Human Heart can be damaged by the presence of cancer elsewhere in the body. This finding surprised physicians and researchers.
Reporter: Aviva Lev-Ari, PhD, RN
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SOURCE
- Heart failure and cardiomyopathies
- Original article
Cardiovascular biomarkers in patients with cancer and their association with all-cause mortality
- Noemi Pavo1,
- Markus Raderer2,
- Martin Hülsmann1,
- Stephanie Neuhold3,
- Christopher Adlbrecht1,
- Guido Strunk4,
- Georg Goliasch1,
- Heinz Gisslinger2,
- Günther G Steger2,
- Michael Hejna2,
- Wolfgang Köstler2,
- Sabine Zöchbauer-Müller2,
- Christine Marosi2,
- Gabriela Kornek2,
- Leo Auerbach5,
- Sven Schneider6,
- Bernhard Parschalk6,
- Werner Scheithauer2,
- Robert Pirker2,
- Johannes Drach2,
- Christoph Zielinski2,
- Richard Pacher1
Author Affiliations
- 1Division of Cardiology, Department of Internal Medicine II, Medical University of Vienna,Vienna, Austria
2Division of Oncology and Hematology, Department of Internal Medicine I, Medical University of Vienna, Austria
3Division of Cardio-Thoracic-Vascular Anesthesia and Intensive Care Medicine, Department of Anesthesia, Medical University of Vienna, Vienna, Austria
4Complexity Research, Vienna, Austria
5Department of Gynecology, Medical University of Vienna, Vienna, Austria
6Department of Otorhinolaryngology, Head and Neck Surgery, Medical University of Vienna, Austria
Abstract
Objective Patients with cancer may display elevated levels of B-type natriuretic peptide (BNP) and high-sensitive troponin T (hsTnT) without clinical manifestation of cardiac disease. This study aimed to evaluate circulating cardiovascular hormones and hsTnT and their association with mortality in cancer.
Methods We prospectively enrolled 555 consecutive patients with a primary diagnosis of cancer and without prior cardiotoxic anticancer therapy. N-terminal pro BNP (NT-proBNP), mid-regional pro-atrial natriuretic peptide (MR-proANP), mid-regional pro-adrenomedullin (MR-proADM), C-terminal pro-endothelin-1 (CT-proET-1), copeptin, hsTnT, proinflammatory markers interleukin 6 (IL-6) and C reactive protein (CRP), and cytokines serum amyloid A (SAA), haptoglobin and fibronectin were measured. All-cause mortality was defined as primary endpoint.
Results During a median follow-up of 25 (IQR 16–31) months, 186 (34%) patients died. All cardiovascular hormones and hsTnT levels rose with tumour stage progression. All markers were significant predictors of mortality with HRs per IQR of 1.54 (95% CI 1.24 to 1.90, p<0.001) for NT-proBNP, 1.40 (95% CI 1.10 to 1.79, p<0.01) for MR-proANP, 1.31 (95% CI 1.19 to 1.44, p<0.001) for MR-proADM, 1.21 (95% CI 1.14 to 1.30, p<0.001) for CT-proET-1, 1.22 (95% CI 1.04 to 1.42, p=0.014) for copeptin and 1.21 (95% CI 1.13 to 1.32, p<0.001) for hsTnT, independent of age, gender, tumour entity and stage, and presence of cardiac comorbidities. NT-proBNP, MR-proANP, MR-proADM and hsTnT displayed a significant correlation with IL-6 and CRP.
Conclusions Circulating levels of cardiovascular peptides like NT-proBNP, MR-proANP, MR-proADM, CT-pro-ET-1 and hsTnT were elevated in an unselected population of patients with cancer prior to induction of any cardiotoxic anticancer therapy. The aforementioned markers and copeptin were strongly related to all-cause mortality, suggesting the presence of subclinical functional and morphological myocardial damage directly linked to disease progression.
SOURCE
http://heart.bmj.com/content/101/23/1874
Can Cancer Itself Damage the Heart?
Both treated and untreated cancer patients had impaired heart function
Seville, Spain – 3 December 2015: Research presented today at EuroEcho-Imaging 2015 raises the possibility that cancer itself may damage heart muscle irrespective of exposure to cancer drug therapies.1 Researchers from the UK’s first dedicated cardio-oncology clinic found that both treated and untreated cancer patients had impaired heart function.
The annual meeting of the European Association of Cardiovascular Imaging (EACVI), a registered branch of the European Society of Cardiology (ESC), is held 2 to 5 December 2015 in Seville, Spain.
“It is well known that chemotherapy is potentially toxic to the heart, making cancer patients more prone to cardiovascular complications such as heart failure, hypertension or myocardial ischaemia,” said Dr Rajdeep S. Khattar, last author of the abstract and consultant cardiologist at the Royal Brompton Hospital in London, UK. “Our study raises the possibility that tumour growth itself may also damage the heart which could have important implications for monitoring.”
The definition of cardiotoxicity is based on a reduced ejection fraction (less than 55%) and symptoms of heart failure. Ejection fraction is a coarse measure of left ventricular function and is assessed by echocardiography. It refers to the percentage of blood pumped into the circulation when the heart contracts. For example, if there is 100 ml of blood in the left ventricle and 65 ml is pumped out, the ejection fraction is 65%.
The current study applied a more subtle measure of left ventricular function using echocardiography called strain. It indicates how well the myocardial fibres contract. Previous studies have shown that cancer patients who have had chemotherapy can have a normal ejection fraction but reduced strain and that this may predict subsequent cardiotoxicity.
Dr Khattar said: “Our study carried this finding a step further to see if untreated cancer patients with a normal ejection fraction also had reduced strain measurements.”
The study compared myocardial strain in three groups with a normal ejection fraction (55% or more): 43 patients with cancer who were currently being treated or had received treatment in the past, 36 patients with as yet untreated cancer, and 20 healthy individuals matched to the cancer groups for age and gender.
The researchers found that both groups of cancer patients had similarly reduced strain measurements, indicating impaired heart function, compared to the healthy individuals.
“All of the cancer patients had a preserved ejection fraction so by this coarse measure their hearts were functioning normally,” said Dr Khattar. “But the strain measurements showed that they did have myocardial dysfunction.”
He continued: “What was really new was the finding of reduced strain, and therefore myocardial dysfunction, in the group of patients with cancer who had not yet received treatment. This raises the possibility that the tumour itself may have a direct and deleterious effect on the function of the heart.”
Patients with reduced strain before they start their cancer drug therapies may be predisposed to developing heart failure during the course of their treatment. “These patients might need closer monitoring,” said Dr Khattar. “This would be a real change because at the moment, cancer patients don’t, as a matter of routine, have a cardiovascular risk assessment by a cardiologist.”
This is only the second study in humans which suggests that cancer might have a direct effect on the heart. A study published in September found elevated cardiovascular biomarkers in patients with as yet untreated cancer.2,3 “It could be that the tumour produces these inflammatory markers which then leads to the reduction in myocardial function that we found,” said Dr Khattar.
Dr Khattar will continue to follow the patients in the current study to find out if their rates of heart failure and death are predicted by the strain measurements. He said: “If it transpires that the patients with reduced strain prior to cancer treatment are more prone to heart failure and death then it would be important to implement closer monitoring of patients with cancer than is conducted currently.”
SOURCE
http://emjreviews.com/press/can-cancer-itself-damage-the-heart/
Early Signs of Heart Damage
The first study was published in September 2015 in the journal Heart. It investigated the presence of cardiovascular biomarkers in cancer patients. Biomarkers are biologically active substances whose presence in the bloodstream indicate the presence or severity of disease. The study’s authors performed blood tests on 555 patients who had been diagnosed with cancer, but not yet treated for it. The tests measured several hormones and proteins closely associated with heart function.
The researchers discovered that the cardiovascular biomarker levels rose as patients’ tumors advanced and that they were significant predictors of death. This was true regardless of the patient’s age, gender, tumor type and whether cardiac disease was apparent at the time of cancer diagnosis.
The second study was the subject of a December 2015 presentation by British doctors at a European conference on echocardiography — a diagnostic technology that uses high-frequency sound waves to produce images of the heart. The researchers used a new-ish echocardiographic test called “strain” to evaluate the heart muscle’s ability to contract while pumping blood.
Strain was measured in three groups of people: 43 with cancer who had already been treated, 36 with cancer who had not yet been treated, and 20 healthy people with similar demographic characteristics. Both groups of cancer patients showed signs of heart dysfunction, while the healthy patients did not.
A More Sensitive Metric
Both the findings and the strain technique used to generate them are significant breakthroughs, according to Chang.
“For the past 50 years, we’ve been relying on ejection fraction to know what’s going on in the heart,” says Chang. “It is a crude measure compared to strain.”
Ejection fraction, also measured with echocardiography, is the traditional metric for gauging heart strength. It’s the percentage of blood that’s ejected or pumped out from the left ventricle of the heart during each heartbeat. Normal ejection fraction is 55 to 75 percent.
Ejection fraction has been a reliable indicator of cardiotoxicity caused principally by radiation to the chest and chemotherapy with anthracyclines, a class of drugs used for breast cancer, leukemia and lymphoma, Chang says. It does not, however, indicate the more subtle signs of dysfunction that are now suspected as being caused by the mere presence of tumor cells.
In other words, heart muscle damage can and does occur even before it can be detected on the basis of ejection fraction measurements, whereas analysis of strain can pick up cardiac dysfunction at the very earliest stage, when the damage is most easily treated.
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