In the Journals

Higher NYHA functional class confers worse HFpEF outcomes; BMI may be factor

In patients with HF with preserved ejection fraction, advanced NYHA functional class is linked to elevated risk for cardiac death and hospitalization for HF, according to data published in the Journal of the American College of Cardiology.

In this population, the common symptom of breathlessness is related to BMI, left ventricular diastolic function and pulmonary vasculature, the researchers wrote.

Researchers evaluated 193 patients with HF with preserved ejection fraction (HFpEF) at the Medical University of Vienna to identify patient-related variables linked to NYHA functional class and to determine how functional class affects outcomes. The primary endpoint was hospitalization for HF or cardiac death. Mean follow-up was 21.9 months.

According to the researchers, patients with NYHA functional classes III and IV were older (P = .008), had higher BMI (P = .004) and were more likely to have arterial hypertension (P = .002) and to be taking diuretic agents (P < .001). In addition, patients with higher functional class also had higher N-terminal pro–B-type natriuretic peptide serum levels (P = .001), lower hemoglobin levels (P = .006) and lower glomerular filtration rates (P = .008).

Parameters of LV dysfunction such as early mitral inflow velocity and early diastolic mitral annual velocity (P = .023), as well as parameters of right ventricular (RV) afterload such as diastolic pulmonary artery pressure (P < .001), were more pronounced in patients with a higher NYHA class, according to Daniel Dalos, MD, from the division of cardiology, department of internal medicine II, Medical University of Vienna, and colleagues.

The following were independently associated with advanced NYHA class: age (P = .007), BMI (P = .002), NT-proBNP (P < .001), early mitral inflow velocity and mitral peak velocity of late filling (P = .031) and diastolic pulmonary artery pressure (P < .001), according to the researchers.

Higher class, worse outcomes

By the end of the follow-up period, the combined endpoint occurred in 64 patients (33.2%). Sixteen patients died from cardiac causes and three from other reasons. The Kaplan-Meier analysis showed that patients with higher NYHA classes had shorter event-free survival compared with those in NYHA class II or II (log-rank P < .001). The researchers wrote that more than 60% of patients categorized as NYHA class IV had events within the first 12 months.

NYHA class was independently associated with the combined endpoint (HR = 2.133; P = .04), NT-proBNP (HR = 1.655; P < .001) and impaired RV function (HR = 2.36; P = .001), Dalos and colleagues found.

“Clinically meaningful therapeutic interventions should target body weight, [LV] stiffness and concomitant pulmonary vascular disease,” the researchers wrote.

Obesity a factor

In an accompanying editorial, Dalane W. Kitzman, MD, of the department of cardiovascular medicine and section on geriatrics and gerontology at Wake Forest School of Medicine in Winston-Salem, North Carolina, and Sanjiv J. Shah, MD, of the division of cardiology, department of medicine, Feinberg Cardiovascular Research Institute, Northwestern University Feinberg School of Medicine, wrote that one of the most novel findings was the link between increased BMI and worsening NYHA class and that “BMI is a key contributor to symptoms of breathlessness in patients with HFpEF.

“Increased adiposity promotes inflammation, hypertension, insulin resistance and dyslipidemia, and also impairs diastolic, systolic, arterial, skeletal muscle and physical function, all of which are abnormal in patients with HFpEF and contribute to its pathophysiology,” Kitzman and Shah wrote. “Unfortunately, obesity has not only been overlooked as a potentially pivotal factor in HFpEF pathophysiology and treatment, it has been actively avoided.” – by Tracey Romero

Disclosure: The researchers report no relevant financial disclosures. Kitzman reports receiving consulting fees from AbbVie, Actavis, Corvia Medical, GlaxoSmithKline, Merck, Regeneron and Relypsa; receiving grant funding from Novartis; and owning stock in Gilead Sciences and Relypsa. Shah reports receiving funding from Actelion, AstraZeneca and Novartis, and consulting fees from AstraZeneca, Bayer, Merck and Novartis.

In patients with HF with preserved ejection fraction, advanced NYHA functional class is linked to elevated risk for cardiac death and hospitalization for HF, according to data published in the Journal of the American College of Cardiology.

In this population, the common symptom of breathlessness is related to BMI, left ventricular diastolic function and pulmonary vasculature, the researchers wrote.

Researchers evaluated 193 patients with HF with preserved ejection fraction (HFpEF) at the Medical University of Vienna to identify patient-related variables linked to NYHA functional class and to determine how functional class affects outcomes. The primary endpoint was hospitalization for HF or cardiac death. Mean follow-up was 21.9 months.

According to the researchers, patients with NYHA functional classes III and IV were older (P = .008), had higher BMI (P = .004) and were more likely to have arterial hypertension (P = .002) and to be taking diuretic agents (P < .001). In addition, patients with higher functional class also had higher N-terminal pro–B-type natriuretic peptide serum levels (P = .001), lower hemoglobin levels (P = .006) and lower glomerular filtration rates (P = .008).

Parameters of LV dysfunction such as early mitral inflow velocity and early diastolic mitral annual velocity (P = .023), as well as parameters of right ventricular (RV) afterload such as diastolic pulmonary artery pressure (P < .001), were more pronounced in patients with a higher NYHA class, according to Daniel Dalos, MD, from the division of cardiology, department of internal medicine II, Medical University of Vienna, and colleagues.

The following were independently associated with advanced NYHA class: age (P = .007), BMI (P = .002), NT-proBNP (P < .001), early mitral inflow velocity and mitral peak velocity of late filling (P = .031) and diastolic pulmonary artery pressure (P < .001), according to the researchers.

Higher class, worse outcomes

By the end of the follow-up period, the combined endpoint occurred in 64 patients (33.2%). Sixteen patients died from cardiac causes and three from other reasons. The Kaplan-Meier analysis showed that patients with higher NYHA classes had shorter event-free survival compared with those in NYHA class II or II (log-rank P < .001). The researchers wrote that more than 60% of patients categorized as NYHA class IV had events within the first 12 months.

NYHA class was independently associated with the combined endpoint (HR = 2.133; P = .04), NT-proBNP (HR = 1.655; P < .001) and impaired RV function (HR = 2.36; P = .001), Dalos and colleagues found.

“Clinically meaningful therapeutic interventions should target body weight, [LV] stiffness and concomitant pulmonary vascular disease,” the researchers wrote.

Obesity a factor

In an accompanying editorial, Dalane W. Kitzman, MD, of the department of cardiovascular medicine and section on geriatrics and gerontology at Wake Forest School of Medicine in Winston-Salem, North Carolina, and Sanjiv J. Shah, MD, of the division of cardiology, department of medicine, Feinberg Cardiovascular Research Institute, Northwestern University Feinberg School of Medicine, wrote that one of the most novel findings was the link between increased BMI and worsening NYHA class and that “BMI is a key contributor to symptoms of breathlessness in patients with HFpEF.

“Increased adiposity promotes inflammation, hypertension, insulin resistance and dyslipidemia, and also impairs diastolic, systolic, arterial, skeletal muscle and physical function, all of which are abnormal in patients with HFpEF and contribute to its pathophysiology,” Kitzman and Shah wrote. “Unfortunately, obesity has not only been overlooked as a potentially pivotal factor in HFpEF pathophysiology and treatment, it has been actively avoided.” – by Tracey Romero

Disclosure: The researchers report no relevant financial disclosures. Kitzman reports receiving consulting fees from AbbVie, Actavis, Corvia Medical, GlaxoSmithKline, Merck, Regeneron and Relypsa; receiving grant funding from Novartis; and owning stock in Gilead Sciences and Relypsa. Shah reports receiving funding from Actelion, AstraZeneca and Novartis, and consulting fees from AstraZeneca, Bayer, Merck and Novartis.