Cardiac positron emission tomography/magnetic resonance imaging (PET/MRI) can assess various cardiovascular diseases. In this study, we intra-individually compared right (RV) and left ventricular (LV) parameters obtained from dual-tracer PET/MRI scan.13N]NH3 (NH3) and [18F]FDG (FDG) PET scans were acquired. The first 2 minutes were used to calculate LV and RV first-pass ejection fraction (FPEF). Additionally, LV end-systolic (LVESV) and end-diastolic (LVEDV) volume and ejection fraction (LVEF) were calculated from the early (EP) and late-myocardial phases (LP). MRI served as a reference.In 22 patients with coronary heart disease (69 ± 9 years) dynamic  and  as well as  and , respectively. Moreover, LVESV, LVEDV and LVEF acquired from LP FDG and NH3 were  and , respectively. The LVESV, LVEDV from MRI were 93 ± 66 mL and 153 ± 71 mL, respectively. Significant correlations were observed for RVFPEF and LVFPEF between FDG and MRI , respectively. LVESV, LVEDV, and LVEF revealed moderate to strong correlations to MRI when they acquired from EP FDG and NH3 in 16 gates . Similarly, all LV parameters from LP FDG and NH3 correlated good to strongly positive with MRI , except EDV from NH3 weakly correlated to EDV of MRI . Generally, Bland-Altman plots showed good agreements between PET and MRI.RVFPEF and LVFPEF from FDG and NH3 and FDG PET is feasible. These results could open a new perspective for further clinical applications of the PET examinations.Deriving LV and RV functional values from various phases of dynamic NHThe online version of this article (10.1007/s12350-020-02391-y) contains supplementary material, which is available to authorized users. Cardiovascular diseases, especially coronary heart disease (CHD), remain the leading cause of death worldwide.13N]NH3 (NH3) PET is often used to estimate myocardial perfusion, while the role of cardiac [18F]fluorodeoxyglucose (FDG) PET is mostly viability assessment, myocardial inflammation and tumor imaging. In patients with ischemic heart disease, the combination of these two tracers enables the identification of hibernating myocardium by identifying regions with perfusion-metabolism mismatch.3The recent development of an integrated PET/MRI imaging system could further facilitate the early diagnosis of plenty cardiovascular conditions, which might consequently improve therapy management and reduce mortality among affected patients.On the other side, whole-body PET examinations using FDG are widely performed for oncological purpose like preoperative staging, characterization of suspicious tissues and lesions and response evaluation after receiving chemo- and/or immunotherapies.In this context, various preclinical and human studies have demonstrated the feasibility of determining LV parameters using FDG PET and showed excellent correlations between left ventricular volume and function in static scans in humans.113 PET scans. As integrated PET/MRI systems enable the simultaneous measurement of both PET and MRI, a simultaneous intra-individual comparison with respective CMR parameters as a reference was feasible.In the present study, we aimed to conduct an intra-individual comparison of the cardiac function and volume parameters of the right (RV) and left (LV) ventricle derived from different phases of dynamic FDG and NH3 and FDG protocol. Only proper and completely performed cardiac dual-tracer PET/MRI studies were included in this retrospective analysis. Prior to the conduction of the scan, all patients have undersigned an informed consent for the examination. The study has been approved by the Ethics Committee of the Medical University of Vienna (EK: 1832/2016).Integrated cardiac PET/MRI  in head-first supine position was performed in patients with coronary heart disease and ischemic cardiomyopathy, who were referred to our department for assessing myocardial perfusion and viability with a dual-tracer NH3 and FDG as well as the CMR examination acquired with the integrated PET/MRI followed well-established protocols that are applied for cardiac PET and CMR.3 scan followed by a 40 minutes dynamic FDG scan at rest in list-mode acquisition, triggered with 16 gates, and during free breathing. Both NH3 and FDG were administered intravenously as a bolus.The cardiac PET examinations for ECG-gated NHThe simultaneously acquired CMR protocol included steady state free precession cine sequences in 2, 3, and 4 chamber view, short axis view, left ventricular outflow tract (LVOT) for evaluation of ventricular function as well as late gadolinium enhancement using phase-sensitive inversion recovery (PSIR) sequences 10 minutes after injection of .15 mL/kg of gadolinium (Gadovist®), as all previously described in detail.3 dynamic PET images, the first 2 minutes of each PET list-mode dataset were reconstructed by dividing them into 15 frames to visualize the time of first-pass of the tracer in the ventricles and creating count-rate plots over the entire heart. From this information, the proper start points and time duration of the first-pass in both ventricles was defined. Gated reconstruction of the first-pass was performed with vendor-based software  using ECG information for dividing the heart cycle into 8 gates. As reconstruction algorithm an ordinary-Poisson ordered-subsets-expectation-maximization (OP-OSEM) with point spread function resolution modeling, three iterations and 24 subsets was used. Data were corrected for attenuation, scatter, normalization, in frame decay, deadtime, and random. The reconstruction included a 4 mm FWHM Gaussian smoothing of the final images. In addition, a further 19 mm FWHM Gaussian smoothing was applied after reconstruction to achieve a smooth representation of the activity distribution within the ventricles.To determine RV and LV first-pass ejection fraction (FPEF) from FDG and NHVolumes-of-interest were placed around the RV and LV in the EDV, in general overestimating the true volume of the respective ventricle but trying to match with the cardiac valves. This was done by manual delineation slice-by-slice in the EDV frame by clinically experienced cardiac nuclear medicine specialists using the software Hermes Hybrid Viewer PDR, version 4.0.0  and merging the individual ROIs to the final VOIs for the RV and LV.total) in the respective ventricle in both, the ED and ES phase. Under the assumption that the activity concentration (Acons) of the blood does not changed during one heart cycle the EF could then be calculated following:Under the assumption that the activity in the myocardium and the background can be neglected compared to the activity in the ventricles during the FP, the total activity within these VOIs corresponds to the total activity within the respective ventricles. Therefore, the total activity in the VOIs were exported in the EDV and ESV gate to obtain the total activity , end-diastolic volume (LVEDV), and ejection fraction (LVEF) from early- (EP) and late-phase (LP), i.e., myocardial-uptake, images was conducted using the software QGS® . Applying count-based calculations and automated delineation of myocardium, the software has measured the myocardial EF from ESV and EDV for the left ventricle automatically of FDG PET  parameters with CMR parameters, which were considered as gold standard. Hence, a correlation coefficient (R) of ≥ .5 and < .6 was considered weak, a R ≥ .6 and < .8 was considered moderate and a R ≥ .8 was considered strong.P-value of < .05 was considered statistically significant.The IBM SPSS Software version 24.0 was used for all data entry and analysis. All obtained data were tested for normality of distribution using the Kolmogorov–Smirnov test. Parameters that showed a normal distribution were presented in mean ± standard deviation (SD). Not normally distributed parameters, if available, were presented in median ±  range and were log2), were eligible for evaluation and the clinical characteristics of these patients and their cardiovascular risk factors are shown in Table 3 activities were 334 ± 35 and 816 ± 95 MBq, respectively. The mean of the heart rate of these patients was 68 ± 12 beats/minute. Seven patients (32%) had type 2 diabetes mellitus, merely 1 (14%) was insulin-dependent and 6 (86%) were treated with only oral antidiabetic therapies, mostly metformin. 77% of the evaluated patients presented with arterial hypertension, 64% with hyperlipidemia, and 14% were active smokers. Approximately 46% of the patients presented with at least one coronary stent and 32% with a coronary bypass graft. 23% of patients had prior myocardial infarction.Twenty-two consecutive patients , 109 (56 to 384 mL), and 41 ± 22%] and , respectively and from LP dynamic NH3 were 79 ± 56 mL, 137 ± 63 mL, and 47 ± 20%, respectively , the LV and the RV FPEF obtained from FDG PET showed positively moderate and weak correlations with the LVEF and RVEF received from CMR  and  respectively. Nevertheless, no significant correlations were observed between LV and RV FPEF obtained from NH3 PET scan as compared to LVEF and RVEF from CMR, all Fig 3 PET . Furthermore, there were significant differences between CMR and LV parameters from early 2 to 10 minutes NH3 PET in 8 and 16 gates (P < .001), except for ESV in 16 gates and EF values in both 8 and 16 gates. However, all the LV parameters moderately to strongly correlated to CMR when they acquired from EP FDG and NH3 in 16 gates , Figure We observed significant differences between CMR and all LV parameters measured from early 2 to 10 minutes of FDG PET in 8 and 16 gates , except EDV from LP NH3 weakly correlated to the EDV of CMR , all shown in Figure There were no significant differences between LV parameters from CMR and LP dynamic from both FDG and NH3 PET scans with 3-Tesla-MRI functional parameters as a standard reference.In a cohort of patients with advanced CHD, we used an integrated PET/MRI system to intra-individually compare cardiac functional parameters obtained from dynamic ECG-gated FDG and NH3. However, a systemic underestimation of the EF was found for both FDG (14%) and NH3 (10%). In this respect, Todica et al. previously acquired ECG-gated FDG PET examinations in seven healthy rats and found a good correlation between LV FPEF from FDG PET and LVEF values from CMR.® software  for evaluating gated FDG blood-pool PET in the studied rats. Similarly, in 24 oncological patients, Bouallègue et al. could recently show possibility of assessing cardiac function from the gated FDG PET studies.3 PET scans in patients with CHD. The disparities in correlations of FDG and NH3 PET with CMR observed in this study might be caused by the fact that both these tracers have different uptake-mechanisms in the myocardium. Due to the more rapid first-pass uptake of NH3 into the myocardium,3. Moreover, the different count statistics within the NH3 images may affected the manual ventricle delineation. Furthermore, the relatively high activity concentration of NH3 (816 ± 95 MBq) applied in our studied cohort should be taken into consideration, as this might increase the number of the detected random events and influencing the deadtime in the PET/MR detector system and affecting the reading of NH3 images.While the first-pass FDG data showed significant correlations between LVFPEF and RVFPEF with those gained from CMR, this was not the case for NH3 and FDG PET scans with that of CMR. In fact, because NH3 is a tracer commonly used to determine myocardial blood flow,3 PET with those acquired from CMR are very limited. In a very recent 3T hybrid PET/MRI study, Nazir et al. could rather demonstrate a feasible quantification of myocardial blood flow with good to moderate agreement between PET and CMR in a phantom and five healthy volunteers undergoing adenosine stress, where NH3 and gadolinium were administered simultaneously.3 PET with that obtained from left ventriculography.3, when FDG cardiac function values were considered as gold standard.26Moreover, results of the early- and late-phase analyses showed overall good to strong correlations between the left ventricular functional parameters such as LVESV, LVEDV, and LVEF acquired from both NH68Ga]Albumin PET, an experimental blood-pool marker, and CMR.3 PET and right and left ventricular parameters acquired from first-pass and late-phase gated FDG PET examination can accurately be used to evaluate cardiac function.Furthermore, results from previous preclinical and human studies acquired with separate PET and CMR scanners using the late-phase FDG PET are in one line with the present study.Nonetheless, the retrospective design and the small sample size of the included cardiac PET/MRI scans, among them data of 32% type 2 diabetic patients, might limit the results of this study. Moreover, the used activity of about 800 MBq was above the peak noise equivalent count rate (NEC) of the system.3 and FDG is feasible and could potentially be estimated from other, mostly oncological routine scans when dynamic list-mode FDG PET acquisition is performed.Based on the results of this study, deriving reliable LV and RV functional parameters from various examination phases of the dynamic NH3 and FDG PET scans using the first 2 as well as early 2 to 10 and late 10 minutes of PET list-mode data. There was a good agreement between the left ventricular ejection fraction calculated from the first-pass FDG PET acquisition and CMR, which could potentially open new perspectives for dynamic PET acquisitions in the oncological field or novel total body PET applications.Findings of this intra-individual PET/MRI analysis in patients with advanced CHD demonstrated the feasibility to calculate left and right ventricular function from several phases of dynamic NHElectronic supplementary material 1 (PPTX 1081 kb)Below is the link to the electronic supplementary material.


The purpose of this paper is to analyse the correlation between cardiac ultrasound-related indicators and cardiac function in patients with coronary heart disease and heart failure.  In this experiment, a total of 160 patients with coronary heart disease and heart failure who were diagnosed and treated in our hospital from June 2019 to March 2021 were recruited as the study group. All were examined by colour Doppler ultrasound instrument, SPSS statistical software was used to analyse the data obtained, and Spearman correlation was used to analyse the correlation between cardiac ultrasound-related indicators and cardiac function in patients with coronary heart disease and heart failure. r = 0.689/0.915/0.928, P=0.001) and significantly negatively correlated with CI, LVFS, and LVEF (r = −0.689/−0.878/−0.912), P=0.001).  In the study group, there were 68 patients with grade II cardiac function, accounting for 42.50%; 74 patients with grade III, accounting for 46.25%; and 18 patients with grade IV, accounting for 11.25%. The ultrasound parameters of the patients in the study group were profiled and calculated, and then statistically analysed with cardiac function grading. Cardiac function classification was significantly positively correlated with LVMI, LAD, and LVEDd ( Cardiac ultrasound-related indicators are associated with patients with coronary heart disease and heart failure. With the decline of cardiac function in patients with coronary heart disease and heart failure, the patient's condition is aggravated. Therefore, cardiac ultrasound-related indicators play a major role in the diagnosis of clinical disease progression. According to data released by the World Health Organization, an estimated 17.9 million people will die from cardiovascular disease in 2019, accounting for 32% of global deaths, and in 85% of deaths, the major factors were heart attacks and strokes. Coronary atherosclerotic heart disease is the result of coronary artery disease caused by ischaemia, hypoxia, or necrosis . CoronarTherefore, it is urgent to conduct early diagnosis and treatment in clinical practice. Cardiac ultrasound, the most common diagnostic method at present, can display the internal structure of the heart . The heaA total of 160 patients with coronary heart disease and heart failure who were diagnosed and treated in our hospital from June 2019 to March 2021 were enrolled, including 88 males and 72 females. The studies involving human participants were reviewed and approved by the ethics committee of Heping Hospital affiliated to Changzhi Medical College (approved no. 2939/81).Clinical Disease Diagnosis and Efficacy Determination Criteria; (2) patients who met the diagnostic criteria for heart failure in Chinese Heart Failure Diagnosis and Treatment Guidelines 2018; (3) patients and their families who were informed of the study and voluntarily signed the consent form; (4) participants who were between 50 and –70 years old; and (5) patients who were examined by colour Doppler ultrasound.The inclusion criteria were as follows: (1) patients who met the relevant diagnostic criteria for coronary heart disease in The exclusion criteria were as follows: (1) patients with acute myocardial infarction combined with heart failure; (2) combined with mental illness or unconsciousness; (3) combined with autoimmune system diseases; (4) patients previously treated with valsartan, diuretics, or spironolactone; and (5) patients undergoing other experiments.All subjects were diagnosed by ultrasound Doppler ultrasound . The attending physician of our hospital applied a phased array probe, with a frequency of the probe of 2.5–4.0 MHz before the examination, then assisted the patient in the appropriate supine position, performed continuous scans of the cardiac structure to obtain normal ultrasound parameters, and observed the overall shape and structure. 2D cardiac echocardiography was used to image the heart, and the direction of the sampling line was determined according to the M-type ECG, and then the layered activity of the upper structure of the heart was observed and recorded.According to the New York Heart Association (NYHA) cardiac function classification, the cardiac function was assessed. Grade I: the patient has heart disease, but the number of daily activities is not limited, and general activities do not cause fatigue, palpitations, dyspnoea, or angina pectoris. Grade II: the physical activity of patients with heart disease is slightly restricted, and there are no symptoms at rest, but fatigue, palpitations, dyspnoea, or angina pectoris occur during normal activities. Grade III: the physical activity of patients with heart disease is significantly limited, and less than the usual general activities can cause the above symptoms. Grade IV: patients with heart disease cannot engage in any physical activity, and symptoms of heart failure also occur at rest, which are aggravated by physical activity.The modified Simpson method was used to monitor the aortic annulus diameter (AAD), aortic sinus diameter (ASD), left atrial diameter (LAD), ventricular septal thickness (IVST), left ventricular end-diastolic diameter (LVEDd), left ventricular end-systolic diameter (LVESd), left ventricular posterior wall thickness (LVPWT), right ventricular diameter (RVD), right ventricular outflow tract (RVOT), right atrial diameter (RAD), main pulmonary artery diameter (MPAD), left ventricular short axis shortening rate (LVFS), left ventricular ejection fraction (LVEF), stroke volume (SV), and cardiac output (CO).Cardiology.2  CI = CO/BSA. BSA is the body surface area, expressed in m  LVMI = LVM (left ventricular mass)/body surface area  Left ventricular mass = 0.8{1.04[([LVEDD + IVSd + PWd]3 − LVEDD3)]} + 0.6The index reflecting ventricular systolic function, cardiac index (CI) and the index reflecting cardiac remodelling, left ventricular myocardial mass index (LVMI) were calculated according to the formula in P < 0.05.Correlation analysis was performed by Spearman correlation. SPSS22.0 software was used to process and analyse the data. The data were tested for normality before analysis, and the correlation was represented by the r value, and the higher the r value, the higher the correlation. Statistical differences were set at 2, average 23.91 ± 0.88 kg/m2; educational background: 48 cases of high school and below, 79 cases of colleges, and 33 cases of undergraduate degree or above  and was significantly negatively correlated with CI, LVFS, and LVEF   see .Currently, there is no complete cure for coronary heart disease in clinical practice. Heart failure is resulted from the inability of the myocardium to contract normally due to various factors and failure to meet the body's needs . It is tThe ejection fraction is the main indicator, which is the percentage of output per beat to the end-diastolic volume of the ventricle  and can be examined by echocardiography and is one of the most important indicators of the type of heart failure. The normal value is 50–70%, with more than 50% generally falling within the normal range, and the ejection fraction at rest in humans is approximately 55% to 65% . Ejectior = 0.689/0.915/0.928, P=0.001) and was significantly negatively correlated with CI, LVFS, and LVEF . This would suggest that the cardiac function classification of patients with coronary heart disease and heart failure is closely related to ultrasound indicators. It is known that LVFS can reflect the sensitivity of myocardial systolic function, heart size, heart rhythm, individual differences, LVESd reflects an important index of left ventricular diastolic function, LAD can directly reflect the size of the left atrium, and CI and LVMI are both indicators calculated from the ultrasound results. All these contribute to provide a comprehensive assessment of the cardiac function of patients with coronary heart disease and heart failure. That would probably suggest that when the patient's cardiac function grade increases, the relevant ultrasound indicators would abnormally change. The above indicators can also restore to normal displayed via ultrasound indicators given proper and effective treatment, which is similar to the results of the previous study.The results of this study showed that cardiac function classification was significantly positively correlated with LVMI, LAD, and LVEDd (The method of traditional Chinese medicine to judge coronary heart disease is firstly through inspection. The inspection first looks at the colour of the tongue coating and tongue. In patients with coronary heart disease, the colour of the tongue coating will generally appear red or purple, and then observe the blood in the veins at the base of the tongue . In mostTo sum up, cardiac ultrasound-related indicators are associated with patients with coronary heart disease and heart failure. With the decline of cardiac function in patients with coronary heart disease and heart failure, the patient's condition is aggravated. Therefore, cardiac ultrasound-related indicators play a major role in the diagnosis of clinical disease progression. The use of ultrasound is widely recognised due to the presence of abnormal ultrasound parameters that are very intuitive in patients with coronary artery disease and heart failure. However, our study found differences in these parameters between patients with different levels of cardiac function, disease severity, and prognosis. Aiming at this difference, it is necessary to design more detailed schemes and divide more subtle exponential partitions for research in subsequent experiments.


Echocardiographic measures are known predictors of cardiovascular disease (CVD) in the general population. This study compared the predictive value of such measures to that of circulating cardiac biomarkers for a composite cardiovascular disease outcome in an aging population.In this prospective population-based cohort study, echocardiography was performed at baseline together with assessments of traditional CVD risk factors and circulating cardiac biomarkers, NT-proBNP and troponin I, in 1016 individuals all aged 70 years. Assessments were repeated at ages 75 and 80. A composite CVD outcome  was charted over 15 years. All echocardiography variables, except for the E/A ratio, were analyzed on a continuous scale.Over 10 years, left atrial (LA) diameter, left ventricular mass index (LVMI) and high E/A ratio (>1.5) increased, while left ventricular ejection fraction (LVEF) remained unchanged. Using Cox proportional hazard analyses with time-updated variables for echocardiographic measures and traditional risk factors, an enlarged LA diameter and a low LVEF were independently related to incident CVD in 222 participants. The addition of LA diameter and LVEF to traditional risk factors increased the C-statistic by 1.5% (p = 0.008). However, the addition of troponin I and NT-proBNP to traditional risk factors increased the C-statistic by 3.0% (p<0.001).An enlarged LA diameter and a low LVEF improved the prediction of incident CVD compared to traditional risk factors. However, given that troponin I and NT-proBNP improved prediction to a similar extent, the use of simple blood tests to improve clinical cardiovascular disease risk prediction is only further supported by this study. Cardiac biomarkers, troponin and N-terminal-pro hormone B-type natriuretic peptide (NT-proBNP), are commonly used in the clinic to diagnose acute coronary syndromes and heart failure, respectively. While cardiac biomarkers can provide insight into cardiovascular events already occurred, there is evidence that they could also be used to predict future cardiovascular diseases and mortality –5. TropoIt has been well established over recent decades that the geometrical and functional data that echocardiography provides can also be used to predict future cardiovascular outcomes and mortality. However, the independent and relative contributions that echocardiographic measures and circulating cardiac biomarkers make towards cardiovascular prognosis remains little known in the elderly. It is also not yet established if echocardiographic measurements improve the predictive power for incident cardiovascular disease over traditional risk factors.Considering this, the primary aim of the present study was to investigate the relationship between echocardiographic variables and incident cardiovascular disease, treated as a composite outcome of fatal and non-fatal myocardial infarction, heart failure and ischemic stroke. Secondly, this study determined if the addition of the echocardiographic variables to traditional risk factors would improve the predictive power of incident cardiovascular disease, comparing any such improvement to that obtained with the addition of Troponin I and NT-proBNP. Finally, in addition to using a composite outcome, this study also assessed the relationships between each form of incident cardiovascular disease, independently, with the echocardiographic variables.To address the aims of this study, data from the Prospective Investigation of the Vasculature in Uppsala Seniors (PIVUS) study was used . BrieflyThe selection of traditional risk factors for assessment was based on previous literature. Blood samples were drawn after over-night fasting. Glucose, triglycerides, low-density-lipoprotein (LDL)- and high-density-lipoprotein (HDL)-cholesterol were measured using standard techniques. Blood pressure was measured after 15 minutes of rest in the supine position using a mercury sphygmomanometer. Diabetes was defined as a fasting glucose ≥7.0 mmol/L and/or the use of antidiabetic medication. Additionally, a standard 12-lead electrocardiogram was performed at each assessment for the diagnosis of atrial fibrillation.A comprehensive two-dimensional and Doppler echocardiography was performed with an Acuson XP124 cardiac ultrasound unit  using a 2.5 MHz transducer. All echocardiography measurements were performed by the same experienced clinician (L.L.) and were evaluated in real-time. Reproducibility data was not available.Left ventricular dimensions were measured with M-mode on-line from the parasternal view, using a leading-edge-to-leading-edge method. Specifically, the left atrial diameter, interventricular septum thickness, posterior wall thickness, and left ventricular diameter during end diastole and end systole were measured.2.7, providing the left ventricular mass index. Left ventricular relative wall thickness and volumes were calculated, the formulas of which are listed immediately below this paragraph. Stroke volume and left ventricular ejection fraction were then calculated using the value obtained from the left ventricular volume calculation.Left ventricular mass was determined using the Penn conversion. It was then indexed to heightLeft ventricular relative wall thickness was calculated as:Left ventricular volumes were calculated according to the Teichholz formula:The left ventricular diastolic filling pattern at the mitral inflow was obtained while the transducer was in the apical position, with the pulsed Doppler sample volume taken between the tips of the mitral valve leaflets during diastole. The peak velocity of the early rapid filling wave (E wave) and the peak velocity of atrial filling (A wave) were recorded, from which the E to A ratio (E/A ratio) was calculated. Left ventricular isovolumic relaxation time was measured as the time between aortic valve closure and the start of mitral flow using the Doppler signal from the area between the left ventricular outflow tract and the mitral flow. A low E/A ratio was defined as <0.7, while a high E/A ratio was defined as >1.5. These two binary variables reflect that the E/A ratio was used rather than the continuous variable due to the pseudo-normalization issues of the E/A ratio.Plasma samples for the analysis of cardiac biomarkers were collected on the same day that the echocardiography assessments were conducted for each the 70, 75, and 80 years of age evaluations. Plasma samples were stored at -80C until analysis. Samples collected during the assessments at 70 and 75 years of age were analysed in one-batch approximately one year after the 75-year evaluation. Samples collected during the assessment at 80 years of age were analysed one year after that evaluation. Some samples collected at the 75-year evaluation were also analysed during the analysis of the 80-year evaluation, confirming that there wasn’t any drift between the sample batches.Cardiac troponin-I was assessed using The ARCHITECT STAT high-sensitive Troponin-I assay  with a detection level of 1.9 ng/L. It has been reported that the lowest measurable concentration with a 10% coefficient of variation is 5.6 ng/L . Plasma Data detailing the causes of death and hospitalizations were retrieved from the Swedish Cause of Death Register and the Swedish Hospital Discharge Register, respectively. Three major cardiovascular diseases were of interest, including myocardial infarction , heart failure  and ischemic stroke . Although the accuracy of the diagnoses in the Swedish registers have been deemed high , the diaAll echocardiographic variables and the two cardiac biomarkers were inverse rank transformed to achieve normal distributions before being transformed into a semantic difference scale in order to be comparable. Firstly, a pairwise correlation matrix (Pearson’s correlation coefficient) was performed to evaluate the relationships between all echocardiographic variables and the two cardiac biomarkers. Changes over time in the echocardiographic variables were evaluated with random effects mixed models.The primary aim, to investigate the relationship between echocardiographic variables and incident cardiovascular disease, was addressed with Cox proportional hazard analyses using time-updated covariates from the three investigations. In brief, the relationship between incident cardiovascular disease  and the echocardiographic variables, the two cardiac biomarkers and the traditional risk factors for cardiovascular disease  were assessed one by one. Two sets of models were investigated: 1) adjusted for sex only ; and 2) adjusted also for traditional risk factors and atrial fibrillation occurring before the cardiovascular disease event. If more than one echocardiographic variable was related to incident cardiovascular disease, then all indices found to have an association were entered into the same model to determine the independent relationships with the outcome. All participants with prevalent cardiovascular disease at baseline (age 70) were excluded from the analyses. Given the use of ten different echocardiographic variables, a p-value of <0.005 was considered statistically significant for the gender-adjusted data. In models adjusted for traditional risk factors and atrial fibrillation occurring before the cardiovascular disease event, p<0.05 was considered significant.To determine if the addition of the echocardiographic variables to traditional risk factors would improve the predictive power of incident cardiovascular disease (the second aim of this study), C-statistics from a logistic regression model that included traditional risk factors and atrial fibrillation occurring before the cardiovascular disease event  were compared to those of a model that also included the echocardiographic variables  found to be related to incident cardiovascular disease after adjustment. These discrimination analyses allowed for any improvement in C-statistics to be detected when NT-proBNP and troponin I were added to the clinical model, forming the clinical-biomarker model. Given that the clinical model was compared to two new models , p = 0.025 was considered statistically significant.The third aim, to assess the relationships between each form of incident cardiovascular disease, was addressed using the same analytical procedure described for the primary aim, but in this case, myocardial infarction, heart failure and ischemic stroke were related separately to the echocardiographic variables and the two cardiac biomarkers. All participants with prevalent cardiovascular disease at baseline (age 70) were, again, excluded from the analyses. Statistical significance was accepted when p<0.05.All statistical analyses were performed using Stata 16 .As expected, many echocardiographic variables were related to each other . Of noteLeft atrial diameter, left ventricular end diastolic diameter, left ventricular mass index and stroke volume, as well as the prevalence in both high and low E/A ratios, increased over 10 years, while both the E wave and A wave and their ratio declined . Over thDuring a median follow-up of 15 years , incident cardiovascular disease events occurred in 222 participants.As detailed in p = 0.015) and a low left ventricular ejection fraction  were significantly related to incident cardiovascular disease ; noting that left atrial diameter remained significantly associated.When left atrial diameter and left ventricular ejection fraction were added to the clinical model, forming the clinical-echo model, the C-statistics for incident cardiovascular disease (combined endpoint) improved significantly , 83 incident cases of myocardial infarction occurred. No echocardiographic variables were significantly related to incident myocardial infarction following adjustment for multiple testing. In contrast, both troponin I and NT-proBNP were related to incident myocardial infarction also following adjustment for traditional risk factors .During a median follow-up of 15 years , 132 incident cases of heart failure occurred. A large left atrial diameter, a low left ventricular ejection fraction, a high E/A ratio, an enlarged interventricular septum, an increased left ventricular end diastolic diameter and an elevated left ventricular mass index were all related to incident heart failure when evaluated one by one and adjusted for multiple testing .When the left atrial diameter, left ventricular ejection fraction, a high E/A ratio and the left ventricular mass index were entered into the clinical model, all four of these echocardiographic variables were significantly related to incident heart failure when adjusted for the traditional risk factors and atrial fibrillation before stroke .When the left ventricular mass index was replaced in the model by interventricular septum thickness and left ventricular end diastolic diameter, both of these markers of left ventricular geometry, along with left atrial diameter, left ventricular ejection fraction and high E/A-ratio, were significantly related to incident heart failure after adjustment for the traditional risk factors and atrial fibrillation before stroke . When a high E/A-ratio was replaced by the A-wave, the A-wave, along with left atrial diameter, left ventricular ejection fraction and left ventricular mass index, was also significantly related to incident heart failure after adjustment for risk factors . Both troponin I and NT-proBNP were related to incident heart failure.During a median follow-up of 15 years , 89 incident cases of ischemic stroke occurred. Of all echocardiographic variables, only left atrial diameter was related to incident ischemic stroke following adjustment for multiple testing, as well as the traditional risk factors and atrial fibrillation before stroke .Based on these findings, it would be more cost-effective to measure two blood-borne biomarkers than performing a rather expensive echocardiography examination, if the sole aim is to assess a patient’s incident cardiovascular disease risk. Indeed, it has long been established that troponin is associated with left ventricular mass . AdditioThe left ventricular mass index, a high E/A ratio, left atrial diameter and left ventricular ejection fraction were independently associated with incident heart failure, consistent with finding from a previous study . While tNoting that this study was designed towards the end of the 1990’s, it must be acknowledged from the outset that this study utilized technologies and methodologies that are not as refined as those available today. Indeed, the Teichholz formula could miss significant wall motion abnormalities, limiting its predictive value. In that context, linear M-mode measurements may not accurately reflect the initial volume or changes over time. Ultimately, though, protocols were purposely maintained throughout the study to be consistent, rather than confounding the data by introducing updated methodologies in the latter assessments. Unfortunately, an echocardiography assessment was not performed at the time of hospitalization for most heart failure cases. Therefore, heart failure cases could not be stratified by those with reduced or preserved ejection fraction. It must also be highlighted that this study was performed in a homogenous elderly population. Thus, studies in other age-groups and ethnicities are needed to allow these findings to be extrapolated more broadly.An enlarged left atrium and low left ventricular ejection fraction were the most prominent echocardiographic predictors of incident cardiovascular disease over 15 years follow-up. Compared to traditional risk factors alone, these two echocardiographic variables improved the prediction of incident cardiovascular disease. However, troponin I and NT-proBNP improved prediction to a similar extent. While the findings of this study further support the use of simple blood tests to improve clinical cardiovascular disease risk prediction, echocardiography remains of great clinical value with its capacity to phenotype other abnormalities of the heart .S1 Table(DOCX)Click here for additional data file.S2 Table(DOCX)Click here for additional data file.S3 Table(DOCX)Click here for additional data file.S4 Table(DOCX)Click here for additional data file.S5 Table(DOCX)Click here for additional data file.S6 Table(DOCX)Click here for additional data file.S7 Table(DOCX)Click here for additional data file.S8 Table(DOCX)Click here for additional data file.S9 Table(DOCX)Click here for additional data file.S10 Table(DOCX)Click here for additional data file.S11 Table(DOCX)Click here for additional data file.S12 Table(DOCX)Click here for additional data file.


Eosinophilic granulomatosis with polyangiitis (EGPA) is a rare form of anti-neutrophil cytoplasm antibody (ANCA)-associated vasculitis. Cardiac involvement is the major cause of morbidity and mortality in these patients. Early recognition and treatment initiation for such manifestations are key to improved patient outcomes.P-ANCA and myeloperoxidase (MPO) antibodies. Overall, the investigation findings supported a diagnosis of ANCA-positive EGPA with acute myocardial involvement. He was initially treated with high-dose corticosteroids, cyclophosphamide, and rituximab. The patient had a good symptomatic and biochemical  recovery. In addition, subsequent TTE showed improvement of LV systolic function and resolution of regional wall motion abnormalities.We report the case of a 60-year-old man with a history of therapy-resistant asthma and rhinitis. He presented with acute chest pain, sinus tachycardia, and marked peripheral eosinophilia. Transthoracic echocardiogram (TTE) showed segmental anterior left ventricular (LV) wall motion abnormalities with impaired systolic function (LV ejection fraction 45%) and a small pericardial effusion. Invasive coronary angiography revealed unobstructed coronary arteries. Cardiac magnetic resonance imaging confirmed the TTE findings and demonstrated oedema and active inflammation of the anterior and anteroseptal LV segments [Short inversion time recovery (STIR)-T2] and an unusual pattern of non-ischaemic late gadolinium enhancement extending across multiple coronary territories. Autoantibody testing detected a positive In this case, prompt diagnosis facilitated early initiation of immunosuppressive therapy and disease remission. CMR provides non-invasive assessment of myocardial tissue characterization and, used in conjunction with other tools, can be instrumental in detecting myocardial involvement in EGPA. Eosinophilic granulomatosis with polyangiitis (EGPA) is an anti-neutrophil cytoplasm antibody (ANCA)-associated vasculitis with cardiac involvement as the major cause of mortality and morbidity.Red flags include unexplained dyspnoea, palpitations, chest pain with or without increased troponin, syncope, arrhythmia and acute or chronic congestive heart failure, aborted sudden cardiac death and fulminant cardiogenic shock.Cardiovascular magnetic resonance (CMR) imaging provides a non-invasive assessment of myocardial characteristics and is a key tool in the diagnosis of acute myocarditis. Interpreted in conjunction with other tests it can be instrumental in diagnosis of myocardial involvement in EGPA.Contemporary medical therapy, including corticosteroids, cyclophosphamide, and rituximab can induce complete remission.3 and is a major cause of morbidity and mortality. The condition is infrequently encountered, and detection of cardiac involvement poses diagnostic challenges. Early recognition and initiation of treatment can positively alter the disease trajectory, preserve cardiac function and reduce associated mortality. We report the case of a 60-year-old man diagnosed with EGPA associated myocarditis—highlighting the diagnostic, treatment, and follow-up in the clinical pathway.Eosinophilic granulomatosis with polyangiitis (EGPA), also known as Churg–Strauss syndrome, is a systemic vasculitis characterized by eosinophil-rich granulomatous inflammation of small to medium-sized arteries which may be associated with anti-neutrophil cytoplasm antibody (ANCA) antibodies. EGPA is one of the most common systemic vasculitides which can affect the heart. The reported frequency of cardiac involvement in these patients varies between 16.0 and 29.0% in different studiesFigure 1); there were no dynamic ST segment changes. Blood tests revealed leucocytosis with elevated WCC of 18.16 × 109/L  and marked peripheral eosinophilia of 27.3% 5.0 . Inflammatory markers were raised with C-reactive protein (CRP) at 92 mg/L  and Erythrocyte sedimentation rate (ESR) of 22 mm/h . Troponin T was raised at 1267 ng/L  and N-terminal pro B-type natriuretic peptide (NT-pro BNP) raised at 6470 ng/L  (Table 1).A 60-year-old man with a past medical history of therapy-resistant asthma and rhinitis presented to the emergency department with a history of severe chest pain, nausea, and sweating. He also gave a history of neck pain, fatigue, and generalized weakness. He had no history of cardiac disease or conventional cardiovascular risk factors. Physical examination showed a blood pressure of 100/60 mmHg with a heart rate of 130 beats/min, normal heart sounds and a clear chest. A 12-lead resting electrocardiogram showed sinus tachycardia with globally flat T-waves . T2w-STIR CMR images demonstrated significant enhancement in the anterior and anteroseptal segments, indicating myocardial oedema and active inflammation in these regions . Late gadolinium enhancement demonstrated subendocardial contrast uptake in a non-ischaemic distribution . Specifically, there was subendocardial enhancement in the mid-apical anteroseptum and anterior walls, the basal to mid lateral wall, and focal near transmural enhancement in the mid anterolateral wall.Transthoracic echocardiography (TTE) revealed segmental anterior left ventricular (LV) wall motion abnormalities with impaired systolic function (LV ejection fraction 45%) and a small pericardial effusion measuring 0.64 cm anteriorly and 1.1 cm to the rear of the right atrium without haemodynamic compromise. Invasive coronary angiography showed unobstructed coronary arteries. Cardiovascular magnetic resonance (CMR) demonstrated borderline hypertrophy of the LV septal wall (thickness12–12.5 mm), regional hypokinesia of the anterior and anteroseptal LV segments extending from base to apex, mildly impaired LV systolic function (LV ejection fraction 48%), and a small pericardial effusion  scan of the neck, thorax, abdomen, and pelvis was unremarkable; in particular showing no significant lymphadenopathy or pulmonary abnormalities. A 24 h Holter monitor excluded any ventricular arrythmias.P-ANCA and positive myeloperoxidase (MPO) antibodies. The clinical findings were consistent with a diagnosis of EGPA and myocarditis. The patient was started on oral prednisolone 60 mg OD. Although he responded well to steroids, he developed steroid-induced psychosis. In view of this, prednisolone dose was decreased to 30 mg OD and he was commenced on intravenous cyclophosphamide therapy (1000 mg each dose) and Rituximab . This was followed by a rapid improvement in symptoms (within 2 weeks), with improvement in inflammatory markers, eosinophil count, NT-pro BNP and troponin T (Table 1). Subsequent TTE showed improvement of his LV systolic function and no regional wall motion abnormalities. He received a further four cycles of cyclophosphamide (six doses of 1000 mg each) with tapering oral prednisolone and was initiated on azathioprine as a maintenance agent. After 2 years of follow-up, the patient remains in remission with normal BNP, Troponin T, negative ANCA, and normal eosinophil counts.Further work up for vasculitis resulted in detection of positive 4 Clinical presentation of myocarditis is non-specific. Red flags may include unexplained dyspnoea, palpitations, chest pain with or without increased troponin, syncope, arrhythmia and acute or chronic congestive heart failure, aborted sudden cardiac death, and fulminant cardiogenic shock.1 The differential diagnosis for eosinophilic myocarditis includes hypersensitivity myocarditis, EGPA, and Loeffler endomyocarditis (hypereosinophilic syndrome). The distinction among these entities is generally made based on clinical grounds.5 EGPA is one of the most common systemic vasculitides which affect the heart.6 and if present is associated with high mortality and a poor prognosis. When EGPA affects the heart, it can lead to a myriad of presentations such as myocarditis with cardiomyopathy, pericarditis with pericardial effusion (up to 25% of patients), heart failure (18%), various ventricular and supraventricular arrhythmias, valve involvement,7 and sudden cardiac death.9EGPA (previously known as Churg–Strauss syndrome) is a rare, systemic, necrotizing small-vessel vasculitis with accompanying bronchial asthma, eosinophilia and eosinophilic tissue infiltration of various tissues with granuloma formation.8 are the two main mechanisms involved in cardiac EGPA. Epicardial coronary artery involvement is rare;9 however, coronary angiography should be considered in patients presenting with angina symptoms to rule out coronary vessel stenosis.Vasculitis related ischaemia and eosinophilic infiltration of the myocardium10 Cardiovascular magnetic resonance has emerged as a sensitive and non-invasive technique in the evaluation of cardiac lesions in EGPA patients. Garcia-Vives et al.11 demonstrated in their study that 45% of asymptomatic patients had an abnormal baseline cardiac evaluation. Similarly, Pakbaz et al.12 studied 62 cases in active disease and demonstrated that cardiac symptoms, electrocardiographic abnormalities, abnormal biomarkers, and abnormal echocardiography were detected in 82.3, 68.5, 77.4, and 96.8%, respectively. In patients with active EGPA, CMR enables detection of cardiac involvement even when cardiac symptoms are not present,13 and these studies recommend prompt cardiac screening in all EGPA patients, instead of a symptoms-guided algorithm.Imaging techniques such as TTE and CMR may help in establishing the diagnosis of EGPA. TTE is an excellent first line modality, allowing rapid assessment of ventricular function. CMR is the reference standard for volumetric chamber quantification, providing more reproducible assessments of ventricular function and permits non-invasive myocardial tissue characterization, including the presence of myocardial oedema, inflammation, and fibrosis.14 The pathognomonic laboratory feature of EGPA is prominent peripheral eosinophilia that commonly exceeds 1500 cells/μL. ANCA is present in ∼40% of patients showing a perinuclear staining pattern (P-ANCA) mostly directed against myeloperoxidase (anti-MPO).7 In the present case, CMR had a key role in establishing the correct diagnosis, providing complementary and additive information to the clinical picture. The CMR findings  in the context of late onset asthma and rhinitis, peripheral eosinophilia, elevated troponins and inflammatory markers , with unobstructed coronaries was consistent with the diagnosis of myocardial EGPA.Our patient fulfilled the recent 2022 ACR/EULAR Classification Criteria for EGPA.15 For patients with severe vasculitis  and acute multi-organ disease, IV glucocorticoids (methylprednisolone) at a dose of 1 g daily for 3 days is given followed by oral glucocorticoid therapy.16 Our patient was started on oral prednisolone 60 mg OD. Although he responded well to steroids, he developed steroid-induced psychosis. In view of this, prednisolone dose was decreased to 30 mg OD, and he was commenced on intravenous cyclophosphamide therapy (1000 mg each dose) and rituximab .International recommended treatment for EGPA are systemic glucocorticoids (prednisone) at a dose of 0.5 to 1 mg/kg per day, cyclophosphamide or rituximab as induction agents, and azathioprine or methotrexate as maintenance agents.In this case, prompt diagnosis with the aid of CMR facilitated treatment with prednisolone, rituximab, and cyclophosphamide and prompt remission of EGPA and associated myocarditis. Cardiovascular magnetic resonance is a safe non-invasive assessment that can be applied across the spectrum of myocarditis irrespective of aetiology. Cardiovascular magnetic resonance data considered in conjunction with clinical and laboratory findings can reliably support a unifying diagnosis without performing an invasive endomyocardial biopsy. While the diagnosis of vasculitis can be established on clinical grounds supported by characteristic radiographic and serological testing, tissue acquision is sometimes necessary when the diagnosis is uncertain. Endomyocardial biopsies are occasionally done, but given the potential risks and low diagnostic yield, it is used sparingly. It may be particularly useful for diagnosis if investigations suggest non-ischaemic myocardial involvement, if there is unexplained or an unexpected change in cardiac status, and if histological confirmation is expected to change management.We present a rare case of eosinophilic myocarditis in a patient with EGPA. Cardiovascular magnetic resonance played a crucial role in the diagnosis of this rare presentation. Early detection and treatment of cardiac involvement in EGPA are key to achieving complete recovery and minimising long term sequalae.ytac307_Supplementary_DataClick here for additional data file.


It has been well established that diabetes mellitus (DM) is considered as a core risk factor for the development of cardiovascular diseases. However, what is less appreciated is the fact that DM may affect cardiac function irrespective of cardiac pathologies to which it contributes, such as coronary artery disease and hypertension. Although echocardiography provides accurate and reproducible diagnostic and prognostic data in patients with DM, its use in these patients is still underappreciated, resulting in progression of DM-related heart failure in many patients. Hence, in the present review, we aimed to discuss the role of echocardiography in the contemporary management of diabetic cardiomyopathy (DCM), as well as the role of emerging echocardiographic techniques, which may contribute to earlier diagnosis and more appropriate management of this complication of DM. In order to improve outcomes, focus must be placed on early diagnosis of this condition using a combination of echocardiography and emerging biomarkers, but perhaps the more important thing is to change perspective when it comes to the clinical importance of DCM. Accounting for more than five million deaths worldwide and with mortality rate of 82.4 per 100,000, diabetes mellitus (DM) has become one of the main global healthcare issues . To put DM is a multifactorial metabolic disorder, which leads to issues concerning increased risk of microvascular and macrovascular pathologies. However, hyperglycemia and other pathophysiological mechanisms operating in DM, such as insulin resistance, dysregulation of sympathetic nervous system (SNS), renin-angiotensin-aldosterone system (RAAS), metabolic disequilibrium, increased oxidative stress, impaired calcium handling, microvascular dysfunction, inadequate immune response, abnormal subcellular function, and accumulation of advanced glycation end-products (AGEs), seem to affect cardiac function irrespective of macrovascular CAD ,11. For In addition to serving as capacitance vessels holding 90% of the myocardial blood volume, the coronary microcirculation is the major source of regulation of myocardial blood flow, a role which becomes vital in the presence of a stenosis where coronary autoregulation is required to maintain flow . Those vDCM is generally asymptomatic during most of the disease course . HoweverConventional echocardiography is considered to be a primary modality for cardiac imaging that enables precise estimation of cardiac structures and function. Furthermore, it is a non-invasive, painless, and risk-free procedure, which has played a fundamental role in assessment of LV diastolic dysfunction during the last few decades ,35. The Pulsed wave Doppler (PW Doppler), an imaging modality based on acquirement of the local erythrocyte flow continuum of a precisely defined area in the heart, is one of the main tools for quantification of DD ,37,38,392, and peak velocity of tricuspid regurgitant jet > 2.8 m/s. DD is considered present in the case when more than half of the above-noted variables meet the cutoff value. Notably, findings are rendered inconclusive to estimate LA pressure when there is 50% discordance or with only one available variable [Tissue Doppler imaging (TDI) is a valuable method to evaluate global and regional myocardial diastolic, as well as systolic function through cardiac cycle by examining longitudinal component of myocardial contraction ,45. The variable .The use of two-dimensional and Doppler techniques assists us to systematically assess cardiac function in diabetics, especially those with DCM . DopplerWhen it comes to LVFP rising in order to continue normal cardiac output, as well as increasing the early filling triggered by impaired relaxation, the intermediary and pseudo normal patterns occur. As previously stated, preload dependence is a factor because of which pseudo normal and normal patterns cannot be separated by transmittal inflow. At this stage, in order to more precisely assess DD, an additional analysis of Valsalva maneuver, myocardial velocities, pulmonary venous flow, and LA volume determination is necessary .A somewhat newer, but promising, approach for myocardial mechanical deformation assessment is Speckle-tracking echocardiography (STE). The technique was developed as an alternative to TDI, and permits a more objective and quantitative evaluation of myocardial tissue function ,55. It iWhen it comes to systolic function assessment in patients with DCM, the most used and more impaired parameter was GLS, followed by global circumferential strain (GCS) and global radial strain (GRS), respectively. The impairments are possibly due to longitudinally oriented subendocardial fibers, which are the most vulnerable during the early stages of DCM and, therefore, first influenced by the pathological processes ,61. The Three-dimensional STE is a recent and less reproducible echocardiographic technique, which also has a high specificity for myocardial dysfunction . EnomotoDM is considered to be one of the fundamental causes of LA remodeling, which also expands the risk of HFpEF, as well as atrial fibrillation. Assessing LA function is permitted by STE measurement even before atrial structural remodeling . DecreasVarious studies pointed out right ventricular (RV) systolic and diastolic dysfunctions in type 1 and type 2 DM patients, as well as RV global and layer-specific strain as an eminent morbidity and mortality predictor ,84. FurtResting echocardiographic methods are not always successful in enlightening clinical status  in patients which are admitted for reasons other than HF. Firstly, symptoms in question are more likely to be exertional, which means they may reflect an altered physiological status to the one that was noticed during the resting echocardiographic study. Natriuretic peptides have been endorsed by many guidelines, as a tool for such discrimination, yet with limited reliability . TherefoWhen it comes to the absence of epicardial coronary artery stenosis, the coronary flow reserve (CFR) is the method that may determine the dysregulation of coronary microcirculation, in association with blood sugar levels, insulin resistance, sympathetic dysregulation, endothelial dysfunction, malfunctions of the renin-angiotensin-aldosterone system, as well as LV architecture remodeling or hypertrophy. DD and impairment of CFR possibly have a similar foundation, as well as being associated in DM ,95. AlthAlthough there are a large number of imaging tools which can detect metabolic perturbations in myocardium, a lot of them have not yet been employed to study DCM. It is important to note that this task is quite challenging in DCM given the complex pathophysiologic processes that underlie it. The most frequently used imaging tools which calculate such perturbations and their downstream effects are single-photon emission computed tomography (SPECT), positron emission tomography (PET), and magnetic resonance (MR) based approaches , and cost efficiency. It is nonetheless unfortunate that there is no long-term echocardiography study available when it comes to defining progression of a disease in more detail. Thus, it makes it demanding to distinguish and stage DCM diagnosis, using standard echocardiography. As a result of lacking agreement between experts, the appropriate diagnostic protocol for echocardiographic evaluation of DCM have not yet been determined among clinicians, in spite of real effort ,111. TheFuture research will have to upgrade DCM strategic approach in order to make it more useful for the clinical practice. A mixture of fairly low cost and precise STE and biomarkers which were shown to be useful in this setting, such as soluble suppression of tumorigenesis-2 (sST2) or markers of collagen turnover ,113. FurAlthough DM is increasingly recognized as a perpetrator of normal cardiac function, even in the absence of coronary artery disease, efforts must be made to transfer this knowledge into clinical practice. Specifically, in consideration of the long asymptomatic phase of DCM, highlight should be put on screening and early diagnosis of this disease. Perhaps the most feasible ways for screening of subclinical DM-related cardiac dysfunction in the future will be echocardiography and serum biomarkers. Among echocardiographic techniques, apart from the well-established indices of diastolic dysfunction obtained using standard echo, advanced echocardiographic techniques, such as STE, CFR, stress echocardiography and three-dimensional echo, may also be helpful in this setting. Nevertheless, future research is needed to establish the most reproducible algorithms and explore the cost–benefit aspect. In this regard, the question remains whether we can affect outcomes of patients with DCM even if we make an early diagnosis. Finally, perhaps the most important message of this review is a need for change in perspective with regards to clinical importance of DCM.


Ebstein's anomaly is a congenital deformity marked by disease of the tricuspid valve and right cardiac hypertrophy. The severity, morphology, and appearance of Ebstein's anomaly cases might vary greatly. We discuss a case of an eight-year-old child with Ebstein's anomaly who presented with supraventricular tachycardia and was effectively treated with amiodarone after initial treatment with adenosine failed to reduce the heart rate. In 1866, Wilhelm Ebstein discovered Ebstein's anomaly (EA) while studying the heart of a 19-year-old laborer who had died from tricuspid regurgitation caused by a severe malformation of the tricuspid valve .EA is characterized by various pathological abnormalities in the heart, including an enlarged right atrium and right ventricle, as well as the presence of atrioventricular (AV) accessory conduction pathways (APs). These abnormalities create a favorable environment for the emergence of supraventricular and ventricular tachyarrhythmias, which refer to abnormal heart rhythms occurring at unusually high rates .Supraventricular tachycardia (SVT) can be terminated through the use of vagal maneuvers, such as the Valsalva maneuver or carotid sinus massage, or through the administration of adenosine or cardioversion . HoweverIn this case, we successfully treated SVT in a child with EA with amiodarone, a class III antiarrhythmic drug, after the child failed to respond to first-line adenosine in an emergency setting.An eight-year-old boy known to have EA with severe tricuspid regurgitation, who was receiving regular diuretics, presented to the emergency department with a history of fever, vomiting, and palpitation for the past three days. On examination, he was an unwell child with central cyanosis, a heart rate of 240 bpm, oxygen saturation of 100%, and blood pressure of 107/84 mmHg. His cardiovascular examination revealed a pansystolic murmur in the tricuspid area. An ECG was performed and showed SVT  were given, and he reverted to a normal rate. An X-ray showed massive cardiomegaly and hilar congestion  cardioversion, but the parents did not give consent, so one dose of amiodarone 5 mg/kg was administered. The patient’s heart rate improved from 217 to 160. He was started on an amiodarone infusion and transferred to the pediatric intensive care unit (PICU). During his stay, his heart rate fluctuated and increased to 190 beats per minute, so the amiodarone dose was increased to 6 mg/kg/minute. He stayed in the PICU for 24 hours during which his heart rate returned to normal, and the infusion was stopped. His laboratory investigations on the second admission are shown in Table Initial submission of this case to Cureus occurred on January 2, 2023.The incidence of EA occurs in one to five of 200,000 live births and constitutes less than 1% of congenital disorders. Patients with EA may present with a range of symptoms, which can depend on various hemodynamic factors such as the severity of tricuspid regurgitation, the degree of right-to-left shunting through a patent foramen ovale or atrial septal defect, and the degree of right ventricular dysfunction. Furthermore, EA is often accompanied by SVT and can be particularly dangerous in individuals with EA due to the associated hemodynamic and anatomic abnormalities .The management of SVT in EA can be challenging due to the complexity of the underlying cardiac anatomy and the potential for concomitant heart failure and other cardiac complications . SVT in Surgical or catheter-based interventions may be recommended for patients with symptoms, although these procedures can be challenging. However, they remain highly effective and curative options for management. Without intervention, these patients are at higher risk of sudden cardiac death rather than heart failure, so pharmacological prevention of SVT may be a reasonable approach .Adenosine is the first line in the management of SVT, particularly atrioventricular nodal reentrant tachycardia (AVNRT) and atrioventricular reentrant tachycardia (AVRT). However, adenosine may not be effective in all patients with SVT in EA . AmiodarIn a patient with SVT, the recommended therapy is the administration of IV adenosine, cardioversion, and catheter ablation. Our case showed that amiodarone is extremely effective in the treatment of children with SVT that is unresponsive to conventional antiarrhythmic drugs. The drug does not worsen the existing condition and is, therefore, excellent for the treatment of patients with EA.


Heart failure is a major public health problem and, despite the constantly emerging, new, effective treatments, it remains a leading cause of morbidity and mortality. Reliable tools for early diagnosis and risk stratification are crucial in the management of HF. This explains a growing interest in the development of new biomarkers related to various pathophysiological mechanisms of HF. In the course of this review, we focused on the markers of congestion and renal dysfunction in terms of their interference with cardiovascular homeostasis. Congestion is a hallmark feature of heart failure, contributing to symptoms, morbidity, and hospitalizations of patients with HF and has, therefore, become a therapeutic target in AHF. On the other hand, impaired renal function by altering the volume status contributes to the development and progression of HF and serves as a marker of an adverse clinical outcome. Early detection of congestion and an adequate assessment of renal status are essential for the prompt administration of patient-tailored therapy. This review provides an insight into recent advances in the field of HF biomarkers that could be potentially implemented in diagnosis and risk stratification of patients with HF. Heart failure (HF) is a multifaceted medical condition with a complex pathogenesis. Implementation of biomarkers that provide insight into a variety of biological processes involved in HF progression will potentially enable better diagnosis and prognosis of this disease . AlthougCongestion is one of the most important mechanisms of heart failure (HF) development as well as being a therapeutic target during acute heart failure (AHF) episodes ,2,3. TheThe incorporation of biomarkers that are involved in the aforementioned mechanisms might potentially increase the complexity of clinical assessment and improve the prognosis of HF patients by personalizing treatment for different phenotypes of the disease. The classification of selected biomarkers is presented in Natriuretic peptides, particularly B-type natriuretic peptide (BNP) and its precursor N-terminal pro-B-type natriuretic peptide (NT-proBNP), have an established role as gold-standard biomarkers in HF management ,10. ThisThe relationship between the heart and renal dysfunction has been widely described and investigated. Mutual cardiac and renal dysfunction worsens the prognosis of patients with the so-called cardiorenal syndrome . ClassicNeutrophil gelatinase-associated lipocalin is a siderophore molecule associated with neutrophils’ activation and an injury of epithelial cells, most interestingly, those located in the kidney. NGAL is also described as an iron-traffic regulator ,48. The The role of NGAL in heart failure (HF) is multidimensional. It has been proven to be independently associated with poor prognosis in terms of mortality and rehospitalizations ,51,52,53It is noteworthy that there is some evidence that NGAL expression is related to heart failure, possibly as a sign of neutrophil activation and inflammation . FurtherNGAL’s superiority over creatinine resides in its independence from diuretic therapy since it reflects renal injury rather than kidney function . On the Kidney injury molecule-1 is a transmembrane glycoprotein expressed in the proximal tubule . KIM-1 iA recent meta-analysis of 14 studies and 3300 patients confirmed its value as a diagnostic tool for AKI, which reached the sensitivity of 0.74 and specificity of 0.84 . KIM-1 hKIM-1, in comparison to the rest of the tubular injury markers , has been most thoroughly evaluated as a drug-induced nephrotoxicity monitoring tool. Conversely, its role in the mortality prognosis of HF remains unclear and is a subject of many studies. Cystatin C is a protein produced by all nucleated cells. CysC is filtered, reabsorbed, and catabolized in the proximal tubule . CysC isThe Heart and Soul study revealed that an increased level of CysC predicts all-cause mortality, cardiovascular events, and incidence of HF among ambulatory patients with coronary heart disease . A meta-Although CysC can constitute a valuable complementary biomarker in the AKI diagnosis and prognosis assessment in heart failure patients, it does not provide much additional data compared to the other renal tubule injury markers. More sophisticated aspects of the cystatin C value in heart failure management require further studies. N-acetyl-ß-D-glucosaminidase is the brush border enzyme expressed in proximal tubule cells . As withAn increased level of NAG in CHF patients in comparison to healthy controls has been noticed regardless of GFR. The NAG was also the predictor of death, heart transplantation, cardiovascular event, or HF hospitalization . NAG wasAmong novel tubular injury markers, NAG seems to be the strongest predictor of long-term mortality in CHF patients . NAG has many advantages, including high sensitivity and a simple method of quantification (easily reproducible spectrophotometric enzymatic assays). As for limitations, it should be emphasized that this marker is nonspecific. Increased levels of NAG have been observed in conditions other than AKI, such as hyperthyroidism and rheumatoid diseases. Additionally, endogenous urea and other neurotoxic substances alter NAG’s concentration ,81.Fibroblast growth factor-23 is a hormone dominantly secreted by osteocytes and osteoblasts in bones; however, it can also be produced by liver and heart muscle under stress ,83. FGF-FGF-23 was reported to be significantly higher in the HF versus healthy controls’ groups . InitialFGF-23 provides novel insight into the previously not evaluated field of the heart–bone axis; however, its predictive value and the differences between its significance in HFpEF and HFrEF have to be elucidated before its implementation into clinical practice.European Society of Cardiology (ESC) guidelines from 2021 recommend navigating decongestive therapy based on the urine sodium excretion . Indeed, a number of studies have confirmed the prognostic and diagnostic value of spot urinary sodium assessment ,92. In tUrine sodium level, at the time of writing this article, is probably the most trustworthy and widely applied biomarker of kidney functions in heart failure, excluding serum creatinine .This review did not entirely cover the topic of cardiorenal cross-talk biomarkers. The role of TIMP2/IGFBP7 ratio assessment is noteworthy, as it is commercially available in the NephroCheck Test. Two multicenter studies confirmed its value in the AKI prediction, with an AUC of 0.8, superior to all existing biomarkers ,96.2+ level [Exosomes are small vesicles excreted by a variety of cells. They are composed of a double layer of the lipid membrane and contain protein, lipid, mRNA, long non-coding RNA, circular RNA, microRNA, DNA, and other molecules ,98. Init2+ level ,113. Heart failure is an end stage of cardiovascular diseases and a consequence of a number of pathological pathways. Multimarker evaluation can provide significant information regarding the disease phenotype by including molecules of a different pathophysiological origin ,114. CurCancer antigen 125 (CA-125), otherwise known as mucin 16, is a membrane glycoprotein synthesized by mesothelial cells. Traditionally, its use has been restricted to screening and therapeutic monitoring of ovarian cancer ,119. HowSeveral studies have established an association between the CA-125 concentration and clinical manifestation of congestion  in the HF population ,128,129.Patients with more severe congestion had, on average, higher level of CA-125 (mean difference of 54.8 U/mL) than patients without congestion . Among pRecently, there has been a substantial increase in the number of studies investigating a prognostic value of CA-125 in risk stratification of the HF population. Results of the various trials demonstrated that the elevation of the CA-125 level was positively correlated with an increased risk of mortality and readmission for HF. CA-125 remained a significant prognostic predictor of poor prognosis, even after adjustment for the relevant baseline covariates ,127,128.The substantial number of studies have recently demonstrated that the concentration of CA-125 changes with the degree of fluid overload and, thus, may reflect treatment-induced alterations in a patient’s volume status ,131,132.CA-125 is associated with congestion, right-sided HF parameters, and an increased risk of adverse clinical events in AHF, beyond standard prognostic factors such as natriuretic peptides . Broad aNeurohormonal activation (expressed by stimulation of the sympathetic system and RAAS) is believed to be a central mechanism underlying HF pathophysiology. Reduced cardiac output induced by myocardial dysfunction activates the neurohormonal axis to maintain hemodynamic stability. Although activation of this system is presumed to be compensatory, over the long term, it contributes to further deterioration of cardiac systolic function and development of heart failure symptoms ,135. WhiAdrenomedullin (ADM) is a newly discovered vasoactive and natriuretic peptide hormone involved in cardiorenal regulation. ADM is widely distributed in the cardiovascular system, kidneys, and adrenal glands ,136,137.ADM might be utilized as a marker of congestion in patients with a new onset and worsening HF ,152,153 The use of MR-proADM in the diagnosis of AHF is limited due to its low specificity. MR-proADM is elevated in various medical conditions  . It is aArginine vasopressin (AVP) is an antidiuretic and vasoconstrictive peptide hormone, released in response to hyperosmolality and hypovolemia. It plays a crucial role in hemodynamics and osmoregulation .Key functions of AVP include solute-free water reabsorption in kidney tubules, an increase in peripheral vascular resistance, and a consequential rise in arterial blood pressure ,156. MorThe evidence of AVP elevation in HF patients has been well documented in the literature ,159,160.Although the biological effect of this biomarker has been widely explored, the optimal use of copeptin in the HF setting remains a question of debate. Copeptin is a sensitive and easily measurable surrogate of AVP, yet it is more stable and has a longer half-life. CT-proAVP exhibits low specificity. The elevation of AVP/CT-proAVP has been associated with a number of diseases, particularly those that are characterized by acute stress . The proWidely recognized as a major marker of neuroendocrine tumor (NET), chromogranin A (CgA) is an acidic protein and a pro-hormone of an active particle, which potentially exerts a biological effect in CHF ,164−1) while class I had the lowest concentration of this protein (median 109.7 ng·mL−1). Furthermore, it was concluded that CgA might be a predictive factor for mortality in HF [A considerable interest in this protein stems from the fact that CgA has been found to be related to the clinical deterioration and higher risk of mortality in patients with AHF and CHF ,165,166.ty in HF . CgA wasty in HF . High coty in HF .Data regarding CgA measurement in cardiology are limited. Its role has been investigated only in studies with a small number of patients. In the current state of research, CgA plasma measurement as a biomarker in heart failure is still being explored and cannot be recommended for general use . FurtherWith a growing prevalence and incidence of HF, novel and reliable diagnostic tools are thoroughly investigated. Currently, B-type natriuretic peptide (BNP) and N-terminal proBNP are the most recognized biomarkers for the diagnosis and treatment of HF; however, they do have certain limitations. They do not serve their prognostic role in some group of patients such as in those with renal failure and are not specific for HFpEF patients. Therefore, further research to explore new markers that would provide additional prognostic information, especially in areas uncovered by classic biomarkers, is required. Novel biomarkers certainly comprise those related to congestion and renal dysfunction, as, in fact, these pathological pathways are closely related to the development and progression of HF. Although it is important to note that the individual clinical value of the aforementioned biomarkers in diagnosis and prognosis is limited due to their lack of specificity, as such, the future of biomarker application in HF management relies on a multimarker panel and clustering strategies that would include a more specific combination of biomarkers representing different pathophysiological processes underlying HF. Multimarker panels’ analysis represents the great potential in prediction, risk stratification, and therapy tailoring in cardiovascular disease. A combination of various biomarkers reflects the cross talk of different pathophysiological pathways, including cardiac remodeling, inflammatory process, renal dysfunction, and neurohormonal activation, all of which play a significant role in heart failure. Machine learning techniques, such as clustering, can constitute helpful tools for elucidating the heterogeneity of the heart failure population and distinguishing important parameters from the immense amounts of data.


The capacity to distinguish hypertrophic cardiomyopathy (HCM) from hypertensive left ventricular hypertrophy (H-LVH) based on morphological features obtained by conventional echocardiography is limited. We investigated the global myocardial work of the left ventricle in two types of hypertrophies using the non-invasive myocardial work index (NMWI).n = 40), H-LVH (n = 35), and healthy people with normal blood pressure and left ventricular structure (n = 32). Except for the conventional echocardiographic parameters, the left ventricular myocardial work parameters based on pressure-strain loops, including global myocardial work index (GWI), global constructive work (GCW), global wasted work (GWW), and global work efficiency (GWE), were evaluated in three groups. Multivariate discriminant analysis and receiver operating characteristic (ROC) curve were used to evaluate the incremental value of NMWI for distinguishing HCM from H-LVH.Conventional echocardiography was performed on 107 subjects with preserved left ventricular ejection fraction (LVEF ≥ 50%), who comprised patients with HCM (P < 0.05), whereas GWI was significantly higher in H-LVH patients. GWW was higher and GWE was significantly decreased in both HCM and H-LVH patients than in the control group (P < 0.05). Multivariate discriminant analysis and ROC curve revealed that the inter-ventricular septum thickness (IVST)/left ventricular posterior wall thickness (LVPWT) and GCW were each able to distinguish HCM from H-LVH. The combination of IVST/LVPWT and GCW discriminated HCM and H-LVH with a higher predictive accuracy of 94.7%.Compared to the control group, GWI and GCW were significantly lower in HCM patients (NMWI may provide additional information in evaluating the myocardial function in patients with HCM and H-LVH. Myocardial work combined with conventional echocardiography could improve the clinical diagnostic accuracy of distinguishing HCM and H-LVH. Hypertrophic cardiomyopathy (HCM) is an autosomal dominant hereditary disease characterized mainly by ventricular wall hypertrophy with an unknown cause (cardiac afterload should be excluded), and it is one of the main causes of sudden cardiac death . HypertePrevious studies have shown that global longitudinal strain (GLS) is a sensitive index for evaluating the left ventricular systolic function and it has potential clinical value for differentiating various types of LVH diseases , 5. HoweWe hypothesized that NMWI might provide incremental value along with conventional echocardiographic parameters for discrimination between HCM and H-LVH. The aim of the present study was to evaluate the difference in myocardial work between patients with HCM and H-LVH and determine whether NMWI is able to provide more detailed information on the systolic function of the left ventricle and possible application for differential diagnosis.n = 40, 70% men, age 46.3 ± 10.7 years) or H-LVH . All drugs were discontinued at least 3 days before the patients' evaluation. In addition, age- and gender-matched healthy individuals with normal electrocardiography, echocardiography, and physical examination and without a history of cardiovascular disease were selected as the control group .Seventy-five patients with left ventricular hypertrophy from the Fuwai Central China Cardiovascular Hospital from March 2019 to April 2020 were selected. Patients were diagnosed with non-obstructive HCM /95 g/m2 .The diagnosis of H-LVH was based on the ESC/ESH arterial hypertension management guidelines in 2018  ≥ 50%, and coronary angiography or coronary computed tomographic angiography showed that the degree of stenosis in the three coronary arteries was <50% were included. Patients with secondary hypertension, New York Heart Association (NYHA) grade III-IV, diabetes, structural heart disease, other types of cardiomyopathies , and severe systemic diseases were excluded. This study was approved by the Ethics Committee of Fuwai Central China Cardiovascular Hospital, and all subjects gave their signed informed consent.A GE Vivid E95  color Doppler ultrasound diagnostic instrument equipped with an M5 Sc-D probe 1.4–4.6 MHz transducer was used. The limb lead electrocardiogram was connected synchronously and patients were in the left lateral decubitus position. The left atrial diameter (LAD), left ventricular end-systolic diameter (LVSd), left ventricular end-diastolic diameter (LVDd), inter-ventricular septum thickness (IVST), and left ventricular posterior wall thickness (LVPWT) were measured routinely. Left ventricular end diastolic volume (LVEDV) and LVEF were measured using the biplane Simpson's rule. LVMI and relative wall thickness (RWT) were calculated as follows: LVMI = left ventricular mass (LVM)/BSA; LVM = 0.8 × {1.04[(LVDd + IVST + LVPWT)3 – LVSd3]} + 0.6; RWT = (IVST + LVPWT)/LVDd. The flow spectrum was collected for the aortic valve and mitral valve, and peak early and late diastole velocity of the mitral valve and the ratio (E/A) were measured.Two-dimensional grayscale images from the apical four-chamber, two-chamber, and three-chamber views were acquired continuously for at least three cardiac cycles at a frame rate of 61.2 ± 7.1 frames/s on average to enable GLS and myocardial work analysis by STE. And the images were collected and stored on a hard disk in original format for offline analysis.Myocardial work was estimated using a commercially available software package , which was constructed from a surrogate of the left ventricular pressure curve combined with GLS acquired with speckle tracking echocardiography, as proposed by Russell et al. , 10. TheThe PSL area represented GWI and indicated the work done from mitral valve closure to mitral valve opening. The work done by the myocardial cell of shortening during systole and elongating during isovolumic diastole was helpful for left ventricular contraction and relaxation represented GCW. The work done by the myocardial cells of elongating during systole and shortening during isovolumic diastolic myocardium was not conducive to left ventricular pumping represented GWW, and GWE was the ratio of GCW to the sum of GCW and GWW .The average time needed to analyze the myocardial work parameters on each patient was approximately 197 ± 48 s.Twenty subjects were randomly selected and analyzed at different times by an observer blinded to the results of previous measurements for the intra-observer variability test. The same images were analyzed by other physicians blinded to the values obtained by the first observer for the inter-observer variability test.-t-test for pairwise comparison. When not normally distributed, expressed as median (interquartile range [IQR]) and the rank sum test was used for comparisons. Categorical data were expressed in terms of frequencies and percentages and compared by the χ2-test.Continuous variables are expressed as mean and standard deviation when normally distributed. One-way analysis of variance (ANOVA) was used to conduct comparisons among three groups, followed by Fisher's least significant difference (LSD)P < 0.05 were entered into the multivariate stepwise discriminant analysis. The discriminant score (Z) and discriminant probability were calculated based on a discriminant function test. Optimal cutoff values, sensitivity, and specificity of parameters for differentiation between HCM and H-LVH were determined by the receiver operating characteristic (ROC) curve. Pearson's correlation analysis was adopted to assess the correlation between variables.The parameters for distinguishing HCM and H-LVH were screened by univariate analysis. Covariables examined included LAD, LVEF, IVST/LVPWT, LVDd, LVMI, E/A, GWI, GCW, GWW, and GWE. The parameters where P < 0.05 were considered to indicate statistical significance.The Bland-Altman analysis was used for the repeatability test of MNWI parameters. SPSS 23.0  software was adopted for statistical analysis. P < 0.05). There were no statistical differences among the three groups in age, sex, BSA, and heart rate (P > 0.05).Seventeen percent (7/40) of HCM patients had a history of or coexisting hypertension. The general clinical data of the study subjects are summarized in P < 0.05). Furthermore, IVST, IVST/LVPWT, RWT, and LVMI were higher in HCM patients than in H-LVH patients (P < 0.05).P < 0.05). Significantly decreased absolute values of GLS and GWE and markedly increased GWW was observed in patients with HCM and H-LVH (P < 0.05). The absolute value of GLS, GWI, GCW, and GWE were significantly decreased in patients with HCM than those in H-LVH patients  and discriminant boundary value were determined  that termined .HCM was diagnosed when Z < −0.542, and H-LVH was diagnosed when Z > −0.542. In our study, the predictive accuracy of the discriminant formula based on IVST/LVPWT and GCW for diagnosing HCM and H-LVH was 94.7%, and interactive validation showed that the sensitivity of the discriminant function was 90.0% and the specificity was 100.0%.r = 0.76, 0.79, 0.67; P < 0.001), whereas GWW was negatively correlated with the absolute value of GLS . GWI, GCW, and GWE were positively correlated with LVEF , whereas GWW was negatively correlated with LVEF , which means that the wall thickness itself had relatively little influence on GCW. The suitability of GCW for use as a parameter to distinguish the two diseases may be attributed to its close correlation with the degree of myocardial fibrosis  for the publication of any potentially identifiable images or data included in this article.QZ and CC collected data, analyzed it, wrote the manuscript, and reviewed and edited the manuscript. YLi, YLiu, DH, YW, YH, RL, and HZ performed this study. LL designed the study, reviewed it, and finally approved the submitted version. All authors read and approved the manuscript.This research was supported by National Natural Science Foundation of China ; National Natural Science Foundation of Henan Province for Excellent Young Scientists (202300410364); and Medical Science and Technology Research Project of Henan Province .The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher.


Tachycardia-induced cardiomyopathy (TIC) is gradually gaining the attention it deserves as one of the most common causes of reversible cardiomyopathy. Although TIC appears common, there has been limited data, especially among young adults. Patients with tachycardia and left ventricular dysfunction should be suspected of having TIC, with or without established etiology of heart failure, because TIC can develop by itself or contribute to cardiac dysfunction.We present a case of a previously healthy 31-year-old woman with persistent nausea and vomiting, poor oral intake, fatigue, and persistent palpitations. Vital signs at presentation were significant for tachycardia of 124 beats per minute, which she reported was similar to her baseline heart rate of 120s per minute. There were no apparent signs of volume overload at the presentation. Labs were significant for microcytic anemia with hemoglobin/hematocrit of 10.1/34.4 g/dL, and mean corpuscular volume was low at 69.4 fL; other labs were unremarkable. Transthoracic echocardiography obtained at admission was significant for mild global left ventricular hypokinesis, systolic dysfunction with an estimated left ventricular ejection fraction of 45-50%, and mild tricuspid regurgitation. Persistent tachycardia was suggested as the primary cause of cardiac dysfunction. The patient was subsequently started on guideline-directed medical therapy, including beta blockers, angiotensin-converting enzyme inhibitors, and spironolactone, with eventual normalization of the heart rate. Anemia too was also treated. Follow-up transthoracic echocardiography done four weeks after was notable for significant interval improvement in left ventricular ejection fraction of 55-60%, with a heart rate of 82 beats per minute.The case illustrates the need for early identification of TIC regardless of the patient’s age. It is essential that physicians consider it in the differential diagnosis of new-onset heart failure because prompt treatment leads to the resolution of symptoms and improvement of ventricular function. Long-standing tachycardia is a well-established cause of left ventricular systolic dysfunction . TachycaA 31-year-old female presented to the emergency department with a six-week history of unintentional weight loss of about 30 pounds, progressive fatigue, and persistent palpitations. Symptoms initially started about three months earlier with epigastric pain, persistent nausea, vomiting, and associated poor oral intake. She also reported dizziness and progressive fatigue, necessitating presentation at an outside facility. An upper endoscopy was significant for gastritis, and she was placed on a proton pump inhibitor. However, with persistent fatigue and palpitations, the patient decided to present to our facility. Of note, she had no previous history of cardiac disease.On physical examination, her height was 64 inches, weight was 54 kg, blood pressure was elevated at 129/94 mmHg, heart rate was elevated at 124 per minute, which she reported was similar to her baseline heart rate at 120s per minute, respiratory rate was 18 per minute, and body temperature was 98.8°F. Jugular venous distention was absent, and no cervical and axial lymphadenopathy was noted. The heart sounds were tachycardic; however, regular with a presystolic gallop (S4). The breath sounds were clear, without rales or wheezing. There was no definite pitting edema or tremors. Otherwise, the physical findings were unremarkable. The patient denied the use of illicit substances.Lab findings at admission were significant for hemoglobin/hematocrit low at 10.1/34.4 g/dL (reference: 12.0-16.0 g/dL), mean corpuscular volume (MCV) low at 69.4 fL (reference: 80.0-99.0 fL), white cell count of 8.8 g/dL (reference: 4.5-10.0 g/dL), D-dimer elevated at 2.12 mg/L (reference: 0.4-2.0 mg/L), and sodium at 138 mmol/L (reference: 136-145 mmol/L). Liver function and thyroid function tests were within normal limits. Troponins and pro-B-type natriuretic peptides were within normal limits. Urinalysis showed 2+ protein and was otherwise unremarkable. Coronavirus disease 2019 (COVID-19) testing was negative. The urine drug screen was negative.The chest radiography film revealed cardiomegaly and was otherwise unremarkable. Electrocardiography (ECG) showed sinus tachycardia with premature atrial complexes and non-specific T-wave abnormalities.The echocardiography (ECHO) revealed mild global left ventricular (LV) hypokinesis and systolic dysfunction with an estimated LV ejection fraction of 45-50%, grade 1 diastolic dysfunction, with aortic root dilation at 4 cm, and mild tricuspid regurgitation  and cardiologist on an outpatient basis. Follow-up at the cardiology clinic four weeks later was notable for regular heart rate, and repeat ECHO noted interval improvement of systolic function with LV ejection fraction of 55-60% Figure .Follow-up visitsThis patient's first suspicion of TIC was during the present admission. Early identification and commencement of rate control medication were vital to the improvement in cardiac function.At the follow-up visit at the PCP office, a beta-blocker dosage adjustment was made. The patient also continued guideline-directed medical therapy with angiotensin-converting enzyme inhibitors/spironolactone as the blood pressure permitted.At the follow-up with the cardiologist, Holter monitoring was significant for a minimum heart rate of 31 beats per minute, a maximum heart rate of 222 beats per minute, and an average heart rate of 92 beats per minute while on a beta blocker, with non-sustained ventricular tachycardia (NSVT) detected within +/- 45 seconds of the symptomatic patient event(s). A repeat transthoracic ECHO revealed an interval improvement in ventricular function with a low normal estimated LV ejection fraction of 55-60%. The patient also underwent a nuclear medicine stress test, which was negative for ischemia, and an elective left heart catheterization, which was negative for obstructive coronary artery disease.PathophysiologyIn this case, we suspect a combined systolic and diastolic cardiac dysfunction related to persistent tachycardia. Clinical studies have found a variable time from the onset of tachyarrhythmia to the development of TIC, ranging from three to 120 days . The heaManagement and cardiac recoveryAlso, it is important to note that because TIC is rate dependent, the higher the heart rate, the higher the risk of TIC development and progression ,9. NormaRole of early suspicion and active surveillanceIn our patient’s case, the timely initiation of rate control medication helped with interval improvement in cardiac function within the one-month follow-up. Also, active treatment of the underlying cause and active surveillance through follow-up visits with the primary care provider and cardiology clinics helped with medication adjustments and monitoring of cardiac function. Early control of tachycardia has been associated with improved survival in TIC, hence, the role of awareness in the management of TIC . PhysiciIt is also important to note that patients who recovered from TIC are at an increased risk of recurrence. In these cases, the left ventricular systolic dysfunction is usually more rapid and severe than in previous TIC events ,15. ThisIn conclusion, we present a case of TIC, which significantly improved with rate control. Early suspicion and treatment are crucial and associated with long-term benefits in most patients. Awareness is vital as it helps with early detection and management. Physicians need to consider TIC as a differential diagnosis in patients of any age who present with persistent tachycardia and heart failure because prompt treatment resolves symptoms and improves ventricular function. There are limited data on the etiologies of TIC in young adults. Hence, future research should focus on this as the burden is gradually increasing. Also, there is a need for further studies on genetic and clinical characteristics guiding risk predictions of TIC, which will help with the early detection of high-risk patients and treatment with the goal of preventing heart failure.


The best treatment for ventricular functional mitral regurgitation still remains unclear. Papillary muscle tugging approximation (PMTA) is a technique known to preserve function of the sub-valvular apparatus, keeping it functionally in synch with the left ventricle systolic and diastolic dynamics. Herein, we present a case of mitral valve replacement with PMTA in a patient with severely impaired left ventricular function 14 years post initial mitral valve repair, which significantly improved during a course of 4 years after the reoperation without any complications. In patients with ventricular functional mitral regurgitation (MR), the best treatment option has been unclear. There is less early postoperative mortality post mital valve (MV) repair than MV replacement, but ~30% of patients post repair develop recurrence of MR, and no difference in mid-term survival between repair and replacement . Regardiet al. reported a novel MV replacement technique (papillary muscle tugging approximation: PMTA) with good outcome . During their 5-year follow-up, only one patient died, resulting in mid-term survival rate of 90% [6]. Our experience with the present patient supports their findings.In conclusion, we experienced a case of recurrent MR with very poor left ventricular function in which PTMA technique was highly effective in the course of 4 years. This technique may be effective for such patients with ventricular functional MR. This technique might improve the short-term outcome of MV replacement in patients with ventricular functional MR.