Mitochondrial ultrastructure in cardiac myocytes is associated with the cardiovascular death in patients with heart failure

Table 1 Clinical and anamnestic characteristics of patients included in the study, n (%)

Parameter		Value
Age, years		66 (57; 71)
Male gender		35 (87.5)
Female gender		5 (12.5)
Arterial hypertension		39 (97.5)
A history of stroke		2 (5)
History of myocardial infarction		34 (85)
AF		14 (35)
BMI, kg/m2		30 (26; 33)
NYHA class	I	2 (5)
	II	22 (55)
	III	15 (37.5)
	IV	1 (2.5)
Decompensation of HF in the last 12 months		11 (27.5)
LVEF, %		38 (30; 45.7)
NTproBNP, pg/mL		170 (73; 316)
The result of the 6MWT, m		355 (295; 400)
CCS angina class	I	6 (15)
	II	14 (35)
	III	20 (50)
	IV	0

AF: Atrial fibrillation; BMI: Body mass index; HF: Heart failure; NYHA: The New York Heart Association; LVEF: Left ventricular ejection fraction; NTproBNP: N-terminal fragment pro B - type natriuretic peptide; 6MWT: 6-minute walk test; CCS: Canadian Cardiovascular Society.

Table 2 Incidence of adverse cardiovascular events within 12 months after coronary artery bypass grafting.

Event	Absolute quantity (n)	Relative quantity (%)
Death from cardiovascular diseases	6	15
Hospitalization due to heart failure	6	15
Acute ischemic events requiring unplanned revascularization (myocardial infarction, progressive angina)	1	2.5
Stroke	0
A combined primary endpoint that includes death from cardiovascular causes, hospitalization for heart failure, acute ischemic events requiring unplanned revascularization (myocardial infarction, progressive angina), and acute cerebrovascular accidents	13	32.5

Table 3 Results of the analysis of associations between the ultrastructural characteristics of mitochondria and the development of adverse cardiovascular events

Parameter		Total area of interfibrillar mitochondria		The ratio of the length of the outer membrane to the length of the inner membrane		Integral indicator
The end point		Value	P value	Value	P value	Value	P value
Death from CVD	No	41 (35; 50)	0.343	29 (20; 33.5)	0.001	1.5 (1; 2.4)	0.024
	Yes	34 (26; 53)		41 (35; 45)		1 (0.7; 1.4)
Hospitalization due to HF	No	40 (34; 48)	0.299	30.5 (24; 37)	0.556	1.3 (0.9; 2.4)	0.619
	Yes	49 (36; 52)		26 (20; 31)		1.8 (1.3; 2.5)
Progression of HF symptoms	No	37 (32; 47)	0.315	28 (19; 36)	0.712	1.4 (0.9; 2.4)	0.573
	Yes	44 (41; 51)		30 (22; 33)		1.7 (0.6; 1.9)
Combined primary end point (MACE)	No	40 (34; 47)	0.795	28 (19; 36)	0.127	1.4 (0.9; 2.4)	0.279
	Yes	44 (31; 51)		33 (26; 41)		1.4 (0.7; 1.9)

CVD: Cardiovascular diseases; HF: Heart failure; MACE: Major adverse cardiovascular events - serious adverse cardiovascular events.

Table 4 Results of a comparative analysis of the baseline clinical, anamnestic, and laboratory-instrumental characteristics between the groups of patients who survived (n = 34) and died (n = 6) during the subsequent one-year prospective follow-up, n (%)

Parameter	Group 1 (n = 34)	Group 2 (n = 6)	P value
Age, years	65 (56; 69)	71 (58; 72)	0.098
Gender: Male	29 (85.3)	6 (100)	0.423
Atrial fibrillation	9 (26.5)	3 (50)	0.243
History of myocardial infarction	28 (82.4)	6 (100)	0.264
CCS angina class			0.402
I	5 (14.7)	1 (16.7)
II	13 (38.2)	1 (16.7)
III	16 (47.1)	4 (66.6)
NYHA class			0.392
I	1 (2.9)	1 (16.7)
II	20 (58.8)	2 (33.3)
III	12 (35.3)	3 (50)
IV	1 (2.9)	0
Decompensation of HF over the past year	7 (20.6)	4 (66.7)	0.039
Chronic obstructive pulmonary disease	9 (26.5)	2 (33.3)	0.536
A history of stroke	2 (5.9)	0	0.719
Body mass index, kg/m2	30 (27; 34)	28 (23; 30)	0.149
Systolic blood pressure, mm Hg	130 (123; 140)	135 (120; 141)	0.726
Diastolic blood pressure, mm Hg	80 (80; 82)	80 (77.5; 82)	0.999
Heart rate, bpm	72 (62; 78)	72 (68; 86)	0.383
Hemoglobin, g/dL	150 (141; 158)	148 (137; 158)	0.926
Creatinine, mg/dL	94 (76; 103)	100 (88; 109)	0.288
eGFR, mL/minute/m2	75 (62; 88)	70 (60; 76)	0.324
Fasting plasma glucose, mmol/L	6.1 (5.2; 6.3)	5.5 (5; 6.8)	0.592
Total cholesterol, mmol/L	4 (3.1; 4.9)	3.7 (2.8; 4.5)	0.592
Triglycerides, mmol/L	1.66 (1.2; 2.2)	1.44 (1; 1.9)	0.541
Low-density lipoproteins, mmol/L	2.2 (1.4; 3)	2.1 (1; 2.7)	0.425
High-density lipoproteins, mmol/L	0.98 (0.8; 1.1)	1 (0.8; 1.2)	0.582
NTproBNP, pg/mL	163 (73; 326)	170 (74; 349)	0.914
LA, mm	43.5 (40; 47)	43 (39; 56)	0.775
LVEDV, mL	176 (130; 206)	184 (150; 188)	0.999
LVESV, mL	111 (73; 140)	122 (89; 134)	0.835
E/e’	11 (8.8; 15)	13 (9; 17)	0.300
LVMI, g/m2	119 (104; 150)	114 (107; 122)	0.483
sPAP, mm Hg	32 (28; 42)	40 (34; 48)	0.103
LVEF, %	39.5 (30; 46)	35 (28; 41)	0.425
SYNTAX score, points	24 (18; 29)	22 (17; 28)	0.449
Number of shunts	3 (3; 3.25)	3 (2; 3.5)	0.823
Complications	18 (52.9)	6 (100)	0.064
Infectious complications	10 (31.3)	2 (40)	0.999
Duration of hospitalization, bed-days	21.5 (19; 27)	27 (23; 34)	0.043
Drug therapy after discharge
Beta-blockers	28 (82.4)	4 (66.6)	0.740
ACE inhibitor	15 (44.1)	2 (33.3)	0.623
ARBs	5 (14.7)	2 (33.3)	0.600
ARNI	10 (29.4)	2 (33.3)	0.848
Any RAAS inhibitor	30 (88)	6 (100)	0.883
iNGLT2	23 (67.6)	3 (50)	0.711
MRAs	25 (73.5)	3 (50)	0.499
Loop diuretics	25 (73.5)	4 (66.6)	0.882
Iron preparations	13 (38.2)	2 (33.3)	0.820

HF: Heart failure; NYHA: The New York Heart Association; CCS: Canadian Cardiovascular Society; eGFR: Estimated glomerular filtration rate; NT-proBNP: N-terminal fragment of pro B-type natriuretic peptide; LA: Left atrium; LVEDV: Left ventricular end-diastolic volume; LVESV: Left ventricular endsystolic volume; E/e’: Ratio of the maximum rate of early diastolic filling of the mitral flow to the early diastolic rate of movement of the fibrous ring of the mitral valve; LVMI: Left ventricular mass index; sPAP: Systolic pulmonary artery pressure; LVEF: Left ventricular ejection fraction; SYNTAX: Synergy between Percutaneous Coronary Intervention with TAXUS and Cardiac Surgery; ACE: Angiotensin converting enzyme; ARBs: Angiotensin receptor blockers; ARNI: Angiotensin receptors and non-lysine inhibitor; RAAS: Renin-angiotensin-aldosterone system; iNGLT2: Type 2 sodium-glucose co-transporter inhibitor; MRAs: Mineralocorticoid receptor antagonists.

Table 5 Results of the univariate logistic regression analysis

Parameter	B (regression coefficient)	The Wald significance test	P value	OR	95%CI
					The lower limit	The upper limit
Ratio of mitochondrial membrane lengths	0.134	4.440	0.035	1.143	1.009	1.295

OR: Odds ratio; CI: Confidence intervals.