Abstract
The discipline of Cardio-Oncology has seen tremendous growth over the past decade. It is devoted to the cardiovascular (CV) care of the cancer patient, especially to the mitigation and ...management of CV complications or toxicities of cancer therapies, which can have profound implications on prognosis. To that effect, many studies have assessed CV toxicities in patients undergoing various types of cancer therapies; however, direct comparisons have proven difficult due to lack of uniformity in CV toxicity endpoints. Similarly, in clinical practice, there can be substantial differences in the understanding of what constitutes CV toxicity, which can lead to significant variation in patient management and outcomes. This document addresses these issues and provides consensus definitions for the most commonly reported CV toxicities, including cardiomyopathy/heart failure and myocarditis, vascular toxicity, and hypertension, as well as arrhythmias and QTc prolongation. The current document reflects a harmonizing review of the current landscape in CV toxicities and the definitions used to define these. This consensus effort aims to provide a structure for definitions of CV toxicity in the clinic and for future research. It will be important to link the definitions outlined herein to outcomes in clinical practice and CV endpoints in clinical trials. It should facilitate communication across various disciplines to improve clinical outcomes for cancer patients with CV diseases.
Graphical Abstract
Graphical Abstract
Outline of the five focus areas of cardiovascular toxicities covered in this definitions document. HF, heart failure.
Purpose
Cardiotoxicity affects 5–16% of cancer patients who receive anthracyclines and/or trastuzumab. Limited research has examined interventions to mitigate cardiotoxicity. We examined the role of ...statins in mitigating cardiotoxicity by performing a systematic review and meta-analysis of published studies.
Methods
A literature search was conducted using PubMed, Embase, Web of Science, ClinicalTrials.gov, and Cochrane Central. A random-effect model was used to assess summary relative risks (RR), weighted mean differences (WMD), and corresponding 95% confidence intervals. Testing for heterogeneity between the studies was performed using Cochran’s
Q
test and the
I
2
test.
Results
Two randomized controlled trials (RCTs) with a total of 117 patients and four observational cohort studies with a total of 813 patients contributed to the analysis. Pooled results indicate significant mitigation of cardiotoxicity after anthracycline and/or trastuzumab exposure among statin users in cohort studies RR = 0.46, 95% CI (0.27–0.78),
p
= 0.004,
I
2
= 0.0% and a non-significant decrease in cardiotoxicity risk among statin users in RCTs RR = 0.49, 95% CI (0.17–1.45),
p
= 0.20,
I
2
= 5.6%. Those who used statins were also significantly more likely to maintain left ventricular ejection fraction compared to baseline after anthracycline and/or trastuzumab therapy in both cohort studies weighted mean difference (WMD) = 6.14%, 95% CI (2.75–9.52),
p
< 0.001,
I
2
= 74.7% and RCTs WMD = 6.25%, 95% CI (0.82–11.68,
p
= 0.024,
I
2
= 80.9%. We were unable to explore publication bias due to the small number of studies.
Conclusion
This meta-analysis suggests that there is an association between statin use and decreased risk of cardiotoxicity after anthracycline and/or trastuzumab exposure. Larger well-conducted RCTs are needed to determine whether statins decrease risk of cardiotoxicity from anthracyclines and/or trastuzumab.
Trial Registration Number and Date of Registration
PROSPERO: CRD42020140352 on 7/6/2020.
Purpose of Review
Immune checkpoint inhibitors (ICIs) have improved the survival of several cancers. However, they may cause a wide range of immune-related adverse events (irAEs). While most irAEs ...are manageable with temporary cessation of ICI and immunosuppression, cardiovascular toxicity can be associated with high rates of morbidity and mortality. As ICIs evolve to include high-risk patients with preexisting cardiovascular risk factors and disease, the risk and relevance of ICI-associated cardiotoxicity may be even higher.
Recent Findings
Several cardiovascular toxicities such as myocarditis, stress cardiomyopathy, and pericardial disease have been reported in association with ICIs. Recent findings also suggest an increased risk of atherosclerosis with ICI use. ICI-associated myocarditis usually occurs early after initiation and can be fulminant. A high index of suspicion is required for timely diagnosis. Prompt treatment with high-dose corticosteroids is shown to improve outcomes.
Summary
Although the overall incidence is rare, ICI cardiotoxicity, particularly myocarditis, is associated with significant morbidity and mortality, making it a major therapy-limiting adverse event. Early recognition and prompt treatment with the cessation of ICI therapy and initiation of high-dose corticosteroids are crucial to improve outcomes. Cardio-oncologists will need to play an important role not just in the management of acute cardiotoxicity but also to reduce the risk of long-term sequelae.
Measurement of the increase in digital pulse volume amplitude (PVA) during reactive hyperemia relative to baseline (PVA-RH) is being applied widely as a convenient test of nitric oxide ...bioavailability. However, evidence linking digital PVA-RH to nitric oxide is currently lacking. Accordingly, we investigated whether nitric oxide is responsible for the increase in digital PVA. During reactive hyperemia, we used a peripheral arterial tonometer to record digital PVA at baseline and during reactive hyperemia. The role of nitric oxide in these responses was investigated in 19 healthy subjects by inhibiting nitric oxide synthesis with N(G)-nitro-L-arginine methyl ester (L-NAME). Ten subjects underwent the identical protocol with saline and five with phenylephrine, a nonspecific vasoconstrictor, instead of L-NAME. The change in digital PVA after drug administration was compared between the three groups. Relative to the response with saline (-5 +/- 2%), baseline PVA was unchanged by L-NAME infusion (-10 +/- 2%), but it decreased significantly with phenylephrine (-50 +/- 12%; P = 0.003). PVA-RH increased slightly with saline infusion (9 +/- 4%). In comparison, PVA-RH was significantly blunted by L-NAME administration (-46 +/- 21%; P = 0.002) and was relatively unchanged by phenylephrine (20 +/- 9%). The present study establishes a central role for nitric oxide in the augmentation of PVA during reactive hyperemia. The measurement of digital PVA-RH may indeed provide a simple means of assessing endothelial function in humans.
Cardiorenal Interactions Nohria, Anju, MD; Hasselblad, Vic, PhD; Stebbins, Amanda, PhD ...
Journal of the American College of Cardiology,
04/2008, Volume:
51, Issue:
13
Journal Article
Peer reviewed
Open access
Cardiorenal Interactions: Insights From the ESCAPE Trial Anju Nohria, Vic Hasselblad, Amanda Stebbins, Daniel F. Pauly, Gregg C. Fonarow, Monica Shah, Clyde W. Yancy, Robert M. Califf, Lynne W. ...Stevenson, James A. Hill Examination of the ESCAPE (Evaluation Study of Congestive Heart Failure and Pulmonary Artery Catheterization Effectiveness) database shows that baseline renal insufficiency impacts outcomes more than worsening renal function (WRF) in patients with advanced decompensated heart failure. Neither baseline renal function nor WRF were explained by measured cardiac hemodynamics. These results suggest that poor forward flow alone does not explain the renal perturbations seen in advanced heart failure. In-hospital hemodynamic optimization using a pulmonary artery catheter–guided treatment strategy does not prevent WRF or improve renal function and short- and long-term outcomes compared with a strategy based on clinical assessment alone.
Background
Radiotherapy (RT) is frequently associated with late cardiovascular (CV) complications. The mean cardiac dose from irradiation of a left‐sided breast cancer is much higher than that for a ...right‐sided breast cancer. However, data is limited on the long‐term risks of RT on CV mortality.
Hypothesis
RT for breast cancer is associated with long term CV mortality and left sided RT carries a greater mortality than right sided RT.
Methods
We searched PubMed, Cochrane Central, Embase, EBSCO, Web of Science, and CINAHL databases from inception through December 2015. Studies reporting CV mortality with RT for left‐ vs right‐sided breast cancers were included. The principal outcome of interest was CV mortality. We calculated summary risk ratio (RR) and 95% confidence intervals (CI) with the random‐effects model.
Results
The analysis included 289 109 patients from 13 observational studies. Women who had received RT for left‐sided breast cancer had a higher risk of CV death than those who received RT for a right‐sided breast cancer (RR: 1.12, 95% CI: 1.07‐1.18, P < 0.001; number needed to harm: 353). Difference in CV mortality between left‐ vs right‐sided breast RT was more apparent after 15 years of follow‐up (RR: 1.23, 95% CI: 1.08‐1.41, P < 0.001; number needed to harm: 95).
Conclusions
CV mortality from left‐sided RT was significantly higher compared with right‐sided RT for breast cancer and was more apparent after ≥15 years of follow‐up.
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