Left Ventricle Myocardial Work Correlated with Functional Capacity in Severe Rheumatic Mitral Stenosis with Preserved Left Ventricular Ejection Fraction.

Background and Aims: Functional capacity is reduced in mitral stenosis (MS) patients. Previous studies showed a correlation between left atrial strain and functional capacity in this population. However, currently, no left ventricle (LV) echocardiographic parameters were associated with functional capacity in patients with MS. Noninvasive LV pressure-strain loop analysis is a new echocardiographic method for evaluating LV function, integrating longitudinal strain from speckle-tracking analysis and noninvasively measured blood pressure to estimate myocardial work (MW) that overcomes the preload-dependent characteristics conventional parameters by integrating afterload. This study aimed to evaluate the association between MW and functional capacity measured using exercise tests in patients with severe MS and preserved LV ejection fraction (LVEF). Methods: Adult patients with symptomatic severe rheumatic MS (mitral valve area <1.5 cm2), and preserved LVEF (>50%) and sinus rhythm who underwent echocardiography and exercise stress test in our hospital from 2019 to 2021 were included. Exclusion criteria were suboptimal image quality for myocardial deformation analysis, significant mitral regurgitation or aortic valve lesions, coronary artery disease, intracardiac shunt, and atrial fibrillation. Standard echocardiographic parameters were measured, and all MW parameters were included. Exercise treadmill testing was performed using the modified Bruce protocol. Results: A total of 33 individuals with isolated severe rheumatic MS in sinus rhythm (age 39.8 ± 9.8 years) were included in the study. Patients with severe isolated MS showed significantly impaired LV-global longitudinal strain values compared to normal reference values. Furthermore, patients with severe MS showed significantly lower values of global work index, global constructive work, and efficiency compared to normal values and higher wasted work. Global work efficiency was significantly correlated to the duration of exercise (P = 0.025, Pearson's r = 0.389). Conclusions: In stable patients with isolated severe mitral stenosis, MW efficiency significantly correlated with functional capacity measured objectively through exercise testing.

Hypothermic and cryogenic preservation of cardiac tissue-engineered constructs.

Cardiac tissue engineering (cTE) has already advanced towards the first clinical trials, investigating safety and feasibility of cTE construct transplantation in failing hearts. However, the lack of well-established preservation methods poses a hindrance to further scalability, commercialization, and transportation, thereby reducing their clinical implementation. In this study, hypothermic preservation (4 °C) and two methods for cryopreservation (i.e., a slow and fast cooling approach to -196 °C and -150 °C, respectively) were investigated as potential solutions to extend the cTE construct implantation window. The cTE model used consisted of human induced pluripotent stem cell-derived cardiomyocytes and human cardiac fibroblasts embedded in a natural-derived hydrogel and supported by a polymeric melt electrowritten hexagonal scaffold. Constructs, composed of cardiomyocytes of different maturity, were preserved for three days, using several commercially available preservation protocols and solutions. Cardiomyocyte viability, function (beat rate and calcium handling), and metabolic activity were investigated after rewarming. Our observations show that cardiomyocytes' age did not influence post-rewarming viability, however, it influenced construct function. Hypothermic preservation with HypoThermosol® ensured cardiomyocyte viability and function. Furthermore, fast freezing outperformed slow freezing, but both viability and function were severely reduced after rewarming. In conclusion, whereas long-term preservation remains a challenge, hypothermic preservation with HypoThermosol® represents a promising solution for cTE construct short-term preservation and potential transportation, aiding in off-the-shelf availability, ultimately increasing their clinical applicability.

Stress hyperglycemia and poor outcomes in patients with ST-elevation myocardial infarction: a systematic review and meta-analysis.

Background: Hyperglycemia, characterized by elevated blood glucose levels, is frequently observed in patients with acute coronary syndrome, including ST-elevation myocardial infarction (STEMI). There are conflicting sources regarding the relationship between hyperglycemia and outcomes in STEMI patients. We aimed to compile evidence to assess the association between hyperglycemia and adverse outcomes. Methods: We conducted a comprehensive search for articles on PubMed and Embase using search strategies which yielded 4,061 articles. After full-text screening, 66 articles were included for systematic review, and 62 articles were further selected for meta-analysis. Results: The 66 included articles spanned the years 2005-2023. Of these, 45 articles reported admission blood glucose, 13 articles used HbA1c, and 7 articles studied fasting blood glucose. Most studies defined STEMI with primary PCI as their inclusion criteria. Mortality was the most often outcome reported related to hyperglycemia. Overall, 55 (83.3%) studies were at low risk of bias. Both admission and fasting blood glucose were significantly related to short- and long-term mortality after STEMI, with a pooled risk ratio (RR) of 3.02 (95%CI: 2.65-3.45) and 4.47 (95% CI: 2.54-7.87), respectively. HbA1c showed substantial association with long-term mortality (HR 1.69, 95% CI: 1.31-2.18)) with a pooled RR of 1.58 (95% CI 1.26-1.97). In subsequent analyses, admission hyperglycemia was associated with an increased risk of reinfarction (pooled RR 1.69, 95% CI 1.31-2.17), heart failure (pooled RR 1.56, 95% CI: 1.37-1.77), cardiogenic shock (pooled RR 3.68, 95% CI 2.65-5.11), repeat PCI or stent thrombosis (pooled RR 1.99, 95% CI 1.21-3.28), and composite major adverse cardiac and cerebrovascular events (MACCE) (pooled RR 1.99, 95% CI: 1.54-2.58). Conclusions: Our study demonstrated that hyperglycemia has a strong association with poor outcomes after STEMI. Admission and fasting blood glucose are predictors for short-term outcomes, while HbA1c is more appropriate for predicting longer-term outcomes in STEMI patients. Systematic Review Registration: PROSPERO 2021 (CRD42021292985).

In-hospital mortality of patients with acute coronary syndrome (ACS) after implementation of national health insurance (NHI) in Indonesia.

BACKGROUND: The National Health Insurance (NHI) was implemented in Indonesia in 2014, and cardiovascular diseases are one of the diseases that have overburdened the healthcare system. However, data concerning the relationship between NHI and cardiovascular healthcare in Indonesia are scarce. We aimed to describe changes in cardiovascular healthcare after the implementation of the NHI while determining whether the implementation of the NHI is related to the in-hospital mortality of patients with acute coronary syndrome (ACS). METHODS: This is a retrospective comparative study of two cohorts in which we compared the data of 364 patients with ACS from 2013 to 2014 (Cohort 1), before and early after NHI implementation, with those of 1142 patients with ACS from 2018 to 2020 (Cohort 2), four years after NHI initiation, at a tertiary cardiac center in Makassar, Indonesia. We analyzed the differences between both cohorts using chi-square test and Mann-Whitney U test. To determine the association between NHI and in-hospital mortality, we conducted multivariable logistic regression analysis. RESULTS: We observed an increase in NHI users (20.1% to 95.6%, p < 0.001) accompanied by a more than threefold increase in patients with ACS admitted to the hospital in Cohort 2 (from 364 to 1142, p < 0.001). More patients with ACS received invasive treatment in Cohort 2, with both thrombolysis and percutaneous coronary intervention (PCI) rates increasing more than twofold (9.2% to 19.2%; p < 0.001). There was a 50.8% decrease in overall in-hospital mortality between Cohort 1 and Cohort 2 (p < 0.001). CONCLUSIONS: This study indicated the potential beneficial effect of universal health coverage (UHC) in improving cardiovascular healthcare by providing more accessible treatment. It can provide evidence to urge the Indonesian government and other low- and middle-income nations dealing with cardiovascular health challenges to adopt and prioritize UHC.

Detection of acute coronary occlusion with a novel mobile electrocardiogram device: a pilot study.

Aims: Many portable electrocardiogram (ECG) devices have been developed to monitor patients at home, but the majority of these devices are single lead and only intended for rhythm disorders. We developed the miniECG, a smartphone-sized portable device with four dry electrodes capable of recording a high-quality multi-lead ECG by placing the device on the chest. The aim of our study was to investigate the ability of the miniECG to detect occlusive myocardial infarction (OMI) in patients with chest pain. Methods and results: Patients presenting with acute chest pain at the emergency department of the University Medical Center Utrecht or Meander Medical Center, between May 2021 and February 2022, were included in the study. The clinical 12-lead ECG and the miniECG before coronary intervention were recorded. The recordings were evaluated by cardiologists and compared the outcome of the coronary angiography, if performed. A total of 369 patients were measured with the miniECG, 46 of whom had OMI. The miniECG detected OMI with a sensitivity and specificity of 65 and 92%, compared with 83 and 90% for the 12-lead ECG. Sensitivity of the miniECG was similar for different culprit vessels. Conclusion: The miniECG can record a multi-lead ECG and rule-in ST-segment deviation in patients with occluded or near-occluded coronary arteries from different culprit vessels without many false alarms. Further research is required to add automated analysis to the recordings and to show feasibility to use the miniECG by patients at home.

ECG-only explainable deep learning algorithm predicts the risk for malignant ventricular arrhythmia in phospholamban cardiomyopathy.

BACKGROUND: Phospholamban (PLN) p.(Arg14del) variant carriers are at risk for development of malignant ventricular arrhythmia (MVA). Accurate risk stratification allows timely implantation of intracardiac defibrillators and is currently performed with a multimodality prediction model. OBJECTIVE: This study aimed to investigate whether an explainable deep learning-based approach allows risk prediction with only electrocardiogram (ECG) data. METHODS: A total of 679 PLN p.(Arg14del) carriers without MVA at baseline were identified. A deep learning-based variational auto-encoder, trained on 1.1 million ECGs, was used to convert the 12-lead baseline ECG into its FactorECG, a compressed version of the ECG that summarizes it into 32 explainable factors. Prediction models were developed by Cox regression. RESULTS: The deep learning-based ECG-only approach was able to predict MVA with a C statistic of 0.79 (95% CI, 0.76-0.83), comparable to the current prediction model (C statistic, 0.83 [95% CI, 0.79-0.88]; P = .054) and outperforming a model based on conventional ECG parameters (low-voltage ECG and negative T waves; C statistic, 0.65 [95% CI, 0.58-0.73]; P < .001). Clinical simulations showed that a 2-step approach, with ECG-only screening followed by a full workup, resulted in 60% less additional diagnostics while outperforming the multimodal prediction model in all patients. A visualization tool was created to provide interactive visualizations (https://pln.ecgx.ai). CONCLUSION: Our deep learning-based algorithm based on ECG data only accurately predicts the occurrence of MVA in PLN p.(Arg14del) carriers, enabling more efficient stratification of patients who need additional diagnostic testing and follow-up.

Automatic triage of twelve-lead electrocardiograms using deep convolutional neural networks: a first implementation study.

Aims: Expert knowledge to correctly interpret electrocardiograms (ECGs) is not always readily available. An artificial intelligence (AI)-based triage algorithm (DELTAnet), able to support physicians in ECG prioritization, could help reduce current logistic burden of overreading ECGs and improve time to treatment for acute and life-threatening disorders. However, the effect of clinical implementation of such AI algorithms is rarely investigated. Methods and results: Adult patients at non-cardiology departments who underwent ECG testing as a part of routine clinical care were included in this prospective cohort study. DELTAnet was used to classify 12-lead ECGs into one of the following triage classes: normal, abnormal not acute, subacute, and acute. Performance was compared with triage classes based on the final clinical diagnosis. Moreover, the associations between predicted classes and clinical outcomes were investigated. A total of 1061 patients and ECGs were included. Performance was good with a mean concordance statistic of 0.96 (95% confidence interval 0.95-0.97) when comparing DELTAnet with the clinical triage classes. Moreover, zero ECGs that required a change in policy or referral to the cardiologist were missed and there was a limited number of cases predicted as acute that did not require follow-up (2.6%). Conclusion: This study is the first to prospectively investigate the impact of clinical implementation of an ECG-based AI triage algorithm. It shows that DELTAnet is efficacious and safe to be used in clinical practice for triage of 12-lead ECGs in non-cardiology hospital departments.

Predictors of major adverse cardiac events among patients with chest pain and low HEART score in the emergency department.

AIM: For patients who present to the emergency departments (ED) with undifferentiated chest pain, the risk of major adverse cardiac events (MACE) may be underestimated in low-HEART score patients. We aimed to identify characteristics of patients who were classified as low risk by HEART score but subsequently developed MACE at 6 weeks. METHODS: We studied a multiethnic cohort of patients who presented with chest pain arousing suspicion of acute coronary syndrome to EDs in the Netherlands and Singapore. Patients were risk-stratified using HEART score and followed up for MACE at 6 weeks. Risk factors of developing MACE despite low HEART scores (scores 0-3) were identified using logistic and Cox regression models. RESULTS: Among 1376 (39.8%) patients with low HEART scores, 63 (4.6%) developed MACE at 6 weeks. More males (53/806, 6.6%) than females (10/570, 2.8%) with low HEART score developed MACE. There was no difference in outcomes between ethnic groups. Among low-HEART score patients with 2 points for history, 21% developed MACE. Among low-HEART score patients with 1 point for troponin, 50% developed MACE, while 100% of those with 2 points for troponin developed MACE. After adjusting for HEART score and potential confounders, male sex was independently associated with increased odds (OR 4.12, 95%CI 2.14-8.78) and hazards (HR 3.93, 95%CI 1.98-7.79) of developing MACE despite low HEART score. CONCLUSION: Male sex, highly suspicious history and elevated troponin were disproportionately associated with MACE. These characteristics should prompt clinicians to consider further investigation before discharge.

Detection of Ischemic ST-Segment Changes Using a Novel Handheld ECG Device in a Porcine Model.

Background: Portable, smartphone-sized electrocardiography (ECG) has the potential to reduce time to treatment for patients suffering acute cardiac ischemia, thereby lowering the morbidity and mortality. In the UMC Utrecht, a portable, smartphone-sized, multi-lead precordial ECG recording device (miniECG 1.0, UMC Utrecht) was developed. Objectives: The purpose of this study was to investigate the ability of the miniECG to capture ischemic ECG changes in a porcine coronary occlusion model. Methods: In 8 animals, antero-septal myocardial infarction was induced by 75-minute occlusion of the left anterior descending artery, after the first or second diagonal. MiniECG and 12-lead ECG recordings were acquired simultaneously before, during and after coronary artery occlusion and ST-segment deviation was evaluated. Results: During the complete occlusion and reperfusion period, miniECG showed large ST-segment deviation in comparison to 12-lead ECG. MiniECG ST-segment deviation was observed within 1 minute for most animals. The miniECG was positive for ischemia (ie, ST-segment deviation ≥1 mm) for 99.7% (Q1-Q3: 99.6%-99.9%) of the occlusion time, while the 12-lead was only positive for 79.8% (Q1-Q3: 81.1%-98.7%) of the time (P = 0.018). ST-segment deviation reached maxima of 10.5 mm [95% CI: 6.5-14.5 mm] vs 5.0 mm [95% CI: 2.0-8.0 mm] for the miniECG vs 12-lead ECG, respectively. Conclusions: MiniECG ST-segment deviation was observed early and was of large magnitude during 75 minutes of porcine transmural antero-septal infarction. The miniECG was positive for ischemia for the complete occlusion period. These findings demonstrate the potential of the miniECG in the detection of cardiac ischemia. Although clinical research is required, data suggests that the miniECG is a promising tool for the detection of cardiac ischemia.

Prognostic implications of invasive hemodynamics during cardiac resynchronization therapy: Stroke work outperforms dP/dtmax.

Background: Invasive measurements of left ventricular (LV) hemodynamic performance can evaluate acute response to cardiac resynchronization therapy (CRT). Objective: The study sought to determine which metric, maximum rate of LV pressure rise (LV dP/dtmax) or LV stroke work (LVSW), is more strongly associated with long-term prognosis. Methods: CRT patients were prospectively included from 3 academic centers. Invasive pressure-volume loop measurements during implantation were performed, and LV dP/dtmax and LVSW were determined at baseline and during biventricular pacing (BVP) as well as their relative increase (%Δ). Hazard ratios (HRs) for the primary outcome of 8-year all-cause mortality were derived using Cox proportional hazards. The secondary endpoint was echocardiographic response, defined as 6-month LV end-systolic volume reduction ≥15%. Results: Paired data from 82 patients were analyzed (67% male; age 66 ± 9 years; QRS duration 158 ± 22 ms, median survival time 72 months). Survival was better when LVSW during BVP was ≥4400 mL∙mm Hg (HR 0.21, 95% CI 0.08-0.58, P < .003) or when ΔLVSW% was ≥10% (HR 0.22, 95% CI 0.08-0.65, P = .006). In multivariate analysis, following direct comparison of continuous measures of acute ΔLV dP/dtmax% and ΔLVSW%, only ΔLVSW% remained associated with the primary endpoint (HR 0.982 per percentage point, P = .028). In contrast to LV dP/dtmax (all P > .05), significant associations with echocardiographic response were found for stroke work during BVP (area under the receiver-operating characteristic curve 0.745, P = .001) and ΔLVSW% (area under the receiver-operating characteristic curve 0.803, P < .001). Conclusion: Stroke work, but not LV dP/dtmax, is consistently associated with long-term prognosis and response after CRT. Our results therefore favor the use of stroke work as the hemodynamic parameter to predict long-term outcome after CRT.