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Review Article | DOI: https://doi.org/10.31579/2692-9759/188
¹Department of Cardiology, Hitit University Erol Olçok Education and Research Hospital, Corum, Turkey.
2Department of Cardiology, Facult of Medicine, Hitit University, Corum, Turkey.
*Corresponding Author: Macit Kalçik, Department of Cardiology, Facult of Medicine, Hitit University, Corum, Turkey.
Citation: Yusuf Solak, Macit Kalçik, Mehmet M. Yilmaz, Osman Karaarslan, Muhammet C. Çelik., et al, (2026), Coronary Microvascular Dysfunction in Ischemic Heart Disease: Diagnostic and Therapeutic Advances, Cardiology Research and Reports, 8(2); DOI:10.31579/2692-9759/188
Copyright: © 2026, Macit Kalçik. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Received: 21 January 2026 | Accepted: 06 February 2026 | Published: 13 February 2026
Keywords: coronary microvascular dysfunction; ischemic heart disease; endothelial dysfunction; coronary flow reserve; microvascular angina
Coronary microvascular dysfunction (CMD) has emerged as a key pathophysiologic mechanism underlying ischemic heart disease (IHD) in the absence or presence of obstructive coronary artery disease. CMD is characterized by structural and functional abnormalities of the coronary microcirculation that impair the ability to match myocardial blood flow to metabolic demand. Endothelial dysfunction, vascular remodeling, oxidative stress, and inflammation constitute the principal biological drivers of this condition. CMD manifests clinically as angina with non-obstructive coronary arteries (INOCA), persistent ischemia after revascularization, or as a contributing mechanism in heart failure with preserved ejection fraction. Diagnosis remains challenging because the microcirculation is invisible to standard angiography and requires advanced non-invasive or invasive physiological testing, such as coronary flow reserve, index of microcirculatory resistance, or perfusion imaging. Current therapeutic strategies rely largely on lifestyle modification, risk factor control, and empiric pharmacologic therapy targeting endothelial function or vasomotion. However, persistent symptoms and adverse prognosis in many patients highlight the need for novel approaches. Emerging therapies—including endothelin antagonists, Rho-kinase inhibitors, SGLT2 inhibitors, nitric oxide modulators, and regenerative or device-based interventions—offer potential to address the underlying vascular dysfunction rather than merely relieving symptoms. Future research should focus on standardizing diagnostic criteria, developing biomarkers, and conducting phenotype-directed trials to enable precision therapy. Recognition and effective management of CMD are critical to improving outcomes in patients with ischemic syndromes extending beyond epicardial coronary disease.
Ischemic heart disease (IHD) has long been defined as a condition resulting from an imbalance between myocardial oxygen supply and demand, traditionally attributed to obstructive atherosclerotic lesions in the epicardial coronary arteries. However, clinical observations have shown that a considerable number of patients with angina and objective evidence of myocardial ischemia do not have significant epicardial stenoses. This discordance has shifted attention toward the role of the coronary microcirculation, whose dysfunction can lead to ischemic syndromes even in the absence of large-vessel obstruction [1]. Coronary microvascular dysfunction (CMD) describes abnormalities in the small resistance vessels that regulate myocardial blood flow. These abnormalities may be functional, structural, or both, and result in inadequate vasodilatory capacity, inappropriate vasoconstriction, or microvascular spasm. CMD is increasingly recognized as a key contributor to ischemia in patients with non-obstructive coronary artery disease (INOCA) and in those with persistent angina despite revascularization [2,3]. The clinical importance of CMD lies in its high prevalence and prognostic implications. Up to half of patients with angina and non-obstructive coronary arteries demonstrate impaired microvascular function when investigated with advanced diagnostic tools [4]. CMD is particularly prevalent among women, possibly reflecting sex-related differences in endothelial function and hormonal influences [5]. Despite the absence of obstructive lesions, these patients are not free from risk; several longitudinal studies have shown that CMD is associated with an increased incidence of adverse cardiovascular events, including myocardial infarction, heart failure, and death [6,7]. The recognition of CMD as a distinct pathophysiologic entity has exposed major diagnostic and therapeutic challenges. There is currently no single gold-standard test for CMD. Invasive measurements of coronary flow reserve and microvascular resistance, along with non-invasive modalities such as positron emission tomography and cardiac magnetic resonance imaging, provide valuable insights but remain underused due to cost, technical complexity, and limited availability. Furthermore, the heterogeneity of CMD, encompassing both structural remodeling and endothelial dysfunction, makes uniform diagnostic criteria difficult to establish. The result is underdiagnosis and empirical management based on conventional antianginal therapy rather than mechanism-specific interventions. Treatment of CMD remains an area of unmet clinical need. Conventional agents such as beta-blockers, calcium channel blockers, and nitrates often fail to provide adequate symptom control. Therapies that target endothelial dysfunction, including angiotensin-converting enzyme inhibitors, statins, and novel vasomodulatory drugs, show promise but require further validation in randomized trials. Beyond pharmacologic options, recent studies have explored device-based and regenerative approaches aimed at restoring microvascular function. In summary, CMD represents an important and underappreciated cause of myocardial ischemia in both obstructive and non-obstructive forms of IHD. It bridges the gap between traditional macrovascular disease and unexplained angina syndromes, with significant prognostic relevance. However, its diagnosis remains complex and its treatment largely empirical. The present review aims to synthesize current understanding of the pathophysiologic mechanisms, diagnostic approaches, and emerging therapeutic strategies for CMD, while highlighting ongoing challenges and future research directions.
Coronary microvascular dysfunction (CMD) arises from an interplay of structural and functional alterations in the small resistance vessels of the heart. These changes degrade the ability of the coronary microcirculation to match myocardial perfusion to metabolic demand. The pathophysiology is multifactorial, involving endothelial dysfunction, smooth muscle cell dysregulation, inflammatory and oxidative pathways, microvascular remodeling, and disturbances in metabolic–vascular coupling.
Endothelial dysfunction is central. In normal physiology the endothelium modulates vasodilation via nitric oxide (NO) release, prostacyclin, and endothelium-dependent hyperpolarization. In CMD, bioavailability of NO is reduced by increased oxidative stress, uncoupling of endothelial nitric oxide synthase (eNOS), and reactive oxygen species (ROS) formation [8] [9]. Concurrent upregulation of vasoconstrictors such as endothelin-1 further disrupts basal tone regulation [10]. The balance shifts toward vasoconstriction, even at the microvascular level, limiting flow reserve and predisposing to microvascular spasm [11].
Structural changes accompany functional derangements. Persistent endothelial injury triggers remodeling in microvascular walls: hypertrophy of vascular smooth muscle cells, perivascular fibrosis, rarefaction (loss of capillary density), basement membrane thickening, and vessel lumen narrowing [12]. Some capillaries may regress (capillary drop-out), reducing overall microvascular cross-sectional area and increasing resistance. Pericyte loss or dysfunction further impairs microvascular integrity and responsiveness [13]. These structural alterations impose a fixed component of resistance unresponsive to vasodilators.
Another layer involves disturbed metabolic–vascular coupling. In a healthy heart, increases in myocardial demand trigger vasodilation via metabolic signals (adenosine, H⁺, CO₂). In CMD, this coupling is disrupted, so metabolic signaling fails to elicit adequate vasodilatory response [11]. Microvascular autoregulation becomes less flexible. This is especially problematic during stress or increased demand, when microcirculation cannot further dilate, causing ischemia.
Inflammation and oxidative stress are additional contributors. Systemic factors (hypertension, diabetes, obesity, chronic kidney disease) foster a proinflammatory milieu, which induces endothelial activation, leukocyte adhesion, and microvascular injury. Activation of NADPH oxidase, xanthine oxidase, and mitochondrial ROS pathways amplifies oxidative stress, damaging microvascular endothelium [12]. Chronic low-grade inflammation contributes to microvascular remodeling and endothelial cell apoptosis [8].
Molecular signaling pathways are implicated: RhoA/Rho-kinase activation increases vascular smooth muscle contraction and impairs relaxation; the NO–cGMP axis is suppressed; signaling via MAP kinases, NF-κB, and TGF-β promote fibrotic changes [12]. Epigenetic modifications (microRNAs, histone modifications) are emerging as modulators that can “lock in” microvascular dysfunction phenotypes [13]. Cross-talk between microvasculature and systemic vascular beds suggests that CMD may reflect a systemic microvascular disease rather than isolated cardiac pathology [11].
In summary, CMD results from the convergence of endothelial failure, structural remodeling, impaired metabolic signaling, and persistent insults such as inflammation and oxidative stress. This multifaceted pathobiology helps explain why diagnosis is difficult and why a one-size-fits-all therapy is unlikely to succeed (Table 1).
| Mechanism | Cellular / Molecular Basis | Consequence | Clinical Manifestation |
| Endothelial dysfunction | Reduced nitric oxide bioavailability, increased endothelin-1, eNOS uncoupling | Vasoconstriction, reduced coronary flow reserve | Exercise-induced ischemia, microvascular spasm |
| Oxidative stress | NADPH oxidase activation, excessive ROS production | Endothelial injury, perivascular fibrosis | Chronic angina, low CFR |
| Inflammation | Activation of NF-κB, IL-1β, TGF-β pathways | Capillary rarefaction, fibrosis | Progression to HFpEF |
| Structural remodeling | Smooth muscle hypertrophy, basement membrane thickening | Increased microvascular resistance | Persistent ischemia |
| Impaired metabolic–vascular coupling | Defective adenosine/H⁺ signaling | Inadequate vasodilation during demand | Stress-induced ischemia |
Table 1: Major Pathophysiological Mechanisms of Coronary Microvascular Dysfunction.
Abbreviations: NO: Nitric oxide; eNOS: Endothelial nitric oxide synthase; ROS: Reactive oxygen species; CFR: Coronary flow reserve; HFpEF: Heart failure with preserved ejection fraction; NF-κB: Nuclear factor kappa B; IL-1β: Interleukin-1 beta; TGF-β: Transforming growth factor beta.
Coronary microvascular dysfunction (CMD) is a heterogeneous condition that manifests across a wide spectrum of ischemic heart disease phenotypes. The clinical expression of CMD ranges from stable angina with non-obstructive coronary arteries to microvascular obstruction following myocardial infarction and the progressive development of heart failure with preserved ejection fraction (HFpEF). Recognition of these phenotypes has expanded the conceptual framework of ischemic heart disease beyond the epicardial vessel–centric model [5].
The most prominent phenotype is ischemia with non-obstructive coronary arteries (INOCA), in which patients present with angina, objective ischemia, and no flow-limiting epicardial stenosis on angiography. Epidemiologic studies have demonstrated that up to 60% of women and 30% of men undergoing coronary angiography for angina have non-obstructive disease, and approximately half of these exhibit evidence of CMD on invasive or imaging-based testing [4]. The Women’s Ischemia Syndrome Evaluation (WISE) study and subsequent trials established CMD as a major mechanism underlying INOCA, particularly in postmenopausal women [14]. Hormonal withdrawal, endothelial dysfunction, and microvascular remodeling contribute to this sex-related predilection.
CMD also plays a critical role in the setting of obstructive coronary artery disease. In patients undergoing percutaneous coronary intervention (PCI), microvascular dysfunction frequently coexists with epicardial atherosclerosis and may limit post-revascularization flow recovery. Microvascular obstruction is a key determinant of infarct size, adverse ventricular remodeling, and long-term prognosis after acute myocardial infarction, even when epicardial reperfusion is successful [15]. The persistence of CMD following revascularization explains why some patients continue to experience angina and impaired perfusion despite patent stents.
Beyond angina and infarction, CMD contributes to the pathophysiology of heart failure with preserved ejection fraction. Systemic endothelial inflammation and microvascular rarefaction have been identified as mechanistic links between metabolic comorbidities, hypertension, obesity, and diabetes, and diastolic dysfunction [16]. In this context, CMD represents the cardiac manifestation of a generalized small-vessel disease that leads to myocardial stiffening and impaired relaxation. The prognostic importance of CMD is now well established. Patients with impaired coronary flow reserve or elevated microvascular resistance have a higher incidence of major adverse cardiovascular events, including myocardial infarction, hospitalization for heart failure, and cardiac death, even in the absence of obstructive CAD [17]. Longitudinal studies confirm that CMD is not a benign finding; rather, it identifies a high-risk subgroup whose outcomes parallel or exceed those with obstructive disease. The presence of CMD also correlates with reduced exercise capacity and impaired quality of life [18]. Despite increasing awareness, CMD remains underdiagnosed due to the absence of standardized criteria and the limited availability of advanced diagnostic testing. This diagnostic gap is particularly concerning given the high prevalence of CMD in women, diabetic patients, and individuals with metabolic syndrome. Recognition of CMD as a distinct entity has important implications for management, emphasizing the need for personalized diagnostic algorithms and mechanism-based therapy rather than uniform application of conventional antianginal drugs [19]. In summary, CMD spans multiple ischemic heart disease phenotypes, ranging from INOCA and myocardial infarction to HFpEF, each representing a clinical expression of impaired microvascular function. Its prevalence, prognostic significance, and under-recognition underscore the necessity for systematic evaluation and early intervention strategies targeting the microcirculation (Table 2).
| Phenotype | Clinical Characteristics | CMD Prevalence | Predominant Patient Group | Prognostic Impact |
| INOCA | Angina with non-obstructive coronary arteries | 40–60% | Women, postmenopausal | Increased MACE and MI risk |
| Post-obstructive CAD | Persistent ischemia after PCI or CABG | 25–30% | Post-PCI patients | Larger infarcts, LV remodeling |
| HFpEF-associated CMD | Dyspnea, diastolic dysfunction | Up to 50% | Hypertensive, diabetic, obese | Higher mortality, HF hospitalization |
Table 2: Clinical Phenotypes and Epidemiology of Coronary Microvascular Dysfunction.
Abbreviations: CMD: Coronary microvascular dysfunction; INOCA: Ischemia with non-obstructive coronary arteries; CAD: Coronary artery disease; PCI: Percutaneous coronary intervention; CABG: Coronary artery bypass grafting; MACE: Major adverse cardiovascular events; MI: Myocardial infarction; LV: Left ventricle; HFpEF: Heart failure with preserved ejection fraction.
The diagnosis of coronary microvascular dysfunction (CMD) remains one of the most complex and debated aspects of ischemic heart disease evaluation. Unlike obstructive coronary artery disease, which can be visualized angiographically, CMD affects small resistance vessels beyond the resolution of standard coronary imaging. This limitation necessitates the use of functional and physiologic testing to detect abnormalities in microvascular flow regulation [20].
Non-invasive imaging techniques have become central to the evaluation of CMD. Positron emission tomography (PET) allows quantification of myocardial blood flow and calculation of coronary flow reserve (CFR), which reflects the vasodilatory capacity of both epicardial and microvascular compartments. PET remains the reference standard for non-invasive assessment of CMD, with reduced CFR (<2.0) serving as a diagnostic threshold associated with adverse outcomes [21]. However, PET’s limited availability, high cost, and requirement for radiotracers restrict its widespread use. Cardiac magnetic resonance (CMR) with stress perfusion imaging provides an alternative method, offering high spatial resolution and the ability to assess myocardial perfusion reserve index (MPRI). Studies have shown good correlation between MPRI and PET-derived CFR, supporting its use in CMD evaluation [22].
Computed tomography (CT)-based approaches, such as CT perfusion imaging and CT-derived fractional flow reserve (CT-FFR), are emerging modalities that combine anatomical and functional assessment. CT perfusion imaging enables visualization of perfusion heterogeneity suggestive of microvascular disease, while CT-FFR allows evaluation of pressure gradients across the coronary tree. Although promising, these techniques are still limited by radiation exposure and the need for standardization of analytical protocols [23]. Transthoracic Doppler echocardiography of the left anterior descending artery, while technically demanding, offers a non-invasive and inexpensive method to measure coronary flow velocity reserve (CFVR). A CFVR value below 2.0 indicates impaired microvascular function and has prognostic implications in both INOCA and heart failure populations [24].
Invasive coronary physiology testing provides the most direct and detailed assessment of microvascular function. Coronary flow reserve and the index of microcirculatory resistance (IMR) are commonly measured using a pressure–temperature sensor guidewire. IMR is calculated from distal coronary pressure and thermodilution-derived mean transit time during maximal hyperemia, providing a quantitative measure of microvascular resistance that is independent of epicardial disease. An IMR value ≥25 is typically considered diagnostic of CMD [25]. In addition, acetylcholine provocation testing is used to assess endothelium-dependent function and identify microvascular or epicardial spasm. Administration of incremental doses of acetylcholine under continuous ECG and angiographic monitoring allows the differentiation of microvascular spasm, characterized by ischemic ECG changes without visible epicardial constriction, from epicardial vasospasm [26].
Despite the availability of these tools, several challenges impede routine implementation. First, invasive testing requires specialized expertise and is limited to tertiary centers. Second, discrepancies between different diagnostic modalities complicate the establishment of universal thresholds for CMD. Third, many patients exhibit overlapping pathophysiologic endotypes, endothelial dysfunction, microvascular spasm, and structural remodeling, making single-parameter diagnosis inadequate [27]. Furthermore, symptom–ischemia dissociation is common: patients may have disabling angina with normal CFR or minimal symptoms despite marked CMD. This clinical variability underscores the need for integrative diagnostic strategies that combine hemodynamic, imaging, and biochemical parameters [28]. Standardization of diagnostic criteria remains a major unmet need. The 2019 European Society of Cardiology guidelines on chronic coronary syndromes formally recognized CMD as a diagnostic entity but did not provide universally accepted cutoffs for each modality. Variations in protocols, patient populations, and measurement techniques contribute to inconsistent results across studies. The ongoing effort toward harmonization, exemplified by the Coronary Vasomotion Disorders International Study Group (COVADIS), seeks to unify definitions and establish reproducible diagnostic algorithms [29].
Overall, the diagnosis of CMD requires a multimodality approach integrating non-invasive and invasive assessments. Advances in physiological testing and imaging have improved understanding, yet practical and logistical barriers continue to limit clinical application. Early recognition of CMD is essential, as impaired coronary microvascular function is a strong predictor of adverse outcomes irrespective of the presence or absence of obstructive coronary artery disease [30] (Table 3).
| Method | Type | Parameter | Diagnostic Threshold | Advantages | Limitations |
| PET | Non-invasive | Coronary Flow Reserve (CFR) | CFR < 2> | Gold standard, strong prognostic value | Expensive, limited availability |
| Cardiac MRI | Non-invasive | Myocardial Perfusion Reserve Index (MPRI) | MPRI < 2> | No radiation, high resolution | Technically demanding |
| Doppler Echocardiography | Non-invasive | Coronary Flow Velocity Reserve (CFVR) | CFVR < 2> | Inexpensive, repeatable | Operator-dependent |
| IMR (Invasive) | Invasive | Index of Microcirculatory Resistance | IMR ≥ 25 | Direct quantitative assessment | Requires expertise |
| Acetylcholine testing | Invasive | Vasomotor response | Ischemic ECG changes without epicardial constriction | Evaluates endothelial function | Potential risk, limited availability |
Table 3: Diagnostic Modalities in Coronary Microvascular Dysfunction
Abbreviations: PET: Positron emission tomography; MRI: Magnetic resonance imaging; MPRI: Myocardial perfusion reserve index; CFVR: Coronary flow velocity reserve; IMR: Index of microcirculatory resistance; ECG: Electrocardiogram.
Management of coronary microvascular dysfunction (CMD) remains a major clinical challenge because treatment is often empirical and not mechanism-specific. Conventional antianginal strategies developed for obstructive coronary artery disease have limited efficacy in CMD, since the underlying pathophysiology involves microvascular rather than epicardial abnormalities. Therapeutic approaches therefore focus on symptom control, improvement of endothelial and vascular function, and mitigation of risk factors that perpetuate microvascular injury [7].
Lifestyle and risk factor modification form the cornerstone of CMD management. Regular aerobic exercise improves endothelial nitric oxide bioavailability, augments coronary flow reserve, and reduces sympathetic tone. Structured exercise training programs have demonstrated significant improvements in both symptoms and perfusion in patients with microvascular angina [31]. Optimal management of hypertension, diabetes, and dyslipidemia is equally important. Antihypertensive therapy not only lowers afterload but also alleviates shear stress–induced endothelial injury. Strict glycemic control mitigates glycation-induced oxidative stress, while statins improve endothelial function independent of their lipid-lowering effect through anti-inflammatory and antioxidative mechanisms [32]. Smoking cessation and weight reduction are critical, as tobacco toxins and visceral adiposity promote systemic inflammation and microvascular remodeling [6].
Pharmacologic treatment for CMD can be divided into conventional antianginal drugs and agents targeting endothelial or metabolic dysfunction. Beta-blockers are often used as first-line therapy because they reduce myocardial oxygen demand and improve diastolic perfusion time; they are particularly useful in patients with elevated heart rates and hypertensive responses. However, their efficacy is limited in patients with vasospastic or predominantly endothelial dysfunction–mediated CMD. Calcium channel blockers, such as amlodipine or diltiazem, are preferred in those with vasospastic components due to their potent vasodilatory effects on both epicardial and microvascular vessels [33]. Long-acting nitrates, while effective in relieving epicardial vasospasm, have inconsistent effects in CMD because tolerance and paradoxical endothelial dysfunction may develop with chronic use [34].
Drugs that improve endothelial and metabolic function show promise for CMD management. Angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin receptor blockers (ARBs) enhance endothelial nitric oxide production, reduce oxidative stress, and improve coronary flow reserve. Clinical trials have shown that ACE inhibition improves angina and perfusion in patients with microvascular angina [35]. Statins also contribute through pleiotropic effects, stabilizing endothelium and suppressing inflammatory cytokines [36]. Ranolazine, a late sodium current inhibitor, has demonstrated symptomatic improvement and increased exercise tolerance in CMD by improving diastolic relaxation and myocardial efficiency, though benefits vary among subgroups [37]. Trimetazidine, which shifts myocardial metabolism toward glucose utilization, enhances ischemic tolerance and may complement conventional antianginal therapy [38].
The use of antiplatelet and anti-inflammatory therapy is rational, as low-grade vascular inflammation contributes to microvascular injury. Low-dose aspirin is often prescribed, though evidence supporting its benefit in isolated CMD is limited and primarily extrapolated from macrovascular disease data. Agents targeting vascular inflammation and oxidative stress remain investigational but represent an active area of research. The anti-inflammatory effects of statins and renin–angiotensin system blockade are likely responsible for part of their benefit in CMD [39].
Despite the availability of these options, outcomes remain suboptimal. Many patients continue to experience angina and reduced quality of life despite apparently adequate medical therapy. The heterogeneity of CMD, encompassing functional and structural subtypes, means that treatment responses vary widely. Current management therefore emphasizes individualized therapy based on the predominant mechanism, whether endothelial dysfunction, vasospasm, or structural rarefaction. This phenotype-directed approach is supported by evidence from the CorMicA trial, in which invasive coronary function testing guided tailored therapy and led to significant improvement in angina and quality of life compared with standard empiric treatment [4].
In summary, CMD management currently relies on a multifaceted strategy combining risk factor optimization, lifestyle modification, and pharmacologic therapy aimed at improving endothelial function and alleviating ischemia. While traditional antianginal agents remain the mainstay, emerging mechanism-based approaches promise to refine treatment in the near future. The persistent symptom burden despite existing therapies highlights the need for novel treatments directly targeting the microcirculation (Table 4).
| Treatment Category | Example Drug / Modality | Mechanism of Action | Evidence Level | Clinical Status |
| Lifestyle / risk modification | Exercise, weight loss, smoking cessation | Improves NO bioavailability, reduces inflammation | High | Foundational |
| Endothelium-targeted therapy | ACEIs, ARBs, statins | Enhance endothelial function, reduce oxidative stress | Moderate | Standard care |
| Metabolic modulation | Ranolazine, trimetazidine | Improves diastolic relaxation, energy efficiency | Moderate | In use |
| Novel pharmacologic agents | Endothelin receptor antagonists, Rho-kinase inhibitors, SGLT2 inhibitors | Promote vasodilation, anti-inflammatory action | Low–moderate | Investigational |
| Device / regenerative therapies | Coronary sinus reducer, EECP, cell-based therapy | Improves microvascular perfusion and angiogenesis | Low–moderate | Under clinical evaluation |
Table 4: Current and Emerging Therapeutic Approaches for CMD
Abbreviations: ACEI: Angiotensin-converting enzyme inhibitor; ARB: Angiotensin receptor blocker; NO: Nitric oxide; SGLT2: Sodium–glucose cotransporter-2; EECP: Enhanced external counterpulsation
The limited efficacy of conventional antianginal and vasodilator therapies in coronary microvascular dysfunction (CMD) has prompted the search for novel treatments targeting the underlying pathophysiology of microvascular disease. These emerging approaches aim to restore endothelial function, reverse microvascular remodeling, and modulate neurohumoral and inflammatory pathways contributing to impaired coronary flow. The current therapeutic landscape includes pharmacologic innovations, regenerative and cell-based strategies, and device-based interventions designed specifically to improve microvascular perfusion [40].
Several pharmacologic agents targeting microvascular tone and endothelial dysfunction are under active investigation. Endothelin receptor antagonists, such as zibotentan and atrasentan, have been evaluated for their potential to counteract endothelin-1–mediated vasoconstriction and inflammation in CMD. Endothelin-1 plays a central role in microvascular constriction and remodeling, and selective blockade may improve microvascular flow and reduce ischemic burden. Early-phase clinical trials have shown favorable hemodynamic effects, though larger outcome studies are required to determine clinical benefit [41]. The Rho-kinase pathway represents another therapeutic target, as its activation promotes vasoconstriction, endothelial dysfunction, and vascular smooth muscle hyperreactivity. Inhibitors such as fasudil have demonstrated improved coronary flow and symptom relief in patients with microvascular angina, highlighting their potential role in treatment-resistant cases [42].
Modulation of nitric oxide (NO) signaling also offers therapeutic promise. Agents that enhance the NO–cGMP pathway, including phosphodiesterase-5 (PDE5) inhibitors and soluble guanylate cyclase (sGC) stimulators, have shown endothelial protective effects in preclinical and early human studies. Sildenafil and related PDE5 inhibitors may improve microvascular vasodilation and myocardial perfusion, particularly in CMD associated with heart failure with preserved ejection fraction [43]. Similarly, the sGC stimulator vericiguat has been shown to improve vascular reactivity and myocardial energetics, suggesting potential benefit in CMD-related ischemia [54].
Sodium–glucose cotransporter-2 inhibitors (SGLT2i) have recently emerged as promising agents with pleiotropic vascular effects extending beyond glycemic control. By reducing oxidative stress, inflammation, and endothelial dysfunction, SGLT2i improve microvascular integrity and coronary flow reserve in both diabetic and non-diabetic populations. Clinical and imaging data indicate improved subendocardial perfusion and reduced myocardial oxygen demand following SGLT2 inhibition, suggesting that these drugs may exert cardioprotective effects partly through microvascular mechanisms [45].
Beyond pharmacotherapy, regenerative and cell-based strategies are being explored as potential approaches to restore microvascular density and function. Endothelial progenitor cell (EPC) therapy and mesenchymal stem cell–derived exosomes have shown the capacity to promote angiogenesis, attenuate fibrosis, and improve perfusion in preclinical models of CMD. Preliminary human studies indicate that intracoronary or transendocardial administration of cell-based products can enhance coronary flow reserve and reduce ischemic symptoms [46]. Although long-term safety and efficacy remain to be confirmed, these findings suggest a path toward biologically restorative therapy for CMD.
Device-based and neuromodulatory interventions represent another frontier. The coronary sinus reducer, a percutaneously implanted device that creates a controlled narrowing in the coronary sinus, has been shown to improve angina and quality of life in patients with refractory microvascular angina. The mechanism is thought to involve redistribution of coronary venous pressure, thereby enhancing subendocardial perfusion. Clinical trials, including the COSIRA study, demonstrated significant symptom and functional improvement in patients with refractory angina and no revascularization options [47]. Enhanced external counterpulsation (EECP), a noninvasive mechanical therapy that augments diastolic coronary perfusion and reduces afterload, has also been associated with improved endothelial function and angina relief in CMD patients [48]. Renal denervation, by reducing sympathetic overactivity, is being explored as a means to modulate neurovascular tone in CMD, although data remain preliminary [49]. Ongoing clinical research continues to expand the therapeutic possibilities. Trials investigating anti-inflammatory strategies targeting interleukin-1β, colchicine, and other inflammatory pathways may further clarify whether vascular inflammation is a modifiable driver of CMD. Similarly, therapies combining pharmacologic and device-based modalities hold potential for synergistic effects. The evolution of these treatments reflects a paradigm shift from symptom suppression toward microvascular repair and functional restoration.
In summary, novel therapies for CMD aim to address the root mechanisms of endothelial dysfunction, microvascular remodeling, and autonomic dysregulation. Although evidence remains early-stage, the cumulative data suggest that precision medicine approaches integrating pharmacologic, regenerative, and mechanical strategies may ultimately redefine the management of microvascular ischemia.
Despite rapid progress in understanding coronary microvascular dysfunction (CMD), major gaps persist in diagnosis, risk stratification, and treatment. CMD remains a pathophysiologically complex and clinically heterogeneous disorder that straddles multiple disease spectra, from stable angina to heart failure with preserved ejection fraction (HFpEF). Future research must aim to refine diagnostic precision, define phenotypes, and develop mechanism-based, individualized therapeutic strategies [28].
A key unmet need is the standardization of diagnostic criteria. Although invasive coronary physiology testing provides detailed insight into endothelial and microvascular function, there is no consensus on diagnostic thresholds across modalities such as coronary flow reserve (CFR), index of microcirculatory resistance (IMR), or myocardial perfusion reserve index (MPRI). Variability in protocols, analytic methods, and patient characteristics limits interstudy comparability. The establishment of unified diagnostic frameworks, such as those proposed by the Coronary Vasomotion Disorders International Study Group (COVADIS), should be prioritized in large-scale, multicenter studies [26]. Standardization will not only improve diagnostic reliability but also facilitate stratified therapeutic trials targeting distinct CMD endotypes.
Future work must also focus on developing reliable biomarkers of CMD. Circulating indicators of endothelial dysfunction, oxidative stress, and inflammation, such as asymmetric dimethylarginine (ADMA), endothelin-1, and high-sensitivity C-reactive protein, have shown promise as surrogates of microvascular health. Metabolomic and proteomic profiling may uncover novel molecular signatures that reflect microvascular injury or remodeling [50]. Integration of these biomarkers with advanced imaging and physiologic data may enable non-invasive diagnosis and monitoring of treatment response. The development of composite diagnostic scores incorporating clinical, imaging, and biomarker data represents an important step toward precision medicine in CMD [51].
Therapeutically, the next decade is likely to see a shift from symptomatic management toward disease-modifying strategies. This includes agents targeting vascular inflammation, fibrosis, and endothelial senescence, key drivers of microvascular dysfunction. Anti-inflammatory drugs such as colchicine or interleukin-1β inhibitors, already validated in macrovascular disease, warrant evaluation in CMD-specific populations. Similarly, antifibrotic and mitochondrial-targeted therapies hold potential to reverse the structural component of CMD [52]. Ongoing work exploring SGLT2 inhibitors, Rho-kinase inhibitors, and nitric oxide–modulating agents may further define the most effective pharmacologic strategies for restoring microvascular function [45].
Another major research frontier is the translation of regenerative and cell-based therapies into clinical practice. Early studies using stem cell–derived products and endothelial progenitor cells have shown improvement in coronary flow reserve and symptomatic relief, but robust evidence on long-term efficacy and safety is lacking. Understanding the mechanisms of benefit, whether through direct angiogenesis, paracrine signaling, or modulation of vascular inflammation, will be essential to optimize such approaches [46]. Future trials should also address patient selection, dosing, and delivery methods to ensure reproducibility and durability of clinical benefit.
Finally, CMD should be increasingly recognized as part of a systemic microvascular disorder rather than an isolated cardiac pathology. Its overlap with other small-vessel diseases, such as renal microangiopathy and cerebral small-vessel disease, suggests shared mechanisms involving endothelial inflammation and vascular rarefaction. Collaborative, interdisciplinary studies linking cardiology, vascular biology, and neurology could yield insights into the systemic nature of CMD and its implications for cardiovascular and cognitive health [20].
In summary, advancing CMD research requires coordinated efforts to standardize diagnosis, refine phenotyping, and develop mechanism-specific therapies. Future directions lie in integrating molecular biomarkers with physiologic and imaging data to enable personalized management. A paradigm shift from empiric symptom control to targeted microvascular restoration represents the ultimate goal for improving outcomes in patients with CMD.
Coronary microvascular dysfunction (CMD) represents a central yet often underrecognized contributor to ischemic heart disease. It challenges the traditional paradigm that attributes myocardial ischemia primarily to epicardial atherosclerotic obstruction. By disrupting the regulation of coronary blood flow at the microvascular level, CMD produces ischemia, angina, and functional impairment even when angiography appears normal.
Over the past two decades, scientific advances have clarified the complex mechanisms underlying CMD, encompassing endothelial dysfunction, vascular remodeling, inflammation, and autonomic imbalance. These discoveries have reframed CMD as a systemic microvascular disorder with cardiac manifestations rather than a purely localized vascular problem. Diagnostic progress, through physiological testing and high-resolution imaging, has enabled identification of CMD phenotypes that carry substantial prognostic risk.
Despite this progress, CMD remains difficult to diagnose and treat. Current management largely depends on empirical therapy derived from macrovascular disease, and many patients continue to experience persistent angina and reduced quality of life. The lack of standardized diagnostic criteria and limited availability of specialized testing further impede effective clinical care.
The emerging era of mechanism-based treatment offers cautious optimism. Advances in pharmacologic modulation of endothelial pathways, regenerative and device-based therapies, and integration of precision diagnostics hold promise for transforming CMD management from symptom control to disease modification. Achieving this transition will require coordinated research, standardization, and multidisciplinary collaboration.
In conclusion, CMD lies at the intersection of vascular biology and clinical cardiology. Recognizing and targeting microvascular dysfunction is essential for improving outcomes in patients with both obstructive and non-obstructive ischemic syndromes. Understanding CMD not as a secondary finding but as a core mechanism of myocardial ischemia will define the next phase in the evolution of cardiovascular medicine.
Contributor ship: All of the authors contributed planning, conduct, and reporting of the work. All authors had full access to all data in the study and take responsibility for the integrity of the data and the accuracy of the data analysis.
Funding: No financial funding was received for this study.
Competing interests: All of the authors have no conflict of interest.
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Dr. Katarzyna Byczkowska My testimonial covering: "The peer review process is quick and effective. The support from the editorial office is very professional and friendly. Quality of the Clinical Cardiology and Cardiovascular Interventions is scientific and publishes ground-breaking research on cardiology that is useful for other professionals in the field.
Thank you most sincerely, with regard to the support you have given in relation to the reviewing process and the processing of my article entitled "Large Cell Neuroendocrine Carcinoma of The Prostate Gland: A Review and Update" for publication in your esteemed Journal, Journal of Cancer Research and Cellular Therapeutics". The editorial team has been very supportive.
Testimony of Journal of Clinical Otorhinolaryngology: work with your Reviews has been a educational and constructive experience. The editorial office were very helpful and supportive. It was a pleasure to contribute to your Journal.
Dr. Bernard Terkimbi Utoo, I am happy to publish my scientific work in Journal of Women Health Care and Issues (JWHCI). The manuscript submission was seamless and peer review process was top notch. I was amazed that 4 reviewers worked on the manuscript which made it a highly technical, standard and excellent quality paper. I appreciate the format and consideration for the APC as well as the speed of publication. It is my pleasure to continue with this scientific relationship with the esteem JWHCI.
This is an acknowledgment for peer reviewers, editorial board of Journal of Clinical Research and Reports. They show a lot of consideration for us as publishers for our research article “Evaluation of the different factors associated with side effects of COVID-19 vaccination on medical students, Mutah university, Al-Karak, Jordan”, in a very professional and easy way. This journal is one of outstanding medical journal.
Dear Hao Jiang, to Journal of Nutrition and Food Processing We greatly appreciate the efficient, professional and rapid processing of our paper by your team. If there is anything else we should do, please do not hesitate to let us know. On behalf of my co-authors, we would like to express our great appreciation to editor and reviewers.
As an author who has recently published in the journal "Brain and Neurological Disorders". I am delighted to provide a testimonial on the peer review process, editorial office support, and the overall quality of the journal. The peer review process at Brain and Neurological Disorders is rigorous and meticulous, ensuring that only high-quality, evidence-based research is published. The reviewers are experts in their fields, and their comments and suggestions were constructive and helped improve the quality of my manuscript. The review process was timely and efficient, with clear communication from the editorial office at each stage. The support from the editorial office was exceptional throughout the entire process. The editorial staff was responsive, professional, and always willing to help. They provided valuable guidance on formatting, structure, and ethical considerations, making the submission process seamless. Moreover, they kept me informed about the status of my manuscript and provided timely updates, which made the process less stressful. The journal Brain and Neurological Disorders is of the highest quality, with a strong focus on publishing cutting-edge research in the field of neurology. The articles published in this journal are well-researched, rigorously peer-reviewed, and written by experts in the field. The journal maintains high standards, ensuring that readers are provided with the most up-to-date and reliable information on brain and neurological disorders. In conclusion, I had a wonderful experience publishing in Brain and Neurological Disorders. The peer review process was thorough, the editorial office provided exceptional support, and the journal's quality is second to none. I would highly recommend this journal to any researcher working in the field of neurology and brain disorders.
Dear Agrippa Hilda, Journal of Neuroscience and Neurological Surgery, Editorial Coordinator, I trust this message finds you well. I want to extend my appreciation for considering my article for publication in your esteemed journal. I am pleased to provide a testimonial regarding the peer review process and the support received from your editorial office. The peer review process for my paper was carried out in a highly professional and thorough manner. The feedback and comments provided by the authors were constructive and very useful in improving the quality of the manuscript. This rigorous assessment process undoubtedly contributes to the high standards maintained by your journal.
International Journal of Clinical Case Reports and Reviews. I strongly recommend to consider submitting your work to this high-quality journal. The support and availability of the Editorial staff is outstanding and the review process was both efficient and rigorous.
Thank you very much for publishing my Research Article titled “Comparing Treatment Outcome Of Allergic Rhinitis Patients After Using Fluticasone Nasal Spray And Nasal Douching" in the Journal of Clinical Otorhinolaryngology. As Medical Professionals we are immensely benefited from study of various informative Articles and Papers published in this high quality Journal. I look forward to enriching my knowledge by regular study of the Journal and contribute my future work in the field of ENT through the Journal for use by the medical fraternity. The support from the Editorial office was excellent and very prompt. I also welcome the comments received from the readers of my Research Article.
Dear Erica Kelsey, Editorial Coordinator of Cancer Research and Cellular Therapeutics Our team is very satisfied with the processing of our paper by your journal. That was fast, efficient, rigorous, but without unnecessary complications. We appreciated the very short time between the submission of the paper and its publication on line on your site.
I am very glad to say that the peer review process is very successful and fast and support from the Editorial Office. Therefore, I would like to continue our scientific relationship for a long time. And I especially thank you for your kindly attention towards my article. Have a good day!
"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".
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.
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.
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.
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.
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.
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.
“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”.
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.
Clinical Cardiology and Cardiovascular Interventions I testity the covering of the peer review process, support from the editorial office, and quality of the journal.
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.
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.
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.
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.
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¨.
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.
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!”
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
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.
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.
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.
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.
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."
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.
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.
"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".
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.
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.
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.
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.
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
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.
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.
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.
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.
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.
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
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.
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.
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.
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.
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
Dear Chrystine Mejia, Editorial Coordinator, Journal of Neurodegeneration and Neurorehabilitation, Auctores Publishing LLC, We would like to thank the editorial team for the smooth and high-quality communication leading up to the publication of our article in the Journal of Neurodegeneration and Neurorehabilitation. The reviewers have extensive knowledge in the field, and their relevant questions helped to add value to our publication. Kind regards, Dr. Ravi Shrivastava.
Dear Clarissa Eric, Editorial Coordinator, Journal of Clinical Case Reports and Studies, Auctores Publishing LLC, USA Office: +1-(302)-520-2644. I would like to express my sincere appreciation for the efficient and professional handling of my case report by the ‘Journal of Clinical Case Reports and Studies’. The peer review process was not only fast but also highly constructive—the reviewers’ comments were clear, relevant, and greatly helped me improve the quality and clarity of my manuscript. I also received excellent support from the editorial office throughout the process. Communication was smooth and timely, and I felt well guided at every stage, from submission to publication. The overall quality and rigor of the journal are truly commendable. I am pleased to have published my work with Journal of Clinical Case Reports and Studies, and I look forward to future opportunities for collaboration. Sincerely, Aline Tollet, UCLouvain.
Dear Ms. Mayra Duenas, Editorial Coordinator, International Journal of Clinical Case Reports and Reviews. “The International Journal of Clinical Case Reports and Reviews represented the “ideal house” to share with the research community a first experience with the use of the Simeox device for speech rehabilitation. High scientific reputation and attractive website communication were first determinants for the selection of this Journal, and the following submission process exceeded expectations: fast but highly professional peer review, great support by the editorial office, elegant graphic layout. Exactly what a dynamic research team - also composed by allied professionals - needs!" From, Chiara Beccaluva, PT - Italy.
Dear Maria Emerson, Editorial Coordinator, we have deeply appreciated the professionalism demonstrated by the International Journal of Clinical Case Reports and Reviews. The reviewers have extensive knowledge of our field and have been very efficient and fast in supporting the process. I am really looking forward to further collaboration. Thanks. Best regards, Dr. Claudio Ligresti
Dear Chrystine Mejia, Editorial Coordinator, Journal of Neurodegeneration and Neurorehabilitation. “The peer review process was efficient and constructive, and the editorial office provided excellent communication and support throughout. The journal ensures scientific rigor and high editorial standards, while also offering a smooth and timely publication process. We sincerely appreciate the work of the editorial team in facilitating the dissemination of innovative approaches such as the Bonori Method.” Best regards, Dr. Matteo Bonori.
I recommend without hesitation submitting relevant papers on medical decision making to the International Journal of Clinical Case Reports and Reviews. I am very grateful to the editorial staff. Maria Emerson was a pleasure to communicate with. The time from submission to publication was an extremely short 3 weeks. The editorial staff submitted the paper to three reviewers. Two of the reviewers commented positively on the value of publishing the paper. The editorial staff quickly recognized the third reviewer’s comments as an unjust attempt to reject the paper. I revised the paper as recommended by the first two reviewers.
Dear Maria Emerson, Editorial Coordinator, Journal of Clinical Research and Reports. Thank you for publishing our case report: "Clinical Case of Effective Fetal Stem Cells Treatment in a Patient with Autism Spectrum Disorder" within the "Journal of Clinical Research and Reports" being submitted by the team of EmCell doctors from Kyiv, Ukraine. We much appreciate a professional and transparent peer-review process from Auctores. All research Doctors are so grateful to your Editorial Office and Auctores Publishing support! I amiably wish our article publication maintained a top quality of your International Scientific Journal. My best wishes for a prosperity of the Journal of Clinical Research and Reports. Hope our scientific relationship and cooperation will remain long lasting. Thank you very much indeed. Kind regards, Dr. Andriy Sinelnyk Cell Therapy Center EmCell
Dear Editorial Team, Clinical Cardiology and Cardiovascular Interventions. It was truly a rewarding experience to work with the journal “Clinical Cardiology and Cardiovascular Interventions”. The peer review process was insightful and encouraging, helping us refine our work to a higher standard. The editorial office offered exceptional support with prompt and thoughtful communication. I highly value the journal’s role in promoting scientific advancement and am honored to be part of it. Best regards, Meng-Jou Lee, MD, Department of Anesthesiology, National Taiwan University Hospital.
Dear Editorial Team, Journal-Clinical Cardiology and Cardiovascular Interventions, “Publishing my article with Clinical Cardiology and Cardiovascular Interventions has been a highly positive experience. The peer-review process was rigorous yet supportive, offering valuable feedback that strengthened my work. The editorial team demonstrated exceptional professionalism, prompt communication, and a genuine commitment to maintaining the highest scientific standards. I am very pleased with the publication quality and proud to be associated with such a reputable journal.” Warm regards, Dr. Mahmoud Kamal Moustafa Ahmed
Dear Maria Emerson, Editorial Coordinator of ‘International Journal of Clinical Case Reports and Reviews’, I appreciate the opportunity to publish my article with your journal. The editorial office provided clear communication during the submission and review process, and I found the overall experience professional and constructive. Best regards, Elena Salvatore.
Dear Mayra Duenas, Editorial Coordinator of ‘International Journal of Clinical Case Reports and Reviews Herewith I confirm an optimal peer review process and a great support of the editorial office of the present journal
Dear Editorial Team, Clinical Cardiology and Cardiovascular Interventions. I am really grateful for the peers review; their feedback gave me the opportunity to reflect on the message and impact of my work and to ameliorate the article. The editors did a great job in addition by encouraging me to continue with the process of publishing.
Dear Cecilia Lilly, Editorial Coordinator, Endocrinology and Disorders, Thank you so much for your quick response regarding reviewing and all process till publishing our manuscript entitled: Prevalence of Pre-Diabetes and its Associated Risk Factors Among Nile College Students, Sudan. Best regards, Dr Mamoun Magzoub.
International Journal of Clinical Case Reports and Reviews is a high quality journal that has a clear and concise submission process. The peer review process was comprehensive and constructive. Support from the editorial office was excellent, since the administrative staff were responsive. The journal provides a fast and timely publication timeline.
Dear Maria Emerson, Editorial Coordinator of International Journal of Clinical Case Reports and Reviews, What distinguishes International Journal of Clinical Case Report and Review is not only the scientific rigor of its publications, but the intellectual climate in which research is evaluated. The submission process is refreshingly free of unnecessary formal barriers and bureaucratic rituals that often complicate academic publishing without adding real value. The peer-review system is demanding yet constructive, guided by genuine scientific dialogue rather than hierarchical or authoritarian attitudes. Reviewers act as collaborators in improving the manuscript, not as gatekeepers imposing arbitrary standards. This journal offers a rare balance: high methodological standards combined with a respectful, transparent, and supportive editorial approach. In an era where publishing can feel more burdensome than research itself, this platform restores the original purpose of peer review — to refine ideas, not to obstruct them Prof. Perlat Kapisyzi, FCCP PULMONOLOGIST AND THORACIC IMAGING.
Dear Grace Pierce, International Journal of Clinical Case Reports and Reviews I appreciate the opportunity to review for Auctore Journal, as the overall editorial process was smooth, transparent and professionally managed. This journal maintains high scientific standards and ensures timely communications with authors, which is truly commendable. I would like to express my special thanks to editor Grace Pierce for his constant guidance, promt responses, and supportive coordination throughout the review process. I am also greatful to Eleanor Bailey from the finance department for her clear communication and efficient handling of all administrative matters. Overall, my experience with Auctore Journal has been highly positive and rewarding. Best regards, Sabita sinha
Dear Mayra Duenas, Editorial Coordinator of the journal IJCCR, I write here a little on my experience as an author submitting to the International Journal of Clinical Case Reports and Reviews (IJCCR). This was my first submission to IJCCR and my manuscript was inherently an outsider’s effort. It attempted to broadly identify and then make some sense of life’s under-appreciated mysteries. I initially had responded to a request for possible submissions. I then contacted IJCCR with a tentative topic for a manuscript. They quickly got back with an approval for the submission, but with a particular requirement that it be medically relevant. I then put together a manuscript and submitted it. After the usual back-and-forth over forms and formality, the manuscript was sent off for reviews. Within 2 weeks I got back 4 reviews which were both helpful and also surprising. Surprising in that the topic was somewhat foreign to medical literature. My subsequent updates in response to the reviewer comments went smoothly and in short order I had a series of proofs to evaluate. All in all, the whole publication process seemed outstanding. It was both helpful in terms of the paper’s content and also in terms of its efficient and friendly communications. Thank you all very much. Sincerely, Ted Christopher, Rochester, NY.
