Efficacy and Tolerability of Very Low-Dose Sacubitril/Valsartan in heart failure with reduced ejection fraction (HFrEF) Patients

Research Article | DOI: https://doi.org/10.31579/2641-0419/487

Efficacy and Tolerability of Very Low-Dose Sacubitril/Valsartan in heart failure with reduced ejection fraction (HFrEF) Patients

  • Abdullah Al Shafi Majumder 1
  • Toufiqur Rahman 2
  • AKM Monowarul Islam 2
  • Mohammad Ullah Firoz 2
  • Md. Alimur Reza 3*
  • Md. Molla Iftekhar Hossain 4
  • Mohsin Ahmed 5
  • Md. Mahbubur Rahman 6
  • Muhammad Shahabuddin 7
  • S. M. Quamrul Huq 8
  • Solaiman Mia 9
  • Abu Zahid Bosunia 6
  • Gobinda Kanti Paul 10
  • Shahriar Kabir 11
  • Shahana Zaman 2
  • Ranjit C. Khan 12
  • Md. Zillur Rahman 2
  • Khondoker Asaduzzaman 13
  • Azizur Rahman Roman 14
  • Md. Durul Hoda 15
  • Md. Khalequzzaman 2
  • Dr. Mezbah Uddin Ahmed 2
  • Moniruzzaman 16
  • Rajesh Kumar Gosh 17
  • Sujit Kumar Chanda (Apu) 18
  • Rayhan Masum Mondol 19
  • Samir Kumar Kundu 11
  • Durba Halder 20
  • Md. Abul Khair 21
  • Anisul Awal 22
  • Rajib Gosh 23
  • Dipankar Chandra Nag 24
  • Ashraf Uddin Chowdhury 25
  • Md. Fakhrul Islam Juwel 26
  • Md. Ajmirul Hoque Sarkar 26
  • Md. Sk. Mamun 27
  • Nur Alam 2
  • Md. Mizanur Rahman 28
  • Syed Nasir Uddin 2
  • Miah Mohammad Jamsidul Hassan 3
  • Mousumi Rahman 3

1Popular Medical College Hospital, Dhaka.

2National Institute of Cardiovascular Diseases, Dhaka.

3Beximco Pharmaceuticals Ltd., Dhaka.

4Rajshahi Medical College Hospital, Rajshahi

5Kurmitola General Hospital, Dhaka.

6Rangpur Medical College Hospital, Rangpur.

7Mount Adora Hospital, Sylhet.

8Ad-Din Akij Medical College Hospital, Khulna.

9Habiganj Medical College Hospital, Habiganj.

10Mymensingh Medical College Hospital, Mymensingh.

11Dinajpur Medical College Hospital, Dinajpur.

12South Apollo Medical College Hospital, Barishal.

13Square Hospital, Dhaka.

14Shaheed M. Monsur Ali Medical College, Sirajganj.

15Shaheed Tajuddin Ahmad Medical College Hospital, Gazipur.

16Enam Medical College Hospital, Dhaka.

17Naogaon Medical College Hospital, Naogaon.

18Nexus hospitals, Mymensingh.

19Bangladesh Medical University, Dhaka

20Sir Salimullah Medical College & Mitford Hospital, Dhaka

21Ibn Sina Diagnostic Center, Uttara.

22Chittagong Medical College Hospital, Chittagong.

23Rangamati Medical College Hospital, Rangamati

24Dhaka National Medical College Hospital, Dhaka

25Sheikh Sayera Khatun Medical College Hospital, Gopalganj.

26Shaheed Ziaur Rahman Medical College Hospital, Bogura.

27Hathazari Health Complex, Chittagong.

28Tangail Medical College Hospital, Tangail.

*Corresponding Author: Mohammed Alimur Reza, Beximco Pharmaceuticals Ltd., Dhaka.

Citation: Abdullah Al S M , Toufiqur Rahman , AKM Monowarul Islam , Mohammad U Firoz , Md. Alimur Reza., et al, (2025), Efficacy and Tolerability of Very Low-Dose Sacubitril/Valsartan in heart failure with reduced ejection fraction (HFrEF) Patients, J Clinical Cardiology and Cardiovascular Interventions, 8(9); DOI: 10.31579/2641-0419/487

Copyright: © 2025, Md. Alimur Reza. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Received: 06 June 2025 | Accepted: 18 June 2025 | Published: 30 June 2025

Keywords: sacubitril/valsartan; heart failure with reduced ejection fraction (hfref); nt-probnp; tolerability; nyha functional class

Abstract

Objective: This study aims to evaluate the efficacy and tolerability of Sacubitril/valsartan commenced at a very low dose in patients with Heart Failure and Reduced Ejection Fraction (HFrEF).

Methods: This was a prospective, real-world study conducted in 33 centres in Bangladesh on adult patients with symptomatic Heart failure and reduced ejection fraction (LVEF ≤ 40%) treated with a very low dose of Sacubitril/valsartan (12/13 mg) twice a day along with other standard treatment, with a 12-week follow-up. The primary endpoint was the mean change in NT-proBNP levels from baseline to week 12.

Results: The study included 655 patients with a mean age of 57.98±11.98 years. The mean NT-proBNP level showed a significant decline from 2867.15 pg/mL to 938.41 pg/mL (p<0.001). Notably, over 55% of patients achieved a reduction of 50% or more NT-proBNP. Concurrently, LVEF improved significantly from 34.80±6.7% at baseline to 39.20±6.4% at 12 weeks (p<0.001). There was also a significant reduction in left ventricular end-diastolic diameter, from 60.26±6.3 mm to 57.34±6.5 mm (p<0.001). Furthermore, more than 85% of patients exhibited favourable changes in the New York Heart Association functional class at 12 weeks (p<0.001). As there was no up-titration of doses, no patients experienced symptomatic hypotension or any other serious adverse events.

Conclusions: Very Low-dose sacubitril/valsartan demonstrates significant efficacy and tolerability in patients with HFrEF, as evidenced by marked reductions in NT-proBNP levels. The administration of a lower dosage may enhance patient tolerability and adherence to treatment; however, further controlled studies are necessary to confirm these findings.

Abbreviations:

ACEI – Angiotensin-Converting Enzyme Inhibitor AF – Atrial Fibrillation

ARB – Angiotensin Receptor Blocker

ARNI – Angiotensin Receptor–Neprilysin Inhibitor BD – Bis in Die (Twice Daily)

BMI – Body Mass Index

CCR – Creatinine Clearance Rate CVD – cardiovascular disease

eGFR – Estimated Glomerular Filtration Rate ESC – European Society of Cardiology

HF – Heart Failure

HFrEF – Heart Failure with Reduced Ejection Fraction HTN – Hypertension

IQR – Interquartile Range

LVEDD – Left Ventricular End-Diastolic Diameter LVEF – Left Ventricular Ejection Fraction

MI – Myocardial Infarction

MRA – Mineralocorticoid Receptor Antagonist

NT-proBNP – N-terminal pro-B-type Natriuretic Peptide NYHA – New York Heart Association

RCT – Randomized Controlled Trial SD – Standard Deviation

SGLT2 – Sodium-Glucose Cotransporter 2

SPSS – Statistical Package for the Social Sciences SV – Sacubitril/Valsartan

VLD – Very Low Dose

Introduction

Heart failure (HF) represents a serious and life-threatening condition impacting an estimated 37.7 million individuals globally (Shah et al., 2017). It presents a significant public health burden due to its chronic nature, coupled with elevated rates of morbidity and mortality, along with frequent hospital admissions. In Bangladesh, heart failure accounts for approximately 28.5% of all cardiovascular diseases, underscoring a considerable public health challenge within the region (Rahman et al., 2017).

Despite adherence to guideline-directed medical therapy—including angiotensin-converting enzyme inhibitors (ACEIs), angiotensin receptor blockers (ARBs), beta-blockers, and mineralocorticoid receptor antagonists—patient outcomes remain suboptimal, particularly for those diagnosed with reduced ejection fraction (HFrEF) (Mozaffarian et al., 2015). Mortality rates and the risk of rehospitalization continue to be exceedingly high, thereby highlighting the urgent need for more effective treatment strategies.

Sacubitril/valsartan, an angiotensin receptor–neprilysin inhibitor (ARNI), has emerged as a promising therapeutic alternative for patients with HFrEF. In the landmark PARADIGM-HF (Prospective Comparison of ARNI With ACEI to Determine Impact on Global Mortality and Morbidity in Heart Failure) trial, sacubitril/valsartan demonstrated a 20% relative risk reduction in cardiovascular death or heart failure hospitalization compared with enalapril, a standard ACEI (McMurray et al., 2014). These findings led to its incorporation into international clinical practice guidelines, with both the European Society of Cardiology (ESC) and American College of Cardiology (ACC)/American Heart Association (AHA) granting it a Class I recommendation for use in patients with chronic symptomatic HFrEF (Ponikowski et al., 2016; Yancy et al., 2017).

Despite strong endorsements for sacubitril/valsartan, its real-world utilization remains limited, with prescription rates falling short of expectations in clinical practice (Du et al., 2019; DeVore et al., 2018; Vicent et al., 2019; Pinto et al., 2019; Greene et al., 2018). Several factors contribute to this gap, many of which originate from treatment protocols used in pivotal trials such as PARADIGM-HF, where patients were required to tolerate a high dose of enalapril before transitioning to sacubitril/valsartan. In real-world settings, many patients are unable to tolerate such doses due to adverse effects like hypotension, renal dysfunction, or hyperkalemia (Oh et al., 2019; Wachter et al., 2019). As a result, clinicians often initiate sacubitril/valsartan at lower doses (50 mg or 100 mg twice daily), and up- titration to the recommended target dose of 200 mg twice daily is frequently not achieved. Observational data suggest that only 27% to 38% of patients reach the target dose in routine practice (Du et al., 2019; Vicent et al., 2019).

Initiating therapy in patients with heart failure with reduced ejection fraction is further complicated by risks such as symptomatic hypotension, renal impairment, and hyperkalemia—particularly in elderly patients or those with low baseline blood pressure or renal dysfunction—leading to delays or underdosing in clinical management (Greene et al., 2018). A low starting dose with a conservative up- titration schedule is recommended. The TITRATION trial shows that gradual dose escalation improves tolerability without affecting long-term efficacy (Desai et al., 2017). Similarly, the PARADIGM-HF trial indicates that patients unable to reach target doses still benefit clinically (McMurray et al., 2014). Real- world studies confirm that low-dose initiation increases acceptance in high-risk groups while allowing for future titration (Greene et al., 2018). A retrospective analysis by Amitabh et al. (2021) involving 45 of 278 patients revealed significant reductions in NT-proBNP levels across low-dose groups, suggesting that this approach can benefit those who are intolerant to higher doses. Additionally, a study by Hyoeun et al. (2020) showed comparable improvements in NT-proBNP levels and left ventricular ejection fraction for patients starting at a conservative 25 mg BID, with similar adverse event rates. Therefore, a low-dose initiation strategy for sacubitril/valsartan may enhance safety, adherence, and therapeutic outcomes in clinical practice.

Patients with HFrEF in Bangladesh often present with multiple comorbidities, including chronic kidney disease, low body weight, and hypotension, which can heighten the risk of adverse effects from standard doses of sacubitril/valsartan. Additionally, limited access to regular laboratory monitoring and follow-up in resource-constrained settings further complicates the safe initiation and titration of the drug. A low-dose approach may offer improved tolerability and greater feasibility for long-term use in this population. Moreover, economic constraints constitute a significant barrier to the widespread adoption of newer heart failure therapies, and initiating treatment at a very low dose may reduce upfront medication costs, improving accessibility and adherence. While global studies, such as the TITRATION trial and data from Korea and California, support the safety and effectiveness of initiating sacubitril/valsartan at lower-than-recommended doses (Desai et al., 2017; Hyoeun et al., 2020; Amitabh et al., 2021), local data are needed to validate this approach in the Bangladeshi population. Therefore, a region-specific study could provide valuable insights into optimizing heart failure treatment in low-resource settings. This study aims to evaluate the efficacy and tolerability of sacubitril/valsartan commenced at a very low dose in patients with HFrEF.

Methods

Study Design and Setting

This was a prospective, observational cohort study conducted to evaluate the real-world effectiveness and safety of sacubitril/valsartan (SV) in patients with HFrEF. The study was carried out across 33 centers in Bangladesh from November 2023 to October 2024. Adult patients diagnosed with HFrEF and prescribed SV as part of routine clinical care were enrolled and followed over a defined period of 12 weeks. All procedures were conducted in accordance with the ethical standards of the Declaration of Helsinki and Good Clinical Practice (GCP) guidelines. Written informed consent was obtained from all participants prior to enrollment.

Study Participants & Procedures

A total of 655 patients diagnosed with symptomatic heart failure and reduced ejection fraction (left ventricular ejection fraction ≤ 40%) who received a very low dose of Sacubitril/valsartan (12/13 mg) administered twice daily, in conjunction with other standard treatments, were enrolled in the study. The inclusion criteria specified that subjects must be male or female adults aged 18 years or older, exhibit symptomatic heart failure characterized by New York Heart Association (NYHA) class II–IV, and present with a left ventricular ejection fraction of 40% or less, alongside a systolic blood pressure ranging from 90 to 100 mmHg. Patients with renal dysfunction defined as endogenous creatinine clearance rate (CCR), 30 ml/min/1.73 m2 and estimated glomerular filtration rate (eGFR)5.4 mmol/l, previous intolerance to recommended target doses of ACEI/ARBs, known history of angioedema, current hospitalization for conditions other than decompensated HF and serum potassium level >5.4 mmol/l were excluded.

At baseline, comprehensive sociodemographic data, clinical history, findings from physical examinations, and laboratory investigations—including NT-proBNP levels, serum creatinine, electrolytes, and liver function tests—were systematically collected. NT-proBNP levels were subsequently reassessed at the second follow-up to evaluate biochemical responses. Patients were monitored at 4 weeks and 12 weeks post-enrollment to assess adverse events, including hypotension, renal impairment, and hyperkalemia, as well as any instances of hospitalization or therapy discontinuation.

Study Outcomes

The primary endpoints of the study included the proportional change in NT-proBNP levels and the improvement in NYHA functional class by Week 12. The secondary endpoints encompassed alterations in left ventricular ejection fraction (LVEF), left ventricular end-diastolic dimension (LVEDD), cardiovascular mortality, hospital re-admission for heart failure, and all-cause mortality, all assessed by Week 12. Additionally, safety endpoints were defined as the percentage of patients withdrawn due to adverse events, as well as the incidence of both adverse events and serious adverse events from baseline to Week 12.

Statistical Analysis

All data were systematically entered and analyzed utilizing SPSS for Windows, version 25.0 (IBM Corp., Armonk, NY, USA). Descriptive statistics were employed to summarize the baseline and follow-up characteristics of the participants. Continuous variables were presented as mean ± standard deviation (SD), accompanied by the interquartile range (IQR), with comparisons made using the paired t-test, as appropriate based on the distribution. Categorical variables were reported as frequencies and percentages, with comparisons conducted using the Chi-square test. A p-value of less than 0.05 was deemed statistically significant for all analyses.

Results

Study Population

A total of 914 patients diagnosed with HFrEF and treated with sacubitril/valsartan were initially enrolled in the study. Ultimately, 655 patients had comprehensive data available for both baseline and follow-up measurements of NT-proBNP. These 655 patients were included in the final analysis.

Sociodemographic Characteristics

Out of 655 patients included in the study, the majority were above 60 years (41.6%). The mean age of total patients was 57.98 ± 11.98 years. Males constituted 69.5% of the study population. Most patients had a healthy BMI (53.5%), while 38.9% were overweight and 4.5% were obese. Regarding smoking history, 43.2% were non-smokers, 40.2% were current smokers, and 18.6% were ex-smokers.

Demographic characteristicsFrequencyPercentage
Age
<50>15423.7%
50-60 years22634.7%
>60 years27141.6%
Sex
Male45569.50%
Female20030.50%
BMI
Underweight143.10%
Healthy Weight23953.50%
Overweight17438.9%
Obesity204.50%
Smoking history
Non-smoker26343.2%
Smoker23340.2%
Ex-smoker11318.6%
Co-morbidity
Stroke365.5%
Diabetes34252.6%
MI35554.6%
AF243.7%
Renal failure6710.3%
HTN33755.7%

Table 1: Demographic characteristics of study populations

Changes in NT-proBNP

Figure 1 and Table 2 provide a summary of the changes observed with sacubitril/valsartan treatment in the primary outcome measure, NT-proBNP, which is an essential biomarker for evaluating the severity of heart failure. At baseline, the mean NT-proBNP level was recorded at 2,867.15 ± 3,817.46 pg/mL. After treatment, this value demonstrated a substantial decrease to 938.41 ± 1,470.22 pg/mL. This reduction was statistically significant (p < 0>

VariablesBaselineAfter 12 weeksP-value
NT-proBNP (pg/mL); Mean± SD2867.15 ± 3817.46938.41 ± 1470.22<0>
LVEF (%); Mean± SD34.80 ± 6.7 (%)39.20 ± 6.4(%)<0>
LVEDD (mm); Mean± SD60.26 ± 6.357.34 ± 6.5<0>
Serum Sodium (mmol/L); Mean ± SD137.92 ± 5.9137.63 ± 4.20.150
Serum Potassium (mEq/L); Mean ± SD4.24 ± 0.74.25 ± 0.60.983
Serum Creatinine (mg/dL); Mean ± SD1.24 ± 0.41.18 ± 0.3<0>

Table 2: Changes under treatment with Sacubitril/Valsartan after 12 weeks of follow-up

Figure 2. Changes after 12 weeks treatment with sacubitril/valsartan- mean NT-proBNP (A) level significantly decreased from 2867.15 pg/mL to 938.41 pg/mL (p<0>

Figure 2 shows the percentage changes across five categories related to the extent of decline or increase. Specifically, 29% of patients exhibited a ≥75

Discussion

This prospective, multicenter, real-world study in Bangladesh assessed the effectiveness and safety of initiating very low-dose sacubitril/valsartan (12/13 mg twice daily) in patients with heart failure with reduced ejection fraction. The results demonstrate clinically meaningful improvements in NT-proBNP levels, LVEF, LVEDD, and NYHA functional class, while maintaining a favorable safety and tolerability profile. These findings are consistent with those reported in both landmark randomized controlled trials and observational studies.

In the PARADIGM-HF trial, sacubitril/valsartan significantly reduced the risk of cardiovascular death or heart failure hospitalization by 20% compared with enalapril (McMurray et al., 2014). Our study similarly showed a notable reduction in NT-proBNP levels—from 2867.15 pg/mL to 938.41 pg/mL (p< .001)—a key biomarker predictive of prognosis in HFrEF. Furthermore, 85% of patients demonstrated an improvement in NYHA class, indicating significant symptomatic benefit.

The present findings align with real-world evidence. For example, Amitabh et al. (2019) reported a significant reduction in NT-proBNP (3703 to 1478 ng/mL, p < .01) among patients in California on very low doses of sacubitril/valsartan. In Korea, Hyoeun et al. (2019) observed a similar NT-proBNP decline (2594 to 2199 pg/mL, p < .001), with no differences in outcomes between standard and very low-dose groups. These studies also reported improvement in NYHA functional class, consistent with our observations.

Jingwen et al. (2019) found a reduction in NT-proBNP (from 2495 to 943 pg/mL, p < .001), a rise in LVEF (from 35.4% to 43.0%, p < .001), and a decrease in LVEDD (from 63.7 to 60.4 mm, p < .01), mirroring our findings (LVEF: 34.80% to 39.20%, p < .001; LVEDD: 60.26 to 57.34 mm, p < .001).

Renal and electrolyte safety were also observed in our cohort. While Amitabh et al. (2019) noted a non- significant rise in serum creatinine and potassium, our study revealed a statistically significant reduction in serum creatinine (1.24 to 1.18 mg/dL; p < .001), with no significant changes in potassium levels. These findings are in line with those from Jingwen et al. (2019), who reported no significant changes in creatinine or potassium levels.

Adverse events in our study were infrequent and generally mild. Tolerable cough was most commonly reported (16.5% at baseline, declining to 9.6% at 12 weeks), followed by hypotension (6.6% to 3.4%) and angioedema (1.4% to 0.8%). Jingwen et al. (2019) reported hypotension in 60% of patients during up-titration, with minimal cough and no angioedema. Similarly, Hyoeun et al. study showed, the most common adverse event was hypotension, but there was no significant difference in the adverse events between the two dose-groups. The most common cause for intolerance during up-titration was dizziness, and more patients complained of dizziness in the SD group compared to the VLD group.

Across various clinical trials and real-world studies, the tolerability and discontinuation rates of sacubitril/valsartan have shown notable variation. In PARADIGM-HF and PARAGON-HF, discontinuation due to adverse events occurred in 10.7% and 25.3% of patients, respectively (McMurray et al., 2014; Solomon et al., 2019). The TRANSITION study showed lower discontinuation rates when therapy was initiated in-hospital (7.1% pre-discharge, 5.6% post-discharge) (Welsh et al., 2019). In contrast, real-world discontinuation rates are generally lower. For instance, Jin Joo et al. (2019) reported a 5.2% rate, Alberto et al. (2018) reported none, and Muhammad et al. (2020) reported a higher rate (19.4%) related to dose adjustments. Remarkably, in our study, no patient discontinued sacubitril/valsartan therapy during the follow-up period, indicating excellent tolerability and adherence.

Importantly, our cohort was initiated on sacubitril/valsartan without a run-in phase or prior tolerance of high-dose ACE inhibitors, unlike the PARADIGM-HF protocol. This deviation was necessitated by the clinical characteristics of our population, which included lower average BMI, higher baseline hypotension, and frequent comorbidities (e.g., diabetes, hypertension). These factors may explain both the need for low-dose initiation and the observed high tolerability.

Limitations and Future Directions

This study has several limitations. First, the absence of a control group limits causal inference, as improvements cannot be definitively attributed to sacubitril/valsartan alone. Second, observational design is subject to potential confounders, such as variability in physician decision-making and adherence. Third, although multicenter, the study population was limited to Bangladesh, potentially reducing generalizability to broader populations. Fourth, the follow-up duration (12 weeks) may not capture long-term outcomes, including mortality and rehospitalization rates. Fifth, the use of echocardiography and laboratory parameters without centralized adjudication may introduce measurement bias.

Conclusion

The findings of this study support the therapeutic potential of initiating sacubitril/valsartan at a very low dose in patients with HFrEF, particularly in real-world clinical settings. Significant improvements in NT-proBNP levels, left ventricular function, and symptom burden, coupled with favorable tolerability, underscore the viability of low-dose initiation strategies—especially for patient populations with heightened sensitivity to standard dosages. Moreover, the enhanced tolerability profile may facilitate better treatment adherence. Nonetheless, these findings should be interpreted within the context of an observational design. Future randomized controlled trials are warranted to confirm the long-term efficacy, safety, and optimal dosing strategies of sacubitril/valsartan in diverse clinical populations.

Acknowledgements

The authors gratefully acknowledge the financial support provided by Beximco Pharmaceuticals Limited, Dhaka, Bangladesh, which was instrumental in facilitating the conduct of this study. The sponsor had no involvement in the study design, data collection, data analysis, interpretation of results, or the preparation and submission of the manuscript. The authors retained complete independence in all aspects of the research.

Conflict of Interest

The authors declare no conflicts of interest

References

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"We recently published an article entitled “Influence of beta-Cyclodextrins upon the Degradation of Carbofuran Derivatives under Alkaline Conditions" in the Journal of “Pesticides and Biofertilizers” to show that the cyclodextrins protect the carbamates increasing their half-life time in the presence of basic conditions This will be very helpful to understand carbofuran behaviour in the analytical, agro-environmental and food areas. We greatly appreciated the interaction with the editor and the editorial team; we were particularly well accompanied during the course of the revision process, since all various steps towards publication were short and without delay".

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Jesus Simal-Gandara

I would like to express my gratitude towards you process of article review and submission. I found this to be very fair and expedient. Your follow up has been excellent. I have many publications in national and international journal and your process has been one of the best so far. Keep up the great work.

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Douglas Miyazaki

We are grateful for this opportunity to provide a glowing recommendation to the Journal of Psychiatry and Psychotherapy. We found that the editorial team were very supportive, helpful, kept us abreast of timelines and over all very professional in nature. The peer review process was rigorous, efficient and constructive that really enhanced our article submission. The experience with this journal remains one of our best ever and we look forward to providing future submissions in the near future.

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Dr Griffith

I am very pleased to serve as EBM of the journal, I hope many years of my experience in stem cells can help the journal from one way or another. As we know, stem cells hold great potential for regenerative medicine, which are mostly used to promote the repair response of diseased, dysfunctional or injured tissue using stem cells or their derivatives. I think Stem Cell Research and Therapeutics International is a great platform to publish and share the understanding towards the biology and translational or clinical application of stem cells.

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Dr Tong Ming Liu

I would like to give my testimony in the support I have got by the peer review process and to support the editorial office where they were of asset to support young author like me to be encouraged to publish their work in your respected journal and globalize and share knowledge across the globe. I really give my great gratitude to your journal and the peer review including the editorial office.

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Husain Taha Radhi

I am delighted to publish our manuscript entitled "A Perspective on Cocaine Induced Stroke - Its Mechanisms and Management" in the Journal of Neuroscience and Neurological Surgery. The peer review process, support from the editorial office, and quality of the journal are excellent. The manuscripts published are of high quality and of excellent scientific value. I recommend this journal very much to colleagues.

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S Munshi

Dr.Tania Muñoz, My experience as researcher and author of a review article in The Journal Clinical Cardiology and Interventions has been very enriching and stimulating. The editorial team is excellent, performs its work with absolute responsibility and delivery. They are proactive, dynamic and receptive to all proposals. Supporting at all times the vast universe of authors who choose them as an option for publication. The team of review specialists, members of the editorial board, are brilliant professionals, with remarkable performance in medical research and scientific methodology. Together they form a frontline team that consolidates the JCCI as a magnificent option for the publication and review of high-level medical articles and broad collective interest. I am honored to be able to share my review article and open to receive all your comments.

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Tania Munoz

“The peer review process of JPMHC is quick and effective. Authors are benefited by good and professional reviewers with huge experience in the field of psychology and mental health. The support from the editorial office is very professional. People to contact to are friendly and happy to help and assist any query authors might have. Quality of the Journal is scientific and publishes ground-breaking research on mental health that is useful for other professionals in the field”.

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George Varvatsoulias

Dear editorial department: On behalf of our team, I hereby certify the reliability and superiority of the International Journal of Clinical Case Reports and Reviews in the peer review process, editorial support, and journal quality. Firstly, the peer review process of the International Journal of Clinical Case Reports and Reviews is rigorous, fair, transparent, fast, and of high quality. The editorial department invites experts from relevant fields as anonymous reviewers to review all submitted manuscripts. These experts have rich academic backgrounds and experience, and can accurately evaluate the academic quality, originality, and suitability of manuscripts. The editorial department is committed to ensuring the rigor of the peer review process, while also making every effort to ensure a fast review cycle to meet the needs of authors and the academic community. Secondly, the editorial team of the International Journal of Clinical Case Reports and Reviews is composed of a group of senior scholars and professionals with rich experience and professional knowledge in related fields. The editorial department is committed to assisting authors in improving their manuscripts, ensuring their academic accuracy, clarity, and completeness. Editors actively collaborate with authors, providing useful suggestions and feedback to promote the improvement and development of the manuscript. We believe that the support of the editorial department is one of the key factors in ensuring the quality of the journal. Finally, the International Journal of Clinical Case Reports and Reviews is renowned for its high- quality articles and strict academic standards. The editorial department is committed to publishing innovative and academically valuable research results to promote the development and progress of related fields. The International Journal of Clinical Case Reports and Reviews is reasonably priced and ensures excellent service and quality ratio, allowing authors to obtain high-level academic publishing opportunities in an affordable manner. I hereby solemnly declare that the International Journal of Clinical Case Reports and Reviews has a high level of credibility and superiority in terms of peer review process, editorial support, reasonable fees, and journal quality. Sincerely, Rui Tao.

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Rui Tao

Clinical Cardiology and Cardiovascular Interventions I testity the covering of the peer review process, support from the editorial office, and quality of the journal.

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Khurram Arshad

Clinical Cardiology and Cardiovascular Interventions, we deeply appreciate the interest shown in our work and its publication. It has been a true pleasure to collaborate with you. The peer review process, as well as the support provided by the editorial office, have been exceptional, and the quality of the journal is very high, which was a determining factor in our decision to publish with you.

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Gomez Barriga Maria Dolores

The peer reviewers process is quick and effective, the supports from editorial office is excellent, the quality of journal is high. I would like to collabroate with Internatioanl journal of Clinical Case Reports and Reviews journal clinically in the future time.

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Lin Shaw Chin

Clinical Cardiology and Cardiovascular Interventions, I would like to express my sincerest gratitude for the trust placed in our team for the publication in your journal. It has been a true pleasure to collaborate with you on this project. I am pleased to inform you that both the peer review process and the attention from the editorial coordination have been excellent. Your team has worked with dedication and professionalism to ensure that your publication meets the highest standards of quality. We are confident that this collaboration will result in mutual success, and we are eager to see the fruits of this shared effort.

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Maria Dolores Gomez Barriga

Dear Dr. Jessica Magne, Editorial Coordinator 0f Clinical Cardiology and Cardiovascular Interventions, I hope this message finds you well. I want to express my utmost gratitude for your excellent work and for the dedication and speed in the publication process of my article titled "Navigating Innovation: Qualitative Insights on Using Technology for Health Education in Acute Coronary Syndrome Patients." I am very satisfied with the peer review process, the support from the editorial office, and the quality of the journal. I hope we can maintain our scientific relationship in the long term.

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Dr Maria Dolores Gomez Barriga

Dear Monica Gissare, - Editorial Coordinator of Nutrition and Food Processing. ¨My testimony with you is truly professional, with a positive response regarding the follow-up of the article and its review, you took into account my qualities and the importance of the topic¨.

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Dr Maria Regina Penchyna Nieto

Dear Dr. Jessica Magne, Editorial Coordinator 0f Clinical Cardiology and Cardiovascular Interventions, The review process for the article “The Handling of Anti-aggregants and Anticoagulants in the Oncologic Heart Patient Submitted to Surgery” was extremely rigorous and detailed. From the initial submission to the final acceptance, the editorial team at the “Journal of Clinical Cardiology and Cardiovascular Interventions” demonstrated a high level of professionalism and dedication. The reviewers provided constructive and detailed feedback, which was essential for improving the quality of our work. Communication was always clear and efficient, ensuring that all our questions were promptly addressed. The quality of the “Journal of Clinical Cardiology and Cardiovascular Interventions” is undeniable. It is a peer-reviewed, open-access publication dedicated exclusively to disseminating high-quality research in the field of clinical cardiology and cardiovascular interventions. The journal's impact factor is currently under evaluation, and it is indexed in reputable databases, which further reinforces its credibility and relevance in the scientific field. I highly recommend this journal to researchers looking for a reputable platform to publish their studies.

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Dr Marcelo Flavio Gomes Jardim Filho

Dear Editorial Coordinator of the Journal of Nutrition and Food Processing! "I would like to thank the Journal of Nutrition and Food Processing for including and publishing my article. The peer review process was very quick, movement and precise. The Editorial Board has done an extremely conscientious job with much help, valuable comments and advices. I find the journal very valuable from a professional point of view, thank you very much for allowing me to be part of it and I would like to participate in the future!”

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Zsuzsanna Bene

Dealing with The Journal of Neurology and Neurological Surgery was very smooth and comprehensive. The office staff took time to address my needs and the response from editors and the office was prompt and fair. I certainly hope to publish with this journal again.Their professionalism is apparent and more than satisfactory. Susan Weiner

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Dr Susan Weiner

My Testimonial Covering as fellowing: Lin-Show Chin. The peer reviewers process is quick and effective, the supports from editorial office is excellent, the quality of journal is high. I would like to collabroate with Internatioanl journal of Clinical Case Reports and Reviews.

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Lin-Show Chin

My experience publishing in Psychology and Mental Health Care was exceptional. The peer review process was rigorous and constructive, with reviewers providing valuable insights that helped enhance the quality of our work. The editorial team was highly supportive and responsive, making the submission process smooth and efficient. The journal's commitment to high standards and academic rigor makes it a respected platform for quality research. I am grateful for the opportunity to publish in such a reputable journal.

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Sonila Qirko

My experience publishing in International Journal of Clinical Case Reports and Reviews was exceptional. I Come forth to Provide a Testimonial Covering the Peer Review Process and the editorial office for the Professional and Impartial Evaluation of the Manuscript.

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Luiz Sellmann

I would like to offer my testimony in the support. I have received through the peer review process and support the editorial office where they are to support young authors like me, encourage them to publish their work in your esteemed journals, and globalize and share knowledge globally. I really appreciate your journal, peer review, and editorial office.

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Zhao Jia

Dear Agrippa Hilda- Editorial Coordinator of Journal of Neuroscience and Neurological Surgery, "The peer review process was very quick and of high quality, which can also be seen in the articles in the journal. The collaboration with the editorial office was very good."

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Thomas Urban

I would like to express my sincere gratitude for the support and efficiency provided by the editorial office throughout the publication process of my article, “Delayed Vulvar Metastases from Rectal Carcinoma: A Case Report.” I greatly appreciate the assistance and guidance I received from your team, which made the entire process smooth and efficient. The peer review process was thorough and constructive, contributing to the overall quality of the final article. I am very grateful for the high level of professionalism and commitment shown by the editorial staff, and I look forward to maintaining a long-term collaboration with the International Journal of Clinical Case Reports and Reviews.

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Cristina Berriozabal

To Dear Erin Aust, I would like to express my heartfelt appreciation for the opportunity to have my work published in this esteemed journal. The entire publication process was smooth and well-organized, and I am extremely satisfied with the final result. The Editorial Team demonstrated the utmost professionalism, providing prompt and insightful feedback throughout the review process. Their clear communication and constructive suggestions were invaluable in enhancing my manuscript, and their meticulous attention to detail and dedication to quality are truly commendable. Additionally, the support from the Editorial Office was exceptional. From the initial submission to the final publication, I was guided through every step of the process with great care and professionalism. The team's responsiveness and assistance made the entire experience both easy and stress-free. I am also deeply impressed by the quality and reputation of the journal. It is an honor to have my research featured in such a respected publication, and I am confident that it will make a meaningful contribution to the field.

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Dr Tewodros Kassahun Tarekegn

"I am grateful for the opportunity of contributing to [International Journal of Clinical Case Reports and Reviews] and for the rigorous review process that enhances the quality of research published in your esteemed journal. I sincerely appreciate the time and effort of your team who have dedicatedly helped me in improvising changes and modifying my manuscript. The insightful comments and constructive feedback provided have been invaluable in refining and strengthening my work".

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Dr Shweta Tiwari

I thank the ‘Journal of Clinical Research and Reports’ for accepting this article for publication. This is a rigorously peer reviewed journal which is on all major global scientific data bases. I note the review process was prompt, thorough and professionally critical. It gave us an insight into a number of important scientific/statistical issues. The review prompted us to review the relevant literature again and look at the limitations of the study. The peer reviewers were open, clear in the instructions and the editorial team was very prompt in their communication. This journal certainly publishes quality research articles. I would recommend the journal for any future publications.

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Dr Farooq Wandroo

Dear Jessica Magne, with gratitude for the joint work. Fast process of receiving and processing the submitted scientific materials in “Clinical Cardiology and Cardiovascular Interventions”. High level of competence of the editors with clear and correct recommendations and ideas for enriching the article.

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Dr Anyuta Ivanova

We found the peer review process quick and positive in its input. The support from the editorial officer has been very agile, always with the intention of improving the article and taking into account our subsequent corrections.

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Dr David Vinyes

My article, titled 'No Way Out of the Smartphone Epidemic Without Considering the Insights of Brain Research,' has been republished in the International Journal of Clinical Case Reports and Reviews. The review process was seamless and professional, with the editors being both friendly and supportive. I am deeply grateful for their efforts.

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Gertraud Teuchert-Noodt

To Dear Erin Aust – Editorial Coordinator of Journal of General Medicine and Clinical Practice! I declare that I am absolutely satisfied with your work carried out with great competence in following the manuscript during the various stages from its receipt, during the revision process to the final acceptance for publication. Thank Prof. Elvira Farina

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Dr Elvira Farina

Dear Jessica, and the super professional team of the ‘Clinical Cardiology and Cardiovascular Interventions’ I am sincerely grateful to the coordinated work of the journal team for the no problem with the submission of my manuscript: “Cardiometabolic Disorders in A Pregnant Woman with Severe Preeclampsia on the Background of Morbid Obesity (Case Report).” The review process by 5 experts was fast, and the comments were professional, which made it more specific and academic, and the process of publication and presentation of the article was excellent. I recommend that my colleagues publish articles in this journal, and I am interested in further scientific cooperation. Sincerely and best wishes, Dr. Oleg Golyanovskiy.

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Dr Oleg Golyanovski

Dear Ashley Rosa, Editorial Coordinator of the journal - Psychology and Mental Health Care. " The process of obtaining publication of my article in the Psychology and Mental Health Journal was positive in all areas. The peer review process resulted in a number of valuable comments, the editorial process was collaborative and timely, and the quality of this journal has been quickly noticed, resulting in alternative journals contacting me to publish with them." Warm regards, Susan Anne Smith, PhD. Australian Breastfeeding Association.

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Dr Susan Anne Smith

Dear Jessica Magne, Editorial Coordinator, Clinical Cardiology and Cardiovascular Interventions, Auctores Publishing LLC. I appreciate the journal (JCCI) editorial office support, the entire team leads were always ready to help, not only on technical front but also on thorough process. Also, I should thank dear reviewers’ attention to detail and creative approach to teach me and bring new insights by their comments. Surely, more discussions and introduction of other hemodynamic devices would provide better prevention and management of shock states. Your efforts and dedication in presenting educational materials in this journal are commendable. Best wishes from, Farahnaz Fallahian.

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Dr Farahnaz Fallahian

Dear Maria Emerson, Editorial Coordinator, International Journal of Clinical Case Reports and Reviews, Auctores Publishing LLC. I am delighted to have published our manuscript, "Acute Colonic Pseudo-Obstruction (ACPO): A rare but serious complication following caesarean section." I want to thank the editorial team, especially Maria Emerson, for their prompt review of the manuscript, quick responses to queries, and overall support. Yours sincerely Dr. Victor Olagundoye.

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Dr Victor Olagundoye

Dear Ashley Rosa, Editorial Coordinator, International Journal of Clinical Case Reports and Reviews. Many thanks for publishing this manuscript after I lost confidence the editors were most helpful, more than other journals Best wishes from, Susan Anne Smith, PhD. Australian Breastfeeding Association.

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Dr Susan Anne Smith

Dear Agrippa Hilda, Editorial Coordinator, Journal of Neuroscience and Neurological Surgery. The entire process including article submission, review, revision, and publication was extremely easy. The journal editor was prompt and helpful, and the reviewers contributed to the quality of the paper. Thank you so much! Eric Nussbaum, MD

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Dr Eric S Nussbaum

Dr Hala Al Shaikh This is to acknowledge that the peer review process for the article ’ A Novel Gnrh1 Gene Mutation in Four Omani Male Siblings, Presentation and Management ’ sent to the International Journal of Clinical Case Reports and Reviews was quick and smooth. The editorial office was prompt with easy communication.

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Hala Al Shaikh

Dear Erin Aust, Editorial Coordinator, Journal of General Medicine and Clinical Practice. We are pleased to share our experience with the “Journal of General Medicine and Clinical Practice”, following the successful publication of our article. The peer review process was thorough and constructive, helping to improve the clarity and quality of the manuscript. We are especially thankful to Ms. Erin Aust, the Editorial Coordinator, for her prompt communication and continuous support throughout the process. Her professionalism ensured a smooth and efficient publication experience. The journal upholds high editorial standards, and we highly recommend it to fellow researchers seeking a credible platform for their work. Best wishes By, Dr. Rakhi Mishra.

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Dr Rakhi Mishra

Dear Jessica Magne, Editorial Coordinator, Clinical Cardiology and Cardiovascular Interventions, Auctores Publishing LLC. The peer review process of the journal of Clinical Cardiology and Cardiovascular Interventions was excellent and fast, as was the support of the editorial office and the quality of the journal. Kind regards Walter F. Riesen Prof. Dr. Dr. h.c. Walter F. Riesen.

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Dr Walter F Riesen

Dear Ashley Rosa, Editorial Coordinator, International Journal of Clinical Case Reports and Reviews, Auctores Publishing LLC. Thank you for publishing our article, Exploring Clozapine's Efficacy in Managing Aggression: A Multiple Single-Case Study in Forensic Psychiatry in the international journal of clinical case reports and reviews. We found the peer review process very professional and efficient. The comments were constructive, and the whole process was efficient. On behalf of the co-authors, I would like to thank you for publishing this article. With regards, Dr. Jelle R. Lettinga.

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Dr Jelle Lettinga

Dear Clarissa Eric, Editorial Coordinator, Journal of Clinical Case Reports and Studies, I would like to express my deep admiration for the exceptional professionalism demonstrated by your journal. I am thoroughly impressed by the speed of the editorial process, the substantive and insightful reviews, and the meticulous preparation of the manuscript for publication. Additionally, I greatly appreciate the courteous and immediate responses from your editorial office to all my inquiries. Best Regards, Dariusz Ziora

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Dariusz Ziora