Applied Cardio-Oncology in Hematological Malignancies: A Narrative Review.

Applied cardio-oncology in hematological malignancies refers to the integration of cardiovascular care and management for patients with blood cancer, particularly leukemia, lymphoma, and multiple myeloma. Hematological cancer therapy-related cardiotoxicity deals with the most common cardiovascular complications of conventional chemotherapy, targeted therapy, immunotherapy, chimeric antigen receptor T (CAR-T) cell and tumor-infiltrating lymphocyte therapies, bispecific antibodies, and hematopoietic stem cell transplantation. This narrative review focuses on hematological cancer-therapy-related cardiotoxicity's definition, risk stratification, multimodality imaging, and use of cardiac biomarkers to detect clinical and/or subclinical myocardial dysfunction and electrical instability. Moreover, the most common cardiotoxic profiles of the main drugs and/or therapeutic interventions in patients with hematological malignancies are described thoroughly.

Neoplastic pericardial disease in lung cancer: impact on outcomes of different treatment strategies. A multicenter study.

BACKGROUND: Local (intrapericardial) chemotherapy has been reported to be useful for the treatment of neoplastic pericardial disease, but it has never been compared to systemic chemotherapy, a combination of the two and simple pericardial drainage or sclerosis. METHODS: We analyzed the clinical and echocardiographic data of 119 patients, suffering of neoplastic pericarditis due to lung cancer (97 with non-small-cell), comparing the outcomes of four different treatment strategies (extended catheter drainage/sclerosis, systemic chemotherapy, local chemotherapy, and combined - local plus systemic - chemotherapy) at the last available follow-up or at the change of therapy after a treatment failure. The outcomes (based on semiquantitative evaluation of pericardial disease) were classified as complete, partial, no response and progressing disease. RESULTS: A complete response was achieved in 37/53 of patients with combined, in 12/22 with local, in 5/27 with systemic chemotherapy, respectively, and in 4/17 after drainage/sclerosis (p<0.001). Overall response was achieved in 51/53 with combined, 18/22 and 16/27 with local or systemic chemotherapy, respectively, and in 5/17 with drainage/sclerosis only (p<0.001). Survival was significantly better after combined chemotherapy (p<0.001) and 12/53 patients (23%) in this subgroup survived more than 1 year. The overall response rate was higher with intrapericardial cisplatinum than with other agents (98% vs 80%, χ(2)=7.69, p<0.01). CONCLUSIONS: Local chemotherapy, alone or with systemic chemotherapy, is effective in treating pericardial metastases from lung carcinoma, leading to a good control of pericardial effusion in 92% of cases, and to complete disappearance of effusion and masses in 65%. Combined therapy is significantly better than any other treatment. Pericardiocentesis and intrapericardial chemotherapy should be used whenever possible in lung cancer neoplastic pericardial disease, not only in case of tamponade.

Brain natriuretic peptide precursor (NT-pro-BNP) levels predict for clinical benefit to sunitinib treatment in patients with metastatic renal cell carcinoma.

BACKGROUND: Sunitinib is an oral, multitargeted tyrosine kinase inhibitor that has been approved for the treatment of metastatic renal cell carcinoma. Although the majority of sunitinib-treated patients receive a clinical benefit, almost a third of the patients will not respond. Currently there is no available marker that can predict for response in these patients. METHODS: We estimated the plasma levels of NT-pro-BNP (the N-terminal precursor of brain natriuretic peptide) in 36 patients that were treated with sunitinib for metastatic clear-cell renal carcinoma. RESULTS: From the 36 patients, 9 had progressive disease and 27 obtained a clinical benefit (objective response or disease stabilization). Increases in plasma NT-pro-BNP were strongly correlated to clinical outcome. Patients with disease progression increased plasma BNP at statistically significant higher levels than patients that obtained a clinical benefit, and this was evident from the first 15 days of treatment (a three-fold increase in patients with progressive disease compared to stable NT-pro-BNP levels in patients with clinical benefit, p < 0.0001). Median progression-free survival was 12.0 months in patients with less than 1.5 fold increases (n = 22) and 3.9 months in patients with more than 1.5 fold increases in plasma NT-pro-BNP (n = 13) (log-rank test, p = 0.001). CONCLUSIONS: This is the first time that a potential "surrogate marker" has been reported with such a clear correlation to clinical benefit at an early time of treatment. Due to the relative small number of accessed patients, this observation needs to be further addressed on larger cohorts. More analyses, including multivariate analyses are needed before such an observation can be used in clinical practice.

Pericardiectomy for radiation-induced constrictive pericarditis.

INTRODUCTION: Of oncological patients who have undergone chest radiation therapy, 20% develop radiation-induced constrictive pericarditis. The purpose of this study was to review our clinic's experience of such cases, focusing on survival and the functional outcome. METHODS: Six patients with a history of previous radiation therapy, aged 33-61 years, most of whom had symptoms of heart failure, underwent radical (2 patients) or partial (4 patients) pericardiectomy. RESULTS: All patients were completely free of cardiovascular events during the 8 years covered by the study. Among the postoperative complications the most serious was low cardiac output syndrome in 4 patients, which was treated successfully. CONCLUSIONS: Radiation-induced constrictive pericarditis is a clinical entity that should be taken into account in the differential diagnosis of oncological patients who show signs of heart failure. Surgery is the only effective treatment. The results are satisfactory, but always depend on associated damage to the myocardium as a result of radiation and on the underlying cancer.

Evaluation of treatment with bosentan in patients with carcinoid heart disease: single center study.

BACKGROUND: The primary aim of this study was to evaluate a combined therapeutic intervention, including the dual endothelin receptor antagonist bosentan, in patients with carcinoid heart disease (CaHD). The efficacy of the treatment protocol was investigated using serological, echocardiographic, and clinical markers. PATIENTS AND METHODS: Since 2003, 40 patients with neuroendocrine tumours were identified; 14 had echocardiographic findings consistent with CaHD. Six of the 14 patients with CaHD and a New York Heart Association (NYHA) functional class >or= III received bosentan and were eligible for inclusion in this study. RESULTS: N-terminal pro-brain natriuretic peptide (NT-pro-BNP) had decreased 6 months after treatment with bosentan (median: 646 pg/ml vs. 400.5 pg/ml; p = 0.02); the right ventricular systolic pressure had decreased after 3 and 6 months (median: 69 mmHg vs. 61 mmHg, p = 0.02; median: 69 mmHg vs. 48.5 mmHg, p = 0.02); the 6-minute walk distance (6MWD) had significantly improved after 3 and 6 months of treatment (median: 293.5 vs. 406.5 m; p = 0.02; median: 293.5 vs. 578.5 m; p = 0.02). The NYHA functional class improved in 5/6 patients receiving bosentan. CONCLUSIONS: Combined treatment with bosentan is effective in patients with CaHD, based on functional class, 6MWD, and NT-pro-BNP. Further clarification of the CaHD fibrosis pathogenesis is needed to facilitate development of targeted antifibrotic therapeutic agents.

Pro-brain natriuretic peptide is a sensitive marker for detecting cardiac metastases in patients with non-small cell lung cancer.

BACKGROUND: B-type natriuretic peptide (BNP) and N-terminal-pro-BNP (NT-pro-BNP) are important diagnostic tools for patients with suspected cardiac disorders. The aim of this study was to evaluate the predictive value of plasma NT-pro-BNP in identifying cardiac metastases in patients with non-small cell lung cancer (NSCLC) and dyspnoea. PATIENTS AND METHODS: A total of 120 patients, median age 62 years (range 46-83), with NSCLC and dyspnoea were studied. Patients with heart failure or documented coronary artery disease were excluded. Echocardiographic imaging was used to detect cardiac metastases and estimate global left ventricular function. Ejection fraction and E/A ratio from transmitral inflow pattern were calculated. Plasma NT-pro-BNP was also measured. 72 patients (72/120, 60%) with cardiac metastases were identified. RESULTS: NT-pro-BNP was significantly higher in patients with metastases (1347.5 +/- 1004.30 pg/ml vs. 159.02 +/- 93.29 pg/ml; p = 0.001). No differences between groups, regarding s-creatinine (p = 0.45), haemoglobin (p = 0.71), left ventricular hypertrophy (p = 0.91), and diastolic dysfunction (p = 0.79), were observed. CONCLUSION: Plasma NT-pro-BNP is remarkably elevated in patients with NSCLC and myocardial/pericardial infiltrations and may be used as a sensitive marker for detecting cardiac metastases in these patients.

Cardiac tamponade as primary manifestation of angioimmunoblastic T-cell lymphoma (AILT). Coexistence with malignant mesothelioma.

BACKGROUND: Cardiac tamponade (CT) as the primary clinical manifestation of lymphomas is extremely rare. Angioimmunoblastic T-cell lymphoma (AILT) is characterised by systemic disease usually presenting with generalised peripheral lymphadenopathy, hepatosplenomegaly, and bone marrow infiltration. CASE REPORT: We report on a 59-year-old male patient with CT as initial clinical manifestation of AILT. Coexistence with malignant pleural mesothelioma was additionally revealed. Cytologic examination of pericardial fluid presented diffuse lymphoid cells and sporadic malignant mesothelial cells. AILT diagnosis was confirmed by thoracoscopic mediastinal lymph node and bone marrow biopsy. Despite the presence of pleural effusion, the diagnosis of mesothelioma was initially established by cytologic ex-amination of pericardial fluid, due to the patient's critical cardiac condition requiring prompt subxiphoid pericardiocentesis. CONCLUSION: CT as primary clinical manifestation of AILT is very rare. This case reflects the differences in the underlying biology of AILT and consequently the vast spectrum of its clinical presentations. Coexistence of AILT with malignant pleural mesothelioma is also extremely rare.

Intraoperative tracheal reconstruction with bovine pericardial patch following iatrogenic rupture.

INTRODUCTION: Iatrogenic injuries of the membranous trachea have become increasingly common and may trigger a cascade of immediate life-threatening complications. CASE PRESENTATION: A case of a 48-year-old man with an iatrogenic membranous tracheal wall rupture after double-lumen intubation during Ivor Lewis esophagogastrectomy is presented. Tracheal injury was successfully managed surgically with the use of bovine pericardial patch and reinforcement with the gastric conduit which was moved toward the posterior wall of the membranous trachea sealing the wall laceration. CONCLUSION: Our technique was proved to be safe, effective and not technically demanding. Early recognition with prompt surgery is the gold standard of managing such cases, although small tears can be managed conservatively.

Intrapericardial cisplatin administration after pericardiocentesis in patients with lung adenocarcinoma and malignant cardiac tamponade.

INTRODUCTION: Patients with lung adenocarcinoma often suffer from metastatic pericardial effusion that may eventually cause cardiac tamponade. Recurrence of pericardial effusion is frequent after pericardial drainage and therapy for the prevention of fluid reaccumulation is still controversial. We evaluated the safety and effectiveness of the intrapericardial infusion of cisplatin, a substance with antineoplastic and sclerosing properties, after pericardiocentesis in patients with lung adenocarcinoma and malignant cardiac tamponade. METHODS: Twenty-five patients (19 males and 6 females, median age 55 years) with lung adenocarcinoma confirmed by cytological examination and cardiac tamponade were studied. All patients underwent subxiphoid pericardiocentesis through catheter insertion, under electrocardiographic, echocardiographic and haemodynamic guidance. After the malignant aetiology of the pericardial effusion had been confirmed by cytological examination, cisplatin was instilled (10 mg in 20 ml normal saline) into the pericardial cavity during three consecutive days. Clinical and echocardiographic evaluation was performed every month thereafter. RESULTS: Pericardial fluid of 350-1700 ml was removed (median 750 ml) and was haemorrhagic in 80% of the cases. Paroxysmal atrial fibrillation was detected in three patients (12%) and non-sustained ventricular tachycardia in two (8%). None of the patients had hypotension or retrosternal pain. One patient suffered from significant pericardial effusion reaccumulation (4%). Laboratory findings were not influenced by systemic drug absorption in any patient. Transthoracic echocardiographic study revealed pericardial thickening without physiology of constriction in 4 patients (16%). After pericardiocentesis, the mean survival period overall was 4.5 months (range 3-92 weeks), and mortality was attributed to widespread disease (respiratory failure). CONCLUSIONS: Intrapericardial administration of cisplatin is safe and effective in preventing the reaccumulation of malignant pericardial effusion in the majority of patients with lung adenocarcinoma.