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All pumped up with Omecamtiv Mercabil

I know this is a bit technical but a new drug has just been through small Phase II clinical trials  with some . The new drug is called Omecamtiv Mercabil and has been developed by a new drug company called Cytokinetics and is licensed to Amgen as reported in the Lancet.

It targets the motor proteins that cause muscle contraction and prolongs the action of the left ventricle of the heart, which pumps blood around the body. Rather than make the heart beat more often like current medicines, omecamtiv mercabil makes the heart muscles contract for longer, which increases the volume of blood the heart pumps with each stroke without increasing the amount of energy used.  That means it should not exhaust the heart, which can occur with currently-used inotropic agents.

The Phase II trial compared the intravenously-administered drug to placebo in 45 heart failure patients with impaired function of the left ventricle, who were also taking background therapy with ACE inhibitors and beta blockers. Omecamtiv mercabil increased left ventricular ejection time and stroke volume compared to control, alongside a small reduction in heart rate, suggesting that the hearts were working more effectively and efficiently.

According to Professor John Cleland of the University of Hull in the UK heart failure affects around 10 million people in the EU alone  who led the trial. “This is a totally new concept,” said Prof Cleland. “We need to see whether the improvements in cardiac function translate into real benefits for patients, in terms of their symptoms and quality of life, and whether it can impact on mortality and morbidity.”

Another Phase IIb trial should start next year, and if successful the drug could be on the market within the next three to four years, said Prof. Cleland. Cytokinetics is also developing oral formulation of omecamtiv mercabil, but this is unlikely to be ready to submit for approval for five years or more.

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.

These are my fish oils –
Fish Oil one
Fish Oil two

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.”

New Complimentary Fish Oils

I have just received my new fish oils from New Zealand from a company called Xtend-Life. You can visit their website via the link but I have my fingers crossed over their Omega 3 QH Ultra product. This is a very refined fish oil but it has a special added ingredient called Ubiquinol.

I will keep it very brief but my aim is to increase my ejection fraction percentage. These fish oils are part of my strategy for this reason. Ubiquinol is reportedly 6 times the strength of the normal Q10 which you buy and it is absorbed fully through the intestinal wall without degrading. Normal Q10 is Ubiquinone not Ubiquinol.

Ok this is where it gets complicated – and i have taken this from Wilkipedia – ” In terms of its functions, ubiquinol’s primary roles are in the synthesis of mitochondrial energy and as a protective antioxidant. The vitamin-like nutrient is found concentrated in the inner mitochondrial membrane where it serves as a carrier of reducing equivalents in the mitochondrial electron transport chain’s I and II complexes. In this process, ubiquinol serves to produce ATP (adenosine triphosphate), the main energy intermediate in living organisms.”

In other words it is vital to cell growth and that includes heart cells.

I will update you as and when I have any further information on the fish oils mentioned.

Understanding Atrial Fibrillation

At Pumping Marvellous we try to keep things simple as we are patients, however we do know a fair bit about our conditions so we do like to share our experiences with our readers. Sometimes it can become a little technical even for us with the conditions and we may need to use reference points to help us be factual but as stated we try to keep things simple.

Atrial fibrillation is a heart condition that causes episodes of irregular and often abnormally fast heart rate.

A normal heart rate should be between 60 and 100 beats a minute at rest. You can measure your heart rate by feeling the pulse in your wrist or neck. In atrial fibrillation, the heart rate may be over 140 beats a minute.

There are three main types of atrial fibrillation:

* Paroxysmal atrial fibrillation. This comes and goes and usually stops within 48 hours without any treatment.
* Persistent atrial fibrillation. This lasts for longer than seven days (or less when it is treated).
* Longstanding persistent atrial fibrillation. This usually lasts for longer than a year.

What happens

When the heart beats normally, its muscular walls contract (tighten and squeeze) to force blood out and around the body. They then relax, so the heart can fill with blood again. This process is repeated every time the heart beats.

In atrial fibrillation, the upper chambers of the heart (atria) contract randomly and sometimes so fast that the heart muscle cannot relax properly between contractions.

This may lead to a number of problems, including dizziness and shortness of breath. You may also be aware of a fast and irregular heartbeat (palpitations) and feel very tired.

Some people with atrial fibrillation have no symptoms and are completely unaware that their heart rate is not regular.

So why does it happens

Atrial fibrillation occurs when abnormal electrical impulses suddenly start firing in the atria. These impulses override the heart’s natural pacemaker, which can no longer control the rhythm of the heart. This causes you to have a highly irregular pulse rate.

The cause is not fully understood, but it tends to occur in certain groups of people and may be triggered by certain situations, such as drinking excessive amounts of alcohol or smoking.

How common is it?

Atrial fibrillation is the most common heart rhythm disturbance and affects up to 500,000 people in the UK.

Who is affected?

Atrial fibrillation can affect adults of any age, but affects men more than women and becomes more common the older you get. It affects about 10% of people over 75.

Atrial fibrillation is more likely to occur in people with other conditions, such as high blood pressure or atherosclerosis.

It is not common in younger people unless they have a heart condition.

Outlook

Atrial fibrillation is generally not life threatening, but it can be uncomfortable and often needs treating.

Treatment may involve medication to control heart rate and/or rhythm, and medication to prevent stroke.

A healthy lifestyle, regular blood pressure checks and treatment for raised blood pressure can reduce the chances of developing the heart problems that cause atrial fibrillation.

What are the ventricles

The right and left ventricles have the same job however the left ventricle has a harder job than the right. The right ventricle contracts and blood is pumped out of the heart through a large vessel. And then has to pump the blood into the lungs. The left ventricle has a lot harder job it actually works six times harder then the right ventricle. The left ventricle has to pump blood through your body and this is generally the ventricle that gets damaged when a patient has heart failure. In other words it doesn’t pump as efficiently as possible.

How the heart interacts with your circulation

This is a simple diagram of how the Heart works with your Circulatory system.