The care for patients with cancer has advanced greatly over the past decades. A combination of earlier cancer diagnosis and greater use of traditional and new systemic treatments has decreased ...cancer-related mortality. Effective cancer therapies, however, can result in short- and long-term comorbidities that can decrease the net clinical gain by affecting quality of life and survival. In particular, cardiovascular complications of cancer treatments can have a profound effect on the health of patients with cancer and are more common among those with recognized or unrecognized underlying cardiovascular diseases. A new discipline termed cardio-oncology has thus evolved to address the cardiovascular needs of patients with cancer and optimize their care in a multidisciplinary approach. This review provides a brief introduction and background on this emerging field and then focuses on its practical aspects including cardiovascular risk assessment and prevention before cancer treatment, cardiovascular surveillance and therapy during cancer treatment, and cardiovascular monitoring and management after cancer therapy. The content of this review is based on a literature search of PubMed between January 1, 1960, and February 1, 2014, using the search terms cancer, cardiomyopathy, cardiotoxicity, cardio-oncology, chemotherapy, heart failure, and radiation.
Diabesity is a term used to describe the combined adverse health effects of obesity and diabetes mellitus. The worldwide dual epidemic of obesity and type 2 diabetes is an important public health ...issue. Projections estimate a sixfold increase in the number of adults with obesity in 40 years and an increase in the number of individuals with diabetes to 642 million by 2040. Increased adiposity is the strongest risk factor for developing diabetes. Early detection of the effects of diabesity on the cardiovascular system would enable the optimal implementation of effective therapies that prevent atherosclerosis progression, cardiac remodelling, and the resulting ischaemic heart disease and heart failure. Beyond conventional imaging techniques, such as echocardiography, CT and cardiac magnetic resonance, novel post-processing tools and techniques provide information on the biological processes that underlie metabolic heart disease. In this Review, we summarize the effects of obesity and diabetes on myocardial structure and function and illustrate the use of state-of-the-art multimodality cardiac imaging to elucidate the pathophysiology of myocardial dysfunction, prognosticate long-term clinical outcomes and potentially guide treatment strategies.
In patients with sarcoidosis, sudden death is a leading cause of mortality, which may represent unrecognized cardiac involvement. Delayed-enhancement cardiovascular magnetic resonance (DE-CMR) can ...detect minute amounts of myocardial damage. We sought to compare DE-CMR with standard clinical evaluation for the identification of cardiac involvement.
Eighty-one consecutive patients with biopsy-proven extracardiac sarcoidosis were prospectively recruited for a parallel and masked comparison of cardiac involvement between (1) DE-CMR and (2) standard clinical evaluation with the use of consensus criteria (modified Japanese Ministry of Health JMH guidelines). Standard evaluation included 12-lead ECG and at least 1 dedicated non-CMR cardiac study (echocardiography, radionuclide scintigraphy, or cardiac catheterization). Patients were followed for 21+/-8 months for major adverse events (death, defibrillator shock, or pacemaker requirement). Patients were predominantly middle-aged (46+/-11 years), female (62%), and black (73%) and had chronic sarcoidosis (median, 7 years) and preserved left ventricular ejection fraction (median, 56%). DE-CMR identified cardiac involvement in 21 patients (26%) and JMH criteria in 10 (12%, 8 overlapping), a >2-fold higher rate for DE-CMR (P=0.005). All patients with myocardial damage on DE-CMR had coronary disease excluded by x-ray angiography. Pathology evaluation in 15 patients (19%) identified 4 with cardiac sarcoidosis; all 4 were positive by DE-CMR, whereas 2 were JMH positive. On follow-up, 8 had adverse events, including 5 cardiac deaths. Patients with myocardial damage on DE-CMR had a 9-fold higher rate of adverse events and an 11.5-fold higher rate of cardiac death than patients without damage.
In patients with sarcoidosis, DE-CMR is more than twice as sensitive for cardiac involvement as current consensus criteria. Myocardial damage detected by DE-CMR appears to be associated with future adverse events including cardiac death, but events were few, and this needs confirmation in a larger cohort.
As the overlap between heart disease and cancer patients increases as cancer-specific mortality is decreasing and the surviving population is aging, it is necessary to identify cancer patients who ...are at an increased risk of death from heart disease. The purpose of this study is to identify cancer patients at highest risk of fatal heart disease compared to the general population and other cancer patients at risk of death during the study time period. Here we report that 394,849 of the 7,529,481 cancer patients studied died of heart disease. The heart disease-specific mortality rate is 10.61/10,000-person years, and the standardized mortality ratio (SMR) of fatal heart disease is 2.24 (95% CI: 2.23-2.25). Compared to other cancer patients, patients who are older, male, African American, and unmarried are at a greatest risk of fatal heart disease. For almost all cancer survivors, the risk of fatal heart disease increases with time.
While clinical gene therapy celebrates its first successes, with several products already approved for clinical use and several hundreds in the final stages of the clinical approval pipeline, there ...is not a single gene therapy approach that has worked for the heart. Here, we review the past experience gained in the several cardiac gene therapy clinical trials that had the goal of inducing therapeutic angiogenesis in the ischemic heart and in the attempts at modulating cardiac function in heart failure. Critical assessment of the results so far achieved indicates that the efficiency of cardiac gene delivery remains a major hurdle preventing success but also that improvements need to be sought in establishing more reliable large animal models, choosing more effective therapeutic genes, better designing clinical trials, and more deeply understanding cardiac biology. We also emphasize a few areas of cardiac gene therapy development that hold great promise for the future. In particular, the transition from gene addition studies using protein-coding cDNAs to the modulation of gene expression using small RNA therapeutics and the improvement of precise gene editing now pave the way to applications such as cardiac regeneration after myocardial infarction and gene correction for inherited cardiomyopathies that were unapproachable until a decade ago.
Anthracycline Chemotherapy and Cardiotoxicity McGowan, John V; Chung, Robin; Maulik, Angshuman ...
Cardiovascular drugs and therapy,
02/2017, Letnik:
31, Številka:
1
Journal Article
Recenzirano
Odprti dostop
Anthracycline chemotherapy maintains a prominent role in treating many forms of cancer. Cardiotoxic side effects limit their dosing and improved cancer outcomes expose the cancer survivor to ...increased cardiovascular morbidity and mortality. The basic mechanisms of cardiotoxicity may involve direct pathways for reactive oxygen species generation and topoisomerase 2 as well as other indirect pathways. Cardioprotective treatments are few and those that have been examined include renin angiotensin system blockade, beta blockers, or the iron chelator dexrazoxane. New treatments exploiting the ErbB or other novel pro-survival pathways, such as conditioning, are on the cardioprotection horizon. Even in the forthcoming era of targeted cancer therapies, the substantial proportion of today’s anthracycline-treated cancer patients may become tomorrow’s cardiac patient.
Cardiac rehabilitation is a comprehensive model of secondary prevention proven to reduce mortality and morbidity. The World Health Organization is developing a Package of Rehabilitation Interventions ...for implementation by ministries of health as part of universal healthcare across the continuum. Through a systematic review, we sought to identify the best-quality cardiac rehabilitation guidelines, and extract their recommendations for implementation by member states. A systematic search was undertaken of academic databases and guideline repositories, among other sources, through to April 2019, for English-language cardiac rehabilitation guidelines from the last 10 years, free from conflicts, and with strength of recommendations. Two authors independently considered all citations. Potentially eligible guidelines were rated for quality using the Appraisal of Guidelines for Research and Evaluation tool, and for other characteristics such as being multi-professional, comprehensive and international in perspective; the latter criteria were used to inform selection of 3–5 guidelines meeting inclusion criteria. Equity considerations were also extracted. Altogether, 2076 unique citations were identified. Thirteen passed title and abstract screening, with six guidelines potentially eligible for inclusion in the Package of Rehabilitation Interventions and rated for quality; for two guidelines the Appraisal of Guidelines for Research and Evaluation tool ratings did not meet World Health Organization minimums. Of the four eligible guidelines, three were selected: the International Council of Cardiovascular Prevention and Rehabilitation (2016), National Institute for Health and Care Excellence (#172; 2013) and Scottish Intercollegiate Guideline Network (#150; 2017). Extracted recommendations were comprehensive, but psychosocial recommendations were contradictory and diet recommendations were inconsistent. A development group of the World Health Organization will review and refine the recommendations which will then undergo peer review, before open source dissemination for implementation.
Anthracycline chemotherapy causes dose-related cardiomyocyte injury and death leading to left ventricular dysfunction. Clinical heart failure may ensue in up to 5% of high-risk patients. Improved ...cancer survival together with better awareness of the late effects of cardiotoxicity has led to growing recognition of the need for surveillance of anthracycline-treated cancer survivors with early intervention to treat or prevent heart failure. The main mechanism of anthracycline cardiotoxicity is now thought to be through inhibition of topoisomerase 2β resulting in activation of cell death pathways and inhibition of mitochondrial biogenesis. In addition to cumulative anthracycline dose, age and pre-existing cardiac disease are risk markers for cardiotoxicity. Genetic susceptibility factors will help identify susceptible patients in the future. Cardiac imaging with echocardiographic measurement of global longitudinal strain and cardiac troponin detect early myocardial injury prior to the development of left ventricular dysfunction. There is no consensus on how best to monitor anthracycline cardiotoxicity although guidelines advocate quantification of left ventricular ejection fraction before and after chemotherapy with additional scanning being justified in high-risk patients. Patients developing significant left ventricular dysfunction with or without clinical heart failure should be treated according to established guidelines. Liposomal encapsulation reduces anthracycline cardiotoxicity. Dexrazoxane administration with anthracycline interferes with binding to topoisomerase 2β and reduces both cardiotoxicity and subsequent heart failure in high-risk patients. Angiotensin inhibition and β-blockade are also protective and appear to prevent the development of left ventricular dysfunction when given prior or during chemotherapy in patients exhibiting early signs of cardiotoxicity.
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