"Stage B HFpEF" may represent transitional state from a healthy heart
Asymptomatic individuals with the earliest structural changes in the heart were at high risk of progressing to heart failure with preserved ejection fraction (HFpEF), researchers found.
Left ventricular (LV) myocardial stiffness was nearly 30% greater among middle-age people with LV hypertrophy and elevated cardiac biomarkers than in healthy controls (LV hypertrophy stiffness constant 0.053 vs 0.042 with preload expressed as transmural filling pressure, P=0.028).
In LV hypertrophy, patients also showed normal contractile function but less distensible LVs requiring smaller volumes for the same filling pressure, according to Benjamin Levine, MD, of Texas Health Presbyterian Hospital Dallas and the University of Texas Southwestern Medical Center, and colleagues in Circulation.
"Together, these findings suggest that these patients should be considered as 'stage B HFpEF' representing a transitional state from a normal healthy-heart to the pathophysiology that is observed in HFpEF," the authors suggested.
Levine's team noted their previous work showing that LV stiffening associated with sedentary aging can be observed by middle age. This can be reversed with 2 years of high-intensity exercise training for healthy, middle-age individuals without LV hypertrophy, however.
"Thus, we speculate that high intensity exercise holds promise as a potential intervention to prevent progression to HFpEF in high risk patients, if implemented at the optimum dose and age," they wrote, acknowledging that further studies are needed as proof.
For the study, the investigators had screened nearly 3,600 people from the population-based Dallas Heart Study. After selecting those who met the inclusion criteria (including ejection fraction at least 50% and documented LV hypertrophy) and getting candidates to phone screening and biomarker testing, they ended up with 46 high-risk patients with NT-proBNP >40 pg/ml or cardiac troponin T >0.6 pg/ml.
People with heart failure, ischemic heart disease, prior MI or stroke, or other comorbidities were excluded, as were those who were unable to exercise.
Selected study participants were matched with 61 healthy but sedentary controls. Average age was around 53 years, and women represented roughly half the cohort.
Even after matching, the LV hypertrophy group had significantly larger body size, higher blood pressure, and greater pulmonary capillary wedge pressure at baseline compared with controls, the researchers noted.
LV pressure-volume relationships were defined using right heart catheterization and 3D-echocardiography.
The difference in baseline body size between the two groups made it a challenge to scale volumetric parameters, Levine and colleagues noted. The research team also did not look at people who had LV hypertrophy without elevated biomarkers.
"We suspect, but cannot prove, that it is unlikely that such patients would have stiffer hearts than patients with LV hypertrophy with elevated biomarkers. Thus, although other groups of patients might also demonstrate an intermediate stage-B phenotype, we can say with some confidence that the specific patients studied here represent a particularly high risk group and should be considered for targeted preventative therapies."
This is important because there are currently few effective treatments for HFpEF -- recent disappointments include inhaled nitrite and sacubitril/valsartan (Entresto).
Some believe that HFpEF is not just one disease, and that coronary microvascular dysfunction may be a therapeutic target for certain patients.
The study was funded by the NIH, the American Heart Association, and the Harry S. Moss Heart Trust.
Levine and co-authors disclosed no relevant relationships with industry.
Source Reference: Hieda M, et al "Increased myocardial stiffness in patients with high risk left ventricular hypertrophy: the hallmark of stage-B HFpEF" Circulation 2019; DOI: 10.1161/CIRCULATIONAHA.119.040332.
Read the original article on Medpage Today: Stiff Heart Seen as Marker of Future HFpEF