Congenital Cardiovascular Disease Research Articles

High-Flow Oscillatory Ventilation: A Possible Therapeutic Option for Pediatric Patients with Cardiovascular Diseases

High-flow oscillatory ventilation (HFOV) is a common rescue treatment in infants and children with respiratory failure. This type of ventilation is an effective technique in numerous diseases that affect a child in the postnatal period, such as ARDS, meconium aspiration syndrome (MIS), postnatal pulmonary bleeding and idiopathic pulmonary hypertension (IPH). Although this ventilation technique is commonly recognized as a valuable therapeutic option in the general pediatric population, this is not the same for children with congenital cardiovascular diseases. The key mechanism of oscillatory ventilation is continuous positive pressure administered within the airways via a small tidal volume at high frequency. Tidal volumes are between 1 and 3 mL/kg delivered at 5–15 Hz, equivalent to 300–900 breaths per minute. A few older studies conducted on humans and animals highlight that HFOV may be dangerous for congenital heart patients. According to these evidences, hemodynamic parameters such as blood pressure, wedge pressure, central venous pressure, heart rate and inotrope level can be dangerously changed for patients with congenital heart disease; therefore, oscillatory ventilation should be avoided. Numerous retrospective studies have pointed out how oscillatory ventilation constitutes a valid therapeutic option in children with congenital heart disease. Recently, new evidences have highlighted how hemodynamic parameters are modified in a non-significant way by this type of ventilation, remaining beneficial as in the normal pediatric population. This narrative review aims to describe the mechanisms of oscillatory ventilation and collect all the available evidences to support its use in pediatric patients with congenital heart problems.

A Case Report on Anomalous Origin of Left Coronary Artery from Pulmonary Artery in a Child

ABSTRACT Anomalous left coronary artery from the pulmonary artery (ALCAPA) is a rare but fatal congenital cardiovascular disease. In this condition, the left coronary artery originates from the pulmonary artery, which should actually originate from the ascending aorta. This causes left ventricular dysfunction/insufficiency. Many a times it is asymptomatic and is missed during the initial months of life. Incidence is 1 in 300000 live births and comprises about 0.25–0.5% of congenital heart disease. In this article, we present a case of a 4-month-old infant who came with complaints of fever and increased work of breathing. On examination, there were signs of respiratory distress. Systemic examination was normal. Electrocardiogram findings showed inverted T waves in leads 1 and aVL, and in leads V5-V6, elevated ST segments were noted. Patient was suspected to have ALCAPA, and the echocardiogram confirmed the diagnosis. Patient was planned for surgery. ALCAPA is a clinical diagnostic challenge as it presents with similar complaints of common pediatric diseases such as bronchiolitis, failure to thrive, gastroesophageal reflux, and cardiomyopathy. Usually, majority of affected children remain undiagnosed and die within the first year of life. Hence, it is of utmost importance to keep a watch for this condition for early diagnosis and surgical intervention which will help in improving the prognosis.

Feto-maternal indicators of cardiac dysfunction as a justification for the cardiac origins for pre-eclampsia.

While the pathophysiology of pre-eclampsia has been postulated as being secondary to placental dysfunction, a cardiac origin has more recently been proposed. Although an association between fetal congenital cardiovascular disease and pre-eclampsia has been demonstrated, no precise pathophysiologic mechanism for this association has been described. This review highlights the current biophysical (including echocardiography and Doppler indices) and biochemical (including proteomic, metabolomic and genetic/transcriptomic) markers of cardiac dysfunction that have been investigated in maternal and fetal cardiac disease and their overlap with predictors of pre-eclampsia. Common pathways of inflammatory and anti-angiogenesis imbalance, endothelial damage, and oxidative stress have been demonstrated in both cardiovascular disease and pre-eclampsia and further investigation into these pathways could help to elucidate the common pathophysiologic mechanisms linking these disorders.

Cardiovascular risk factors and their relationship to age of onset of Alzheimer’s disease in people with Down syndrome

AbstractBackgroundPeople with Down syndrome (DS) are at ultra‐high risk of developing Alzheimer’s dementia (AD). This is primarily due to the triplication of amyloid precursor protein on chromosome 21. Despite common genetic drivers there are large variations in the age of AD onset. In sporadic AD poor cardiovascular health has been associated with increased risk of AD. It has not been established whether the same risks apply to people with DS.MethodLarge population‐based cohort study utilising data from UK‐based primary care electronic health records. Measurements of nine cardiovascular parameters were used to analyse patterns across adulthood. These were systolic blood pressure (SBP), diastolic blood pressure (DBP), pulse pressure (PP), body mass index (BMI), total cholesterol, high and low density lipoproteins, triglycerides, and glycated haemoglobin (HbA1c). Survival curves were fitted with hazard ratios (HR) and crude incident rates calculated using cardiovascular parameters measured between age 25‐34 years as predictor variables and incidence of dementia as the outcome. Age, sex, level of intellectual disability, history of congenital heart disease (CHD), cardiovascular disease, hypothyroidism and diabetes were included as covariates.Result6,424 adults with DS were identified, matched to 23,143 controls. Low PP (<40mmHg), HR 1.45; low DBP (<62mmHg), HR 1.77, and low SBP (<100mmHg), HR 1.83 increased risk of dementia incidence. High SBP (>140mmHg), HR 2.04 increased risk but few people had high values. Raised BMI >25kg/m2 increased incidence dementia risk (HR 1.63). The risk was the same whether someone was overweight or obese. Hypothyroidism, history of CHD, male sex were significant contributors in the models. There was a cumulative effect of risk. People with 1 or 2 risk factors had HRs of 3.15 compared to those with zero risks, whilst people with 3 or more cardiovascular risk factors had HRs of 5.69.ConclusionCardiovascular health in earlier adulthood affects age of AD onset in people with DS. Cardiovascular multi‐morbidity was associated with increased incidence dementia risk suggesting that risks interact in a cumulative fashion. Reducing the number of risks by actively screening and managing medical co‐morbidities in people with DS may therefore help delay the onset of AD. Multi‐domain interventions may be particularly important.

Clinical characteristics and factors associated with severe COVID-19 in hospitalized children during the SARS-CoV-2 Omicron pandemic in Taiwan.

Since April 2022, a notable increase in COVID-19 cases with the rapid spread of the SARS-CoV-2 Omicron variant has been reported in Taiwan. In the epidemic, children were one of the most vulnerable groups, so we analyzed their clinical presentations and factors associated with severe complications of COVID-19 in children. We included hospitalized patients under 18 years old with lab-confirmed SARS-CoV-2 infection from March 1, 2022, to July 31, 2022. We collected the demographic and clinical characteristics of the patients. Patients requiring intensive care were defined as severe cases. Among the 339 enrolled patients, the median age was 31 months (interquartile range (IQR), 8-79.0 months); and 96 patients (28.3%) had underlying diseases. Fever was noted in 319 patients (94.1%) with a median duration of two days (IQR 2-3 days). Twenty-two patients (6.5%) were severe cases, including 10 patients (2.9%) with encephalopathy with abnormal neuroimaging and ten patients (2.9%) with shock. Two patients (0.6%) died. Patients with congenital cardiovascular disease (aOR: 21.689), duration of fever up to four days or more (aOR: 6.466), desaturation (aOR: 16.081), seizure (aOR: 20.92), and procalcitonin >0.5ng/mL (aOR: 7.886) had a higher risk of severe COVID-19. Vital signs need close monitoring, early management and/or intensive care may be applied in COVID-19 patients with congenital cardiovascular diseases, fever lasting ≥4 days, seizures, desaturation and/or elevated procalcition since they are at higher risks of severe diseases.

Nf1 in heart development: a potential causative gene for congenital heart disease: a narrative review.

Congenital heart disease is the most frequent congenital disorder, affecting a significant number of live births. Gaining insights into its genetic etiology could lead to a deeper understanding of this condition. Although the Nf1 gene has been identified as a potential causative gene, its role in congenital heart disease has not been thoroughly clarified. We searched and summarized evidence from cohort-based and experimental studies on the issue of Nf1 and heart development in congenital heart diseases from various databases. Available evidence demonstrates a correlation between Nf1 and congenital heart diseases, mainly pulmonary valvar stenosis. The mechanism underlying this correlation may involve dysregulation of epithelial-mesenchymal transition (EMT). The Nf1 gene affects the EMT process via multiple pathways, including directly regulating the expression of EMT-related transcription factors and indirectly regulating the EMT process by regulating the MAPK pathway. This narrative review provides a comprehensive account of the Nf1 involvement in heart development and congenital cardiovascular diseases in terms of epidemiology and potential mechanisms. RAS signaling may contribute to congenital heart disease independently or in cooperation with other signaling pathways. Efficient management of both NF1 and cardiovascular disease patients would benefit from further research into these issues.

Features of technological regulation for cardiac bioimplants

Patients with congenital heart defects and cardiovascular diseases are required new approaches to surgical intervention. The use of biological cardiac implants, which are made from the extracellular matrix, is a promising trend in modern regenerative medicine. These bioimplants can completely replace defective tissue or organs, and when manufactured with strict protocols and quality control measures, can be safe and effective for therapeutic applications. The process of manufacturing bioimplants involves various risks that need to be assessed and mitigated with ongoing monitoring and evaluation necessary to ensure the highest standards of quality. Overall, this study was successfully evaluated the requirements for introducing a new medical device into practice and created a technical file that meets all necessary documentation for certification.

Temporal evolution of mechanical stimuli from vascular remodeling in response to the severity and duration of aortic coarctation in a preclinical model

Coarctation of the aorta (CoA) is one of the most common congenital cardiovascular diseases. CoA patients frequently undergo surgical repair, but hypertension (HTN) is still common. The current treatment guideline has revealed irreversible changes in structure and function, yet revised severity guidelines have not been proposed. Our objective was to quantify temporal alterations in mechanical stimuli and changes in arterial geometry in response to the range of CoA severities and durations (i.e. age of treatment) seen clinically. Rabbits were exposed to CoA resulting in peak-to-peak blood pressure gradient (BPGpp) severities of ≤ 10, 10–20, and ≥ 20 mmHg for a duration of ~ 1, 3, or 20 weeks using permanent, dissolvable, and rapidly dissolvable sutures. Elastic moduli and thickness were estimated from imaging and longitudinal fluid–structure interaction (FSI) simulations were conducted at different ages using geometries and boundary conditions from experimentally measured data. Mechanical stimuli were characterized including blood flow velocity patterns, wall tension, and radial strain. Experimental results show vascular alternations including thickening and stiffening proximal to the coarctation with increasing severity and/or duration of CoA. FSI simulations indicate wall tension in the proximal region increases markedly with coarctation severity. Importantly, even mild CoA induced stimuli for remodeling that exceeds values seen in adulthood if not treated early and using a BPGpp lower than the current clinical threshold. The findings are aligned with observations from other species and provide some guidance for the values of mechanical stimuli that could be used to predict the likelihood of HTN in human patients with CoA.

Hemodynamic features of pregnant women with atrial septal defect in the third trimester of pregnancy: A literature review

Due to the decline in mortality rates among children with heart disease, a significant number of such children have reached reproductive age. However, since knowledge about the impact of pregnancy on haemodynamics in women with heart disease is limited, this study is extremely relevant. The study aimed to provide a comprehensive review of current scientific sources and consolidate the knowledge gained on haemodynamic features in pregnant women with atrial septal defects. Several methods were used in the study: analysis, including comparative analysis, synthesis, bibliography, systematisation, and categorisation. A two-stage approach in the form of a systematic literature review was also used. The complex haemodynamic changes that occur in pregnant women, both in normal and pathological conditions, in particular in pregnant women with atrial septal defect, are considered. The question is specified as to why hemodynamic changes become most significant in the third trimester of pregnancy, their impact on the course of pregnancy, and the outcome of labor completion. The topic of acute and chronic complications of atrial septal defect and modern principles of their prevention and treatment are covered. Special attention is paid to the methods of correction of this heart defect, considering their advantages, disadvantages and possible complications. The experience of perinatal centres in several European countries in managing pregnancies in women with cardiovascular disease, in particular with atrial septal defects, is reviewed. Gaps in knowledge about the prevalence of these defects and risk factors were filled. The study addressed the lack of a comprehensive view of this problem: from pathophysiological basis and epidemiology to treatment and modification of risk factors. The study is of great practical value for healthcare professionals, as it can serve as a basis for the development of preventive programmes and other interventions for pregnancies of women with congenital cardiovascular disease

Lateral thinking in syndromic congenital cardiovascular disease.

Syndromic birth defects are rare diseases that can present with seemingly pleiotropic comorbidities. Prime examples are rare congenital heart and cardiovascular anomalies that can be accompanied by forelimb defects, kidney disorders and more. Whether such multi-organ defects share a developmental link remains a key question with relevance to the diagnosis, therapeutic intervention and long-term care of affected patients. The heart, endothelial and blood lineages develop together from the lateral plate mesoderm (LPM), which also harbors the progenitor cells for limb connective tissue, kidneys, mesothelia and smooth muscle. This developmental plasticity of the LPM, which founds on multi-lineage progenitor cells and shared transcription factor expression across different descendant lineages, has the potential to explain the seemingly disparate syndromic defects in rare congenital diseases. Combining patient genome-sequencing data with model organism studies has already provided a wealth of insights into complex LPM-associated birth defects, such as heart-hand syndromes. Here, we summarize developmental and known disease-causing mechanisms in early LPM patterning, address how defects in these processes drive multi-organ comorbidities, and outline how several cardiovascular and hematopoietic birth defects with complex comorbidities may be LPM-associated diseases. We also discuss strategies to integrate patient sequencing, data-aggregating resources and model organism studies to mechanistically decode congenital defects, including potentially LPM-associated orphan diseases. Eventually, linking complex congenital phenotypes to a common LPM origin provides a framework to discover developmental mechanisms and to anticipate comorbidities in congenital diseases affecting the cardiovascular system and beyond.

Care of the Fetus With Congenital Cardiovascular Disease: From Diagnosis to Delivery.

The majority of congenital cardiovascular disease including structural cardiac defects, abnormalities in cardiac function, and rhythm disturbances can be identified prenatally using screening obstetrical ultrasound with referral for fetal echocardiogram when indicated. Diagnosis of congenital heart disease in the fetus should prompt assessment for extracardiac abnormalities and associated genetic abnormalities once maternal consent is obtained. Pediatric cardiologists, in conjunction with maternal-fetal medicine, neonatology, and cardiothoracic surgery subspecialists, should counsel families about the details of the congenital heart defect as well as prenatal and postnatal management. Prenatal diagnosis often leads to increased maternal depression and anxiety; however, it decreases morbidity and mortality for many congenital heart defects by allowing clinicians the opportunity to optimize prenatal care and plan delivery based on the specific lesion. Changes in prenatal care can include more frequent assessments through the remainder of the pregnancy, maternal medication administration, or, in selected cases, in utero cardiac catheter intervention or surgical procedures to optimize postnatal outcomes. Delivery planning may include changing the location, timing or mode of delivery to ensure that the neonate is delivered in the most appropriate hospital setting with the required level of hospital staff for immediate postnatal stabilization. Based on the specific congenital heart defect, prenatal echocardiogram assessment in late gestation can often aid in predicting the severity of postnatal instability and guide the medical or interventional level of care needed for immediate postnatal intervention to optimize the transition to postnatal circulation.

Cardiovascular Magnetic Resonance Imaging Patterns in Rare Cardiovascular Diseases

Rare cardiovascular diseases (RCDs) have low incidence but major clinical impact. RCDs' classification includes Class I-systemic circulation, Class II-pulmonary circulation, Class III-cardiomyopathies, Class IV-congenital cardiovascular diseases (CVD), Class V-cardiac tumors and CVD in malignancy, Class VI-cardiac arrhythmogenic disorders, Class VII-CVD in pregnancy, Class VIII-unclassified rare CVD. Cardiovascular Magnetic Resonance (CMR) is useful in the diagnosis/management of RCDs, as it performs angiography, function, perfusion, and tissue characterization in the same examination. Edema expressed as a high signal in STIRT2 or increased T2 mapping is common in acute/active inflammatory states. Diffuse subendocardial fibrosis, expressed as diffuse late gadolinium enhancement (LGE), is characteristic of microvascular disease as in systemic sclerosis, small vessel vasculitis, cardiac amyloidosis, and metabolic disorders. Replacement fibrosis, expressed as LGE, in the inferolateral wall of the left ventricle (LV) is typical of neuromuscular disorders. Patchy LGE with concurrent edema is typical of myocarditis, irrespective of the cause. Cardiac hypertrophy is characteristic in hypertrophic cardiomyopathy (HCM), cardiac amyloidosis (CA) and Anderson-Fabry Disease (AFD), but LGE is located in the IVS, subendocardium and lateral wall in HCM, CA and AFD, respectively. Native T1 mapping is increased in HCM and CA and reduced in AFD. Magnetic resonance angiography provides information on aortopathies, such as Marfan, Turner syndrome and Takayasu vasculitis. LGE in the right ventricle is the typical finding of ARVC, but it may involve LV, leading to the diagnosis of arrhythmogenic cardiomyopathy. Tissue changes in RCDs may be detected only through parametric imaging indices.

Healing the Broken Hearts: A Glimpse on Next Generation Therapeutics

Cardiovascular diseases are the leading cause of death worldwide, accounting for 32% of deaths globally and thus representing almost 18 million people according to WHO. Myocardial infarction, the most prevalent adult cardiovascular pathology, affects over half a million people in the USA according to the last records of the AHA. However, not only adult cardiovascular diseases are the most frequent diseases in adulthood, but congenital heart diseases also affect 0.8–1.2% of all births, accounting for mild developmental defects such as atrial septal defects to life-threatening pathologies such as tetralogy of Fallot or permanent common trunk that, if not surgically corrected in early postnatal days, they are incompatible with life. Therefore, both congenital and adult cardiovascular diseases represent an enormous social and economic burden that invariably demands continuous efforts to understand the causes of such cardiovascular defects and develop innovative strategies to correct and/or palliate them. In the next paragraphs, we aim to briefly account for our current understanding of the cellular bases of both congenital and adult cardiovascular diseases, providing a perspective of the plausible lines of action that might eventually result in increasing our understanding of cardiovascular diseases. This analysis will come out with the building blocks for designing novel and innovative therapeutic approaches to healing the broken hearts.

Congenital Anomalies of Aortic Arch: A Pictorial Essay.

Aortic abnormalities account for 15 to 20% of all congenital cardiovascular diseases. The purpose of this pictorial essay is to illustrate various congenital anomalies of the aortic arch, which influence patient management and outcome.

A sensitive UPLC-MS/MS method for simultaneous quantification of one-carbon metabolites & co-factors in human plasma

One-carbon metabolism is an important metabolic pathway involved in many diseases, such as congenital malformations, tumours, cardiovascular diseases, anaemia, depression, cognitive diseases and liver disease. However, the current methods have specific defects in detecting and qualifying the related compounds of one-carbon metabolism. In this study, a validated method was established to simultaneously quantify 22 one-carbon metabolites & co-factors in human plasma and applied to the study of correlation between one-carbon metabolism and colorectal cancer in human plasma samples, which were from 44 healthy subjects and 55 colorectal cancer patients. The method used ultra-high performance liquid chromatography coupled with triple quadrupole mass spectrometry (UPLC-MS/MS), and the analytes included betaine, L-carnitine, L-cystathionine, L-cysteine, dimethylglycine, DL-homocysteic acid, homocysteine, methionine, pyridoxal hydrochloride, pyridoxamine dihydrochloride, pyridoxine dihydrochloride, S-(5′-Adenosyl)-L-homocysteine, serine, choline chloride, folic acid, glycine, pyridoxal phosphate monohydrate, riboflavin, taurine, 5-methyltetrahydrofolate, S-(5′-adenosyl)-L-methionine disulfate salt, trimethylamine oxide. The developed method was successfully applied to the quantification of 22 one-carbon metabolites & co-factors in human plasma from colorectal cancer patients and healthy individuals. The plasma concentrations of dimethylglycine was significantly decreased in the patients compared with the healthy individuals, while L-cystathionine was increased.

Fetal Congenital Cardiac and Vascular Disorders Associated with Sertraline Treatment during Pregnancy: Analysis of FAERS Data.

Objective Sertraline is one of the most commonly used antidepressants worldwide and is one of the first-choice treatments for depression during pregnancy. This study is aimed at testing the possible association between sertraline intrauterine exposure and congenital cardiac and vascular disorder occurrences by assessing the publicly available US Food and Drug Administration Adverse Event Reporting System (FAERS). Methods Disproportionality analysis and Bayesian analysis were used to mine FAERS for suspected congenital cardiac and vascular disorder data for sertraline intrauterine exposure from the first quarter of 2004 to the second quarter of 2021. Results Among the 914 cases of sertraline used with congenital cardiovascular disease in the FAERS database, the reporting areas were mainly in the United States and Europe. The number of adverse events reported every year since 2004 has no many differences. Congenital anomalies are the most frequently reported serious clinical outcome. Among the 69 positive signals detected from 914 cases, 31 were invalid signals, and 38 were valid signals according to criteria. The most common ones are heart disease congenital, atrial septal defect, ventricular septal defect, patent ductus arteriosus, and persistent fetal circulation. Conclusions Mining FAERS data can analyze and study the adverse reactions of sertraline in a more comprehensive and in-depth manner, thereby effectively reducing the risk of clinical medication.

Multi-modality Imaging Evaluation of a Rare and Complex Case of Single Ventricle Physiology; the important role of Cardiac MR.

Congenital heart diseases (CHD) represent a major clinical and diagnostic challenge for correct abnormality identification and subsequent successful therapy; even more challenging is following-up patient health after multiple post-interventional corrections often required in complex cardio-vascular abnormalities. We describe a multi-modality imaging evaluation of a complex congenital cardio-vascular diseases, underlining the relevance of cardiac magnetic resonance to non invasively solve some issues related to postsurgical changes.

Glottic and Subglottic Injury and Development of Pediatric Airway Stenosis.

To determine how often children with airway injury at the time of tracheostomy develop airway stenosis. A 7-year retrospective review of a prospectively maintained database of pediatric patients who underwent endotracheal intubation followed by tracheostomy with concurrent and follow-up direct laryngoscopy. Tertiary care hospital. Outcomes included glottic or subglottic injury and progression to stenosis. Univariate and multivariate analyses were performed via SPSS. Of the 222 patients (median age at surgery, 0.6 years; 54% male) who met study criteria, 46% had airway injury at the time of tracheostomy. Patients with congenital cardiovascular disease had 2.33-times increased risk of developing airway injury (P = .01). Patients with airway injury on initial direct laryngoscopy developed stenosis significantly more frequently than those without injury (30% vs 12%, P < .01). Risks factors for developing stenosis in children with airway injury include prematurity (P = .02), younger age at time of surgery (P < .01), endotracheal tube size (P < .01), Down syndrome (P = .03), and neonatal (P = .02) and/or congenital cardiovascular (P < .01) diagnosis. However, none of these variables were significant on multivariate analysis. Intubated patients with evidence of glottic or subglottic injury at the time of tracheotomy are more likely to develop airway stenosis than those without. Congenital heart disease was associated with twice the risk of developing airway injury, while progression to stenosis was associated with younger age, prematurity, and/or comorbid diagnoses.

Sex Differences and Cardiovascular Diseases in Down Syndrome

Congenital heart disease and cardiovascular disease are the leading causes of death for individuals with Down Syndrome (Ds) (Zhu, J.L., et al, 2013). A systematic review was conducted in June 2021 to address the research question “Are there reported sex differences for cardiovascular disease and cardiovascular physiological function in Ds”. Since there are significant sex differences in the risk of congenital heart and cerebrovascular disease in the general population, we hypothesized that these differences are present in the Ds population. Four domains were developed: congenital heart disease, baseline physiology and risk factors, heart disease and hypertension, and cerebrovascular disease. Exclusion criteria were applied to identify studies that addressed sex differences. The systematic review shows that women with Ds have a higher rate of congenital heart disease, coronary and cerebrovascular events and Moyamoya. Following the systematic review, a retrospective medical chart review of the University of Iowa Hospitals and Clinics was conducted using the platform TriNetX to identify the incidence of congenital and cardiovascular diseases in males and females. Relative risk was computed comparing Ds to general patient counts as well as men and women within each population. Ds patients did not share most of the sex differences in risk factors observed in the general population, however there are important sex differences in each domain that may contribute to earlier mortality in women with Ds. Several studies report women have an increased probability of developing risk factors for cardiovascular disease, such as obesity. Therefore, future research to understand the mechanism underlying these sex differences is necessary.ReferencesZhu, J.L., et al., Survival among people with Down syndrome: a nationwide population‐basedstudy in Denmark. Genetics in Medicine, 2013. 15(1): p. 64‐69.

Molecular Proteomics and Signalling of Human Platelets in Health and Disease

Platelets are small anucleate blood cells that play vital roles in haemostasis and thrombosis, besides other physiological and pathophysiological processes. These roles are tightly regulated by a complex network of signalling pathways. Mass spectrometry-based proteomic techniques are contributing not only to the identification and quantification of new platelet proteins, but also reveal post-translational modifications of these molecules, such as acetylation, glycosylation and phosphorylation. Moreover, target proteomic analysis of platelets can provide molecular biomarkers for genetic aberrations with established or non-established links to platelet dysfunctions. In this report, we review 67 reports regarding platelet proteomic analysis and signalling on a molecular base. Collectively, these provide detailed insight into the: (i) technical developments and limitations of the assessment of platelet (sub)proteomes; (ii) molecular protein changes upon ageing of platelets; (iii) complexity of platelet signalling pathways and functions in response to collagen, rhodocytin, thrombin, thromboxane A2 and ADP; (iv) proteomic effects of endothelial-derived mediators such as prostacyclin and the anti-platelet drug aspirin; and (v) molecular protein changes in platelets from patients with congenital disorders or cardiovascular disease. However, sample sizes are still low and the roles of differentially expressed proteins are often unknown. Based on the practical and technical possibilities and limitations, we provide a perspective for further improvements of the platelet proteomic field.