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cBIN1: the marker that could “set the score” for the heart

A team led by a Cedars-Sinai physician-scientist has discovered a biomarker – a protein found in the blood – for the most common type of heart failure, a new study published today in JAMA Cardiology shows. Heart failure with preserved ejection fraction (HFpEF) affects more than 6.5 million Americans each year. And now, thanks to the discovery of the first-ever biomarker for HFpEF, a simple blood test can reveal whether a patient’s heart is not making enough of an important protein. If the protein levels are decreased, the biomarker signal increases and physicians will be able to diagnose heart failure sooner, prescribe corrective medicines and prevent further disease progression. Heart failure with preserved ejection fraction is a condition where the heart can contract, but has problems relaxing–limiting the heart’s ability to fill with blood between each beat–and therefore lowers the amount of blood moving forward with each contraction. Prior to the discovery of the biomarker, clinicians had to wait for patients to have symptoms to make a diagnosis of HFpEF and had to barely use an echocardiogram. This pivotal research has the potential to impact millions of people and serve as a critical tool for preventive heart care.

Symptoms of heart failure typically appear as fatigue, fluid weight gain, leg swelling and shortness of breath. Heart failure with preserved ejection fraction is typically diagnosed in elderly people or those living with high blood pressure, diabetes, elevated cholesterol, hypertension, obesity, obstructive sleep apnea, anemia, iron deficiency or diabetes. Its prevalence is projected to rise drastically over the coming decades. Previous studies have shown that women represent the majority of patients diagnosed with the disease. There was no method to gauge the health of the heart muscle before symptoms developed or determine the severity of disease once symptoms were present. The biomarker, named cBIN1 Score, or CS for short–allows doctors to measure muscle deterioration and measure a protein that regulates the heart’s ability to both contract and relax. Cardiac bridging integrator 1 (cBIN1) is a circulating membrane scaffolding protein that is essential for transverse tubule health, and its plasma level declines with disease. As the protein decreases, CS increases, serving as an indication of onset heart failure.

The analysis examined the ability of the CS and N-terminal pro-B-type natriuretic peptide (NT-proBNP) results to differentiate among patients with HFpEF, healthy control participants, and control participants with risk factors for heart failure. The CS biomarker can be measured using a simple blood draw. The CS biomarker is designed to be used in an outpatient clinic setting. For patients with known HFpEF, doctors can draw a CS level and use it to both guide current care, including medication adjustments, and predict the chances of a patient being admitted to the hospital in the next 12 months. Robin Shaw, MD, PhD, the Wasserman Endowed Chair in Cardiology and professor of Medicine at the Smidt Heart Institute at Cedars-Sinai and principal investigator on the study; and Eduardo Marbán, MD, PhD, director of the Smidt Heart Institute, explain: “By the time heart failure symptoms develop, the critical window for corrective therapy has typically closed. Our discovery allows us to not only diagnose the disease sooner, but also to treat patients before that critical period of early intervention for lifesaving care has closed. More broadly, this discovery will allow the most at-risk patients–including older patients and patients with high blood pressure, diabetes or dyslipidemia–to be checked during an annual exam from their primary care physician”.

As next steps, researchers plan preventive interventions in which cBIN1 could be useful, including sex-based differences, for those who have undergone a heart transplant, valve replacement as well as individuals with no known heart disease.

  • Edited by Dr. Gianfrancesco Cormaci, PhD, specialist in Clinical Biochemistry.

Scientific references

Nikolova AP, Hitzeman TC et al. JAMA Cardiol. 2018 Oct 31.

Cho JH, Kilfoil PJ et al. JCI Insight. 2018 Oct 4; 3(19).

Cho JH et al. Circ Arrhythm Electrophysiol. 2018 Aug;11(8).

Gallet R et al. JACC Basic Transl Sci. 2016; 1(1-2):14-28.

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Dott. Gianfrancesco Cormaci
Dott. Gianfrancesco Cormaci
Laurea in Medicina e Chirurgia nel 1998, specialista in Biochimica Clinica dal 2002, ha conseguito dottorato in Neurobiologia nel 2006. Ex-ricercatore, ha trascorso 5 anni negli USA alle dipendenze dell' NIH/NIDA e poi della Johns Hopkins University. Guardia medica presso la casa di Cura Sant'Agata a Catania. In libera professione, si occupa di Medicina Preventiva personalizzata e intolleranze alimentari. Detentore di un brevetto per la fabbricazione di sfarinati gluten-free a partire da regolare farina di grano. Responsabile della sezione R&D della CoFood s.r.l. per la ricerca e sviluppo di nuovi prodotti alimentari, inclusi quelli a fini medici speciali.

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