Conclusion: CMR reveals abnormalities in a significant proportion of patients with frequent idiopathic VAs. Male gender, age and non-outflow tract PVC origin can be clinical indicators for CMR referral. Background: A routine diagnostic work-up does not identify structural abnormalities in a substantial proportion of patients with idiopathic ventricular arrhythmias (VAs). We investigated the added value of cardiac magnetic resonance (CMR) imaging in this group of patients. Methods: A single-centre prospective study was undertaken of 72 patients  with frequent premature ventricular contractions (PVCs ≥ 500/24 h) and/or non-sustained ventricular tachycardia (NSVT), an otherwise normal electrocardiogram, normal echocardiography and no coronary artery disease. Results: CMR provided an additional diagnostic yield in 54.2% of patients. The most prevalent diagnosis was previous myocarditis (23.6%) followed by possible PVC-related cardiomyopathy (20.8%), non-ischaemic cardiomyopathy (8.3%) and ischaemic heart disease (1.4%). The predictors of abnormal CMR findings were male gender, age and PVCs/NSVT non-outflow tract-related or with multiple morphologies. Patients with VAs had an impaired peak left ventricular (LV) global radial strain (GRS) compared with the controls (28.88% (IQR: 25.87% to 33.97%) vs. 36.65% (IQR: 33.19% to 40.2%),  Ventricular arrhythmias (VAs) are frequent in the general population and can present with a wide range of clinical manifestations from benign premature ventricular contractions (PVCs) to life threatening episodes of complex VAs such as ventricular tachycardia or fibrillation . PVCs caThe diagnosis, prognostication and treatment of patients with VAs are challenging. A routine diagnostic workup with transthoracic echocardiography and an assessment for the presence of coronary artery disease (CAD) as suggested by current clinical guidelines  cannot rThe purpose of this study was to evaluate the added value of CMR including feature-tracking strain CMR (FT-CMR) in identifying underlying SHD in a relatively ‘healthy’ population of patients with VAs but normal echocardiography and testing for CAD.A single-centre, longitudinal and prospective study was undertaken of 72 consecutive patients referred for a CMR scan due to frequent PVCs and/or NSVT, normal findings on echocardiography and no evidence of CAD. The echocardiographic studies were performed by the referring physicians. All participants provided written informed consent and the study protocol was approved by the Ethics Committee of our institution. The CMR findings were compared with those from 72 healthy volunteers matched for age and body surface area (BSA) without a history of PVCs/NSVT or palpitations. The electrocardiogram (ECG) recordings of patients were analysed by an expert electrophysiologist (RW) blinded to the CMR findings to determine the possible arrhythmic focus. 2, significant electrolyte abnormalities, any contraindication to the MR environment , pregnancy and claustrophobia. The inclusion criteria were the presence of frequent PVCs (≥500/24 h) or NSVT on ECG and/or Holter monitoring; otherwise, a normal ECG with no changes suggestive of structural heart disease, normal echocardiography findings and no evidence of CAD on anatomical and/or functional imaging. All echocardiograms were performed by the referring physicians; the assessment of the LV systolic function was performed with the biplane Simpson disk summation method. The exclusion criteria were a known history of cardiac disease , any severe systemic disease that could affect the heart, an allergy to gadolinium-based contrast agents, an estimated glomerular filtration rate < 30 mL/min/1.73 mThe scans were performed on a 1.5 T Magnetom Avanto  scanner using phased-array radiofrequency receiver surface coils and dedicated cardiac software. The images were obtained with breath-holding instructions and ECG gating. A standard cardiac protocol was used including balanced steady state free precession cine images (repetition time (TR) ~45.30 ms, echo time (TE) 1.27 ms, flip angle 55°, field of view (FOV) 360 to 420 mm, base resolution 256 × 200, sequential 7 mm slices with a 3 mm interslice gap, 30 phases per cardiac cycle) of three long-axes, short-axis slices and RV dedicated views and axial RV slices ; T2-weighted fat-suppressed turbo spin echo imaging  and late gadolinium enhancement imaging . Arrhythmia detection and sorting algorithms were used in patients with occasional PVCs.®, vial 1 g/10 mL) was administered on the scanner table at intermittent i.v. bolus doses of 50 mg every minute until the suppression of PVCs was achieved or a maximum dose of 10 mg/kg was reached. Procainamide acts mainly by delaying repolarisation and increasing the effective refractory period of atrial and ventricular fibres [In patients with a high burden of PVCs (bigeminy or trigeminy), we administered procainamide on the scanner table to acquire high quality retrospective cine images, which has been shown to be effective and safe for the suppression of PVCs as previously described . More spr fibres . The onsr fibres ,15. The r fibres . During The CMR scans were analysed using dedicated cardiac software . The ventricular volumes and mass were quantified from the cine short-axis stack with a manual contouring of the epicardium and endocardium at the end-diastole and end-systole; the left ventricular (LV) papillary muscles were included in the volumes. Different types of non-ischaemic cardiomyopathy (NICM) were diagnosed using the published diagnostic criteria in the absence of other cardiac or systemic diseases that could explain the cardiac appearances ,18. A diThe myocardial strain was measured using the feature-tracking CMR technique (FT-CMR) on the SSFP short-axis cine stack and three long-axes. The base was selected as the slice closest to the mitral valve annulus on the short-axis images without through plane distortion from the LV outflow tract; the apical slice was selected as the most apical short-axis slice with clear epicardial and endocardial contours. Left and right ventricular (RV) endocardial and epicardial borders were manually drawn in the end-diastole and were automatically propagated through the cardiac cycle. An analysis of a random set of scans by two of the investigators  showed an excellent reproducibility for all strain variables (r > 0.90). The normal FT-CMR strain values were similar to those derived from speckle-tracking echocardiography (STE), with a good inter-technique agreement for the LV and a moderate intermodality agreement for the RV. Among the strain parameters derived on the FT-CMR, the LV global circumferential strain showed the smallest interobserver and intraobserver variability ,24,25,26t-test or a Mann–Whitney U-test  or by ANOVA (for more groups). We selected the optimum cut-off for the peak LV GRS by identifying the value that maximised Youden’s J statistic. We assessed the independent ability of the peak LV GRS to identify patients using a multivariable logistic regression model adjusted for LVEF, LV end-diastolic volume index, age, sex, BMI, smoking, hypertension and dyslipidaemia. Statistical analyses were performed in the R environment (R version 3.6.0 and R Studio version 1.2.1335). All tests were two-sided and α was set at 0.05. We present continuous variables as means (SD) or medians (25th to 75th percentile), as appropriate. The normality of distribution was tested using the Shapiro–Wilk test. We compared the categorical variables between two or more groups with the chi-squared test and we compared the continuous variables with either a Student’s The main baseline characteristics of the patients and healthy control subjects are shown in CMR detected abnormal findings in 39 of the 72 patients (54.2%) with possible previous myocarditis being the most prevalent diagnosis . A significant proportion of the patients  with a borderline or only a mildly impaired LV systolic function but without LV dilatation or any other imaging evidence suggestive of an NICM were diagnosed with possible PVC-induced cardiomyopathy, as described above. Six patients (8.3%) were diagnosed with NICMs  while only one patient had a previous subendocardial infarction .The differences between patients with a normal CMR scan and those who had abnormal CMR findings are shown in Procainamide was administered intravenously in 29 (40.3%) of the patients on the scanner table prior to CMR scanning. The average dose of procainamide administered was 536 ± 200 mg (range 200–1000 mg). There was a small but statistically significant drop in systolic blood pressure after procainamide administration but no significant drop in diastolic blood pressure or heart rate see . None ofp = 0.02) after adjusting for age and number of ectopics. The majority of the patients  had PVCs originating from the ventricular outflow tracts; eleven patients had a probable LV origin, two had a presumed RV focus and three patients had two different PVC morphologies see . When thAn FT-CMR analysis was performed for 67 patients (93.1%). Four patients were excluded due to an impaired image quality from frequent PVCs; the patient with a previous MI was also excluded. p < 0.001) and global circumferential strain (GCS) (−17.66% (IQR: −19.62% to −16.23%) vs. −20.66% (IQR: −21.72% to −19.6%), p < 0.001)  (28.88% (IQR: 25.87% to 33.97%) vs. 36.65% (IQR: 33.19% to 40.2%), < 0.001) A. p < 0.001) (The peak LV GRS showed a good diagnostic accuracy in detecting patients from the control subjects (AUC: 0.78 (95% CI: 0.69–0.86), < 0.001) B. MoreovTen patients with pathological CMR findings  underwent catheter ablation for the ventricular ectopy compared with three patients (9%) with normal CMR findings. One patient with an abnormal CMR was offered catheter ablation but refused. The catheter ablations were requested by the referring physicians. The rest of the patients in both groups remained stable with medical treatment. The present study showed that (i) CMR could identify underlying heart disease in a substantial number of patients with VAs and normal transthoracic echocardiography, (ii) myocardial deformation indices  were more sensitive than the ejection fraction to depict contractile dysfunction in this cohort and (iii) male gender, age and the origin of VAs were independent predictors of abnormal CMR findings . ImportaBased on the CMR findings, a definitive diagnosis of underlying SHD was established in 33.4% of patients with frequent PVCs/NSVT, a normal echo and no evidence of CAD. Additionally, approximately one in five patients (20.8%) was found to have a borderline or mildly impaired LV systolic function most likely related to the high ectopic burden, which was not detected on echocardiography. Therefore, CMR provided an additional diagnostic yield in 54.2% of patients considered to have normal hearts. Importantly, CMR, being the gold standard method for the assessment of myocardial volumes and function, demonstrated an impaired systolic function in a proportion of patients who had not been diagnosed on the echocardiogram performed by the referring physicians. Our findings were consistent with those from previous CMR studies that showed the additive value of CMR in 31.6% to 78.8% of patients with frequent VAs and normal echocardiography ,6,7,8,27Predictors of abnormal CMR findings on the univariate regression analysis were male gender and age, as has been previously shown in patients with idiopathic VAs , especiaAlthough EF is the most commonly used measure of systolic function, myocardial strain has emerged as a superior index of systolic performance with an incremental prognostic value . More imCMR has an important clinical role in patients with idiopathic VAs. First of all, it can diagnose patients with cardiomyopathy and re-classify their risk of future adverse cardiac events and SCD. Second, it can identify the presence and location of scar tissue  and guide treatment with ablation . MoreoveA few limitations of this study should be acknowledged. First, our sample size was relatively small and referral bias could not be avoided. Another limitation of the study was the lack of data from the speckle-tracking strain analysis as echocardiograms were performed by referring physicians so the correlation of the strain measurements on the FT-CMR with STE in our patient cohort was not possible. Furthermore, it should also be noted that arrhythmia-related cardiomyopathy is a clinical diagnosis and requires follow-up and reassessment of the LV systolic function after the suppression of VAs otherwise a mild/early dilated cardiomyopathy phenotype cannot be excluded with certainty. In addition, although we diagnosed possible previous myocarditis in patients with the typical subepicardial/mid-wall pattern of LGE , other NCMR revealed structural abnormalities concealed to conventional diagnostic investigations in a significant proportion of patients with PVCs/NSVT and normal transthoracic echocardiography. Male gender, older age and non-outflow tract PVC origin but not the arrhythmic burden could be used as clinical indicators for referring for a CMR scan. The assessment of myocardial contractility should go beyond the simple measurement of the ejection fraction as the peak LV GRS and the peak LV GCS on the FT-CMR constitute markers of myocardial dysfunction on top and independently of EF.


Most researchers use features of diastolic murmurs to identify coronary artery disease. However, the diastolic murmurs of coronary artery disease are usually very weak and are easily contaminated by noise and valvular murmurs. Therefore, the diagnostic accuracy of coronary artery disease when only using diastolic murmurs is not well. An algorithm for improving the accuracy in the identification of coronary artery disease by combining the features of the first heart sound and diastolic murmurs was proposed. Firstly, a first heart sound feature extraction algorithm was used to identify coronary artery disease from noncoronary artery disease. Secondly, the Empirical Wavelet Transform algorithm was used to decompose the diastolic heart sound into three modes, and the spectral energy of each mode was calculated to distinguish coronary artery disease from noncoronary artery disease. Then, the features of the fist heart sound, the second diastolic spectral energy, and the parameter P3, which was used to discriminate the diastolic murmurs in coronary artery disease and in valvular disease, were combined together to improve the diagnostic accuracy of coronary artery disease. The comparison experiment results show that the accuracy of the proposed algorithm is superior to some state-of-the-art methods when they are used to diagnose coronary artery disease. Coronary artery disease (CAD), identified by the World Health Organization as the “number one killer”, kills about 17.3 million people each year globally, and it is expected to increase to 23.6 million by 2030 –9. The lThe diagnostic methods of CAD are classified into two categories: invasive diagnosis and noninvasive diagnosis. Noninvasive diagnostic techniques for CAD are generally on the bases of the electrical activity and pumping activity of heart, such as ECG (electrocardiogram), dynamic ECG, echocardiography, NMR (nuclear magnetic resonance), CT (computer tomography), and PET-CT (positron emission computed tomography). The invasive CAD detection mainly refers to coronary arteriography.Electrocardiogram (ECG) is the earliest, most commonly used, and most basic diagnostic method for CAD. But not all patients with CAD can be diagnosed by ECG. If the degree of coronary artery stenosis is light, the heart can also maintain the need for myocardial blood supply under normal circumstances. Then, ECG is normal. Therefore, it is difficult to achieve the early diagnosis of CAD using ECG .An ECG load test is for patients with suspected CAD but normal ECG. After increasing the patients' activity and the burden of heart, ECG may become abnormal and the symptoms of myocardial ischemia may be identified. The ECG load test plays a certain role in improving the diagnostic rate of CAD only using ECG. However, the load test is not suitable for some old and weak people with limited mobility .Echocardiography can show the size of each chamber of the heart, the thickness of interventricular septum and ventricular wall, and the active state of each valve. For a CAD patient, echocardiography can reflect the change of its heart structure and the decrease of heart function. However, not all patients with CAD have these changes. If the degree of coronary blockage is light, echocardiography can be normal .The current isotopic myocardial scanning has a certain value in the diagnosis of CAD. In the quiet state, the amount of radioisotopes entering the ischemic area due to compensatory action was similar to that entering the normal myocardium, and the scan showed a uniform distribution of radioactivity. When the myocardial oxygen consumption increases significantly after exercise, the coronary artery blood flow also increases correspondingly. However, due to coronary artery stenosis, blood flow cannot be increased correspondingly in ischemic areas. Therefore, the amount of radioisotopes entering the normal myocardium is significantly different from the amount entering the diseased myocardium, which can be used to diagnose CAD. Because coronary perfusion has a strong reserve capacity, it is not meaningful when coronary stenosis is relatively mild.Modern medical imaging technologies, such as NMR, CT, and PET, have powerful functions and can intuitively show the pathological state of the heart , 9. The Coronary angiography is currently the “gold standard” for the diagnosis of CAD, which can determine whether the coronary artery has stenosis and the location and degree of the stenosis. However, coronary angiography is an invasive detection method with certain risks, serious complications, and even death. The mortality rate of the relevant data is around 0.1%. Moreover, the process is complicated and expensive, which makes it unsuitable for large-scale detection of CAD , 10.Previous studies have shown that, driven by blood pressure, blood flowing through the stenosis of coronary arteries will consume more energy. After blood flowing through the stenosis, separation between the flow layers will occur at the expansion of the outlet, and further vortices will form. Therefore, high-frequency murmurs will occur in diastolic heart sound when stenosis occurs due to coronary artery occlusion –17. The As a matter of fact, diastolic high-frequency murmurs can be caused by other valvular diseases either . MoreoveReference , one of an investigation of the effectiveness of the proposed method in reference  for disce(2) of CAD and non-CAD, in which e(2) is the spectral energy corresponding to the 150~500 Hz of diastolic heart soundsan investigation of the effectiveness of the Empirical Wavelet Transform (EWT) for discriminating the second diastolic spectral energy e(2) and P3 to distinguish CAD from non-CAD in order to improve the accuracy in diagnosis of CAD based on feature extraction of heart soundsa pioneer combining features of S1 and Therefore, the key contributions of this paper aree(2) and P3 to distinguish CAD from non-CAD is for the first time. Through comparative studies, the effectiveness of the proposed method in improving the accuracy of the identification of CAD and non-CAD has been proved.Until now, no one has studied the characteristic features of S1 in CAD. The proposed method which combines features of S1 and This paper is organized as follows: The proposed method consists of three subalgorithms: feature extraction of first heart sound of CAD, feature extraction of P3, and feature extraction of diastolic murmurs using EWT. The literature  focuses Clinical auscultations of CAD are weak heart contractions and weakened first heart sound (S1). Using the proposed method in Reference , the chaAt first, after extracting the envelop of heart sound by the Shannon Energy, S1s are extracted by algorithms of double threshold segmentation and localization. Then, Empirical Wavelet Transform (EWT) is applied to divide the spectrum of S1. The EWT algorithm divides the Fourier spectrum of a signal to construct some wavelet filter banks and extracts the AM-FM components of the signal with tight support spectrum through orthogonal Empirical Wavelet Transform (EWT). In order to find the right instantaneous frequency (IF) of M1 and T1 accurately and quickly, the peak values in the S1s' spectrum are sorted firstly. Then, the first two maximum values located with a distance greater than 20 Hz are selected. The nearest minimum values on both sides of the selected maximum values are used as the boundary points to divide the spectrum of S1.Secondly, S1s are decomposed into five modes according to the segmentation of the spectrum. Only the second mode and the fourth mode signals are single-frequency components. The other modal components have no practical significance. The second and fourth modes correspond exactly to the maximum subsignals of M1 and T1.k-means algorithm is used to carry out clustering analysis of the IF of the five modes. The IF of second mode and the fourth mode can form continuous curve after Hilbert Transform and k-means clustering analysis. The values of time, frequency, and amplitude corresponding to the IF with the maximum amplitude in M1 and T1 can be easily found.Thirdly, the instantaneous frequency (IF) of each modal signal is calculated through Hilbert Transform, and the Hilbert Huang Transform (HHT) is defined as , 2), , , 5) and and5) anh(t) = 1/πt, ∗ means convolution operation. x(t) is each filter's output and where This analytical signal's instantaneous frequency can be expressed asAfter all the modes are evaluated using Hilbert Transform, the analytical signal can be expressed asEquation  reveals The values of the amplitude, frequency, and time interval of the IF of different S1's M1 and T1 are different and have their own characteristics. The comparative study results will be presented in the next section.Pathological heart sounds often contain all kinds of systolic and diastolic murmurs or S3 and S4 both in CAD and in valvular heart disease, which will make the segmentation of diastolic heart sound become difficult and then greatly affect the accuracy of CAD's identification based on the feature extraction of diastolic murmurs. The wavelet threshold denoising algorithm is used to denoise the heart sound signal firstly [The noise type of heart sound data collected by MEMS electronic stethoscope is simple, and the wavelet threshold denoising algorithm is used to denoise heart sound data. Sym3 wavelet basis and three-layer decomposition can be uniformly adopted. The threshold function is uniformly set as (7)βj=σjNj is the length of the signal at the decomposition scale or layer j.  σjNoise is the noise variance of layer j; it can be calculated through formula  is used to separate the murmurs and heart sounds, and then, the double threshold segmentation algorithm is used to extract the pure diastolic heart sounds, and finally, the original diastolic heart sounds with murmurs can be extracted according to the position of the pure diastolic heart sounds.e(1). The second spectral energy from 150 to 500 Hz is denoted as e(2). The third spectral energy for frequencies higher than 500 Hz is denoted as e(3). Every spectral energy is calculated as the square algebraic sum of the amplitude of each frequency value in the frequency band.Thirdly, in order to extract the coronary blood flow with maximum diastolic murmur and clearly avoid acoustic interference of the valve cover, a fixed window function is used to extract diastolic heart sounds from each cardiac cycle: a period of 128 ms starting at 100 ms after finishing S2. The Fourier spectrum of the extracted diastolic heart sound is divided into three modes according to the segmentation boundaries: 150 and 500 Hz using EWT. The frequency distributions of the three modes are 0-150 Hz, 150-500 Hz, and >500 Hz. The spectrums of three modes are obtained through FFT. The first spectral energy between 0 and 150 Hz is denoted as Studies have shown that some heart diseases can also experience weak heart contractions and reduced S1, such as mitral tricuspid regurgitation. There are also some CAD patients with less stenosis of coronary and no obvious weak heart contractions and reduced S1. Therefore, the accuracy of distinguishing CAD from non-CAD by using the parameters of S1 alone is not well.e(2) alone to identify CAD and non-CAD, but it is also not accurate because diastolic murmurs are not only caused by CAD but also caused by valvular heart disease [It is also feasible to use second diastolic spectral energy  disease .e(2), and P3. P3 can be used to identify the diastolic murmurs from CAD and from valvular disease [Therefore, in order to improve the accuracy in identifying CAD from non-CAD, it is proposed to combine the features of T1,  disease . It is wE(3) is the third spectral energy.where The performance of this method is evaluated using sensitivity (Se), positive predictivity (Pp), and overall accuracy (Oa), which are defined ashttps://www.med.umich.edu/lrc/psb/heartsounds/index.htm.In this paper, some heart sound signals are from Michigan Heart Sounds and Murmur Database (MHSDB). This database is provided by the University of Michigan Health System. The PCG signals in MHSDB are sampled at 44100 Hz. In order to speed up the signal processing, all the heart sound signals are resampled at 2000 Hz in the pretreatment process. MHSDB includes 23 different clean heart sound recordings from 23 different subjects with a time length of 69 s for each recording. There are about 80 cardiac circles for each recording. The database is intended to teach medical students auscultation and therefore comprises high-quality recordings of very pronounced murmurs . It inclThe other part of heart sound signals used in this paper is from Self-Collection Database (SCDB) using MEMS electronic stethoscope as shown in Standard normal S1, S1 of mitral stenosis, S1 split, and S1 of CAD were selected from MHSDB for comparative analysis. Then, mode decomposition results of different S1 are obtained as shown in k-means clustering analysis. The values of time, frequency, and amplitude corresponding to the IF with the maximum amplitude in M1 and T1 can be easily found. By comparing Figures In order to find the difference of diastolic modal spectrum between normal subjects and patients with CAD, a comparative study was carried out.2 lower than the modal spectral components corresponding to CAD's diastolic heart sounds.e(1), the spectral energy corresponding to the 150~500 Hz modal component was denoted as e(2), and the spectral energy corresponding to the 500~1000 Hz modal component was denoted as e(3); P1 = (e(2))/(e(1)), P2 = (e(3))/(e(1))and the average value of the three modal spectral energy of 6 diastolic heart sounds in normal subject and in patient with CAD. It was found that the diastolic second mode spectral energy e(2) significantly increased in patients with CAD. In e(2) of CAD is 1.7e − 6, while the average value of e(2) of normal subject is 2.0e − 8. The low-frequency energy (0~150 Hz) of diastolic heart sounds decreased in patients with CAD. The average value of e(1) of CAD is 8.6e − 4, while this average value of normal subject is 0.0010. In a word, the middle-frequency energy e(2) (150~500 Hz) and high-frequency energy e(3) (>500 Hz) of CAD's diastolic heart sounds increased significantly. These conclusions are consistent with those of many scholars who have studied the characteristics of diastolic heart sound in CAD [Then, the spectral energy corresponding to 0~150 Hz modal component was denoted as d in CAD .e(2), diastolic third modal spectral energy e(3), frequency of M1 and T1 in S1, and P3 which is the ratio of spectral energy greater than 250 Hz to spectral energy less than 250 Hz in the third diastolic mode [lic mode . The chae(2), and P3 are selected to compose the feature set and the decision tree classifier is designed based on the statistical data in According to the selection rule, features with the greatest informational entropy in the same attribute, T1, e(2) and e(3). There are also some diseases that do not have diastolic murmurs but have decreased frequency of T1 and M1, such as elderly themselves with weaken contraction of the heart. Therefore, the design of decision tree needs to combine the features T1, e(2), and P3.The decision tree classifier design process takes into account not only the features of CAD itself but also other diseases' features that may interfere with the diagnostic results, such as valvular diseases , which lead to an increase in In order to verify the performance of the proposed method in the identification of CAD and non-CAD, comparison experiments were carried out. The methods of empirical mode decomposition (EMD), wavelet analysis, FFT, eigenvector method, an autoregressive (AR) model, and an autoregressive moving average (ARMA) model were chosen for acoustic detection of CAD. The common feature of these methods is that only diastolic analysis of CAD is carried out.The comparison results show that the proposed algorithm has great advantages over the other method in identification of CAD and non-CAD as shown in e(2), and P3. Considering the diastolic murmurs of CAD are easily contaminated by noise and valve sounds, the MEMS electronic stethoscope with high SNR is used to collect heart sounds and wavelet threshold de-noising algorithm is used for denoising firstly. Then, a fixed diastolic window function is selected to extract the diastolic heart sound reflecting maximum coronary blood flow. The EWT algorithm is applied in feature extraction of CAD's S1 and diastolic murmurs. The algorithm for the detection and classification of S1 is described in more detail in Reference [e(2) in CAD patients was significantly higher than that in normal subject. Therefore, the three features—T1, e(2), and P3—are combined together to identify CAD and non-CAD. Comparison experiment results show that the performance of proposed method is superior to most existing methods based on diastolic murmurs in identification CAD and non-CAD because the proposed method considered the most interference to the diagnostic rate of CAD when using diastolic murmurs.High-frequency murmurs in diastolic heart sounds are generally believed the typical characteristic of CAD. However, this high-frequency murmurs are usually interfered by the murmurs in valvular disease or high-frequency noise. This paper proposed a method to improve the accuracy in identifying CAD and non-CAD by combining first heart sound characteristic parameter (T1), the second diastolic modal spectral energy eference , and it eference . It was


Pericardial decompression syndrome (PDS) is a rare and serious complication that follows often-initially-uncomplicated pericardial drainage in patients with pericardial effusion and tamponade physiology. The pathophysiology of PDS is not yet completely understood, although several mechanisms have been postulated. In this report, we present a case of PDS in a 70-year-old male with end-stage renal disease (ESRD) after he underwent a surgical pericardial window for drainage of a moderate pericardial effusion with tamponade physiology. This case provides further evidence that rapid pericardial decompression, notably with pericardiotomy, can lead to acute life-threatening low cardiac output heart failure, particularly in patients with underlying cardiac risk factors. Early recognition, diagnosis, and supportive treatment in the ICU are crucial for improving survival rates in these patients. Cardiac tamponade is a medical emergency that is caused by fluid accumulation in the pericardial space. When fluid accumulates rapidly or excessively, it can lead to inappropriate filling of cardiac chambers, ultimately resulting in impaired cardiac hemodynamics, hypotension, and eventually cardiac arrest . Often uSeveral plausible mechanisms have been put forward to explain the etiology of this syndrome, incorporating hemodynamic effects of a sudden increase in venous return following fluid drainage, acute myocardial stunning, and acute withdrawal of sympathetic overdrive. PDS incidences are very rare and often go underreported. Hence, close hemodynamic monitoring and judicious pericardial fluid drainage in patients undergoing either pericardiocentesis or surgical pericardiectomy are of paramount importance.A 70-year-old male with a significant past medical history of diabetes, hypertension, hyperlipidemia, and end-stage renal disease (ESRD) on regular hemodialysis presented to our facility's emergency department after he had been found to have significant dyspnea, hypoxia, and hypotension at the outpatient pulmonary clinic. His chest X-ray showed stable bilateral chronic pleural effusions and a significant increase in cardiac silhouette. Transthoracic echocardiogram (TTE) in the ER showed moderate pericardial effusion with echocardiographic evidence of tamponade physiology. His left ventricular ejection fraction (EF) was found to be 50-54%.The patient underwent an uncomplicated emergent surgical pericardiotomy with a pericardial window; 400 ccs of serosanguineous effusion were drained and he was sent to the ICU unit for postoperative recovery and close monitoring with a pericardial drain in place. His vital signs initially improved after the drainage of pericardial fluid, with normalization of blood pressure and reduced oxygen requirements from 5 L to 2 L.However, a few hours after the surgery, the patient started to develop pulmonary edema and respiratory acidosis, requiring noninvasive positive pressure ventilation; his blood pressure significantly dropped, necessitating escalating vasopressor support. The patient was later intubated and mechanically ventilated for impending respiratory failure. Notably, a previous TTE done two months before this hospital admission had shown a normal left ventricular systolic function (EF estimated at 70%) and preserved right ventricular systolic function as well with only trace pericardial effusion.TTE done in the ICU postoperatively showed a new finding of moderately reduced left ventricular EF of 30-34%, with moderate global myocardial wall hypokinesis more pronounced at apical, lateral, and inferior walls; right ventricular systolic function was significantly reduced as well [tricuspid annular plane systolic excursion (TAPSE): 0.9] Figure .EKG showed no acute ischemic changes; cardiac biomarkers were elevated at 155 ng/L, and trended up to 156 ng/L but with no significant serial rise in the setting of ESRD (flat curve). A diagnosis of PDS was made. Acute pulmonary embolism (PE) was excluded by Wells criteria, absence of deep vein thrombosis (DVT) by venous duplex, as well as atypical echocardiographic features for massive PE in this patient. Sepsis workup was negative as well, and hemopericardium/myocardial puncture was excluded.Supportive treatment in the ICU unit was continued, and vasopressors were weaned off gradually over a period of three days. The patient was successfully extubated, and his fluid status improved with continuous renal replacement therapy. The pericardial drain was removed after 72 hours as well; another 200 mL of serosanguineous fluid was drained before it was removed. An echocardiogram done after the patient hemodynamically stabilized showed improved left ventricular systolic function with EF estimated at 45-49%; inferior wall hypokinesis had improved with remaining mild lateral and apical walls hypokinesis. He was transferred to the stepdown unit and later discharged after 13 days of admission.A follow-up TTE six months after discharge showed normalization of his left ventricular systolic function with EF estimated at 50-54%, and no significant wall motion abnormalities were observed.Pericardial decompression syndrome is a term that was first proposed by Angouras et al. in 2010 . It is aVandyke et al. have proposed that preload/afterload mismatch is the mechanism behind pulmonary edema and PDS development . RapidlyIn addition to the above-mentioned hemodynamic theory, Wolfe and Edelman have reported that pericardial decompression and deactivation of the adaptive autonomic/sympathetic stress response with tamponade might unmask an underlying myocardial dysfunction, and, interestingly, can lead to new-onset (de novo) transiently impaired systolic function similar to that in patients with Takotsubo cardiomyopathy . Lastly,Patients who develop PDS usually present with left ventricular failure with or without shock and pulmonary edema; isolated right ventricular failure and biventricular failure have also been reported. The onset of symptoms can be immediate or delayed up to 48 hours after pericardial fluid drainage . Other cWhile treatment is usually supportive and focused on the management of cardiogenic shock in a critical care unit ,11, prevSmall volume, staged pericardial fluid drainage  is often recommended so that PDS can be prevented. The initial amount of fluid removed should be guided by the clinical and echocardiographic improvement of tamponade physiology ,13. HoweIn our case, we suspect that the patient developed transient biventricular failure and subsequent cardiogenic shock with pulmonary edema secondary to preload/afterload mismatch. This was precipitated by significantly increased venous return after a sudden release of intrapericardial pressure and persistently increased afterload due to sympathetic overdrive. Sympathetic stress response might have also precipitated myocardial stunning as evidenced by significant myocardial hypokinesis seen in the patient’s echocardiogram.PDS is an underreported, potentially fatal complication in cardiac tamponade patients who undergo pericardial fluid drainage. Our report is the first one to document the development of PDS following a relatively small volume (400 ml) of pericardial window drainage of pericardial effusion associated with tamponade. Physicians’ familiarity with the syndrome, risk factors, and clinical presentation are crucial to establishing an early diagnosis and providing prompt treatment in a critical care setting.


Degenerative mitral valve disease is a common heart problem in dogs. The aims are to evaluate the relationships between right and left ventricular function, and blood lactate concentrations, assess prognostic contribution, and investigate whether serum peptidomics profile could reveal markers or determine the stage in dogs with valve degeneration.Ninety-three dogs were evaluated in this study. Thirty-nine dogs' serum was collected and analyzed using matrix-assisted laser desorption/ionization-time of flight mass spectrometry. The Kaplan–Meier curve was used to predict the outcomes of mitral valve disease. Follow-up was obtained by a questionnaire or telephone to determine a survival time.The BUN/creatinine ratio, vertebral heart score, and left atrium/aorta ratio were the independent predictors of cardiac mortality. Right ventricular systolic dysfunction was found in 50% of dogs with mitral valve disease. Dogs with right ventricular dysfunction had a significantly higher incidence of lower fractional shortening and larger right ventricular dimensions. The occurrence of right-sided dysfunction is proportionate to age and the degree of left ventricular dysfunction. High blood lactate concentrations were investigated in dogs with mitral valve disease stage C compared with stage B. The peptides such as mitogen-activated protein kinase, kallikrein, and tenascin-C appeared in the heart disease progression group.Right-hearted function assessment, blood lactate levels, and peptidomics analysis may help early detection and prognosis of this disease in dogs. Peptidomics profiles from this study demonstrate the possibility for prognosis indicators of heart valve degeneration. Left-sided congestive heart failure is commonly associated with mitral valve degeneration and is a significant heart problem in dogs , 2. LeftRight ventricular function is an essential determinant of a human's clinical status with chronic heart failure . The rigProteome analysis is a novel tool for exploring the changes in protein composition, and proteomics network analysis has been widely used to identify protein biomarkers in many diseases . It has The present study aimed to assess the prognostic information about valvular heart disease in dogs, examine the echocardiographic alterations, assess the right ventricular function associated with mitral valve disease, determine the blood lactate concentrations, and MS-based identification of proteins and protein interacting in the mitral valve degeneration dogs.This study was performed in clinical cases at Kasetsart University Veterinary Teaching Hospital Kamphaeng Saen from January 2019 to April 2020 . The folBlood samples were obtained from a cephalic vein, and the blood lactate concentration was measured with a blood lactate analyzer  before the echocardiography examination. Dogs underwent transthoracic echocardiography  to diagnose and observe disease progression. The measurement was performed when the dog was on lateral recumbence with no sedation. Echocardiographic images were captured and evaluated offline by only one sonographer. Left and right ventricular dimension and function were calculated from two-dimensional and M-mode images. The cardiac parameters were measured during diastole and systole, such as interventricular septum thickness during diastole (IVSd), interventricular septum thickness during systole (IVSs), left ventricular internal diameter during diastole (LVIDd), left ventricular internal diameter during systole (LVIDs), left ventricular proximal wall thickness during diastole (LVPWd), and left ventricular proximal wall thickness during systole (LVPWs). The diameter of the left atrium (LA) and aortic root (AO) ratio (LA/AO) were assessed at the level of the aorta when the aortic valves were closed during diastole.Right ventricular dimensions were measured at end-diastole using the left apical 4-chamber view. Three sites are commonly used to determine the right ventricle size: (1) the basal distance measurement, (2) the mid-right ventricular measurement, and (3) the base to apex measurement, as shown in Tricuspid annular plane systolic excursion (TAPSE) was evaluated by placing the M mode cursor through the tricuspid valve in the apical 4-chamber view, as shown in Dogs were divided into two groups according to the presence of impaired right ventricular systolic function, which was defined as the presence of FAC <30%. Group A included dogs with normal right ventricular function, and group B included dogs with impaired right ventricular function.The protein concentration in serum was determined by the Lowry method . The abst-test model was used to estimate and compare the parameters between two groups. Statistical analysis was performed using commercially available software . A value of p < 0.05 was considered statistically significant. The continuous variable showed a mean ± SEM. The survival analysis was analyzed using the Kaplan–Meier survival curve.Paired There were 93 dogs; at the end of the follow-up, 34 dogs had died due to their cardiac problems, and 59 dogs remained alive. The association between variable parameters and survival is shown in However, group B had a significantly higher incidence of left atrial and left ventricle dilation . Group BIn the present study, we aimed to examine the peptide complement of the serum isolated from control dogs (group A) and dogs with impaired right ventricular function (group B). For preliminary comparison of the expression levels of the peptide's profiles, peptide mass fingerprint  was usedThis study's objective was to assess the prognostic information about valvular heart disease in dogs and investigate the right ventricular systolic function and blood lactate concentration. Dogs with clinical signs of congestive heart failure can be controlled, and they can live longer with better life quality by the appropriate medical treatment. Previous studies have reported the association with survival of echocardiographic variables such as left atrium and aorta ratio (LA/AO ratio), left ventricular internal diameter (LVID), and mitral E velocity. Our study also showed that heart size had an essential predictive value; left atrium dimension and vertebral heart score are associated with decreased survival in patients with degenerative mitral valve disease. However, the stage of mitral valve degeneration, systolic left ventricular internal diameter (LVIDs), and quality of life score were not indicators for survival predictors in our sample population. In addition, the percent survival in variables such as VHS, LA/AO ratio, and QOL was better in group B. Patients in group B contain more dogs in stage C, which had been treated with therapeutic drugs such as pimobendan, diuretic, and angiotensin-converting enzyme inhibitor. The results suggested that early treatment of MMVD patients in early stage B may improve the percent survival, which is similar to the ACVIM guideline .The previous study reported the proteome expression in heart failure patients associated with the inflammation response and oxidative stress , 22, simRenal dysfunction can use as a neuro-humoral change in heart disease. Our study showed that the BUN/creatinine ratio impacts the predictive value of degenerative mitral valve disease in dogs. Dogs with mitral valve degeneration ACVIM stage C had higher blood lactate concentrations than dogs in stage B2. Although dogs in groups A and B were not found to have significant differences in the lactate values, the previous studies showed a significant difference between active vs. non-active subjects . Thus, iThis study suggested that the right and left ventricular functions are functionally related to each other. Right ventricular systolic dysfunction was relatively common in dogs with left-sided congestive heart failure, as 50% of the dogs in this study had right ventricular systolic dysfunction. Dogs with right ventricular systolic dysfunction had significant left atrium dilation. A worse ACVIM stage of congestive heart failure than dogs without right ventricular dysfunction was observed, as 34% of dogs in group B had ACVIM stage C, but 18% had it in group A. The current study demonstrated that less TAPSE was associated with left-sided systolic and diastolic dysfunction. The E deceleration time was significantly shorter in dogs with right ventricular dysfunction. An explanation for right heart dysfunction could be that the alterations in preload and afterload that occur secondarily to left-sided congestive heart failure may alter the right heart function described earlier , 26.In discordance with the present study, dogs with right heart systolic dysfunction had no significant difference in end-systolic and end-diastolic dimensions or left ventricular internal diameter. Right ventricular imaging was considered a limitation of the present study. Right ventricular imaging in dogs with congestive heart failure is challenging due to the cardiac remodeling that could affect the echocardiographic measurement. Cardiovascular magnetic resonance imaging is recommended as the standard gold technique for the right-side assessment due to the complexity of the right-side heart anatomy.Dogs with mitral valve degeneration can have a mild increase in blood lactate values. In addition, dogs with right ventricular systolic dysfunction defined as FAC <30% and TAPSE <110 mm showed a significantly larger RV dimension at the basal level and a significantly worse degree of tricuspid regurgitation. Right ventricular dysfunction in degenerative mitral valve disease is common and is independent of left ventricular volume but is proportional to left contraction impairment. Peptidomics analysis results in this study suggested that these proteins may represent novel biomarkers of the disease progression in dogs with mitral valve degeneration. Our results in this present study will help in the detection and prognosis of mitral valve disease in dogs.https://www.uniprot.org/.The datasets presented in this study can be found in online repositories. The names of the repository/repositories and accession number(s) can be found below: The study protocol was approved by the Ethics Committee, Kasetsart University (ACKU-62-VET-002). Written informed consent was obtained from the owners for the participation of their animals in this study.SP wrote the original article, prepared the figures, and was a major contributor in writing the article. MY, MK, BI, and TP analyzed and interpreted the data. All authors contributed to the article and approved the submitted version.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.


Background: Myocardial efficiency should be maintained stable under light-to-moderate stress conditions, but ischemia puts the myocardium at risk for impaired functionality. Additionally, the measurement of such efficiency typically requires invasive heart catheterization and exposure to ionizing radiation. In this work, we aimed to non-invasively assess myocardial power and the resulting efficiency during pharmacological stress testing and ischemia induction.Methods: In a cohort of n = 10 healthy Landrace pigs, dobutamine stress testing was performed, followed by verapamil-induced ischemia alongside cardiac magnetic resonance (CMR) imaging. External myocardial power, internal myocardial power, and myocardial efficiency were assessed non-invasively using geometrical and functional parameters from CMR volumetric as well as blood flow and pressure measurements.Results: External myocardial power significantly increased under dobutamine stress  and significantly decreased under verapamil-induced ischemia . Internal myocardial power [baseline: 5.9 (4.6–8.5) W/m2] was not affected by dobutamine  nor verapamil . Myocardial efficiency did not change from baseline to dobutamine  but decreased significantly during verapamil-induced ischemia .Conclusion: In healthy Landrace pigs, dobutamine stress increased external myocardial power, whereas myocardial efficiency was maintained stable. On the contrary, verapamil-induced ischemia substantially decreased external myocardial power and myocardial efficiency. Non-invasive CMR was able to quantify these efficiency losses and might be useful for future clinical studies evaluating the effects of therapeutic interventions on myocardial energetics. Myocardial efficiency represents the ratio between the external mechanical power required to maintain blood flow against systemic vascular resistance and the contraction power required by the left ventricular (LV) myocardium , 2. ThisChanges in myocardial efficiency can be triggered and altered by several factors, such as medical treatment  or surgiNevertheless, even in resting conditions, the quantification of myocardial efficiency has not been established as a clinical standard since it is traditionally based on invasive measurements , 4. Moren = 10 (51 ± 10 kg) Landrace pigs were selected from an already published study cohort from our group  were acutely instrumented, and the animals were transported to the MRI facility for measurements. The pigs were ventilated with an MRI-compatible machine . After the baseline measurements, two steps were performed as follows: (I) dobutamine-induced stress (Dob) and (II) verapamil-induced ischemia (Ver). Dobutamine infusion was titrated, aiming at a 25% heart rate increase compared to the baseline values, while verapamil was given at boli of 2.5 mg each, aiming at a 25% decrease of CI. At each protocol, MRI images were acquired at short axis (SAX), 2Ch, 3Ch, and 4Ch views. After the MRI measurements, the animals were transported back to the operating room for sacrifice.The experimental protocol has been already described in two published papers from our group , 17. Bri2, reconstructed voxel size = 1.0 x 1.0 mm2, slice thickness 8 mm, 40 reconstructed cardiac phases, and number of averages (NSA) 2. Flow was quantified using two-dimensional phase-contrast MRI: TR 3.9, ms; TE, 2.4 ms; flip angle, 15°; 30 reconstructed cardiac phases; acquired in-plane voxel size, 2.1 × 2.1 mm2; reconstructed voxel size, 1.5 × 1.5 mm2; slice thickness, 10 mm; velocity encoding, 200 cm/s; and NSA, 2. The sequences were obtained (a) perpendicular to the aorta to assess peak flow and aortic valve regurgitation as well as (b) between the mitral valve inflow and the left ventricular outflow tract to quantify the auxobaric contraction time, the isovolumetric contraction time, and the aortic pressure gradient, respectively. All images were acquired during normal respiration with no respiratory motion correction, as respiration-induced bulk cardiac motion was absent or very small in these animals. All images were analyzed offline using Medis Suite  and View Forum  in accordance to the consensus for quantification function and flow using CMR.All CMR images were acquired in a supine position using a 3T  MRI scanner with a flexible anterior and a built-in posterior receive coil, where up to 30 coil elements were employed depending on the respective anatomy. All animals were scanned using identical comprehensive imaging protocols. The study protocol included initial scouts to determine the cardiac imaging planes. Cine images were acquired using an ECG-gated balanced steady-state free precession sequence in three LV long-axis  planes. The ventricular two- and four-chamber planes were used to plan stack of SAX slices covering the entire LV. The following imaging parameters were used: repetition time (TR) = 2.9 ms, echo time (TE) = 1.45 ms, flip angle = 45°, acquired in-plane voxel size = 1.9 × 1.9 mmThe clinical imaging and post-processing workflow to obtain CMR-derived myocardial power and efficiency is described in Power is the rate of transferring or converting energy per unit time. Cardiac power output (CPO) defines the power needed to pump blood against a given afterload of the systemic circulation.total = total cardiac output (converted from L/min to qm/s). Cardiac output (CO) was calculated by the Simpson method to measure LV volumes using SAX MRI images. Simpson's technique is based on Simpson's rules, which for our purposes were essentially the sum of the cross-sectional areas of each slice accounting for slice thickness and the interval between slices in a stack of contiguous slices covering the entire LV. LV contours in all slices required to measure the cross-sectional areas in each slice were assessed manually. External myocardial power (EMP) defines the power needed to pump blood against a given afterload at the LVOT.with MAP = mean arterial pressure (converted from mmHg to Pa) measured invasively, 451 = the unit conversion in watt, and COmean△PAV is the mean pressure gradient across the aortic valve. In our cohort, EMP is nearly equivalent to the concept of cardiac power output and circulatory power  , 18:Vwall = myocardial wall volume, σwall = peak systolic wall stress, and tCS = left ventricular systolic contraction time. EMP and IMP have been indexed to body surface area (BSA) to allow a better comparison between individuals. Wall stress was calculated using a simplified approach of the law of Laplace:where PSYS = LV peak systolic pressure, RBP = mean radius of the blood pool, and Swall = mean myocardial wall thickness. Swall and RBP during systole were averaged from LV segmentations, considering LV as a cylindrical geometry for the correction of potential regional differences. Psys = sum of the systolic blood pressure measured at the right arm and the maximum pressure gradient across the aortic valve. The ratio between IMP to the resulting EMP (IMP/EMP) is defined as myocardial efficiency.Where Continuous data are expressed as median and interquartile range (Q1–Q3) unless stated otherwise. Data distribution was tested using Shapiro–Wilk and Shapiro–Francia tests. The correlations between the CMR parameters of indexed IMP, indexed EMP, myocardial efficiency, and the hemodynamic parameters of CPO, CI, and left ventricular ejection fraction (LVEF) were assessed by linear regression analysis.Wilcoxon signed rank test was used to assess differences between baseline and the intervention. The significance level was set at 0.05. Data were analyzed using Stata 15.1  and GraphPad 8.0.2 .n = 10 pigs. The hemodynamic and the CMR-based geometrical and functional parameters of the pigs at rest, under dobutamine and under verapamil, are reported in Power and efficiency analyses were performed in Relevant differences for systolic blood pressure were seen between pigs under stress, whereas no differences were seen for diastolic blood pressure and mean arterial pressure between interventions (stress and ischemia) and rest. After stress induction with dobutamine, the heart rate increased significantly, while HR did not change after ischemia induction with verapamil.CO, calculated by the Simpson method, significantly increased during stress with dobutamine and also significantly decreased vs. baseline during ischemia. Invasively measured CPO significantly increased during dobutamine stress, and a significant decrease was observed during ischemia with verapamil. LVEF increased non-significantly during dobutamine but significantly decreased during verapamil.EMP, IMP, and myocardial efficiency were assessed in all groups using CMR. EMP changed significantly during both dobutamine-induced stress and also after ischemia induction . There wThe linear regression analysis showed a good correlation between EMP and CPO  and betwThe results of our non-invasive MRI approach show that myocardial efficiency was not altered during dobutamine stress testing, whereas efficiency was decreased during verapamil-induced ischemia. While external myocardial power directly reflects the resulting hemodynamic responses under both stress and ischemic conditions, myocardial efficiency reveals the coupling between the left ventricle and the circulatory system.External power has been shown to predict mortality in patients with cardiogenic shock or outcome in chronic heart failure patients better than LVEF , 20. In 2). A surrogate for the mechanical internal power that does not require exposure to ionizing radiation and that can be related to the resulting external power  has been recently introduced , and conform to the European Convention for the Protection of Vertebrate Animals used for Experimental and other Scientific Purposes .Professor Dragun passed away on December 28, 2020. This publication is dedicated to her memory as a mentor, role model, and stellar scientist.SK, HP, AA, and MK: conceptualization and methodology. LG: software. MK, AF, and LG: formal analysis. CL, MZ, NG, MK, and AF: writing—original draft preparation. AF, AA, CL, MZ, NG, FL, BS, CS, TK, HP, LG, EN, BP, SK, and MK: writing—review and editing. All authors contributed to the article and approved the submitted version.Journal of the American College of Cardiology. SK reports receiving grants from Philips Healthcare and speaker honoraria from Medis. CS and BS are employees of Philips Healthcare. The remaining 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.BP reports having received consultancy and lecture honoraria from Bayer Daiichi Sankyo, MSD, Novartis, Sanofi-Aventis, Stealth Peptides, and Vifor Pharma and editor honoraria from the 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.


On the 23rd day after the initiation of ARNI, even though the patient was not using hypoglycemic drugs, his fasting blood glucose markedly decreased to 70 mg/dL without hypoglycemic symptoms, and his fasting blood insulin decreased to 5.4 µU/mL . These results imply that ARNI has the potential to improve insulin resistance and the islet beta-cell function in patients with heart failure, in addition to the original effect of improving the hemodynamics, although the effect of improving the glucose metabolism is also considered to have been influenced by the improvement of the heart failure status and other drugs that the patient was taking.A recent study suggested that angiotensin receptor/neprilysin inhibitor  can improve functional capacity and cardiac reverse remodeling in patients with heart failure with reduced ejection fraction (HFrEF). Another study suggested that ARNI reduced glycated hemoglobin (HbA1c) in patients with diabetes and HFrEF; however, the details of its efficacy are unknown. We herein report a case of HFrEF with abnormal glucose metabolism in which ARNI was initiated. On the 7 Patients with heart failure with reduced ejection fraction (HFrEF) are at high risk for disease progression, hospitalization, and mortality. Angiotensin-converting enzyme (ACE) inhibitors have long been the cornerstone of treatment for heart failure, including HFrEF . A recenA previous study suggested that ARNIs can improve the functional capacity and cardiac reverse remodeling in patients with HFrEF, and that this anti-remodeling effect may lead to the prevention of ventricular arrhythmia and even sudden death . In addiA 76-year-old man without a history of hospital visits for medical illness, presented with bilateral leg edema that persisted for 2 months, and exertional breathlessness and orthopnea that had persisted for 2 weeks. On admission, a physical examination revealed the following: blood pressure 134/106 mmHg; heart rate 101 bpm; body temperature 36.4ºC; and saturation of percutaneous oxygen 97% on room air. A 12-lead electrocardiogram revealed sinus rhythm at 100 bpm with normal intervals, left axis deviation, and flattening of the T wave in I, aVL, V5, and V6. Chest X-ray showed cardiomegaly (cardiothoracic ratio (CTR): 73%) and pulmonary congestion Figure . Transth We described a case of HFrEF in which insulin resistance and the islet beta-cell function were significantly improved early after the initiation of ARNI treatment, although the effect of improving the glucose metabolism is also considered to have been influenced by the improvement of the heart failure status and other drugs that the patient was taking. This result implied that the administration of ARNI may improve the abnormal glucose metabolism in patients with HFrEF.Diabetes is an important risk factor for the development of heart failure. Conversely, the severity of heart failure is also strongly related to the development of diabetes . PreviouA previous study reported that, in congestive heart failure patients, the addition of ARB to ACE inhibitor significantly decreased fasting insulin levels and HOMA-IR values at 16 weeks, but fasting blood glucose levels did not change significantly . AnotherIn patients with heart failure, anemia adversely affects the hemodynamics, and parenteral iron replacement therapy was shown to improve subjective symptoms and exercise capacity . A previIn conclusion, we encountered a case of HFrEF in which insulin resistance and the islet beta-cell function significantly improved after the initiation of ARNI treatment, although the effect of improving the glucose metabolism is considered to have also been influenced by the improvement of the heart failure status and other drugs  that the patient was taking. Therefore, in heart failure patients with diabetes or impaired glucose tolerance, ARNI may improve derangement of the glucose metabolism, in addition to the original effect of improving the hemodynamics.


Many patients with mitral regurgitation are denied open-heart surgery due to perceived high risk. Transcatheter mitral valve replacement is a therapeutic alternative for patients at high surgical risk. This study aimed to assess the feasibility of a new self-expanding valved stent for transcatheter mitral valve replacement via apex in an acute animal model.Eight porcine experiments were performed in the acute study. A left thoracotomy was performed, and the new self-expanding transcatheter valved stent was deployed under fluoroscopic guidance in the native mitral annulus via apex. Hemodynamic data were recorded before and after implantation. Mitral annulus diameter and valve area were measured using echocardiography. Transvalvular and left ventricular outflow tract pressure gradients were measured using invasive methods.2. Trace-to-mild central and paravalvular leaks were detected in 7 valves. The mean pressure gradient across the self-expanding device was 2.00 ± 0.82 mmHg; the corresponding gradient across the LVOT was 3.28 ± 1.11 mmHg. Postmortem evaluation confirmed precise device positioning in 7 animals with no signs of LVOT obstruction.Seven animals underwent successful transapical mitral valve replacement; the implantation was unsuccessful in one animal. The mean procedure time, defined from placement to tightening of the purse-string suture, was 17.14 ± 7.86 min. Hemodynamic data before and after transapical mitral valve replacement showed no difference in statistical analysis. The mean diameter of the self-expanding device after implantation was 2.58 ± 1.04 cm; the mean functional area was 2.70 ± 0.26 cmTranscatheter mitral replacement of the new valved stent was confirmed feasible in acute preclinical models. The new stent reveals optimal design parameters. Mitral regurgitation is one of the most common heart valve diseases worldwide , 2. AlthIn the past decade, transcatheter aortic valve implantation (TAVI) is used increasingly with exciting results as a surgical alternative for high-risk patients , 9. TranWe developed a new self-expanding valved stent for transcatheter mitral valve replacement via apex. This study tests its feasibility in an acute animal model.The new stent Fig.  is a selThe delivery system Fig. d is desiThe study was approved by the local Ethics Research Board. Animals received care in compliance with the “Guide for the Care and Use of Laboratory Animals” prepared by the Institute of Laboratory Animal Resources and published by the National Institute of Health .Eight porcine experiments (mean body weight of pigs was 46.45 ± 3.72 kg) were performed in this acute study. After administering general anesthesia with tracheal intubation and mechanical ventilation , a coronary sinus electrode was inserted into the right internal regular vein using digital subtraction angiography (DSA) guidance to confirm the position of the mitral annulus. The right femoral artery was catheterized for monitoring blood pressure and blood sampling. The left femoral artery was implanted with a 5F pigtail into the aortic root for aortic valve localization and angiograph. Arterial pressure, central venous pressure, oxygen saturation, and electrocardiography were monitored continuously.A 5-cm left thoracotomy was performed. Double-purse string sutures were placed at the optimal access site of the left ventricular apex. The valved stent was 10% larger than the diameter of the native mitral annulus measured by CT and epicardial echocardiography. Left ventricular angiography was performed to determine the position of the mitral annulus. A stiff wire was introduced across the mitral valve into the pulmonary vein; the delivery system was advanced along the guide wire into the left atrium, using DSA guidance. The atrial brim was expanded first. It was necessary to gradually adjust the conveyor to the proper position so that the flat aspect of the D-shaped stent was aligned with the aorta. . The delivery system was pulled down until the atrial flange was seated firmly on the floor of the left atrium. The ventricular body was deployed without rapid ventricular pacing, and the clip was released to hold the anterior valve. After achieving stability, the stent was completely separated from the conveyor. Three tethering strings attached to the stent were pulled out of the apex with the conveyer withdrawn. The length of the tethering strings was adjusted under real-time monitoring using echocardiography. The apical access site was closed with purse-string sutures. The tethering strings were fixed at the epicardial surface by knotting the polyester felts. The procedure was performed under fluoroscopic guidance Fig. .Fig. 2aDevice function and hemodynamic impact were assessed using epicardial echocardiography Fig.  and angiContinuous hemodynamic measurements were recorded for another 6–8 h. The animals were sacrificed for postmortem evaluation and device inspection Fig. .Fig. 4PData were analyzed using SPSS v19 software for Windows. Variables were reported as mean ± standard deviation (SD), and Student’s T-test was used for comparison.2 on echocardiographic evaluation; the mean diameter of the self-expanding device after implantation was 2.58 ± 1.04 cm, and the mean functional area was 2.70 ± 0.26 cm2. No statistical difference existed in mitral diameter before and after implantation. However, the functional mitral valve areas showed significant differences before and after the procedure . Of the 7 successful implants, all valve leaflets had normal mobility and function. Trace or mild central and paravalvular regurgitation was detected in 7 valves , the development of transcatheter mitral valve replacement faces unique challenges. The mitral valve is a complicated anatomic apparatus, including mitral leaflets, chordae, and papillary muscles. The non-circular saddle-shaped annulus is pliable and changes during the cardiac cycle. Several vital structures, such as the circumflex coronary artery, atrioventricular node, and left ventricular outflow tract, are adjacent to the mitral valve . SpecifiAlthough several challenges exist in TMVR, the TMVR system is rapidly expanding, with over 10 devices currently under development . SeveralThe atrial portion of our device is “D” shaped to match the native mitral annulus. It is conducive to stent fixation and reduces paravalvular leakage. The flange section of the two edges is wider than the flat aspect and the arc, specifically designed to fit the saddle-shaped mitral annulus. The asymmetric flange minimizes left ventricular outflow tract obstruction and prevents stent displacement. A circular ventricular stent has three anchoring structures. First, radially struts are arranged on the ventricular component of the valved stent to penetrate the mitral leaflet and the valvular apparatus and prevent the device retrograde dislodgement into the atrium during systole. Second, a clip on the ventricular portion corresponds to the position of the anterior leaflet of the mitral valve. It is released to hold the anterior leaflet of the mitral valve after the ventricular component opens completely. The design minimizes left ventricular outflow tract obstruction caused by the native anterior leaflet. It also prevents the movement of the device into the left atrium. During the operation, we did not deliberately capture the anterior leaflet. As long as the flat aspect of the D-shaped stent is aligned with the anterior annulus of the mitral valve, the clip can easily hold the anterior leaflet after the left ventricular body is fully opened. Third, three tethering strings are attached to the lower part of the stent and fixed to the apex of the heart to prevent stent displacement. The early experiments showed that the posterior side of the stent shifted to the left atrium during systole. This finding may be related to the insufficient anchoring force between the device and the posterior annulus. We did not include a clip on the posterior of the stent as Tiara to avoid the risk of penetrating the posterior wall of the left ventricle. Therefore, we added three strings attached to the stent symmetrically that could be pulled out with the delivery system and sutured to the apex. Current TMVR devices presenting anchoring systems with clips or tethering strings have proved to be reliable. Tiara® has three clips, two anterior and one posterior. Medtronic has two clips, called support arms. In our device, the single-clip design makes it easier to hold the anterior leaflet. Tendyne™ uses a ventricular fixation system connected to the LV apex through a polyethylene tether ; the comOur self-expanding stent valve achieved good hemodynamic performance in the acute porcine model with no stent displacement and left ventricular outflow tract obstruction. Although a significant difference exists in the effective functional area between the stent valve and the natural valve, it was comparable to the conventional bioprosthetic valve. Therefore, this study confirmed the feasibility of the new valved stent and the delivery system. We plan to conduct a long-term animal experiment to observe the reliability of valve stents.A limitation of this study is the use of healthy animal models with normal cardiac anatomy and physiology. The healthy pig is significantly different from the patient presenting with functional mitral regurgitation. Another limitation is that the study is an acute experiment. It is necessary to carry out chronic experiments to verify the reliability of valve stents.The new transapical valved stent was feasible and safe for mitral valve replacement and showed promising hemodynamic performance in an acute study.


The high incidence of cardiovascular disease (CVD) in patients with autoimmune rheumatic diseases (ARDs) is the main driver towards increased mortality in this patient group. Cardiovascular magnetic resonance (CMR) can non-invasively and robustly detect CVD in ARD patients at an early stage of development. The review summarises the diagnostic information provided by CMR in ARD patients.CMR uses a strong magnetic field combined with radio-frequency pulses (pulse sequences) to generate images. Firstly, balanced steady-state free precession (bSSFP) can be used for evaluating cardiac anatomy, mass, wall motion, atrial/ventricular function. Secondly, T2-weighted imaging (T2-W) can be used for oedema detection, which appears as a high signal intensity area on STIR (short tau inversion recovery) images. T2 mapping is a newer T2-W technique that can provide more optimal identification of myocardial oedema. Lastly, late gadolinium enhanced (LGE) T1-W images, taken 15 min. after injection of contrast agent, allow the detection of myocardial replacement fibrosis, which appears as a bright area in a background of black myocardium. However, LGE has inherent disadvantages for the assessment of diffuse myocardial fibrosis. Therefore, T1 mapping and extracellular volume fraction (ECV) have been developed to quantify diffuse myocardial fibrosis.Although multicentre studies are still missing, the CMR parameters have been extensively applied for the identification of oedema/fibrosis and treatment decision making in ARDs.Tissue characterisation with CMR allows early and robust identification of CVD in ARD patients and contributes to personalized management in the patients. The mainstay of therapy is immunomodulatory treatment as to prevent inappropriate immune activation. Although new targeted treatments currently available for the management of ARDs have resulted in significant reductions of disease-associated mortality, patients with ARDs still have a lower average life expectancy compared with the general population,8 Irrespective of aetiology, CVD in this patient population usually presents asymptomatically or with few subtle symptoms, which are often overlooked or written off as constitutional symptoms. Clinically overt CVD presents late in the course of ARDs and carries a poor prognosis, as it indicates advanced disease progression and/or decompensation.9 Therefore, robust and early identification of patients with ARDs that develop CVD, as well as appropriate treatment to prevent disease progression and reduce morbidity and mortality are essential for improving prognosis in this patient group.CVD in patients with ARDs can be caused by various pathophysiologic phenomena. These include systemic and/or cardiovascular inflammation, perfusion defects due to micro-/macro-vascular coronary artery disease (CAD), abnormal vasoreactivity, myocardial fibrosis, coagulation abnormalities, pulmonary hypertension due to cardiac/pulmonary involvement, valvular diseases, and effects of immunomodulatory medication.11 The aim of this review is to present a concise summary of the diagnostic information that can be provided by the complete array of CMR-generated images in patients with ARDs, and to discuss their clinical significance in the context of the early detection of CVD in these patients.Regarding the early identification of patients with ARDs and CVD, many strategies have been investigated including clinical examination, circulating biomarkers, and cardiovascular imaging modalities. Cardiovascular magnetic resonance imaging (CMR) has emerged as the most effective diagnostic modality for this purpose, as it can evaluate cardiac function and characterize myocardial tissues with regard to oedema/fibrosis in the same examination without making use of ionizing radiation.10 In contrast to echocardiography, image acquisition with CMR is operator-independent and has excellent reproducibility.10 This is because images are acquired by using a strong magnetic field and a sequence of radio frequency photon pulses , which are not limited by parameters such as sufficient acoustic window, as in the case of echocardiography. The basic pulse sequences that are used in the clinical setting include10 balanced steady-state free precession (bSSFP), as well as a variety of T1-weighted (T1-W) and T2-weighted (T2-W) sequences. We have previously described the basic physics behind CMR as well as how each pulse sequence functions in detail.11 These will now be presented with less emphasis on technical details and more focus on their clinical utility, combined with illustrative example images for each one. As a side note, since CMR uses a strong magnetic field to generate images, the strength of said magnetic field is measured in Tesla units (abbreviated as T); currently, most CMR scanners operate using a magnetic field strength of 1.5 or 3 T.The greatest advantage of CMR lies in that it can provide direct information about the status of all cardiac tissues in a non-invasive manner and without employing ionising radiation.Figure 1).12Balanced steady-state free precession at a magnetic field strength of 1.5 Tesla is considered the gold standard for characterising cardiac anatomy, myocardial mass, wall motion, atrial, and ventricular function of both the left and right ventricles (LV/RV)  or diffuse, subendocardial or transmural following the territory of coronary arteries as in CAD, subepicardial as in myocarditis  and diffuse subendocardial as in vasculitis.Acquisition of these images is based on the prolongation of the transverse relaxation time (T2) caused by water accumulation due to oedema.16The pulse sequence originally developed for the identification and quantification of myocardial oedema is named short tau inversion recovery (STIR). Oedema appears as a high signal intensity area on images derived using the STIR sequence, where the signal from fat and the blood pool is suppressed to improve the contrast between oedema, normal myocardium, and the LV cavity. However, the utility of STIR images may be limited by poor contrast between healthy and oedematous areas, high dependency on magnetic field homogeneity, loss of signal due to cardiac motion, subendocardial slow flow hyperintensity, susceptibility to motion artifacts, and subjective visual interpretation by different readers.18To overcome these limitations of STIR, a new imaging approach called T2 mapping has been developed. T2 mapping is a technique used to construct a map of the myocardium based on the individual T2 value of each voxel. At a magnetic field strength of 1.5 Tesla, the mean and standard deviation of T2 mapping in the myocardium of healthy adults was 52±3ms in a study by Giri et al. in 14 participants, and 55±5ms in a study by Wassmuth et al. in 73 participants. These values are independent of body surface area and/or heart rate and have excellent reproducibility.19 Similar to T2-W imaging, acquisition of T1-W images is based on the prolongation of the longitudinal relaxation time (T1). This can be caused by expansion of the extracellular space as occurs in the case of deposition of extracellular matrix as part of myocardial fibrosis, or volume shift from the intravascular to the extravascular compartment due to inflammatory processes, leading to increased vascular permeability.19 Different T1-W pulse sequences have different sensitivities to these processes as described below.The T1 relaxation time is a key parameter of soft tissue contrast in MRI.10 Standard gadolinium-based contrast agents are distributed throughout the extracellular space and shorten T1 relaxation times of myocardium proportional to the local concentration of gadolinium. Areas of fibrosis and scar will therefore exhibit shorter T1 relaxation times, in particular, after contrast administration. This appears as a bright area in a background of nulled, black myocardium, giving rise to the characteristic pattern of “bright is dead”.10 According to the type and location of LGE, the cause of the fibrosis could be attributed to CAD if the lesion is subendocardial, or transmural along the distribution of the coronary arteries . In contrast, subepicardial or patchy LGE usually in the inferolateral wall is characteristic of any kind of myocarditis . Finally, a diffuse subendocardial pattern of fibrosis is typically seen in small vessel disease, as in the case of systemic sclerosis, antiphospholipid syndrome, rheumatoid arthritis and small vessel vasculitides .10Late gadolinium enhanced T1-W images (LGE) obtained using standardized pulse sequences 15 min. after the infusion of paramagnetic gadolinium-based contrast agent, allow the detection of myocardial fibrotic tissue (scar).10 This approach allowed the early detection of perfusion defects in patients with systemic sclerosis not experiencing any cardiovascular symptoms,20 and those with antiphospholipid syndrome.21 Lastly, by injecting a bolus of paramagnetic contrast agent, it is possible to perform non-invasive angiography, which can provide important information about great vessel patency and mural inflammation in great vessel vasculitides.10T1-W imaging after pharmacologic stress with adenosine and bolus injection paramagnetic contrast agent can provide an accurate and reproducible evaluation of myocardial perfusion during stress.23 To overcome this limitation, a CMR imaging technique called T1 mapping has been developed. T1 mapping can be measured without paramagnetic contrast agent (native or pre-contrast T1 mapping) and after administration of paramagnetic contrast agent (post-contrast T1 mapping). Similar to T2 mapping, T1 mapping provides a quantitative assessment of tissue characterization and enables identification of early myocardial fibrosis, which is otherwise undetectable by currently used circulating biomarkers.24 The mean and standard deviation of T1 mapping values in healthy volunteers are 995.8±30.9ms and 1183.8±37.5ms at a magnetic field strength of 1.5 T and 3T, respectively.25Although LGE is well-validated as the technique of choice for the detection of focal myocardial scars (replacement fibrosis), it has inherent limitations with regard to the assessment of diffuse myocardial fibrosis, as it is based on the signal intensity differences between scarred and normal myocardium to generate image contrast. Since a normal myocardial reference value is required for the LGE images, this approach is unlikely to detect diffuse fibrosis if there is no clear distinction between fibrotic tissue and normal myocardium, as is often the case in patients with ARDs.Native (pre-contrast) and post-contrast T1 mapping can also be used for the calculation of extracellular volume fraction (ECV). Unlike native T1 relaxation times, contrast-enhanced T1 values are more variable and dependent on contrast agent dosing, the time interval between contrast administration and measurement, and renal clearance. The estimation of the ECV (interstitium and extracellular matrix) requires measurement of myocardial and blood T1 before and after administration of contrast agents as well as the patient’s haematocrit value according to the formula:28 ECV measures also exhibit better agreement with histological measures of the collagen volume fraction than isolated post-contrast T1 mapping.29 Normal ECV values of 25.3±3.5% have been reported in healthy individuals at a magnetic field strength of 1.5T.26 Apart from deposition of amyloid fibrils in the extracellular space, an increased ECV is most often due to excessive collagen deposition as in systemic sclerosis,26 and therefore represents a more robust measure of myocardial fibrosis. Low ECV values occur in thrombus and fat/lipomatous metaplasia. ECV can be calculated either from myocardial regions-of-interest or visualized on ECV maps similar to T1 and T2 mapping.27 Using this approach, ARD patients were found to have higher T1 and T2 values, as well as expanded ECV compared to controls, with most significant differences between native T1 and T2, which seem to be independent of the presence of LGE.30 Furthermore, native T1 mapping is sensitive to myocardial oedema, iron overload, and the presence of myocardial infarcts and scarring,19 and allows to follow longitudinal changes during treatment trials.19ECV represents a physiological parameter and is more reproducible between different magnetic field strengths, vendors, and acquisition techniques than either native or post-contrast T1 mapping.32 Particularly for patients with ARDs, a CMR protocol including biventricular function assessment, LGE, T1, T2 mapping, and ECV, which can be performed in less than one hour, can be proposed as a sufficient clinical tool for every day clinical practice. If there are other queries, such as valvular disease quantification or vascular assessment, then other more sophisticated approaches should be added. It should be kept in mind that a CMR examination should be individualised according to the clinical scenario of the individual patient, and not performed uniformly as a one-size-fits-all approach in all ARD patients, since this might increase scanning time without necessarily answering providing additional information regarding the reason of referral.In general, the limitations of CMR examinations are centred around their high costs and time-consuming nature, both of which limit its everyday applicability in general cardiology. However, the impressive yield of CMR examinations with regard to the diagnosis of silent cardiac involvement that is often missed by other imaging modalities has been recognised in recent practice guidelines.1)If there is a mismatch between patient symptoms and results of blood and/or imaging biomarkers;2)In cases of new-onset HF and/or arrhythmia;3)If the patient does not respond adequately to the immunomodulatory treatment;4)If the underlying disease is quiescent, but the patient has cardiac symptoms; or5)At the time of diagnosis for patients with systemic sclerosis and systemic lupus erythematosus, since cardiac involvement may be present and require immunomodulatory intervention, even if the systemic signs of SSc or SLE are minimal.To summarise, although no practice guidelines currently provide specific indications for a CMR examination in patients with ARDs, the authors recommend that a CMR examination should be considered in the following cases:Until recently, the evaluation of cardiac involvement in patients with ARDs was based on the presence of cardiac symptoms and the assessment of cardiac functional changes that only manifest as late findings. Currently, cardiac tissue characterisation using CMR allows for the early and robust identification of pathophysiologic phenomena that take place before clinically overt cardiac disease can manifest. As such, CMR provides considerable diagnostic utility and can inform early clinical decision-making with regard to appropriate immunomodulatory therapies. These in turn permit the individualization of patient treatment, ultimately leading to a truly personalized medicine.