January 7, 2016
It was a scenario cardiologist Kavita Sharma encountered time and again during her residency at Johns Hopkins. The patient, usually a woman, typically in her 50s or 60s, would present with textbook signs of heart failure—shortness of breath, edema, fatigue, orthopnea—but a remarkably robust ejection fraction. Yet the patient was clearly in serious, often advanced, heart failure with a constellation of companion disorders including hypertension, diabetes, atrial fibrillation and kidney disease.
Heart failure with preserved ejection fraction, or HFpEF, accounts for nearly half of the 6.6 million cases of heart failure in the U.S. and kills nearly half 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 in the country. The centerpiece of the program is a clinic dedicated to diagnosis and treatment. The clinic actively follows about 150 HFpEF cases; Sharma sees about four to five new patients a week.
All patients admitted to the hospital in acute heart failure with left ventricular ejection fraction greater than 50 percent are referred to the clinic, where they undergo echocardiograms with strain analyses and pulmonary function and cardio-metabolic stress tests. Some patients also get right-heart catheterizations and heart biopsies.
Ruling out underlying pathologies that can lead to secondary HFpEF is vital, Sharma says. A handful of patients, for example, have cardiac amyloidosis, which can often manifest as HFpEF. On the flip side, nephrologists and pulmonologists refer many patients who initially present with kidney disease or pulmonary hypertension, all of which makes interdisciplinary crosspollination key.
Clinical management focuses on removing fluid, reducing recurrent edema and treating comorbidities including secondary hypertension, atrial fibrillation, diabetes and chronic kidney disease, all of which are commonly seen in HFpEF patients. 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 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 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 the heart failure transplantation program at Johns Hopkins. “The challenges posed by this disease demand nothing less.”
WHAT ARE CARDIAC CELLS DOING IN HFPEF?
Johns Hopkins is the only site in the United States performing cardiac biopsies to better define the morphology of cardiac cells in HFpEF and glean insights about any molecular aberrations that account for the signature myocardial stiffness seen in HFpEF. The investigators are also performing genetic analyses seeking to pinpoint any DNA alterations that might illuminate heritable patterns of disease behavior.
“Much of our insights into human heart failure come from studies of muscle tissue from explanted hearts, but because HFpEF patients are generally not transplanted, our understanding of this disease is far more limited,” says David Kass, director of Johns Hopkins’ Center for Molecular Cardiobiology. “Cardiac biopsies will give us much-needed information about the characteristics and behavior of cardiac cells in HFpEF.”