Phenotype-oriented approach to clinical evaluation of patients with chronic heart failure with preserved left ventricular ejection fraction
Authors: K. M. Amosova  , K. I. Chernyayeva  , Yu. V. Rudenko  , A. B. Bezrodniy  , N. V. Shyshkina  
Published: October 2018

The aim — to establish the clinical significance of the phenotype‑based approach to assessing patients with verified heart failure (HF) with preserved left ventricular (LV) ejection (LV) fraction and its relationship with the character and severity of morphofunctional changes in the heart and blood vessels.Materials and methods. The study involved 120 patients diagnosed with HF and preserved LVEF of IIA or IIB stage, II or III functional class by NYHA, with LV EF ≥ 50 % and signs of LV diastolic dysfunction according to transthoracal echocardiography data. The patients underwent general clinical examination, determination of the level of N‑terminal fragment of the brain natriuretic peptide precursor, transthoracal doppler sonography, applanation tonometry, 6‑minute walk test. The frequency of non‑cardiac and cardiac comorbid states was analyzed.Results and discussion. Patients were divided into four groups: phenotype «aging» (n = 26), «obesity» (n = 23), «coronary artery disease» (n = 27), «pulmonary hypertension» (n = 27). The control group included 17 patients with arterial hypertension without criteria specific to other phenotypes of HF with preserved EF, matched by age and blood pressure. Central systolic blood pressure in patients with phenotypes of «aging» (2), «obesity» (3), «coronary artery disease» (4), «pulmonary hypertension» (5) and patients of the control group (1) was 140.5 ± 8.9, 140.1 ± 11.4, 131.6 ± 13.2, 137.9 ± 8.8 and 136.5 ± 11.0 mm Hg, respectively (p1 — 2, 1 — 3, 1 — 4, 1 — 5, 2 — 4, 3 — 4 < 0.05), central pulse arterial pressure — 68.1 ± 9.1, 57.4 ± 12.6, 53.9 ± 11.5, 49.7 ± 7.9 and 59.1 ± 12.9 mm Hg (p1 — 2, 1 — 5, 2 — 3, 2 — 4, 2 — 5 < 0.05), pulse wave velocity — 12.4 ± 1.8, 12.3 ± 1.4, 12.8 ± 1.6, 13.3 ± 6.7 and 11.8 ± 1.2 m/s (all p < 0.05), augmentation index is standardized to the heart rate rate of 75 per 1 min — 37.4 ± 7.9, 34.9 ± 8.3, 39.7 ± 8.7, 48.9 ± 5.7 and 36.9 ± 6.4 (p1 — 4 < 0.05; p1 — 5, 2 — 5, 3 — 5, 4 — 5 < 0.01), augmentation pressure — 20.3 ± 4.4, 19.8. ± 5.2, 19.8 ± 4.8, 25.0 ± 2.9 and 21.3 ± 4.0 (p1 — 5, 2 — 5, 3 — 5, 4 — 5 < 0.01), the index of myocardial mass of LV — 180.4 ± 34.1, 196.7 ± 45.7, 195.0 ± 28.5, 186.9 ± 25.4 and 173.1 ± 32.9 g/m2 (p1 — 2, 1 — 3, 1 — 4, 1 — 5, 2 — 3, 2 — 4, 3 — 5, 4 — 5 < 0.05), left atrium volume index — 39.5 ± 7.4, 42.7 ± 6.9, 39.0 ± 3.8, 49.1 ± 10.3 and 38.8 ± 4.9 ml/m2 (p2 — 3, p3 — 4, 1 — 5, 2 — 5, 4 — 5 < 0.01, p1 — 3, 3 — 5 < 0.05), E/e¢ at rest — 14.1 ± 0.7, 14.3 ± 2.2, 14.2 ± 1.3, 15.9 ± 2.3 and 13.8 ± 3.2 (p1 — 2, 1 — 4, 1 — 4, 1 — 5, 2 — 5, 3 — 5, 4 — 5 < 0.05), the time of isovolumic relaxation — 95.5 ± 13.7, 84.4 ± 20.5, 95.1 ± 12.6, 84.7 ± 12.5 and 101.6 ± 13.2 ms (p1 — 3, 1 — 4, 1 — 5, 2 — 3, 2 — 5, 3 — 5, 4 — 5 < 0.05), e¢ser — 6.1  ±  1.8, 5.5 ± 1.1, 5.0 ± 1.0, 4.6 ± 0.7 and 6.4 ± 1.5 cm/s (p1 — 5, 2 — 5, 3 — 5 < 0.01, p1 — 3, 1 — 4, 4 — 5 < 0.05), the distance of 6 minute walk — 371.5 ± 81.9, 362.9 ± 81.0, 350.7 ± 50.2, 310.4 ± 67.2 and 472.9 ± 78.4 m (p1 — 5, 2 — 4, 3 — 4, 2 — 5, 3 — 5 < 0.01, p1 — 2, 1 — 3, 1 — 4, 4 — 5 < 0.05), the level of N‑terminal fragment of the brain natriuretic peptide precursor — 462.5 ± 237.3, (605. 9 ± 242.2), 626.3 ± 203.9, 1069.9 ± 315.3 and 287.1 ± 134.4 ng/ml (all p < 0.01), the number of patients with HF of III function class by NYHA — 13 (50.0 %), 12 (52.2 %), 17 (62.9 %), 16 (59.3 %) (p1 — 2, 1 — 3, 1 — 4, 1 — 5 < 0.05).Conclusions. The phenotype of «aging» most clearly reflects an increase in rigidity of the aorta, which leads to an increase in central aortic pressure and more pronounced diastolic dysfunction. The phenotype of «obesity» is characterized by considerable volume overload, LV hypertrophy and its diastolic dysfunction with higher filling pressures. The «coronary artery disease» phenotype is more often developed in men, is accompanied by diastolic dysfunction of LV mainly due to myocardial ischemia, a smaller volume of viable cardiomyocytes, and aortic stiffness, which in this case is conditioned by atherosclerotic calcification. The «pulmonary hypertension» phenotype is more characteristic of women and is accompanied by a significant increase in post‑loading on the LV, more pronounced structural changes in the myocardium with the involvement of the right heart, as well as the initial systolic dysfunction of the LV.