This study sought to define the risk of stent thrombosis (ST) and myocardial infarction (MI) in cancer patients compared with noncancer patients after percutaneous coronary intervention (PCI).
Cancer ...patients are considered to be at high thrombotic risk, but data on whether this is the case after PCI remain inconclusive.
Cancer patients undergoing PCI at Mayo Clinic Rochester from January 1, 2003, to December 31, 2013, were identified by cross-linking institutional cancer and PCI databases and by propensity score matching to noncancer patients. The combined primary endpoint was all-cause mortality, MI, and revascularization rate at 5-year follow-up. Secondary endpoints were the individual primary endpoint components, cause of mortality, ST, and Bleeding Academic Research Consortium 2+ bleeding.
The primary endpoint occurred in 48.6% of 416 cancer and in 33.0% of 768 noncancer patients (p < 0.001). In competing risk analyses, cancer patients had a higher rate of noncardiac death (24.0% vs. 10.5%; p < 0.001) and a lower rate of cardiac death (5.0% vs. 11.7%; p < 0.001). Cancer patients had a higher rate of MI (16.1% vs. 8.0%; p < 0.001), ST (6.0% vs. 2.3%; p < 0.001), repeat revascularization (21.2% vs. 10.0%; p < 0.001), and bleeding (6.7% vs. 3.9%; p = 0.03). The most critical period for ST in cancer patients was in the first year after PCI. The dual antiplatelet therapy score was predictive of thrombotic and ischemic events in both groups.
Cancer patients have a higher risk of thrombotic and ischemic events after PCI, identifiable by a high dual antiplatelet therapy score. These findings have important implications for antiplatelet therapy decisions.
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Out-of-hospital cardiac arrest (OHCA) is frequently triggered by acute myocardial ischemia. Coronary angiography is an important component of post-resuscitation care for patients with OHCA without an ...evident noncardiac cause, to identify underlying coronary artery disease and allow revascularization. Most patients undergoing coronary angiography after OHCA have obstructive coronary artery disease, and nearly one-half of patients have acute coronary occlusion. Early coronary angiography and percutaneous coronary intervention after OHCA have been associated with improved survival in observational studies, but these studies demonstrate selection bias, and randomized trials are lacking. Selection of patients for coronary angiography after OHCA can be challenging, particularly in comatose patients whose outcomes are driven primarily by anoxic brain injury. As for other patients with acute coronary syndromes, patients with ST-segment elevation after OHCA have a high probability of acute coronary occlusion warranting emergent coronary angiography. Patients with cardiogenic shock after OHCA are a high-risk population also requiring emergent coronary angiography. Among patients in stable condition after OHCA without ST-segment elevation, other clinical predictors can be used to identify those needing early coronary angiography to identify obstructive coronary artery disease. Despite the challenges with early neurological prognostication in comatose patients with OHCA, those with multiple objective markers of poor prognosis appear less likely to benefit from revascularization, and early coronary angiography may be reasonably deferred in appropriately selected patients meeting these criteria. The authors propose an algorithm to guide patient selection for coronary angiography after OHCA that combines clinical predictors of acute coronary occlusion and early clinical predictors of severe brain injury.
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•Coronary artery disease is the leading cause of out-of-hospital cardiac arrest (OHCA), and both early coronary angiography and percutaneous coronary intervention have been associated with improved survival after OHCA.•Guidelines recommend immediate coronary angiography for OHCA patients with ST-elevation myocardial infarction, cardiogenic shock or recurrent ventricular arrhythmias, and consideration should be given to performing coronary angiography for all OHCA patients without an apparent noncardiac arrest etiology.•The decision to perform early coronary angiography for OHCA patients should balance the potential benefit of treating a coronary culprit lesion with the possibility of severe anoxic brain injury which could mitigate this benefit. Ongoing randomized clinical trials will provide needed evidence to guide these clinical decisions.
Purpose of Review
Cancer patients nearly universally experience a decline in quality of life, with fatigue and reduced exercise tolerance as cardinal reflections. A routine exercise program can ...improve these signs and symptoms as well as overall outcomes. The review provides an updated overview of the field and its translation to clinical practice.
Recent Findings
A wealth of clinical studies have documented the safety and benefits of exercise after and during cancer therapy, and pilot and larger-scale studies are currently ongoing to integrate exercise into the treatment program for cancer patients undergoing active therapy (EXACT pilot, OptiTrain, and TITAN study). More recently, efforts have emerged to commence exercise programs before the start of cancer therapy, so-called pre-habilitation. The concept of increasing the cardiovascular reserve beforehand is intuitively attractive. In agreement, preclinical studies support exercise as an effective preventive means before and during cardiotoxic drug exposure. Assuming that a pronounced drop in exercise tolerance will occur during cancer therapy, pre-habilitation can potentially curtail or raise the nadir level of exercise tolerance. Furthermore, such efforts might serve as pre-conditioning efforts in reducing not only the nadir, but even the magnitude of drop in cardiovascular reserve. Initiated beforehand, cancer patients are also more likely to continue these efforts during cancer therapy. Finally, an active exercise routine (≥ 150 min/week moderate intensity or ≥ 75 min/week vigorous intensity or combination) in conjunction with the other six American Heart Association’s cardiovascular health metrics (BMI < 25 kg/m
2
, blood pressure < 120/80 mmHg, fasting plasma glucose < 100 mg/dL, total cholesterol < 200 mg/dL, 4–5 component healthy diet, no smoking) reduces not only the cardiovascular but also the cancer disease risk.
Summary
Exercise can reduce the risks of developing cancer, the detrimental effects of its treatment on the cardiovascular system, and overall morbidity and mortality. Exercise should become an integral part of the care for every cancer patient.
Furthermore, a very recent report indicates that coronary microvascular dysfunction is still evident in 90% of patients, days to years out from presentation and recovery from apical ballooning ...syndrome 20. ...rather than relying on reverse reversibility dynamics of microvascular and cardiac function, one would have to note the opposite and ideally prove that coronary microvascular dysfunction is the primary cause and not a secondary phenomenon. ...CAD is frequently present in these patients, and this is a point well made by Drs. Petersen and Pepine in their article as well.
Anthracyclines are among the most potent chemotherapeutics; however, cardiotoxicity significantly restricts their use. Indeed, anthracycline-induced cardiotoxicity (AIC) fares among the worst types ...of cardiomyopathy, and may only slowly and partially respond to standard heart failure therapies including β-blockers and ACE inhibitors. No therapy specifically designed to treat anthracycline cardiomyopathy at present, and neither is it known if any such strategy could be developed. To address this gap and to elucidate the molecular basis of AIC with a therapeutic goal in mind, zebrafish has been introduced as an
vertebrate model about a decade ago. Here, we first review our current understanding of the basic molecular and biochemical mechanisms of AIC, and then the contribution of zebrafish to the AIC field. We summarize the generation of embryonic zebrafish AIC models (eAIC) and their use for chemical screening and assessment of genetic modifiers, and then the generation of adult zebrafish AIC models (aAIC) and their use for discovering genetic modifiers
forward mutagenesis screening, deciphering spatial-temporal-specific mechanisms of modifier genes, and prioritizing therapeutic compounds
chemical genetic tools. Several therapeutic target genes and related therapies have emerged, including a retinoic acid (RA)-based therapy for the early phase of AIC and an autophagy-based therapy that, for the first time, is able to reverse cardiac dysfunction in the late phase of AIC. We conclude that zebrafish is becoming an important
model that would accelerate both mechanistic studies and therapeutic development of AIC.
We report here a patient with stage IV mucosal melanoma treated with dual immune checkpoint inhibitor (ICI) therapy (Nivolumab/Ipilimumab) who experienced rapid disease progression and metastatic ...spread within three weeks of first infusion. Surprisingly, this patient also developed fulminant myocarditis within the same time frame. Immunohistochemical staining of the primary tumor and a metastatic omental lesion revealed robust CD8
PD-1
T cell infiltration after ICI treatment, as would be expected following immune activation. However, the CD8
T cell infiltrate was largely negative for both Granzyme B and TIA-1, suggesting these T cells were not capable of effective tumor lysis. We discuss the possibility that heightened pro-inflammatory T cell activity (rather than tumor-directed cytolytic activity) was induced by anti-PD-1 and anti-CTLA-4, which could have provoked both rapid tumor resistance mechanisms and myocarditis. This case highlights the fact that the mere presence of tumor infiltrating lymphocytes (TILs) does not necessarily correlate to ICI response and that additional functional markers are necessary to differentiate between inflammatory and cytolytic CD8
TILs.
Background Trastuzumab is life-extending therapy for breast cancer patients overexpressing the human epidermal growth factor receptor 2 ( HER 2+), but has known cardiotoxic risk. We sought to ...determine if trastuzumab can be administered to patients with reduced baseline cardiac function at no higher cardiotoxicity risk than in those with normal cardiac function at baseline. Methods and Results We performed a retrospective study of women treated with trastuzumab for human epidermal growth factor receptor 2 breast cancer at Mayo Clinic Rochester between January 1, 2000 and August 31, 2015 with pre- and on-therapy echocardiograms available for review. A left ventricular ejection fraction (LVEF) <53% was considered abnormal, and a ≥10% decline in LVEF as evidence of cardiotoxicity based on the criteria of the American Society of Echocardiography. A total of 428 women were identified; 408 had a normal cardiac function ( LVEF 63.4±5%) and 20 had an impaired cardiac function ( LVEF 45.4±7%) before trastuzumab. Seven women (35%) with reduced LVEF at baseline had a ≥10% reduction in LVEF , compared with 179 (43.9%) of those with normal LVEF before trastuzumab initiation ( P= NS ). Symptomatic heart failure developed more often in patients with reduced versus normal baseline LVEF (25% versus 4.2%, P<0.05). After adjusting for patient age and breast cancer disease stage, survival rates over 5 years from time of diagnosis were found to be lower for patients with reduced baseline LVEF compared with patients with normal baseline LVEF ( P<0.001); the adjusted proportion of patients surviving at 5 years for those with low LVEF at baseline was 79% and for those with normal LVEF was 93%. Conclusions Women undergoing trastuzumab therapy for breast cancer with impaired baseline cardiac function experience no higher risk of LVEF decline, but more frequently develop symptomatic heart failure. While trastuzumab could be considered, these patients should be co-managed by a cardiologist.
Over the past decade, the role of the ubiquitin-proteasome system (UPS) has been the subject of numerous studies to elucidate its role in cardiovascular physiology and pathophysiology. There have ...been many advances in this field including the use of proteomics to achieve a better understanding of how the cardiac proteasome is regulated. Moreover, improved methods for the assessment of UPS function and the development of genetic models to study the role of the UPS have led to the realization that often the function of this system deviates from the norm in many cardiovascular pathologies. Hence, dysfunction has been described in atherosclerosis, familial cardiac proteinopathies, idiopathic dilated cardiomyopathies, and myocardial ischemia. This has led to numerous studies of the ubiquitin protein (E3) ligases and their roles in cardiac physiology and pathophysiology. This has also led to the controversial proposition of treating atherosclerosis, cardiac hypertrophy, and myocardial ischemia with proteasome inhibitors. Furthering our knowledge of this system may help in the development of new UPS-based therapeutic modalities for mitigation of cardiovascular disease.
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