Higher Mortality in Patients With Diffuse Large B-cell Lymphoma Pre-Existing Arterial Hypertension-Real World Data of the Polish Lymphoma Research Group.

BACKGROUND: Arterial hypertension is mentioned as a risk factor in Cardio-oncology. This study aimed to assess the long-term prognostic value of arterial hypertension (AH) in diffuse large B-cell lymphoma (DLBCL). METHODS: We analysed data collected by the Polish Lymphoma Research Group for the evaluation of the outcomes associated with the use of first-line rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone therapy in patients with DLBCL with coexisting AH. Patients with other cardiovascular comorbidities or premature chemotherapy discontinuation due to cardiovascular toxicity were excluded. RESULTS: Pre-existing AH was diagnosed in 65 of 232 patients with DLBCL (28%) included in the study, and was associated with significantly shorter overall survival values (p<0.00001). The rates of DLBCL recurrence, administration of second-, third-, or fourth-line chemotherapy, and lymphoma-related deaths were similar in patients with and those without AH. Cardiovascular deaths were significantly more frequently observed in patients with pre-existing AH (38.5% vs 3.6%, p<0.0001). In the univariate analysis, AH (p=0.000001), older age (p<0.000001), and diabetes (p=0.0065) were identified as significant predictors of all-cause mortality; however, cardiovascular mortality was associated with AH (p<0.000001), older age (p=0.000008), and dyslipidaemia (p=0.03). Multivariate analysis revealed AH as an age-independent significant predictor of all-cause (p=0.00045) and cardiovascular mortality (p<0.000001). CONCLUSION: In the long-term follow-up of patients with DLBCL, the role of AH, as an important age-independent predictor of premature cardiovascular mortality, was so strong that it may have value for use in close surveillance in cardio-oncology clinics.

Characteristics of patients with newly diagnosed hematological malignancies referred for echocardiography.

Objective: The importance of cardio-hemato-oncology programs is increasing. The main aim of the study was to identify all coexisting cardiovascular disorders in patients with new hematological malignancies referred for echocardiography during baseline evaluation before anticancer therapy. Material and methods: The study was based on 900 echocardiographic examinations performed within 12 months at the Institute of Hematology and Transfusion Medicine in Poland: 669 tests (74.3%) were dedicated to hemato-oncology patients at the different stages of cancer therapy, however almost a third of the tests (277, 30.8%) were part of a baseline evaluation before starting first line anticancer therapy due to newly diagnosed hematological malignancies. Results: The group of 277 patients with new hematological malignancies (138 women, 49.82%) with a median age of 66 years (interquartile range: 53-72 years) was included in the main analyses. The three most frequent new histopathological diagnoses were: non-Hodgkin lymphoma (63 cases; 22.74%), acute myeloid leukaemia (47 cases; 16.97%), and multiple myeloma (45 cases; 16.25%). The three most common clinical cardiology disorders were arterial hypertension (in 133 patients, 48.01%), arrhythmias (48 patients, 17.33%), and heart failure (39 patients, 14.08%). Among 48 patients with arrhythmias there were 22 cases with atrial fibrillation. The most frequently detected echocardiographic abnormality was Left Atrial Volume Index >34 ml/m2 which was present in 108 of 277 patients (38.99%) and associated with a significantly greater chance of concomitant diagnosis of arrhythmias (OR=1.98; p=0.048) especially atrial fibrillation (OR=3.39; p=0.025). The second most common echocardiographic finding was diastolic dysfunction 2nd or 3rd degree revealed in 43 patients (15.52%) and associated with a greater chance of simultaneous diagnosis of heart failure (OR=8.32; p<0.0001) or arrhythmias (OR=4.44; p<0.0001) including atrial fibrillation (OR=5.40; p=0.0003). Conclusions: In patients with newly diagnosed hematological malignancies left ventricular diastolic dysfunction is a common abnormality in echocardiography and may determine diagnoses of heart failure or arrhythmias.

Left and right ventricular global longitudinal strain assessment together with biomarker evaluation may have a predictive and prognostic role in patients qualified for hematopoietic stem cell transplantation due to hematopoietic and lymphoid malignancies - a pilot study description.

The hematopoietic stem cell transplantation (HSCT) procedure is considered a cardiovascular burden. This is due to the potentially cardiotoxic cytostatic agents used before and the risks associated with peri-transplant procedures. We designed a pilot study to determine the clinical utility of the new ST2 marker; furthermore, we routinely assessed cardiac parameters in HSCT recipients. Based on previous cardio-oncology experience in lung and prostate cancer, we can confirm the prognostic and predictive value of classic cardiac biomarkers and modern echocardiography parameters such as global longitudinal strain of the left and right ventricle. After conducting this pilot study we can create a predictive and prognostic model for patients undergoing HSCT. This will greatly enrich our clinical practice, especially in treating older people.

Global Cardio Oncology Registry (G-COR): Registry Design, Primary Objectives, and Future Perspectives of a Multicenter Global Initiative.

BACKGROUND: Global collaboration in cardio-oncology is needed to understand the prevalence of cancer therapy-related cardiovascular toxicity in different risk groups, practice settings, and geographic locations. There are limited data on the socioeconomic and racial/ethnic disparities that may impact access to care and outcomes. To address these gaps, we established the Global Cardio-Oncology Registry, a multinational, multicenter prospective registry. METHODS: We assembled cardiologists and oncologists from academic and community settings to collaborate in the first Global Cardio-Oncology Registry. Subsequently, a survey for site resources, demographics, and intention to participate was conducted. We designed an online data platform to facilitate this global initiative. RESULTS: A total of 119 sites responded to an online questionnaire on their practices and main goals of the registry: 49 US sites from 23 states and 70 international sites from 5 continents indicated a willingness to participate in the Global Cardio-Oncology Registry. Sites were more commonly led by cardiologists (85/119; 72%) and were more often university/teaching (81/119; 68%) than community based (38/119; 32%). The average number of cardio-oncology patients treated per month was 80 per site. The top 3 Global Cardio-Oncology Registry priorities in cardio-oncology care were breast cancer, hematologic malignancies, and patients treated with immune checkpoint inhibitors. Executive and scientific committees and specific committees were established. A pilot phase for breast cancer using Research Electronic Data Capture Cloud platform recently started patient enrollment. CONCLUSIONS: We present the structure for a global collaboration. Information derived from the Global Cardio-Oncology Registry will help understand the risk factors impacting cancer therapy-related cardiovascular toxicity in different geographic locations and therefore contribute to reduce access gaps in cardio-oncology care. Risk calculators will be prospectively derived and validated.

Cardiac Arrhythmias in Oncological Patients-Epidemiology, Risk Factors, and Management within the Context of the New ESC 2022 Guidelines.

PURPOSE OF REVIEW: To provide an update on epidemiology, risk factors, and management of cardiac arrhythmias in oncological patients within the context of the new European Society of Cardiology 2022 guidelines on cardio-oncology. RECENT FINDINGS: One of the side effects of different chemotherapeutics is their pro-arrhythmic activity. Both atrial and ventricular arrhythmias may be induced by cancer itself or by anticancer treatment. Recent studies report on the cardiotoxic activity of such promising therapies as BRAF and MEK inhibitors, or CAR-T therapy. Risk factors of arrhythmias in oncological patients overlap with cardiovascular diseases risk factors, but there are some groups of anticancer drugs that increase the risk of cardiotoxicity. It is crucial to be aware of the risks associated with the oncological treatment and know how to act in case of cardiotoxicity.

Long COVID syndrome after SARS-CoV-2 survival in patients with pulmonary arterial hypertension and chronic thromboembolic pulmonary hypertension.

Pulmonary arterial hypertension (PAH) and chronic thromboembolic pulmonary hypertension (CTEPH) patients have a more severe COVID-19 course than the general population. Many patients report different persistent symptoms after SARS-CoV-2 infection. The aim of our study is to analyze the prevalence of long COVID-19 symptoms and assess if COVID-19 affects pulmonary hypertension (PH) prognosis. PAH/CTEPH patients who survived COVID-19 for at least 3 months before visiting the PH centers were included in the study. The patients were assessed for symptoms in acute phase of SARS-CoV-2 infection and persisting in follow-up visit, WHO functional class, 6-min walk distance, NT-proBNP concentration. The COMPERA 2.0 model was used to calculate 1-year risk of death due to PH at baseline and at follow-up. Sixty-nine patients-54 (77.3%) with PAH and 15 (21.7%) with CTEPH, 68% women, with a median age of 47.5 years (IQR 37-68)-were enrolled in the study. About 17.1% of patients were hospitalized due to COVID-19 but none in an ICU. At follow-up (median: 155 days after onset of SARS-CoV-2 symptoms), 62% of patients reported at least 1 COVID-19-related symptom and 20% at least 5 symptoms. The most frequently reported symptoms were: fatigue (30%), joint pain (23%), muscle pain (17%), nasal congestion (17%), anosmia (13%), insomnia (13%), and dyspnea (12%). Seventy-two percent of PH patients had a low or intermediate-low risk of 1-year death due to PH at baseline, and 68% after COVID-19 at follow-up. Over 60% of PAH/CTEPH patients who survived COVID-19 suffered from long COVID-19 syndrome, but the calculated 1-year risk of death due to PH did not change significantly after surviving mild or moderate COVID-19.

Beta Blockers with Statins May Decrease All-Cause Mortality in Patients with Cardiovascular Diseases and Locally Advanced Unresectable Non-Small-Cell Lung Cancer after Chemoradiotherapy.

The study was conducted in the era when maintenance immunotherapy with durvalumab was not available in clinical practice after chemoradiotherapy (CRT) in unresectable non-small-cell lung cancer (NSCLC). The main aim of the study was to check whether the presence of cardiovascular diseases (CVD) and their pharmacotherapy affects the overall survival (OS) in such NSCLC patients undergoing sequential CRT. The group of 196 patients were analyzed: 101 patients with CVD (51.53%) and 95 patients with other reasons of qualification for sequential CRT (decreased performance status, older age, and other non-cardiovascular co-morbidities). Although patients with CVD were more often in older age, and they more often experienced cardiac and nephrological complications (p < 0.05 for all), there was a statistically nonsignificant trend for lower all-cause mortality in patients with CVD. The lowest all-cause mortality was observed in patients treated with beta-blockers and statins after two (HR = 0.31; 95%CI: 0.1-0.98; p = 0.047), three (HR = 0.33; 95%CI: 0.13-0.81; p = 0.015) and even four (HR = 0.45; 95%CI: 0.22-0.97; p = 0.027) years of follow-up. The benefit in OS remained significant in 101 patients with CVD treated with beta-blockers (HR = 0.65; 95%CI: 0.43-0.99; p = 0.045), and eventually statin, throughout the whole follow-up (log-rank p < 0.05). Further prospective studies are necessary to confirm the role of beta-blockers and statins in reduction of mortality in NSCLC patients undergoing radical CRT.

Savolitinib for non-small cell lung cancer.

Savolitinib is a highly selective MET tyrosine kinase inhibitor. MET is involved in numerous cellular processes such as proliferation, differentiation and the formation of distant metastases. MET amplification and MET overexpression are quite common in many cancers, but MET exon 14 skipping alteration is most common in non-small cell lung cancer (NSCLC). The role of MET signaling as a bypass pathway in the development of acquired resistance to tyrosine kinase inhibitor (TKI) epidermal growth factor receptor (EGFR) therapy in cancer patients with EGFR gene mutation was documented. Potential beneficiaries of savolitinib therapy are patients with NSCLC and initial diagnosis of MET ex 14 skipping mutation. Savolitinib therapy can be effective in NSCLC patients with EGFR-mutant MET with progression during first-line treatment with an EGFR-TKI. Antitumor activity of savolitinib in combination with osimertinib is very promising as first-line therapy of patients with advanced EGFR-mutated NSCLC, initially with MET expression. The safety profile of savolitinib as monotherapy and in combination with osimertinib or gefitinib is so favorable in all available studies that this drug has become a very promising therapeutic option and is being intensively investigated in ongoing clinical trials.

Performance-Status Deterioration during Sequential Chemo-Radiotherapy as a Predictive Factor in Locally Advanced Non-Small Cell Lung Cancer.

The role of sequential chemoradiotherapy in non-small cell lung cancer (NSCLC) patients who are not eligible for concurrent therapy has not been clearly defined. The aim of this study was to determine the usefulness of Karnofsky performance status (KPS) monitoring and to define the factors determining clinical deterioration during sequential chemoradiotherapy in patients treated from July 2009 to October 2014. The study included 196 patients. The clinical stage was defined as III A in 94 patients (48%) and III B in 102 patients (52%). Reduced KPS was found in 129 patients (65.8%). Baseline KPS had no significant prognostic significance. Deterioration of KPS during chemoradiotherapy was observed in 53 patients (27%) and had a negative predictive value for both worse-progression free survival (HR = 1.44; 95% CI: 1.03-1.99; p = 0.03) and overall survival (HR = 1.42; 95% CI: 1.02-1, 99; p = 0.04). The deterioration of KPS correlated with the disease control rate 6 weeks after the end of chemoradiotherapy (p = 0.0085). The risk of KPS worsening increased with each subsequent day between the end of chemotherapy and the start of radiotherapy (OR = 1.03; 95%CI: 1.01-1.05; p = 0.001), but decreased with each year of older age of patients (OR = 0.94, 95% CI: 0.9-0.98, p = 0.009). The time between the end of chemotherapy and the start of radiotherapy determined the prognosis of NSCLC after chemoradiotherapy. It should be adjusted to the age of patients.

Outcomes of COVID-19 in patients vaccinated and unvaccinated against SARS-CoV-2 and suffering from pulmonary arterial hypertension and chronic thromboembolic pulmonary hypertension.

INTRODUCTION: Pulmonary arterial hypertension (PAH) and chronic thromboembolic pulmonary hypertension (CTEPH) lead to progressive right heart failure. The mortality rates in PAH and CTEPH patients due to COVID­19 are high, and vaccination against COVID­19 is recommended in this group. OBJECTIVES: We analyzed the incidence and outcomes of COVID­19in the PAH/CTEPH patients for 2 years of the pandemic, as well as the predictors of worse outcomes of COVID­19 in this group. PATIENTS AND METHODS: PAH/CTEPH patient data for this observational, cohort study were obtained from 3 pulmonary hypertension centers between March 11, 2020 and March 11, 2022. RESULTS: A total of 364 consecutive patients with PAH/CTEPH (248/122; 232 women [64%]; median [interquartile range] age, 61 years [18-92]) were included in the study. All the patients had advanced pulmonary hypertension at baseline. Eighty­five patients (23%) suffered from COVID­19. Seven of them (8%), all of whom were unvaccinated, died of COVID­19. The unvaccinated patients suffered from COVID­19 more often than the vaccinated ones (46% vs 9%; P <0.001). As many as 31% of the PAH/CTEPH patients with COVID­19 needed hospitalization, in 8% of cases in the intensive care unit. Age equal to or above 65 years and severe pulmonary hypertension defined as a World Health Organization functional class 3 or 4 were associated with severe COVID­19 in the PAH/CTEPH patients. CONCLUSIONS: The vaccinated PAH/CTEPH patients suffered from COVID­19 less frequently than the unvaccinated ones. The mortality rate and hospitalization due to COVID­19 were higher in the PAH/CTEPH patients than in the general population. All efforts should be made to convince the PAH/CTEPH patients to vaccinate against COVID­19.

Cardiac Biomarkers and Geriatric Assessment in Metastatic Castrate-Resistant Prostate Cancer During Abiraterone Acetate Therapy - A Cardio-Oncology Study.

BACKGROUND: Abiraterone acetate (AA) is a drug used in advanced prostate cancer. However, known clinical factors with predictive and prognostic value are scarce. This study evaluated cardiovascular (CV) factors and geriatric scales as potential markers of superior response during AA therapy. METHODS: This is a prospective observational study. Serum levels of high sensitivity troponin T (hsTnT), D-dimer, NT-proBNP and left ventricle ejection fraction (LVEF) were used for CV evaluation. Questionnaires of G8, VES-13, Activities of Daily Living (ADL), Instrumental Activities of Daily Living (iADL), and Geriatric Depression Scale (GDS) were included in the geriatric screening assessment. All measures were taken before AA initiation. Survival curves and Cox proportional hazard models (univariate and multivariate) were used to determine the predictors for a longer time to treatment failure (TTF). RESULTS: Forty nine patients were included in the study. Overall median TTF was 7.9 months (95% CI: 5.9-12.4). In univariate analysis, factors associated with inferior TTF were (P-value < .05): visceral metastases - HR 2.34; 95% CI: 1.24-4.45, history of coronary artery disease - HR 3.02; 95% CI: 1.19-7.66; LVEF < 50% - HR 2.53; 95% CI: 1.03-6.17; P = .041; age-adjusted D-dimer > upper reference limit (URL) - HR 3.53; 95% CI: 1.81-6.85; P < .001; hsTnT > URL - HR 2.17; 95% CI: 1.13-4.16; P = .016; NT-proBNP ≥ 300 pg/mL - HR 2.3; 95% CI: 1.22-4.34; P = .01; G8 score ≤14 points - HR 2.47; 95% CI: 1.29-4.74; P = .007. In multivariate analysis, age-adjusted D-dimer > URL, G8 score ≤ 14 points and visceral metastases remained statistically significant in prediction of inferior TTF. The number of these factors was associated with shorter median TTF: 0-1 factor - 14.1 months; 2 factors - 5.9 months; 3 factors - 2.7 months; P < .001, log-rank). CONCLUSIONS: Age-adjusted D-dimer, and geriatric G8 scores may predict TTF in men with metastatic castration-resistant prostate cancer during AA therapy. These observations require further study in a larger population.

Are cardiovascular comorbidities always associated with a worse prognosis in patients with lung cancer?

Many factors contribute to mortality in lung cancer, including the presence of concomitant cardiovascular disease. In the treatment of early stage of lung cancer, the presence of comorbidities and occurence of cardiotoxicity may be prognostic. The effect of cardiotoxicity of radiotherapy and chemoradiotherapy on overall survival has been documented. Acute arterial and venous thromboembolic events seem to correlate with the degree of the histological malignancy, its clinical advancement, and even with optimal cardiac treatment, they may influence the survival time. In the case of high-grade and advanced lung cancer stage especially in an unresectable stadium, the prognosis depends primarily on the factors related to the histopathological and molecular diagnosis. Electrocardiographic and echocardiographic abnormalities may be prognostic factors, as they seem to correlate with the patient's performance status as well as tumor localization and size.

Echocardiography-Assessed Changes of Left and Right Ventricular Cardiac Function May Correlate with Progression of Advanced Lung Cancer-A Generating Hypothesis Study.

Advanced lung cancer causes damage to lung tissue and the alveolar−capillary barrier, leading to changes in pulmonary circulation and cardiac function. This observational study included 75 patients with inoperable lung cancer. Two echocardiographic assessments were performed: one before the initiation of systemic anticancer therapy and another after the first radiological evaluation of the efficacy of anticancer treatment. In retrospective analysis, diagnosis of early cancer progression was associated significantly (p < 0.05) with some echocardiographic changes: a decrease in EF of at least 5 percentage points (OR = 5.78), an increase in LV GLS of 3 percentage points (OR = 3.81), an increase in E/E' ratio of at least 3.25 (OR = 3.39), as well as a decrease in RV free wall GLS of at least 4 percentage points (OR = 4.9) and an increase in FAC of at least 4.1 percentage points (OR = 4.9). Cancer therapeutics-related cardiac dysfunction was diagnosed in accordance with the definition of the International Cardio-Oncology Society and was found more frequently in patients with radiologically confirmed lung cancer disease progression (p = 0.003). In further prospective studies, the hypothesis about the possible coexistence of the cardiotoxic effect of cancer therapy and cardiac dysfunction related to the progression of inoperable lung cancer should be clarified.

EHA Guidelines on Management of Antithrombotic Treatments in Thrombocytopenic Patients With Cancer.

In cancer patients, thrombocytopenia can result from bone marrow infiltration or from anticancer medications and represents an important limitation for the use of antithrombotic treatments, including anticoagulant, antiplatelet, and fibrinolytic agents. These drugs are often required for prevention or treatment of cancer-associated thrombosis or for cardioembolic prevention in atrial fibrillation in an increasingly older cancer population. Data indicate that cancer remains an independent risk factor for thrombosis even in case of thrombocytopenia, since mild-to-moderate thrombocytopenia does not protect against arterial or venous thrombosis. In addition, cancer patients are at increased risk of antithrombotic drug-associated bleeding, further complicated by thrombocytopenia and acquired hemostatic defects. Furthermore, some anticancer treatments are associated with increased thrombotic risk and may generate interactions affecting the effectiveness or safety of antithrombotic drugs. In this complex scenario, the European Hematology Association in collaboration with the European Society of Cardiology has produced this scientific document to provide a clinical practice guideline to help clinicians in the management of patients with cancer and thrombocytopenia. The Guidelines focus on adult patients with active cancer and a clear indication for anticoagulation, single or dual antiplatelet therapy, their combination, or reperfusion therapy, who have concurrent thrombocytopenia because of either malignancy or anticancer medications. The level of evidence and the strength of the recommendations were discussed according to a Delphi procedure and graded according to the Oxford Centre for Evidence-Based Medicine.

Physical Activity in Pulmonary Arterial Hypertension during Pandemic COVID-19 and the Potential Impact of Mental Factors.

One of the non-pharmacological recommendations for stable patients with pulmonary arterial hypertension (PAH) is to increase physical activity. The study aimed to analyze the degree of physical activity of PAH patients and check if mental factors may have a potential negative impact during the COVID-19 pandemic. Forty patients with stable PAH were included in the study. Physical activity was assessed by pedometer (Omron HJ-321-E) for four weeks. At baseline, in addition to the 6 min walk test (6MWT) and functional assessment, patients completed the quality-of-life questionnaire SF-36, fear of COVID-19 scale, and hospital anxiety and depression scale (HADS). The mean age of the study group was 45.5 years, 80% were women, and 62.5% had idiopathic/heritable PAH. Low physical activity defined as <5000 steps/day had 19 (47.5%), and moderate/high physical activity (≥5000 steps/day) had 21 (52.5%) patients. Patients with low physical activity less frequently worked compared with the moderate−high-activity sub-group, 42% vs. 81%, p = 0.03, and had the shorter distance in 6-6MWT, p = 0.03. There was no significant correlation between steps/day and different mental factors. Almost half of the study group had low activity during the pandemic. Mental factors did not impact physical activity in PAH patients during the pandemic.

Baseline Electrocardiographic and Echocardiographic Assessment May Help Predict Survival in Lung Cancer Patients-A Prospective Cardio-Oncology Study.

Cardiovascular disease and cancer coexist and lead to exertional dyspnea. The aim of the study was to determine the prognostic significance of cardiac comorbidities, ECG and baseline echocardiography in lung cancer patients with varying degrees of reduced performance status. This prospective study included 104 patients with histopathologically confirmed lung cancer, pre-qualified for systemic treatment due to metastatic or locally advanced malignancy but not eligible for thoracic surgery. The patients underwent a comprehensive cardio-oncological evaluation. Overall survival negative predictors included low ECOG 2 (Eastern Cooperative Oncology Group) performance status, stage IV (bone or liver/adrenal metastases in particular), pleural effusion, the use of analgesics and among cardiac factors, two ECG parameters: atrial fibrillation (HR = 2.39) and heart rate >90/min (HR = 1.67). Among echocardiographic parameters, RVSP > 39 mmHg was a negative predictor (HR = 2.01), while RVSP < 21 mmHg and RV free wall strain < −30% were positive predictors (HR = 0.36 and HR = 0.56, respectively), whereas RV GLS < −25.5% had a borderline significance (HR = 0.59; p = 0.05). Logistical regression analysis showed ECOG = 2 significantly correlated with the following echocardiographic parameters: increasing RVSP, RV GLS, RV free wall strain and decreasing ACT, FAC (p < 0.05). Selected echocardiographic parameters may be helpful in predicting poor performance in lung cancer patients and, supplemented with ECG evaluation, broaden the possibilities of prognostic evaluation.

Management of Anticoagulation in Cancer Patients with Atrial Fibrillation.

BACKGROUND: Atrial fibrillation is becoming an increasingly important problem in cardio-oncology. Specific risk factors for atrial fibrillation occurrence include type of cancer disease and anticancer drugs. Anticoagulation is often abandoned. The CHA2DS2-VASc and CHA2DS2 scores may be important not only in predicting stroke but also in mortality. The role of new direct oral anticoagulants is growing, but they need to be used in a personalized approach depending on the risk of unbeneficial interactions with cancer treatment and the risk of bleeding.