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Abstract

Introduction: Ventricular remodeling is a mal-adaptive process. Both angiotensin-converting enzyme inhibitors and sacubitril/valsartan have been shown to reverse remodeling in mostly uncontrolled observational studies. There is a lack of head-to-head studies. Methods: This cohort study compares the remodeling effects of angiotensin receptor blockers combined with a neprilysin inhibitor (ARNI) and perindopril in heart failure with reduced ejection fraction (HFrEF) patients between January 2017 and December 2020. Inclusion criteria: (i) age > 18 years, (ii) recent diagnosis of de-novo HFrEF (EF < 40%), (iii) baseline echocardiography performed not more than 2 months prior to treatment onset, and (iv) follow-up echocardiography performed not earlier than 6 months and not later than 18 months posttreatment onset. No prior treatment with renin–angiotensin–aldosterone system inhibitors was permitted in the ARNI group. Left ventricular ejection fraction (LVEF), left ventricular end-diastolic volume (LVEDV), and left ventricular end-systolic volume (LVESV) were analyzed. A two-way repeated measure ANOVA (for normally distributed) and generalized estimating equation test for nonnormally distributed interval dependent variables. Mean comparison between and within groups was performed using the Bonferroni test. Results: Following an average treatment period of 9 months, LVEF improved from 24.9% to 36.4% for ARNI and from 28.7% to 40.5% for perindopril, increments of 11.5% and 11.8% resp. (Bonferroni test [P ≤ .05]). LVEDV was reduced by 8.4 mL and 3.2 mL, and LVESV by 17.9 mL and 10.8 mL for ARNI and perindopril resp. Only the reduction of LVESV for ARNI was statistically significant (P = .007). Conclusion: Both ARNI and perindopril yielded a significant improvement in the LVEF within 9 months. The remodeling effect of ARNI seems stronger because of the greater improvements in left ventricular volumes.

Keywords

heart failure ARNI remodeling ACE-inhibition perindopril echocardiography heart disease

Introduction

Heart failure (HF) is one of the leading causes of morbidity and mortality worldwide. HF with reduced ejection fraction (HFrEF) is the most prevalent subtype of HF.¹ Until 2016, guideline-based treatment of HFrEF comprised mainly of the renin–angiotensin–aldosterone system (RAAS) inhibitors and beta-blockers.^2–6 There has been a great development in the management of HFrEF patients over the last decade. Angiotensin receptor blockers combined with neprilysin inhibitors (ARNIs) and sodium-glucose cotransporter 2 inhibitors (SGLT2i) have been approved for all HFrEF patients to reduce mortality and HF hospitalizations.^7–9

The term left ventricular (LV) remodeling describes a mal-adaptive process that results in changes in LV geometry and function that are associated with worse outcomes.¹⁰ It is believed to be a response to myocardial injury, commonly following myocardial infarction. Interstitial collagen deposition, cardiomyocyte hypertrophy, and elongation in the noninfarcted areas are the histological hallmarks of the process.^11,12 The development of HF is related to the extent of LV remodeling.^11,13 LV ejection fraction (LVEF), LV volumes, and LV mass are the most commonly employed metrics to quantify remodeling and have all been shown to be predictors of death and HF rehospitalization.^14–19

It has been demonstrated that contemporary HFrEF therapies with the inhibition of the RAAS can result in increased LVEFs and reductions in LV volumes.¹⁰ Outcomes are better when the remodeling process can be abated.²⁰ The ARNI sacubitril/valsartan demonstrated improvements in cardiac volumes and function that correlated well with NT-proBNP concentrations.^21–23 However, the positive effects of ARNI in reversing cardiac remodeling and in improving systolic function in HFrEF patients have primarily been illustrated in uncontrolled observational studies.²¹ Furthermore, to our knowledge, there are no head-to-head studies comparing the remodeling effects of ARNIs with angiotensin-converting enzyme inhibitors (ACEi). There is also a lack of data on the effects of ARNI on cardiac remodeling in Asian populations.

Therefore, the aim of this study was to compare the effects between ARNI and ACEi therapy on cardiac remodeling in a population of HFrEF patients.

Methods

Patient Selection

This was a retrospective cohort study. It was approved by the institutional ethics committee (MECID. No 2020421-8543). Data was collected from January 2017 until December 2020.

Inclusion and Exclusion Criteria

Patients were included in the study if they fulfilled the following criteria: (i) age > 18 years, (ii) recent diagnosis of de-novo HFrEF (EF < 40%), (iii) baseline echocardiography performed no more than 2 months prior to the initiation of ARNI or perindopril, (iv) echocardiography reassessment performed no earlier than 6 months and no later than 18 months post initiation of ARNI or perindopril, and (v) the HFrEF must have been diagnosed not more than 6 months prior to initiation of therapy. No prior treatment with RAAS inhibitors in the ARNI group was permitted. An equal number of HFrEF patients with similar clinical characteristics and treated with perindopril were identified and analyzed in the same manner.

Echocardiography Measurements

Epidemiological, laboratory, and clinical variables were retrieved from the electronic medical record system. Echocardiographic parameters analyzed include LV ejection fraction (LVEF), LV end-diastolic volume (LVEDV), and LV end-systolic volume (LVESV) measured with the modified Simpson's method. These measurements were performed according to established guidelines.²⁴ Measurements were performed at baseline and within 6 to 18 months from the initiation of the therapy.

Statistical Analysis

SPSS 25.0 software program (SPSS Inc., Chicago, IL) was used to analyze the data. For categorical variables, descriptive statistics such as frequencies and percentages were calculated and for continuous variables, the mean, median, and standard deviation were computed. To test the differences between the 2 groups, the chi-square test was used for categorical data, while the independent t-test was used for continuous data. This was a longitudinal study with baseline and follow-up data. For normally distributed variables, a two-way repeated measure analysis of variance was applied. Nonnormally distributed variables were analyzed with the generalized estimating equation. The Bonferroni test was used to compare mean values between and within groups. The level of statistical significance for all analyses was set at 5% (P < .05).

Results

Profile of Study Participants

The demographic information, comorbidities, and medications of the participants are summarized in Table 1. Apart from atrial fibrillation, chronic kidney disease, and ivabradine use, neither group showed statistically significant differences. The 3 variables were not considered potential covariates as there was no significant association between them and the dependent variables.

Table 1.

Group Comparison of Demographic Characteristics, Comorbidities and Medications.

		Sacubitril/valsartan (n=40)	Perindopril (n=40)	P value
		Mean ± SD	Mean ± SD	P value
Age (years)		56.9 ± 11.6	59.7 ± 11.2	.276
BMI (kg/m²)		25.0 ± 4.6	24.8 ± 5.4	.821
Treatment duration prior to follow-up ECHO (months)		9.28 ± 4.24	9.55 ± 3.86	.763
		N (%)	N (%)
Gender	Male	30 (75.0)	29 (72.5)	.82
	Female	10 (25.0)	11 (27.5)
Comorbidities	Hypertension	20 (50.0)	26 (65.0)	.175
	Diabetes	23 (57.5)	23 (57.5)	1
	Atrial fibrillation	1 (2.5)	9 (22.5)	.007
	Ischaemic heart disease	27 (67.5)	25 (62.5)	.64
	CVA	4 (10.0)	10 (25.0)	.077
	Dyslipidaemia	10 (55.6)	14 (82.4)	.088
	CKD	1(5.6)	6 (35.3)	.028
Medications	MRA	17 (42.5)	20 (50.0)	.507
	Beta-blocker	39 (97.5)	36 (90.0)	.17
	Ivabradine	8 (20.0)	1 (2.5)	.013
	Digoxin	5 (12.5)	5 (12.5)	1
	Calcium channel blocker	0 (0.0)	3 (7.5)	.075
	Diuretic	32 (80.0)	30 (75.0)	.60
	Initiation as inpatient	17 (42.5)	25 (62.5)	.45

Abbreviations: BMI, body mass index; CVA, cerebrovascular accident; CKD, chronic kidney disease; RAAS, renin–angiotensin–aldosterone system; MRA, mineralocorticoid receptor antagonist; ECHO, echocardiogram.

Normality Testing of Outcome Parameters

All outcome parameters underwent normality testing prior to data analysis. A two-way repeated measure ANOVA was used to compare the parameters between and within groups for systolic blood pressure (SBP), heart rate (HR), and LVEF as they were normally distributed. Due to the nonnormal distribution of the NYHA status, LVEDV, LVESV, and diastolic blood pressure (DBP), generalized estimating equation (GEE) analysis was employed to analyze differences for those parameters between groups and over time.

Comparison of Haemodynamic Parameters

There was no statistically significant difference between the changes in SBP for both groups at different points in time (F_{(1, 77)} = 2.413. P = .124, η² = 0.03). Patients receiving ARNI had however a significant difference between baseline and follow-up SBP (P = .031).

For HR, there was no statistically significant interaction between group and time (F_{(1, 78)} = 0.016. P = .900, η² = 0.001), indicating that changes in HR in both groups were not substantially different over time. There was no discernible change in HR between baseline and follow-up (P > .05) for both groups. The pattern for DBP in terms of interaction between group and time (χ² = 0.038, P = 1) and between baseline and follow-up was also not significant (P > .05).

Comparison of Functional Outcome Parameters

Results for the NYHA class showed that there was no significant interaction between group and time (χ² = 0.498, P = .480) indicating no significant difference in the rate of change of NYHA in the 2 groups over time. However, the initial and follow-up NYHA status was significantly different for both groups (P < .001).

Comparison of Echocardiographic Outcome Parameters

There was no statistically significant interaction between group and time (F_{(1, 78)} = 0.014. P = .906, η² = 0.001) for LVEF. However, both groups showed a significant increase in LVEF at follow-up compared to baseline (P < .05).

There was no significant interaction between group and time for LVEDV (χ² = 0.725, P = .394). No substantial difference between baseline and follow-up in either group was found for LVEDV (P > .05).

For LVESV, there was no statistically significant interaction between group and time (χ² = 0.725, P = .394), indicating that the changes in LVESV in both groups were not significantly different over time. However, only the ARNI group demonstrated a significant increase in LVESV during follow-up compared to baseline (P = .007) (Table 2 and Figure 1).

Figure 1.

Remodeling effects of sacubitril/valsartan versus perindopril.

Table 2.

Mean Comparison Between and Within Groups.

Variable	Group	Baseline			Follow-up
Variable	Group	Mean	SD	Comparison between groupP value	Mean	SD	Comparison between groupP value	Comparison between baseline ad follow-up testP value
SBP	ARNI	123.6	23.783	.846	115.9	19.158	.072	.031
SBP	Perindopril	125.95	18.847		125.2	17.723		.968
DBP	ARNI	75.43	15.389	1	69.38	10.621	1	.051
DBP	Perindopril	75.95	14.031		70.58	10.791		.084
HR	ARNI	81.17	15.848	.859	77.03	12.955	.728	.183
HR	Perindopril	81.78	14.305		78.17	16.371		.247
NYHA	ARNI	2.23	0.768	.498	1.53	0.598	.847	<.001
NYHA	Perindopril	2.10	0.871		1.55	0.552		.001
LVEF	ARNI	24.93	7.972	.033	36.42	12.345	.201	<.001
LVEF	Perindopril	28.65	7.364		40.52	15.855		<.001
LVESV	ARNI	106.2	51.249	.086	88.34	50.721	.415	.007
LVESV	Perindopril	85.23	27.991		74.41	49.376		.243
LVEDV	ARNI	142.03	64.298	.425	133.65	60.219	.843	.843
LVEDV	Perindopril	121.36	36.502		118.19	54.882		.843

Abbreviations: SBP: systolic blood pressure; DBP: diastolic blood pressure; HR: heart rate; NYHA: New York Heart Association class; LVEF: left ventricular ejection fraction; LVESV: left ventricular end-systolic volume; LVEDV: left ventricular end-diastolic volume; ARNI, angiotensin receptor blockers combined with neprilysin inhibitor.

All statistically significant values (p<0.05) were highlighted in “bold”.

Discussion

Both ARNI and perindopril resulted in significant improvements in cardiac remodeling in this observational study: LVEF improved from 24.9% to 36.4% for ARNI and from 28.7% to 40.5% for perindopril, with statistically significant increments of 11.5% and 11.8%, respectively. Reductions in end-systolic and end-diastolic volumes were recorded for both groups. Following an average treatment period of 9 months, end-diastolic LV volumes were reduced by 8.4 and 3.2 mL, and end-systolic LV volumes by 17.9 and 10.8 mL for ARNI and perindopril, respectively. However, only the reduction in the end-systolic volume for ARNI was statistically significant. The improvements seen in NYHA class were identical for both treatment groups. Haemodynamically, both ARNI and perindopril treatment resulted in the reductions of mean SBP and DBP as well as HR, but only the SBP reduction with ARNI was statistically significant. It is noteworthy, that only 25% of patients tolerated the maximum and target dose of ARNI.

The positive impact of ARNI on cardiac remodeling in HFrEF has previously been demonstrated in single-arm studies without comparison groups.^17,18 LVEF increments (ranging from 4.8% to 9.5%) and LV volume reductions of both end-systolic and end-diastolic volumes at high significance levels occurred as early as 3 months after initiation of therapy. The findings reported by the PROVE-HF investigators²¹ after 12 months of the ARNI therapy with LVEF increments of 9.4% and volume reductions of 12.3 and 15.3 mL/m² for LVEDV and LVESV, respectively, are comparable to our study (Table 3, Section a).

Table 3.

Overview Studies on the Remodeling Effects of ARNI and ACEi.

Reference	Study design	Study population	Intervention	Treatment duration	N	LVEF (%) [pre → post]	P value	LVEDVI (mL/m²) */LVEDV (mL) [pre → post]	P value	LVESVI(mL/m²) /LVESV (mL) [pre → post]	P value
Reference	Study design	Study population	Intervention	Treatment duration	N	Mean change (%)	P value	Mean change (%)	P value	Mean change (%)	P value
(a) ARNI effects on remodeling—uncontrolled studies
Januzzi et al²¹	Prospective cohort	HFrEF	ARNI	12 months	794	28.2% → 37.8%	< .001	86.9 → 74.1 [−12.2 mL] *	< .001	61.7 → 45.5 [−16.2 mL] *	< .001
Januzzi et al²¹	Prospective cohort	HFrEF	ARNI	12 months	794	+9.4%	< .001	−14%	< .001	−26.2%	< .001
Almufleh et al¹⁸	Retrospective cohort	HFrEF	ARNI	3 months	48	25.3% → 30.1%	< .001	221.4 → 207.5 [−4.9 mL]	= .02	165 → 143.7 [−21.3 mL]	= .04
Almufleh et al¹⁸	Retrospective cohort	HFrEF	ARNI	3 months	48	+4.8%	< .001	−2.2%	= .02	−12.9%	= .04
De Diego et al²⁵	Prospective cohort	HFrEF	ARNI	18 months	250	31% → 36.5%	= .002	141 → 119 [−22.0 mL]	< .02	NA	NA
De Diego et al²⁵	Prospective cohort	HFrEF	ARNI	18 months	250	+5.5%	= .002	−15.6%	< .02	NA	NA
Martens et al²²	Prospective cohort	HFrEF	ARNI	5 months	125	29.6% → 34.8%	< .001	206 → 197 [−9.0 mL]	= .027	147 → 129 [−18 mL]	< .001
Martens et al²²	Prospective cohort	HFrEF	ARNI	5 months	125	+5.2%	< .001	−4.3%	= .027	−12.2%	< .001
Galvan Ruiz et al²³	Retrospective cohort	HFrEF	ARNI	11 months	291	30.6% → 38.3%	< .001	65.2 → 60.8 [−4.4 mL]	< .001	NA	NA
Galvan Ruiz et al²³	Retrospective cohort	HFrEF	ARNI	11 months	291	+7.7%	< .001	−6.7%	< .001	NA	NA
(b) ACEi effects on remodeling—controlled studies
Bonarjee et al²⁶ (Consensus)	Prospective cohort	AMI	Enalapril	6 months	Placebo: 226	Baseline LVEF 45%	NA	49.4 → 54.2 [+4.8 mL] *	= .047	28.4 → 29.8 [−1.4 mL] *	= .052
					Placebo: 226	NA		+9.7%		−4.9%
					Enalapril: 202	Baseline LVEF 45%		48.3 → 51.1 [+2.8 mL] *		27.3 → 27.2 [−0.1 mL] *
					Enalapril: 202	NA		+5.8%		−0.4%
Nicolosi et al²⁷ (GISSI-3)	Prospective cohort	MI	Lisinopril	6 months	Placebo: 3219	Baseline LVEF 47%	NA	94.7 → 96.4 [−1.7 mL]	= .0155	NA	NA
					Placebo: 3219	NA		−1.8%		NA
					Lisinopril: 3186	Baseline LVEF 47%		94.4 → 95.4 [−1 mL]		NA
					Lisinopril: 3186	NA		−1%		NA
Borghi et al²⁸ (FAMIS)	Prospective cohort	AMI	Fosinopril	3 months	Placebo: 142	51% → 53%	NS	56.1 → 63.3 [+7.2 mL] *	NS	27.8 → 30.5 [+2.7 mL] *	NS
					Placebo: 142	+2%		+12.8%		+9.7%
					Fosinopril: 143	49% → 52%		56.7 → 61.7 [+5 mL] *		28.9 → 30.5 [+1.6 mL] *
					Fosinopril: 143	+3%		+8.8%		+5.5%
Solomon et al¹⁹ (Valiant)	Prospective cohort	AMI and LV dysfunction	ValsartanCaptopril	20 months	Valsartan: 202	39.6% → 40.9%	NS (P = .30)	119.5 → 121.5 [+2 mL]	NS (0.94)	73.1 → 72.91 [−0.91 mL]	NS (P = .67)
					Valsartan: 202	+1.3%		+1.7%		−1.2%
					Captopril: 204	38.8% → 41.5%		119.8 → 122.3 [+2.5 mL]		73.9 → 92.96 [−0.94 mL]
					Captopril: 204	+2.7%		+2.1%		−1.3%
					Both: 197	39.3% → 41.2%		118.8 → 121.5 [+2.7 mL]		72.9 → 72.69 [−0.21 mL]
					Both: 197	+1.9%		+2.3%		−0.3%
Konstam et al²⁹	Prospective cohort	HFrEF	Enalapril versus placebo	12 months	Placebo: 25	25% → 24%	= .04	136 → 151 [+15 mL] *	P = .008	103 → 116 [+13 mL] *	= .002
					Placebo: 25	−4%		+11%		+12.6%
					Enalapril: 31	25% → 29%		140 → 127 [−13 mL] *		106 → 93 [13 mL] *
					Enalapril: 31	+4%		−9.3%		−12.3%
Konstam et al³⁰	Prospective cohort	HFrEF	Losartan versus captopril	12 months	Losartan: 13	NA	NA	135 →128 [−7 mL]	NS	97 →90 [−7 mL]	NS
					Losartan: 13	NA		−5.2%		−7.2%
					Captopril: 16	NA		142 →131 [−11 mL]		98 →89 [−9 mL]
					Captopril: 16	NA		−7.7%		−9.2%
Ferrari et al³¹	RCT	Elderly AMI	Perindopril versus placebo	12 months	Perindopril: 631	NA	NA	81.1 → 81.8 [+0.7 mL]	P < .001	NA	NA
					Perindopril: 631	NA		+0.9%		NA
					Placebo: 621	NA		79.6 → 83.6 [+4 mL]		NA
					Placebo: 621	NA		+5%		NA
(c) RCTs examining ARNI versus RAAS blocker effects on remodeling
Desai et al³²	RCT	HFrEF	ARNI versus Enalapril	12 weeks	ARNI 231	34% → 36%	NS (P = .24)	75.1 → 70.3 [−4.8 mL] *	NS (P = .02)	50.8 → 46.3 [−4.5 mL] *	NS (P = .045)
					ARNI 231	+2%		−6.4%		−8.9%
					Enalapril 233	33% → 35%		79.1 → 75.6 [−3.5 mL] *		54.1 → 50.6 [−3.5 mL] *
					Enalapril 233	+2%		−4.4%		−6.5%
Kang et al¹⁷	RCT	Functional MR	ARNI versus Valsartan	12 months	ARNI: 51	NA	NA	186.4 → 164.4 [−22 mL]	P = .044	122.9→ 105.2 [−17.7 mL]	= .16
					ARNI: 51	NA		−11.8%		−14.4%
					Valsartan: 53	NA		205 → 193.3 [−11.7 mL]		138.6 → 125.6 [−13 mL]
					Valsartan: 53	NA		−5.7%		−0.7%
Mamdouh Abdin et al³³	RCT	HFrEF	ARNI versus RAAS Blocker	6 months	ARNI: 50	29.9 →34.5%	= .028	240 →190 [−50 mL]	P = .038	145 →105 [−40 mL]	< .001
					ARNI: 50	+15.4%		−20.8%		−27.6%
					RAAS Blocker: 50	30.8→32.3%		230 → 220 [−10 mL]		150 → 145 [−5 mL]
					RAAS Blocker: 50	+4.9%		−4.3%		−3.3%

Abbreviations: ARNI, angiotensin receptor neprilysin inhibitor; ACEi, angiotensin-converting enzyme inhibitor; LVEF, left ventricular ejection fraction; LVEDV, left ventricular end-diastolic volume; LVEDVI, left ventricular end-diastolic volume index; LVESV, left ventricular end-systolic volume; LVESVI, left ventricular end-systolic volume index; HFrEF, heart failure with reduced ejection fraction; AMI, acute myocardial infarction; RCT, randomized controlled trial; MR, mitral regurgitation.

The evidence of the impact of ACE inhibition on remodeling stems to a large extent from older studies on acute myocardial infarction (AMI) patients.^26–28,31 The more recent ARNI studies were mostly conducted in HF patient populations thereby limiting the comparability of the findings. Generally, ACE-inhibition in AMI populations seems to result in increased LVEF; however, the reported improvements are fairly small (ranging from 1.3% to 4%) and are mostly nonsignificant in comparison to placebo. The best evidence of the beneficial effects of ACE inhibitors on remodeling is from HFrEF populations.³⁰ The SOLVD investigators demonstrated as early as 1992 the effects of enalapril for the prevention and the reversal of progressive remodeling in HFrEF patients.^29,34 The efficacy of ACE inhibitors on remodeling parameters appears less impressive than those of ARNIs – a finding that might be related to time and selection bias (Table 3, Section b).

It is difficult to draw conclusions about the comparative treatment efficacy of ARNI and ACEi as for the lack of randomized trials. Studies comparing ARNI with RAAS blockers documented typical LVEF increments for both treatment modalities.^32,33 The magnitude of the increments, however, differs widely. All studies showed a significantly larger reduction in end-systolic and end-diastolic volumes with ARNI when compared to RAAS inhibition. De Diego et al²⁵ demonstrated that switching standard ACEi therapy to ARNI resulted in additional remodeling benefits with further LVEF increments and LV volume reductions. A metanalysis comparing the relative efficacy of ARNI versus RAAS blockers in HFrEF patients reported better effects with ARNI on LV size and hypertrophy³⁵ (Table 3, Section c).

It must be highlighted that the findings of our study have to be interpreted with caution due to the small sample size, the observational character, and the relatively short follow-up period. Randomization was not carried out and although statistical analysis showed that both groups were well matched at baseline, patients who were prescribed ARNI may have been intrinsically different from patients prescribed with ACEi, potentially resulting in selection bias.

Conclusions

From our study, both ARNI and ACEi resulted in significant improvements in LVEF in patients with recently diagnosed HFrEF. There was a trend for both ARNI and ACEi to reduce LV volumes, but only ARNI therapy resulted in significant reductions in end-systolic volumes. In addition, the systolic blood pressure lowering effect of ARNI was significantly stronger than that of ACEi. Although functional improvement was similar for both treatment modalities, the remodeling effect of ARNI appeared to be superior in view of the greater improvements in LV volumes. Head-to-head trials are needed to answer that question conclusively.

Footnotes

Acknowledgments

N/A

Author Contributions

AA and MF designed the study protocol. AA, MF, and VT collected clinical data and performed echocardiographic assessments. MD performed statistical analysis, interpreted the data, and reviewed the manuscript. AA and MD were major contributors to writing the manuscript. AL wrote the manuscript. All authors read and approved the final manuscript.

Availability of Data and Materials

Data will be made available upon reasonable request to the corresponding author.

Declaration of Conflicting Interests

The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Ethics Approval

Ethics approval was obtained from the Ethics Committee of the University Malaya Medical Centre prior to the commencement of the study (MECID. No 2020421-8543).

Funding

The author(s) received no financial support for the research, authorship, and/or publication of this article.

Human Rights Statement

Data was obtained in accordance with the principles outlined in the Declaration of Helsinki.

Informed Consent

Written informed consent was obtained from all patients whose data was collected.

ORCID iDs

Victoria Wen Yeng Teoh

Alexander Loch

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ARNI Versus Perindopril for Remodeling in HFrEF. A Cohort Study

Abstract

Keywords

Introduction

Methods

Patient Selection

Inclusion and Exclusion Criteria

Echocardiography Measurements

Statistical Analysis

Results

Profile of Study Participants

Normality Testing of Outcome Parameters

Comparison of Haemodynamic Parameters

Comparison of Functional Outcome Parameters

Comparison of Echocardiographic Outcome Parameters

Discussion

Conclusions

Footnotes

Acknowledgments

Author Contributions

Availability of Data and Materials

Declaration of Conflicting Interests

Ethics Approval

Funding

Human Rights Statement

Informed Consent

ORCID iDs

References