Overview of Heart Failure and Ejection Fraction
Heart failure with preserved ejection fraction (HFpEF) is a condition where the heart will contract normally but will not relax as it should, leading to an inadequate filling of the heart with blood. The improper relaxing of the heart muscles is commonly referred to as diastolic dysfunction. Common symptoms of people with this condition are shortness of breath, fatigue, and fluid retention.
The ejection fraction (EF) is the percentage of blood the heart pumps out with each beat from the left ventricle to be carried to the rest of the body. This percentage is typically 50% or higher in a normal functioning heart. People with HFpEF will have a normal EF, but the muscle does not relax as it should which prevents the heart from adequately refilling. Underlying issues that typically cause HFpEF include hypertension, obesity, and diabetes (Kaye & Nanayakkara 2019).
Conversely, those with heart failure with reduced ejection fraction (HFrEF) will have an EF of less than 40%. This leads to ineffective blood circulation throughout the body. Typical symptoms of HFrEF are like those of HFpEF but include a rapid or irregular heartbeat.
The overall quality of life, functional limitations, and survival rates of HFpEF and HFeEF are similar (Kaye & Nanayakkara 2019). It is much more difficult to treat HFpEF. As of now, there are more evidence-based interventions for HFrEF. Doctors are seeing an increased prevalence of HFpEF, catalyzing the clinical development of a device-based therapy treating HFpEF.
Diagnosing Heart Failure
Typical diagnostic tools echocardiography and natriuretic peptide assays.
An echocardiogram is a non-invasive ultrasound of the heart and its nearby blood vessels. Echocardiography is considered one of the most useful tests in diagnosing HFpEF (Handoko 2016). Due to its spatial and temporal resolution, it provides a way to estimate the filling pressures of the heart. Diastolic dysfunction (improper relaxing of the heart muscles) is the hallmark of identifying HFpEF (Cleveland Clinic). Doctors will search for this in the echocardiography utilizing the Doppler parameters. An echo will show an elevated E/e’ ratio (>15mmHG) for patients with diastolic dysfunction (Park & Marwick 2011). An E wave is the early diastolic flow velocity of blood moving from the left atrium to the left ventricle. The e’ wave is the velocity of the diastolic velocity of the ring-like structure at the base of the mitral valve called the mitral annulus. An increased E/e’ ratio indicates increased pressure in the left ventricle (Park & Marwick 2011).
Note: Diastole refers to the phase of the heartbeat when the heart muscles relax, allowing the chambers to fill with blood. In a blood pressure reading, the diastolic pressure is the number on the bottom.
(Photo from Pick 2008)
Close-up of the mitral valve which separates the left atrium and left ventricle. The pressures calculated here create the E/e’ ratio which is a key indicator of diastolic dysfunction.
The second option to help diagnose HFpEF is natriuretic peptide assays. Natriuretic peptides are proteins that the heart and blood vessels make. A higher level of these peptides in the bloodstream may be an indication of heart failure. Healthcare providers have the option of measuring for two different types of natriuretic peptides.
A brain natriuretic peptide (BNP) is a type of hormone that can be thought of as a chemical messenger. These "messengers" are released by the heart when it is working harder than normal to pump blood. A BNP will signal to the blood vessels to open wider to excrete water and salt through urine, thus reducing the blood pressure by decreasing the amount of blood your body must pump. A patient experiencing HF will have a higher level of BNP because the heart will be struggling to circulate enough blood, requiring the heart to work harder.
An N-terminal pro b-type natriuretic peptide (NT-proBNP) can be thought of as an ingredient to make the BNP hormone. Again, if the heart is working harder to pump blood as it would in a patient experiencing HF, it will make larger amounts of NT-proBNP.
An assay measures the amount of these peptides within the bloodstream. It is done by taking a sample of blood from an arm vein or a fingerstick. Higher levels of these specific peptides will usually indicate HF (MedlinePlus).
Treatment Options for Patients with HFpEF
Drug Therapies
Treatments that are effective for HFrEF are typically ineffective for those with HFpEF (Kaye & Nanayakkara 2019). Studies have been performed to determine if a medicinal approach is an effective measure to treat HFpEF. Specifically, these studies tested medicines attempting to improve diastolic performance by improving blood flow, inducing relaxation, and reversing the stiffness of the heart muscles (myocardial stiffness). These studies have not identified an agent that is effective in achieving the desired results.
Device-Based Approach
The increased prevalence of HFpEF and the lack of a medicinal fix are driving the demand to develop devices to treat HFpEF. Shunts placed within the heart are one such device. Shunts redirect blood flow within the heart to hopefully correct any type of dysfunction. Computer-based studies suggested that an 8-millimeter shunt would lessen the activity-based rise in left atrium pressure and not cause excessive diversion (Kaye & Nanayakkara 2019). Corvia Medical has developed an interatrial shunt device (IASD) that is positioned within the atrial septum (the muscular wall that separates the left and right atriums). This shunt provides continuous passage of blood from the left atrium to the right atrium which in turn lowers the peak left atrial pressure.
(Photo from Kaye & Nanayakkara 2019)
Photos A & B are the IASD.
Photo C is the delivery of the IASD from continuous X-ray beams showing real-time images of a procedure (fluoroscopic imaging).
Photo D shows the left-to-right flow of blood through the shunt on an echo.
Does it Work?
A non-randomized study of the 8mm IASD was conducted on 64 patients with follow-ups at six months and one year. The study excluded patients who were at risk of having pressure in the right atrium exceeding that of the left. The implementation during this trial resulted in no device-related complications. Based on the 6-month follow-up, there were signs of mild but statistically significant increases in right atrial pressure, right atrial volume, and right ventricular volume (Kaye & Nanayakkara 2019). This led to an increase in cardiac output giving patients an improvement in quality of life.
Based on this trial, a randomized trial including 608 patients conducted over five years has been started. This will build upon the data gathered in the first trial to confirm or deny the seemingly positive outcomes of the shunt.
Ending Thoughts
The benefits of the IASD seem promising. However, the complex nature of HFpEF requires further study to adequately claim that the IASD is the “go-to” solution for HFpEF. The results from the ongoing clinical trial will provide better information to decide whether the IASD is the best measure to improve patients' quality of life and long-term outcomes.
References
Cleveland Clinic. (n.d.). Diastolic dysfunction. Cleveland Clinic. https://my.clevelandclinic.org/health/diseases/23434-diastolic-dysfunction
Handoko, M. L. (2016). How to diagnose heart failure with preserved ejection fraction: The value of invasive stress testing. Netherlands Heart Journal, 24(4), 244-251. https://doi.org/10.1007/s12471-016-0811-0
Heart Valve Surgery. (2008, September 2). Mitral valve annulus: Definition, diagrams, prolapse, calcification, treatment. https://www.heart-valve-surgery.com/heart-surgery-blog/2008/09/02/mitral-valve-annulus-definition-diagrams-prolapse-calcification-treatment/
Kaye, D. M., & Nanayakkara, S. (2019). Interatrial shunt device for heart failure with preserved ejection fraction. Frontiers in Cardiovascular Medicine, 6, 464015. https://doi.org/10.3389/fcvm.2019.00143
MedlinePlus. (n.d.). Natriuretic peptide tests (BNP and NT-proBNP). U.S. National Library of Medicine. https://medlineplus.gov/lab-tests/natriuretic-peptide-tests-bnp-nt-probnp/
Park, H., & Marwick, T. H. (2011). Use and limitations of E/e' to assess left ventricular filling pressure by echocardiography. Journal of Cardiovascular Ultrasound, 19(4), 169-173. https://doi.org/10.4250/jcu.2011.19.4.169 Assessed and Endorsed by the MedReport Medical Review Board