It was a scenario cardiologist Kavita Sharma encountered time and again during her residency at Johns Hopkins: A patient would present with signs of heart failure—shortness of breath, edema and fatigue—but a robust ejection fraction, or the amount of blood leaving the heart when it contracted.

Heart failure with preserved ejection fraction, or HFpEF, accounts for nearly one-half of the 6.6 million cases of heart failure in the U.S. and kills nearly 50 percent of people diagnosed with it within five years.

Although there are at least nine well-studied treatments for heart failure with reduced ejection fraction, HFpEF has poorly understood pathophysiology and virtually no proven therapies.

The mysteries of the condition intrigued Sharma, and within months of finishing her cardiology fellowship in 2014, she launched the Johns Hopkins HFpEF program—one of only a handful of such programs in the country. The centerpiece of the program is a clinic dedicated to diagnosis and treatment. Sharma sees about four to five new patients a week.

Clinical management focuses on reducing recurrent edema and treating comorbidities, including secondary hypertension, atrial fibrillation, diabetes and chronic kidney disease—all of which are commonly seen in patients with HFpEF. These therapies are also the cornerstones of treating classic heart failure, but HFpEF may require modifications that address its idiosyncrasies.

For example, a recent study led by Sharma showed that patients with HFpEF are more vulnerable to acute kidney injury as a result of standard fluid-removal therapies when admitted to the hospital and require more delicate approaches to fluid removal. The Johns Hopkins group is using low-dose intravenous dopamine experimentally. Some evidence suggests that dopamine promotes blood flow to the kidneys, and the strategy, Sharma says, may help mitigate injury.

The Johns Hopkins program is also a main site in several ongoing federal studies to assess treatment strategies and disease progression. Sharma and colleagues are collecting demographic, lifestyle, risk factor and laboratory data to help clarify the pathophysiology of HFpEF and understand the mechanisms that fuel the racial and gender disparities observed in the condition.

“Our program goals are ambitious, but how could they not be?” says Stuart Russell, co-director of the HFpEF program and director of heart failure and transplantation at Johns Hopkins. “The challenges posed by this disease demand nothing less.”