Emerging Heart Failure Research
Heart failure (HF) is a chronic condition where the heart does not pump properly. The heart may not fill with enough blood or produce enough force to pump out enough oxygenated blood to supply the body. HF affects more than 6.5 million people in the US and is a leading cause of hospitalization and death. The incidence of heart failure is expected to rise as our population continues to age.1-2
Heart failure doesn’t mean your heart stops, it means it is not working properly. This results in symptoms that cause a decrease in quality of life, due in part to the extent of effort required to carry out everyday activities. HF treatment is commonly focused on relieving symptoms and preventing the progression of the disease. Symptoms of heart failure include shortness of breath, edema -swelling in the feet, legs and ankles and abdomen, as well as fatigue. Lifestyle changes can be used as preventive measures and combined with medication which can stop or delay disease progression.1
Current research is looking to better understand and diagnose HF in its earliest stages, to develop new therapeutic approaches to manage symptoms and to slow the progression of the disease. Scientists are also looking at ways to prevent HF from ever developing.
Some of the research areas include:
- Emerging pharmacological treatment
- Cardiac imaging
- Genetic testing
- Devices and non-surgical interventions
- Mechanical circulatory support and heart transplants
Selected areas of focus in current HF research are briefly summarized below.
Clinical trials for new drugs to treat HF
Traditionally the U.S. Food and Drug Administration (FDA) granted approval of new HF medications that show an impact on morbidity and mortality (how long people live with HF and how often they are hospitalized). Despite hundreds of drugs in Phase 2 clinical trials, HF drugs often fail in Phase 3, meaning they are not approved for use.1
Yet a new approach to drug approvals is to support drugs that improve symptoms or physical function when added to standard care and prove to be valuable even without improving survival or reducing the need for hospitalization. Substantial and persistent improvement in symptoms or function, especially for patients classified with New York Heart Association Class III or IV heart failure, with some decrease in survival “would be acceptable”.1
Pharmacological treatment has evolved with an improved understanding of the pathophysiology of the heart and the development of new drugs.2
Drug therapy advances have been continuous for managing heart failure with reduced ejection fraction (HFrEF) but there are fewer treatment options for those diagnosed with heart failure with preserved ejection fraction (HFpEF). Presently, controlling symptoms and treating risk factors and comorbidities is considered the optimal approach for HFpEF. Researchers continue to investigate new medication options that could decrease mortality for these patients.2-3
Sodium–glucose cotransporter 2 (SGLT2)
Phase 3 drug trials are looking at new products, new indications for existing HF drugs, and new indications for non-HF drugs. Of note are some medications developed for type 2 diabetes (T2D), that have demonstrated significant cardioprotective benefits resulting in a 35% reduction in hospitalizations.4-6
New class of diabetes medicines
This class of diabetes medicines is called sodium-glucose cotransporter 2 (SGLT2) inhibitors. They are novel antihyperglycemic agents that increase the elimination of glucose through the urine.2 There is evidence to expect a reduction in blood pressure and improved glycemic control resulting in weight loss and improved insulin sensitivity. They have cardioprotective effects due to improving cardiac metabolism.
These drugs are changing the treatment approach for diabetics with cardiovascular disease and they are being studied for their effectiveness in treating heart failure in people without diabetes.6 Farxiga (dapagliflozin), Jardiance (empagliflozin), and Invokana (canagliflozin), all came to the market to reduce A1C levels in people with type 2 diabetes. They are now being evaluated for a potential class effect for treating HF.4,7-8
Farxiga® an AstraZeneca product was recently approved in the US to reduce the risk of hospitalization for heart failure in patients with type 2 diabetes.4,7,9 Jardiance® is looking to receive approval for new indications in 2020.8Fast Track designationThe FDA granted Fast Track designation to empagliflozin for the reduction of the risk of cardiovascular death and hospitalization for heart failure in people with chronic heart failure. The Fast Track designation is issued when new therapies that might fill an unmet medical need for serious conditions could expedite the availability of new treatment options.8Empagliflozin is currently prescribed in combination with diet and exercise to lower blood sugar and reduce the risk of cardiovascular death in adults with type 2 diabetes and known cardiovascular disease. It is in clinical trials to evaluate its safety and efficacy in patients with chronic heart failure with HFpEF and HFrEF.5,8Invokana® (canagliflozin) is also being studied for additional diabetes indications and improvements for cardiovascular outcomes such as the risk of heart attack, stroke or cardiovascular death, including those related to HF.1ImagingRadiographic, ultrasound, nuclear, and magnetic resonance methods have become indispensable in the management of heart failure. Doctors use imaging results to guide clinical decision making. Advances in non-invasive imaging technologies provide additional information about coronary arteries and heart tissue, coronary strain, the function and structure of the heart.10Genetic testingGenetic testing for inherited heart disease can identify both the cause and who is at risk of developing heart disease. The Heart Failure Society of America (HFSA) recommends that genetic testing is appropriate in patients with specific cardiomyopathies, conditions that affect the heart muscle.11Genetic testing can supply information regarding any familial origin of HF. It could lead to the development of targeted therapy that could result in better clinical outcomes. Although they have a low incidence rate, inherited cardiomyopathies differ in the way they are diagnosed, their clinical manifestations, and prescribed treatment.11As both testing and understanding of inherited conditions improve, thorough medical histories continue to be essential in identifying candidates for genetic testing. Information is constantly under investigation as to whether a particular gene mutation can cause heart disease.11Devices and non-surgical interventionsWork is being done through the traditional route and the FDA’s Breakthrough Devices Program looking to make advances in devices to assist people with heart failure to achieve clinical improvement. Device therapy is more prevalent in the management of arrhythmias and clinical heart failure. New capabilities have resulted in improvements in the size and functioning of devices like implantable cardioverter-defibrillator (ICD) and cardiac resynchronization therapy (CRT) devices.4,10Remote monitoringThese devices rely on remote monitoring which becomes one of the newest areas of HF management. Volumes of information are available from implantable electronic devices including heart rate, how well the wires are working, battery status and arrhythmias.For example, CardioMEMS is a heart sensor that permits hemodynamic monitoring via a wireless implantable pulmonary artery pressure monitoring system. It could significantly reduce the need for hospitalizations.4Mechanical circulatory support and heart transplantsMechanical circulatory supportNew devices, particularly ventricular assist devices (VADs), are being used in the treatment of advanced HF. Designed to prevent death or clinical worsening in patients waiting for a transplant, they are now approved as destination therapy, used to prolong life for people with end-stage heart failure.1-2New kinds of VADs are coming to market, in more durable and portable forms. They represent a new option for treatment.1-2Heart transplantationA heart transplant is considered a standard treatment for certain people with end-stage HF to extend life. Improvements in immunosuppressive drugs, availability of donors and donor procurement, surgical techniques, and post-transplant care have resulted in a substantial decrease in rejection.1-2Heart failure is becoming an increasingly important disease entity with the aging of society. According to its increasing prevalence, many new drugs and devices have been studied to improve clinical outcomes in terms of mortality and quality of life for HF patients. Although few studies showed encouraging results, researchers are attempting to find subgroups in whom certain medications or devices could be most effective, new methods for better diagnosis and prediction of prognosis in HF patients, and new tools for treating heart failure.1-2