Monitoring Of Cardiac Patients Research Articles

Predicting physical fitness levels from resting ECG data: a machine learning approach in cardiovascular assessment

Abstract Background Exercise Stress Testing (EST), an inexpensive noninvasive modality, is widely used for preliminary cardiovascular evaluation and ongoing monitoring of cardiac patients. The MET (Metabolic Equivalent of Task) score from EST, indicating physical fitness, is associated with overall mortality risk and is extremely helpful for preoperative evaluation. Artificial Intelligence (AI) advances, particularly Deep Learning (DL) for resting ECG analysis, have significantly improved cardiac diagnostic accuracy. Objectives This study explores AI's ability to predict MET scores from resting ECGs, aiming to streamline fitness assessments and detect early changes in fitness levels. Methods The current analysis encompasses 45,518 consecutive EST evaluations from 31,532 individual patients from 2017 to 2023. MET scores were automatically computed using an established formula, while interpretations by certified cardiologists provided a benchmark for the AI model. Poor fitness was defined as being within the lowest quartile of MET scores, adjusted for sex and age. A deep learning framework was developed to process a 10-second snippet of resting phase ECG in raw waveform, predicting the likelihood of diminished fitness and thus acting as a binary classifier. The efficacy of this Poor Fitness AI model (PF-AI model) was assessed through metrics such as the area under the receiver operating characteristic curve (AUROC), along with sensitivity, specificity, and accuracy rates. Results The average age of the study group was 55±10 years, predominantly male (68.8%, n = 31,337). Among them, 1,152 were identified as having poor fitness. Applying the model to the entire cohort through 5-fold cross-validation yielded a sensitivity of 78%, a specificity of 81%, and an AUROC of 0.87 in predicting poor fitness. Conclusions Leveraging merely 10 seconds of resting ECG data, the PF-AI model proves to be a robust tool in predicting poor fitness levels, comparable to the outcomes of comprehensive stress testing.

Recommendations of an expert group for the cardiac assessment of non-dystrophic myotonia adult patients treated with mexiletine

Mexiletine (NaMuscla™) is indicated for the symptomatic treatment of myotonia in adults with non-dystrophic myotonia. A cardiac assessment is required as mexiletine may have a pro-arrhythmic effect. Long-term safety data supporting the use of mexiletine in patients with non-dystrophic myotonia combined with the extensive clinical experience of an expert group resulted in creation of an algorithm for cardiac monitoring of patients treated with mexiletine. To define the treatment algorithm, several expert workshops including three neurologists, five cardiologists from different French neuromuscular reference centers and one pharmacologist from Italy were set up. These workshops aimed to define the screening and surveillance tools required to ensure the safe use of mexiletine in patients. The recommendations are based on the summary of product characteristics (SmPC), a review of the literature on the safety of mexiletine-treated patients with non-dystrophic myotonia, and the expertise of the authors. The expert group concluded that the cardiac safety profile of mexiletine in these patients appears to be similar to that in the general population. Therefore, patients with non-dystrophic myotonia treated with mexiletine should be monitored as per any patient with cardiac problems who are prescribed a class 1b anti-arrhythmic.

CDK4/6 inhibitor ribociclib induces cardiotoxicity in dynamic engineered heart tissues, mitigated by E2F1 overexpression

Abstract Funding Acknowledgements Type of funding sources: Public grant(s) – EU funding. Main funding source(s): European Research Council CDK4/6 inhibitor Ribociclib induces cardiotoxicity in dynamic engineered heart tissues, mitigated by E2F1 overexpression Background Ribociclib, a novel chemotherapeutic agent for metastatic breast cancer, functions as a cyclin-dependent kinase 4/6 (CDK4/6) inhibitor1. Its mechanism of action involves the CDK4/6-Rb-E2F1 pathway. Ribociclib use has very recently been associated with development of heart failure (HF)2, yet the causality of its cardiac effects remains to be explored. Aims This study aims to investigate ribociclib's cardiotoxic effects in dynamic human engineered heart tissues (dyn-EHTs), focusing on the CDK4/6-Rb-E2F1 axis. Methods and Results Dyn-EHTs were generated using human induced pluripotent stem cell derived cardiomyocytes (iPSC-CMs) and treated with repeated doses of ribociclib (7 µM) to mimic clinical drug administration. Post-treatment, dyn-EHTs exhibited a 17.0% (p<0.001) increase in tissue dilatation, an 8.9% (p<0.001) decrease in systolic force generation, and a 22.1% (p<0.001) increase in systolic stress, indicating significant cardiac dysfunction. Additionally, an increase in phosphorylation levels of Rb protein (Ser249 and Thr252) was observed (FC=0.445, p=0.009). Overexpression of E2F1 in iPSCs resulted in a threefold increase in E2F1 protein expression and successfully mitigated the ribociclib-induced tissue dilatation (p=0.007), decreased systolic force generation (p=0.005), and increase in systolic stress (p=0.004) making their performance comparable to healthy controls, as shown by linear regression analysis. Conclusions Our study demonstrates that ribociclib induces significant cardiotoxic effects in dyn-EHTs and iPSC-CMs through the CDK4/6-Rb-E2F1 pathway. The prevention of these effects by E2F1 overexpression highlights the pathway's involvement in ribociclib's cardiotoxic profile. These findings emphasize the need for careful cardiac monitoring in patients treated with CDK4/6 inhibitors and suggest further research into specific mechanisms of cardiotoxicity in cancer therapeutics.Graphical Abstract

Classification of the Cardiac Arrhythmia Using Combined Feature Selection Algorithms

The prediction of heart disease has gained great importance in recent years. Efficient monitoring of cardiac patients can save tremendous number of lives. This paper presents a method for classification and prediction of electrocardiogram data obtained from 452 patients representing the risk of cardiac arrhythmia. The aim of the study is to select highly related features with arrhythmia risk by using three different feature selection algorithms. In addition, various machine learning models are utilized for the classification task such as k-Nearest Neighbors (k-NN), Support Vector Machines (SVM) and Decision Tree (DT). The experimental results show that combination of a purposed feature selection method which later is called “Matched Selection” using SVM classifier outperforms other combinations and have an accuracy of 81.27% while k-NN and DT classifiers have an accuracy of 69.66% and 73.50% respectively. The study, in which detailed analyses are presented comparatively, is promising for the future studies.

The Metabolic Fingerprint of Doxorubicin-Induced Cardiotoxicity in Male CD-1 Mice Fades Away with Time While Autophagy Increases.

The cardiotoxicity of doxorubicin (DOX) may manifest at the beginning/during treatment or years after, compromising patients' quality of life. We intended to study the cardiac pathways one week (short-term, control 1 [CTRL1] and DOX1 groups) or five months (long-term, CTRL2 and DOX2 groups) after DOX administration in adult male CD-1 mice. Control groups were given saline, and DOX groups received a 9.0 mg/Kg cumulative dose. In the short-term, DOX decreased the content of AMP-activated protein kinase (AMPK) while the electron transfer flavoprotein-ubiquinone oxidoreductase (ETF-QO) increased compared to CTRL1, suggesting the upregulation of fatty acids oxidation. Moreover, mitofusin1 (Mfn1) content was decreased in DOX1, highlighting decreased mitochondrial fusion. In addition, increased B-cell lymphoma-2 associated X-protein (BAX) content in DOX1 pointed to the upregulation of apoptosis. Conversely, in the long-term, DOX decreased the citrate synthase (CS) activity and the content of Beclin1 and autophagy protein 5 (ATG5) compared to CTRL2, suggesting decreased mitochondrial density and autophagy. Our study demonstrates that molecular mechanisms elicited by DOX are modulated at different extents over time, supporting the differences on clinic cardiotoxic manifestations with time. Moreover, even five months after DOX administration, meaningful heart molecular changes occurred, reinforcing the need for the continuous cardiac monitoring of patients and determination of earlier biomarkers before clinical cardiotoxicity is set.

The Flt3-inhibitor quizartinib augments apoptosis and promotes maladaptive remodeling after myocardial infarction in mice

BackgroundTyrosine kinase inhibitors (TKIs) targeting fms-like tyrosine kinase 3 (Flt3) such as quizartinib were specifically designed for acute myeloid leukemia treatment, but also multi-targeting TKIs applied to solid tumor patients inhibit Flt3. Flt3 is expressed in the heart and its activation is cytoprotective in myocardial infarction (MI) in mice.ObjectivesWe sought to test whether Flt3-targeting TKI treatment aggravates cardiac injury after MI.Methods and resultsCompared to vehicle, quizartinib (10 mg/kg/day, gavage) did not alter cardiac dimensions or function in healthy mice after four weeks of therapy. Pretreated mice were randomly assigned to MI or sham surgery while receiving quizartinib or vehicle for one more week. Quizartinib did not aggravate the decline in ejection fraction, but significantly enhanced ventricular dilatation one week after infarction. In addition, apoptotic cell death was significantly increased in the myocardium of quizartinib-treated compared to vehicle-treated mice. In vitro, quizartinib dose-dependently decreased cell viability in neonatal rat ventricular myocytes and in H9c2 cells, and increased apoptosis as assessed in the latter. Together with H2O2, quizartinib potentiated the phosphorylation of the pro-apoptotic mitogen activated protein kinase p38 and augmented H2O2-induced cell death and apoptosis beyond additive degree. Pretreatment with a p38 inhibitor abolished apoptosis under quizartinib and H2O2.ConclusionQuizartinib potentiates apoptosis and promotes maladaptive remodeling after MI in mice at least in part via a p38-dependent mechanism. These findings are consistent with the multi-hit hypothesis of cardiotoxicity and make cardiac monitoring in patients with ischemic heart disease under Flt3- or multi-targeting TKIs advisable.

Heartbeat Detection in Gyrocardiography Signals without Concurrent ECG Tracings.

A heartbeat generates tiny mechanical vibrations, mainly due to the opening and closing of heart valves. These vibrations can be recorded by accelerometers and gyroscopes applied on a subject's chest. In particular, the local 3D linear accelerations and 3D angular velocities of the chest wall are referred to as seismocardiograms (SCG) and gyrocardiograms (GCG), respectively. These signals usually exhibit a low signal-to-noise ratio, as well as non-negligible amplitude and morphological changes due to changes in posture and the sensors' location, respiratory activity, as well as other sources of intra-subject and inter-subject variability. These factors make heartbeat detection a complex task; therefore, a reference electrocardiogram (ECG) lead is usually acquired in SCG and GCG studies to ensure correct localization of heartbeats. Recently, a template matching technique based on cross correlation has proven to be particularly effective in recognizing individual heartbeats in SCG signals. This study aims to verify the performance of this technique when applied on GCG signals. Tests were conducted on a public database consisting of SCG, GCG, and ECG signals recorded synchronously on 100 patients with valvular heart diseases. The results show that the template matching technique identified heartbeats in GCG signals with a sensitivity and positive predictive value (PPV) of 87% and 92%, respectively. Regression, correlation, and Bland-Altman analyses carried out on inter-beat intervals obtained from GCG and ECG (assumed as reference) reported a slope of 0.995, an intercept of 4.06 ms (R2 > 0.99), a Pearson's correlation coefficient of 0.9993, and limits of agreement of about ±13 ms with a negligible bias. A comparison with the results of a previous study obtained on SCG signals from the same database revealed that GCG enabled effective cardiac monitoring in significantly more patients than SCG (95 vs. 77). This result suggests that GCG could ensure more robust and reliable cardiac monitoring in patients with heart diseases with respect to SCG.

Cardiovascular toxicity induced by SSRIs: Analysis of spontaneous reports submitted to FAERS

Depression diagnoses have surged recently, and selective serotonin reuptake inhibitors (SSRIs) are the go-to treatment. However, studies indicate that long-term use of SSRIs can increase cardiovascular risk without systematic evaluation of the drug class. To offer clinical guidance, we performed an evaluation of the association between the six most commonly prescribed SSRIs and cardiovascular adverse events. Using the FDA Adverse Event Reporting System (FAERS) from Q1 2004 to Q2 2022, we conducted a disproportionality analysis and determined the magnitude of significant signals using statistical shrinkage transformations. Our study revealed that arrhythmias, torsades de pointes/QT prolongation, cardiomyopathy, and hypertension were among the most prevalent adverse events linked to SSRIs. Our analysis also showed a significant association between SSRIs and the aforementioned adverse events, with higher incidence in middle-aged and elderly patients and women. We further observed a rising trend in the incidence of arrhythmias, torsades de pointes/QT prolongation, and hypertension, highlighting the need for heightened cardiac monitoring in patients on SSRIs.

The Presence of Pneumonia Is Strongly Associated With Higher Prevalence of Non-ST-Elevation Myocardial Infarction Using a Large NIS Database.

Inflammation is a risk factor for myocardial infarction. Pneumonia leads to severe inflammatory response. Some studies suggest higher risk of myocardial infarction in patients with pneumonia. We used a large inpatient database (National Inpatient Sample) to evaluate this association. This study includes patients from a Nationwide Inpatient Sample hospital in 2005 to 2014 with International Classification of Diseases, Ninth Revision, and Clinical Modification codes consistent with pneumonia and non-ST elevation myocardial infarction (NSTEMI). Subjects were stratified into all hospitalized patients aged 30 and above. Univariate and multivariate analysis was performed adjusting for age, race, gender, tobacco use, diabetes mellitus, hypertension, and hyperlipidemia. NSTEMI was present in 3.2% of pneumonia patients versus 1.8% in the non-pneumonia population over 10-year period. For example, the 2005 database: [odds ratio (OR), 1.77; 95% confidence interval (CI), 1.73-1.80; P < 0.001]. For 2014, NSTEMI was present in 4.1% of pneumonia patients (PNA) versus 2.4% in the non-pneumonia population (OR, 1.72; 95% CI, 1.70-1.75; P < 0.001). NSTEMI remained independently associated with pneumonia following a multivariate analysis in 2005 (OR, 1.477; 95% CI, 1.447-1.508; P < 0.001) with a similar value in 2014 (OR, 1.445; 95% CI, 1.421-1.469; P < 0.001). Using a large inpatient database, we found that NSTEMI was strongly associated with PNA versus non-pneumonia population over a 10-year period. Suggesting acute inflammatory cytokines or hypoxia which occurs during lung infection may play a role in NSTEMI development, reinforcing the importance of acute cardiac monitoring in patients with PNA.

A novel method for assessing cardiac function in patients with coronary heart disease based on wrist pulse analysis

BackgroundThe timely assessment of B-type natriuretic peptide (BNP) marking chronic heart failure risk in patients with coronary heart disease (CHD) helps to reduce patients’ mortality.ObjectiveTo evaluate the potential of wrist pulse signals for use in the cardiac monitoring of patients with CHD.MethodsA total of 419 patients with CHD were assigned to Group 1 (BNP < 95 pg/mL, n = 249), 2 (95 < BNP < 221 pg/mL, n = 85), and 3 (BNP > 221 pg/mL, n = 85) according to BNP levels. Wrist pulse signals were measured noninvasively. Both the time-domain method and multiscale entropy (MSE) method were used to extract pulse features. Decision tree (DT) and random forest (RF) algorithms were employed to construct models for classifying three groups, and the models’ performance metrics were compared.ResultsThe pulse features of the three groups differed significantly, suggesting different pathological states of the cardiovascular system in patients with CHD. Moreover, the RF models outperformed the DT models in performance metrics. Furthermore, the optimal RF model was that based on a dataset comprising both time-domain and MSE features, achieving accuracy, average precision, average recall, and average F1-score of 90.900%, 91.048%, 90.900%, and 90.897%, respectively.ConclusionsThe wrist pulse detection technology employed in this study is useful for assessing the cardiac function of patients with CHD.

Effect of implantable cardiac monitors on preventing stroke: A systematic review and meta-analysis of randomized clinical trials.

Implantable cardiac monitors (ICM) can facilitate the detection of asymptomatic atrial fibrillation episodes. We performed a systematic review and meta-analysis to investigate whether ICM can prevent stroke in patients with prior stroke and risk factors for stroke. This study included randomized controlled trials comparing ICM with conventional (non-ICM) external cardiac monitoring in patients with prior stroke and risk factors for stroke. We searched Medline, Embase, and CENTRAL from inception until January 5, 2022, without language restriction. Quantitative pooling of the data was undertaken using a random-effects model. The primary outcome was ischemic stroke at the longest follow-up. Four trials comprising 7237 patients were included. ICM was significantly associated with decreased risk of ischemic stroke (RR 0.76; 95% CI, 0.59-0.97; moderate-quality evidence) in patients with prior stroke and risk factors for stroke. ICM was associated with higher detection of atrial fibrillation (RR 4.21, 95% CI 2.26-7.85) and use of oral anticoagulants (RR 2.29, 95% CI 2.07-2.55). ICM results in a significantly lower risk of ischemic stroke than conventional (non-ICM) external cardiac monitoring in patients with prior stroke and risk factors for stroke. Due to the clinical heterogeneity of study population and limited related studies, more trials were needed to furtherly explore the topic in patients with prior stroke or high risk of stroke.

Enhanced cardiovascular disease prediction model using random forest algorithm

Cardiovascular diseases (CVDs) such as hypertension, heart failure, stroke, and coronary artery disease are now the major causes of early death worldwide, particularly in low and middle-income countries. Early detection of these disorders could lower the number of people who die prematurely. Researchers have proposed many techniques for CVD prediction, such as data mining, machine learning (ML), and the Internet of Things (IoT), for the early detection and monitoring of cardiac patients. Although these techniques are suggested and sometimes used, there is still much worry regarding their efficacy in situations where the error rate is high and accuracy is doubtful. As a result, it is necessary to select a prediction technique that can deliver more accuracy and fewer errors. This paper proposes an effective ensemble method based on the Random Forest (RF) algorithm for improving accuracy by combining multiple feature selection techniques. A classification model is built using training datasets and produces several decision trees. These datasets adjust for any missing data and include estimates of important classification variables. Data preparation and feature selection approaches such as correlation coefficients and data mining feature selection techniques are applied to remove outliers. Finally, a cardiovascular disease prediction model is created, and the model's increased performance accuracy is tested using a confusion matrix. A dataset from the Kaggle repository with 1025 data points and 14 attributes is used. The saved data are then preprocessed, yielding a dataset of 769 records and 13 variables that are evaluated using RF and compared to various models such as K-Nearest Neighbor (K-NN), Support Vector Machine (SVM), and Logistic Regression (LR) for the prediction of heart disorders. After employing several techniques, the proposed model achieves an accuracy of 99%, which shows a significant improvement over the other assessed models.

Insertable cardiac monitoring devices versus external cardiac monitoring for detecting atrial fibrillation and preventing the recurrence of stroke: A systematic review and meta-analysis

BackgroundAtrial Fibrillation (AF) is a major risk factor for stroke, which is the second leading cause of death worldwide. It remains uncertain whether insertable cardiac monitors (ICMs) enhance the ability to recognize AF over external cardiac monitoring in patients who have experienced a stroke. AimWe conducted a systematic review and meta-analysis to determine whether ICM devices are more effective than external cardiac monitoring for the detection of AF in stroke patients. MethodsWe included studies that reported an AF detection rate in stroke patients with a follow-up of at least 12 months. We analyzed the data of 1233 patients from 3 randomized control trials (RCTs). ResultsWhen compared to external cardiac monitoring, ICM devices (Medtronic Reveal LINQ and Reveal XT) showed a significantly higher detection rate of AF (RR = 5.04, 95% CI = 2.93–8.68; p < 0.05; ARR = 10.47%, NNT = 10). The ICM arm had significantly higher usage of oral anticoagulants (OAC) as compared to the control arm. (RR = 2.76, 95% CI = 1.89–4.02, p < 0.05). Additionally, ICM usage was associated with a higher incidence of mild to moderate adverse events (RR = 10.52, 95% CI =1.35–82.14; p = 0.02) and a higher number of severe adverse events as compared to the control arm (RR = 7.61, 95% CI = 1.36–42.51; p = 0.02). ConclusionICM devices are associated with better detection rates of AF and higher usage of OAC as compared to external cardiac monitoring in post-stroke patients. However, ICM insertion is associated with a higher incidence of mild/moderate and severe adverse effects.

Integrin α7 Mutations Are Associated With Adult-Onset Cardiac Dysfunction in Humans and Mice.

Background Integrin α7β1 is a major laminin receptor in skeletal and cardiac muscle. In skeletal muscle, integrin α7β1 plays an important role during muscle development and has been described as an important modifier of skeletal muscle diseases. The integrin α7β1 is also highly expressed in the heart, but its precise role in cardiac function is unknown. Mutations in the integrin α7 gene (ITGA7) have been reported in children with congenital myopathy. Methods and Results In this study, we described skeletal and cardiac muscle pathology in Itga7-/- mice and 5 patients from 2 unrelated families with ITGA7 mutations. Proband in family 1 presented a homozygous c.806_818del [p.S269fs] variant, and proband in family 2 was identified with 2 intron variants in the ITGA7 gene. The complete absence of the integrin α7 protein in muscle supports the ITGA7 mutations are pathogenic. We performed electrocardiography, echocardiography, or cardiac magnetic resonance imaging, and histological biopsy analyses in patients with ITGA7 deficiency and Itga7-/- mice. The patients exhibited cardiac dysrhythmia and dysfunction from the third decade of life and late-onset respiratory insufficiency, but with relatively mild limb muscle involvement. Mice demonstrated corresponding abnormalities in cardiac conduction and contraction as well as diaphragm muscle fibrosis. Conclusions Our data suggest that loss of integrin α7 causes a novel form of adult-onset cardiac dysfunction indicating a critical role for the integrin α7β1 in normal cardiac function and highlights the need for long-term cardiac monitoring in patients with ITGA7-related congenital myopathy.

Improving cardiac monitoring in patients with early-stage breast cancer receiving cardiotoxic chemotherapy in a multidisciplinary cancer center.

191 Background: Patients with early stage breast cancer commonly receive anthracycline and anti-Her2 directed therapies which can result in cardiotoxicity, making cardiac monitoring crucial. In 2018, our rate of obtaining a follow up echocardiogram in this patient population was 38%. Subsequently, use of myocardial strain imaging in conjunction with echocardiography became available at our institution, allowing for potential earlier detection of cardiac dysfunction. We aimed to increase utilization of strain imaging and rate of follow up echocardiogram monitoring to at least 50% in hopes of enhancing prevention efforts. Methods: We developed a standardized protocol for cardiac monitoring in patients receiving cardiotoxic chemotherapy. We provided education to staff and workflow modification to include standard orders for strain echocardiogram in all relevant chemotherapy plans. Chart review for Stage 1-3 breast cancer patients who received anthracycline or trastuzumab based therapy at our ambulatory cancer center from January 2019 to December 2021 was performed. Completion of follow up echocardiogram and rate of strain imaging before and after July 2020 was assessed, as this is when strain imaging became widely available. Results: Rates of obtaining baseline echocardiogram were excellent. Rates of strain echocardiogram use improved from 26.3% to 97.9% following July 2020. Follow up echocardiograms were obtained regularly in those receiving trastuzumab based therapy before and after July 2020 at rates of 91.8% and 87.5%. Rates of follow up echocardiograms in those receiving anthracycline-based therapy also improved to our goal of greater than 50%, but was lower than the trastuzumab group at 57%. However, assessment of follow up cardiac imaging in the 2021 treatment group is still ongoing. Conclusions: We successfully implemented a program to standardize cardiac monitoring in patients undergoing cardiotoxic chemotherapy for breast cancer at our institution. We anticipate this will enhance detection of cardiotoxicity and utilization of consultative cardio-oncology services. Additional efforts to improve follow up cardiac imaging through collaboration with our survivorship program are ongoing.[Table: see text]

European Stroke Organisation (ESO) guideline on screening for subclinical atrial fibrillation after stroke or transient ischaemic attack of undetermined origin.

We aimed to provide practical recommendations for the screening of subclinical atrial fibrillation (AF) in patients with ischaemic stroke or transient ischaemic attack (TIA) of undetermined origin. These guidelines are based on the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) methodology. Five relevant Population, Intervention, Comparator, Outcome questions were defined by a multidisciplinary module working group (MWG). Longer duration of cardiac rhythm monitoring increases the detection of subclinical AF, but the optimal monitoring length is yet to be defined. We advise longer monitoring to increase the rate of anticoagulation, but whether longer monitoring improves clinical outcomes needs to be addressed. AF detection does not differ from in- or out-patient ECG-monitoring with similar monitoring duration, so we consider it reasonable to initiate in-hospital monitoring as soon as possible and continue with outpatient monitoring for more than 48 h. Although insertable loop recorders (ILR) increase AF detection based on their longer monitoring duration, comparison with non-implantable ECG devices for similar monitoring time is lacking. We suggest the use of implantable devices, if feasible, for AF detection instead of non-implantable devices to increase the detection of subclinical AF. There is weak evidence of a useful role for blood, ECG and brain imaging biomarkers for the identification of patients at high risk of AF. In patients with patent foramen ovale, we found insufficient evidence from RCT, but prolonged cardiac monitoring in patients >55 years is advisable for subclinical AF detection. To conclude, in adult patients with ischaemic stroke or TIA of undetermined origin, we recommend longer duration of cardiac rhythm monitoring of more than 48 h and if feasible with IRL to increase the detection of subclinical AF.

Can Seismocardiogram Fiducial Points Be Used for the Routine Estimation of Cardiac Time Intervals in Cardiac Patients?

The indexes of cardiac mechanics can be derived from the cardiac time intervals, CTIs, i.e., the timings among the opening and closure of the aortic and mitral valves and the Q wave in the ECG. Traditionally, CTIs are estimated by ultrasound (US) techniques, but they may also be more easily assessed by the identification of specific fiducial points (FPs) inside the waveform of the seismocardiogram (SCG), i.e., the measure of the thorax micro-accelerations produced by the heart motion. While the correspondence of the FPs with the valve movements has been verified in healthy subjects, less information is available on whether this methodology may be routinely employed in the clinical practice for the monitoring of cardiac patients, in which an SCG waveform distortion is expected because of the heart dysfunction. In this study we checked the SCG shape in 90 patients with myocardial infarction (MI), heart failure (HF), or transplanted heart (TX), referred to our hospital for rehabilitation after an acute event or after surgery. The SCG shapes were classified as traditional (T) or non-traditional (NT) on whether the FPs were visible or not on the basis of nomenclature previously proposed in literature. The T shape was present in 62% of the patients, with a higher ∓ prevalence in MI (79%). No relationship was found between T prevalence and ejection fraction (EF). In 20 patients with T shape, we checked the FPs correspondence with the real valve movements by concomitant SCG and US measures. When compared with reference values in healthy subjects available in the literature, we observed that the Echo vs. FP differences are significantly more dispersed in the patients than in the healthy population with higher differences for the estimation of the mitral valve closure (−17 vs. 4 ms on average). Our results indicate that not every cardiac patient has an SCG waveform suitable for the CTI estimation, thus before starting an SCG-based CTI monitoring a preliminary check by a simultaneous SCG-US measure is advisable to verify the applicability of the methodology.

Prospective real-time evaluation of the QTc interval variation after low-dose droperidol among emergency department patients.

To assess the QTc interval variation after low-dose droperidol in a population of undifferentiated, stable, and non-agitated patients receiving droperidol in the emergency department. Prospective cohort study of patients aged ≥12years of age who received low-dose droperidol (≤ 2.5mg) for indications other than acute behavioral disturbances. QTc intervals were monitored in real-time during pre-specified observation periods in the ED. Primary outcome was variation of QTc interval after droperidol administration, defined as the maximum delta (change) of QTc interval. Other outcomes included proportion of patients with a QTc≥500ms after droperidol, delta≥+60ms, and incidence of clinical adverse events. Patients were monitored up to 30min after IV bolus and up to 46min after infusion. A total of 68 patients were included (mean age 42.1years, 66.2% females). The median dose of droperidol was 1.875mg (range 0.625mg, 2.5mg) and 94.1% received droperidol for headache management. Most patients received droperidol as a 2-min bolus (n=41, 60.3%). The mean maximum delta of QTc interval after droperidol across all 68 patients was +29.9ms (SD 15). A total of 12 patients (17.6%) experienced a QTc interval≥500ms during the observation period after droperidol, and 3 patients (4.4%) had a delta QTc≥+60ms. There were no serious arrhythmias, such as TdP, or deaths among the 68 participants in this study (0/68). However, 13.2% (n=9) had at least one non-serious adverse event including restlessness and/or anxiety. The QTc interval slightly increased after droperidol administration, but these prolongations were brief, mostly below 500msec and did not lead to serious arrhythmias. The yield of continuous cardiac monitoring in patients receiving low doses of droperidol is likely low.

Clinical and genetic features of infancy-onset congenital myopathies from a Chinese paediatric centre

BackgroundCongenital myopathies are a group of rare neuromuscular diseases characterized by specific histopathological features. The relationship between the pathologies and the genetic causes is complex, and the prevalence of myopathy-causing genes varies among patients from different ethnic groups. The aim of the present study was to characterize congenital myopathies with infancy onset among patients registered at our institution.MethodThis retrospective study enrolled 56 patients based on the pathological and/or genetic diagnosis. Clinical, histopathological and genetic features of the patients were analysed with long-term follow-up.ResultsTwenty-six out of 43 patients who received next-generation sequencing had genetic confirmation, and RYR1 variations (12/26) were the most prevalent. Eighteen novel variations were identified in 6 disease-causing genes, including RYR1, NEB, TTN, TNNT1, DNM2 and ACTA1. Nemaline myopathy (17/55) was the most common histopathology. The onset ages ranged from birth to 1 year. Thirty-one patients were followed for 3.83 ± 3.05 years (ranging from 3 months to 11 years). No patient died before 1 year. Two patients died at 5 years and 8 years respectively. The motor abilities were stable or improved in 23 patients and deteriorated in 6 patients. Ten (10/31) patients developed respiratory involvement, and 9 patients (9/31) had mildly abnormal electrocardiograms and/or echocardiograms.ConclusionThe severity of congenital myopathies in the neonatal/infantile period may vary in patients from different ethnic groups. More concern should be given to cardiac monitoring in patients with congenital myopathies even in those with static courses.

A Randomized Trial Comparing 3- versus 4-Monthly Cardiac Monitoring in Patients Receiving Trastuzumab-Based Chemotherapy for Early Breast Cancer.

Purpose: The optimal frequency for cardiac monitoring of left ventricular ejection fraction (LVEF) in patients receiving trastuzumab-based therapy for early breast cancer (EBC) is unknown. We conducted a randomized controlled trial comparing 3- versus 4-monthly cardiac monitoring. Patients and Method: Patients scheduled to receive trastuzumab-containing cancer therapy for EBC with normal (>53%) baseline LVEF were randomized to undergo LVEF assessments every 3 or 4 months. The primary outcome was the change in LVEF from baseline. Secondary outcomes included the rate of cardiac dysfunction (defined as a decrease in the LVEF of ≥10 percentage points, to a value <53%), delays in or discontinuation of trastuzumab therapy, and cardiology referral. Results: Of the 200 eligible and enrolled patients, 100 (50%) were randomized to 3-monthly and 100 (50%) to 4-monthly cardiac monitoring. Of these patients, 98 and 97 respectively underwent at least one cardiac scan. The estimated mean difference in LVEF from baseline was −0.94% (one-sided 95% lower bound: −2.14), which exceeded the pre-defined non-inferiority margin of −4%. There were also no significant differences between the two study arms for any of the secondary endpoints. The rate of detection of cardiac dysfunction was 16.3% (16/98) and 12.4% (12/97) in the 3- and 4-monthly arms, respectively (95% CI: 4.0 [−5.9, 13.8]). Conclusions: Cardiac monitoring every 4 months was deemed non-inferior to that every 3 months in patients with HER2-positive EBC being treated with trastuzumab-based therapy. Given its costs and inconvenience, cardiac monitoring every 4 months should be considered standard practice. Registration: NCT02696707, 18 February 2016.