Cardiol Res

Cardiology Research, ISSN 1923-2829 print, 1923-2837 online, Open Access

Article copyright, the authors; Journal compilation copyright, Cardiol Res and Elmer Press Inc

Journal website https://cr.elmerpub.com

Original Article

Volume 16, Number 2, April 2025, pages 140-152

Effect of Dapagliflozin on Ventricular Arrhythmic Events in Heart Failure Patients With an Implantable Cardioverter Defibrillator

↓ Figure 1. Inclusion and exclusion criteria for the patients’ identification. ICD: implantable cardioverter defibrillator.

↓ Figure 2. Observational study protocol main phases. ICD: implantable cardioverter defibrillator; VAb: ventricular arrhythmia burden; NYHA: New York Heart Association; NT-proBNP: N-terminal B-type natriuretic peptide.

↓ Figure 3. Trend of total ventricular arrhythmic events considering the basal NYHA functional class. Dapa: dapagliflozin; NYHA: New York Heart Association.

↓ Figure 4. Interaction chart between VTA improvement and NYHA class, obtained by a two-way ANOVA test. VTA: total ventricular arrhythmias; NYHA: New York Heart Association; ANOVA: analysis of variance; Dapa: dapagliflozin.

↓ Figure 5. Trend of total ventricular arrhythmic events considering the ventricular reverse remodeling. ΔLVEF < 15%: patients without ventricular reverse remodeling; ΔLVEF > 15%: patients with ventricular reverse remodeling). Dapa: dapagliflozin; NYHA: New York Heart Association; LVEF: left ventricular ejection fraction.

↓ Figure 6. Interaction chart between VTA improvement and ventricular reverse remodeling, obtained by a two-way ANOVA test. VTA: total ventricular arrhythmias; LVEF: left ventricular ejection fraction; ANOVA: analysis of variance; Dapa: dapagliflozin.

↓ **Table 1.** Baseline Demographic, Etiology, Comorbidity, and Pharmacotherapy History Data
	N	%	Male, n	Male, %	Female, n	Female, %
ICD: implantable cardioverter defibrillator; NYHA: New York Heart Association; HTN: hypertension; ICM: ischemic cardiomyopathy; NICM non-ischemic cardiomyopathy; DM: diabetes mellitus; AFib-c: chronic atrial fibrillation; AFib-p: paroxysmal atrial fibrillation; ICD-dc: dual-chamber implantable cardioverter defibrillator; ICD-biv: biventricular implantable cardioverter defibrillator; ICD-sc: single-chamber cardioverter defibrillator; CKD: chronic kidney disease; COPD: chronic obstructive pulmonary disease; ACEI: angiotensin-converting enzyme inhibitors; ARBs: angiotensin receptor blockers; MRA: mineralocorticoid receptor antagonists; APT antiplatelet therapy.
Demographic and clinical data
Age, years	70.3 ± 11.4
NYHA I/II	62	52.4
NYHA III/IV	55	47.3
Women	36	30.8
Etiology and comorbidity
NICM	67	57.3	45	55.6	22	61.1
ICM	50	42.7	36	44.4	14	38.9
HTN	79	67.4	57	70.4	22	61.0
DM	35	29.9	24	29.6	11	30.5
AFib-c	17	14.5	7	8.6	10	27.7
AFib-p	21	17.9	17	21.0	4	11.1
ICD-dc	30	25.6	23	28.4	7	19.4
ICD-biv	65	55.5	45	55.5	20	55.5
ICD-sc	22	18.8	14	17.2	8	22.2
Ablate and Pace	7	6.0	3	3.7	4	11.1
COPD	21	17.9	14	17.3	7	19.4
CKD	29	24.8	21	25.9	8	22.2
Pharmacotherapy
ACEI/ARBs	40	34.1
ARNI	71	60.6
Beta blocker	111	94.8
MRA	72	61.5
Furosemide	82	70.0
Digoxin	10	8.5
Amiodarone	30	26.2
Statin	69	59.4
Anticoagulants	38	32.3
APT	71	61.2

↓ Table 1. Baseline Demographic, Etiology, Comorbidity, and Pharmacotherapy History Data

Male, n

Male, %

Female, n

Female, %

ICD: implantable cardioverter defibrillator; NYHA: New York Heart Association; HTN: hypertension; ICM: ischemic cardiomyopathy; NICM non-ischemic cardiomyopathy; DM: diabetes mellitus; AFib-c: chronic atrial fibrillation; AFib-p: paroxysmal atrial fibrillation; ICD-dc: dual-chamber implantable cardioverter defibrillator; ICD-biv: biventricular implantable cardioverter defibrillator; ICD-sc: single-chamber cardioverter defibrillator; CKD: chronic kidney disease; COPD: chronic obstructive pulmonary disease; ACEI: angiotensin-converting enzyme inhibitors; ARBs: angiotensin receptor blockers; MRA: mineralocorticoid receptor antagonists; APT antiplatelet therapy.

Demographic and clinical data

Age, years

70.3 ± 11.4

NYHA I/II

52.4

NYHA III/IV

47.3

Women

30.8

Etiology and comorbidity

NICM

57.3

55.6

61.1

ICM

42.7

44.4

38.9

HTN

67.4

70.4

61.0

29.9

29.6

30.5

AFib-c

14.5

8.6

27.7

AFib-p

17.9

21.0

11.1

ICD-dc

25.6

28.4

19.4

ICD-biv

55.5

ICD-sc

18.8

17.2

22.2

Ablate and Pace

6.0

3.7

11.1

COPD

17.9

17.3

19.4

CKD

24.8

25.9

22.2

Pharmacotherapy

ACEI/ARBs

34.1

ARNI

60.6

Beta blocker

111

94.8

MRA

61.5

Furosemide

70.0

Digoxin

8.5

Amiodarone

26.2

Statin

59.4

Anticoagulants

32.3

APT

61.2

↓ **Table 2.** Echocardiographic Data and Laboratory Tests
	All	NYHA I/II	NYHA III/IV	P
NYHA: New York Heart Association; LVEF: left ventricular ejection fraction; GLS: global longitudinal strain; E/E’; ventricular filling index; PASP: pulmonary arterial systolic pressure; eGFR: estimated glomerular filtration rate; NT-proBNP: N-terminal B-type natriuretic peptide.
Echocardiographic data
LVEF, %	25.9 ± 2.3	26.8 ± 1.3	24.9 ± 3.7	0.01
GLS, %	-12.6 ± 0.9	-12.3 ± 1.1	-12.3 ± 1.9	0.30
E/E’	15.2 ± 2.3	14.4 ± 0.6	16.2 ± 2.3	0.03
PASP, mm Hg	37.9 ± 3.9	35.7 ± 1.8	40.5 ± 3.6	0.01
Laboratory tests
Creatinine, mg/dL	1.19 ± 0.4	1.11 ± 0.6	1.21 ± 0.5	0.41
eGFR, mL/min/1.73m²	71.1 ± 20	74.1 ± 23	64.1 ± 30	0.03
Hemoglobin, g/dL	12.9 ± 2.4	13.1 ± 2.7	12.8 ± 2.7	0.08
Hematocrit, %	40 ± 4.6	41.1 ± 3.9	36.9 ± 4.3	0.03
NT-proBNP, pg/L	1,333.7 ± 564.3	1,302.3 ± 272	1,368.1 ± 420	0.08

↓ Table 2. Echocardiographic Data and Laboratory Tests

All

NYHA I/II

NYHA III/IV

NYHA: New York Heart Association; LVEF: left ventricular ejection fraction; GLS: global longitudinal strain; E/E’; ventricular filling index; PASP: pulmonary arterial systolic pressure; eGFR: estimated glomerular filtration rate; NT-proBNP: N-terminal B-type natriuretic peptide.

Echocardiographic data

LVEF, %

25.9 ± 2.3

26.8 ± 1.3

24.9 ± 3.7

0.01

GLS, %

-12.6 ± 0.9

-12.3 ± 1.1

-12.3 ± 1.9

0.30

E/E’

15.2 ± 2.3

14.4 ± 0.6

16.2 ± 2.3

0.03

PASP, mm Hg

37.9 ± 3.9

35.7 ± 1.8

40.5 ± 3.6

0.01

Laboratory tests

Creatinine, mg/dL

1.19 ± 0.4

1.11 ± 0.6

1.21 ± 0.5

0.41

eGFR, mL/min/1.73m²

71.1 ± 20

74.1 ± 23

64.1 ± 30

0.03

Hemoglobin, g/dL

12.9 ± 2.4

13.1 ± 2.7

12.8 ± 2.7

0.08

Hematocrit, %

40 ± 4.6

41.1 ± 3.9

36.9 ± 4.3

0.03

NT-proBNP, pg/L

1,333.7 ± 564.3

1,302.3 ± 272

1,368.1 ± 420

0.08

↓ **Table 3.** Changes in the Echocardiographic Parameters and NT-proBNP
	Basal	Follow-up	P
LVEF: left ventricular ejection fraction; GLS: global longitudinal strain; E/E’; ventricular filling index; PASP: pulmonary arterial systolic pressure; NT-proBNP: N-terminal B-type natriuretic peptide.
LVEF, %	25.9 ± 2.3	28,7 ± 3,6	0.025
GLS, %	-12.6 ± 0.9	-14.7 ± 1.2	0.03
E/E’	15.2 ± 2.3	13.1 ± 1.1	0.035
PASP, mm Hg	37.9 ± 3.9	34.1 ± 3.2	0.064
NT-proBNP, pg/L	1,333.74 ± 564.3	1,136.1 ± 629.5	0.02

↓ Table 3. Changes in the Echocardiographic Parameters and NT-proBNP

Basal

Follow-up

LVEF: left ventricular ejection fraction; GLS: global longitudinal strain; E/E’; ventricular filling index; PASP: pulmonary arterial systolic pressure; NT-proBNP: N-terminal B-type natriuretic peptide.

LVEF, %

25.9 ± 2.3

28,7 ± 3,6

0.025

GLS, %

-12.6 ± 0.9

-14.7 ± 1.2

0.03

E/E’

15.2 ± 2.3

13.1 ± 1.1

0.035

PASP, mm Hg

37.9 ± 3.9

34.1 ± 3.2

0.064

NT-proBNP, pg/L

1,333.74 ± 564.3

1,136.1 ± 629.5

0.02

↓ **Table 4.** Arrhythmic Events and ICD Therapy Were Assessed in Two Distinct Groups Before and After Dapagliflozin (DAPA) Introduction
	Before DAPA	After DAPA	P
ICD: implantable cardioverter defibrillator; VTA: total ventricular arrhythmias; sVT: sustained ventricular tachycardia; nsVT: non-sustained ventricular tachycardia; VF: ventricular fibrillation; ICDt: ICD therapies.
VTA	4.5 ± 2.0	2.9 ± 1.8	0.01
sVT	1.2 ± 0.9	0.51 ± 0.77	0.001
nsVT	3.84 ± 0.64	2.65 ± 1.58	0.01
VF	0.05 ± 0.02	0.0 ± 0.0	0.11
ICDt	0.89 ± 1.38	0.49 ± 0.76	0.014

↓ Table 4. Arrhythmic Events and ICD Therapy Were Assessed in Two Distinct Groups Before and After Dapagliflozin (DAPA) Introduction

Before DAPA

After DAPA

VTA

4.5 ± 2.0

2.9 ± 1.8

0.01

sVT

1.2 ± 0.9

0.51 ± 0.77

0.001

nsVT

3.84 ± 0.64

2.65 ± 1.58

0.01

0.05 ± 0.02

0.0 ± 0.0

0.11

ICDt

0.89 ± 1.38

0.49 ± 0.76

0.014

↓ **Table 5.** Arrhythmic Events and ICD Therapy That Were Assessed in Two Distinct Groups According to the Basal Functional Class (NYHA I/II and NYHA III/IV)
	NYHA I/II	NYHA III/IV
ICD: implantable cardioverter defibrillator; NYHA: New York Heart Association; VTA: total ventricular arrhythmias; sVT: sustained ventricular tachycardia; nsVT: non-sustained ventricular tachycardia; VF: ventricular fibrillation; DAPA: dapagliflozin; ICDt: ICD therapies; ATP: anti-tachycardia pacing.
VTA	4.5 ± 2.2	3.5 ± 2.1	0.02	5.5 ± 1.8	2.2 ± 0.8	0.001
sVT	0.7 ± 0.2	0.6 ± 0.1	NS	1.9 ± 0.3	0.4 ± 0.2	0.02
nsVT	3.9 ± 1.0	2.9 ± 0.9	0.02	3.9 ± 1.2	1.7 ± 1.0	0.01
VF	0.0 ± 0.0	0.0 ± 0.0	NS	0.2 ± 0.1	0.0 ± 0.0	NS
ICDt	069 ± 0,33	0.52 ± 0.41	NS	1.1 ± 1.08	0.66 ± 0.46	0.02
ICD-sc	0.1 ± 0.0	0.0 ± 0.0	NS	0.2 ± 0.1	0.1 ± 0.0	NS
ATP	0.6 ± 0.2	0.6 ± 0.1	NS	1.5 ± 0.6	0.4 ± 0.2	0.003

↓ Table 5. Arrhythmic Events and ICD Therapy That Were Assessed in Two Distinct Groups According to the Basal Functional Class (NYHA I/II and NYHA III/IV)

NYHA I/II

NYHA III/IV

Before DAPA

After DAPA

Before DAPA

After DAPA

ICD: implantable cardioverter defibrillator; NYHA: New York Heart Association; VTA: total ventricular arrhythmias; sVT: sustained ventricular tachycardia; nsVT: non-sustained ventricular tachycardia; VF: ventricular fibrillation; DAPA: dapagliflozin; ICDt: ICD therapies; ATP: anti-tachycardia pacing.

VTA

4.5 ± 2.2

3.5 ± 2.1

0.02

5.5 ± 1.8

2.2 ± 0.8

0.001

sVT

0.7 ± 0.2

0.6 ± 0.1

1.9 ± 0.3

0.4 ± 0.2

0.02

nsVT

3.9 ± 1.0

2.9 ± 0.9

0.02

3.9 ± 1.2

1.7 ± 1.0

0.01

0.0 ± 0.0

0.2 ± 0.1

0.0 ± 0.0

ICDt

069 ± 0,33

0.52 ± 0.41

1.1 ± 1.08

0.66 ± 0.46

0.02

ICD-sc

0.1 ± 0.0

0.0 ± 0.0

0.2 ± 0.1

0.1 ± 0.0

ATP

0.6 ± 0.2

0.6 ± 0.1

1.5 ± 0.6

0.4 ± 0.2

0.003

↓ **Table 6.** Arrhythmic Events and ICD Therapy That Were Assessed in Two Groups Divided by Ventricular Reverse Remodeling
	Δ LVEF < 15%	ΔLVEF > 15%
ICD: implantable cardioverter defibrillator; VTA: total ventricular arrhythmias; sVT: sustained ventricular tachycardia; nsVT: non-sustained ventricular tachycardia; VF: ventricular fibrillation; DAPA: dapagliflozin; ICDt: ICD therapies; ICD-sc: single-chamber cardioverter defibrillator; ATP: anti-tachycardia pacing.
VTA	4.9 ± 2.1	4.5 ± 2.1	NS	5.1 ± 1.6	2.5 ± 1.1	0.01
sVT	0.9 ± 0.3	0.5 ± 0.2	NS	1.2 ± 0.3	0.8 ± 0.2	0.02
nsVT	3.4 ± 1.1	2.9 ± 1.0	0.03	3.9 ± 1.5	1.8 ± 1.1	0.002
VF	0.0 ± 0.0	0.0 ± 0.0	NS	0.2 ± 0.0	0.0 ± 0.0	NS
ICDt	0.58 ± 0.31	0.53 ± 0.40	NS	1.0 ± 1.1	0.77 ± 0.42	0.02
ICD-sc	0.0 ± 0.0	0.0 ± 0.0	NS	0.2 ± 0.1	0.0 ± 0.0	NS
ATP	0.7 ± 0.2	0.6 ± 0.2	NS	1.4 ± 0.3	0.9 ± 0.2	0.001

↓ Table 6. Arrhythmic Events and ICD Therapy That Were Assessed in Two Groups Divided by Ventricular Reverse Remodeling

Δ LVEF < 15%

ΔLVEF > 15%

Before DAPA

After DAPA

Before DAPA

After DAPA

ICD: implantable cardioverter defibrillator; VTA: total ventricular arrhythmias; sVT: sustained ventricular tachycardia; nsVT: non-sustained ventricular tachycardia; VF: ventricular fibrillation; DAPA: dapagliflozin; ICDt: ICD therapies; ICD-sc: single-chamber cardioverter defibrillator; ATP: anti-tachycardia pacing.

VTA

4.9 ± 2.1

4.5 ± 2.1

5.1 ± 1.6

2.5 ± 1.1

0.01

sVT

0.9 ± 0.3

0.5 ± 0.2

1.2 ± 0.3

0.8 ± 0.2

0.02

nsVT

3.4 ± 1.1

2.9 ± 1.0

0.03

3.9 ± 1.5

1.8 ± 1.1

0.002

0.0 ± 0.0

0.2 ± 0.0

0.0 ± 0.0

ICDt

0.58 ± 0.31

0.53 ± 0.40

1.0 ± 1.1

0.77 ± 0.42

0.02

ICD-sc

0.0 ± 0.0

0.2 ± 0.1

0.0 ± 0.0

ATP

0.7 ± 0.2

0.6 ± 0.2

1.4 ± 0.3

0.9 ± 0.2

0.001

↓ **Table 7.** Change in the Ventricular Arrhythmic Events in Various Subgroups
	Male	Female	Gender interaction
VTA	4.7 ± 2.7	3.7 ± 2.9	0.025	4.9 ± 2.0	3.7 ± 2.9	0.02	0.25/0.021
ICDt	0.54 ± 0.7	0.40 ± 0.3	0.02	0.51 ± 0.7	0.43 ± 0.5	0.02
VTA	4.6 ± 1.9	3.1 ± 2.3	0.02	4.7 ± 1.8	3.3 ± 2.4	0.025	0.20/0.039
ICDt	0.79 ± 1.3	0.47 ± 0.7	0.01	0.69 ± 1.4	0.39 ± 0.5	0.018
VTA	5.3 ± 1.2	2.9 ± 1.9	0.01	4.4 ± 2.1	3.1 ± 2.1	0.02	0.20/0.033
ICDt	0.49 ± 0.9	0.38 ± 0.3	0.025	0.51 ± 0.7	0.43 ± 0.6	0.02
VTA	4.4 ± 2.1	3.1 ± 2.4	0.02	5.0 ± 1.5	3.5 ± 2.5	0.015	0.15/0.043
ICDt	0.56 ± 0.8	0.44 ± 0.3	0.03	0.69 ± 0.7	0.57 ± 0.6	0.025
ICD: implantable cardioverter defibrillator; VTA: total ventricular arrhythmias; ICDt: ICD therapies; ICM: ischemic cardiomyopathy; NICM non-ischemic cardiomyopathy; GDMT: guideline- directed medical therapy.
VTA	4.3 ± 2.0	2.7 ± 1.6	0.015	4.9 ± 1.4	4.2 ± 2.4	0.035	0.03/0.184
ICDt	0.51 ± 0.8	0.40 ± 0.4	0.02	0.57 ± 0.7	0.49 ± 0.6	0.03

↓ Table 7. Change in the Ventricular Arrhythmic Events in Various Subgroups

Male

Female

Gender interaction

Before

After

Before

After

P/η²

VTA

4.7 ± 2.7

3.7 ± 2.9

0.025

4.9 ± 2.0

3.7 ± 2.9

0.02

0.25/0.021

ICDt

0.54 ± 0.7

0.40 ± 0.3

0.02

0.51 ± 0.7

0.43 ± 0.5

0.02

Diabetic

Non-diabetic

Diabetes interaction

Before

After

Before

After

P/η²

VTA

4.6 ± 1.9

3.1 ± 2.3

0.02

4.7 ± 1.8

3.3 ± 2.4

0.025

0.20/0.039

ICDt

0.79 ± 1.3

0.47 ± 0.7

0.01

0.69 ± 1.4

0.39 ± 0.5

0.018

ICM

NICM

ICM/NICM interaction

Before

After

Before

After

P/η²

VTA

5.3 ± 1.2

2.9 ± 1.9

0.01

4.4 ± 2.1

3.1 ± 2.1

0.02

0.20/0.033

ICDt

0.49 ± 0.9

0.38 ± 0.3

0.025

0.51 ± 0.7

0.43 ± 0.6

0.02

Amiodarone

No amiodarone

Amiodarone interaction

Before

After

Before

After

P/η²

VTA

4.4 ± 2.1

3.1 ± 2.4

0.02

5.0 ± 1.5

3.5 ± 2.5

0.015

0.15/0.043

ICDt

0.56 ± 0.8

0.44 ± 0.3

0.03

0.69 ± 0.7

0.57 ± 0.6

0.025

GDMT

Suboptimal GDMT

GDMT interaction

Before

After

Before

After

P/η²

ICD: implantable cardioverter defibrillator; VTA: total ventricular arrhythmias; ICDt: ICD therapies; ICM: ischemic cardiomyopathy; NICM non-ischemic cardiomyopathy; GDMT: guideline- directed medical therapy.

VTA

4.3 ± 2.0

2.7 ± 1.6

0.015

4.9 ± 1.4

4.2 ± 2.4

0.035

0.03/0.184

ICDt

0.51 ± 0.8

0.40 ± 0.4

0.02

0.57 ± 0.7

0.49 ± 0.6

0.03