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Treatment of HFpEF in type 2 diabetes critical in improving outcomes
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PHILADELPHIA — Ways to effectively manage and diagnose HF with reduced ejection fraction in patients with type 2 diabetes have become a point of concern, according to a speaker at the Heart in Diabetes conference.
The incidence of HF in type 2 diabetes has increased to the point where it has become more common as the initial presentation of CVD in these patients than acute MI, David Fitchett, MD, a cardiologist at St. Michael’s Hospital in Toronto, said during his presentation.
“Diabetes is increasing in near-epidemic proportions,” Fitchett told Cardiology Today. “Particularly in women, with a fivefold increased incidence compared with nondiabetic individuals, there is a high overall prevalence of HF in diabetes, and in fact, in elderly patients, HF may be present in up to 30% if you look for it, especially in obese patients.”
As HF incidence increases, the risk for HF with preserved ejection fraction has become greater as it is often unrecognized and has a lack of proven treatment compared with HFrEF, leading to poor quality of life, he said.
Based on data between 2006 and 2020, HFpEF has been on an upward trend while the relative incidence of HFrEF is on an apparent decline, according to Fitchett.
“It’s projected by next year that 65% of patients hospitalized with HF will have an ejection fraction of greater than 40%,” he said. “But it’s important to recognize that in comparison to HFrEF, comorbidity is a very important association both in the development of the disease and in its progression.”
Phenotypes of HFpEF
Predisposition phenotypes in HFpEF include metabolic syndrome, overweight and obesity, renal dysfunction, hypertension and CAD, which are also components all found in patients with diabetes, Fitchett said.
“We also recognize that HFpEF is not a single disease of diastolic dysfunction, and there are these heterogenous phenotypes associated with diastolic impairment,” he said.
Shortness of breath and lung congestion were some of the most common presentations of HFpEF in patients, as well as decreased exercise performance affected by chronotropic incompetence, pulmonary hypertension and atrial fibrillation, according to Fitchett.
Systemic inflammation is also believed to be a critical component in signaling HFpEF, which is driven by a combination of metabolic syndromes and renal insufficiency affecting the heart, peripheral musculature and the kidneys, he said.
“The heart is affected by oxidative stress but also inflammation leading to a combination of hypertrophy and fibrosis, which affects diastolic dysfunction,” Fitchett said. “However, this present review makes a very important comment — that understanding and targeting the pathological processes that contribute to the phenotypes of HFpEF may have a greater benefit than targeting the final pathway of cardiac dysfunction alone.”
Diagnosis a challenge
Among patients with diabetes, HFpEF most often occurred in younger patients, mostly men, who had a high BMI, Fitchett said. The severity of HFpEF is tied to increased morbidities in patients with diabetes, including renal dysfunction, hypertension and chronic obstructive pulmonary disease, as well as increased left ventricular mass, LV diastolic volume and greater LV filling pressures and increased diabetic biomarkers.
In data from the CHARM study, patients with diabetes had a twofold increase in incidence of hospitalization or CV mortality in both HFrEF (adjusted HR = 1.6; 95% CI, 1.44-1.77) and HFpEF (aHR = 2; 95% CI, 1.7-2.36) compared with patients without diabetes, Fitchett said.
In HFrEF, 80% to 85% of patients die of CV causes, whereas in HFpEF, 60% die of CV causes, 30% die of non-CV causes and 10% die of multiorgan failure, he said.
Diagnosis of HFpEF is “a challenge,” Fitchett said, as plasma B-type natriuretic peptide levels may not necessarily be elevated, and it may take an exercise stress test to measure filling pressures to diagnose.
“We recognize that HF is often missed in patients with diabetes,” he said.
In findings from a study from the Netherlands, 28% of patients with diabetes with no history of HF were found to have unrecognized HF, with most of those patients having HFpEF, Fitchett said. The prevalence of HF was greater in older adults, women, patients with obesity, dyspnea or hypertension and those who complained of fatigue.
Management of HFpEF
Treatments have been ineffective in managing HFpEF in patients with diabetes, as there are no HF agents proved to improve outcomes, no benefits were seen from tight glycemic control and the use of type 2 diabetes medications such as thiazolidinediones and saxagliptin (Onglyza, AstraZeneca) increased HF risk, Fitchett said.
Data from the STENO-2 study showed intensive risk factor therapy reduced HF hospitalization in patients with diabetes compared with conventional therapy (HR = 0.51; 95% CI, 0.34-0.76) while decreasing the instance of HF by 50% during a 20-year period since randomization, he said.
“I wonder if a substantial number of these patients were patients with HFpEF?” Fitchett said. “We don’t know, but in patients with diabetes, clearly intensive risk factor management is important for many reasons, but it may be beneficial in patients with HFpEF.”
Studies focusing on SGLT2 inhibitors, which have reduced the incidence of HF, may suggest the possibility of lowering incidence of HFpEF, he said.
Although EMPA-REG, CANVAS, DECLARE-TIMI 58 and CREDENCE have shown a similar reduction of HF hospitalization in patients with diabetes, the studies lacked the consistent measure of ejection fraction and echocardiographic data, Fitchett said.
“There are a substantial portion of patients in the CANVAS study and the DECLARE study in whom we don’t know what their ejection fractions were,” he said. “There is an urgent need for research to improve outcomes in patients with HFpEF, especially with diabetes who have a high risk of adverse outcomes.” – by Earl Holland Jr.
Reference:
Fitchett D, et al. Heart failure with preserved ejection fraction and diabetes. Presented at: Heart in Diabetes CME Conference; July 12-14, 2019; Philadelphia.
Disclosures: Fitchett reports he received consultant fees and honoraria from AstraZeneca, Boehringer Ingelheim, Eli Lilly and Janssen, served on the steering committee for a trial sponsored by Boehringer Ingelheim and served on the data safety monitoring board for two trials sponsored by Novo Nordisk.