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Abstract Background Integration of a patient’s non-invasive imaging data in a digital twin (DT) of the heart can provide valuable insight into the myocardial disease substrates underlying left ventricular (LV) mechanical discoordination. However, when generating a DT, model parameters should be identifiable to obtain robust parameter estimations. In this study, we used the CircAdapt model of the human heart and circulation to find a subset of parameters which were identifiable from LV cavity volume and regional strain measurements of patients with different substrates of left bundle branch block (LBBB) and myocardial infarction (MI). To this end, we included seven patients with heart failure with reduced ejection fraction (HFrEF) and LBBB (study ID: 2018-0863, registration date: 2019–10–07), of which four were non-ischemic (LBBB-only) and three had previous MI (LBBB-MI), and six narrow QRS patients with MI (MI-only) (study ID: NL45241.041.13, registration date: 2013–11–12). Morris screening method (MSM) was applied first to find parameters which were important for LV volume, regional strain, and strain rate indices. Second, this parameter subset was iteratively reduced based on parameter identifiability and reproducibility. Parameter identifiability was based on the diaphony calculated from quasi-Monte Carlo simulations and reproducibility was based on the intraclass correlation coefficient ( $${ICC}$$ ICC ) obtained from repeated parameter estimation using dynamic multi-swarm particle swarm optimization. Goodness-of-fit was defined as the mean squared error ( $${{{\chi}}}^{{2}}$$ χ 2 ) of LV myocardial strain, strain rate, and cavity volume. Results A subset of 270 parameters remained after MSM which produced high-quality DTs of all patients ( $${{{\chi}}}^{{2}}$$ χ 2

Abstract Background The National Health Insurance (NHI) was implemented in Indonesia in 2014, and cardiovascular diseases are one of the diseases that have overburdened the healthcare system. However, data concerning the relationship between NHI and cardiovascular healthcare in Indonesia are scarce. We aimed to describe changes in cardiovascular healthcare after the implementation of the NHI while determining whether the implementation of the NHI is related to the in-hospital mortality of patients with acute coronary syndrome (ACS). Methods This is a retrospective comparative study of two cohorts in which we compared the data of 364 patients with ACS from 2013 to 2014 (Cohort 1), before and early after NHI implementation, with those of 1142 patients with ACS from 2018 to 2020 (Cohort 2), four years after NHI initiation, at a tertiary cardiac center in Makassar, Indonesia. We analyzed the differences between both cohorts using chi-square test and Mann-Whitney U test. To determine the association between NHI and in-hospital mortality, we conducted multivariable logistic regression analysis. Results We observed an increase in NHI users (20.1% to 95.6%, p

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

ABSTRACT: Background: While late gadolinium enhancement (LGE) is proposed as a diagnostic criterion for arrhythmogenic right ventricular cardiomyopathy (ARVC), the potential of LGE to distinguish ARVC from differentials remains unknown. We aimed to assess the diagnostic value of LGE for ARVC diagnosis. Methods: We included 132 subjects (60% male, 47 ± 11 years) who had undergone cardiac magnetic resonance imaging with LGE assessment for ARVC or ARVC differentials. ARVC was diagnosed as per 2010 Task Force Criteria (n = 55). ARVC differentials consisted of familial/genetic dilated cardiomyopathy (n = 25), myocarditis (n = 13), sarcoidosis (n = 20), and amyloidosis (n = 19). The diagnosis of all differentials was based on the most current standard of reference. The presence of LGE was evaluated using a 7-segment right ventricle (RV) and 17-segment left ventricle (LV) model. Subsequently, we assessed LGE patterns for every patient individually for fulfilling LV- and/or RV-LGE per Padua criteria, independent of their clinical diagnosis (i.e. phenotype). Diagnostic values were analyzed using sensitivity and specificity for any RV-LGE, any LV-LGE, RV-LGE per Padua criteria, and prevalence graphs for LV-LGE per Padua criteria. The optimal integration of LGE for ARVC diagnosis was determined using classification and regression tree analysis. Results: One-third (38%) of ARVC patients had RV-LGE, while half (51%) had LV-LGE. RV-LGE was less frequently observed in ARVC vs non-ARVC patients (38% vs 58%, p = 0.034) leading to a poor discriminatory potential (any RV-LGE: sensitivity 38%, specificity 42%; RV-LGE per Padua criteria: sensitivity 36%, specificity 44%). Compared to ARVC patients, non-ARVC patients more often had LV-LGE (91% vs 51%, p

Abstract Diastolic dysfunction of the left ventricle (LVDD) is equally common in elderly women and men. LVDD is a condition that can remain latent for a long time but is also held responsible for elevated left ventricular filling pressures and high pulmonary pressures that may result in (exercise-induced) shortness of breath. This symptom is the hallmark of heart failure with preserved ejection fraction (HFpEF) which is predominantly found in women as compared to men within the HF spectrum. Given the mechanistic role of LVDD in the development of HFpEF, we review risk factors and mechanisms that may be responsible for this sex-specific progression of LVDD towards HFpEF from an epidemiological point-of-view and propose future research directions.

Abstract Backgrounds The increasing burden of cardiovascular disease (CVD) has become a major challenge globally, including in Indonesia. Understanding the readiness of primary health care facilities is necessary to confront the challenge of providing access to quality CVD health care services. Our study aimed to provide information regarding readiness to deliver CVD health services in public primary health care namely Puskesmas. Methods The study questionnaire was adapted from the World Health Organization (WHO) Service Availability and Readiness Assessment (SARA), modified based on the package of essentials for non-communicable disease (PEN) and the Indonesian Ministry of health regulation. Data were collected from all Puskesmas facilities (N = 47) located in Makassar city. We analysed relevant data following the WHO-SARA manual to assess the readiness of Puskesmas to deliver CVD services. Human resources, diagnostic capacity, supporting equipment, essential medication, infrastructure and guidelines, and ambulatory services domain were assessed based on the availability of each tracer item in a particular domain. The mean domain score was calculated based on the availability of tracer items within each domain. Furthermore, the means of all domains’ scores are expressed as an overall readiness index. Higher scores indicate greater readiness of Puskesmas to deliver CVD-related health care. Results Puskesmas delivers health promotion, disease prevention, and prompt diagnosis for cardiovascular-related diseases, including hypertension, diabetes, coronary heart disease (CHD), and stroke. Meanwhile, basic treatments were observed in the majority of the Puskesmas. Long-term care for hypertension and diabetes patients and rehabilitation for CHD and stroke were only observed in a few Puskesmas. The readiness score of Puskesmas to deliver CVD health care ranged from 60 to 86 for. Furthermore, there were 11 Puskesmas (23.4%) with a score below 75, indicating a sub-optimal readiness for delivering CVD health services. A shortage of essential medicines and a low capacity for diagnostic testing were the most noticeable shortcomings leading to suboptimal readiness for high-quality CVD health services. Conclusion Close cooperation with the government and other related stakeholders is required to tackle the identified shortcomings, especially the continuous monitoring of adequate supplies of medicines and diagnostic tools to achieve better CVD care for patients in Indonesia.

Multivalvular heart disease (MVD) implies the presence of concomitant valvular lesions on two or more heart valves. This condition has become common in the few last years, mostly due to population aging. Every combination of valvular lesions uniquely redefines the hemodynamics of a patient. Over time, this may lead to alterations in left ventricle (LV) dimensions, shape and, eventually, function. Since most of the echocardiographic parameters routinely used in the valvular assessment have been developed in the context of single valve disease and are frequently flow- and load-dependent, their indiscriminate use in the context of MVD can potentially lead to errors in judging lesion severity. Moreover, the combination of non-severe lesions may still cause severe hemodynamic consequences, and thereby systolic dysfunction. This review aims to discuss the most frequent combinations of MVD and their echocardiographic caveats, while addressing the opportunities for a multimodality assessment to achieve a better understanding and treatment of these patients.

Abstract Backgrounds The majority of risk factors for cardiovascular diseases (CVDs) are modifiable. Continuous monitoring and control of these factors could significantly reduce the risk of CVDs-related morbidity and mortality. This study estimated the prevalence of modifiable risk factors in Indonesia and its co-occurence of multiple risk factors stratified by prior CVDs diagnosis status and sex. Methods Adult participants (> 15 years, N = 36,329, 57% women) with median age of 40 years were selected from a nationwide Indonesian cross-sectional study called Basic Health Research or Riset Kesehatan Dasar (Riskesdas) conducted in 2018. Thirteen risk factors were identified from the study, including smoking, a high-risk diet, inadequate fruit and vegetable consumption, a low physical activity level, the presence of mental-emotional disorders, obesity, a high waist circumference (WC), a high waist-to-height ratio (WtHR), hypertension, diabetes, a high total cholesterol level, a high low-density lipoprotein (LDL) cholesterol level, and a low high-density lipoprotein (HDL) cholesterol level. Age-adjusted prevalence ratios stratified by CVDs status and sex were calculated using Poisson regression with the robust covariance estimator. Results CVDs were found in 3% of the study population. Risk factor prevalence in the overall population ranged from 5.7 to 96.5% for diabetes and inadequate fruit and vegetable consumption respectively. Smoking, a high-risk food diet, and a low HDL cholesterol level were more prevalent in men, whereas a low physical activity level, the presence of mental-emotional disorders, obesity, a high WC, a high WtHR, hypertension, diabetes, a high total cholesterol level, and a high LDL cholesterol level were more prevalent in women. Approximately 22% of men and 18% of women had at least 4 risk factors, and these proportions were higher in participants with prior CVDs diagnosis. Conclusions There is a high prevalence of modifiable risk factors in the Indonesian adult population. Sex, age, and the presence of CVD are major determinants of the variations in risk factors. The presence of multiple risk factors, which are often inter-related, requires a comprehensive approach through health promotion, lifestyle modification and patient education.

Background: Mitral regurgitation (MR) burdens the left and right ventricles with a volume or pressure overload that leads to a series of compensatory adaptations that eventually lead to ventricular dysfunction, and it is well known that in rheumatic heart disease (RHD) that the inflammatory process not only occurs in the valve but also involves the myocardial and pericardial layers. However, whether the inflammatory process in rheumatic MR is associated with ventricular function besides hemodynamic changes is not yet established. Purpose: Evaluate whether rheumatic etiology is associated with ventricular dysfunction in patients with chronic MR. Methods: The study population comprised patients aged 18 years or older included in the registry who had echocardiography performed at the National Cardiovascular Center Harapan Kita in Indonesia during the study period with isolated primary MR due to rheumatic etiology and degenerative process with at least moderate regurgitation. Results: The current study included 1,130 patients with significant isolated degenerative MR and 276 patients with rheumatic MR. Patients with rheumatic MR were younger and had a higher prevalence of atrial fibrillation and pulmonary hypertension, worse left ventricle (LV) ejection fraction and tricuspid annular plane systolic excursion (TAPSE) value, and larger left atrium (LA) dimension compared to patients with degenerative mitral regurgitation (MR). Gender, age, LV end-systolic diameter, rheumatic etiology, and TAPSE were independently associated with more impaired LV ejection fraction. Whereas low LV ejection fraction, LV end-systolic diameter, and tricuspid peak velocity (TR) peak velocity >3.4 m/s were independently associated with more reduced right ventricle (RV) systolic function (Table 3). Conclusions: Rheumatic etiology was independently associated with more impaired left ventricular function; however, rheumatic etiology was not associated with reduced right ventricular systolic function in a patient with significant chronic MR.

IntroductionDespite advances in diagnostic and treatment, morbidity and mortality due to infective endocarditis (IE) has not decreased. There is a discrepancy in epidemiology of IE between developed and developing countries. Over the last years, increased early detection and consequently prevalence of rheumatic heart disease (RHD) and congenital heart disease (CHD) which are considered predisposing conditions for IE, is noted. Here, we present a review of literature on IE in developing countries.MethodsWe conducted a systematic literature search of IE studies in developing countries through PubMed and Embase. We have divided the studies into two groups: studies published before 2015 (group 1) and studies ≥ 2015 (group 2). The outcome was defined as a difference in epidemiology, microbiology, treatment, and mortality over time. The Scale for Assessment of Narrative Review Articles guidelines was applied.FindingsIn total, 16 studies were included. The total number of IE cases was 1,098 and 1,505 in groups 1 and 2, respectively. We compared 4/7 cohorts from group 1 (n = 789) with 5/9 cohorts from group 2 (n = 636). Six studies were not included in the comparison because they were interacting between the two cohorts. Males predominated in all studies. Rheumatic heart disease was higher in group 1 than in group 2 (42.3% vs. 30.3%, p < 0.001) while for CHD there was no change (17.6% vs. 16.7%, p = 0.672). Streptococci infections was lower in group 1 than group 2 (26.2% vs. 37.7%, p < 0.001). The proportion of Staphylococcus aureus was 15.3% in group 1 and 23.6% in group 2, p < 0.001. Negative blood culture (NBC) was higher in group 1 than in group 2 (42.2% vs. 34.1%, p = 0.002). Patients in group 1 received more surgery than in group 2 (38.8% vs. 28.8%, p < 0.001). Mortality was similar in the two groups (20.9% vs. 22.3%, p = 0.518).ConclusionThis review shows a scarcity of studies on IE in developing countries. Rheumatic heart disease and congenital heart disease are common predisposing conditions. Other risk factors are prosthetic valves, degenerative valve disease (DVD), intravenous drug use, and human immunodeficiency virus infection. While the proportion of IE cases caused by Streptococcus and Staphylococcus has increased, the number of NBC and patients getting surgery has decreased. Mortality has not changed over time. Timely diagnosis and management of patients with RHD and CHD and comprehensive management of IE are warranted.

Background Idiopathic ventricular fibrillation (IVF) is diagnosed in patients with ventricular fibrillation of which the origin is not identified after extensive evaluations. Recent studies suggest an association between mitral annulus disjunction (MAD), mitral valve prolapse (MVP), and ventricular arrhythmias. The prevalence of MAD and MVP in patients with IVF in this regard is not well established. We aimed to explore the prevalence of MAD and MVP in a consecutive cohort of patients with IVF compared with matched controls. Methods and Results In this retrospective, multicenter cohort study, cardiac magnetic resonance images from patients with IVF (ie, negative for ischemia, cardiomyopathy, and channelopathies) and age‐ and sex‐matched control subjects were analyzed for the presence of MAD (≥2 mm) and MVP (>2 mm). In total, 72 patients (mean age 39±14 years, 42% women) and 72 control subjects (mean age 41±11 years, 42% women) were included. MAD in the inferolateral wall was more prevalent in patients with IVF versus healthy controls (7 [11%] versus 1 [1%], P=0.024). MVP was only seen in patients with IVF and not in controls (5 [7%] versus 0 [0%], P=0.016). MAD was observed in both patients with (n=4) and without (n=3) MVP. Conclusions Inferolateral MAD and MVP were significantly more prevalent in patients with IVF compared with healthy controls. The authors advocate that evaluation of the mitral valve region deserves extra attention in the extensive screening of patients with unexplained cardiac arrest. These findings support further exploration of the pathophysiological mechanisms underlying a subset of IVF that associates with MAD and MVP.

Abstract Background Anthracycline-induced cardiac dysfunction (ACD) is a notorious side effect of anticancer treatment. It has been described as a phenomenon of a continuous progressive decline of cardiac function, eventually leading to dilated cardiomyopathy (DCM). This progressive nature suggests that patients with a delayed ACD diagnosis have greater compromise of cardiac function and more adverse remodeling, with a poor response to heart failure (HF) treatment. This study aimed to delineate the impact of a delayed ACD diagnosis on echocardiographic characteristics and response to HF treatment. Methods and results From the population of our cardio-oncology outpatient clinic, 92 ACD patients were included in this study (age 51.6 ± 16.2 years, median cumulative anthracycline dose 329 [200–329] mg/m2), and a median follow-up of 25.0 [9.6–37.2] months after ACD diagnosis. Median time to ACD diagnosis for patients diagnosed early ( 1 year) was 4.0 vs. 47.7 months respectively. There were no echocardiographic differences between patients diagnosed early vs. late (LVEF 43.6 ± 4.9% vs. 43.0 ± 6.2% and iEDV 63.6 vs. 62.9 mL/m2). Eighty-three percent of patients presented with mild LV dysfunction and in 79% the LV was not dilated. Patients diagnosed early were more likely to have (partial) recovery of cardiac function upon HF treatment initiation (p = 0.015). Conclusions In the setting of a cardio-oncology outpatient clinic, patients with ACD presented with a hypokinetic non-dilated cardiomyopathy, rather than typical DCM. Timing of ACD diagnosis did not impact HF disease severity. However, in patients receiving an early diagnosis, cardiac function was more likely to recover upon HF treatment.

Objectives The ankle brachial index (ABI) can be used to diagnose peripheral arterial disease (PAD). The clinical relevance of the ABI, especially in patients with known clinically manifest cardiovascular disease (CVD), is unknown. The authors set out to investigate the relationship between a screen-detected ABI and the risk for future cardiovascular morbidity and mortality in patients with clinically manifest CVD. Design, materials and methods Patients with clinically manifest CVD were selected from the UCC-SMART cohort (n = 8360) and divided into four groups: normal ABI (0.91–1.39), screen-detected low ABI ≤ 0.9, screen-detected high ABI ≥ 1.4, and patients with known PAD irrespective of their ABI. Adjusted Cox Proportional Hazard Ratios (HRs) for Major Adverse Cardiovascular Events (MACE), Major Adverse Limb Events (MALE), and all-cause mortality were calculated. In addition, stratified analyses for women and men and for the presence of diabetes were performed. Results During a median follow-up of 8.3 years (IQR 7.7) 1646 MACE, 601 MALE and 1958 all-cause mortalities were observed. Compared with normal ABI patients, patients with a screen-detected low ABI and patients with manifest PAD had a higher risk of MACE, MALE, and all-cause mortality with HRs of 1.9 (95% CI 1.6–2.2) for MACE, 7.6 (95% CI 5.7–10.1) for MALE, 1.7 (95% CI 1.5–2.0) for mortality and 1.3 (95% CI 1.2–1.5) for MACE, 13.8 (95% CI 11.1–17.1) for MALE, 1.7 (95% CI 1.5–1.9) for mortality, respectively. Screen-detected high ABI did not increase the risk of either MACE or MALE, however, was associated with lower risk of all-cause mortality with a HR of 0.6 (95% CI 0.5–0.9). Stratified analyses for women & men and for diabetes status were comparable for all three outcomes. Conclusions In patients with manifest CVD but without PAD, a screen-detected low ABI is a powerful risk indicator for cardiovascular events, limb events, and all-cause mortality.

Introduction: Computational models of the cardiovascular system are widely used to simulate cardiac (dys)function. Personalization of such models for patient-specific simulation of cardiac function remains challenging. Measurement uncertainty affects accuracy of parameter estimations. In this study, we present a methodology for patient-specific estimation and uncertainty quantification of parameters in the closed-loop CircAdapt model of the human heart and circulation using echocardiographic deformation imaging. Based on patient-specific estimated parameters we aim to reveal the mechanical substrate underlying deformation abnormalities in patients with arrhythmogenic cardiomyopathy (AC).Methods: We used adaptive multiple importance sampling to estimate the posterior distribution of regional myocardial tissue properties. This methodology is implemented in the CircAdapt cardiovascular modeling platform and applied to estimate active and passive tissue properties underlying regional deformation patterns, left ventricular volumes, and right ventricular diameter. First, we tested the accuracy of this method and its inter- and intraobserver variability using nine datasets obtained in AC patients. Second, we tested the trueness of the estimation using nine in silico generated virtual patient datasets representative for various stages of AC. Finally, we applied this method to two longitudinal series of echocardiograms of two pathogenic mutation carriers without established myocardial disease at baseline.Results: Tissue characteristics of virtual patients were accurately estimated with a highest density interval containing the true parameter value of 9% (95% CI [0–79]). Variances of estimated posterior distributions in patient data and virtual data were comparable, supporting the reliability of the patient estimations. Estimations were highly reproducible with an overlap in posterior distributions of 89.9% (95% CI [60.1–95.9]). Clinically measured deformation, ejection fraction, and end-diastolic volume were accurately simulated. In presence of worsening of deformation over time, estimated tissue properties also revealed functional deterioration.Conclusion: This method facilitates patient-specific simulation-based estimation of regional ventricular tissue properties from non-invasive imaging data, taking into account both measurement and model uncertainties. Two proof-of-principle case studies suggested that this cardiac digital twin technology enables quantitative monitoring of AC disease progression in early stages of disease.

Cancer therapy–related cardiac dysfunction (CTRCD) is one of the most concerning cardiovascular side effects of cancer treatment. Important reviews within the field of cardio-oncology have described various agents to be associated with a high risk of CTRCD, including mitomycin C, ifosfamide, vincristine, cyclophosphamide, and clofarabine. The aim of this study was to provide insight into the data on which these incidence rates are based. We observed that the reported cardiotoxicity of mitomycin C and ifosfamide is based on studies in which most patients received anthracyclines, complicating the interpretation of their association with CTRCD. The high incidence of vincristine-induced cardiotoxicity is based on an incorrect interpretation of a single study. Incidence rates of clofarabine remain uncertain due to a lack of cardiac screening in clinical trials. The administration of high-dose cyclophosphamide (>1.5 g/m2/day) is associated with a high incidence of CTRCD. Based on our findings, a critical re-evaluation of the cardiotoxicity of these agents is warranted.

Rheumatic heart disease (RHD) is common in developing countries and poses a big medical challenge and burden. The pathogenesis of RHD is influenced by the triad of host, agent, and environment. Autoantigens generated from Group A Streptococcus (GAS) infection are captured by the resident dendritic cells (DCs) in the heart's valvular endothelium. DCs differentiate into antigen presenting cells (APC) in the valve interstices. APC induces activation of autoreactive T cells, which triggers inflammation and tissue fibrosis. Cardiac fibrosis is promoted through the activation of Mitogen activated protein kinases (MAPKs) and its downstream signaling, including its interaction with transforming growth factor-β (TGF-β) and Smad proteins. TGF-β-induced phosphorylation of Smad2 complexes with Smad3 and Smad4, and translocates into the nucleus. Angiotensin II enhances the migration, maturation, and presentation of DC. In RHD, Angiotensin II induces fibrosis via the stimulation of TGF-β, which further increases the binding of IL-33 to sST2 but not ST2L, resulting in the upregulation of Angiotensin II and progression of cardiac fibrosis. This cascade of inflammation and valvular fibrosis causes calcification and stiffening of the heart valves in RHD. Angiotensin converting enzyme inhibitors (ACEIs) inhibit Angiotensin II production, which in turn decreases TGF-β expression and the onset of overt inflammatory response. This condition leads to a reduction in the sST2 as the decoy receptor to “steal” IL-33, and IL-33 binds to ST2L and results in cardioprotection against cardiac fibrosis in the pathogenesis of RHD.

Abstract Background Although mechanical dyssynchrony parameters derived by speckle tracking echocardiography (STE) may predict response to cardiac resynchronization therapy (CRT), comparability of parameters derived with different STE vendors is unknown. Methods In the MARC study, echocardiographic images of heart failure patients obtained before CRT implantation were prospectively analysed with vendor specific STE software (GE EchoPac and Philips QLAB) and vendor-independent software (TomTec 2DCPA). Response was defined as change in left ventricular (LV) end-systolic volume between examination before and six-months after CRT implantation. Basic longitudinal strain and mechanical dyssynchrony parameters (septal to lateral wall delay (SL-delay), septal systolic rebound stretch (SRSsept), and systolic stretch index (SSI)) were obtained from either separate septal and lateral walls, or total LV apical four chamber. Septal strain patterns were categorized in three types. The coefficient of variation and intra-class correlation coefficient (ICC) were analysed. Dyssynchrony parameters were associated with CRT response using univariate regression analysis and C-statistics. Results Two-hundred eleven patients were analysed. GE-cohort (n = 123): age 68 years (interquartile range (IQR): 61–73), 67% male, QRS-duration 177 ms (IQR: 160–192), LV ejection fraction: 26 ± 7%. Philips-cohort (n = 88): age 67 years (IQR: 59–74), 60% male, QRS-duration: 179 ms (IQR: 166–193), LV ejection fraction: 27 ± 8. LV derived peak strain was comparable in the GE- (GE: -7.3 ± 3.1%, TomTec: −6.4 ± 2.8%, ICC: 0.723) and Philips-cohort (Philips: −7.7 ± 2.7%, TomTec: −7.7 ± 3.3%, ICC: 0.749). SL-delay showed low ICC values (GE vs. TomTec: 0.078 and Philips vs. TomTec: 0.025). ICC’s of SRSsept and SSI were higher but only weak (GE vs. TomTec: SRSsept: 0.470, SSI: 0.467) (Philips vs. QLAB: SRSsept: 0.419, SSI: 0.421). Comparability of septal strain patterns was low (Cohen’s kappa, GE vs. TomTec: 0.221 and Philips vs. TomTec: 0.279). Septal strain patterns, SRSsept and SSI were associated with changes in LV end-systolic volume for all vendors. SRSsept and SSI had relative varying C-statistic values (range: 0.530–0.705) and different cut-off values between vendors. Conclusions Although global longitudinal strain analysis showed fair comparability, assessment of dyssynchrony parameters was vendor specific and not applicable outside the context of the implemented platform. While the standardization taskforce took an important step for global peak strain, further standardization of STE is still warranted.

Background In patients with chronic heart failure and chronic kidney disease, correction of anemia with erythropoietin‐stimulating agents targeting normal hemoglobin levels is associated with an increased risk of cardiovascular morbidity and mortality. Emerging data suggest a direct effect of erythropoietin on fibroblast growth factor 23 (FGF23), elevated levels of which have been associated with adverse outcomes. We investigate effects of erythropoietin‐stimulating agents in patients with both chronic heart failure and chronic kidney disease focusing on FGF23. Methods and Results In the EPOCARES (Erythropoietin in CardioRenal Syndrome) study, we randomized 56 anemic patients (median age 74 [interquartile range 69–80] years, 66% male) with both chronic heart failure and chronic kidney disease into 3 groups, of which 2 received epoetin beta 50 IU/kg per week for 50 weeks, and the third group served as control. Measurements were performed at baseline and after 2, 26, and 50 weeks. Data were analyzed using linear mixed‐model analysis. After 50 weeks of erythropoietin‐stimulating agent treatment, hematocrit and hemoglobin levels increased. Similarly, C‐terminal FGF23 levels, in contrast to intact FGF23 levels, rose significantly due to erythropoietin‐stimulating agents as compared with the controls. During median follow‐up for 5.7 (2.0–5.7) years, baseline C‐terminal FGF23 levels were independently associated with increased risk of mortality (hazard ratio 2.20; 95% CI, 1.35‐3.59; P=0.002). Conclusions Exogenous erythropoietin increases C‐terminal FGF23 levels markedly over a period of 50 weeks, elevated levels of which, even at baseline, are significantly associated with an increased risk of mortality. The current results, in a randomized trial setting, underline the strong relationship between erythropoietin and FGF23 physiology in patients with chronic heart failure and chronic kidney disease. Clinical Trial Registration URL: http://www.clinicaltrials.gov. Unique identifier: NCT00356733.

BackgroundClinical decision-making in symptomatic patients after mitral valve (MV) repair remains challenging as echocardiographic reference values are lacking. In native MV disease intervention is recommended for mean transmitral pressure gradient (TPG) >15 mmHg or systolic pulmonary artery pressure (SPAP) >60 mmHg at peak exercise. Insight into standard stress echo parameters after MV repair may therefore aid to clinical decision-making during follow-up.HypothesisStress echocardiography derived parameters in asymptomatic patients after successful MV repair differ from current guidelines for native valves.Material and methodsIn 25 patients (NYHA I) after MV repair stress echocardiography was performed on a semi-supine bicycle. Doppler flow records and MV related hemodynamics at rest and peak were obtained. Linear regression analysis was performed for mean TPG and SPAP at peak, using predetermined variables and confounders.ResultsMean TPG at rest (3.2 ± 1.4 mmHg) significantly increased at peak (15.0 ± 3.4 mmHg) but was always 57 mmHg. Only the indexed MV ring diameter was inversely correlated to mean TPG at peak in a multivariable model.ConclusionIn contrast to current recommendations in native MV disease, our data indicate that the standard value for mean TPG during stress echocardiography in asymptomatic patients after successful MV repair was above the guideline threshold of 15 mmHg in >50%, but always

BackgroundPhysical activity reduces the risk of vascular disease. This benefit is not entirely explained through an effect on vascular risk factors. We examined the relationship of physical activity and characteristics of the carotid artery wall in patients with vascular disease or risk factors. Methods and ResultsCross‐sectional analyses were performed in 9578 patients from the SMART (Second Manifestations of Arterial Disease) study, a prospective cohort study among patients with vascular disease or risk factors. Physical activity was assessed using questionnaires. Carotid intima‐media thickness and carotid artery stenosis of both common carotid arteries was measured. In a subset of 3165 participants carotid diastolic diameter and distension were assessed. Carotid stiffness was expressed as the distensibility coefficient and Young's elastic modulus. Regression analyses adjusted for vascular risk factors showed that physical activity was inversely associated with diastolic diameter (fifth versus first quintile B=−0.13 mm; 95% CI, −0.21 to −0.05) and decreased risk of carotid artery stenosis (relative risk, 0.58; 95% CI, 0.48–0.69). A light level of physical activity was associated with less carotid stiffness (second versus first quintile; Young's elastic modulus B=−0.11 kPa−1×10−3; 95% CI, −0.16 to −0.06; distensibility coefficient B=0.93 kPa×103; 95% CI, 0.34–1.51), but there was no additional benefit with increasing levels of physical activity. In patients with vascular disease, physical activity was inversely associated with common carotid intima‐media thickness, but not in patients with vascular risk factors. ConclusionsIn patients with vascular disease or risk factors, increased physical activity was associated with smaller carotid diastolic diameter, decreased risk of carotid artery stenosis, and less carotid stiffness, but it only showed benefits on carotid intima‐media thickness in patients with vascular disease.

Left ventricular volume–time curves (VTCs) provide hemodynamic data, and may help clinical decision making. The generation of VTCs using echocardiography, however, is time-consuming and prone to inter-operator variability. In this study, we used a new non-invasive, operator-independent technique, the hemodynamic cardiac profiler (HCP), to generate VTCs. The HCP, which uses a low-intensity, patient-safe, high-frequency applied AC current, and 12 standard ECG electrodes attached on the thorax in a pre-defined pattern, was applied to five young healthy volunteers, five older healthy volunteers, and five patients with severe mitral regurgitation. From the VTCs generated by the HCP, the presence or absence of an isovolumetric contraction phase (ICP) was assessed, as well as the left ventricular ejection time (LVET), time of the pre-ejection period (tPEP), and ratio of the volumes of the early (E) and late (A) diastolic filling (EV/AV ratio), and compared to 2D transthoracic echocardiography (2D TTE) at rest. The reproducibility by two different operators showed good results (RMS  =  5.2%). For intra-patient measurement RMS was 2.8%. Both LVET and the EV/AV ratio showed a strong significant correlation between HCP and 2D TTE derived parameters (p  <  0.05). For tPEP, the correlation was still weak (p  =  0.32). In all five patients with mitral regurgitation, the ICP was absent in the VTC from the HCP, whereas it was present in the 10 healthy volunteers, which is in accordance with pathophysiology. We conclude that the HCP seems to be a method for reproducible VTC generation, and may become a useful early screening tool for cardiac dysfunction in the future. [ABSTRACT FROM AUTHOR]

Abstract Background The assessment of outcomes of interventions based on the patient’s perspective using patient-reported outcome measures (PROMs) has been increasingly highlighted in clinical practice. However, health related quality of life (HRQoL), one of the common constructs measured by PROMs remain unknown among patients after heart valve replacement (HVR) in Tanzania. Objectives To assess the HRQoL amongst patients operated on for rheumatic mitral stenosis at Jakaya Kikwete Cardiac Institute (JKCI). Methods A prospective study of patients operated on due to rheumatic mitral stenosis at JKCI from January 2020 to April 2021 was undertaken. The HRQoL was assessed by using the MacNew questionnaire, addressing three domains (physical, emotional, and social function); the score ranges from 0 to 7. We categorized HRQoL as low (mean score ≤ 4.9), moderate (5–6) and high (> 6). We analysed several sociodemographic and clinical variables for HRQoL. Results Out of 54 patients, there were 34 females and 20 males. Their mean (± SD) age was 37.98 (± 12.58) years. The reliability of translated Kiswahili version of MacNew was good. The mean (± SD) global scores were 3.47 ± 0.59, 4.88 ± 0.71 and 6.14 ± 0.50 preoperatively, at 3 months and 6 months respectively (p-values

Purpose The Utrecht Cardiovascular Cohort–Second Manifestations of Arterial Disease (UCC-SMART) Study is an ongoing prospective single-centre cohort study with the aim to assess important determinants and the prognosis of cardiovascular disease progression. This article provides an update of the rationale, design, included patients, measurements and findings from the start in 1996 to date.Participants The UCC-SMART Study includes patients aged 18–90 years referred to the University Medical Center Utrecht, the Netherlands, for management of cardiovascular disease (CVD) or severe cardiovascular risk factors. Since September 1996, a total of 14 830 patients have been included. Upon inclusion, patients undergo a standardised screening programme, including questionnaires, vital signs, laboratory measurements, an ECG, vascular ultrasound of carotid arteries and aorta, ankle-brachial index and ultrasound measurements of adipose tissue, kidney size and intima–media thickness. Outcomes of interest are collected through annual questionnaires and adjudicated by an endpoint committee.Findings to date By May 2022, the included patients contributed to a total follow-up time of over 134 000 person-years. During follow-up, 2259 patients suffered a vascular endpoint (including non-fatal myocardial infarction, non-fatal stroke and vascular death) and 2794 all-cause deaths, 943 incident cases of diabetes and 2139 incident cases of cancer were observed up until January 2020. The UCC-SMART cohort contributed to over 350 articles published in peer-reviewed journals, including prediction models recommended by the 2021 European Society of Cardiology CVD prevention guidelines.Future plans The UCC-SMART Study guarantees an infrastructure for research in patients at high cardiovascular risk. The cohort will continue to include about 600 patients yearly and follow-up will be ongoing to ensure an up-to-date cohort in accordance with current healthcare and scientific knowledge. In the near future, UCC-SMART will be enriched by echocardiography, and a food frequency questionnaire at baseline enabling the assessment of associations between nutrition and CVD and diabetes.

BackgroundChronic kidney disease (CKD) and atrial fibrillation (AF) are both risk factors for bleeding, stroke and mortality. The aim of our study was to investigate the interaction between CKD and atrial fibrillation and outcomes.MethodsWe included 12,394 subjects referred to the University Medical Center Utrecht (the Netherlands) from September 1996 to February 2018 for an out-patient visit (Utrecht Cardiovascular Cohort Second Manifestation of Arterial disease cohort). Hazard ratios (HRs) with 95% confidence intervals (CIs) for bleeding, ischemic stroke or mortality were calculated with Cox proportional hazard analyses. Presence of interaction between AF and CKD was examined by calculating the relative excess risk due to interaction (RERI), the attributable proportion (AP) due to interaction and the synergy index (S).ResultsOf the 12,394 patients, 699 patients had AF, 2,752 patients had CKD and 325 patients had both AF and CKD. Patients with both CKD and AF had a 3.0-fold (95% CI 2.0-4.4) increased risk for bleeding, a 4.2-fold (95% CI 3.0-6.0) increased ischemic stroke risk and a 2.2-fold (95% CI 1.9-2.6) increased mortality risk after adjustment as compared with subjects without atrial fibrillation and CKD. We did not find interaction between AF and CKD for bleeding and mortality. However, we found interaction between AF and CKD for ischemic stroke risk (RERI 1.88 (95% CI 0.31-3.46), AP 0.45 (95% CI 0.17-0.72) and S 2.40 (95% CI 1.08-5.32)).ConclusionAF and CKD are both associated with bleeding, ischemic stroke and mortality. There is a positive interaction between AF and CKD for ischemic stroke risk, but not for bleeding or mortality.

Introduction Achieving optimal placement of the left ventricular (LV) lead in cardiac resynchronisation therapy (CRT) is a prerequisite in order to achieve maximum clinical benefit, and is likely to help avoid non-response. Pacing outside scar tissue and targeting late activated segments may improve outcome. The present study will be the first randomised controlled trial to compare the efficacy of real-time image-guided LV lead delivery to conventional CRT implantation. In addition, to estimate the cost-effectiveness of targeted lead implantation, an early decision analytic model was developed, and described here.Methods and analysis A multicentre, interventional, randomised, controlled trial will be conducted in a total of 130 patients with a class I or IIa indication for CRT implantation. Patients will be stratified to ischaemic heart failure aetiology and 1:1 randomised to either empirical lead placement or live image-guided lead placement. Ultimate lead location and echocardiographic assessment will be performed by core laboratories, blinded to treatment allocation and patient information. Late gadolinium enhancement cardiac magnetic resonance imaging (CMR) and CINE-CMR with feature-tracking postprocessing software will be used to semi-automatically determine myocardial scar and late mechanical activation. The subsequent treatment file with optimal LV-lead positions will be fused with the fluoroscopy, resulting in live target-visualisation during the procedure. The primary endpoint is the difference in percentage of successfully targeted LV-lead location. Secondary endpoints are relative percentage reduction in indexed LV end-systolic volume, a hierarchical clinical endpoint, and quality of life. The early analytic model was developed using a Markov-model, consisting of seven mutually exclusive health states.Ethics and dissemination The protocol was approved by the Medical Research Ethics Committee Utrecht (NL73416.041.20). All participants are required to provide written informed consent. Results will be submitted to peer-reviewed journals.Trial registration number NCT05053568; Trial NL8666.

PurposeTo assess specific risk factors and biomarkers associated with intimal arterial calcification (IAC) and medial arterial calcification (MAC).MethodsWe conducted a cross-sectional study in patients with or at risk of vascular disease from the SMART study(n = 520) and the DCS cohort(n = 198). Non-contrast computed tomography scanning of the lower extremities was performed and calcification in the femoral and crural arteries was scored as absent, predominant IAC, predominant MAC or indistinguishable. Multinomial regression models were used to assess the associations between cardiovascular risk factors and calcification patterns. Biomarkers for inflammation, calcification and vitamin K status were measured in a subset of patients with IAC(n = 151) and MAC(n = 151).ResultsFemoral calcification was found in 77% of the participants, of whom 38% had IAC, 28% had MAC and 11% were scored as indistinguishable. The absolute agreement between the femoral and crural arteries was high(69%). Higher age, male sex, statin use and history of coronary artery disease were associated with higher prevalences of femoral IAC and MAC compared to absence of calcification. Smoking and low ankle-brachial-index (ABI) were associated with higher prevalence of IAC and high ABI was associated with less IAC. Compared to patients with IAC, patients with MAC more often had diabetes, have a high ABI and were less often smokers. Inactive Matrix-Gla Protein was associated with increased MAC prevalence, while osteonectin was associated with decreased risk of MAC, compared to IAC.ConclusionsWhen femoral calcification is present, the majority of the patients have IAC or MAC throughout the lower extremity, which have different associated risk factor profiles.

Heart failure with a preserved ejection fraction (HFpEF) is associated with multiple comorbidities, such as old age, hypertension, type 2 diabetes and obesity and is more prevalent in females. Although the male obese ZSF1 rat has been proposed as a suitable model to study the development of diastolic dysfunction and early HFpEF, studies in female animals have not been performed yet. Therefore, we aimed to characterize the cardiac phenotype in female obese ZSF1 rats and their lean counterparts. Additionally, we aimed to investigate whether differences exist in disease progression in obese male and female ZSF1 rats. Therefore, male and female ZSF1 rats, lean as well as obese (N = 6-9/subgroup), were used. Every two weeks, from 12 to 26 weeks of age, systolic blood pressure and echocardiographic measurements were performed, and venous blood was sampled. Female obese ZSF1 rats, as compared to female lean ZSF1 rats, developed diastolic dysfunction with cardiac hypertrophy and fibrosis in the presence of severe dyslipidemia, increased plasma growth differentiation factor 15 and mild hypertension, and preservation of systolic function. Although obese female ZSF1 rats did not develop hyperglycemia, their diastolic dysfunction was as severe as in the obese males. Taken together, the results from the present study suggest that the female obese ZSF1 rat is a relevant animal model for HFpEF with multiple comorbidities, suitable for investigating novel therapeutic interventions.

BACKGROUND:Heart failure with preserved left ventricular ejection fraction (HFPEF) affects about half of all patients diagnosed with heart failure. The pathophysiological aspect of this complex disease state has been extensively explored, yet it is still not fully understood. Since the sympathetic nervous system is related to the development of systolic HF, we hypothesized that an increased sympathetic nerve activation (SNA) is also related to the development of HFPEF. This review summarizes the available literature regarding the relation between HFPEF and SNA. METHODS AND RESULTS:Electronic databases and reference lists through April 2014 were searched resulting in 7722 unique articles. Three authors independently evaluated citation titles and abstracts, resulting in 77 articles reporting about the role of the sympathetic nervous system and HFPEF. Of these 77 articles, 15 were included for critical appraisal: 6 animal and 9 human studies. Based on the critical appraisal, we selected 9 articles (3 animal, 6 human) for further analysis. In all the animal studies, isoproterenol was administered to mimic an increased sympathetic activity. In human studies, different modalities for assessment of sympathetic activity were used. The studies selected for further evaluation reported a clear relation between HFPEF and SNA. CONCLUSION:Current literature confirms a relation between increased SNA and HFPEF. However, current literature is not able to distinguish whether enhanced SNA results in HFPEF, or HFPEF results in enhanced SNA. The most likely setting is a vicious circle in which HFPEF and SNA sustain each other.

BACKGROUND:Previous studies suggested that diagnosing coronary artery disease (CAD) is more difficult in women than in men. Studies investigating the predictive value of clinical signs and symptoms and compare its combined diagnostic value between women and men are lacking. METHODOLOGY:Data from a large multicenter prospective study was used. Patients admitted to the emergency department (ED) with chest pain but without ST-elevation were eligible. The endpoint was proven CAD, defined as a significant stenosis at angiography or the diagnosis of a non-ST-elevation myocardial infarction or cardiovascular death within six weeks after presentation at the ED. Twelve clinical symptoms and seven cardiovascular risk factors were collected. Potential predictors of CAD with a p-value

Response to cardiac resynchronization therapy (CRT) is often assessed six months after implantation. Our objective was to assess the number of patients changing from responder to non-responder between six and 14 months, so-called late non-responders, and compare them to patients who were responder both at six and 14 months, so-called stable responders. Furthermore, we assessed predictive values of six and 14-month response concerning clinical outcome.105 patients eligible for CRT were enrolled. Clinical, laboratory, ECG, and echocardiographic parameters and patient-reported health status (Kansas City Cardiomyopathy Questionnaire [KCCQ]) were assessed before, and six and 14 months after implantation. Response was defined as ≥15% LVESV decrease as compared to baseline. Major adverse cardiac events (MACE) were registered until 24 months after implantation. Predictive values of six and 14-month response for MACE were examined.In total, 75 (71%) patients were six-month responders of which 12 (16%) patients became late non-responder. At baseline, late non-responders more often had ischemic cardiomyopathy and atrial fibrillation, higher BNP and less dyssynchrony compared to stable responders. At six months, late non-responders showed significantly less LVESV decrease, and higher creatinine levels. Mean KCCQ scores of late non-responders were lower than those of stable responders at every time point, with the difference being significant at 14 months. The 14 months response was a better predictor of MACE than six months response.The assessment of treatment outcomes after six months of CRT could be premature and response rates beyond might better correlate to long-term clinical outcome.