Our aim was to analyze the association of the presence of public physical activity (PA) facilities and participation in public PA programs with leisure-time PA, with an emphasis on the moderating role of educational level and income.We used data of 88,531 adults , with a mean age of 47.2 ± 17.1y, from the 2019 Brazilian National Health Survey. Leisure-time PA (dichotomized considering 150 min/week), the presence of a public PA facility near the household (yes or no), participation in public PA programs (yes or no), educational level (divided into quintiles) and per capita income (divided into quintiles) were all self-reported through interviews. Adjusted logistic regression models were used for the analyses.The presence of public PA facilities near the household and the participation in public PA programs were associated with higher leisure-time PA among all quintiles of income and educational level. However, multiplicative interactions revealed that participating in PA programs  and the presence of public PA facilities near the household  were more associated with higher odds of being active in the leisure-time among the lowest quintile of educational level.The presence of public PA facilities and participation in public PA programs are environmental correlates that may be relevant for designing effective public health interventions to reduce social inequalities in leisure-time PA among adults in low-income areas. Physical activity (PA) is a protective factor for different health outcomes, including cardiovascular diseases, mental disorders, cancer and all-cause mortality , 2. HoweSpecifically in Brazil, leisure-time PA has increased over the years , 8, but However, the majority of the previous studies did not include nationally representative samples when testing the association of the presence of public PA facilities and participation in public PA programs with leisure-time PA. In addition, the role of income and educational level in this association is not clear. Therefore, we aimed to analyze the association of the presence of public PA facilities and participation in public PA programs with leisure-time PA, with an emphasis on the moderating role of educational level and income. We hypothesize that the presence of public PA facilities and participation in public PA programs will be associated with leisure-time PA and considering the lower opportunities among people with lower educational level and income, the presence of public PA facilities and participation in public PA programs could have a stronger association with leisure-time PA in these groups.We used data from the Brazilian National Health Survey, which was a cross-sectional epidemiological study, conducted with a nationally representative sample of people ≥15 years old, during 2019 in Brazil. The sampling process was in three stages. Firstly, census tracts were randomly selected; next, households were randomly selected; and finally, in the households, one inhabitant (≥15 years old) was randomly selected. More details of the sampling process and weighting have been previously published elsewhere [Leisure-time PA was self-reported based on a questionnaire previously validated for Brazilian adults . The queThe participation in public PA programs was assessed through the dichotomic questions (yes/no): “Do you know of any public program to encourage the practice of physical activity in your city?” and “Do you participate in this public program to encourage the practice of physical activity in your city?”. The presence of public PA facilities near the household was also assessed through the dichotomic question (yes/no): “Is there a public place close to your home  to walk, exercise or play sports?”. The last two questions were adopted as exposures.The per capita income and educational level were categorized as quintiles. For the quintiles of income, we considered the household per capita income in monetary value and divided into quintiles, which the first quintile (Q1) represents the lowest level and the fifth quintile (Q5) the highest level. The classification values were (in Brazilian reais - BRL): Q1: ≤BRL417.00; Q2: ≥ BRL418.00 and ≤ BRL750.00; Q3: ≥ BRL750.00 and ≤ BRL1,099.00; Q4: ≥ BRL1,100.00 and ≤ BRL1,999.00; Q5: ≥ BRL2,000.00. For the quintiles of educational level, categories of highest educational achievement were grouped in order to have balanced groups in each survey , based on a previous study [Gender, age group, TV-viewing, urban/rural and ethnicity were used as confounders in the analyzes. Age group was classified as 18-34y, 35-49y, 50-64y, and 65+. Ethnicity was assessed according to the self-reported skin color and classified as white, black, mixed, or other. TV-viewing was self-reported and classified using the cut-off point of ≥3 h/day.Characteristics of the sample were described using values of absolute and relative frequencies as well as 95% confidence interval. Logistic regression models were created to estimate the joint associations of participation in public PA programs and the presence of public PA facilities near the household with income and educational level in predicting leisure-time PA, adjusting for sex, age group, TV-viewing, urban/rural and ethnicity. In addition, multiplicative interactions were used to assess the moderation of income and educational level in the associations of participation in public PA programs and the presence of public PA facilities near the household with leisure-time PA. Also, the associations of participation in public PA programs and the presence of public PA facilities near the household with leisure-time PA stratifying by quintiles of per capita income and educational level were tested.The final sample was composed of 88,531 adults , with a mean age of 47.2 ± 17.1 years. The characteristics of the sample according to leisure-time PA are presented in Table Figure Figure The combined associations of educational level and income with PA programs and public PA facilities near the household in the association with leisure-time PA are presented in Table We aimed to investigate the association of the presence of public PA facilities near the household and participation in public programs of PA with leisure-time PA as well as whether income and educational level could moderate this association, using a nationally representative sample of Brazilian adults. Our main findings were that the presence of public PA facilities near the household and participation in public PA programs were associated with higher leisure-time PA among all quintiles of income and educational level. However, these associations were more pronounced among the lowest quintiles of educational level and income.Our findings confirm that the presence of public PA facilities near the household and participation in public PA programs are associated with a higher leisure-time PA practice as reported in previous findings , 18, 19.There are marked PA inequalities especially in the leisure-time domain, in which people with higher educational level and income present higher PA practice , 8. In tOur findings highlight that the building and revitalization of public PA facilities such as parks and recreational centers for PA practice need to be prioritized in areas with lower socioeconomic development. Despite the association with PA, the proximity to public PA facilities could also be positive for well-being and quality of life . Howeverfavelas” [Also, the expansion of community health programs for the stimulation of PA should be prioritized, especially in deprived areas. Although Brazil has a large program that includes PA professionals in primary health care (Multidisciplinary Primary Care Teams), the distribution of the units with PA interventions is unequal considering different geographical regions . The supfavelas” , 27. AlsThe strength of our study is including a large nationally representative sample of Brazilian adults with data on PA, proximity to public PA facilities, income and educational level. However, our findings should be inferred in light of possible limitations. First, our study has a cross-sectional design and causal relations should be avoided. Second, our findings were based on self-reported measures, which can present bias. Third, the levels of participation in public PA programs were considerably low, which is a reflection of the low coverage of health programs involving physical education professionals, which may have reduced the sampling power. However, up to the moment, there is no feasible method to estimate domains of PA in large population studies. Also, both perceived and objectively-assessed built environmental characteristics are associated with PA .In conclusion, we found participation in public PA programs and presence of public PA facilities near the household to be associated with higher leisure-time PA and the associations are stronger in the group with lower educational level. Our findings suggest that presence of public PA facilities and participation in public PA programs are built environmental correlates that could be relevant for designing effective public health intervention for reducing social inequalities in leisure-time PA among adults in low-income areas of Brazil. Future studies should evaluate whether revitalization and the building of open spaces in areas of lower socioeconomic conditions could increase leisure-time PA among people with lower socioeconomic status.


They also showed a significantly higher prevalence of anterior STEMI and considerably wider QRS complex after PCI, while QRS duration measurement at baseline showed no significant difference. Additionally, patients presenting with LVSD after 6 months showed markedly more severe ischemia on admission, as assessed with the Sclarovsky-Birnbaum ischemia score, smaller reciprocal ST-segment depression at baseline and less profound ST-segment resolution post PCI. In multivariate regression analysis adjusted for demographic, clinical, biochemical and angiographic variables, anterior location of STEMI , post-PCI QRS duration  expressed per increments of 10 ms and impaired post-PCI flow in the infarct-related artery  were identified as independent predictors of LVSD (Nagelkerke’s pseudo R2 for the logistic regression model = 0.462). Similarly, in multiple regression analysis, anterior location of STEMI, wider post-PCI QRS, higher baseline number of pathological Q-waves and a higher baseline Sclarovsky-Birnbaum ischemia score, together with impaired post-PCI flow in the IRA, higher values of body mass index and glucose concentration on admission were independently associated with lower values of LVEF at 6 months . Conclusions: According to our study, baseline and post-PCI ECG parameters are of modest value for the prediction of LVSD occurrence 6 months after a first STEMI.Objective: To assess the performance of ten electrocardiographic (ECG) parameters regarding the prediction of left ventricular systolic dysfunction (LVSD) after a first ST-segment-elevation myocardial infarction (STEMI). Methods: We analyzed 249 patients  treated with primary percutaneous coronary intervention (PCI) included into a single-center cohort study. We sought associations between baseline and post-PCI ECG parameters and the presence of LVSD (defined as left ventricular ejection fraction [LVEF] ≤ 40% on echocardiography) 6 months after STEMI. Results: Patients presenting with LVSD ( Electrocardiography (ECG), invented by Willem Einthoven nearly 120 years ago, remains one of the essential diagnostic modalities in cardiology ,4.It is estimated that left ventricular systolic dysfunction (LVSD), recognized as a long-term consequence of myocardial infarction (MI), may affect up to 60% of post-MI patients . Its occLeft ventricular ejection fraction (LVEF), measured with echocardiography, is by far the most popular method for diagnosing LVSD in the clinical setting .LVSD is a well-recognized marker of unfavorable prognosis in post-MI patients , translaThere are many reports regarding the predictive value of ECG with respect to the development of LVSD after STEMI ,16,17. AOur investigation aims to assess the relationship between selected baseline and post-PCI ECG variables and the presence of LVSD 6 months after a first STEMI.The investigation was a prospective cohort trial including patients receiving primary PCI with stent implantation for a first STEMI. Study design, including the inclusion and exclusion criteria, was described in detail in our previous publication exploring associations of ECG with post-MI left ventricular remodeling (LVR) . Here, wheart rate,location of STEMI,number of leads with ST-segment elevation,sum of ST-segment elevation in all leads,maximal ST-segment elevation in a single lead,ST-segment resolution,presence of reciprocal ST-segment depression ≥0.1 mV on admission to hospital,number of leads with pathological Q-waves ,Sclarovsky-Birnbaum ischemia score ,QRS complex duration.The analyzed ECG parameters included:The primary study endpoint was the occurrence of LVSD 6 months after STEMI. LVSD was defined as LVEF ≤40% on transthoracic echocardiography. This cut-off value was previously shown to be associated with unfavorable prognosis ,22,23,24First, we planned to compare the clinical, biochemical, angiographic and echocardiographic characteristics. We also assessed differences in ECG parameters between patients with and without LVSD 6 months after STEMI. Second, we prespecified uni- and multivariate analyses aimed at identifying predictors of post-infarct LVSD. A particular focus was placed on the investigated ECG parameters.As a final step, we planned to check whether the variables predictive of the primary study endpoint were associated with lower values of LVEF (expressed as a continuous parameter) 6 months after STEMI.Details of coronary angiography, PCI technique and ECG evaluation were also published in our previous publication . ImportaInformed consent for participation in the study was obtained from each participant. The study received approval from the local Bioethics Committee of Collegium Medicum, Nicolaus Copernicus University in Toruń (protocol code KB 440/2004). Throughout the entire course of the study, the Declaration of Helsinki and the principles of good clinical practice were applied.Two-dimensional transthoracic echocardiography was performed in order to evaluate left ventricular systolic function using a Philips Sonos 7500 device  at two time points: before hospital discharge and after 6 months. Image acquisitions and measurements were performed according to the recommendations of the European Association of Echocardiography and the American Society of Echocardiography ,28. The Relevant data were collected and initially analyzed using Microsoft Excel spreadsheet software . No missing data were present.p-values of <0.1 were included in the multivariate models. Stepwise backward selection was employed to select variables included in the best-fitting models. To identify predictors of LVEF at 6 months, we used multiple linear regression. Variables showing univariate p-values of <0.1 were considered eligible for multivariate analyses. The variables were then removed via stepwise backward selection. p-values of <0.05 were considered significant. Data analysis was conducted using Statistica version 13  and SPSS version 23 .Descriptive analysis was used to summarize participant characteristics. Categorical data are presented as frequencies and percentages. Continuous variables are reported as medians and interquartile ranges. Correspondence with normal distribution was verified with the Shapiro-Wilk test. Between-group differences were tested using the Mann-Whitney U test for continuous variables and the Pearson Chi-square and Mantel-Haensztel tests for categorical variables. In order to identify predictors of LVSD at 6 months, logistic regression was used. The results are presented as odds ratios (OR) with 95% confidence intervals. Only variables with univariate The final analysis included 249 patients. A detailed description of the course of the study can be found in our previous publication .The study cohort was primarily composed of middle-aged men. At baseline, patients who presented with LVSD after 6 months of follow-up showed a higher prevalence of diabetes mellitus, left anterior descending artery (LAD) as the IRA and TIMI 0 flow before PCI, but less frequent TIMI 3 flow post PCI. Slightly worse kidney function (assessed based on glomerular filtration rate), higher plasma glucose concentration on admission to hospital, larger enzymatic infarct size , higher concentration of B-type natriuretic peptide (BNP) and more common usage of GPIIb/IIIa inhibitors during PCI could also be found in this group. Detailed characteristics of the study population are presented in p < 0.001; n = 39), when compared with those presenting with LVEF ≤40% both at hospital discharge and LVSD 6 months after STEMI (n = 45), had a lower proportion of the LAD as the IRA , more frequent TIMI 3 flow in the IRA following PCI  and lower values of cardiac biomarkers, including maximal concentration of cardiac troponin I , maximal activity of CK-MB  and BNP concentration on hospital discharge .Interestingly, patients with LVEF ≤ 40% at the time of discharge from hospital, but not 6 months after STEMI (Detailed baseline and post-PCI electrocardiographic data are reported in p < 0.001) and diuretic  more frequently than their LVSD (–) counterparts.As reported in p = 0.180) and after PCI . We also noticed significantly lower values of LVEF in the highest tercile of baseline and post-PCI QRS duration, compared with the lowest and middle terciles  group. These include faster heart rate, more widespread ST-segment elevation and Q-wave development and higher total and maximal ST-segment elevation. More pronounced ischemia in LVSD (+) patients was also evidenced by a higher incidence of anterior wall location, reciprocal ST-segment depression ≥1 mm and grade 3 according to Sclarovsky-Birnbaum ischemia grading system at baseline. In post-PCI ECG assessment, lower incidence and degree of ST-segment resolution and longer duration of the QRS complex were associated with the presence of LVSD after 6 months. A detailed comparison of ECG parameters is reported in iles see .Initially, we performed a univariate regression analysis, including electrocardiographic parameters and the variables from Among the analyzed angiographic variables, LAD as the IRA and usage of GP IIb/IIIa inhibitor were identified as predictors of LVSD occurrence, while TIMI 0 flow before PCI and TIMI 3 flow post PCI were associated with a lower incidence of LVSD after 6 months. The biochemical variables predicting LVSD occurrence included glucose concentration on admission, maximal cardiac troponin I concentration and CK-MB activity, as well as BNP concentration at discharge from hospital. The only clinical variable predictive of LVSD was the presence of diabetes mellitus.Next, in order to determine possible independent predictors of LVSD after 6 months, a multivariate logistic regression analysis was performed. We identified anterior location of STEMI, longer post-PCI QRS duration and impaired post-PCI flow in the IRA as the independent predictors of LVSD 6 months after STEMI .In an attempt to more thoroughly explore the relationship between ECG parameters and LVEF, multiple linear regression analysis with a backward elimination was applied . We founAccording to our results, the majority of the analyzed electrocardiographic parameters measured at baseline and directly after PCI were associated with LVSD 6 months after STEMI. However, when we considered demographic, clinical, angiographic and biochemical characteristics of our study participants, among all assessed ECG parameters, only anterior location of STEMI and longer post-PCI QRS duration remained independent predictors of post-MI LVSD. Additionally, in our study, anterior location of STEMI, longer post-PCI QRS duration, higher baseline number of pathological Q-waves and higher baseline Sclarovsky-Birnbaum ischemia score, together with impaired post-PCI flow in the IRA, higher values of body mass index and glucose concentration on admission, were independently associated with lower LVEF at 6 months.All electrocardiographic parameters selected for our analysis have been described in the literature to have some predictive value towards LVEF and LVSD. However, many of these reports come from the thrombolysis era and from inhomogeneous cohorts of patients. Our study cohort is characterized by homogeneity concerning the form of acute coronary syndrome presentation (exclusively patients with a first STEMI), reperfusion therapy (exclusively primary PCI) and subsequent pharmacotherapy . This unIncreased heart rate is a well-recognized risk factor for all-cause and cardiovascular mortality in the general population ,33,34,35However, we have not found any relevant reports in the literature on the relation of heart rate in the early phase of STEMI with LVEF and the development of post-MI LVSD.Anterior wall location of STEMI is a strong independent predictor of bad prognosis, including death  and the We also evaluated three parameters related to ST-segment elevation . According to Rodríguez-Palomares et al., the first two of the three parameters measured in pre-PCI ECG correlated with the size of myocardium at risk . In reseResolution of ST-segment elevation of ≥50% is considered a reliable indicator of patency of the IRA. However, restoration of myocardial tissue perfusion occurs only when complete (≥70%) ST-elevation resolution is achieved. Complete (≥70%) resolution of ST-segment elevation predicts lower 1–3 year mortality and lower rates of cardiovascular adverse events ,62,63 anBesides ECG changes recorded in leads overlying the area of STEMI, the presence of reciprocal ST-segment depressions at baseline may also hold prognostic value. In literature reports it reflected larger infarct area and multivessel coronary artery disease and was associated with increased mortality and higher rates of heart failure, cardiogenic shock and second- and third-degree heart block in a manner proportional to their extent and amplitude ,70. AddiThe number of leads with pathological Q-waves is another well-recognized predictor of post-MI mortality. It successfully predicted lack of recovery of left ventricular systolic function (defined as absolute LVEF improvement by <10%) within 6 months after STEMI . The preBased on the morphology of the terminal portion of the QRS complex and the relative magnitude of ST-segment elevation, the score identifies three grades of ischemia, with grade 3 reflecting most severe ischemia  and beinProlonged QRS duration is another well-established predictor of increased mortality in STEMI patients ,87,88. TAs one can surmise from the above review of the prognostic value of the electrocardiographic parameters, the majority of the literature concerns their association with mortality, while there is a scarcity of data concerning associations with LVSD or LVEF. This fact precludes direct comparison of our results with the cited investigations. However, recognizing LVSD as a surrogate for cardiovascular mortality, the results of our investigation support the prognostic value of ECG regarding prognosis assessment following STEMI.The results of our investigation basically support the data from the literature. Our study participants who presented with LVSD 6 months after STEMI, in comparison to those without LVSD, had significantly higher values of heart rate, number of leads with ST-segment elevation and pathological Q-waves, sum of ST-segment elevation and maximal ST-segment elevation on admission to hospital and directly after PCI. They also showed a higher prevalence of anterior STEMI and considerably wider QRS after PCI, while QRS duration measurement at baseline showed no significant difference. Additionally, patients presenting with LVSD after 6 months showed more severe ischemia on admission, as assessed with Sclarovsky-Birnbaum ischemia score, smaller reciprocal ST-segment depression at baseline and less profound ST-segment resolution post PCI. In univariate analysis, all but one of the ECG parameters predicted LVSD occurrence 6 months after STEMI, the most powerful being anterior location of STEMI . Our analysis also indicates good predictive value of ST-segment resolution and grade 3 according to the Sclarovsky-Birnbaum ischemia score, which came in as the second and third most powerful LVSD predictors. However, it is important to remember that some of the remaining parameters were reported per increments, which means that their actual final impact potentiates when the increments are multiplied in measurements. The only exception was QRS duration at baseline, which did not show statistical significance. In contrast to literature data, in our investigation, the presence of reciprocal ST-segment depressions diminished the likelihood of LVSD occurrence 6 months after STEMI. Whether this could be a consequence of shorter time-to-balloon delay in this group, compared with patients without reciprocal ST-segment depressions, remains a matter of speculation and requires verification in a larger group since the difference in time-to-balloon between patients with and without LVSD was not statistically significant.p < 0.001) and post-PCI QRS duration  expressed per increment of 10 ms. The highest tercile of post-PCI QRS duration  was associated with the highest prevalence of LVSD after 6 months and therefore appears to have the best discriminative value. The highest terciles of baseline and post-PCI QRS duration were also associated with significantly lower values of LVEF, compared with lower terciles.In the model adjusted for demographic, clinical, biochemical and angiographic variables, however, the majority of the ECG parameters did not maintain statistical significance. The only two parameters contributing to the multivariate regression model and thus recognized as independent predictors of LVSD in 6-month follow-up were anterior location of STEMI  were revascularized electively . This fact might have some impact on the study findings. Eighth, in a substantial number of our study participants, maximal concentration of cardiac troponin I exceeded 50 ng/mL. These serum samples were not further diluted, preventing precise estimation of the biochemical infarct size. Ninth, patients with left bundle branch block, isolated posterior myocardial infarction, isolated right ventricular myocardial infarction or permanent atrial fibrillation were excluded from the study. Therefore, the study findings may not to be attributable to such patients. Finally, post-reperfusion ECG parameters in time points other than directly after PCI were not assessed.According to our study, baseline and post-PCI ECG parameters possess a modest predictive value for LVSD occurrence within 6 months of a first STEMI.


Cardiomyopathies are a group of structural and/or functional myocardial disorders which encompasses hypertrophic, dilated, arrhythmogenic, restrictive, and other cardiomyopathies. Multimodality cardiac imaging techniques are the cornerstone of cardiomyopathy diagnosis; transthoracic echocardiography should be the first-line imaging modality due to its availability, and diagnosis should be confirmed by cardiovascular magnetic resonance, which will provide more accurate morphologic and functional information, as well as extensive tissue characterization. Multimodality cardiac imaging techniques are also essential in assessing the prognosis of patients with cardiomyopathies; left ventricular ejection fraction and late gadolinium enhancement are two of the main variables used for risk stratification, and they are incorporated into clinical practice guidelines. Finally, periodic testing with cardiac imaging techniques should also be performed due to the evolving and progressive natural history of most cardiomyopathies. Cardiomyopathies constitute a heterogeneous group of diseases that affect the muscle of the heart and present a very diverse etiology. Classically, the European Society of Cardiology (ESC) classifies these diseases as hypertrophic, dilated, arrhythmogenic, restrictive, or other cardiomyopathies . AdditioThe patient evaluation includes anamnesis, physical examination, an electrocardiogram, and transthoracic echocardiography (TTE) that may raise suspicion of cardiomyopathy. This information is usually complemented with a cardiovascular magnetic resonance (CMR) that provides more precise anatomic and functional evaluation, as well as excellent tissue characterization with prognostic implications. Additionally, some patients may require a nuclear medicine test or cardiovascular computed tomography (CT).In this manuscript, we will review the information that the different imaging techniques offer in the diagnosis and management of these patients. Hypertrophic cardiomyopathy (HCM) is defined by an increase in left ventricular (LV) wall thickness and/or LV mass, unexplained by LV loading conditions. HCM is the most prevalent cardiomyopathy, affecting approximately 1:500 of the adult population, and is usually caused by mutations in sarcomeric genes ,3. TTE is the first-line imaging modality for HCM evaluation: a maximal wall thickness >15 mm  or asymmetric septal hypertrophy  ratio >1.3 (or >1.5 in hypertensive patients) is suggestive of HCM  4]. A w. A w4]. TTE allows for localization of the hypertrophy and hence identification of different phenotypes: septal, septal reverse, apical, or diffuse HCM, among others . In addiMoreover, the presence of LV outflow tract obstruction (LVOTO) can be easily evaluated and is defined as a peak gradient higher than 30 mm Hg at rest or after provocative maneuvers  has been associated with worse outcomes in HCM , even thCMR has become the gold standard technique for HCM evaluation and should be performed in all patients . Beyond LGE is a frequent finding in HCM (about 60% of patients) ,12,13, cQuantification of LGE, usually as the percentage of total LV mass using the five standard deviation method , has emeEmerging CMR sequences, such as T1 and T2 mapping and extracellular volume (ECV), allow for quantitative analysis of tissue characteristics and are more sensitive than LGE for the detection of myocardial fibrosis, especially in case of diffuse interstitial fibrosis  20]. Fu. Fu20]. Stress echocardiography (SE) is another useful technique in the assessment of HCM because one-third of patients have latent LVOTO. SE is safe and usually performed in a semi-supine position, while the use of dobutamine is not recommended in HCM. LVOTO, LV systolic function (LVEF and GLS), LV diastolic function (E/E’), dynamic mitral regurgitation  and tricuspid regurgitation (TR) velocity should be evaluated at rest, at peak stress, and post-exercise  24]. Ex. Ex24]. The role of cardiac CT in HCM is secondary and may be considered to exclude coronary artery disease. Recently, assessment of myocardial fibrosis by delayed enhanced CT has been described with an adequate agreement with LGE by CMR . Even thDilated cardiomyopathy (DCM) is defined by LV (or biventricular) systolic dysfunction (LVEF < 45%) and dilatation  not attributed to loading conditions or coronary artery disease . DCM affTTE allows for both anatomical and functional assessment. Three-dimensional transthoracic echocardiography (3D TTE) is increasingly used due to improvements in technology and automated software and has the advantage of direct LV measurements with no geometric assumptions . Most imLVEF remains the strongest predictor of events in DCM; thus, patients with an LVEF ≤35% must be considered for optimal medical treatment and prophylactic ICD  ,30. HoweStress echocardiography (SE) is also useful for risk stratification in DCM. Dobutamine is most often used, with either low or high-dose protocols (10 or 40 μg/kg/min), and the contractile response is assessed. An increase by ≥5% in LVEF at peak stress is defined as a contractile reserve and is associated with improved outcomes and reverse remodeling in DCM ,34. SE mCMR should be performed at least once in all DCM patients since it is the gold standard technique for the assessment of biventricular volumes, systolic function, and tissue characterization. LGE is common in DCM and traduces myocardial fibrosis ,36, usuaThe extension, localization, and pattern of LGE have also been associated with prognosis ,42; a hiGLS by CMR  has beenAssessment of right ventricle (RV) size and systolic function is recommended in all patients since RV systolic dysfunction is a common finding and an independent predictor of poor outcome . DiffereOther imaging modalities are rarely used in DCM. Nuclear imaging can analyze cardiac sympathetic innervation, which has been associated with ventricular arrhythmias and adverse prognosis . CardiacRestrictive cardiomyopathies (RCM) account for less than 5% of all cardiomyopathies and have a highly varied etiology .RCM is characterized by a marked alteration of myocardial compliance: severe diastolic dysfunction and a preserved systolic function (at least in early stages). The initial diagnosis is performed by TTE showing a normal/increased LV wall thickness , a restrictive pattern by Doppler, absence of left ventricular dilatation, preserved LVEF, and a marked biatrial dilatation . HoweverIdiopathic restrictive cardiomyopathy is a very uncommon disease affecting predominantly children and young adults with a familial pattern. It is characterized by the presence of a restrictive diastolic filling pattern (increased left ventricular end-diastolic pressure), normal left ventricular dimensions, absence of an increased left ventricular mass, normal left and right ventricular function, and absence of any other cardiac or pericardial diseases . Cardiac amyloidosis (CA) is an infiltrative disease caused by an extracellular accumulation of amyloid fibers. Most patients are affected by light chains (primary or AL amyloidosis) or by transthyretin (ATTR amyloidosis), either the hereditary form (ATTRm) or the wild type (ATTRwt) . Among the main TTE findings, the following “red flags” should raise suspicion of CA : left veThe presence of a reduced GLS presents prognostic implications; a GLS >−14.8% has been associated with an increase in global mortality . AlthougCMR provides high-resolution structural and functional information, allows tissue characterization , and perAs the disease progresses, there is an increase in LGE uptake, which is initially subendocardial and progressively becomes transmural  . AdditioEither 99m technetium diphosphonate (Tc-DPD) or pyrophosphate (Tc-PYP) scintigraphy play a relevant role in diagnosing ATTR amyloidosis and allow early detection of cardiac involvement before TTE and CMR, however, false positives can be present . ResultsAnderson–Fabry disease (FD) is a rare  genetic lysosomal storage disorder caused by a mutation in the alpha-galactosidase A (GLA) gene with an X-linked inheritance.The presence of concentric left-ventricular hypertrophy (LVH) is the most common finding in FD, however, other patterns have also been described: septal, asymmetric, or apical . LVH is Generally, the biventricular systolic function is preserved until advanced stages of the disease, at least in terms of LVEF. However, FD patients show reduced values of GLS and GCS compared to controls, which are more reduced in those with inferolateral LGE C; thus, The most common finding in CMR is also the presence of concentric LVH. The typical LGE pattern is an intramyocardial uptake at the basal LV inferolateral wall, which is present in up to 50% of patients , and mayThe presence of LGE is indicative of irreversible myocardial damage; tfhus, clinical practice guidelines recommend starting treatment with a class I indication when there is no or minimal fibrosis . The preT1 and T2 mapping techniques may identify the presence of early myocardial damage before the onset of myocardial fibrosis. Given that the degree of myocardial infiltration is diffuse, it is recommended to assess the value of native T1 in all myocardial segments  77]. Na. Na77]. FD must also be considered a chronic inflammatory disease. Thus, unlike patients with HCM, the presence of high native T2 values suggest FD, initially affecting the inferolateral wall and becoming progressively diffuse. Using 18F-fluorodeoxyglucose positron emission tomography (PET), an increase in the uptake of the tracer has also been described, confirming the presence of myocardial inflammation . FinallyIron overload cardiomyopathy (IOC) is a secondary form of cardiomyopathy resulting from iron accumulation in the myocardium mainly because of genetically-determined iron metabolism disorders or multiple transfusions . It has IOC can be very difficult to diagnose by TTE, therefore, CMR T2* imaging is considered the reference standard for detecting and quantifying myocardial iron overload. Abnormalities in CMR T2* can occur before the development of systolic or diastolic dysfunction and may be used to guide iron chelation therapy to prevent heart failure or death .For easy classification into different IOC risk groups, the following classification has been adopted using a 1.5 Tesla MR scanner: patients with T2* >20 ms are regarded as not having cardiac iron overload, between 10–20 ms have mild to moderate cardiac iron load and those <10 ms are considered to have a heavy cardiac iron load .Sarcoidosis is an inflammatory granulomatous disease that can involve any organ, with cardiac involvement  in a quarter of patients. Clinical manifestations include heart block, atrial and ventricular arrhythmias, and heart failure. Diagnosis can be challenging but with the increased availability of advanced cardiac imaging, more cases are being identified.TTE has limited sensitivity and specificity for the diagnosis of CS, however, it is often the initial imaging study. The TTE main findings include ventricular hypertrophy, diastolic dysfunction/restrictive filling pattern, wall motion abnormalities with a non-coronary distribution, aneurysms, and LV or RV systolic dysfunction . CS patiCMR plays an important role in the diagnosis and risk stratification of patients with CS. Although the presence of LGE may be non-specific, the subepicardial location, multifocal distribution, high signal intensity, and contiguous extension from the left to the right ventricle may increase the specificity of this finding for the diagnosis of CS . Many stCardiac PET using 18F-FDG has emerged as a cornerstone in the clinical diagnosis, prognostic evaluation, and monitoring of therapy in CS. FDG-PET/CT has a fair diagnostic accuracy for CS . The claEndomyocardial fibrosis (EMF) is a rare form of RCM characterized by an abnormal thickening of the endocardium due to fibrous tissue deposit  secondarCMR is the gold standard for EMF evaluation and specifically for localization, characterization, and quantification of fibrous tissue by LGE sequences. LGE strongly correlates with histopathological findings and its extension is associated with increased mortality risk . CMR mayArrhythmogenic cardiomyopathy (ACM) is an inherited heart muscle disorder predisposing to SCD, particularly in young patients and athletes. It is a cell-to-cell junction cardiomyopathy, typically caused by genetically-determined abnormalities of cardiac desmosomes. Pathological features include loss of myocytes and fibrofatty replacement of right or left ventricular myocardium. ACM diagnosis does not rely on a single gold standard test but is classically achieved using a scoring system, which encompasses familial and genetic factors, ECG abnormalities, arrhythmias, and structural/functional ventricular alterations . The scoTTE is the initial diagnostic approach in ACM patients. A thorough RV assessment with dedicated RV planes is recommended if clinical suspicion is high . The preLV involvement is identified in more than half of patients with ACM, and biventricular as well as predominant LV ACM forms may occur , which aEmerging TTE parameters in the evaluation of patients with suspected or established ACM include the measurement of tricuspid annular plane systolic excursion (TAPSE), RV basal diameter, GLS (RV and LV), mechanical dispersion (RV and LV), and the use of 3D TTE. In particular, RV GLS is affected in early ACM phases , TAPSE  is a heterogeneous entity characterized by prominent LV trabeculae, deep intertrabecular recesses, and a thin compacted (C) myocardial layer  Figure . HypertrDifferent diagnostic criteria have been described for LVNC . By TTE,TTE is the first-line imaging technique for both quantification and localization of the trabeculae: the apex and lateral segments are the most frequently involved. Contrast echocardiography may be used to enhance trabeculation measurement and exclude the presence of intertrabecular thrombi B. AssessCMR should be performed in all LVNC patients. The presence of LV dilatation ,115 and Finally, cardiac CT is rarely used in LVNC, with its main objective being to exclude coronary artery disease. However, a large population study has demonstrated that the degree of hypertrabeculation measured by CT was independently related to outcomes . TherefoCardiac imaging techniques are an essential tool in the study of cardiomyopathies, and they provide both diagnostic and prognostic relevant information. Transthoracic echocardiography should always be the first technique used due to its availability and cost, as well as the possibility of periodic testing. Cardiovascular magnetic resonance should also be performed in all patients due to its additional anatomical and functional information as well as thorough tissue characterization, with important prognostic implications. Other techniques  may be applied in selected entities while more advanced imaging analysis  offer promising but still preliminary results. Altogether, multimodality cardiac imaging plays an important role in clinical decision-making and helps to improve patients’ management and outcomes.


To compare the accuracy of heart rate detection properties of a novel, wireless, dry-electrode electrocardiogram (ECG) device, NeoBeat®, to that of a conventional 3-lead gel-electrode ECG monitor (PropaqM®) in newborns.p = 0.44). There was a deviation of more than 10 bpm in 7.4% of the data pairs, which primarily (78%) was attributed to ECG signal disturbance, and secondly (22%) due to algorithm differences between the devices. Excluding these outliers, the correlation was equally consistent (r2 = 0.96) in the full range of heart rate captured measurements with a mean difference of − 0.16 (3.09) bpm. The mean difference was less than 1 bpm regardless of whether outliers were included or not.The study population had a mean gestational age of 39 weeks and 2 days (1.5 weeks) and birth weight 3528 g (668 g). There were 950 heart rate notations from each device, but heart rate was absent from the reference monitor in 14 of these data points, leaving 936 data pairs to compare. The mean (SD) difference when comparing NeoBeat to the reference monitor was -0.25 (9.91) beats per minute (bpm) (The online version contains supplementary material available at 10.1186/s13104-021-05576-x. Approximately 5–6% of newborns require resuscitation at birth –3. HeartTo obtain rapid and reliable heart rate monitoring during newborn resuscitation is challenging. Comparative studies show that electrocardiogram (ECG) provide feedback of heart rate earlier than pulse oximetry, and pulse oximetry can underestimate initial heart rate –9. The IThe aim of this study was to correlate the heart rate detection properties of a dry-electrode ECG device, NeoBeat , to that of a conventional 3-lead gel electrode ECG, PropaqM® (Zoll) in newborns.This single-centre observational study was conducted in the maternity unit at Stavanger University Hospital, Stavanger, Norway. Healthy newborns with birth weight ≥ 1500 g were included during their first day of life April 12th–May 26th 2019. Inclusion happened on random days when the investigators were on call and time permitted. Newborns in need of medical interventions at birth or admission in the Neonatal Intensive Care Unit were excluded. All parents of approached eligible newborns agreed to participate in the study.The sample size was estimated using single population proportion formula with the assumption of proportion (p) for deviation score, p = 10%, with the standard deviation 95% level of certainty (2.5), and margin of error 0.1. This gave an estimate of 525 data points. An addition of 20% for missing data due to potential technical errors gave an estimate of 630 data points. We included a sample of 50 newborns in the analyses, sampled every 10 s for 3 min, resulting in a total of 950 data points from each device.The wireless, dry-electrode ECG device NeoBeat  was developed for heart rate monitoring in newborns. The device can be rapidly applied to the newborns wet torso or abdomen after birth, and presents heart rate on a display on the sensor. For comparison, we used a reference monitor, a conventional 3-lead gel-electrode ECG  with BlueSensor ECG electrodes . In both devices, ECG biosensors and algorithms detect and display the heart rate based on QRS complex detection. An internal algorithm in each device designed by the manufacturer determines how QRS detection is transformed into heart rate displayed on the screen. Differences in this algorithm i.e. how many QRS complexes are used for averaging heart rate, will have an effect on the heart rate displayed.During data collection, the newborns were placed in the supine position. The conventional 3-lead gel-electrode ECG was connected to the newborn’s torso as per the device’s instructions and the dry-electrode device attached across the torso. Electrodes of the two devices were located apart from each other Fig. .Heart rates displayed from the two devices were video-recorded for three minutes. Two researchers, HP and SR, reviewed the videos individually and registered heart rate from each device at 10-s intervals for 3 min, providing 19 notations per device per participant. The resulting 950 heart rate data points per device gave 950 data pairs to compare. To avoid human error in the notation process, discrepancies in the heart rate of more than five beats per minute (bpm) between the two researchers led to a re-examination of the video recordings and consensus on correct heart rate was reached. The notations from the two researchers were averaged for the subsequent analyses.Data were analyzed with Matlab . Continuous variables were expressed as mean (standard deviation) unless otherwise stated. The devices were compared using a paired t-test. The device differences were illustrated using a correlation plot and a Bland–Altman plot. In analysis of the two devices, the conventional 3-lead gel-electrode ECG was the reference monitor for comparison. We defined outliers as ≥ 10 bpm rate difference between the devices and these were further analyzed to find the likely reason for the deviation, including re-examination of the video recordings.The study population (n = 50) had a mean gestational age of 39 weeks and 2 days (1.5 weeks) and birthweight 3528 g (668 g). All data were checked with double entry and the inter-reviewer agreement correlated well (Pearsons’ r = 0.9993).p = 0.44)  difference when comparing NeoBeat to the reference monitor was − 0.25 (9.91) bpm  with a deviation ≥ 10 bpm. Poor ECG signal in the reference monitor was noted as the reason in 54/69 (78%) data points. 30 of these 54 were because of ECG signal disturbance due to newborn movements . The remaining data points were due to heart rate recovery thereof (i.e. when the monitor heart rate averaged back to “correct” heart rate).In the reminding 15 of 69 data pairs (22%), newborn movements could not explain the deviations.2 = 0.96) in the full range of captured heart rate measurements. The mean difference, when comparing the dry-electrode sensor to the reference monitor, excluding outliers was − 0.16 (3.09) bpm (Fig. When the 69 outliers were removed, the devices showed consistent correlation (rs − 0.16 .09 bpm (In this study, we found no systematic errors or discrepancies between the two devices. The dry-electrode device showed a high degree of correlation with the reference ECG monitor, with less than 1 bpm difference. This finding was valid regardless of whether the outliers were included or not. The outliers observed were predominantly due to episodes of poor ECG signal in the reference monitor, mostly due to spontaneous movement of the newborns.In 1.6% of the data points the discrepancies between the two devices were probably attributable to differences in the internal algorithm of the two devices. Heart rate frequency can be detected from ECG signal by different algorithms, based on QRS complex detection where heart rate is computed from the distance between the QRS complexes. We speculate that the reference monitor has a shorter averaging window for heart rate detection and presentation on the screen than NeoBeat. Although the systematic difference was minimal, heart rate from the 3-lead gel-electrode ECG monitor increased or decreased some seconds before heart rate from the dry-electrode device. This observed difference between the devices is clinically insignificant.Our findings suggest that the reference monitor can be motion sensitive. This is important to consider in a resuscitation situation when interpreting the readings of any ECG device is crucial. A concern identified by ILCOR is initiated treatment based on a false positive low heart rate reading . The dryThe findings of this study have important clinical implication demonstrating that heart rate measurements obtained by NeoBeat dry-electrode ECG correlate well with conventional gel-electrode ECG in healthy newborns. Correlation studies comparing accuracy of heart rate detection properties at low and high heart rates during newborn resuscitations are warranted.NeoBeat dry-electrode ECG was equally reliable and accurate over time as compared to a conventional 3-lead ECG device. The mean difference was less than 1 bpm regardless of whether outliers were included or not. Clinically insignificant, short-duration deviations were documented. These could be attributed to internal algorithm differences between the two devices.A limitation of our study was that correlation analysis was performed in healthy newborns with heart rate measurements in the normal range 100–160 bpm, not during resuscitation when lower and higher heart rates would be expected (Additional file Additional file 1: Figure S1. Heart rate variability between devices. Figure S1. Heart rate variability over time in an individual newborn.Additional file 2. Heart rate data pairs from the two devices by the two observers.


The coronary slow flow phenomenon (CSFP) is common in coronary angiography, however its impact on left atrial (LA) function is still controversial. This study aims to evaluate the LA structure and function of patients with CSFP using two-dimensional speckle tracking echocardiography (2D-STE). Consecutive patients scheduled for coronary angiography from January 2016 to September 2017 were enrolled in this study. Patients’ demographic data, clinical histories, laboratory and angiographic findings were collected and recorded. Diagnostic criteria for CSFP is based on Beltrame et al. proposed in 2012. Meanwhile 139 patients who have no significant stenosis (≤ 40%) and normal blood flow were selected as control. All patients received an echocardiographic examination 24 h before coronary angiography. LA structure and function were measured with echocardiography and 2D-STE. Our results showed that among the 1,954 patients who had received coronary angiography, 512 patients were included in the analysis after the exclusion criteria was implemented. Of those, 101 patients met the CSFP criteria (5.5%). CSFP is mainly seen in LAD (~ 70%). There was no statistical difference in baseline characteristics between the CSFP group and control group, except for a higher proportion of smokers in the CSFP group (P = 0.001). The percentage of monocytes is an independent risk factor for the occurrence of CSFP (P = 0.036) after binary logistic regression analysis. The LA global longitudinal strain  decreased and LA strain rate at late diastole  increased in patients with CSFP compared to the control group (P < 0.05). Correlation test of continuous variables by Pearson test suggested that LA-GLS was negatively correlated with TIMI frame count (TFC). We concluded that the percentage of monocytes is an independent risk factor for the CSFP; the LA reservoir and booster functions were impaired in patients with CSFP; LA-GLS is negatively correlated with TFC. The CSFP is diagnosed based on the results of coronary angiography. The current adapted diagnostic criteria was proposed by Beltrame2 where CSFP is characterized by delayed distal vessel opacification of contrast in the absence of significant epicardial coronary stenosis (coronary artery stenosis ≤ 40%), with the Thrombolysis in Myocardial Infarction (TIMI) blood flow grade of 2 or corrected TIMI frame count (cTFC) of greater than 27 frames in one or more epicardial vessels. CSFP is still a "phenomenon" because its definition is based on visual findings of delayed contrast filling of the distal coronary artery in the absence of significantly obstructive vascular disease. Its pathophysiological mechanism remains unclear. Some researchers believe it represents a pathology related to an underlying dysfunction of microvascular resistance, thrombocyte dysfunction, oxidative stress, systemic/local inflammation, and/or a combination of all listed factors5.Since the coronary slow flow phenomenon (CSFP) was firstly described by Tambe8. Some cardiologists believe it is often underrecognized, and the incidence could be as high as 34%9. The clinical manifestations of patients with CSFP are diverse, but more than 80% of patients can have repeated chest pain episodes that could last for an extended period of time10 and could also occur at rest11. The clinical symptoms range from severe, such as acute coronary syndrome, or mild, such as chest tightness, and sometimes CSF can even cause fatal ventricular arrhythmias14. Studies have shown that younger patients are more likely to develop CSFP, and the prevalence is higher in men than women7. CSFP is more likely seen in smokers13, patients with metabolic syndrome and high BMI15, and patients with anxiety, depression16 and sleep apnea17.CSFP is not rare, with an incidence of approximately 1–5.5% in patients scheduled for coronary angiography19. However, the effect of CSFP on left atrial function has been minimally investigated. A few studies can be found in the existing literature, but the conclusion is controversial21. The left atrium serves an integral role in cardiac performance and is closely related to left ventricle function. Hemodynamic changes in the left atrium promote the formation of thrombosis, causing thromboembolism, stroke, and atrial fibrillation23. Abnormal left atrial function can affect left ventricular filling and cause a decrease in cardiac output. Accurate evaluation of the structure and function of the left atrium has important significance in clinic settings24. Traditional methods using two-dimensional (2D) echocardiography for left atrial function assessment gives limited information depending on hemodynamic loading and geometric measurements25 and may not fully reflect the left atrial function. 2D speckle tracking echocardiography (2D-STE) is a relatively new echocardiographic technique developed for quantitative evaluation of cardiac function. This technology quantifies the movement of the myocardium by tracking the trajectory of the myocardial acoustic spot during the cardiac cycle. Because it is a more sensitive technique for the evaluation of cardiac function versus traditional echocardiography, it could provide greater accuracy when determining LA function in CSFP patients26. In this study we used 2D-STE for evaluating the LA deformation in patients with CSFP and compared the findings with control patients to investigate the effect of CSFP on LA structure and function.CSFP can cause left ventricular dysfunction, mainly left ventricular diastolic dysfunctionAll consecutive patients scheduled for coronary angiography from January 2016 to September 2017 in the Heart Center of affiliated Zhongshan Hospital of Dalian University were enrolled. The following patients were excluded if they have (1) myocardial infarction, (2) a history of cardiac surgery or percutaneous coronary intervention, (3) severe uncontrollable hypertension or left ventricular hypertrophy, (4) severe liver and kidney dysfunction, (5) heart valve disease, (6) cardiomyopathy, (7) severe infection, (8) malignant tumor, (9) cardiac insufficiency NYHA grade II or above, (10) coronary artery spasm and dilation, (11) myocardial bridge, (12) anemia, (13) thyroid disease, (14) the left bundle branch block or paced rhythm, (15) atrial fibrillation, (16) poor coronary angiography or cardiac ultrasound images. Concurrently, 139 control patients were randomly selected from the Coronary Angiography Data Bank of our hospital. These control patients had insignificant or no coronary stenosis (no more than 40%) and normal blood flow determined by coronary angiography.Patients’ general clinical information including gender, age, height, weight, BMI, blood pressure, heart rate, as well as laboratory test results , were collected within 3 days before angiography was performed. All patients underwent routine echocardiography within 24 h before coronary angiography.Written informed consent was obtained from all patients before enrollment. The study protocol was approved by the Dalian University Ethics Committee and was conducted in accordance with the ethical guidelines of the 1975 Declaration of Helsinki.2. Briefly, there was no coronary artery stenosis or stenosis ≤ 40% at coronary angiography and the delay of distal angiographic contrast agent filling reaches corrected TIMI frame count (cTFC) value > 27 frames (30 frames/s), at least one coronary artery is involved.Coronary angiography was performed using the GE Medical System (USA). A catheter was introduced through either the right or left radial artery in all patients and multi-positional images were acquired to fully visualize every segment of the right and left coronary arteries. Iohexol or iopamidol was used as the contrast agent. The diagnostic criteria for CSFP is based on the recommendations of Beltrame JF proposed in 201227. The inner diameter of the left atrium was measured at the end of the ventricular systole, including the antero-posterior diameter (LA-ap), the long diameter (LA-l), and the transverse diameter of the left atrium (LA-t). The mean LA diameter was calculated as the average value of the left atrial inner diameter (mLAD), mLAD = (LA-ap + LA-l + LA-t)/3, and the left atrial diameter index (LADI),is calculated as LADI = mLAD/ body surface area (BSA). The two-plane Simpson method was used to calculate the left atrial volume and ejection fraction. The maximum and minimum volumes of the left atrium were corrected with the BSA to obtain the left atrial maximal volume index (LAVI-max), LAVI-max = LAV-max/BSA, and the left atrial minimum volume index (LAVI-min), LAVI-min = LAV-min/BSA. All LA sizes and volume measurements were the average of three different cardiac cycles.Echocardiography was performed on all patients within 24 h before coronary angiography using the Phillips Color Doppler Ultrasound Scanner . The optimal frame rate for 2D image acquisition was set between 60 and 100 frames per second, and images are continuously acquired for three cardiac cycles. All acquired images and cardiac structure measurement methods are based on the 2016 Chinese Adult Echocardiography Examination Measurement GuidelinesFor 2D-STE, echocardiographic images were stored at 60–100 frames per second in three cardiac cycles. The strain and strain rate were measured at apical 4- (AP4) and 2-chamber (AP2) views respectively using Qlab10.5 workstation. Initially, the endocardial border of the LA was manually traced in aCMQ mode at end ventricular systole, the epicardial borders of the LA wall were automatically defined through software, and the width was manually adjusted so that the tracking area covered the full thickness of the myocardium. After the adjustment and confirmation of these traced borders, the software automatically calculated and displayed the results , gender (P = 0.46), prevalence of hypertension (P = 0.94), diabetes (p = 0.07), systolic blood pressure (P = 0.94), diastolic blood pressure (P = 0.96), heart rate (P = 0.47), and body mass index (P = 0.07), except for smoking history  . At the same time, 139 patients who had normal coronary angiography were selected as the control group from the same data pool. Among 101 patients with CSFP, 50 patients (49.5%) were observed to have all three vessel involvement, 28 patients (27.7%) with two vessel involvement, and 23 patients (22.8%) with only one vessel involvement. The LAD was the most frequently engaged (70.3% of cases), followed by RCA (55.4%) and LCX (46.5%) respectively. Using corrected TIMI frame count (cTFC) to quantify the blood flow velocity, we found that there was a statistical difference between the CSF group and control group, and it was independent of use of different contrast agents  Table .Table 3BThe univariate variables with statistical differences were then incorporated into the binary logistic regression equation, with the CSF group assigned “1” and the control group assigned “0”. The results showed that the percentage of monocytes was an independent risk factor for the occurrence of coronary artery slow blood flow  , left atrium minimum volume index (LAVI-min), left atrium global longitudinal strain (LA-mGLS) and late diastolic strain rate (LA-mSRA) (P < 0.05) Table .Table 6CThe correlation of continuous variables was selected for analysis by Pearson test, and was aimed at exploring whether the mean blood flow velocity mTFC of the three vessels was correlated with the left atrial strain index. The results showed that there was a negative correlation between LA-GLS and mTFC (P < 0.05), and there was no correlation between LA-SRS, LA-SRE, LA-SRA, and mTFC  mononuclear cells can be activated by risk factors such as smoking, diabetes, hypertension, and hyperlipidemia, which accelerates the progression of atherosclerosis, (2) mononuclear cells participate in the inflammatory response in the acute phase of unstable plaque rupture, acute coronary syndrome, and other homeostatic imbalances, (3) mononuclear cells can enter myocardial tissue in the hypoxic phase during acute coronary events, promoting myofibroblast regeneration, angiogenesis, and repair and remodeling of the myocardium. Although there are studies indicating the involvement of HDL in the regulation of monocyte functions40, we did not find a statistical difference in HDL between the CSF group and the control group in our study. In addition, we also noticed a higher prevalence of smoking and a higher BMI in the CSF group than that of the control group, which can be linked with some recent findings. There are several studies indicating that smoking can induce endothelial dysfunction through oxidative stress42, which is involved in the development of CSFP. Metabolic syndrome  has similar effects on vascular endothelium. Obesity and a high BMI can cause endothelial dysfunction through an imbalance in the production of vasodilatory agents, thus inducing CSFP43.In this study, we found a statistically significant difference in the percentage of monocytes between the CSF group and the control group. The percentage of monocytes was determined to be an independent risk factor for the occurrence of CSFP after using regression analysis. Monocytes play an important role in the occurrence and development of atherosclerosis, which precipitates the progression of atherosclerotic plaques from a stable state to an unstable state44. The LA size and function has an important clinical and prognosis impact24. Evaluation of LA size and function can be obtained by traditional 2D-echocardiography, however these parameters are morphometric and static. 2D-STE is a relatively new echocardiographic technique which uses standard B-mode images for regional and global myocardial function analysis. The technology tracks the spatial dislocation of speckles, which is assumed to represent myocardial deformation45. 2D-STE analysis gives an excellent assessment of the atrial deformation profile during an entire cardiac cycle by closely following the LA physiology47. In contrast to Doppler derived parameters, speckle tracking has the advantages of being angle-independent, less load-dependent than ejection fraction, and less affected by reverberations, side lobes and drop out artifacts. 2D-STE was found to be a feasible, reproducible and sensitive method to assess LA function49. Several studies have shown that strain imaging can detect LA dysfunction before the manifestation of LA structural changes51.The left atrium plays an important role in ensuring proper performance of left ventricular function and the systemic circulation. From a hemodynamic perspective, the left atrium possesses three functions: as a reservoir, passive conduit and booster pump52. Wang et al.52 evaluated the LA function in 82 patients with CSFP and compared with normal control participants. They observed decreased LA conduit function and increased LA pump function in patients with CSFP, but no significant differences regarding LA phasic emptying volume and emptying fraction were observed between the two groups. However, in another study with 1:1 patient-control matching design for age, sex, hypertension, diabetes mellitus and the LV function by Fallah20, the authors did not find significant differences regarding triphasic LA functions assessed through 2D-STE between the CSFP group and control group. In this study, our results showed that minimum left atrial volume index (LAVImin) increased and left atrial ejection fraction (LA-EF) decreased in the CSFP group compared with the control group, although no statistically significant differences were found in the LA size  and maximum left atrium volume index (LAVIm) between the two groups. Meanwhile, we found that patients with CSF have lower LA-mLGS and higher late diastolic strain rate (LA-mSRA), suggesting an impairment of left atrial reservoir function and booster function in patients with CSFP. The correlation test revealed a negative correlation between LA-mGLS and mTFC, suggesting that the overall LA function will further decrease with a decrease in coronary blood flow velocity.The effect of CSFP on LA functions remains controversialFirstly, this is a single-center conducted retrospective study and 2D-STE data was measured by a single-skilled echocardiologist. Secondly, the patients’ usage of medications was not taken into consideration. Finally, no follow-up data was provided at this time.In conclusion, the CSFP was relatively frequent. The percentage of mononuclear cells can be considered independent predictors of this phenomenon. The functions of the LA  were impaired in patients with the CSFP as evaluated through 2D-STE.


TBX1 was originally thought to be the main cause of the 22q11.2 microdeletion syndrome phenotype, but TBX1 is not included in the atypical central 22q11.2 microdeletion. Previous reports have suggested an association between TAPVC and the 15q11.2 BP1-BP2 microdeletion. Our report does not support this association as the maternal aunt, who harbors both microdeletions, is unaffected by TAPVC, and the male infant affected by TAPVC does not harbor the 15q11.2 BP1-BP2 microdeletion. Our findings support that genes located in the central 22q11.2 region are important for heart development and that haploinsufficiency of these genes plays a crucial role in the development of the rare heart defect TAPVC.In this clinical report, we describe a male infant and his mother, who had similar congenital heart defects. They were both diagnosed neonatally with total anomalous pulmonary venous connection (TAPVC) in combination with other heart defects. Neither of the two had any other organ malformations or dysmorphic facial features. SNP-array identified a central 22q11.2 microdeletion in the male infant and his mother as well as in the maternal grandmother and maternal aunt. The mother and the maternal aunt additionally harbored a 15q11.2 BP1-BP2 microdeletion. The maternal grandmother was unaffected by heart disease. However, heart computed tomography scan of the maternal aunt revealed a quadricuspid aortic valve. Additionally, the maternal grandmother and the maternal aunt both had significant learning disabilities. Rarely, TAPVC has been described in patients with the common 22q11.2 microdeletions. However, to the best of our knowledge, TAPVC has not previously been reported in patients with this small central 22q11.2 microdeletion. Haploinsufficiency of  Chromosome 22q11.2 includes a number of regions with highly repetitive DNA sequences referred to as low copy repeats (LCRs). These sequences are named LCR22-A to LCR22-H and cause chromosomal instability as they predispose to nonhomologous recombinations that lead to frequent microdeletions and microduplications in this region.The common 22q11.2 microdeletions have a size of approximately 3 Mb spanning from LCR22-A to LCR22-D  [2]. HowTBX1, CRKL, and MAPK1 [CRKL is deleted in the central microdeletion . In TAPVC, venous blood from the pulmonary veins drains directly into the systemic veins or the coronary sinus. The incidence of TAPVC is 5.9–7.1 per 100,000 live births, and TAPVC represents only 1–5% of all congenital heart defects . FamiliaIn this clinical report, we want to draw attention to the rare small central 22q11.2 microdeletion that seems to be associated with TAPVC in a mother and her son.The proband was a male infant born at gestational age 40 + 2 to nonconsanguineous Caucasian parents. The pregnancy was complicated by gestational diabetes, but all prenatal scans had been unremarkable. The birth weight was 3320 g.Right after birth, the male infant needed treatment with continuous positive airway pressure (CPAP) and developed during the first night an increasing need for supplemental oxygen. Therefore, he was transferred to a larger hospital for more intensive care. An echocardiogram revealed a heart defect with TAPVC, where the pulmonary veins drained to the coronary sinus. The left atrium and left ventricle were hypoplastic, and a patent foramen ovale with right-to-left flow was seen. Also, he had a patent ductus arteriosus (PDA). Despite repeated surgeries, he died at the age of 12 days.The autopsy revealed a heart with surgically corrected TAPVC, a hypoplastic left ventricle, and right coronary artery origin above the sinus of Valsalva. No other malformations were found, neither was he found to have dysmorphic features. Histology showed consequences of surgery and treatment with extracorporeal membrane oxygenation (ECMO), such as infarction in the myocardium, liver, and right adrenal gland.His mother was also born with a congenital heart defect. She underwent surgery when she was five weeks old for TAPVC, PDA, atrial septal defect (ASD), and ventricular septal defect (VSD). Ultrasound examination of the kidneys was normal. She is 157 cm tall and has completed mainstream school. No other diseases were reported in her medical history.Since the mother and son suffered from similar severe and rare congenital heart defects, the mother was referred for genetic counselling.Trio-exome sequencing of the mother, father, and son did not identify any pathogenic or likely pathogenic variants in genes previously associated with congenital heart defects.Single-nucleotide polymorphism array (SNP-array) analysis of the son identified a 1.1 Mb 22q11.2 microdeletion . This deleted region is referred to as LCR B-to-D. Subsequently, the same microdeletion was identified in the mother. Additionally, a 15q11.2 BP1-BP2 microdeletion  was identified in the mother. SNP-array of the maternal grandfather, who was born with cleft lip and palate, did not identify the 22q11.2 microdeletion, but only the 15q11.2 BP1-BP2 microdeletion. The maternal grandmother had died of lymphoma. Therefore, DNA extracted from paraffin-embedded tissue was tested postmortem. SNP-array was not possible, but multiplex ligation-dependent probe amplification (MLPA) assay identified the identical 22q11.2 microdeletion in the maternal grandmother. She was not diagnosed with any heart disease, but she had significant learning disability and had attended special school. Lastly, SNP-array of the maternal aunt identified the 22q11.2 microdeletion as well as the 15q11.2 BP1-BP2 microdeletion. The maternal aunt is 155 cm tall. Echocardiography and ultrasound examination of the kidneys were normal, but heart computed tomography scan revealed a quadricuspid aortic valve. She has significant learning disability and has attended the same special school as her mother. Also, several minor dysmorphic facial features were noted, see pedigree .Written informed consent for publication was obtained from the mother, the maternal aunt, and the maternal grandfather.In this clinical report, we report a male infant and his mother, who had similar severe, isolated heart defects and were both found to have a small central 22q11.2 microdeletion. For this reason, we assume that the microdeletion plays a crucial role in the development of this specific congenital heart defect, TAPVC. To our knowledge, the small central microdeletion has not previously been associated with TAPVC. Congenital heart defects are previously reported in patients with the central 22q11.2 microdeletion, but they are usually less severe.CRKL but not TBX1, had congenital heart defects [In the DECIPHER database , we iden defects . Subsequ defects .TBX1 as well as CRKL.One study has described an association between 22q11.2 copy number variants and anomalous pulmonary venous connection (APVC) [The importance of the size of the 22q11.2 microdeletions has been studied previously. It has repeatedly been found that the size of the microdeletions seems not to correlate with the clinical symptoms , 10, 14.CRKL gene has previously been proposed to play an important role in the development of congenital heart defects, either independently or through modification of TBX1 expression [CRKL expression have supported that CRKL has a role in the development of congenital heart defects [The central 22q11.2 microdeletion overlaps 40 HGNC genes of which 16 genes are OMIM genes. None of the individual genes are known to cause disease in humans when deleted in heterozygous form. However, particularly the pression , 10. Als defects –17.CRKL gene, the PI4KA and LZTR1 genes, which are also included in this central 22q11.2 microdeletion, are implicated in the heart phenotype [PI4KA loss-of-function disrupts the brain, heart, and trunk development [PI4KA in the heart phenotype has not been supported in mammalian model organisms, but multiple reports implicate PI4KA in the neuropsychiatric phenotype [PI4KA are known to cause perisylvian polymicrogyria, cerebellar hypoplasia, and arthrogryposis in humans [Motahari et al. have suggested that besides from the henotype . In zebrelopment . Howeverhenotype , 19, andn humans .LZTR1 cause Noonan syndrome. Heart malformations are common in Noonan syndrome, particularly pulmonary valve stenosis, septal defects, and coarctation of the aorta. Steklov et al. demonstrated that LZTR1 haploinsufficiency in mice recapitulates the Noonan syndrome phenotype including various heart malformations [Heterozygous and biallelic, pathogenic variants in rmations .CRKL and LZTR1 seem to be the strongest candidate genes in the central 22q11.2 region implicated in the heart phenotype.Overall, SNAI1, HMGA2, and VAV2 that seemed to be important for the development of TAPVC [Other genes outside the 22q11.2 region have also been proposed to be associated with the development of TAPVC. One study investigated 178 TAPVC patients by next-generation sequencing and identified three candidate genes Another study investigated 231 TAPVC patients and found 13 patients with a 15q11.2 microdeletion, whereas the 15q11.2 microdeletion was not found in 200 controls . HoweverCRKL and LZTR1 are important for heart development, and with this case, we suggest that CRKL and LZTR1 haploinsufficiency may play a crucial role in the development of TAPVC, although the phenotype may vary even within the same family.This clinical report supports the previous assumption that


Significant interaction was observed between age and PVC with young age people at greater risk of developing heart failure for having PVC. The incidence of ventricular arrhythmia was also significantly increased in people with PVC . Age and chronic kidney disease had significant interactions with PVC. In conclusion, the incidence of heart failure and ventricular arrhythmia was significantly increased in people with PVC. Outpatient follow-up of people with PVC can be helpful to detect early signs of heart failure or advanced forms of ventricular arrhythmia.Premature ventricular contraction (PVC), a common arrhythmia affecting 1–2% of the general population, has been considered to have a benign clinical course. However, people with PVC often develop heart failure and ventricular arrhythmias such as ventricular tachycardia. We aimed to clarify the risk of heart failure and lethal ventricular arrhythmias in people with PVC. The Korean National Health Insurance Service database was used for this study. People who underwent nationwide health check-ups in 2009 were enrolled in this study and clinical follow-up data until December 2018 were analyzed. Newly diagnosed PVC in 2009 (≥ 1 inpatient or outpatient claim) were identified and cumulative incidence of heart failure (≥ 1 inpatient claim) and ventricular arrhythmias (≥ 1 inpatient or outpatient claim) were compared. A total of 4515 people were first diagnosed with PVC in 2009 among 9,743,582 people without prior history of PVC, heart failure, or ventricular arrhythmias. People with newly diagnosed PVC in 2009 had a significantly higher incidence of heart failure compared to those without PVC [adjusted hazard ratio (HR)  1.371; 95% confidence interval (CI)  1.177–1.598;  People with PVC suffer from associated symptoms such as palpitations, skipped beats, chest pain, and dizziness4. Although the adverse effects of PVC are usually limited to symptoms and impaired quality of life, it can provoke other medical conditions like PVC-induced heart failure, ventricular tachycardia, or ventricular fibrillation6. Our previous work suggested that PVC can also be associated with increased risk of atrial fibrillation and ischemic stroke. Therefore, PVC can be associated with major adverse cardiac events in a subset of patients.A significant proportion of the general population is affected by premature ventricular contraction (PVC)7. Yarlagadda et al. also reported significant improvement in left ventricular systolic function after successful catheter ablation in patients with PVC8. However, evidence for chronological association between PVC and heart failure is currently lacking. The subsets of ventricular tachycardia (VT) and ventricular fibrillation (VF) are triggered by PVC and can be successfully ablated by targeting those triggering PVC10. However, the risk of developing VT or VF in patients with PVC remains to be elucidated, especially by chronological data and not just cross-sectional data. We aimed to evaluate the incidence of heart failure and lethal ventricular arrhythmias  in people with and without PVC using the Korean National Health Insurance Service (K-NHIS) database.The currently available evidence for PVC-induced heart failure is limited. Duffee and colleagues reported a significant improvement in left ventricular function after suppressing PVC with amiodarone in five patientshttps://nhiss.nhis.or.kr/), medical researchers are able to analyze healthcare information data stored in the K-NHIS database.We used the K-NHIS database to conduct this study. The majority of residents of the Republic of Korea are mandatory subscribers of K-NHIS, the single medical insurer managed by the government. Therefore, data obtained from the K-NHIS represents the entire population of the Republic of Korea. Healthcare information such as inpatient and outpatient service records; diagnostic codes for various disease such as PVC, heart failure, VT, ventricular flutter, and VF; prescription records; and mortality data are stored in the K-NHIS database. A nationwide health check-up service is provided regularly for all subscribers. People who underwent a nationwide health check-up at certain times can comprise a valuable research cohort with a significantly large sample size. If the study protocols are approved by the official review committee  those diagnosed with PVC in 2009 and (2) those not diagnosed with PVC in 2009. Follow-up data were available until 2018. The incidence of heart failure and ventricular arrhythmia composite was compared between people with and without PVC. Newly developed PVCs after 2009 was censored. The incidence of heart failure and ventricular arrhythmia composite was defined as the number of events calculated for 1000 person * years of follow-up.Two criteria were used to identify people with PVC: (1) one outpatient record (PVC 1) or (2) two or more outpatient records or one inpatient record (PVC 2) of International Classification of Disease, Tenth Revision (ICD-10) codes in the K-NHIS database. People with highly symptomatic PVC will likely seek frequent medical assistance. Therefore, PVC 2 which was diagnosed with more intensified criteria can represent more symptomatic form of PVC.12. Diagnostic codes to identify PVC, heart failure, VT, ventricular flutter, VF, and SCD are described in Supplementary Table Heart failure was diagnosed by one inpatient record for heart failure. Diagnosis of VT, ventricular flutter, and VF required one outpatient or inpatient record. The robustness of this definition has been validated in previous studiesData regarding age, sex, body mass index (BMI), smoking status, alcohol consumption status, and medical conditions such as hypertension, diabetes mellitus, chronic kidney disease, and dyslipidemia were retrieved from the K-NHIS database.t test was used for continuous variables and categorical variables were analyzed with chi-square test or Fisher’s exact test as appropriate. Kaplan–Meier curve analysis with log-rank t test was used to compare the cumulative incidence of heart failure and ventricular arrhythmia composite in people with and without PVC. Non-adjusted and adjusted hazard ratios (HR) with 95% confidence intervals (CI) were calculated with Cox regression analysis. Three different multivariate models were used: (1) model 1: adjusted for age and sex; (2) model 2: adjusted for age, sex, smoking status, alcohol consumption status, regular physical activity, and BMI; and (3) model 3: adjusted for age, sex, smoking status, alcohol consumption status, regular physical activity, BMI, hypertension, diabetes mellitus, and dyslipidemia. All tests were two-tailed, and p  values ≤ 0.05 were considered statistically significant. All statistical analyses were performed with SAS version 9.2 .Student’s In 2009, 10,601,284 people underwent nationwide health check-ups. People who were (1) under 20 years or (2) had a prior history of PVC, heart failure, VT, ventricular flutter, VF, SCD, AF, or ischemic stroke were excluded. After excluding people with missing data, 9,743,582 were included in the analysis. Figure p  < 0.001). Kaplan–Meier curve analysis also showed significantly higher cumulative incidence of newly detected heart failure in people with PVC . In people with PVC, 165 newly detected heart failure occurred during the 40,899 person * year follow-up  occurred during the 89,718,315 person * year follow-up in people without PVC (incidence = 0.282). In people with PVC, 92 ventricular arrhythmia composite occurred during the 40,922 person * year follow up . Chronological demonstration of the increased incidence of heart failure and ventricular arrhythmia composite based on a nationwide cohort data is the strength of our study. We performed subgroup analyses and found that age had significant interactions with PVC in developing heart failure and ventricular arrhythmia composite. People with prior diagnosis of PVC identified by ICD-10 codes will have heterogeneous duration of PVC. Therefore, we excluded people who had a prior diagnosis of PVC during 2002 to 2008 and analyzed those who were newly diagnosed with PVC in 2009. With sufficient duration of follow-up and large sample size, we were able to analyze chronological influence of newly diagnosed PVC on heart failure and lethal ventricular arrhythmias.14. The diagnosis of PVC-induced cardiomyopathy in these studies are all based on inference: the diagnosis was made after improvement in left ventricular systolic function with PVC suppression15. In a recent analysis, improved survival was observed when PVC-induced cardiomyopathy was treated with amiodarone.Prior studies reported a significant improvement of left ventricular systolic function after successful suppression of PVC16. Another study reported that 4% among patients with PVC eventually developed left ventricular dysfunction during median 60.0 months17. Our results are in accordance with prior studies and demonstrated that the incidence of heart failure is significantly higher in people with PVC (HR  1.371). The presence of PVC can be a marker of preexisting cardiomyopathy. To rule out this possibility we excluded people with medical history of heart failure during the screening period. Prior diagnosis of PVC was also an exclusion criterion since these people could have had PVC for several years and might already have sub-clinical cardiomyopathy related with PVC. Therefore, we analyzed the incidence of heart failure in people who was diagnosed with new-onset PVC in 2009. We believe this selection process helped to reveal the true impact of PVC on development of heart failure.Previous observational study reported a 71% increased risk of heart failure in people with PVC with annual incidence close to 1%21. A previous study by Leclercq et al. showed that various cardiac hemodynamics, such as cardiac output, pulmonary capillary wedge pressure, right atrial pressure, pulmonary artery pressure, and left ventricular ejection fraction, are better in AAI pacing, which preserves both normal atrioventricular and biventricular synchrony as compared to DDD or VVI pacing21. Intermittent dyssynchronous contraction of ventricles induced by PVC may cause adverse hemodynamic changes similar to ventricular pacing and gradually provoke cardiomyopathy and clinical heart failure.The underlying mechanism of PVC-induced cardiomyopathy remains controversial. In theory, mechanistic features of PVC-induced cardiomyopathy and pacing-induced cardiomyopathy may be similar: a ventricular dyssynchrony22. Kowlgi et al. reported that post-extrasystolic potentiation at baseline might predict future occurrence of PVC-induced cardiomyopathy as it reflects the myocardial adaptation reserve to PVCs23. In the other hand, the higher post-extrasystolic potentiation in patients with already developed PVC-induced cardiomyopathy indicated the lower contractile function when ectopy is not present23. Echocardiographic evaluation of post-extrasystolic potentiation might assist us to identify patients at risk of developing PVC-induced cardiomyopathy and to select who would benefit most from PVC suppression23.Another important feature of PVC is post-extrasystolic potentiation a phenomenon of a transient increase in contractility following PVC. Billet et al. reported that patients with PVC-induced cardiomyopathy had higher percentage of PVCs with post-extrasystolic potentiation compared to patients with PVC but without cardiomyopathy suggesting post-extrasystolic potentiation can lead to myocardial burnout24. Dukes et al. reported that attributable risk of PVC for heart failure was comparable to other traditional risk factors for heart failure such as hypertension, age, and coronary artery disease especially when the burden of PVC is high24. Premature ventricular contraction can be suppressed by medications or radiofrequency catheter ablation, which can provide the diagnosis of PVC-induced cardiomyopathy if LV function improves or recovers19. Significant interaction between age and PVC was observed in our study with young people more vulnerable to adverse impact of PVC on heart failure and ventricular arrhythmias which is in accordance with prior study25. The underlying mechanism of such interaction is unclear but PVC in young people might represent more malignant form of PVC and therapeutic impact of aggressive suppression of PVC in young people is an area of future research.Prior studies suggested that the burden of PVC is a significant risk factor for PVC-induced cardiomyopathy26. A total of 404 students were found to have PVC in their baseline ECG and the authors obtained follow-up electrocardiogram data of 166 students. Three students among 166 developed VT during follow-up but without any statistical significance. Due to lack of follow-up data of students without PVC, they were not able to compare the incidence of VT between those with and without PVC. In people with a structurally normal heart, PVC has a benign prognosis28. However, our study revealed that people with PVC are subject to a 5.6-fold increased risk of developing lethal events such as VT, ventricular flutter, or VF. Since atrial premature contraction, especially that originating from the pulmonary veins, can induce atrial tachycardia or AF, it is not surprising that PVC can trigger VT or VF30. Furthermore, PVC and lethal ventricular arrhythmias might share similar substrates. Ghannam and colleagues demonstrated that the presence and amount of myocardial scarring observed in delayed enhancement cardiac magnetic resonance imaging was associated with future risk of VT31. Huizar and his colleagues suggested that in addition to myocardial dysfunction, electrical remodeling, autonomic dysregulation, and myocardial fibrosis by PVC can lead to increased risk of sudden cardiac death32. Whether PVC suppression by radiofrequency catheter ablation can reduce the incidence of sudden cardiac death is a promising area of future research since PVC suppression will not only improve heart function but can also eliminate the trigger of lethal ventricular arrhythmias32.The incidence of ventricular arrhythmias such as VT or VF in people with PVC is not well reported. Nomura et al. reported the prevalence of PVC among 170,088 Japanese students24. Lack of PVC burden quantification in our study might be the cause of this disparity. In a recent post-hoc analysis of the CHF-STAT study, improved survival was observed when PVC-induced cardiomyopathy was treated with amiodarone suggesting potential association between PVC and increased risk of all-cause mortality33.In contrast to prior report, all-cause mortality did not differ between people with and without PVC in our analysis34. Fourth, the results of this study cannot be directly applied to different ethnic groups since our cohort consists exclusively of East Asians. Finally, our coding strategy for PVC needs further validation despite our prior publication using the same method to identify PVC35.Several limitations exist in this study. First, the burden of PVC measured by Holter monitoring was not available since the K-NHIS database does not have any information about PVC burden. However, we divided people with PVC into PVC 1 and PVC 2; the diagnosis of PVC 2 was based on intensified criteria and therefore represents more severe forms of PVC. The risk of ventricular arrhythmia composite was higher in PVC 2 than PVC 1. Second, we were not able to analyze future risk of heart failure and ventricular arrhythmia composite according to the morphology or coupling interval of PVC. Dyssynchronous ventricular contraction can be affected by the origin of PVC and might impact the development of cardiomyopathy. The short coupling interval of PVC can have a higher risk of triggering VT or VF. Third, due to the nature of our study design—a retrospective analysis based on a nationwide health care database—there could be coding inaccuracies, missing data, inaccurate reporting, and selection bias, although our coding and selection strategy has been validated in multiple previous studiesThe incidence of heart failure and ventricular arrhythmia composite is significantly increased in people with PVC. Serial outpatient follow-up of people with PVC can be helpful for early detection of heart failure and lethal ventricular arrhythmias.Supplementary Information.