Effect of Sacubitril/Valsartan Combined with Dapagliflozin on Long-Term Cardiac Mortality in Heart Failure with Reduced Ejection Fraction

Karabulut, Umut; Keskin, Kudret; Karabulut, Dilay; YİĞİT, Ece; Yiğit, Zerrin

doi:10.1177/00033197211047329

Cited by 13 publications

(18 citation statements)

References 31 publications

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“…Hongbo Yang et al found that phase standard deviation and bandwidth negatively correlated with LVEF in chronic total occlusion (CTO) lesions, while the skewness and kurtosis of the phase map positively correlated with LVEF [ 20 ], which is consistent with our findings. Note that LVEF is a powerful predictor of cardiac mortality [ 21 ]. Our study showed that the worse left ventricular mechanical contraction synchrony leads to decreased LVEF, making the systolic synchrony parameters valuable in the prediction of cardiac mortality.…”

Section: Discussionmentioning

confidence: 99%

Relationship between left ventricular mechanical synchrony and left ventricular systolic function: a CZT-SPECT analysis

Sun

Huang

et al. 2022

BMC Cardiovasc Disord

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Background CZT-SPECT has good agreement in the evaluation of mechanical synchronization compared with conventional SPECT. The aim of this study was to evaluate the correlation between left ventricular mechanical contraction synchrony and left ventricular systolic function by gated myocardial perfusion imaging (GMPI) using cadmium–zine–telluride (CZT) single photon emission computed tomography (SPECT). Methods This retrospective study involved 371 patients (239 males and 132 females, mean age 61.06 ± 11.78 years old) who underwent GMPI at the Nuclear Medicine Department of Shanxi Cardiovascular Hospital from January 2020 to August 2020. Systolic synchrony parameters and left ventricular systolic function parameters were calculated via Emory Cardiac Toolbox, including PP, PSD, PHB, HS, HK, EDV, ESV, and LVEF. Based on LVEF value, patients were divided into the severe reduction group (group 1, 127 cases, EF < 35%), moderate reduction group (group 2, 47 cases, 35% ≤ EF < 45%), mild reduction group (group 3, 50 cases, 45% ≤ EF < 50%) and normal group (group 4, 147 cases, EF ≥ 50%). Differences in PP, PSD, PHB, HS and HK among the four groups were compared using one-way ANOVA. Differences between two groups were compared using LSD-t test. The correlation among functional and mechanical contraction synchrony factors were analyzed using Pearson test. Results PP, PSD, PHB, HS and HK were significantly different among the four groups (F = 5.20, 188.72, 202.88, 171.05, 101.36, P < 0.001). Pairwise comparison tests showed significant differences in PSD and PHB in each two groups, and HS and HK in each two groups except for group 2 and 3 (t = 0.28 and 0.39, both P > 0.001). PP was significantly higher in group 1, relative to group 3 (t = 2.43, P < 0.001) and group 4 (t = 3.67, P < 0.001). Pearson correlation analysis revealed that LVEF negatively correlates with PP, PSD, PHB (r = 0.194, − 0.790, − 0.799, all P < 0.001). HS and HK showed positive correlation for LVEF (r = 0.778 and 0.795, P < 0.001), PSD, PHB and ESV were had good positive correlation (r = 0.778, 0.795, P < 0.001), PSD, PHB and EDV had good positive correlation (r = 0.722, 0.732, P < 0.001). However, PP had poor correlation with EDV (r = 0.095, P > 0.001). HS and HK were negatively correlated with EDV and ESV (r = − 0.700 to − 0.594, P < 0.001). Conclusion CZT SPECT GMPI provided left ventricular mechanical contraction synchrony parameters that correlated well with left ventricular systolic function. Worse left ventricular mechanical contraction synchrony lead to decreased LVEF, making the systolic synchrony parameters valuable in the prediction of left ventricular systolic function.

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Section: Discussionmentioning

confidence: 99%

Relationship between left ventricular mechanical synchrony and left ventricular systolic function: a CZT-SPECT analysis

Sun

Huang

et al. 2022

BMC Cardiovasc Disord

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“…Then, the results revealed that, compared with ARNI monotherapy, the risk of a patient having heart failure hospitalization 3,4,8,9 was significantly reduced by the combination therapy [risk ratio ¼ 0.65, 95% CI (0.53-0.79), Z ¼ 4.23, P < 0.001], the result from both RCTs [risk ratio ¼ 0.62, 95% CI (0.47-0.81), Z ¼ 3.49, P < 0.001] and cohort studies [risk ratio ¼ 0.69, 95% CI (0.52-0.93), Z ¼ 2.44, P ¼ 0.01], respectively. The risk of cardiovascular death 3,4,8 was also significantly reduced by the combination therapy [risk ratio ¼ 0.65, 95% CI (0.46-0.93), Z ¼ 2.37, P ¼ 0.02], especially the result from the only cohort study [risk ratio ¼ 0.38, 95% CI (0.16-0.87), Z ¼ 2.30, P ¼ 0.02]. In addition, the risk of a patient having all-cause death 3,4,8,9 was significantly reduced by the combination therapy [risk ratio ¼ 0.70, 95% CI (0.54-0.92), Z ¼ 2.59, P ¼ 0.01], especially the results from two cohort studies [risk ratio ¼ 0.59, 95% CI (0.36-0.95), Z ¼ 2.18, P ¼ 0.03] (Fig.…”

Section: Risk Of Bias Assessmentmentioning

confidence: 99%

“…The risk of cardiovascular death 3,4,8 was also significantly reduced by the combination therapy [risk ratio ¼ 0.65, 95% CI (0.46-0.93), Z ¼ 2.37, P ¼ 0.02], especially the result from the only cohort study [risk ratio ¼ 0.38, 95% CI (0.16-0.87), Z ¼ 2.30, P ¼ 0.02]. In addition, the risk of a patient having all-cause death 3,4,8,9 was significantly reduced by the combination therapy [risk ratio ¼ 0.70, 95% CI (0.54-0.92), Z ¼ 2.59, P ¼ 0.01], especially the results from two cohort studies [risk ratio ¼ 0.59, 95% CI (0.36-0.95), Z ¼ 2.18, P ¼ 0.03] (Fig. 3 and Table 3).…”

Section: Risk Of Bias Assessmentmentioning

confidence: 99%

Effectiveness and safety of angiotensin receptor-neprilysin inhibitor and sodium–glucose cotransporter-2 inhibitors for patients with heart failure with reduced ejection fraction: a meta-analysis

Huang¹,

Chongbo²,

Zhang³

et al. 2023

Journal of Cardiovascular Medicine

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The current review aimed to study the effectiveness and safety of angiotensin receptor-neprilysin inhibitor (ARNI) combined with sodium–glucose cotransporter-2 (SGLT2) inhibitors versus ARNI or SGLT2 inhibitors monotherapy in patients with heart failure with reduced ejection fraction (HFrEF). Studies containing patients with HFrEF who used ARNI combined with SGLT2 inhibitors versus ARNI or SGLT2 inhibitors alone were retrieved from the Medline, Embase, and Cochrane Library databases. From the selected studies, the pooled risk ratios with 95% confidence intervals of dichotomous outcomes were assessed by a random or fixed effects model in our meta-analysis. Compared with ARNI monotherapy, the reduction in ARNI combined with SGLT2 inhibitors in a composite of the first hospitalization for heart failure or cardiovascular death was 32%, hospitalization for heart failure was 35% and cardiovascular death was 35%; also all-cause death was 30%, worsening renal function was 35%, respectively, for patients with HFrEF. In addition, compared with SGLT2 inhibitors monotherapy, the reduction in ARNI combined with SGLT2 inhibitors in cardiovascular death was 36% and all-cause death was 28%, respectively, for patients with HFrEF. Although the estimated treatment effect is a 55% increase in volume depletion, overall, ARNI combined with SGLT2 inhibitors might be effective and safe for patients with HFrEF, and volume depletion should be given more attention.

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“…Combination therapy of sacubitril/valsartan therapy with SGLT2 inhibitors—originally developed as anti-diabetic drugs—has shown additional benefits in patients with diabetic cardiomyopathy ( Kim et al, 2021 ; Karabulut et al, 2022 ). The combination exhibits synergistic effects through independent mechanisms that offer greater prominent improvements in cardiac function, observed with the augmented LVEF and reduction in E/E’ ratio, as well as a decrease in the risk of cardiovascular death.…”

Section: Mechanistic Roles Of Sacubitril/valsartan In Cardiac Remodelingmentioning

confidence: 99%

“…In addition, sacubitril/valsartan improves fractional shortening, cardiac output, loaddependent indices of left ventricular contractility (dp/dt max ), and relaxation (dp/dt min ) in animal heart failure models (Maslov et al, 2019b;Ge et al, 2020;Liu Y. et al, 2021;Raj et al, 2021) (Table 2). Combination therapy of sacubitril/valsartan therapy with SGLT2 inhibitors-originally developed as anti-diabetic drugs-has shown additional benefits in patients with diabetic cardiomyopathy (Kim et al, 2021;Karabulut et al, 2022). The combination exhibits synergistic effects through independent mechanisms that offer greater prominent improvements in cardiac function, observed with the augmented LVEF and reduction in E/E' ratio, as well as a decrease in the risk of cardiovascular death.…”

Section: Effects On Cardiac Functionmentioning

confidence: 99%

Molecular mechanisms of sacubitril/valsartan in cardiac remodeling

Mustafa

Jalil²,

Zainalabidin³

et al. 2022

Front. Pharmacol.

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Cardiovascular diseases have become a major clinical burden globally. Heart failure is one of the diseases that commonly emanates from progressive uncontrolled hypertension. This gives rise to the need for a new treatment for the disease. Sacubitril/valsartan is a new drug combination that has been approved for patients with heart failure. This review aims to detail the mechanism of action for sacubitril/valsartan in cardiac remodeling, a cellular and molecular process that occurs during the development of heart failure. Accumulating evidence has unveiled the cardioprotective effects of sacubitril/valsartan on cellular and molecular modulation in cardiac remodeling, with recent large-scale randomized clinical trials confirming its supremacy over other traditional heart failure treatments. However, its molecular mechanism of action in cardiac remodeling remains obscure. Therefore, comprehending the molecular mechanism of action of sacubitril/valsartan could help future research to study the drug’s potential therapy to reduce the severity of heart failure.

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Effect of Sacubitril/Valsartan Combined with Dapagliflozin on Long-Term Cardiac Mortality in Heart Failure with Reduced Ejection Fraction

Cited by 13 publications

References 31 publications

Relationship between left ventricular mechanical synchrony and left ventricular systolic function: a CZT-SPECT analysis

Relationship between left ventricular mechanical synchrony and left ventricular systolic function: a CZT-SPECT analysis

Effectiveness and safety of angiotensin receptor-neprilysin inhibitor and sodium–glucose cotransporter-2 inhibitors for patients with heart failure with reduced ejection fraction: a meta-analysis

Molecular mechanisms of sacubitril/valsartan in cardiac remodeling

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