Chronic digitalis therapy in patients before heart transplantation is an independent risk factor for increased posttransplant mortality

Figures & data

Table 1 Demographic and clinical characteristics

Parameter	Chronic digitalis before HTX (n=347)	No chronic digitalis before HTX (n=183)	P-value
Recipient data
Age in years, mean ± SD	51.9±10.4	51.5±10.5	0.7164
Male sex, n (%)	273 (78.7)	139 (76.0)	0.4745
Body mass index (kg/m^2), mean ± SD	24.6±3.8	25.2±3.9	0.0793
Coronary artery disease, n (%)	142 (40.9)	80 (43.7)	0.5354
Arterial hypertension, n (%)	187 (53.9)	101 (55.2)	0.7750
Dyslipidemia, n (%)	225 (64.8)	114 (62.3)	0.5615
Diabetes mellitus, n (%)	131 (37.8)	51 (27.9)	0.0227*
Renal insufficiency,^ n (%)	208 (59.9)	97 (53.0)	0.1245
Glomerular filtration rate, mean ± SD	60.5±19.4	60.4±23.4	0.9753
Principal diagnosis for HTX
Nonischemic CMP, n (%)	204 (58.8)	80 (43.7)	0.0009*
Ischemic CMP, n (%)	114 (32.9)	67 (36.6)	0.3856
Valvular heart disease, n (%)	23 (6.6)	6 (3.3)	0.1069
Cardiac amyloidosis, n (%)	6 (1.7)	30 (16.4)	<0.0001*
Donor data
Age in years, mean ± SD	38.9±13.0	41.1±13.6	0.0713
Male sex, n (%)	163 (47.0)	74 (40.4)	0.1501
Body mass index (kg/m^2), mean ± SD	24.4±3.6	24.9±4.5	0.1622
Transplant sex mismatch
Mismatch, n (%)	148 (42.7)	81 (44.3)	0.7219
Donor (m) to recipient (f), n (%)	19 (5.5)	8 (4.4)	0.5826
Donor (f) to recipient (m), n (%)	129 (37.2)	73 (39.9)	0.5406
Perioperative data
Biatrial HTX, n (%)	124 (35.8)	37 (20.2)	0.0002*
Bicaval HTX, n (%)	65 (18.7)	50 (27.3)	0.0225*
Total orthotopic HTX, n (%)	158 (45.5)	96 (52.5)	0.1291
LOS (days), mean ± SD	42.5±23.7	44.0±20.4	0.4396
Initial posttransplant medication
ASA, n (%)	25 (7.2)	16 (8.7)	0.5285
β-Blocker, n (%)	46 (13.3)	33 (18.0)	0.1421
Calcium channel blocker, n (%)	87 (25.1)	42 (22.9)	0.5885
Dihydropyridine, n (%)	33 (9.5)	18 (9.8)	0.9037
Non-dihydropyridine, n (%)	54 (15.6)	24 (13.1)	0.4496
ACE inhibitor/ARB, n (%)	163 (47.0)	77 (42.1)	0.2815
Diuretic, n (%)	347 (100.0)	183 (100.0)	na
Gastric protection (PPI/H2 blocker), n (%)	347 (100.0)	183 (100.0)	na

Notes:

^ Glomerular filtration rate <60 mL/min/1.73 m²;

* statistically significant (P<0.0500).

Abbreviations: ASA, acetylsalicylic acid; ACE inhibitor, angiotensin-converting enzyme inhibitor; ARB, angiotensin II receptor blocker; CMP, cardiomyopathy; f, female; H2 blocker, histamine receptor blocker; HTX, heart transplantation; LOS, length of initial hospital stay; m, male; n, number; na, not applicable; PPI, proton pump inhibitor; SD, standard deviation.

Figure 1 Thirty-day survival after HTX (Kaplan–Meier estimator).

Note: Patients with chronic digitalis therapy before HTX had a statistically significant inferior 30-day posttransplant survival, compared to patients without chronic digitalis therapy before HTX (P=0.0148).
Abbreviation: HTX, heart transplantation.

Figure 2 Two-year survival after HTX (Kaplan–Meier estimator).

Note: Patients with chronic digitalis therapy before HTX had a statistically significant inferior 2-year posttransplant survival, compared to patients without chronic digitalis therapy before HTX (P=0.0473).
Abbreviation: HTX, heart transplantation.

Table 2 Multivariate analysis for mortality within 30 days after HTX

Variable	Hazard ratio	95% confidence interval	P-value
Chronic digitalis therapy before HTX (in total)	2.097	1.036–4.248	0.0397*
Diabetes mellitus (in total)	0.868	0.488–1.542	0.6282
Nonischemic CMP (in total)	0.661	0.381–1.147	0.1414
Cardiac amyloidosis (in total)	0.327	0.042–2.510	0.2821
Biatrial HTX (in total)	1.228	0.675–2.234	0.5004
Bicaval HTX (in total)	0.779	0.350–1.736	0.5419

Note:

* Statistically significant (P<0.0500).

Abbreviations: CMP, cardiomyopathy; HTX, heart transplantation.

Table 3 Causes of death within 30 days after HTX

Parameter	Chronic digitalis before HTX (n=347)	No chronic digitalis before HTX (n=183)	P-value
Transplant failure, n (%)	31 (8.9)	6 (3.3)	0.0151*
Acute rejection, n (%)	1 (0.3)	1 (0.5)	0.6448
Infection/sepsis, n (%)	7 (2.0)	2 (1.1)	0.4335
Stroke/ICH, n (%)	3 (0.9)	1 (0.5)	0.6874
All causes, n (%)	42 (12.1)	10 (5.4)	0.0146*

Note:

* Statistically significant (P<0.0500).

Abbreviations: HTX, heart transplantation; ICH, intracranial hemorrhage; n, number.

Table 4 Echocardiographic features within 30 days after HTX

Parameter	Chronic digitalis before HTX (n=347)	No chronic digitalis before HTX (n=183)	P-value
End-diastolic diameter
Normal RA (<35 mm), n (%)	170 (49.0)	118 (64.5)	0.0007*
Normal LA (<40 mm), n (%)	147 (42.4)	106 (57.9)	0.0006*
Normal RV (<30 mm), n (%)	285 (82.1)	160 (87.4)	0.1140
Normal LV (<55 mm), n (%)	316 (91.1)	176 (96.2)	0.0302*
LVEF
≥55%, n (%)	308 (88.8)	174 (95.1)	0.0159*
<55%, n (%)	39 (11.2)	9 (4.9)
45%–54%, n (%)	9 (2.6)	3 (1.6)
30%–44%, n (%)	7 (2.0)	0 (0.0)
<30%, n (%)	23 (6.6)	6 (3.3)
Mitral regurgitation
No, n (%)	265 (76.4)	139 (76.0)	0.9155
Yes, n (%)	82 (23.6)	44 (24.0)
Mild, n (%)	81 (23.3)	42 (22.9)
Moderate, n (%)	1 (0.3)	2 (1.1)
Severe, n (%)	0 (0.0)	0 (0.0)
Tricuspid regurgitation
No, n (%)	216 (62.2)	123 (67.2)	0.2576
Yes, n (%)	131 (38.8)	60 (32.8)
Mild, n (%)	76 (21.9)	36 (19.7)
Moderate, n (%)	32 (9.3)	20 (10.9)
Severe, n (%)	23 (6.6)	4 (2.2)

Note:

* Statistically significant (P<0.0500).

Abbreviations: HTX, heart transplantation; LA, left atrium; LV, left ventricle; LVEF, left ventricular ejection fraction; n, number; RA, right atrium; RV, right ventricle.

Figure 3 Freedom from early posttransplant atrial fibrillation (Kaplan–Meier estimator).

Note: There was no statistically significant difference between patients with and without chronic digitalis therapy before HTX in the occurrence of 30-day posttransplant AF (P=0.1327).
Abbreviations: AF, atrial fibrillation; HTX, heart transplantation.