Heart Failure is a Metabolic Disease

Targeting Metabolism Earlier Leads to Better Outcomes

Distended Jugular Veins Are a Sign of Heart Failure

Congestive heart failure is one of the largest barriers to a longer healthier life. It dramatically limits endurance, and it is very dangerous. Five year mortality is about 75% and median survival is just over 2 years from the time of diagnosis. That has improved very little with medical advances. It is a problem we are very likely to face personally. If you are 45 years old, the chance that you will develop heart failure in your lifetime is about 40%. That means it is very likely that heart failure will affect you or someone close to you. If you develop heart failure, a longer healthier life is not likely. Even if it does not impact you directly, it still has a big impact on you. Thirty four percent of Medicare spending is tied to individuals with a heart failure diagnosis. That consumes billions of dollars of tax revenue and that cost is increasing.

The number of people with heart failure is increasing due to an older, heavier population. New scientific findings suggest that we may finally be learning how to dramatically reduce the number of people who develop heart failure and how to treat them better. One of the puzzles has been the difference in the types of heart failure. In one type of heart failure, the heart muscle is weak. In the other type, the heart muscle is stiff, and the heart does not fill well. In both types, the amount of blood pumped in a minute is reduced, but beyond that they are very different. The weak muscle type responds much better to treatments like spironolactone, lisinopril, and carvedilol. Most treatment for the stiff muscle type is aimed at reducing symptoms.

There is a new editorial in the New England Journal of Medicine that suggests both forms of heart failure are metabolic diseases because expensive drugs like Jardiance and Wegovy are beneficial in both categories. That is true, but it misses an important point. Jardiance and Wegovy were both developed to treat type 2 diabetes. Jardiance inhibits the function of a very specific protein in the blood that causes more sugar to be lost in urine. (SGLT2) That brings the glucose level in the blood down and favors weight loss. But that is not how Jardiance reduces heart failure hospitalizations by 30%. Jardiance reduces heart failure hospitalizations by 30% whether the patient is diabetic or not because it switches on the master metabolic survival switch AMPK. That mimics the effect of caloric restriction, intermittent fasting, and exercise. When AMPK is switched on, mTOR is switched off. That is probably the key relationship.

Age is itself the greatest risk factor for congestive heart failure independent of other factors such as high blood pressure, smoking, diabetes, obesity, and high cholesterol. Smoking and excess weight switch on mTOR and switch off AMPK very early on which contributes to developing high blood pressure, diabetes, and high cholesterol to further amplify the risk of congestive heart failure. These factors in combination make the heart bigger, the arteries thicker, increase scar tissue formation, and kill heart muscle cells. mTOR activation and downstream genes it switches on is a metabolic root cause congestive heart failure and that insight opens the door to real therapeutic opportunities.

There is a study of people with type 2 diabetes and chronic kidney disease with an average age of 55 years upon entering the trial. These patients were sick. Chronic kidney disease and heart failure are driven by the same metabolism. In fact, Jardiance reduces admissions for heart failure and chronic kidney disease progression by about the same amount— 30%. That is because it switches on AMPK and switches off mTOR. The diabetes management in this study reduced heart failure admissions by 70% over 21 years. The protocol used specified using losartan or lisinopril for blood pressure, atorvastatin for cholesterol, metformin for diabetes, and aspirin to prevent clot formation. This protocol reduced heart failure admission by 70% because each of those interventions blocks the metabolic changes that are root causes of heart failure. They switch off mTOR and switch on AMPK and your can get a month’s supply of all for between $30 and $40.

People with type 2 diabetes and chronic kidney disease are much higher risk that diabetics without chronic kidney disease. Chronic kidney disease and heart failure are driven by the same changes in gene expression and metabolism. That is a key point. In the diabetes study, half the patients got best practice care guided by a protocol using the medications I mentioned. Half got usual care—the care most of us receive in the community. By the time eight years had passed, the differences in complications were so great that it was unethical to continue usual care, and everyone went on best practice care. There appears to be a point in the disease progress where best practice care doesn’t make as much difference. The difference in complications between best practice care and usual care continued to increase. By age 68 half the usual care patients were dead and that group had 4 times as many heart attacks, five times as many strokes, and 6 times as many people went on dialysis. This is overwhelming evidence that these complications, including heart failure, are primarily metabolic. We understand many of those changes and we can interfere with them.

Shouldn’t it be unethical to have patients on usual care in community practice if optimal medical therapy is proven to be so much more effective? Shouldn’t we begin to scale and spread this improved treatment of metabolic diseases and their complications.