Cardiotoxicity from bruton tyrosine kinase inhibitors (BTKi)-an analysis of an administrative health claims database.

BACKGROUND: First generation Bruton tyrosine kinase inhibitors (BTKi) such as ibrutinib have been associated with cardiovascular toxicities. Newer generation BTKi (e.g.,acalabrutinib and zanabrutinib) have been associated with lower incidence of cardiotoxicity in clinical trials. OBJECTIVE: Given paucity in real-world data on the overall cardiac risk factor profile, especially with the newer BTKi, our study evaluated the incidence of cardiotoxicity with various BTKi among a large, commercially insured population of patients. METHODS: We performed a retrospective cohort analysis of all adults with a diagnosis of B-cell malignancy undergoing treatment with BTKi acalabrutinib and ibrutinib between January 2018 and June 2020 using Optum's de-identified Clinformatics® Data Mart Database. We then identified patients who had pre-existing cardiac disease one year prior to starting BTKi. New incidence of atrial fibrillation/flutter, hypertension, bleeding, ventricular tachycardia/fibrillation and sudden cardiac death from the time of index presciption were compared with standard Chi Square or Student t-test where appropriate. Multivariate logistic regression models were also estimated to evaluate for confounding. RESULTS: A total of 1691 patients were included in the final analysis. 1595 (94%, median age 75 (19-90) years, 61% male gender) patients received ibrutinib, and 96 (6%, median age 73.5 (32-90) years, 62.5% male gender) patients received acalabrutinib. The median duration of drug exposure of ibrutinib was 238 (2-1084) days vs. 150 (30-870) days for acalabrutinib. There was lower new incidence of atrial fibrillation/flutter (4.6%-vs-17%, p = 0.013), hypertension (6.3%-vs-25%, p = NS), sudden cardiac arrest/death (0% vs. 1.5%, p = NS) in the acalabrutinib group compared to ibrutinib, of which only the lower incidence of atrial fibrillation/flutter was statistically significant. This was despite the finding of a higher prevalence of atrial fibrillation/flutter at baseline in patients receiving acalabrutinib. CONCLUSIONS: There was lower incidence of new atrial fibrillation/flutter with acalabrutinib when compared to ibrutinib in a real-world cohort of patients.

Cardiovascular disease and chimeric antigen receptor cellular therapy.

Chimeric antigen receptor T-cell (CAR T) therapy is a revolutionary personalized therapy that has significantly impacted the treatment of patients with hematologic malignancies refractory to other therapies. Cytokine release syndrome (CRS) is a major side effect of CAR T therapy that can occur in 70-90% of patients, with roughly 40% of patients at grade 2 or higher. CRS can cause an intense inflammatory state leading to cardiovascular complications, including troponin elevation, arrhythmias, hemodynamic instability, and depressed left ventricular systolic function. There are currently no standardized guidelines for the management of cardiovascular complications due to CAR T therapy, but systematic practice patterns are emerging. In this review, we contextualize the history and indications of CAR T cell therapy, side effects related to this treatment, strategies to optimize the cardiovascular health prior to CAR T and the management of cardiovascular complications related to CRS. We analyze the existing data and discuss potential future approaches.

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

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

Cardiovascular Magnetic Resonance in Early Detection of Radiation Associated Cardiotoxicity With Chest Radiation.

Background: Chest radiation therapy (RT) is known to be associated with cardiotoxicity. However, the changes in myocardial tissue characterization with radiation-induced cardiotoxicity are not well-understood. Objectives: This study sought to assess the changes in left ventricular function and tissue characterization using cardiovascular magnetic resonance (CMR) in patients receiving RT. Materials and Methods: Between June 2015 and July 2018, we enrolled patients with breast, lung cancer, or lymphoma with plan to receive chest radiation after chemotherapy. CMR was performed using a 1.5T scanner at baseline and 6 months after RT. Myocardial volume, function, strain analysis using feature tracking, and tissue characterization including late gadolinium enhancement (LGE), T1, T2, T1ρ (rho), and extracellular volume fraction (ECV) were measured and compared using non-parametric methods. Results: The final cohort consisted of 16 patients, 11 of whom completed both baseline and follow-up CMRs. Patients were matched to 10 healthy controls. At baseline prior to RT, compared to controls, patients had lower global circumferential strain (GCS) (15.3 ± 2.2% vs.18.4 ± 2.1%, p = 0.004), and elevated T2 (47.9 ± 4.8 ms vs. 45.0 ± 1.5 ms, p = 0.04) and T1ρ values (78.4 ± 5.9 vs. 66.9 ± 4.6 ms, p < 0.001). Two patients had LGE. There was no significant difference in the average T1 values or ECV. There was a trend toward lower LV ejection fraction and global longitudinal strain (GLS). At 6-month follow-up after RT, there were no significant changes in all the CMR parameters. Conclusion: At 6-month following chest radiation therapy, there was no change in LV and RV EF, LV and RV GLS, LV GCS, and myocardial tissue characterization using LGE, T1, ECV, T2, and T1ρ in a small cohort of patients. However, the baseline T2 and T1ρ were elevated and LV GCS was reduced compared to controls indicating ongoing myocardial edema and subclinical dysfunction post-chemotherapy.

Cardiotoxicity of Systemic Melanoma Treatments.

OPINION STATEMENT: Melanoma is the least common but most dangerous skin cancer, accounting for 75% of all deaths from a primary cutaneous malignancy, with incidence rates rising significantly over the last decade. Traditional treatments for melanoma including interferon and cytotoxic chemotherapy had marginal efficacy. With the advent of targeted and immunotherapies, the prognosis for patients with advanced melanoma has significantly improved including those with metastatic disease to the heart. BRAF and MEK inhibitors as well as immune checkpoint inhibitors have become front line therapy for eligible patients with metastatic melanoma and have led to long-term durable response and in some cases can be curative. Despite these oncologic advances, various treatment-limiting side effects can occur. In particular, cardiovascular toxicities can contribute to overall morbidity and mortality in these patients. Toxicities range from asymptomatic QT prolongation and mild LV dysfunction to fulminant myocarditis and potentially life-threatening arrhythmias. A multidisciplinary approach to the care of these patients which includes cardio-oncology evaluation is necessary to develop both risk mitigation and treatment strategies to ensure patients continue receiving necessary and effective melanoma treatments while minimizing long-term adverse cardiovascular effects.

Prevalence and Significance of Patient Prosthesis Mismatch Following Edwards SAPIEN XT and SAPIEN 3 Transcatheter Aortic Valve Replacement.

Background Severe patient prosthesis mismatch (sPPM) after surgical aortic valve replacement is associated with worse outcomes. Limited data exists on the impact of sPPM on outcomes after transcatheter aortic valve replacement (TAVR), especially regarding the newer generation valves. The aim of this study was to evaluate the incidence, determinants, and outcomes of sPPM in patients undergoing TAVR with Edwards SAPIEN XT (ES XT) and Edwards SAPIEN 3 (ES3) valves (Edwards Lifesciences, Irvine, CA, USA). Methods We retrospectively reviewed 366 patients who underwent TAVR with ES XT (n = 114) or ES3 (n = 252) valves between July 2012 and June 2018. sPPM was defined as indexed effective orifice area (iEOA) <0.65 cm2/m2. Kaplan-Meier survival estimates were used to determine outcomes. Results Multivariate linear regression analysis was utilized to determine potential independent effects of PPM on outcomes. sPPM was present in 40 (11%) of the patients [8 (7%) ES XT and 32 (13%) ES3] and was associated with female sex, smaller left ventricular outflow tract (LVOT) diameter and aortic valve annular area, absence of prior coronary artery bypass graft (CABG) surgery, shorter height, higher body mass index, and smaller pre-TAVR valve area (all p < 0.05). Among those with ES3 valves, the incidence of sPPM was inversely proportional to the valve size (50%, 25%, 5% and 3% for 20-, 23-, 26- and 29-mm valve sizes, respectively; p < 0.001). At a mean follow-up period of 3.5 ± 1.5 years, there was no difference in all-cause mortality (22.5% vs. 25.6%, p = 0.89) or a composite endpoint of heart failure, arrhythmias, stroke, and myocardial infarction (30% vs. 34%, p = 0.24) in those with or without sPPM. Conclusion ES3 was associated with a higher incidence of sPPM, particularly with smaller valve sizes. However, the presence of sPPM as defined by iEOA was not an independent predictor of adverse outcomes in patients undergoing TAVR within an intermediate follow-up period.

Massive left ventricular thrombosis in pericardial decompression syndrome.

BACKGROUND: Pericardial decompression syndrome (PDS) is defined as paradoxical hemodynamic deterioration associated with left, right, or bi-ventricular dilation and systolic dysfunction following pericardiocentesis. It is uncommon yet under-recognized, underreported, and associated with significant morbidity and mortality. CASE REPORT: We report a unique case of PDS associated with left ventricular (LV) systolic dysfunction and massive apical thrombosis following surgical removal of 800 ml of pericardial fluid in a 72-year-old man with undiagnosed lung cancer. Treatment with anticoagulation and anti-remodeling medications resulted in complete resolution of the thrombus and recovery of LV function. CONCLUSIONS: PDS, although rare, can lead to significant morbidity and mortality. Left ventricular apical thrombosis could result from PDS in the setting of hypercoagulable state. Treatment of the underlying disease may lead to successful resolution of PDS and its complications.

Role of cardiovascular magnetic resonance in early detection and treatment of cardiac dysfunction in oncology patients.

The purpose of this review is to provide an overview of the essential role that cardiovascular magnetic resonance (CMR) has in the field of cardio-oncology. Recent findings: CMR has been increasingly used for early identification of cancer therapy related cardiac dysfunction (CTRCD) due to its precision in detecting subtle changes in cardiac function and for myocardial tissue characterization. Summary: CMR is able to identify subclinical CTRCD in patients receiving potentially cardiotoxic chemotherapy and guide initiation of cardio protective therapy. Multiparametric analysis with myocardial strain, tissue characterization play a critical role in understanding important clinical questions in cardio-oncology.

Marijuana: A systems-based primer of adverse effects associated with use and an overview of its therapeutic utility.

Marijuana use is on the rise in the United States. By the end of 2019, 33 states have legalized marijuana use and marijuana byproduct use for medical purposes. However, marijuana use does not come without side effects. This manuscript reviews the increasing usage of marijuana and the different forms (natural and synthetic) that patients may use when presenting to clinicians. It also addresses the biochemical and behavioral changes observed with marijuana use, including the location and changes associated with cannabinoid receptors (abbreviated CB1 and CB2). These two topics lead into an extensive review of the side effects of marijuana use. This manuscript discusses gastrointestinal side-effects, such as Cannabinoid Hyperemesis Syndrome, pancreatitis, and hepatotoxicity. It also briefly reviews cardiovascular, neurologic, and pulmonary side effects. This article provides an overview of therapeutic effects of marijuana including the antiemetic effect, its medical utility as an appetite stimulant, and usefulness in cancer patients post-chemotherapy. A thorough social history pertaining to marijuana use is an important consideration for clinicians in patients presenting with a variety of symptoms, including those effecting the gastrointestinal, cardiovascular, pulmonary, or neurologic systems.

Cardiac Amyloidosis for the Primary Care Provider: A Practical Review to Promote Earlier Recognition of Disease.

Cardiac amyloidosis is increasingly recognized as an underdiagnosed cause of heart failure. Diagnostic delays of up to 3 years from symptom onset may occur, and patients may be evaluated by more than 5 specialists prior to receiving the correct diagnosis. Newly available therapies improve clinical outcomes by preventing amyloid fibril deposition and are usually more effective in early stages of disease, making early diagnosis essential. Better awareness among primary care providers of the clinical presentation and modern treatment landscape is essential to improve timely diagnosis and early treatment of this disease. In this review, we provide practical guidance on the epidemiology, clinical manifestations, diagnostic evaluation, and treatment of transthyretin and light chain cardiac amyloidosis to promote earlier disease recognition among primary care providers.

Stress cardiomyopathy induced during dobutamine stress echocardiography.

BACKGROUND: Catecholamines play a central role in pathogenesis of stress cardiomyopathy (SC). We aimed to review the clinical characteristics, procedural details and outcomes of patients with SC during dobutamine stress echocardiography (DSE). METHODS/RESULTS: A total of 20 adults [age 64±15 years, 80% women, 67% hypertension, 20% diabetes, 33% hypercholesterolemia, 19% chronic kidney disease, 13% known anxiety disorder] with SC during DSE were identified from local digital archives of our laboratory (n=3) or reports in English literature (n=17). Indication for DSE was suspected coronary artery disease (CAD) in all patients. Left ventricular (LV) ejection fraction was normal at baseline. SC developed at a blood pressure of 154±47/86±24 mmHg, heart rate of 130±17 bpm (88±10% predicted maximum) and peak rate-pressure product of 20559±3898 mmHg*bpm. ST segment elevation was seen in 65%. SC occurred at peak dobutamine infusion rate of 38±6 µg/kg/min in 85% and during recovery in 15%. Atropine [0.7±0.6 (0.25-2) mg] was given to 7 patients. LV ejection fraction dropped to 30±6% with apical (40%), apical and mid (45%) or basal and mid (10%) circumferential LV ballooning. One patient (5%) had a mixed pattern of wall motion abnormality. LV outflow tract obstruction developed in 15%. Major adverse cardiac events occurred in 7 (35%) and included death (n=1), congestive heart failure (n=2), hypotension (n=3) and atrial fibrillation with heart failure (n=1). At a mean follow up duration of 19±19 days, complete or partial recovery of LV wall motion abnormality was seen in 18 and 1 patient, respectively. CONCLUSION: SC uncommonly occurs during DSE. However, death and other adverse events (hypotension, heart failure and atrial fibrillation) may occur and require urgent attention. Once managed, complete recovery is expected in most patients.

Cannabis-induced basal-mid-left ventricular stress cardiomyopathy: A case report.

Cannabis, popularly known as marijuana, is a recreational drug derived from the plant Cannabis Sativa. It has been recognized as the most widely used mood-altering substance in the world and is falsely perceived as a safe substance by the public at large. This is mostly due to lack of awareness of its adverse effects as well as successful attempts for legalization of its use in many states. We present a unique case of a 56-year-old man who presented with neurological deficits concerning for stroke. Soon after presentation, he required endotracheal intubation for airway protection due to worsening mental status changes and pulmonary edema. Echocardiogram revealed severe hypokinesis of the basal and mid-left ventricular (LV) walls with hyperdynamic motion of the apex (reverse takotsubo). Coronary angiography revealed no obstructive disease. Urine toxicology screen was positive for Δ-9-tetrahydrocannabinol. The patient then stated to have used excess marijuana before the symptom onset, while denying any recent emotional stressors. The findings were consistent with stress cardiomyopathy (SC) triggered by marijuana use. Myocardial infarction, stroke, and peripheral arteriopathy have been increasingly reported in younger individuals using marijuana. SC appears to be another unique complication of marijuana use triggered through its effects on the autonomic nervous and endocannabinoid systems.

COVID-19 and Hypercoagulability: A Review.

Thrombotic complications of the novel coronavirus (COVID-19) are a concerning aspect of the disease, due to the high incidence in critically ill patients and poor clinical outcomes. COVID-19 predisposes patients to a hypercoagulable state, however, the pathophysiology behind the thrombotic complications seen in this disease is not well understood. Several mechanisms have been proposed and the pathogenesis likely involves a host immune response contributing to vascular endothelial cell injury, inflammation, activation of the coagulation cascade via tissue factor expression, and shutdown of fibrinolysis. Treatments targeting these pathways may need to be considered to improve clinical outcomes and decrease overall mortality due to thrombotic complications. In this review, we will discuss the proposed pathophysiologic mechanisms for thrombotic complications in COVID-19, as well as treatment strategies for these complications based on the current literature available.

Transbronchial Needle Aspiration Cytology and Purulent Pericarditis.

Endobronchial ultrasound with transbronchial needle aspiration (TBNA) is commonly performed for the evaluation of mediastinal lymphadenopathy. Purulent pericarditis is a rare, yet potentially fatal complication of TBNA. It commonly presents with nonspecific symptoms such as chest pain, shortness of breath, palpitations, or vague abdominal discomfort. Additionally, more severe symptoms such as cardiac tamponade and even death have been reported. In this article, we present the case of a 58-year-old male who developed purulent pericardial effusion with tamponade thought to be caused by TBNA cytology. This case raises an important question regarding the current guidelines for prophylactic antibiotic treatment for patients at high risk of developing purulent pericarditis as a complication of TBNA.

Commissural fusion as etiology of bioprosthetic mitral stenosis in a patient with rheumatic heart disease.

We report commissural fusion as a unique morphologic etiology of early bioprosthetic mitral valve failure in a woman with a history of rheumatic mitral stenosis. She had undergone mitral valve replacement with a 25-mm Edwards Magna Ease bovine pericardial bioprosthesis 3 years earlier and presented with progressive dyspnea. Transesophageal echocardiography revealed severe bioprosthetic stenosis due to commissural fusion. She underwent percutaneous valve-in-valve implantation with a 26-mm Edwards Sapien 3 prosthesis. Marked symptomatic improvement was noted postprocedurally. We speculate that commissural fusion may be a unique pathologic feature of failing bioprosthetic valves in patients with prior rheumatic mitral valve disease.

Recent trends in hospital admissions and outcomes of cardiac Chagas disease in the United States.

BACKGROUND: Chagas disease (CD), caused by Trypanosoma cruzi, has been increasingly encountered as a cause of cardiovascular disease in the United States. We aimed to examine trends of hospital admissions and cardiovascular outcomes of cardiac CD (CCD). METHODS: Search of 2003-2011 Nationwide Inpatient Sample database identified 949 (age 57±16 years, 51% male, 72.5% Hispanic) admissions for CCD. RESULTS: A significant increase in the number of admissions for CCD was noted during the study period (OR=1.054; 95% CI=1.028-1.081; P< 0.0001); 72% were admitted to Southern and Western hospitals. Comorbidities included hypertension (40%), coronary artery disease (28%), hyperlipidemia (26%), tobacco use (12%), diabetes (9%), heart failure (5%) and obesity (2.2%). Cardiac abnormalities noted during hospitalization included atrial fibrillation (27%), ventricular tachycardia (23%), sinoatrial node dysfunction (5%), complete heart block (4%), valvular heart disease (6%)] and left ventricular aneurysms (5%). In-hospital mortality was 3.2%. Other major adverse events included cardiogenic shock in 54 (5.7%), cardiac arrest in 30 (3.2%), acute heart failure in 88 (9.3%), use of mechanical circulatory support in 29 (3.1%), and acute stroke in 34 (3.5%). Overall, 63% suffered at least one adverse event. Temporary (2%) and permanent (3.5%) pacemakers, implantable cardioverter defibrillators (10%), and cardiac transplant (2.1%) were needed for in-hospital management. CONCLUSIONS: Despite the remaining concerns about lack of awareness of CCD in the US, an increasing number of hospital admissions were reported from 2003-2011. Serious cardiovascular abnormalities were highly prevalent in these patients and were frequently associated with fatal and nonfatal complications.

Cardiac transplantation for hypertrophic cardiomyopathy in the United States 2003-2011.

BACKGROUND: Cardiac transplant (CT) is the sole option in a minority of hypertrophic cardiomyopathy (HC) adults with refractory symptoms or end-stage disease. AIMS/METHODS: We aimed to examine the trends and hospital outcomes of CT in HC using 2003-2011 Nationwide Inpatient Sample database. RESULTS: HC comprised 1.1% of CT (151 of 14,277) performed during this time period (age 45±12 years, 67% male, 79% Caucasians). Number of HC CT increased from 2003 to 2011 (odds ratio=1.174; 95% confidence interval=1.102-1.252; P< 0.001). Comorbidities included congestive heart failure (76%), hypertension (23%), chronic kidney disease (23%), hyperlipidemia (19%), diabetes (13%), and coronary artery disease (10%). Acute in-hospital major adverse events occurred in 1 in 4 (23%) patient and 1 in 25 (3.8%) patients died perioperatively. Other major adverse events included allograft rejection or vasculopathy (23%), postoperative stroke or transient ischemic attack (3.5%), acute renal failure (43%), respiratory failure requiring mechanical ventilation (13%), sepsis (10%) or need for blood transfusion (10%). Compared to 1990-2004 United Network of Organ Sharing registry data (n=303), patients in current cohort had more comorbid conditions [diabetes (13%-vs-0%); chronic obstructive lung disease (9%-vs-1%); P < 0.001 for both), were more likely to be male (66%-vs-48% P< 0.001), were less likely to be Caucasian (79%-vs-86%; P < 0.001) or smokers (3%-vs-17%; P < 0.001) and less often required perioperative circulatory support or hemodialysis (17%-vs-49%, P < 0.001 and 3.2%-vs-8.3%, P = 0.04, respectively). CONCLUSION: HC comprises a small proportion of patients undergoing CT. The annual number of CT in HC has increased in recent years at least in part due to inclusion of patients with more comorbid conditions. Transplant recipients in the current cohort, however, required less postoperative circulatory support or renal replacement therapy.

Cardiovascular involvement by osteosarcoma: an analysis of 20 patients.

BACKGROUND: Although hematogenous spread of osteosarcoma is well known, the imaging findings of cardiovascular involvement by osteosarcoma are seldom reported and can be difficult to recognize. The enhanced resolution of modern CT and MRI scanners may lead to better detection of cardiovascular involvement. OBJECTIVE: To describe the key imaging findings and clinical behavior of cardiovascular involvement by osteosarcoma. MATERIALS AND METHODS: We retrospectively reviewed the imaging findings and clinical characteristics of 20 patients with cardiovascular involvement by osteosarcoma identified by two pediatric radiologists from a review of imaging studies at our institution from 2007 to 2013. RESULTS: At initial diagnosis, the median age of the patients was 15.1 years (range 4.8-24.6 years), and 7 (35%) patients had detectable metastases. Median time to detection of cardiovascular metastases was 1.8 years (range 0-7.3 years). Sixteen patients died of disease; 4 have survived a median of 7.4 years since initial diagnosis. The sites of cardiovascular involvement were the systemic veins draining the primary and metastatic osteosarcoma, pulmonary arteries, pulmonary veins draining the pulmonary metastases, and heart. A dilated and mineralized terminal pulmonary arteriole is an early sign of metastatic osteosarcoma in the lung. Unfamiliarity with the imaging features resulted in under-recognition and misinterpretation of intravascular tumor thrombus as bland thrombus. CONCLUSION: Knowledge of imaging findings in the era of modern imaging modalities has enhanced our ability to detect cardiovascular involvement and lung metastases early and avoid misinterpreting tumor thrombus in draining systemic veins or pulmonary arteries as bland thrombus.