Onco-Hypertension in Patients with Kidney Disease.

BACKGROUND: Cancer, hypertension, and kidney disease are closely interrelated. Knowledge of the potential hypertensive and nephrotoxic effects of antineoplastic medications is critical to minimizing interruptions in cancer treatment. SUMMARY: Antineoplastic medications can cause hypertension, proteinuria, and kidney injury, often mediated by common mechanisms. Notably, inhibitors of the vascular endothelial growth factor pathway have the strongest association with both hypertension and proteinuria, typically acute in onset and often reversible after drug discontinuation. The abrupt rise in blood pressure can cause clinically significant hypertensive syndromes and contribute to overall morbidity. Significant proteinuria can herald kidney failure. Close monitoring of blood pressure and renal function during antineoplastic therapy and appropriate hypertension treatment are important. This article reviews available literature and proposes a step-by-step approach to manage cancer patients with concurrent hypertension and kidney disease. KEY MESSAGES: For antineoplastic medications with known hypertensive effect, blood pressure should be checked at baseline and serially during cancer treatment. Hypertensive crisis with end-organ damage, significant proteinuria, microscopic hematuria, or unexplained acute kidney injury necessitates drug cessation until further evaluation and resolution. In patients with chronic kidney disease and cancer therapy-related hypertension, angiotensin-converting enzyme inhibitor or angiotensin receptor blocker is the preferred antihypertensive choice. Finally, multidisciplinary collaboration in these patients will yield the best results.

Cardiovascular disease and lung cancer.

Lung cancer is the second most common cancer worldwide and the leading cause of cancer-related death. While survival rates have improved with advancements in cancer therapeutics, additional health challenges have surfaced. Cardiovascular disease (CVD) is a leading cause of morbidity and mortality in patients with lung cancer. CVD and lung cancer share many risk factors, such as smoking, hypertension, diabetes, advanced age, and obesity. Optimal management of this patient population requires a full understanding of the potential cardiovascular (CV) complications of lung cancer treatment. This review outlines the common shared risk factors, the spectrum of cardiotoxicities associated with lung cancer therapeutics, and prevention and management of short- and long-term CVD in patients with non-small cell (NSCLC) and small cell (SCLC) lung cancer. Due to the medical complexity of these patients, multidisciplinary collaborative care among oncologists, cardiologists, primary care physicians, and other providers is essential.

Evaluation of Brain Rotational Injury Criteria (BrIC) in vehicle frontal crashes.

OBJECTIVE: The objective of this study was to estimate strains in the human brain in regulatory, research, and due care frontal crashes by simulating those impacts. In addition, brain strain simulations were estimated for belted human volunteer tests and in impacts between two players in National Football League (NFL), some with no injury and some with mild Traumatic Brain Injuries (mTBI). METHODS: The brain strain responses were determined using version 5 of the Global Human Body Modeling Consortium (GHBMC) 50th percentile human brain model. One hundred and sixty simulations with the brain model were conducted using rotational velocities and accelerations of Anthropomorphic Test Devices (ATD's) or those of human volunteers in sled or crash tests, as inputs to the model and strain related responses like Maximum Principal Strains (MPS) and Cumulative Strain Damage Measure (CSDM) in various regions of the brain were monitored. The simulated vehicle tests ranged from sled tests at 24 and 32 kph delta-V with three-point belts without airbags to full scale crash and sled tests at 56 kph and a series of Research Mobile Deformable Barrier (RMDB) tests described in Prasad et al. RESULTS: The severity of rotational input into the model as represented by BrIC, averaged between 0.5 and 1.2 for the various test conditions, and as high as 1.5 for an individual case. The MPS responses for the various test conditions averaged between 0.28 and 0.86 and as high as 1.3 in one test condition. The MPS responses in the brain for volunteers, low velocity sled, and NCAP tests were similar to those in the no-mTBI group in the NFL cases and consistent with real world accident data. The MPS responses of the brain in angular crash and sled tests were similar to those in the mTBI group. CONCLUSIONS: The brain strain estimations do not indicate the likelihood of severe-to-fatal brain injuries in the crash environments studied in this paper. However, using the risk functions associated with BrIC, severe-to-fatal brain injuries (AIS4+) are predicted in several environments in which they are not observed or expected.

Management of hypertension in patients with cancer: challenges and considerations.

The survival rates of many cancers have significantly improved due to recent advancements in cancer screening and therapeutics. Although better cancer outcomes are encouraging, additional health challenges have surfaced, the utmost of which is the burden imposed by various cardiovascular and renal toxicities of anticancer therapies. To improve the overall outcome of patients with cancer, it is essential to understand and manage these treatment-related adverse effects. The cardiovascular side effects of antineoplastic therapies are well-known and include left ventricular dysfunction, heart failure, myocardial ischaemia, QT prolongation, arrhythmia and hypertension. Among these, hypertension is the most common complication, prevalent in about 40% of all cancer patients, yet frequently overlooked and undertreated. This review explores the intricate connection between cancer and hypertension and provides distinct approaches to diagnosing, monitoring and managing hypertension in patients with cancer. We also outline the challenges and considerations that are relevant to the care of patients receiving anticancer drugs with prohypertensive potential.

Case report: Non-thrombotic iliac vein lesion: an unusual cause of unilateral leg swelling in a patient with endometrial carcinoma.

81-year-old female presented with subacute right lower extremity edema due to iliac vein compression by a markedly enlarged external iliac lymph node later identified as newly relapsed metastatic endometrial carcinoma. The patient underwent a full evaluation of the iliac vein lesion and cancer and had an intravenous stent placed with complete resolution of symptoms post-procedure.

Cardiac and noncardiac biomarkers in patients undergoing anthracycline chemotherapy - a prospective analysis.

BACKGROUND: Biomarkers represent a potential tool to identify individuals at risk for anthracycline-induced cardiotoxicity (AICT) prior to symptom onset or left ventricular dysfunction. METHODS: This study examined the levels of cardiac and noncardiac biomarkers before, after the last dose of, and 3-6 months after completion of doxorubicin chemotherapy. Cardiac biomarkers included 5th generation high-sensitivity cardiac troponin T (cTnT), N-terminal pro-brain natriuretic peptide, growth/differentiation factor-15 (GDF-15), and soluble suppression of tumorigenesis-2 (sST2). Noncardiac biomarkers included activated caspase-1 (CASP-1), activated caspase-3, C-reactive protein, tumor necrosis factor-α, myeloperoxidase (MPO), galectin-3, and 8-hydroxy-2'-deoxyguanosine. Echocardiographic data (LVEF and LVGLS) were obtained at pre- and post-chemotherapy. Subanalysis examined interval changes in biomarkers among high (cumulative doxorubicin dose ≥ 250 mg/m2) and low exposure groups. RESULTS: The cardiac biomarkers cTnT, GDF-15, and sST2 and the noncardiac biomarkers CASP-1 and MPO demonstrated significant changes over time. cTnT and GDF-15 levels increased after anthracycline exposure, while CASP-1 and MPO decreased significantly. Subanalysis by cumulative dose did not demonstrate a larger increase in any biomarker in the high-dose group. CONCLUSIONS: The results identify biomarkers with significant interval changes in response to anthracycline therapy. Further research is needed to understand the clinical utility of these novel biomarkers.

Crochet Leads the Way.

The crochetage sign-a notch near the R-wave peak in the inferior leads-in conjunction with right axis deviation, complete or incomplete right bundle branch block, and right ventricular hypertrophy (R/S ratio >1 in lead V1) on 12-lead electrocardiogram are highly suggestive of atrial septal defect. (Level of Difficulty: Intermediate.).

Etiology and Management of Dyslipidemia in Patients With Cancer.

Patients with cancer are now living longer than ever before due to the growth and expansion of highly effective antineoplastic therapies. Many of these patients face additional health challenges, of which cardiovascular disease (CVD) is the leading contributor to morbidity and mortality. CVD and cancer share common biological mechanisms and risk factors, including lipid abnormalities. A better understanding of the relationship between lipid metabolism and cancer can reveal strategies for cancer prevention and CVD risk reduction. Several anticancer treatments adversely affect lipid levels, increasing triglycerides and/or LDL-cholesterol. The traditional CVD risk assessment tools do not include cancer-specific parameters and may underestimate the true long-term CVD risk in this patient population. Statins are the mainstay of therapy in both primary and secondary CVD prevention. The role of non-statin therapies, including ezetimibe, PCSK9 inhibitors, bempedoic acid and icosapent ethyl in the management of lipid disorders in patients with cancer remains largely unknown. A contemporary cancer patient needs a personalized comprehensive cardiovascular assessment, management of lipid abnormalities, and prevention of late CVD to achieve optimal overall outcomes.

Mediastinal irradiation and valvular heart disease.

Anticancer therapy has the potential to cause unwanted cardiovascular side effects. Utilization of radiation therapy to treat tumors near the heart can result in radiation-induced valvular heart disease among other cardiovascular pathologies. The aim of this review is to describe the epidemiology, pathophysiology, risk prediction, non-invasive imaging modalities and management of radiation-induced valvular heart disease with a focus on pre-operative risk assessment and contemporary treatment options.

Atrial fibrillation in older adults with cancer.

Cancer and atrial fibrillation (AF) are common co-morbid conditions in older adults. Both cancer and cancer treatment increase the risk of developing new AF which increases morbidity and mortality. Heart rate and rhythm control along with anticoagulation therapy remain the mainstay of treatment of AF in older adults with both cancer and AF. Adjustments to the treatment may be necessary because of drug interactions with concurrent chemotherapy. Cancer and old age increase the risk of both, thromboembolism and bleeding. The risk of these complications is further enhanced by concomitant cancer therapy, frailty, poor nutrition status and, coexisting geriatric syndromes. Therefore, careful attention needs to be given to the risks and benefits of using anticoagulant medications. This review focuses on the management of AF in older patients with cancer, including at the end-of-life care.

Outcomes of acute pulmonary embolism in hospitalized patients with cancer.

BACKGROUND: Cancer-associated pulmonary embolism (PE) places a significant burden on patients and health care systems. METHODS: A retrospective cross-sectional analysis of the National Inpatient Sample (NIS) database was performed in patients with acute PE from 2002 to 2014. Among patients hospitalized with PE, we investigated the differences in clinical outcomes and healthcare utilization in patients with and without cancer. A multivariate logistic regression model was applied to calculate adjusted odds ratios (OR) to estimate the impact of cancer on clinical outcomes. Wilcoxon rank sum tests were used to determine the differences in healthcare utilization between the two cohorts. RESULTS: Among 3,313,044 patients who were discharged with a diagnosis of acute PE, 84.2% did not have cancer, while 15.8% had cancer as a comorbidity (56% metastatic cancer, 35% solid tumor without metastasis, and 9% lymphoma). Patients with cancer had a higher mean age but lower rates of common comorbidities except for coagulation deficiency than patients without a cancer diagnosis. In patients with cancer, the rate of IVC filter placement was higher (21.7% vs. 13.11%, OR 1.76 (95% CI 1.73-1.79); p < 0.0001) and thrombolytic use lower (1.34% vs. 2.15%, OR 0.68 (95% CI 0.64-0.72); p < 0.0001). Patients with cancer hospitalized for PE had a higher all-cause in-hospital mortality (11.8% vs. 6.6%, OR 1.79 (95% CI 1.75-1.83); p < 0.0001), longer length of stay (6 vs. 5 days; p < 0.0001), higher total charge per hospitalization ($30,885 vs. $27,273; p < 0.0001), and higher rates of home health services upon discharge (35.8% vs. 23.2%; p < 0.0001) compared with those without cancer. CONCLUSION: Concurrent cancer diagnosis in patients hospitalized for acute PE was associated with a 90% increase in all-cause mortality, longer length of stay, higher total charge per hospitalization, and higher rates of home health services upon discharge. The majority (56%) of patients with cancer had metastatic disease. Furthermore, there were identifiable differences in the intervention for acute PE between the two groups.

Etiology and management of hypertension in patients with cancer.

The pathophysiology of hypertension and cancer are intertwined. Hypertension has been associated with an increased likelihood of developing certain cancers and with higher cancer-related mortality. Moreover, various anticancer therapies have been reported to cause new elevated blood pressure or worsening of previously well-controlled hypertension. Hypertension is a well-established risk factor for the development of cardiovascular disease, which is rapidly emerging as one of the leading causes of death and disability in patients with cancer. In this review, we discuss the relationship between hypertension and cancer and the role that hypertension plays in exacerbating the risk for anthracycline- and trastuzumab-induced cardiomyopathy. We then review the common cancer therapies that have been associated with the development of hypertension, including VEGF inhibitors, small molecule tyrosine kinase inhibitors, proteasome inhibitors, alkylating agents, glucocorticoids, and immunosuppressive agents. When available, we present strategies for blood pressure management for each drug class. Finally, we discuss blood pressure goals for patients with cancer and strategies for assessment and management. It is of utmost importance to maintain optimal blood pressure control in the oncologic patient to reduce the risk of chemotherapy-induced cardiotoxicity and to decrease the risk of long-term cardiovascular disease.

Subaortic Membranes in Patients With Hereditary Hemorrhagic Telangiectasia and Liver Vascular Malformations.

Background Patients with hereditary hemorrhagic telangiectasia have liver vascular malformations that can cause high-output cardiac failure (HOCF). Known sequelae include pulmonary hypertension, tricuspid regurgitation, and atrial fibrillation. Methods and Results The objectives of this study were to describe the clinical, echocardiographic, and hemodynamic characteristics and prognosis of hereditary hemorrhagic telangiectasia patients with HOCF who were found to have a subaortic membrane (SAoM). A retrospective observational analysis comparing patients with and without SAoM was performed. Among a cohort of patients with HOCF, 9 were found to have a SAoM in the left ventricular outflow tract by echocardiography (all female, mean age 64.8±4.0 years). The SAoM was discrete and located in the left ventricular outflow tract 1.1±0.1 cm below the aortic annular plane. It caused turbulent flow, mild obstruction (peak velocity 2.8±0.2 m/s, peak gradient 32±4 mm Hg), and no more than mild aortic insufficiency. Patients with SAoM (n=9) had higher cardiac output (12.1±1.3 versus 9.3±0.7 L/min, P=0.04) and mean pulmonary artery pressures (36±3 versus 28±2 mm Hg, P=0.03) compared with those without SAoM (n=19) during right heart catheterization. Genetic analysis revealed activin receptor-like kinase 1 mutations in each of the 8 patients with SAoM who had available test results. The presence of a SAoM was associated with a trend towards higher 5-year mortality during follow-up. Conclusions SAoM with mild obstruction occurs in patients with hereditary hemorrhagic telangiectasia and HOCF. SAoM was associated with features of more advanced HOCF and poor outcomes.

5-Fluorouracil Rechallenge After Cardiotoxicity.

BACKGROUND 5-Fluorouracil (5-FU) is a widely used intravenous chemotherapy agent that is highly effective in the treatment of a variety of solid malignancies. Cardiotoxicity related to 5-FU is a complex clinical entity associated with significant morbidity and mortality. Whether a patient who experienced a major cardiac side effect from 5-FU can be safely rechallenged with this drug is a clinical dilemma. CASE REPORT We present the case of a patient with stage III colorectal adenocarcinoma who experienced ventricular fibrillation during the first cycle of FOLFOX (5-FU, folinic acid, and oxaliplatin) regimen in the adjuvant setting. Post-resuscitation electrocardiogram revealed ST-elevation in the inferior leads with reciprocal changes. Coronary angiogram revealed no obstructive coronary artery disease. Cardiac workup led to the conclusion of probable fluorouracil-induced vasospasm as the cause of his cardiac arrest. He received implantable cardioverter defibrillator. The decision was made to hold 5-FU. At 3-month follow-up, there was evidence of progressive metastasis. After comprehensive risk-benefit discussions, the decision was made for palliative chemotherapy using 5-FU/leucovorin. A pre-treatment regimen including isosorbide dinitrate, diltiazem, and metoprolol was used. The patient tolerated 5-FU rechallenge without recurrent cardiovascular complication. CONCLUSIONS The cardiotoxicity profile of 5-FU can range from anginal chest pain to sudden cardiac death. When considering 5-FU rechallenge, clinicians should adopt a multidisciplinary approach, favor using prophylactic antianginal therapy, change to bolus dosing, and use continuous telemetry monitoring. Screening patients for dihydropyrimidine dehydrogenase deficiency prior to 5-FU administration may facilitate an individualized strategy for optimal dosing and safety.

Cushing syndrome cardiomyopathy: an unusual manifestation of small-cell lung cancer.

Cushing syndrome is a rare cause of dilated cardiomyopathy and heart failure with reduced ejection fraction. Cases describing this association are scarce. We describe a patient presenting with acute heart failure, new cardiomyopathy, refractory hypokalaemia, severe hyperglycaemia, and uncontrolled hypertension who was found to have hypercortisolism secondary to an ectopic adrenocorticotropic hormone-secreting primary lung neoplasm. This case highlights the effects of hypercortisolism on the myocardium. The finding of a non-dilated cardiomyopathy in this case is unique because the majority of previously reported Cushing syndrome cardiomyopathy cases have described left ventricular dilatation or significant left ventricular hypertrophy. In addition, small-cell lung cancer with adrenocorticotropic hormone production causing Cushing syndrome cardiomyopathy is rare.

Metastatic squamous cell carcinoma to the heart: an unusual cause of ST elevation-a case report.

BACKGROUND: Cardiac tumours are typically secondary in nature, and the most common malignancies metastasizing to the heart are cancers of the lung, breast, oesophagus, melanoma, and lymphoma. We present a unique case of squamous cell carcinoma of the tongue, metastasizing to the heart and manifesting with ST elevation in the inferior-leads on electrocardiogram (ECG). CASE SUMMARY: A 25-year-old woman was initially diagnosed with squamous cell carcinoma of the tongue at the age of 23 and treated with hemi-glossectomy with clear-margins. Sixteen months later, the tumour recurred in the oropharynx and the left upper lobe of the lung. She was treated with chemotherapy; however, the tumour progressed. Thus, she was initiated on immunotherapy and radiation therapy. One month later, she presented with chest pain. Electrocardiogram revealed ST elevation in the inferior-leads. Troponin-I was elevated. Transthoracic echocardiogram revealed focal areas of thickening within the left and right ventricular myocardium with associated hypokinesis. These findings suggested ECG changes were likely secondary to infiltrative metastases and not acute-coronary-syndrome. Cardiac magnetic resonance imaging showed infiltrative masses with increased T2-signal and heterogeneous enhancement on perfusion and delayed enhancement sequences. Imaging also demonstrated numerous extra-cardiac metastases. She was treated with analgesics and discharged to home hospice. DISCUSSION: Head and neck cancers are a rare cause of cardiac metastasis. ST elevation and troponin release are thought to be due to tumour extension into the myocardium. Cardiac metastases usually present in patients with advanced widespread malignancy. In a cancer patient with cardiac symptoms or ECG changes, it is important to consider a broad differential diagnosis and entertain the possibility of cardiac metastasis.

Multimodality Imaging of a Right Atrial Cardiac Mass.

Work up of a right atrial mass usually requires multimodality imaging and sometimes a biopsy to affirm histological diagnosis. We present a case of a 74-year-old woman with primary cutaneous melanoma (wildtype BRAF) of the right toe who was found to have a large heterogeneous mass in the right atrium on routine surveillance CT scan. She did not have any cardiac symptoms. Vital signs and physical examination were unremarkable. Cardiac magnetic resonance (CMR) imaging demonstrated a bilobed mass with an intramural component and a mobile blood pool component, with interposed thrombus. Three-dimensional transesophageal echocardiogram (3D-TEE) revealed the mass and its site of attachment on the lateral wall of the right atrium. Given the large size of the tumor and its potential for obstruction of tricuspid inflow, the right atrial mass was surgically resected. Pathology confirmed metastatic melanoma. The patient tolerated cardiac surgery well and was discharged shortly thereafter. In the present case, a large cardiac metastasis was discovered in the absence of clinically detectable disease elsewhere. CMR allowed a comprehensive evaluation of the location, extension, and tissue characterization of the cardiac mass. Transthoracic echocardiogram (TTE) and 3D-TEE allowed assessment of the hemodynamic consequences of this mass and aided in operative planning.

Takotsubo cardiomyopathy in cancer patients.

BACKGROUND: Cancer is a chronic condition that induces significant emotional and physical stress, which may increase the risk for developing Takotsubo cardiomyopathy (TCM). MAIN BODY: Takotsubo cardiomyopathy, also known as stress cardiomyopathy, is a clinical syndrome that generally presents as chest pain mimicking acute coronary syndrome or as an acute heart failure characterized by severe left ventricular systolic dysfunction in response to emotional, physical, or medical stress. The potential triggers for Takotsubo syndrome in cancer patients include the emotional turmoil of a cancer diagnosis, the inflammatory state of the cancer itself, and the physical stress of cancer surgery, systemic anti-neoplastic therapy, and radiation treatment. TCM is becoming increasingly recognized among patients with cancer and has been associated with adverse outcomes in this patient population. In this study, we searched the Pubmed database using keywords "Takotsubo cardiomyopathy", "cancer", and "anti-neoplastic therapy" to review case reports of Takotsubo syndrome occurring in oncologic patients after systemic anti-neoplastic therapy. Clinical presentation, electrocardiogram, laboratory data, transthoracic echocardiogram and coronary angiogram results, and patient outcomes were collected and analyzed. CONCLUSION: Patients with cancer are at an elevated risk for developing stress cardiomyopathy, and it is important to know which cancer drugs have been associated with the development of the Takotsubo syndrome.

Reversible Left Ventricular Systolic Dysfunction Secondary to Pazopanib.

Pazopanib is a tyrosine kinase inhibitor used for the treatment of advanced renal cell carcinoma and advanced soft tissue sarcoma. We describe a case report of a patient with spindle cell sarcoma who developed severe left ventricular systolic dysfunction after starting pazopanib therapy with subsequent recovery of left ventricular ejection fraction upon stopping therapy.