Why carry out this study? |
Cardiac resynchronization therapy (CRT) fails to improve echocardiographic parameters and clinical outcome in up to 40% of patients. |
Sacubitril/valsartan (SV) applied as a replacement for angiotensin-converting enzyme 2 inhibitor (ACE2i) or angiotensin receptor blocker (ARB) resulted in left ventricular (LV) reverse remodeling and improved clinical outcomes in patients with heart failure with reduced ejection fraction (HFrEF). |
Herein, we investigated whether SV would also result in cardiac remodeling in the specific subgroup of CRT non-responders (CRT-NRs), similarly to what was demonstrated in general patients with HFrEF. |
What was learned from the study? |
This study demonstrated that a minimum 6-month treatment with SV induced LV reverse remodeling in CRT-NRs, evidenced by a significant increase in left ventricular ejection fraction (LV EF), a reduction in LV end-systolic diameter, and a decrease in plasma N-terminal pro-B-type natriuretic peptide (NT-proBNP) concentration. |
The extent of improvement in CRT non-responders was similar to what was observed in general patients with HFrEF with no CRT. |
Introduction
Methods
Endpoints
Statistical Analysis
Results
Baseline Patient Data
Group I (n = 70) | Group II (n = 70) | Group III (n = 135) | p (Gr. I vs II vs III) | p (Gr. I vs II) | p (Gr. I vs III) | p (Gr. II vs III) | |
---|---|---|---|---|---|---|---|
Age (years) | 66.1 ± 9.1 | 65.5 ± 11.3 | 62.4 ± 11.3 | 0.018 | 0.879 | 0.011 | 0.036 |
Female sex (%) | 9 (12.9%) | 9 (12.9%) | 31 (22.9%) | 0.128 | 0.831 | 0.134 | 0.087 |
Body weight (kg) | 90.9 ± 18.8 | 89.1 ± 20.9 | 92.3 ± 23.6 | 0.669 | 0.433 | 0.901 | 0.411 |
NYHA class I | 1 (1.4%) | 0 (0.0%) | 0 (0.0%) | 0.231 | 0.315 | 0.163 | ø |
NYHA class II | 19 (27.2%) | 28 (40%) | 43 (31.9%) | 0.256 | 0.107 | 0.486 | 0.244 |
NYHA class III | 47 (67.2%) | 37 (52.8%) | 86 (63.7%) | 0.181 | 0.084 | 0.624 | 0.132 |
NYHA class IV | 3 (4.3%) | 5 (7.1%) | 6 (4.5%) | 0.663 | 0.466 | 0.301 | 0.753 |
LV EF (%) | 25.2 ± 5.7 | 28.3 ± 5.9 | 26.6 ± 6.5 | 0.005 | 0.001 | 0.121 | 0.027 |
NT-proBNP (pg/mL) | 2058 [1041–4502] | 1474 [655–5274] | 2223 [1233–4795] | < 0.001 | 0.037 | 0.850 | 0.014 |
Ischemic etiology | 33 (47.2%) | 26 (37.1%) | 66 (48.9%) | 0.264 | 0.259 | 0.737 | 0.106 |
Non-ischemic etiology | 37 (52.9%) | 44 (62.8%) | 69 (51.2%) | 0.744 | 0.304 | 0.769 | 0.104 |
Systolic BP (mmHg) | 122.9 ± 20.3 | 122.1 ± 16.4 | 117.7 ± 14.5 | 0.181 | 0.910 | 0.148 | 0.111 |
Diastolic BP (mmHg) | 77.1 ± 10.6 | 76.4 ± 12.5 | 77.3 ± 13.1 | 0.907 | 0.687 | 0.763 | 0.701 |
eGFR (mL/min/1.73 m2) | 65.7 ± 17.8 | 66.9 ± 18.3 | 68.3 ± 18.1 | 0.591 | 0.636 | 0.306 | 0.649 |
Potassium (mmol/mL) | 4.6 ± 0.5 | 4.5 ± 0.7 | 4.5 ± 0.5 | 0.679 | 0.639 | 0.379 | 0.734 |
Hypertension n (%) | 67 (97.7%) | 49 (70%) | 89 (65.9%) | < 0.001 | < 0.001 | < 0.001 | 0.553 |
Diabetes n (%) | 42 (60%) | 35 (50%) | 48 (35.6%) | 0.003 | 0.271 | 0.061 | 0.045 |
Atrial fibrillation n (%) | 39 (55.7%) | 23 (32.8%) | 46 (34.1%) | 0.006 | 0.008 | 0.003 | 0.887 |
Dyslipidemia n (%) | 64 (91.4%) | 36 (51.4%) | 74 (54.9%) | 0.001 | < 0.001 | < 0.001 | 0.639 |
Smoking n (%) | 18 (25.7%) | 19 (27.1%) | 36 (26.7%) | 0.968 | 0.868 | 0.836 | 0.943 |
Hyperuricemia n (%) | 25 (35.7%) | 20 (28.5%) | 37 (27.4%) | 0.492 | 0.379 | 0.246 | 0.861 |
Chronic renal failure n (%) | 26 (37.2%) | 31 (44.2%) | 36 (26.7%) | 0.033 | 0.351 | 0.139 | 0.011 |
ACEi/ARB | 70 (100%) | 68 (97.1%) | 135 (100%) | 0.052 | 0.496 | 0.999 | 0.115 |
Beta-blockers | 67 (95.7%) | 68 (97.1%) | 127 (94.1%) | 0.661 | 0.376 | 0.888 | 0.450 |
MRA | 65 (92.8%) | 67 (95.7%) | 124 (91.8%) | 0.355 | 0.170 | 0.731 | 0.240 |
Medical Therapy
Primary Endpoints
LVEDD (mm) | LVESD (mm) | LVOT VTI (m) | Stroke volume (mL) | dP/dt (mmHg/s) | |
---|---|---|---|---|---|
Before SV initiation | 68.4 ± 8.1 | 56.6 ± 9.0 | 0.13 ± 0.4 | 45.4 ± 12.3 | 617.7 ± 201.2 |
Group I | |||||
After SV initiation | 67.2 ± 7.4 | 54.3 ± 8.7 | 0.14 ± 0.5 | 48.2 ± 12.8 | 645.7 ± 221.1 |
p value | 0.085 | 0.004 | 0.006 | 0.144 | 0.084 |
Baseline | 65.1 ± 11.1 | 52.2 ± 10.7 | 0.13 ± 0.4 | 48.7 ± 10.2 | 595.0 ± 156.8 |
Group II | |||||
End of follow-up | 64.4 ± 11.1 | 51.0 ± 11.6 | 0.14 ± 0.5 | 48.5 ± 11.9 | 662.7 ± 165.7 |
p value | 0.108 | 0.131 | 0.651 | 0.950 | 0.239 |
Before SV initiation | 68.6 ± 9.5 | 55.9 ± 9.9 | 0.12 ± 0.5 | 45.8 ± 16.3 | 652.3 ± 168.3 |
Group III | |||||
After SV initiation | 67.8 ± 10.7 | 54.3 ± 11.2 | 0.14 ± 0.6 | 48.1 ± 17.2 | 642.4 ± 163.6 |
p value | 0.262 | 0.021 | 0.067 | 0.108 | 0.292 |
SBP (mmHg) | DBP (mmHg) | eGFR (mL/min/1.73 m2) | Potassium (mmol/mL) | |
---|---|---|---|---|
Before SV initiation | 122.8 ± 20.2 | 77.1 ± 10.5 | 65.7 ± 17.8 | 4.5 ± 0.5 |
Group I | ||||
After SV initiation | 116.1 ± 18.1 | 73.2 ± 10.6 | 63.1 ± 20.3 | 4.6 ± 0.5 |
p value | 0.018 | 0.015 | 0.026 | 0.442 |
Baseline | 122.1 ± 16.4 | 76.4 ± 12.5 | 69.9 ± 18.3 | 4.5 ± 0.7 |
Group II | ||||
End of follow-up | 119.7 ± 18.2 | 76.1 ± 9.8 | 65.8 ± 18.3 | 4.6 ± 0.5 |
p value | 0.209 | 0.753 | 0.285 | 0.152 |
Before SV initiation | 117.7 ± 17.7 | 77.3 ± 13.1 | 68.3 ± 18.1 | 4.5 ± 0.4 |
Group III | ||||
After SV initiation | 111.8 ± 7.9 | 72.1 ± 11.9 | 68.5 ± 18.7 | 4.6 ± 0.5 |
p value | < 0.001 | < 0.001 | 0.896 | 0.037 |