Heart Disease Patients Research Articles

Clinical Efficacy of Fractional Flow Reserve-Guided Percutaneous Coronary Intervention in Coronary Heart Disease Patients with SYNTAX Score ≥33 and Euro Score ≥6: A Single-Center Retrospective Analysis

Objective: To observe clinical efficacy of fractional flow reserve (FFR)-guided percutaneous coronary intervention (PCI) in coronary heart disease patients with SYNTAX scores (SS) ≥33 and Euro Scores (ES) ≥6 who are unsuitable for or have declined coronary artery bypass graft (CABG). Methods: A total of 117 patients with SS ≥33 and Euro Score (ES) ≥6 who were unsuitable for and/or who had declined CABG between Jan 2021 and June 2022 were enrolled in this retrospective analysis. All patients accepted optimal medical therapy and some accepted an FFR-guided PCI procedure. Patients who only underwent optimal medical therapy were divided into the optimal medical therapy group (OMT group) and patients who simultaneously underwent FFR-guided PCI procedure were divided into the PCI group in this retrospective analysis. All patients accepted follow-up for at least 12 months after discharge. Results: SS and ES in the two groups were not statistically different (p > 0.05). Patients with chronic total occlusion accounted for a greater proportion in the PCI subgroup (31.3%, 5/16) than in other subgroups. Eighteen (18.6%, 18/97) cases in the PCI group developed major adverse cardiac and cerebrovascular events (MACCEs). There were 12 (60%, 12/20) cases of MACCEs in the OMT group, which was statistically different from the PCI group (p < 0.05). Conclusions: Based on optimal medical therapy, FFR-guided PCI can still have clinical benefit to coronary artery disease patients with SS ≥33 who were not suitable for CABG.

Heart Diseases in Patients with Organic Acidemia

Objective: Organic acidemias are intoxication-type inborn errors of the metabolism with multiple organ involvement. Patients with organic acidemia usually present in the neonatal or infantile period with high anion gap metabolic acidosis and hyperammonemia. The present study investigates the presence of congenital heart defects and secondary heart diseases in patients with organic acidemia. Material and Methods: Included in the study were 31 patients of whom 14 were diagnosed with methylmalonic acidemia (MMA), 11 with propionic acidemia and six with isovaleric acidemia. The cardiac findings of all patients included in the study were evaluated. Results: Of the sample, 63.64% were identified with accompanying congenital heart disease, with the most common diagnosis being propionic acidemia and the most common heart defects being atrial septal defects and mitral regurgitation. Conclusion: The accumulation of toxic intermediate metabolites due to enzyme deficiency is thought to be the main mechanism behind the cardiac involvement noted in organic acidemias. In the presence of unexplained deterioration, the potential for organic acidemia to accompany congenital heart disease should be kept in mind, and so it is important to screen patients with organic acidemias by echocardiography.

Patients Perceived Autonomy Support Affecting Treatment Motivation, Depression, Anxiety and Stress in CHD and Diabetes Mellitus

The study was aimed to investigate the impact of perceived autonomy support on treatment motivation, depression, anxiety and stress among patients of coronary heart disease and diabetes mellitus. Study was completed through correlational research design and 310 patients were selected as sample of study by applying convenient sampling technique. Three questionnaires were utilized as research instruments to measure variables; Health Care Climate Questionnaire (Ryan, 1995), Treatment Motivation Questionnaire (Ryan, 1995), and DASS (Lovibond, 1995). Findings revealed that treatment motivation was positively correlated with perceived autonomy support. Results suggest that there was negative correlation among depression, anxiety, stress and perceived autonomy support. Perceived autonomy support is significant positive predictor of treatment motivation. In addition no difference was investigated between gender on PAS and TM. Level of depression anxiety and stress was reported higher among female as compared to male patients of CHD and DM. It was suggested that treatment motivation must be explored as mediator between PAS and DAS among patients in future.

The Impact of Integration of a Genetic Clinic Into a Pediatric Cardiac Unit.

Previously published studies suggest that genetic or environmental causes can be observed in 20-30% of congenital heart disease (CHD) patients, which include aneuploidy, single gene defects, pathological copy number variations, and de novo autosomal dominant and recessive inheritance. Moreover, the genetic background of childhood cardiomyopathies (CMs) has not been elucidated well. The study highlights the value of genetic assessment in diagnosing and family counseling for CHD and pediatric CM patients referred to the genetic clinic in a pediatric cardiology department. The study involved patients less than 18 years of age attending the cardiogenetic clinic in the pediatric cardiology department between December 2010 and February 2019. The following patient categories who had genetic evaluation were included: CHD in the presence of a syndromic phenotype, patients with CHD having extracardiac congenital anomalies or delayed development, hypertrophic and dilated CM patients, patients with dilated aortic root and ascending aorta,significant CHD in siblings or first-degree relatives,suspected channelopathies; and interrupted aortic arch abnormalities. A total of 285 patients were evaluated in the cardiogenetic clinic. The mean age was 20.2 months, with a range of 0-168. Females and males constituted 153 (53.7%) and 132 (46.3%), respectively. The most commoncause of referral to the genetic clinic was the presence of CM (N=134 (46.3%)): hypertrophic CM in 24% and dilated CM in 20% of cases. Seventy-six patients (26.7%) had positive genetic results. The most common genetic abnormality was familial infantile hypertrophic CM-causing gene ELAC2 in 19 (23.5%) cases. It may be beneficial for any pediatric cardiology unit to provide an established genetic clinic. Using a genetic clinic will enhance understanding of CHD pathophysiology, family education, and genetic counseling. Agreement on a well-written protocol and the way forward to specify what congenital heart conditions require genetic investigation should be clarified.

THE ANALYSIS OF DIET AND PHYSICAL ACTIVITY PATTERNS IN NURSING MANAGEMENT FOR CORONARY HEART DISEASE PATIENTS

Cardiovascular disease caused by impaired function of the heart and blood vessels, such as coronary heart disease, heart failure, hypertension and stroke caused by improper diet and physical activity patterns. The purpose of this study was to describe the pattern of eating and physical activity patterns in coronary heart disease patients with a history of hypertension. The research method used is descriptive analysis using a cross-sectional approach. The sampling technique used was accidental sampling with a total sample of 130 respondents. The instruments used are Food Frequency Questioinnaire (FFQ) for diet and Global Physical Activity Questioinnaire (GPAQ) for physical activity patterns. The results showed that the picture of the eating pattern in coronary heart disease patients with a history of hypertension was poor diet (53.1%), the description of the pattern of physical activity was the most in the light category (50.0%). Conclusion: In this study, it was found that diet and physical activity patterns in coronary heart disease patients with a history of hypertension were found to have poor diet and light physical activity patterns.Keywords: coronary heart disease, eating pattern, hypertension, physical activity patterns

Estimation of the Levels of IL-6, IL-8, and CRP in Women Patients of Osteoporosis and Heart diseases in Samarra city

Estimation of the Levels of IL-6, IL-8, and CRP in Women Patients of Osteoporosis and Heart diseases in Samarra city

Association between serum PCSK9 and coronary heart disease in patients with type 2 diabetes mellitus

Background and aimsProprotein convertase subtilisin/kexin type 9 (PCSK9) is considered a new biomarker for atherosclerosis, but its ability to predict cardiovascular outcomes has been controversial. This study aimed to address the lack of data on PCSK9, coronary heart disease (CHD) severity, and major cardiovascular events (MACEs) in patients with type 2 diabetes mellitus (T2DM).MethodsA total of 2984 T2DM patients underwent selective coronary angiography, and their serum PCSK9 levels were measured using enzyme-linked immunosorbent assay. Correlation and logistic regression analyses were performed to investigate the association between PCSK9 expression and CHD severity. This study used Cox regression analysis to assess the association between circulating PCSK9 levels and the risk of MACEs.ResultsCirculating PCSK9 levels were significantly higher in the CHD group than in the non-CHD group [554.62 (265.11) ng/mL vs. 496.86 (129.05) ng/mL, p < 0.001]. Circulating PCSK9 levels positively correlated with CHD severity (diseased vessels: r = 0.35, p < 0.001; Gensini score: r = 0.46, p < 0.001). Elevated PCSK9 levels are an independent risk factor for CHD risk and severity (CHD group vs. non–CHD group: OR = 2.829, 95% CI: 1.771–4.520, p < 0.001; three vessel disease group vs. one vessel disease group: OR = 4.800, 95% CI: 2.387–9.652, p < 0.001; high GS group vs. low GS group: OR = 5.534, 95% CI: 2.733–11.208, p < 0.001). Through a six-year follow-up and multivariate Cox regression analysis, elevated circulating PCSK9 levels were found to be independently associated with MACEs in all participants (HR: 3.416, 5% CI: 2.485–4.697, p < 0.001; adjusted HR: 2.780, 95% CI: 1.930–4.004, p < 0.001).ConclusionsSerum PCSK9 levels were positively correlated with multi-vessel CHD and Gensini score. Elevated circulating PCSK9 levels are an independent risk factor for CHD and increased incidence of MACEs in T2DM.

Statins adherence and associated muscle symptoms in elderly coronary heart disease patients

Statins adherence and associated muscle symptoms in elderly coronary heart disease patients

Effects of trimetazidine on cardiac function in adult cyanotic congenital heart disease patients: Protocol for a 3-month multicenter, randomized, double-blind controlled trial

Nearly 20% Patients with cyanotic congenital heart disease (CCHD) are not able to receive surgery. These patients experience a decline in cardiac function as they age, which has been demonstrated to be associated with changes in energy metabolism in cardiomyocytes. Trimetazidine (TMZ), a metabolic regulator, is supposed to alleviate such maladaptation and reserve cardiac function in CCHD patients. This is a randomized, double-blind, placebo-controlled clinical trial. Eighty adult CCHD patients will be recruited and randomized to the TMZ (20 mg TMZ 3 times a day for 3 months) or placebo group (placebo 3 times a day for 3 months). The primary outcome is the difference in cardiac ejection fractions (EF) measured by cardiac magnetic resonance (MRI) between baseline and after 3 months of TMZ treatment. The secondary outcomes include TMZ serum concentration, rate of cardiac events, NYHA grading, fingertip SpO2, NT-proBNP levels, 6-minute walking test (6MWT), KCCQ-CSS questionnaire score, echocardiography, ECG, routine blood examination, liver and kidney function test, blood pressure and heart rate. This trial is designed to explore whether the application of TMZ in adult CCHD patients can improve cardiac function, reduce cardiac events, and improve exercise performance and quality of life. The results will provide targeted drug therapy for CCHD patients with hypoxia and support the application of TMZ in children with CCHD.

The segregation of physician networks providing care to black and white patients with heart disease: Concepts, measures, and empirical evaluation

Black-White disparities in cardiac care may be related to physician referral network segregation. We developed and tested new geographic physician network segregation measures. We used Medicare claims to identify Black and White Medicare heart disease patients and map physician networks for 169 hospital referral regions (HRRs) with over 1000 Black patients. We constructed two network segregation indexes ranging from 0 (integration) to 100 (total segregation): Dissimilarity (the unevenness of Black and White patient distribution across physicians [Dn]) and Absolute Clustering (the propensity of Black patients’ physicians to have closer ties with each other than with other physicians [ACLn]). We employed conditional logit models to estimate the probability of using the best (lowest mortality) geographically available hospital for Black and White patients undergoing coronary artery bypass grafting (CABG) surgery in 126 markets with sufficient sample size at increasing levels of network segregation and for low vs. high HRR Black patient population. Physician network segregation was lower than residential segregation (Dissimilarity 21.9 vs. 48.7, and Absolute Clustering 4.8 vs. 32.4) and positively correlated with residential segregation (p < .001). Network segregation effects differed by race and HRR Black patient population. For White patients, higher network segregation was associated with a higher probability of using the best available hospitals in HRRs with few black patients but unchanged (ACLn) or lower (Dn) probability of best hospital use in HRRs with many Black patients. For Black patients, higher network segregation was not associated with a substantial change in the probability of best hospital use regardless of the HRR Black patient population size. Measuring physician network segregation is feasible and associated with nuanced effects on Black-White differences in high-quality hospital use for heart disease. Further work is needed to understand underlying mechanisms and potential uses in health equity policy.

Treatment-related cardiovascular events in patients with non-small cell lung cancer: Evidence from real-world data with a competing risks approach.

Understanding cancer treatment-related cardiovascular (CV) events is important for cancer care; however, comprehensive evaluation of CV events in patients with lung cancer is limited. This study aimed to assess the cumulative incidence and associated risks of various CV event types in patients with non-small cell lung cancer (NSCLC). A total of 7868 individuals aged 40years and older, recently diagnosed with NSCLC (2007-2018), were assessed with data obtained from the National Cancer Center, Korea. This study included nine types of CV events. A 2-year cumulative incidence function (CIF) of CV events was estimated, with death as a competing event. The associated risks were assessed by subdistribution hazard ratio (sHR) in the Fine-Gray competing risks model. CV events were observed in 7.8% of patients with NSCLC, with the most frequently observed types being atrial fibrillation and flutter (AF) (2.7%), venous thromboembolic disease (2.0%), and cerebrovascular disease (CeVD) (1.5%). Overall, all CV events were highest in the group treated with systemic therapy (CIF, 10.6%; 95% confidence interval [CI], 9.5%-11.8%), followed by those treated with surgery (CIF, 10.0%; 95% CI, 8.6%-11.6%); the incidence of AF (CIF, 5.7%; 95% CI, 4.6%-7.0%) was highest in patients treated with surgery. Individuals treated with systemic therapy were found to exhibit a higher CeVD risk than those treated with surgery (sHR, 4.12; 95% CI, 1.66-10.23). Among the patients who underwent surgery, those with lobectomy and pneumonectomy had a higher AF risk (vs. wedge resection/segmentectomy; sHR, 7.79; 95% CI, 1.87-32.42; sHR, 8.10; 95% CI, 1.60-40.89). These findings revealed treatment-related CV event risks in patients with NSCLC, which suggests that the risk of AF in surgery and CeVD in systemic therapy should be paid more attention to achieve a better prognosis and improve cancer survivorship outcomes. Atrial fibrillation and flutter (AF) is the most common cardiovascular event, particularly at a high risk in patients with non-small cell lung cancer (NSCLC) undergoing surgery. Patients receiving surgery with poor performance status, diagnosed with regional stage, and undergoing lobectomy or pneumonectomy are at a high risk of AF. Systemic/radiotherapy is associated with cerebrovascular and ischemic heart disease in patients with NSCLC.

Comparison of Models for Predicting Outcomes in Patients for Heart Disease

Comparison of Models for Predicting Outcomes in Patients for Heart Disease

Characterization of genomic variants associated with congenital heart disease in patients from southwestern Colombian

Congenital heart diseases correspond to errors during embryogenesis, generating structural and functional malformations. Congenital heart diseases are the most prevalent congenital malformations and are responsible for the highest infant morbidity and mortality. Among these cases, 8 % can be attributed to variants in genes associated with cardiac development. To establish the population frequency of genomic variants that cause congenital heart disease, a review of the scope of prevalent genes was carried out, complete exome sequencing results of 320 patients without suspicion of congenital heart disease were used, the exome sequencing is a technique based on DNA extraction using a Qiagen kit, with massive sequencing of Nextera TM libraries using an Illumina platform with 100X coverage, alignment with reference genome GRCh38/hg19, and analysis with the CRAVAT program; clinical characterization, significance classification, and gene interaction networks were performed. The scope analysis allowed to determine that the genes NKX2-5, TBX20, GATA4, NOTCH1, PTPN11 are the most prevalent, the variants with the highest allelic frequency were c.63A > G (0.2844), c.39T > C (0.3406), c.1132A > G (0.0406), c.1669+9T > C (0.3531) and c.854-30T > C (0.0875) respectively; 4 variants were reclassified by in silico tools, in the NKX2-5 gene c.335-311_335-303del from benign to probably pathogenic, in the NOTCH1 gene c.2354-24C > T from benign to pathogenic, and in the PTPN11 gene c.2354-24C > T and c.854-30T > C from benign to pathogenic. 17 % of intronic variants and 4.8 % of missense variants were identified. This work contributes to knowledge about the frequency with which genomic variants associated with congenital heart disease are present in the population, generating a tool for early diagnosis, early treatment, thus reducing morbidity and mortality, with a view to future universal molecular neonatal screening of congenital heart disease.

ANGIOGRAPHIC FINDINGS IN PATIENTS PRESENTING WITH CHEST PAIN IN EASTERN ZONE OF AFGHANISTAN

Aim: Coronary artery disease is the leading cause of mortality and morbidity globally. Its diagnosis starts with workup of routine examinations and is confirmed by coronary angiography. The main purpose of the study was to find out angiographic findings in patients presenting with chest pain with or without electrocardiogram abnormalities.&#x0D; Methods: It was a retrospective descriptive single setting hospital based study conducted at Afghan Momand Medical complex, a tertiary care center in Nangarhar, Afghanistan. The study included 372 patients with chest pain with or without electrocardiogram abnormalities.&#x0D; Results: Mean age of the study population was 56.6 ± 11.7 years. 50 (13.4%) patients with chest pain had normal coronary angiography (CAG) while 64 (17.2%) patient had non critical CAG and the rest had significant disease on CAG described as64 (17.2%) patients had single vessel disease (SVD) while 40 (10.8%)had double vessel disease (DVD) and the rest 82 (22%) had triple vessel disease (TVD). Left anterior descending coronary artery was the leading involved artery (206, 45%) followed by right coronary artery (133, 29%) and left circumflex (119, 26%) respectively. Incidences of TVD increased with increasing age as it was not involved in the lowest two age groups (0. 0%) while it was in involved in 24 (29.3%), 33 (40.2%), and 15 (18.3%) in the age groups 50-59, 60-69, and 70 through highest age groups respectively.&#x0D; Conclusion: We concluded that coronary angiography precisely prescribed is a gold standard investigation to find out ischemic heart disease in patients with chest pain and/or electrocardiogram abnormalities. In fact, left anterior descending coronary artery was the most leading diseased artery in the forms of both single vessel disease and multiple vessel disease. Moreover, prevalence of triple vessel disease significantly increased with increasing age. Angioplasty was a matter of concern which needs to be evaluated with further researches about why some patients with single vessel disease did not undergo subsequent angioplasty and some with triple vessel disease underwent angioplasty.

Post-traumatic stress disorder among heart disease patients: a clinical follow-up of individuals with myocardial infarction in the Tromsø Study

BackgroundMyocardial infarction is likely to be experienced as a life-threatening and potentially traumatic event. Approximately one-third of patients with myocardial infarction experience clinically significant symptoms of anxiety/depression. However, it is unclear how many of these patients experience these symptoms because of post-traumatic stress disorder (PTSD). We conducted a clinical screening of individuals with a confirmed myocardial infarction diagnosis. Our goal was to examine the prevalence of PTSD in myocardial infarction patients and study how PTSD symptoms were associated with exposure to potentially traumatic events.MethodThis is epidemiological research with a cross-sectional design following up participants from the Tromsø Study with a confirmed diagnosis of myocardial infarction. We sent invitations to participants in the Tromsø Study with clinically significant self-reported anxiety or depression symptoms following myocardial infarction. A cross-sectional sample of N = 79 participants (61 men and 18 women) was collected. During an interview, participants completed the Stressful Life Events Screening Questionnaire and the PTSD checklist PCL-5.ResultsWe found nine participants (11.6%) with probable PTSD. This was significantly higher than the postulated population prevalence in Norway (p < 0.015). We found no direct association between myocardial infarction as illness trauma and symptom levels (p = 0.123). However, we found a significant linear trend (p = 0.002), indicating that symptom severity increased proportionately as the number of post-traumatic events increased.ConclusionPTSD prevalence in myocardial infarction patients was related to lifetime exposure to traumatic events, not the myocardial infarction event alone. More research is required to examine the interaction between myocardial infarction and PTSD. Clinicians should be aware that anxiety or depression symptoms after MI could be secondary symptoms of PTSD.

INCREASE MIGRATION OF PERIPHERAL BLOOD DERIVED ENDOTHELIAL PROGENITOR CELLS OF STABLE CORONARY ARTERY DISEASE PATIENT WITH ANGIOTENSIN CONVERTING ENZYME INHIBITORS

This research is based on refractory angina pectoris, which remains a problem despite advances in coronary heart disease treatment. Stem cell therapy is still in preclinical research stages to address refractory angina. Endothelial progenitor cells (EPCs) aid in improving endothelium and the growth of new blood vessels. Heart medication has shown to enhance both the quantity and function of EPCs in patients at cardiovascular risk or with heart disease. Previous studies reported that ACE inhibitors (ACEI) have a positive effect on EPCs. Thus, this study analyzes the impact of three different ACE inhibitors on EPC migration in laboratory conditions. Its aim is to ascertain the increase in EPC migration in stable coronary heart disease patients after ACEI administration. The research methodology involves an experimental design with a control group and post-treatment assessment only. Mononuclear cells are isolated from stable coronary heart disease patients' peripheral blood and incubated for 3 days. The EPCs are then divided into captopril, ramipril, lisinopril, and a control group, observed for 48 hours. EPC migration is assessed by counting the cells moving from the upper chamber to the membrane facing the lower chamber using a transwell migration assay after 20 hours, observed with a light microscope and Giemsa staining. Data analysis via ANOVA statistical tests indicates increased EPC migration in the captopril, ramipril, and lisinopril groups compared to the control. Captopril shows the highest effect among the groups, while no significant difference is observed between captopril and lisinopril, as well as between ramipril and lisinopril.

Outcomes of cardiac resynchronization therapy in congenital heart disease: A meta-analysis and systematic review.

Cardiac resynchronization therapy (CRT) is a standard treatment for patients with heart failure with reduced ejection fraction. However, there is still a gap of evidence in congenital heart disease (CHD) patients regarding resynchronization therapy. We performed a meta-analysis and systematic review of CHD patients who received CRT implantation. We comprehensively searched the databases of MEDLINE, EMBASE, and Cochrane database from inception to June 2023. Studies that reported response rate to CRT, total mortality rate, change in QRS duration, change in left ventricular ejection fraction, and change in New York Heart Association functional class were included. A total of 14 studies were included in the study. There were 10 studies that reported response rates after implantation. The overall response rate to CRT in CHD patients was 68% (95% confidence interval [CI] 61%-75%, I2 32%). The response rates in patients with systemic right ventricle (RV), systemic left ventricle (LV), and single ventricle were 58% (95% CI 46%-70%, I2 0%), 80% (95% CI 74%-86% I2 14%), and 67% (95% CI 49%-80% I2 0%). Response to CRT in systemic RV was inferior to systemic LV with an odds ratio of 0.38 (95% CI 0.15-0.95, I2 38%). The total mortality rate from sevenstudies was 12% (95% CI 8%-18%, I2 55%). The parameters which represented ventricular dyssynchrony improved after CRT implantation. The overall response rate to CRT in CHD was 68%. Patients with systemic RV had a lower response rate to CRT when compared to patients with systemic LV. The total mortality rate after CRT implantation was 12%.

Correlation between Mean Platelet Volume and Gensini Score in Patients with Coronary Heart Disease in Different Diabetic States.

To investigate the correlation between mean platelet volume (MPV) levels and Gensini scores in stable coronary heart disease (CHD) patients with or without diabetes. A retrospective analysis was conducted on 2525 patients with stable CHD in Zhongshan Hospital, Fudan University. There were 1274 in the low MPV group and 1251 in the high MPV group, divided by a median MPV level of 10.9 fL. In the total population, 1605 patients were non-diabetic and 920 were diabetic. The severity of coronary artery disease was quantified using the Gensini score. The Gensini score was significantly higher in the high MPV group than in the low MPV group (p < 0.001). MPV levels increased significantly with the number of stenotic (>50%) coronary vessels (p < 0.001). The Spearman analysis showed a positive correlation between MPV and Gensini score (r = 0.189, p < 0.001), which was more significant in the diabetic subgroup (r = 0.232, p < 0.001). Receiver operating characteristic (ROC) curves were employed to assess the predictive value of MPV for high Gensini scores, using the median value of 32 points as the cutoff. MPV levels in the diabetes cohort exhibited a higher predictive value for high Gensini scores (area under the curve: 0.635 [0.614-0.657], p < 0.001). Multivariate linear regression analysis showed that diabetes and MPV were independently associated with Gensini scores. MPV levels in stable CHD patients can predict the severity of coronary artery stenosis. This correlation is more significant in the presence of diabetes.

Correlation between Apolipoprotein B Levels with Coronary Lesion Area Based on the Gensini Scores in Coronary Heart Disease Patients

Correlation between Apolipoprotein B Levels with Coronary Lesion Area Based on the Gensini Scores in Coronary Heart Disease Patients

Gene editing and cardiac disease modelling for the interpretation of genetic variants of uncertain significance in congenital heart disease

BackgroundGenomic sequencing in congenital heart disease (CHD) patients often discovers novel genetic variants, which are classified as variants of uncertain significance (VUS). Functional analysis of each VUS is required in specialised laboratories, to determine whether the VUS is disease causative or not, leading to lengthy diagnostic delays. We investigated stem cell cardiac disease modelling and transcriptomics for the purpose of genetic variant classification using a GATA4 (p.Arg283Cys) VUS in a patient with CHD.MethodsWe performed high efficiency CRISPR gene editing with homology directed repair in induced pluripotent stem cells (iPSCs), followed by rapid clonal selection with amplicon sequencing. Genetic variant and healthy matched control cells were compared using cardiomyocyte disease modelling and transcriptomics.ResultsGenetic variant and healthy cardiomyocytes similarly expressed Troponin T (cTNNT), and GATA4. Transcriptomics analysis of cardiomyocyte differentiation identified changes consistent with the patient’s clinical human phenotype ontology terms. Further, transcriptomics revealed changes in calcium signalling, and cardiomyocyte adrenergic signalling in the variant cells. Functional testing demonstrated, altered action potentials in GATA4 genetic variant cardiomyocytes were consistent with patient cardiac abnormalities.ConclusionsThis work provides in vivo functional studies supportive of a damaging effect on the gene or gene product. Furthermore, we demonstrate the utility of iPSCs, CRISPR gene editing and cardiac disease modelling for genetic variant interpretation. The method can readily be applied to other genetic variants in GATA4 or other genes in cardiac disease, providing a centralised assessment pathway for patient genetic variant interpretation.