) metabolomics to identify the molecular characteristics of the pathophysiology of pulmonary arterial hypertension. The clinical relevance of this study constitutes the selection of a metabolic panel that can potentially detect and properly diagnose the disease.

Case report: Transected Hickman catheter and its thrombotic occlusion in a patient with idiopathic pulmonary arterial hypertension-can a catheter replacement be avoided?

A 25-year-old female with idiopathic pulmonary arterial hypertension (PAH), who had a Hickman catheter implanted for continuous intravenous epoprostenol infusion, was admitted to the clinic after inadvertently cutting the catheter with nail scissors during a routine dressing change. Approximately 7 cm of the external segment of the Hickman catheter remained intact, with the distal end knotted by paramedics. A decision was made to repair the damaged Hickman catheter. However, it was discovered that its lumen was completely occluded by thrombosis. Therefore, catheter patency was mechanically restored using a 0.035-inch stiff guidewire in a sterile operating theatre setting, under fluoroscopy guidance. Successful aspiration and catheter flushing were achieved. Continuity of the Hickman catheter was then restored using a repair kit (Bard Access Systems) as per the manufacturer's instructions, with no visible leakage thereafter. Epoprostenol infusion through the Hickman catheter was resumed 24 h later, and the patient was discharged in good general condition two days afterward.

Impact of diabetes mellitus on disease severity and patient survival in idiopathic pulmonary arterial hypertension: data from the Polish multicentre registry (BNP-PL).

BACKGROUND: Recent studies revealed that alterations in glucose and lipid metabolism in idiopathic pulmonary arterial hypertension (IPAH) are associated with disease severity and poor survival. However, data regarding the impact of diabetes mellitus (DM) on the prognosis of patients with IPAH remain scarce. The aim of our study was to determine that impact using data from a national multicentre prospective pulmonary hypertension registry. METHODS: We analysed data of adult patients with IPAH from the Database of Pulmonary Hypertension in the Polish population (BNP­PL) between March 1, 2018 and August 31, 2020. Upon admission, clinical, echocardiographic, and haemodynamic data were collected at 21 Polish IPAH reference centres. The all-cause mortality was assessed during a 30-month follow-up period. To adjust for differences in age, body mass index (BMI), and comorbidities between patients with and without DM, a 2-group propensity score matching was performed using a 1:1 pairing algorithm. RESULTS: A total of 532 patients with IPAH were included in the study and 25.6% were diagnosed with DM. Further matched analysis was performed in 136 patients with DM and 136 without DM. DM was associated with older age, higher BMI, more advanced exertional dyspnea, increased levels of N-terminal pro-brain natriuretic peptide, larger right atrial area, increased mean right atrial pressure, mean pulmonary artery pressure, pulmonary vascular resistance, and all-cause mortality compared with no DM. CONCLUSIONS: Patients with IPAH and DM present with more advanced pulmonary vascular disease and worse survival than counterparts without DM independently of age, BMI, and cardiovascular comorbidities.

Echocardiographic Findings in Asymptomatic Mediastinal Lymphoma Survivors Years after Treatment Termination.

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.

Role of catheter-directed therapies in the treatment of acute pulmonary embolism. Expert opinion of the Polish PERT Initiative, Working Group on Pulmonary Circulation, Association of Cardiovascular Interventions, and Association of Intensive Cardiac Care of the Polish Cardiac Society.

Thanks to advances in interventional cardiology technologies, catheter-directed treatment has become recently a viable therapeutic option in the treatment of patients with acute pulmonary embolism at high risk of early mortality. Current transcatheter techniques allow for local fibrinolysis or embolectomy with minimal risk of complications. Therefore, these procedures can be considered in high-risk patients as an alternative to surgical pulmonary embolectomy when systemic thrombolysis is contraindicated or ineffective. They are also considered in patients with intermediate-high-risk pulmonary embolism who do not improve or deteriorate clinically despite anticoagulation. The purpose of this article is to present the role of transcatheter techniques in the treatment of patients with acute pulmonary embolism. We describe current knowledge and expert opinions in this field. Interventional treatment is described in the broader context of patient care organization and therapeutic modalities. We present the organization and responsibilities of pulmonary embolism response team, role of pre-procedural imaging, periprocedural anticoagulation, patient selection, timing of intervention, and intensive care support. Currently available catheter-directed therapies are discussed in detail including standardized protocols and definitions of procedural success and failure. This expert opinion has been developed in collaboration with experts from various Polish scientific societies, which highlights the role of teamwork in caring for patients with acute pulmonary embolism.

Global Longitudinal Strain in Cardio-Oncology: A Review.

Several therapies used in cancer treatment are potentially cardiotoxic and may cause left ventricular (LV) dysfunction and heart failure. For decades, echocardiography has been the main modality for cardiac assessment in cancer patients, and the parameter examined in the context of cardiotoxicity was the left ventricular ejection fraction (LVEF). The assessment of the global longitudinal strain (GLS) using speckle tracking echocardiography (STE) is an emerging method for detecting and quantifying subtle disturbances in the global long-axis LV systolic function. In the latest ESC guidelines on cardio-oncology, GLS is an important element in diagnosing the cardiotoxicity of oncological therapy. A relative decrease in GLS of >15% during cancer treatment is the recommended cut-off point for suspecting subclinical cardiac dysfunction. An early diagnosis of asymptomatic cardiotoxicity allows the initiation of a cardioprotective treatment and reduces the risk of interruptions or changes in the oncological treatment in the event of LVEF deterioration, which may affect survival.

Apple Watch-guided diagnosis of AVNRT in a pregnant woman-A case report and literature review.

Cardiac arrhythmias occurring during pregnancy pose a therapeutic problem as antiarrhythmic drugs can be potentially harmful to the fetus. A 35-years-old woman in the 20th week of pregnancy was admitted to the Department of Cardiology due to the first episode of arrhythmia in her life. During the event, the patient was wearing an Apple Watch Series 6, which records a 30-sec single-channel ECG. The recording showed narrow QRS complex tachycardia of 216 bpm, and short RP interval and atrioventricular nodal reentrant tachycardia (AVNRT) was recognized. Due to the mild nature of the arrhythmia, antiarrhythmic pharmacotherapy was not initiated. The use of mobile health (mHealth) devices such as wearables and health monitoring applications is now a valuable addition to routine cardiac diagnostics for patients of all ages and levels of cardiovascular risk.

Deciphering the Regulatory Circuits of RA3 Replication Module - Mechanisms of the Copy Number Control.

The RA3 plasmid, the archetype of IncU incompatibility group, represents a mosaic-modular genome of 45.9 kb. The replication module encompasses repA and repB (initiator) surrounded by two long repetitive sequences DR1 and DR2 of unknown function. Here, we mapped the origin of replication oriV to the 3' end of repB and showed that oriV was activated by the transcription coming from orf02revp in the adjacent stability module. Using various in vivo and in vitro methods we demonstrated that the repB expression proceeded either from repBp located in the intergenic repA-repB region or from the upstream strong repAp that was autoregulated by RepA. Additionally, the repBp activity was modulated by the transcription from the overlapping, divergently oriented repXp. Both repXmRNA (antisense for repAmRNA) and its small polypeptide product, RepX, were strong incompatibility determinants. Hence, we showed that the sophisticated RA3 copy number control combined the multivalent regulation of repB expression, RepB titration by DR1, and transcriptional activation of oriV, dependent on the RA3 global regulatory network. Similarly organized replicons have been found in diverse bacterial species confirming the significance of these mechanisms in establishing the IncU plasmids in a broad spectrum of hosts.

Impact of the COVID-19 Pandemic on Pulmonary Hypertension Patients: Insights from the BNP-PL National Database.

We aimed to evaluate the clinical course and impact of the SARS-CoV-2 pandemic on the rate of diagnosis and therapy in the complete Polish population of patients (pts) with pulmonary arterial hypertension (PAH-1134) and CTEPH (570 pts) treated within the National Health Fund program and reported in the national BNP-PL database. Updated records of 1704 BNP-PL pts collected between March and December 2020 were analyzed with regard to incidence, clinical course and mortality associated with COVID-19. Clinical characteristics of the infected pts and COVID-19 decedents were analyzed. The rates of new diagnoses and treatment intensification in this period were studied and collated to the proper intervals of the previous year. The incidence of COVID-19 was 3.8% (n = 65) (PAH, 4.1%; CTEPH, 3.2%). COVID-19-related mortality was 28% (18/65 pts). Those who died were substantially older and had a more advanced functional WHO class and more cardiovascular comorbidities (comorbidity score, 4.0 ± 2.1 vs. 2.7 ± 1.8; p = 0.01). During the pandemic, annualized new diagnoses of PH diminished by 25-30% as compared to 2019. A relevant increase in total mortality was also observed among the PH pts (9.7% vs. 5.9% pre-pandemic, p = 0.006), whereas escalation of specific PAH/CTEPH therapies occurred less frequently (14.7% vs. 21.6% pre-pandemic). The COVID-19 pandemic has affected the diagnosis and treatment of PH by decreasing the number of new diagnoses, escalating therapy and enhancing overall mortality. Pulmonary hypertension is a risk factor for worsened course of COVID-19 and elevated mortality.