EXPERT ANALYSIS FROM WCIRDC 2017

LOS ANGELES (FRONTLINE MEDICAL NEWS) Heart failure in the presence of type 2 diabetes has a 5-year survival rate on par with some of the worst diseases, such as lung cancer, because diabetes makes the pathophysiology of heart failure worse, according to Mark Kearney, MD.

“Diabetes amplifies the neurohormonal response to heart failure, so it drives progressive heart failure and increases the risk for sudden death,” Dr. Kearney said at the World Congress on Insulin Resistance, Diabetes & Cardiovascular Disease. “As left ventricular function goes down, patients with diabetes have heightened activation of the renin angiotensin system. They have increased left ventricular hypertrophy, and they have increased sympathetic nervous system activation.”

Dr. Kearney , a cardiologist who directs the Leeds Institute of Cardiovascular & Metabolic Medicine at Leeds (England) University, offered a “four Ds” framework that clinicians can use to improve prognosis in these patients.

The four Ds include:

1. Use a loop diuretic to control symptoms. “If the patient has fluid retention, it’s important to get them out of congestive cardiac syndrome as quickly as possible,” he said.

2. Disease modification with beta-blockers and ACE inhibitors, to the maximal dose tolerated. “These are still the mainstays of treatment for patients with heart failure, and they’re even more important in patients with diabetes and heart failure,” he said.

3. Consider device therapy, including defibrillators and resynchronization therapy. 4. Optimize diabetes management.

“If you keep these things in your mind as you see a patient with heart failure and diabetes, it will give you a guide to approaching these patients,” said Dr. Kearney, who is also research lead for heart failure services at the University of Leeds. “When I see patients, I’ll check for edema right away. If they have it, I’ll increase the diuretic, and I’ll think about the different steps in the treatment pathway.”

He described heart failure due to systolic dysfunction as a reduction in cardiac output that doesn’t meet the demands of the body, the endpoint of a whole range of insults to the left ventricle.

“The most common cause today is ischemic heart disease; it used to be hypertension,” he said. “People over 40 have a one in five chance of developing heart failure, so it’s really important for all of us to improve outcomes in this terrible syndrome.”

According to a study of nearly 2,000 unselected patients conducted by Dr. Kearney and his associates, those with diabetes and heart failure are more likely to have ischemia, compared with those who have heart failure and no diabetes (75% vs. 58%, respectively), lower hemoglobin (13 g/dL vs. 13.7 g/dL), and worse renal function (eGFR of 51 mL/min per 1.732 m2 vs 57 mL/min per 1.732 m2) ( Diab Vasc Dis Res. 2013 Jul;10[4]:330-6 ).

He added that type 2 diabetes is a sudden death risk equivalent to patients with ischemic heart disease and left ventricular systolic dysfunction ( Heart 2016 May 15;102[10]:735-40) .

“So, if you have diabetes and the U.K. National Institute for Health and Care Excellence guidelines indication for a defibrillator, your risk of sudden death in 5 years is probably 50%,” Dr. Kearney said. “The best treatment in this case is a prophylactic defibrillator.”

ACE inhibitors are used to protect these patients against cardiac myocyte cell death and vasoconstriction, while beta-blockers are used to protect against the activation of the sympathetic nervous system.

“Often, patients don’t like taking beta-blockers because they say they make them feel tired – when in fact they don’t realize it’s their heart failure that’s making them feel tired,” Dr. Kearney said.

He and his associates examined the effect of different drugs doses on all-cause mortality at 5 years. They found that, among patients with heart failure, reduced ejection fraction, and no diabetes, ramipril conferred a 3% improvement in mortality per milligram. At the same time, the mortality among patients with diabetes and heart failure who did not receive a beta-blocker was about 7%.

However, the absolute gain from beta-blocker use in patients with diabetes and heart failure was three times that of patients without diabetes.

“So, every milligram you increase the dose by, there’s an associated improvement in risk,” Dr. Kearney said. “Over 5 years, comparing the lowest beta-blocker dose to the highest beta-blocker dose, it was 1 year of life gained. So, when I see my patients and they ask about side effects of beta-blockers, I now say to them, ‘The side effects actually make you live longer.’”

He concluded his remarks by noting that while he is not a diabetes expert, it’s clear that diabetes is intimately linked to the pathophysiology of heart failure.

“If you’re insulin resistant, you have hypertension, hyperglycemia, you have inflammation and bone marrow dysfunction – all of which can exacerbate left ventricle dysfunction,” he said. “You have a syndrome in which you have cardiac dysfunction and metabolic dysfunction that conspire to lead to worsening of left ventricular dysfunction.”

Dr. Kearney disclosed that he has been a speaker for Merck.

dbrunk@frontlinemedcom.com

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