Reclassification of Treatment Strategy with Fractional Flow Reserve in Cancer Patients with Coronary Artery Disease.

Background and Objectives: Cancer and coronary artery disease (CAD) often coexist. Compared to quantitative coronary angiography (QCA), fractional flow reserve (FFR) has emerged as a more reliable method of identifying significant coronary stenoses. We aimed to assess the specific management, safety and outcomes of FFR-guided percutaneous coronary intervention (PCI) in cancer patients with stable CAD. Materials and Methods: FFR was used to assess cancer patients that underwent coronary angiography for stable CAD between September 2008 and May 2016, and were found to have ≥50% stenosis by QCA. Patients with lesions with an FFR > 0.75 received medical therapy alone, while those with FFR ≤ 0.75 were revascularized. Procedure-related complications, all-cause mortality, nonfatal myocardial infarction, or urgent revascularizations were analyzed. Results: Fifty-seven patients with stable CAD underwent FFR on 57 lesions. Out of 31 patients with ≥70% stenosis as measured by QCA, 14 (45.1%) had an FFR ≥ 0.75 and lesions were reclassified as moderate and did not receive PCI nor DAPT. Out of 26 patients with <70% stenosis as measured by QCA, 6 (23%) had an FFR < 0.75 and were reclassified as severe and were treated with PCI and associated DAPT. No periprocedural complications, urgent revascularization, acute coronary syndromes, or cardiovascular deaths were noted. There was a 22.8% mortality at 1 year, all cancer related. Patients who received a stent by FFR assessment showed a significant association with decreased risk of all-cause death (HR: 0.37, 95% CI 0.15−0.90, p = 0.03). Conclusions: Further studies are needed to define the optimal therapeutic approach for cancer patients with CAD. Using an FFR cut-off point of 0.75 to guide PCI translates into fewer interventions and can facilitate cancer care. There was an overall reduction in mortality in patients that received a stent, suggesting increased resilience to cancer therapy and progression.

Immune Checkpoint Inhibitor (ICI)-Related Cardiotoxicity.

The growing success of immune checkpoint inhibitors (ICIs) has led to improved outcomes in several types of cancers with studies looking for expanding their indications and use. However immune-related adverse events have been recognized of which myocarditis is associated with a high mortality. Other cardiac events such as arrhythmias, pericardial disease, and coronary atherosclerosis have been observed in patients on ICI therapy. These cardiac toxicities are thought to be the result of increased inflammatory responses after inhibition of specific checkpoint proteins on T cells. Although cardiotoxicities related to immunotherapy are reportedly rare, they can be severe and associated with life-threatening conditions such as fulminant myocarditis, hemodynamic instability, and cardiac arrest. We will review the most commonly reported cardiovascular toxicities associated with ICIs and their management.

Opportunities for improved cardiovascular disease prevention in oncology patients.

PURPOSE OF REVIEW: Cancer patients often have cardiovascular risk factors at the time of cancer diagnosis, which are known to increase the risk of cardiotoxicity. Cancer survivors have significantly higher cardiovascular risk. Current cardiovascular disease prevention guidelines are based on studies that largely excluded these patients. We reviewed recent data regarding cardiovascular disease prevention in this population. RECENT FINDINGS: Nonpharmacologic therapies aiming to reduce 'lifestyle toxicity' produced by cancer treatments have demonstrated potential to decrease the incidence of adverse outcomes. Exercise before, during and after cancer treatment not only promotes higher quality of life and cardiorespiratory fitness but also reduces adverse cardiovascular outcomes. Lipid and cardiometabolic disease management is paramount but predominantly based on data that excludes these populations of cancer patients and survivors. SUMMARY: A comprehensive approach including medical evaluation, prescriptive exercise, cardiac risk factor modification, education, counseling, pharmacologic and behavioral interventions are needed in cancer patients. These interventions constitute the core of cardio-oncology rehabilitation programs, which if implemented appropriately may help reduce cardiovascular events in this population. Knowledge gaps in these areas are starting to be addressed by ongoing clinical trials.

Management strategies and clinical outcomes of acute myocardial infarction in leukaemia patients: Nationwide insights from United States hospitalisations.

BACKGROUND: Patients with leukaemia are at increased risk of cardiovascular events. There are limited outcomes data for patients with a history of leukaemia who present with an acute myocardial infarction (AMI). METHODS: We queried the Nationwide Inpatient Sample (2004-2014) for patients with a primary discharge diagnosis of AMI, and a concomitant diagnosis of leukaemia, and further stratified according to the subtype of leukaemia. Multivariable logistic regression was conducted to identify the association between leukaemia and major acute cardiovascular and cerebrovascular events (MACCE; composite of mortality, stroke and cardiac complications) and bleeding. RESULTS: Out of 6 750 878 AMI admissions, a total of 21 694 patients had a leukaemia diagnosis. The leukaemia group experienced higher rates of MACCE (11.8% vs 7.8%), mortality (10.3% vs 5.8%) and bleeding (5.6% vs 5.3%). Following adjustments, leukaemia was independently associated with increased odds of MACCE (OR 1.26 [1.20, 1.31]) and mortality (OR 1.43 [1.37, 1.50]) without an increased risk of bleeding (OR 0.86 [0.81, 0.92]). Acute myeloid leukaemia (AML) was associated with approximately threefold risk of MACCE (OR 2.81 [2.51, 3.13]) and a fourfold risk of mortality (OR 3.75 [3.34, 4.22]). Patients with leukaemia were less likely to undergo coronary angiography (CA) (48.5% vs 64.5%) and percutaneous coronary intervention (PCI) (28.2% vs 42.9%) compared with those without leukaemia. CONCLUSION: Patients with leukaemia, especially those with AML, are associated with poor clinical outcomes after AMI, and are less likely to receive CA and PCI compared with those without leukaemia. A multi-disciplinary approach between cardiologists and haematology oncologists may improve the outcomes of patients with leukaemia after AMI.

Immune Checkpoint Inhibitors (ICIs)-Related Cardiotoxicity.

The growing success of immune checkpoint inhibitors (ICIs) has led to effectively treating several types of cancers. Even though their use has been associated with the development of cardiac adverse effects, which may decrease the overall survival in cancer patients. These cardiac toxicities are thought to be the result of targeting specific checkpoint proteins on normal myocardial cells leading to over stimulation of the immune system as well as secondary downstream off-target effects on normal tissue.Although cardiotoxicities related to immunotherapy are reportedly rare, they can be severe and associated with life-threatening conditions such as fulminant myocarditis, hemodynamic instability, and cardiac arrest.We will review the most commonly reported cardiovascular toxicities associated with ICIs and their management.

Cardiac toxicities of anticancer treatments: chemotherapy, targeted therapy and immunotherapy.

PURPOSE OF REVIEW: Current oncologic treatments have shown improvement in overall survival in cancer patients. However, the cardiac toxicities of cancer therapeutics, particularly chemotherapy, targeted therapy and immunotherapy can have life-threatening side effects. RECENT FINDINGS: A MEDLINE search for cardiovascular toxicities associated with Federal Drug Administration (FDA)-approved cancer treatments including chemotherapy, targeted therapy and immunotherapy was performed. We included comprehensive articles and research articles establishing the incidence, diagnosis, monitoring and management of cardiovascular toxicities related to cancer treatments until January 2019.This review highlights the mechanisms and epidemiology of cardiotoxicity associated with some cancer treatments. The most common cardiovascular side-effects are discussed at an introductory level with emphasis on those related with the development of heart failure. SUMMARY: Cardiovascular side effects of cancer treatments are common and might affect the survival in cancer patients. Recognition and management of these side effects require understanding of their mechanisms and their clinical manifestations. A multidisciplinary approach with understanding of both the cardiovascular and oncologic risks is necessary in order to provide well tolerated and effective cardio-oncology care.

Phase I Trial of Definitive Concurrent Chemoradiotherapy and Trametinib for KRAS-Mutated Non-Small Cell Lung Cancer.

OBJECTIVE: This phase I trial (NCT01912625) evaluated the safety and pharmacokinetics of definitive concurrent chemoradiotherapy (cCRT) and the radiosensitizer trametinib (MEK1/2 inhibitor) for KRAS-mutated nonmetastatic non-small cell lung cancer (NSCLC). METHODS: Patients received cCRT (carboplatin/paclitaxel and 60 Gy/30 fractions radiotherapy); oral trametinib (7 days/week) commenced on day 1 and completed on the final day of radiotherapy. Dose-finding of trametinib was done using the time-to-event continual reassessment method (TiTE-CRM); dose levels were 0.5mg (level -1), 1mg (initial, level 1), 1.5mg (level 2), and 2mg (level 3). Progression-free (PFS) and overall survival (OS) times were also recorded. RESULTS: Fifteen patients (stage III, variety of KRAS mutations) were treated, with 1/5/4/5 at dose levels -1/1/2/3, respectively. Five patients received dose reductions (n=2, levels 2 and 3; n=1, level 1). Twelve patients completed the full cCRT course. One patient (following 12d trametinib) was taken off protocol for an unrelated/unresolved grade 1 event and later experienced grade 5 sepsis/respiratory failure. There was one grade 4 retinal detachment; grade 3 events included skin rash (n=2) and ventricular dysfunction, pneumonitis, pain, fatigue, and diarrhea (n=1 each). The final dose selected by the TiTE-CRM of trametinib was 1.5 mg. Pharmacokinetic profiles were elucidated and extensively described. At median follow-up of 70 months, median PFS was 11 months and median OS was 38 months. CONCLUSIONS: The MTD for trametinib when combined with cCRT is 1.5 mg, with encouraging preliminary outcomes. This combination merits further study to combine with consolidation durvalumab in non-metastatic KRAS mutant NSCLC.

Trigger related outcomes of takotsubo syndrome in a cancer population.

Background: Takotsubo syndrome (TTS) occurs more frequently in cancer patients than in the general population, but the effect of specific TTS triggers on outcomes in cancer patients is not well studied. Objectives: The study sought to determine whether triggering event (chemotherapy, immune-modulators vs. procedural or emotional stress) modifies outcomes in a cancer patient population with TTS. Methods: All cancer patients presenting with acute coronary syndrome (ACS) between December 2008 and December 2020 at our institution were enrolled in the catheterization laboratory registry. Demographic and clinical data of the identified patients with TTS were retrospective collected and further classified according to the TTS trigger. The groups were compared with regards to major adverse cardiac events, overall survival and recovery of left ventricular ejection fraction (LVEF) and global longitudinal strain (GLS) after TTS presentation. Results: Eighty one of the 373 cancer patients who presented with ACS met the Mayo criteria for TTS. The triggering event was determined to be "cancer specific triggers" (use of chemotherapy in 23, immunomodulators use in 7, and radiation in 4), and "traditional triggers" (medical triggers 22, and procedural 18 and emotional stress in 7). Of the 81 patients, 47 died, all from cancer-related causes (no cardiovascular mortality). Median survival was 11.9 months. Immunomodulator (IM) related TTS and radiation related TTS were associated with higher mortality during the follow-up. Patients with medical triggers showed the least recovery in LVEF and GLS while patients with emotional and chemotherapy triggers, showed the most improvement in LVEF and GLS, respectively. Conclusion: Cancer patients presenting with ACS picture have a high prevalence of TTS due to presence of traditional and cancer specific triggers. Survival and improvement in left ventricular systolic function seem to be related to the initial trigger for TTS.

Cardiac Toxicities Associated with Immune Checkpoints Inhibitors: Mechanisms, Manifestations and Management.

Immune checkpoint inhibitor (ICI) associated cardiovascular adverse events (CVAE) have become more frequent with the growing use of cancer immunotherapy. CVAEs include a wide spectrum of diseases such as myocarditis, pericarditis, heart failure, arrhythmias, coronary artery disease, and hypertension. The induction of cardiovascular side effects by ICI use is hypothesized to occur due to inflammation and immune dysregulation of normal tissue in response to immunotherapy. Management of ICI-associated CVAEs mitigates an overactive immune response by utilizing steroids, immunomodulatory drugs and hemodynamic stabilization. However, few controlled studies on the cardiovascular safety of ICIs exist and treatment of their side effects are mostly from limited case series. Our review seeks to provide the most recent understanding of ICI-associated CVAEs and their management.

Transcatheter and surgical aortic valve replacement impact on outcomes and cancer treatment schedule.

BACKGROUND: Recent data suggest that transcatheter aortic valve replacement (TAVR) for the treatment of severe aortic stenosis (AS) is viable in cancer patients. TAVR may be preferred in cancer patients due to its minimally invasive nature and smaller impact on oncologic therapies compared to SAVR. Objectives We sought to determine if TAVR is an acceptable alternative to SAVR in cancer patients and whether TAVR allows for earlier initiation or resumption of anti-cancer therapies. METHODS: Cancer patients in a tertiary cancer center diagnosed with severe AS were retrospectively included. Patients accepted by the heart team underwent either TAVR or SAVR, while remaining patients received medical therapy alone. Time intervals to initiation of cancer treatment and the impact of cancer treatment on the replaced valves were recorded. Logistic regression was performed to determine the impact of treatment strategy on overall survival (OS) in all 3 subgroups. RESULTS: One hundred and eighty-seven cancer patients diagnosed with severe AS were identified. AVR was associated with better OS compared to medical therapy alone (p < 0.0001). TAVR was associated with better OS at 72 months (HR = 0.468, p < 0.001) compared to medical therapy alone, with no difference in OS observed between SAVR and TAVR. Time intervals to initiation of cancer treatments were shorter in the TAVR group, with no valve deterioration or infection observed in all groups. CONCLUSION: Cancer patients with severe AS benefit from AVR. TAVR is a viable alternative to SAVR in high-risk cancer patients to prolong survival and allow for earlier administration or resumption of anti-neoplastic therapies.

Acute myocardial infarction in a high-risk cancer population: Outcomes following conservative versus invasive management.

BACKGROUND: The benefits of invasive versus noninvasive management in oncology patients with acute myocardial infarction (AMI) are unclear. We aimed to retrospectively determine outcome differences between conservative and invasive management of AMI in cancer patients. METHODS: Patients from our institution between March 2016 and December 2018 with type 1 and type 2 AMI (excluding STEMI) were classified into 2 groups: medical therapy only and invasive strategies. Analyzed outcomes were overall survival (OS), procedural complications, subsequent events, and hospice referral. Kaplan-Meier method and log-rank test were used to compare OS between subgroups. Cox proportional hazards regression analyses were conducted to find factors associated with OS. RESULTS: We included 201 patients. Type 1 MI was seen in 152 patients (76%) and type 2 MI in 49 (24%). Median OS was 13 months. Most presented with symptoms other than dyspnea or chest pain (49%) and with ECG revealing changes other than ST-segment depression and T-wave inversion (62%). Patients with type 2 MI had worse OS than patients with type 1 MI (HR = 2.3, p = 0.0002). Early coronary angiography (≤72 h; HR = 0.327, p < 0.0001), late coronary angiography (>72 h; HR = 0.496, p = 0.0426), and percutaneous coronary intervention (HR = 0.481, p = 0.0116) were associated with better OS than noninvasive approaches. Single and dual agent antiplatelet therapy, beta blockers, and statins were each associated with better OS. CONCLUSIONS: Cancer patients without STEMI who underwent invasive treatment for AMI had better OS compared with those treated only medically, with the highest benefit when coronary angiography was performed within 72 h of admission for AMI.

Immunomodulatory treatment of immune checkpoint inhibitor-induced myocarditis: Pathway toward precision-based therapy.

Immune checkpoint inhibitor (ICI)-induced myocarditis carries a poor prognosis and is not fully understood. Similar to lymphocytic myocarditis and acute cellular rejection in heart transplant, ICI-induced myocarditis requires immune suppressive strategies. We aimed to describe ICI-induced myocarditis by presenting findings of comprehensive cardiovascular evaluations and outcomes of patients following a therapeutic approach similar to autoimmune disorders or allograft transplant rejection, and to discuss the molecular basis of the benefits of immune modulation and statins in ICI-myocarditis. Three patients with ICI-induced myocarditis (2 with positive biopsies and 1 based on cardiac magnetic resonance imaging with negative biopsy) underwent a complete cardiovascular workup, including cardiac catheterization with endomyocardial biopsy. Treatment was with intravenous immunoglobulins (IVIG) and statins in all cases, with additional colchicine (2 cases) or hydroxychloroquine (1 case). Immunohistochemical analysis demonstrated varied subsets of T cells involved in the inflammatory response. Therapy with IVIG and statins led to symptom resolution and cardiac function normalization at 1-month follow-up in all patients. Cancer therapy was resumed in all patients. One patient expired 10 months after the myocarditis episode due to advanced malignancy; two patients were alive, free of heart failure symptoms and cancer progression, at 1-year follow-up, and 1 patient was rechallenged with ICI. We suggest that treatment with IVIG and statins may allow for a prompt resumption of anti-cancer therapy (including ICI) and improve outcomes.

Identifying Hemostatic Thresholds in Cancer Patients Undergoing Coronary Angiography Based on Platelet Count and Thromboelastography.

Objectives: To evaluate the role of platelet count and thromboelastogram (TEG) in the treatment of thrombocytopenic cancer patients with suspected coronary artery disease (CAD). Background: Cancer patients with CAD and thrombocytopenia are often treated non-invasively (i.e., without coronary angiography when clinically indicated) due to perceived high risk of bleeding. We sought to evaluate coagulability based on TEG and determine if platelet count and TEG could predict bleeding risk/mortality among cancer patients undergoing coronary angiography (CA). Methods: Baseline demographics, platelet count, and TEG parameters were recorded among cancer patients that underwent CA and had a concomitant TEG. Logistic regression and univariate proportional hazards regression analysis were performed to determine the impact of platelet count and coagulability on 24-month overall survival (OS). Results: All patients with platelet count <20,000/mm3 and nearly all patients with platelet count 20,000-49,000/mm3 were hypocoagulable based on TEG results. In contrast, nearly all patients with platelet counts of 50,000-99,999/mm3 had normal TEG results and OS similar to those with platelet counts of ≥100,000/mm3. Coagulability based on TEG was not associated with OS. However, a platelet count of <50,000/mm3 was associated with worse 24-month OS (hazard ratio = 2.76; p = 0.0072) when compared with a platelet count of ≥100,000/mm3. No major bleeding complications were observed in all groups. Conclusion: The majority of cancer patients with platelet counts of <50,000/mm3 were hypocoagulable based on TEG and had worse OS at 24 months. The relatively normal TEGs in the >50,000/mm3 groups, as well as the improved survival, suggest that with appropriate clinical indication and risk/benefit assessment, a cut-off of 50,000/mm3 platelets can be considered for CA in cancer patients.

Percutaneous Coronary Intervention and Outcomes in Patients With Lymphoma in the United States (Nationwide Inpatient Sample [NIS] Analysis).

Characteristics and outcomes of patients with lymphoma undergoing percutaneous coronary intervention (PCI) are unknown. Therefore, we analyzed clinical characteristics and outcomes in patients that underwent PCI and had a concomitant diagnosis of Hodgkin's (HL) or non-Hodgkin's (NHL) lymphoma. We analyzed patients with and without lymphoma diagnosis from the Nationwide Inpatient Sample in the United States who underwent PCI procedure during 2004 to 2014. Multivariable regression analysis was performed to examine the association between lymphoma diagnosis and clinical outcomes post-PCI including short-term complications and in-hospital mortality. A total of 7,119,539 PCI procedures were included in the analysis and 18,052 patients had a diagnosis of lymphoma (0.25%). These patients were likely to experience in-hospital mortality (odds ratio [OR] 1.39, 95% confidence interval [CI] 1.25 to 1.54), stroke or transient ischemic attack (OR 1.75, 95% CI 1.61 to 1.90), and any in-hospital complication (OR 1.31, 95% CI 1.25 to 1.37), following PCI. In the lymphoma subtype-analysis, diagnosis of HL was associated with an increased odds of in-hospital death (OR 1.40, 95% CI 1.24 to 1.56), any in-hospital complication (OR 1.31, 95% CI 1.25 to 1.38), bleeding complications (OR 1.12 95% CI 1.05 to 1.20), and vascular complications (OR 1.13 95% CI 1.06 to 1.20) whereas these odds were not significantly associated with non-Hodgkin's diagnosis. Finally, both types of lymphoma were associated with increased odds of stroke/transient ischemic attack following PCI (OR 1.82, 95% CI 1.67 to 1.99 and OR 1.31, 95% CI 1.05 to 1.63, respectively). In conclusion, while the prevalence of lymphoma in the observed PCI cohort was low, a diagnosis of lymphoma was associated with an adverse prognosis following PCI, primarily in patients with the HL diagnosis.

Multimodality imaging in carcinoid heart disease.

Neuroendocrine neoplasms arise from the gastrointestinal tract and can lead to carcinoid syndrome. Carcinoid heart disease affects more than half of these patients and is the initial presentation of carcinoid syndrome in up to 20 % of patients. Carcinoid heart disease typically leads to valve dysfunction, but in rare instances, carcinoid tumours can also metastasise to the endocardium and myocardium. Cardiovascular imaging plays an integral role in the diagnosis and prognosis of carcinoid heart disease. The use of multimodality imaging techniques including echocardiography, cardiac MRI, cardiovascular CT and positron emission tomography have allowed for a more comprehensive assessment of carcinoid heart disease. In this review, we discuss the features of carcinoid heart disease observed on multimodality imaging, indications for obtaining imaging studies and their role in carcinoid heart disease management.

Role of cardiovascular imaging for the diagnosis and prognosis of cardiac amyloidosis.

Cardiac amyloidosis (CA) describes the pathological process of amyloid protein deposition in the extracellular space of the myocardium. Unfortunately, the diagnosis of CA is often made late and when the disease process is advanced. However, advances in cardiovascular imaging have allowed for better prognostication and establishing diagnostic pathways with high sensitivity and specificity. This review discusses the role of echocardiography, cardiac MRI and nuclear cardiology in current clinical practice for diagnosis and prognosis of CA.

Safety of Diagnostic and Therapeutic Cardiac Catheterization in Cancer Patients With Acute Coronary Syndrome and Chronic Thrombocytopenia.

Little data is available on the bleeding risk and outcomes of cancer patients with chronic thrombocytopenia who underwent cardiac catheterization. We sought to assess the safety of coronary angiography, percutaneous coronary intervention, and antiplatelet therapy in cancer patients with acute coronary syndrome (ACS) and chronic thrombocytopenia. We performed a retrospective study of patients with chronic thrombocytopenia who underwent cardiac catheterization for ACS between November 2009 and November 2015. Preprocedural platelet counts were classified into 3 groups: mild thrombocytopenia (50,000 to 100,000/µL), moderate thrombocytopenia (30,000 to 50,000/µL), and severe thrombocytopenia (<30,000/µL). Postprocedural bleeding complications and overall survival (OS) were recorded. A total of 98 patients were included. Mean platelet count on admission was 47.63 ± 29.85 K/µL. Severe thrombocytopenia was identified in 36 patients (36.7%), moderate thrombocytopenia in 20 patients (20.4%), and mild thrombocytopenia in 42 patients (42.9%). Aspirin therapy (alone or in combination with clopidogrel) was used in 66 patients (67.3%), whereas 27 patients (27.6%) were on dual antiplatelet therapy. One procedure-related retroperitoneal hematoma and 3 procedure-related small hematomas were identified. No cerebrovascular events related to the procedure or the antiplatelet therapy were noted. Moderate thrombocytopenia was associated with decreased OS, whereas aspirin, dual antiplatelet therapy, and statin use showed a trend of improved OS. In conclusion, we suggest that coronary angiography and percutaneous coronary intervention can be performed safely in cancer patients with chronic thrombocytopenia. Aspirin therapy and dual antiplatelet therapy should be considered in cancer patients with chronic thrombocytopenia and ACS.

Dynamic and differential changes in myocardial and plasma endothelin in patients undergoing cardiopulmonary bypass.

OBJECTIVE: The bioactive peptide endothelin modulates left ventricular function by changing afterload, coronary vascular tone, and myocardial contractility. However, whether increased plasma endothelin levels observed in patients during and after coronary revascularization and cardiopulmonary bypass reflect actual myocardial interstitial levels are unknown. METHODS: A microdialysis probe (outer diameter: 0.77 mm; length: 4 mm) was placed in the left ventricular apical midmyocardium in 20 patients and myocardial interstitial fluid was collected (2.5 microL/min) at baseline and up to 30 minutes after cardiopulmonary bypass. Myocardial interstitial and systemic arterial endothelin were measured by radioimmunoassay. RESULTS: Baseline myocardial interstitial endothelin was over 6-fold higher than plasma (20.11 +/- 2.07 vs 3.19 +/- 0.25 fmol/mL, P < .05). Plasma endothelin increased by 23% +/- 12% at 60 minutes of cardiopulmonary bypass whereas myocardial interstitial endothelin increased by 105% +/- 24%, P < .05), and this change was higher than in the plasma ( P < .05). Although no further change in plasma endothelin occurred during cardiopulmonary bypass, myocardial interstitial levels increased further after crossclamp removal (400% +/- 75%) and remained significantly higher than plasma at separation from cardiopulmonary bypass. CONCLUSION: The unique findings of this study were 2-fold: First, significant compartmentalization of endothelin exists within the human myocardium. Second, a significantly higher and temporally disparate change in myocardial interstitial endothelin occurs during and after cardiopulmonary bypass when compared with systemic levels. These dynamic changes in myocardial endothelin likely influence coronary vascular tone and contractility.

Chemotherapy and QT Prolongation: Overview With Clinical Perspective.

OPINION STATEMENT: Cardiotoxic adverse events are of concern to physicians treating cancer patients; they are encountered with a variety of agents. Cardiac events may delay the approval of new drugs or impose burdensome monitoring requirements as either part of the pre-approval process or in the daily use of these agents. Among the cardiac issues are the development of QT prolongation and the fear of torsades de pointes (TdP), an unusual yet potentially fatal form of ventricular tachycardia associated with QT prolongation. Several risk factors, including electrolyte imbalance and polypharmacy with concomitant QT prolonging agents use can increase the risk of TdP in cancer patients; separating the individual contributions of the various triggers for TdP remains problematic. Understanding the individual risk of QT prolongation associated with particular chemotherapies can better differentiate between those shown to have higher risk vs. those with lower risk potential. Cardiac monitoring and electrocardiogram analysis require recognition of the common challenges with regard to the precise measurement of the QT interval such as the presence of U waves, intraventricular conduction delays, and heart rate correction. Rapid identification and treatment of QT prolongation and TdP is critical in mitigating the risk of sudden cardiac death in cancer patients. A multidisciplinary treatment approach among cardiologists and oncologists should be employed to help facilitate an appropriate balance between oncologic efficacy and adverse cardiac events.