A drug often used to treat chronic heart failure may not ease symptoms in people with one form of the disease, a new study suggests.
Spironolactone failed to improve symptoms or quality of life among 422 patients with diastolic heart failure — a form of the disease that affects about half of all people with heart failure.
The drug did, however, benefit the structure and function of patients’ hearts. And experts said it’s too early to know what to make of the results, which appear in the Feb. 27 issue of the Journal of the American Medical Association.
“It would be premature to say this is not beneficial,” said Dr. Sanjiv Shah, a cardiologist at Northwestern University Feinberg School of Medicine, in Chicago, who was not involved in the study.
Shah is involved in an ongoing study of spironolactone’s effects in people with diastolic heart failure. And that trial is focusing on the big questions: Can the drug prevent or delay hospitalizations, or prolong people’s lives?
Spironolactone is in a class of drugs called aldosterone receptor antagonists. They cause the kidneys to eliminate excess water and sodium from the body, so they can lower blood pressure and get rid of fluid build-up in some people with heart failure.
Studies have shown that spironolactone can extend the lives of some heart failure patients — namely, those with a low “ejection fraction.
The problem is that heart failure is a “syndrome” - or a collection of signs and symptoms – rather than a disease. So a treatment that works for some patients may not work as well for others.
In systolic heart failure, the heart’s left ventricle (the main pumping chamber) cannot contract strongly enough, and many people with this form of heart failure have a reduced ejection fraction.
In the diastolic form, the left ventricle doesn’t relax enough between contractions, which means it cannot fill up with as much blood as it should. But the heart’s ejection fraction is actually normal.
Diastolic heart failure is trickier to diagnose, and doctors know less about how to best treat it, said Dr. John Cleland, a cardiologist at Hull York Medical School in Kingston-upon-Hull who co-wrote an editorial published with the study.
He agreed that it’s too soon to draw conclusions from the current findings, and that doctors will know more when Shah’s study results are in.
Stem cells taken from a patient’s own heart have, for the first time, been used to repair damaged heart tissue, researchers claim. The study, published in the Lancet, was designed to test the procedure’s safety, but also reported improvements in the heart’s ability to pump blood.
The authors said the findings were “very encouraging”
Other experts said techniques with bone marrow stem cells were more advanced and that bigger trials were needed. The scientists say this is the first reported case of cardiac stem cells being used as a treatment in people after earlier studies had shown benefits in animals.
The preliminary trial was on patients with heart failure who were having heart bypass surgery. During the operation, a piece of heart tissue, from the right atrial appendage, was taken. While the patient was being sown up, researchers isolated cardiac stem cells from the sample and cultured them until they had about two million stem cells for each patient. The cells were injected about 100 days later. Doctors measured how efficiently the heart was pumping using the left ventricle ejection fraction – what percentage of blood was leaving one of the heart’s main chamber with every beat. Dr Roberto Bolli University of Louisville said “We believe these finding are very significant”
In the 14 patients given the treatment, the percentage increased from 30.3% at the beginning of the trial, to 38.5% after four months.
There was no change in the ejection fraction in the seven patients who were not injected with stem cells.
“Our results indicate that cardiac stem cells can markedly improve the contractile function of the heart.”
However the heart is not the only source of potentially useful stem cells. Trials have already taken place using stems cells from bone marrow.
Prof Anthony Mathur, from Barts and the London School of Medicine and Dentistry, and Prof John Martin, from University College London, are already conducting large randomised clinical trials. Prof Peter Weissberg British Heart Foundation “This is positive, but the crucial next steps are to see whether this improvement is confirmed in the final completed trial”
Prof Mathur said of the cardiac stem cell study: “Caveats very much apply. It’s a phase one trial so while the early results are great and promising, they need to design a big study to see if the results translate.”
He also cautioned that improvements in ejection fraction were not the same as increasing survival or quality of life.
Prof Martin said he was “concerned” that the seven patients in the control group showed no improvement in ejection fraction, which would normally be expected, and that they were not given a sham treatment to account for the placebo effect.
He said that was acceptable when just testing a procedure’s safety, but not when looking at effectiveness, which relies on the difference between the treated and control groups. Prof Peter Weissberg, medical director at the British Heart Foundation, argued that the improvement in heart function was similar to those in other studies.
“This is positive, but the crucial next steps are to see whether this improvement is confirmed in the final completed trial, and to understand whether the cells are actually replacing damaged heart cells or are secreting molecules that are helping to heal the heart,” he added.
Dr Bolli argues that stem cells from the heart might be more useful as “their natural function is to replace the cells that continuously die in the heart due to wear and tear”. He hopes to start the next phase of clinical trials in 2012
More evidence – Fish Oil and Heart Failure
This article has taken excerpts from the American Heart Failure Society. It is very important to note that the EPA levels were high which indicates very refined fish oil – this is very important.
This article has been reviewed by Dori F. Zaleznik, MD; Associate Clinical Professor of Medicine, Harvard Medical School, Boston. Oh and sorry it is a bit technical but it needs to be.
“Patients with early-stage nonischemic cardiomyopathy derived significant functional and echocardiographic benefits from the addition of omega-3 fatty acids to optimized medical therapy, results of a randomized clinical trial showed. Omega-3 supplementation was associated with significantly greater improvement in left ventricular ejection fraction (LVEF, P=0.0001), exercise capacity (P<0.00), and hospitalization for heart failure (P=0.0002), as compared with medical management plus placebo.
"Whether this intervention will have similar effects for patients with other etiologies, more advanced stages of heart failure, or for patients who are not on evidenced-based therapy remains unknown," Mihai Gheorghiade, MD, of Northwestern University in Chicago, said here at the Heart Failure Society of America meeting.
"I am hoping that further studies will be conducted to assess the effects of this potentially important therapy on left ventricular function and clinical outcomes in other patients."
The results build on previous evidence from an Italian intergroup study showing that omega-3 polyunsaturated fatty acid supplementation improved outcomes in patients with chronic heart failure, irrespective of etiology or LVEF (Lancet 2008; 372: 1090-1098).
In an effort to clarify the spectrum of benefits, Gheorghiade and colleagues performed a multicenter, randomized clinical trial involving patients with nonischemic cardiomyopathy and minimal or no symptoms; 93 patients were included in the final analysis.
Eligible patients had left ventricular systolic dysfunction associated with an LVEF ?45% on evidenced-based treatment for at least six months and stable clinical status for at least three months.
Patients were randomized to 850 to 882 mg a day of eicosapentaenoic acid (EPA) or docosahexaenoic acid (DHA) or matching placebo. Treatment continued for a year, and patients had monthly follow-up assessments.
Assessments performed at baseline and at the end of the study included electrocardiography, echocardiography, renal function, and concentrations of inflammatory cytokines and fatty acids. The echocardiographic evaluation included left ventricular end-diastolic and end-systolic diameter and volume, LVEF, shortening fraction, and extent of mitral regurgitation.
In the final analysis, measurement of EPA and DHA levels showed significant increases from baseline (P<0.001) and compared with levels of those in the placebo group (P<0.001), whose fatty acid concentrations did not change significantly from baseline to 12 months.
Cytokine assessment showed that concentrations of tumor necrosis factor-alpha, interleukin-8, and interleukin-1 all increased significantly in the placebo group (P<0.001) and decreased significantly in patients who received omega-3 supplementation (P<0.001).
Between-group comparisons showed significantly lower levels of all three cytokines in the omega-3 group (P<0.001 for all comparisons).
LVEF decreased from about 37% at baseline to about 35% at 12 months in the placebo group (P<0.001) but increased from about 35% at baseline to more than 38% at 12 months in the group that received the supplements (P<0.001 versus baseline and versus placebo).
Exercise tests showed significant improvement in the omega-3 group from baseline to 12 months compared with the placebo group, whether expressed as peak VO2 (P<0.001) or percent VO2 max (P=0.006).
In the supplementation group, patterns of NYHA functional class showed a shift from class I to class II and no patients in class III at baseline or 12 months. In the placebo group, the proportion of patients in class I did not change, the proportion in class II declined, and a substantial proportion of patients progressed from class II to class III.
The trial was not designed to assess the impact of supplementation on hospitalization rates. However, an exploratory analysis showed that the addition of omega-3 supplements to medical therapy was associated with significantly fewer heart failure hospitalizations (6% versus 30%, P=0.0002) and cardiovascular hospitalization (~15% versus 30%, P=0.0029) and a trend toward fewer hospitalizations for any reason (<30% versus >40%, P=0.0599).
Results of the study support the case for a “real” effect of omega-3 fatty acids in heart failure, Stephen Goldsmith, MD, of the University of Minnesota in Minneapolis, said during an invited discussion of the study.
“Given that some experts are already calling for the addition of omega-3 fatty acids to the guidelines for heart failure therapies, a second large randomized controlled trial would seem indicated, including both ischemic and nonischemic patients across a range of clinical severity,” said Goldsmith.
“It would be desirable in any such trial to include substudies dealing with left ventricular functional parameters, exercise capacity, and biomarkers, to confirm the current findings and potentially extend their applicability.”
Colostrum and Heart Health
I have just received my tub of powdered Colostrum from Synertek. My first installment will be tomorrow morning so I will keep all our readers up to date with how I get on. My aim is to restore my Ejection Fraction % to 50%, it is currently 35% after having heart failure diagnosed in January 2010.
Obviously looking forward to it working as it would be a worthwhile investment indeed.