Matters of the Heart

The heart of an average urbanite is at a higher risk as each day passes. Obesity, diabetes and sustained high blood pressure are all factors that result in blockages in the heart, leading to cardiac failure, popularly termed heart attacks. What options are available to treat these? By Deepali Gupta.

As stress, sedentary lifestyles, and irregular meal patterns increasingly characterise urban routine, the human body and more so the human heart are plagued by lifestyle disorders.

In simple terms, cardiac arrest happens due to blood clots, caused by malfunction in platelet related clotting process or narrowing of arterial vessels because of cholesterol deposition. It affects the vessels that provide blood to the heart, causing the heart to beat irregularly or stop altogether. Nevertheless, this is not the day and age for unexplained deaths. In fact, today a person in the middle-income bracket is tested and can start cardiac care well before anything untoward happens.

Intervention as prevention

Dr SB Gupta, Cardiologist

Doctors believe that there can be no better cure than modification in lifestyle, the most natural way to avert any heart-related negligence. Pharma companies however, have sworn to provide enough options for those who can afford medical intervention. The foremost is the use of aspirin and cholesterol-reducing drugs such as statins, ace inhibitors that prevent plaque formation and beta-blockers that increase the heart's capacity to work.

Statins themselves have several variants. The one in the news recently is Pfizer's blockbuster, Lipitor, because of the IPR challenge posed by Ranbaxy. Atorvastatin has a bioavailability of approximately 12 percent and is excreted through bile. Other statins include fluvastatin, lovastatin, pravastatin, rouvastatin, and cerivastatin.

The future of statins lies in innovative pathways of delivery. Dr SB Gupta, Cardiologist says some of the newer statins have already broken free from the cP450 pathway delivery to prevent interaction with other drugs that may be delivered in the system, thus increasing the efficiency of both drugs.

Statins, says Gupta, have been shown to cause damage to muscle tissue and could affect the liver in some cases.

Repair options

After an attack, several repair technologies are available. For instance, doctors now have fairly effective thrombolytic solutions for dissolving clots. The procedure involves the insertion of enzymes such as streptokinase, urokinase and alteplase in the blood stream, which then help disintegrate the clot. Ideally, thrombolysis should begin within an hour of infarction. If administered soon enough it can prevent all damage.

Unfortunately, in India only infusible thrombolysis is available. Internationally easily dispensable injections are available so that the doctor can administer it on the spot rather than wait until the patient reaches the hospital.

Surgical alternatives

As far as surgery is concerned, medicine has seen tremendous growth over the past five years. Rather than open-heart surgery or bypass surgery, doctors are now adopting angioplasty.

In angioplasty, the heart is not exposed and doctors do not have to saw the ribcage open, or extract vessels from other parts of the body such as the legs.

The procedure involves inserting a folded balloon-like object into the vessel that has narrowed, from the arm or leg. Once positioned at the point of narrowing, the balloon is inflated to help the vessel open.

Researchers also found that leaving behind a metal stent in the vessel provides a long-term solution to the re-clogging of arteries. A stent is a flexible wire mesh that holds the blood vessel open even after the balloon is removed. While stents in themselves were innovative, pharma companies soon found they could offer a better solution—a drug-coated stent.

Gilding the lily

Stents and the angioplasty are perceived as an injury in the human system. Therefore, the body initiates healing process and there is re-growth of tissue, which leads to further blockage in the artery. Even if that is prevented at a post-operative stage, the deposition over the stent continues.

A drug-coated stent has a coating of growth inhibitors and drugs used as anti-cancer agents to help arrest re-growth of blockages. Primarily the drugs used to coat the stents include paclitaxel, that limit healing growth, everolimus, and sirolimus, an immunosuppressant.

The far-reaching impact of drug-coated stents will be tested over time, but for now doctors consider it a good surgical solution.

Issues were raised regarding the flaking and possible disintegration of drug-coated stents, but that does not change the effectiveness as far as doctors are concerned. "Bare metal stents have a 20 to 30 percent chance of closing whereas with the drug coating that number is reduced to five to ten percent, even in diabetic patients and those with proximal lesions," says Gupta.

Promoting growth

While surgical intervention has resulted in saving many lives, there is a perennial search for non-invasive methods to treat diseases. For the heart, researchers have found some growth factors result in angiogenesis or a growth of additional vessels.

The problem with that says Gupta, is that it results in a similar growth in other parts of the body too. Therefore, what researchers need to work on is targeted growth merely in the heart.

Vascular endothelial growth factor (VEGF) is a potent mitogen for endothelial cells. It stimulates capillary formation and increases vascular permeability. Its characteristics give VEGF an important theoretical specificity. It thereby decreases the risk of pathological neovascularisation at distant sites, for example in the retina, haemangioma formation, or accelerating pre-existing atherosclerotic plaques through the stimulation of smooth muscle cell proliferation. Currently it is undergoing clinical trials both as gene therapy and as direct administration of protein. In rabbits, myocardial angiogenesis has been demonstrated with both intra-arterial and intramuscular injection of recombinant VEGF.

Fibroblast growth factors (FGF) are a family of at least seven structurally related polypeptides characterised by a high affinity to heparin. Basic fibroblast growth factor (bFGF) has a widespread tissue distribution including cardiac tissue. FGF are stored primarily in the endothelial basement membrane protected from degradation by heparin and heparin-like proteoglycans.

Angiopoietin-1 appears to mediate the migration of smooth muscle cells to the walls of microvessels. Its therapeutic angiogenic potential is yet unexplored.

Nitric oxide (NO) stimulates endothelial proliferation and angiogenesis. Its advantage is that a variety of pharmacological agents (both NO donors and blockers) are available to manipulate the system. There is conflicting data on its net effect on angiogenesis.

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