Advances in cancer therapy have resulted in a steady decline in cancer-related mortality rates since the 1990s. In the United States alone, there are currently approximately 14.5 million cancer survivors, and that number is expected to increase to 20 million by 2021.¹ This growing population is more likely to experience increased cardiovascular morbidity and mortality secondary to cancer treatment (chemotherapy or radiation), which is more than ever before and is generating the call for "onco-cardiology." Although the focus has been on cardiotoxicity, cancer therapies can also cause significant injury to the vasculature, resulting in angina, acute coronary syndromes (ACS), arrhythmias, and heart failure, even independently from a direct myocardial effect. Moreover, cancer is associated with a hypercoagulable state, which increases the risk of acute thrombotic events; thus, the need for invasive evaluation and management in the cardiac catheterization laboratory rises. Unique issues can present, such as procedural timing in relation to oncologic treatment course to address the wide range of comorbid diseases including thrombocytopenia and paraneoplastic disease, difficulties with vascular access, coagulopathies, and a lack of prior outcome-driven data for interventions in this patient population. Often, a combined medical and interventional approach is required in order to best balance the risk-benefit profile of these patients.

The intent of this article is to highlight the challenges posed and tools and methods available to optimize interventional cardiovascular care in patients with cancer.

Pre-Cancer Risk Stratification

Risk stratification of patients with cancer is needed to evaluate and manage short- and long-term effects of different cancer management. Pre-cancer therapy risk stratification serves multiple purposes and allows us to obtain a baseline of cardiovascular disease for further decision-making strategies. History taking and physical examination, along with electrocardiography and echocardiography, represent the initial approach. Complete assessment should follow standing American College of Cardiology and American Heart Association guidelines.² Recently published expert consensus documents recommend pre-chemotherapy cardio-protection with beta-blockers, angiotensin antagonists, statins, or dexrazoxane to decrease cardiotoxicity;³ hypertension to be controlled following Joint National Committee guidelines;⁴ and use of angiotensin-converting enzyme, beta-blockers, aspirin, and statins for patients with coronary artery disease (CAD).^4-6

Invasive Evaluation and Management of CAD in Patients With Cancer

Initial coronary artery anatomy assessment (angiography or computed tomography angiography), including physiology assessment (stress test, cardiac positron emission tomography, and fractional flow reserve [FFR]), seems appropriate in these patients to complete a thorough evaluation.

Diagnostic cardiac catheterization incorporates both imaging and hemodynamic procedures aimed at providing information to document specific cardiovascular disease.⁷ Other techniques have limited ability to evaluate for plaque in the coronary arteries. The importance of FFR-guided management is highlighted below.

Access Site Decision

Vascular complications remain one of the most common adverse outcomes of the procedure and have been recognized as an important factor in morbidity and mortality after cardiac catheterization.⁸ Pseudoaneurysm formation, access-site vein occlusion, hematomas, and arteriovenous fistula have been recognized. Specific characteristics of the patient may affect access site complications:⁴

• Effect of cancer and cancer treatment on the hematopoietic system
• Presence of hypercoagulable state
• Potential interactions between cancer and cardiac drugs

To decrease the occurrence of negative outcomes, the use of ultrasound guidance, micropuncture needles, and fluoroscopic guidance should be considered.⁴ The current recommended approach is highlighted in Figure 1.

Figure 1: Access Site Decision

FFR

In the general population, an FFR ≤ 0.80 indicates a hemodynamically significant stenosis with an accuracy > 90%. De Bruyne et al.,⁹ in the FAME II (Fractional Flow Reserve-Guided Percutaneous Coronary Intervention Plus Optimal Medical Treatment Versus Optimal Medical Treatment Alone in Patients With Stable Coronary Artery Disease) study, evaluated clinical outcomes of patients with CAD treated with optimal medical therapy alone with those who underwent percutaneous coronary intervention (PCI) and received optimal medical therapy. Patients with hemodynamically significant stenosis were included and randomly assigned to both groups. Results showed that patients who underwent PCI and optimal medical therapy had better prognosis, lower rates of urgent revascularization, and a decreased risk of death and myocardial infarction when compared with those who received optimal medical therapy alone. In contrast, with the COURAGE (Clinical Outcomes Utilizing Revascularization and Aggressive Drug Evaluation) trial,¹⁰ the importance of FFR guided-PCI was demonstrated in the treatment of ischemic coronary disease and can help guide coronary revascularization.¹¹ Nascimento¹² et al. have provided further validation of FFR in ischemic coronary disease via a meta-analysis looking at a total of 19 studies, further suggesting safety in deferral of patients with normal FFR and those receiving intervention with an abnormal FFR.

Curzen et al. published a large registry study showing FFR versatility redefining stenosis severity and management strategies for patients referred for diagnostic angiography.¹³ The study showed a change in strategy made in as many as 43% of their patients, whereby a third of a priori medical strategy was changed to revascularization and about half of a priori revascularization strategy was changed to medical therapy.¹³ Similar findings were seen in the RIPCORD (Does Routine Pressure Wire Assessment Influence Management Strategy at Coronary Angiography for Diagnosis of Chest Pain?) study in which FFR results changed management in 26% of the 200 patients with stable chest pain referred for coronary angiography.¹⁴

Intravascular Ultrasound and Optical Coherence Tomography

Because of its higher spatial resolution and imaging of the vascular wall, intravascular ultrasound (IVUS) allows better characterization of luminal processes and earlier detection of procedural-related complications and suboptimal stent expansion compared with conventional angiography.^15,16

Optical coherence tomography (OCT) is capable of characterizing the morphological features of vulnerable plaque, such as a thin fibrous cap, lipid-rich plaque, and thrombus formation.¹⁷ Likewise, it allows identification of stents considered "low risk" and "high risk" for thrombosis according to strut endothelialization under expansion and residual stenosis.¹⁸

A Society for Cardiovascular Angiography and Interventions cardio-oncology consensus document recommends that IVUS and OCT be liberally used to assure adequate stent expansion, apposition, and lack of edge dissection.⁴

Aortic Stenosis and Aortic Valve Replacement

Aortic stenosis (AS) is the third most common cardiovascular disease after CAD and hypertension, especially in the elderly.¹⁹ Aortic valve replacement (AVR) is the only definite treatment to improve survival rates.^20,21 Yusuf et al.¹⁹ retrospectively analyzed patients with cancer and severe AS and measured overall survival among those who had AVR in contrast with those who were treated medically alone; in a multivariable Cox proportional hazard regression analysis, AVR was the only significant predictor of longer survival (adjusted hazard ratio = 0.22, p = .028) (Figure 2).

Figure 2: Kaplan-Meier Plot of Survival by AS Treatment

Transcatheter AVR has been accepted as a Class I indication in patients with severe symptomatic AS.²² Limited data are found in the literature regarding its use in patients with cancer. Stachon et al. evaluated 2-year survival of patients screened for transcatheter AVR with potentially malignant incidental findings in initial body computed tomography and concluded that it didn't influence 2-year survival after a decision to intervene was made.²³

ACS/Takotsubo (Stress) Cardiomyopathy During Cancer Therapy

ACS, and more specifically ST-segment elevation myocardial infarction, has a higher mortality rate in patients with an oncologic diagnosis than those without. In particular, those with a malignancy diagnosed within 6 months of an ST-segment elevation myocardial infarction who undergo PCI have a three-fold higher mortality rate than those diagnosed with a malignancy more than 6 months ago.²⁴ The National Heart, Lung, and Blood Institute ACS registry showed similar findings, with cancer being one of the strongest independent predictors of in-hospital death and 1-year mortality.²⁵

Takotsubo cardiomyopathy has been shown to be associated with malignancies. Pelliccia et al., in a systematic review of more than 1,000 patients with Takotsubo, revealed that the prevalence of this pathology in patients diagnosed with malignancy is 10-20%.²⁶

Recent unpublished data from the MD Anderson Cancer Center comparing Takotsubo cardiomyopathy with non-ST-segment elevation myocardial infarction controls showed that Takotsubo cardiomyopathy could represent a detrimental event in the overall prognosis of the patient with cancer, making this syndrome less benign than previously considered. Median survival in patients with cancer was 30 months (rather than 60 months in patients with non-ST-segment elevation myocardial infarction).

Recurrence risk should be individualized according to the triggering event and co-existing medical condition. Five-year recurrent rates range 5-22%, with the second episode occurring 3 months to 10 years after the first.²⁷

Interventions in Patients With Cancer With Thrombocytopenia (ACS/Pericardiocentesis)

Thrombocytopenia does not protect from ischemic heart disease. ACS have been described in patients with low platelets counts, such as those with thrombotic thrombocytopenic purpura,²⁸ acute and chronic myeloid leukemia,²⁹ and breast cancer.³⁰

Special considerations should be taken for patients with cancer with thrombocytopenia undergoing cardiac catheterization. Society for Cardiovascular Angiography and Interventions consensus recommendations follow (Figure 3):⁴

• Usage of radial artery favored over femoral access. It decreases bleeding risk and increases patient satisfaction.
• Prophylactic platelet transfusion is not recommended routinely and should follow oncology/hematology recommendations (platelet counts <20.000 in the setting of a patient with fever, leukocytosis, rapid fall in platelet count or solid tumors as bladder, gynecologic, or colorectal receiving therapy).
• Platelet transfusion in patients developing bleeding complications during or after the procedure.
• Recommended heparin dose for thrombocytopenic patients undergoing PCI who have platelets <50,000/mL is 30-50 U/kg of unfractionated heparin.
• Aspirin administration may be used when platelet counts are >10,000/mL.
• Dual antiplatelet therapy with clopidogrel may be used in patients with platelet counts 30,000-50,000/mL. Prasugrel, ticagrelor, and IIB-IIIA inhibitors should not be used in patients with platelet counts <50,000.
• If platelet counts are <50,000, the duration of dual antiplatelet therapy may be restricted to 2 weeks following percutaneous transluminal coronary angioplasty alone, 4 weeks after bare-metal stent, and 6 months after second or third generation drug-eluting stents if optimal stent expansion was confirmed by IVUS or OCT.
• There is no minimum platelet count to perform a diagnostic coronary angiogram.

Figure 3

Pericardiocentesis and Low Platelets

Thrombocytopenia has been considered a relative contraindication to pericardiocentesis; however, the use of micropuncture technique and a lateral approach to pericardiocentesis should be considered to decrease bleeding risk in patients with hepatomegaly or in those with unfavorable anatomy.

Combined echocardiographic and fluoroscopic guidance should also be used when possible to increase the safety of the procedure. Platelet transfusion might not modify the overall risk of the procedure due to platelet refractoriness.

References

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Keywords: Acute Coronary Syndrome, Adenosine, Aged, Aneurysm, False, Angina Pectoris, Angioplasty, Balloon, Coronary, Angiotensins, Aortic Valve, Aortic Valve Stenosis, Arrhythmias, Cardiac, Arteriovenous Fistula, Aspirin, Blood Platelets, Breast Neoplasms, Cardiac Catheterization, Cardiomyopathies, Cardiotoxicity, Constriction, Pathologic, Coronary Angiography, Coronary Artery Disease, Dexrazoxane, Drug-Eluting Stents, Echocardiography, Electrocardiography, Exercise Test, Heart Failure, Hematology, Hematoma, Hematopoietic System, Hemodynamics, Heparin, Hepatomegaly, Hydroxymethylglutaryl-CoA Reductase Inhibitors, Hypertension, Leukemia, Myelogenous, Chronic, BCR-ABL Positive, Leukocytosis, Lipids, Myocardial Infarction, Pericardiocentesis, Platelet Count, Platelet Transfusion, Positron-Emission Tomography, Purpura, Thrombotic Thrombocytopenic, Radial Artery, Registries, Regression Analysis, Survival Rate, Takotsubo Cardiomyopathy, Thrombosis, Ticlopidine, Tomography, Optical Coherence

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