Impaired Left Ventricular Relaxation Research Articles

Energy wavelet signal processed ECG and standard 12 lead ECG: Diagnosis of early diastolic dysfunction.

Left ventricular (LV) diastolic dysfunction (LVDD) is the result of impaired LV relaxation and identifies those at risk of developing heart failure. Echocardiography has been used as the gold standard to identify early LVDD. The signal processed electrocardiogram (hsECG) has demonstrated effectiveness to detect early LVDD. Whether or not the standard 12‑lead electrocardiogram (ECG) can accurately predict early LVDD is not known. A standard 12‑lead ECG including signal processing (hsECG) was performed in 569 patients. Patients with atrial fibrillation, bundle branch block, pre-excitation, left ventricular hypertrophy or known cardiovascular disease were excluded, leaving 464 examinations for analysis. Early LVDD was diagnosed by established methods using echocardiography. Repolarization abnormalities (T wave discordance) in V1, V6, I and aVL and the hsECG were compared to the echocardiographic findings to establish diagnostic accuracy. A total of 84 (18.1%) patients were diagnosed with early LVDD. A combination of a borderline or abnormal finding on the hsECG produced the best diagnostic model (sensitivity 84.5%, specificity 47.9%). The best performing ECG lead was V1 with a sensitivity of 38.1% and specificity of 92.1%. Regression analysis demonstrated increasing age and V1 to be predictive of LVDD. The hsECG displayed reasonable ability to detect early LVDD. Other than V1, repolarization abnormalities on the standard 12‑lead ECG did not. While lead V1 showed promise in detecting LVDD, whether this or any other simple ECG variable can predict future LVDD would be of further interest.

Percutaneous Coronary Intervention in a Saphenous Vein Graft Failure: A Case Report

Abstract: Recent published data from the Society of Thoracic Surgery (STS) national database displayed that among patients aged >65 years old who survived following an initial coronary artery bypass graft (CABG) operation, rates of repeat revascularization at 1, 5, 10, and 18 years were 2%, 8%, 16%, and 25%, respectively. The most preferred mode of revascularization was percutaneous coronary intervention (PCI). While remain the most frequently used conduits beside left internal mammary artery (LIMA), saphenous vein grafts (SVGs) have high failure rates. Percutaneous coronary intervention in SVGs is associated with an increased risk of distal coronary embolization, commonly resulting in periprocedural MI. We reported a 79-year-old male patient admitted due to progressive symptoms of chronic coronary syndrome. The patient had a history of hypertension and a CABG surgery in 2012. Electrocardiogram showed ischemia and old myocardial infarction (OMI) in inferior leads as well as poor R wave progression in the precordial leads. Transthoracic echocardiogram displayed a normal ejection fraction but impaired left ventricular (LV) diastolic relaxation. Diagnostic coronary angiography revealed a 70% tubular stenosis in proximal part of SVG supplying posterior descending artery, patent LIMA graft to left anterior descending artery, and complex lesion on native vessel (chronic total occlusion in mid right coronary artery). Implantation of drug eluting stent in SVG-posterior descending artery was performed. Direct-stenting PCI technique using undersized-stent was done to prevent any complications. In conclusion, despite the high risk of complications, vein graft intervention was successfully performed without any complications. Since the high rates of in-stent restenosis following PCI in SVGs, long-term dual antiplatelet therapy should be commenced in this patient. Keywords: saphenous vein graft; vein graft intervention; percutaneous coronary intervention

Evaluation of Intraoperative Left-Ventricular Diastolic Function by Myocardial Strain in On-Pump Coronary Artery Bypass Surgery

Left ventricular (LV) diastolic function strongly predicts outcomes after cardiac surgery, but there is no consensus about appropriate intraoperative assessment. Recently, intraoperative diastolic strain-based measurements assessed by transesophageal echocardiography (TEE) have shown a strong correlation with LV relaxation, compliance, and filling, but there are no reports about evaluation through the entire perioperative period. Therefore, the authors describe the intraoperative course of this novel assessment technique in patients who underwent coronary artery bypass grafting, and compare it with conventional echocardiographic measures and common grading algorithms of LV diastolic dysfunction (LVDD). Prospectively obtained data. A single university hospital. Thirty adult patients scheduled for isolated on-pump coronary artery bypass grafting surgery with preoperative preserved left and right ventricular systolic function, without significant heart valve disease and pulmonary hypertension, and an uneventful intraoperative course were included. Transesophageal echocardiography was performed after induction of anesthesia (T1), after termination of cardiopulmonary bypass (T2), and after sternal closure (T3). Echocardiographic evaluation was performed in stable hemodynamic conditions, in sinus rhythm or atrial pacing, and vasopressor support with norepinephrine ≤0.1 µg/kg/min. Strain-based measurements of peak longitudinal strain rate during isovolumetric relaxation (SR-IVR) and during early (SR-E) and late (SR-A) LV filling were assessed using EchoPAC v204 software (GE Vingmed Ultrasound AS, Norway). Evaluation of conventional echocardiographic parameters included transmitral Doppler measures of early (E) and late (A) LV filling, as well as lateral-tissue Doppler velocity assessed during early (e´) and late (a´) LV filling, tricuspid regurgitation, and left atrial dilatation. Evaluation and grading of LV diastolic function by myocardial strain was feasible in all included patients at all time points of assessment. Using conventional grading algorithms, however, a substantial number of patients could not be sufficiently graded, falling into an indeterminate zone and not reliably estimating LVDD (T1, 40%; T2, 33%; T3, 36%). There was significant impairment of LV diastolic function after bypass, as measured by SR-IVR (T1 v T2, 0.28 s-1 [IQR 0.23; 0.31) v 0.18 s-1 [IQR 0.14; 0.22]; p < 0.001), SR-E (T1 v T2, 0.95 ± 0.34 s-1v 1.28 ± 0.36 s-1; p < 0.001), and E/SR-IVR (T1 v T2, 2.3 ± 1.0 m v 4.5 ± 2.1 m; p < 0.001]. Conventional echocardiographic measures remained unchanged during the same period (E/A T1 v T2, 1.27 [IQR 0.94; 1.59] v 1.21 [IQR 1.03; 1.47] [p = 1] and E/e´ T1 v T2, 7.0 [IQR 5.3; 9.6] v 6.35 [IQR 5.7; 9.9] [p = 0.9]). There were no significant changes in the values of SR-IVR, SR-E, SR-A, E/SR-IVR, E/A, and E/e´ before and after sternal closure (T2 v T3). Intraoperative assessment of strain-based measurements of LV diastolic function and strain-based LVDD grading was feasible in this group of selected patients, whereas conventional parameters failed to describe LVDD sufficiently in a substantial number of patients. Diastolic strain-based measurements showed impairment of LV relaxation and compliance after bypass, which was not detected by conventional echocardiographic parameters. Therefore, diastolic myocardial strain analysis might be more sensitive in detecting myocardial diastolic dysfunction by TEE in the perioperative setting, with its dynamic changes of loading conditions, and might provide valuable and additional information on the perioperative changes of LV diastolic function.

Mapping individual cardiac cell types and their contribution in the development of heart failure in a multiple comorbidity porcine model

Abstract Background Heart failure with preserved ejection fraction (HFpEF) is characterized by impaired left ventricular (LV) relaxation and filling due to increased myocardial stiffness and hypertrophy. The development of HFpEF is associated with multiple, interrelated risk factors including obesity, chronic kidney disease (CKD), diabetes mellitus (DM), hypertension. Mechanistic studies have implied that comorbidity-driven chronic inflammation, oxidative stress, and endothelial dysfunction act as contributors to the onset and development of HFpEF. Multiple studies that support this HFpEF paradigm highlight the complexity of the disease with different pathways active in and across different cell types. A recently developed multiple comorbidity swine (MCS) model with DM, CKD hypercholesterolemia, demonstrate inflammation, microvascular endothelial dysfunction and LV diastolic dysfunction. This model mimics the slow progression of disease in patients and is therefore ideal to study the earliest mechanisms underlying HFpEF. Purpose Here we hypothesize that single nuclei RNA (snRNA) sequencing aid in mapping the contribution of each individual cardiac cell cluster to disease development, to improve our mechanistic understanding of HFpEF. Methods We performed snRNA sequencing to analyze the transcriptional landscape of the cardiac environment in the well validated MCS model. Frozen left ventricle myocardial samples of MCS (n=4) and healthy control (n=3) swine were used. Results The analysis included ∼100.000 individual nuclei and offers new insights in cell type specific mechanisms during HFpEF onset and development against the background of common comorbidities. We identified 34 different cell clusters, which together represent 6 major cell types. Besides cardiomyocytes (CMs), endothelial cells (ECs) and fibroblasts, a large population of immune cells and smaller populations of mural cells and neurons were present in both MCS and control swine. IPA pathway analysis predicts transcriptomic changes within the cell clusters in response to comorbidities including activation of semaphoring and estrogen signaling in the largest CM cluster (CM2) and activation of EIF2 signaling in ECs (Fig. 1). Gene set enrichment analysis confirmed the activation of HFpEF paradigm pathways in the MCS dataset. Overlap of human HFpEF heart bulk RNA sequencing data and the MCS dataset showed overlapping disease processes including interferon gamma (IFNG) signaling. Moreover, IFNG signaling and IFNG associated transcription factor STAT1 were activated in most of the CM and EC clusters. Conclusion These findings suggest an essential role of multiple pathways during the onset and development of HFpEF. Further improvement of our understanding of underlying molecular mechanisms and crosstalk between cell populations, could pinpoint drug targets and aid the development of new treatments for HFpEF.Top 5 IPA predicted canonical pathways

Haemodynamic effects of hypertension and type 2 diabetes: Insights from a 4D flow MRI-based personalized cardiovascular mathematical model.

Type 2 diabetes (T2D) and hypertension increase the risk of cardiovascular diseases mediated by whole-body changes to metabolism, cardiovascular structure and haemodynamics. The haemodynamic changes related to hypertension and T2D are complex and subject-specific, however, and not fully understood. We aimed to investigate the haemodynamic mechanisms in T2D and hypertension by comparing the haemodynamics between healthy controls and subjects with T2D, hypertension, or both. For all subjects, we combined 4D flow magnetic resonance imaging data, brachial blood pressure and a cardiovascular mathematical model to create a comprehensive subject-specific analysis of central haemodynamics. When comparing the subject-specific haemodynamic parameters between the four groups, the predominant haemodynamic difference is impaired left ventricular relaxation in subjects with both T2D and hypertension compared to subjects with only T2D, only hypertension and controls. The impaired relaxation indicates that, in this cohort, the long-term changes in haemodynamic load of co-existing T2D and hypertension cause diastolic dysfunction demonstrable at rest, whereas either disease on its own does not. However, through subject-specific predictions of impaired relaxation, we show that altered relaxation alone is not enough to explain the subject-specific and group-related differences; instead, a combination of parameters is affected in T2D and hypertension. These results confirm previous studies that reported more adverse effects from the combination of T2D and hypertension compared to either disease on its own. Furthermore, this shows the potential of personalized cardiovascular models in providing haemodynamic mechanistic insights and subject-specific predictions that could aid in the understanding and treatment planning of patients with T2D and hypertension. KEY POINTS: The combination of 4D flow magnetic resonance imaging data and a cardiovascular mathematical model allows for a comprehensive analysis of subject-specific haemodynamic parameters that otherwise cannot be derived non-invasively. Using this combination, we show that diastolic dysfunction in subjects with both type 2 diabetes (T2D) and hypertension is the main group-level difference between controls, subjects with T2D, subjects with hypertension, and subjects with both T2D and hypertension. These results suggest that, in this relatively healthy population, the additional load of both hypertension and T2D affects the haemodynamic function of the left ventricle, whereas each disease on its own is not enough to cause significant effects under resting conditions. Finally, using the subject-specific model, we show that the haemodynamic effects of diastolic dysfunction alone are not sufficient to explain all the observed haemodynamic differences. Instead, additional subject-specific variations in cardiac and vascular function combine to explain the complex haemodynamics of subjects affected by hypertension and/or T2D.

Diastolic Function Assessment by Echocardiography at Dhulilkhel Hospital

IntroductionDiastolic dysfunction (DD) is understood as impaired Left ventricular relaxation. Echocardiography is the key in diagnosis. In 2016 recommendation by American Society of Echocardiography(ASE) and the European Association of Cardiovascular Imaging (EACVI) was updated. In our country we do not have a general consensus. Diastolic dysfunction is reported on the basis of E/A ratio of mitral flow, that has the chance of missing a lot of patients with pseudo-normalization. This study carried out to look at importance of evaluation of other parameters to diagnose a patient with diastolic dysfunction.Methods: It is a retrospective cross-sectional descriptive study. Echocardiography report from the year 2018 and 2019 was collected from database and the patients with diagnosis of Diastolic dysfunction were selected. Patient profile and the echocardiographic parameter were recorded. Echocardiography was reported according to 2016 ASE and EACVI update.Results: Total of 1982 patients selected for analysis. E/A &lt; 0.8 was seen in 702(35.4%) patients, E/A 0.8- 2.0 was seen in 1136 (57.3%) patients and E/A &gt; 2.0 was found in 144(7.3%) patients. The most common finding being E/e’ 1470 (74.2%) of patients followed by TR velocity &gt; 2.8m/s 1422 (71.7%), Septal e’ velocity &lt; 7 cm/s or Lateral e’ velocity &lt;10 cm/s 1334 (67.3%) and LA area &gt;20 cm2 1286 (64.8%) respectively.Conclusions: Diastolic dysfunction should be evaluated using all the parameters recommended by 2016 ASE andEACVI guideline update. Measurement of only E/A ratio has a chance of missing large number of patient with DD.

Machine learning-based classification of cardiac relaxation impairment using sarcomere length and intracellular calcium transients

Impaired relaxation of cardiomyocytes leads to diastolic dysfunction in the left ventricle. Relaxation velocity is regulated in part by intracellular calcium (Ca2+) cycling, and slower outflux of Ca2+ during diastole translates to reduced relaxation velocity of sarcomeres. Sarcomere length transient and intracellular calcium kinetics are integral parts of characterizing the relaxation behavior of the myocardium. However, a classifier tool that can separate normal cells from cells with impaired relaxation using sarcomere length transient and/or calcium kinetics remains to be developed. In this work, we employed nine different classifiers to classify normal and impaired cells, using ex-vivo measurements of sarcomere kinematics and intracellular calcium kinetics data. The cells were isolated from wild-type mice (referred to as normal) and transgenic mice expressing impaired left ventricular relaxation (referred to as impaired). We utilized sarcomere length transient data with a total of n = 126 cells (n = 60 normal cells and n = 66 impaired cells) and intracellular calcium cycling measurements with a total of n = 116 cells (n = 57 normal cells and n = 59 impaired cells) from normal and impaired cardiomyocytes as inputs to machine learning (ML) models for classification. We trained all ML classifiers with cross-validation method separately using both sets of input features, and compared their performance metrics. The performance of classifiers on test data showed that our soft voting classifier outperformed all other individual classifiers on both sets of input features, with 0.94 and 0.95 area under the receiver operating characteristic curves for sarcomere length transient and calcium transient, respectively, while multilayer perceptron achieved comparable scores of 0.93 and 0.95, respectively. However, the performance of decision tree, and extreme gradient boosting was found to be dependent on the set of input features used for training. Our findings highlight the importance of selecting appropriate input features and classifiers for the accurate classification of normal and impaired cells. Layer-wise relevance propagation (LRP) analysis demonstrated that the time to 50% contraction of the sarcomere had the highest relevance score for sarcomere length transient, whereas time to 50% decay of calcium had the highest relevance score for calcium transient input features. Despite the limited dataset, our study demonstrated satisfactory accuracy, suggesting that the algorithm can be used to classify relaxation behavior in cardiomyocytes when the potential relaxation impairment of the cells is unknown.

Postpartum Detection of Diastolic Dysfunction and Nondipping Blood Pressure Profile in Women With Preeclampsia.

Left ventricular diastolic dysfunction and nocturnal "nondipping" of blood pressure detected via ambulatory blood pressure monitoring are predictors of increased cardiovascular morbidity. A prospective cohort study including normotensive women with a history of preeclampsia in their current pregnancy was conducted. All cases were subjected to 24-hour ambulatory blood pressure monitoring and 2-dimensional transthoracic echocardiography 3 months after delivery. This study included 128 women with a mean (SD) age of 28.6 (5.1) years and a mean (SD) basal blood pressure of 123.1 (6.4)/74.6 (5.9) mm Hg. Among the participants, 90 (70.3%) exhibited an ambulatory blood pressure monitoring profile illustrating nocturnal blood pressure "dipping" (the mean night to day time blood pressure ratio ≤ 0.9), whereas 38 (29.7%) were nondippers. Diastolic dysfunction (impaired left ventricular relaxation) was present in 28 nondippers (73.7%), whereas none of the dippers exhibited diastolic dysfunction. Women with severe preeclampsia were more frequently nondippers (35.5% vs 24.2%; P = .02) and experienced diastolic dysfunction (29% vs 15%; P = .01) than were those with mild preeclampsia. Severe preeclampsia (odds ratio [OR], 1.08; 95% CI, 1.05-10.56; P < .001) and history of recurrent preeclampsia (OR, 1.36; 95% CI, 1.3-4.26; P ≤ .001) were significant predictors for nondipping status and diastolic dysfunction (OR, 1.55; 95% CI, 1.1-2.2; and OR, 1.23; 95% CI, 1.2-2.2, respectively; P < .05). Women with a history of preeclampsia were at higher risk for developing late cardiovascular events. The severity and recurrence of preeclampsia were significant predictors of both nondipping profile and diastolic dysfunction.

Echocardiography E/A Abnormality is Associated with the Development of Primary Left Ventricle Remodeling in Middle-Aged and Elderly Women: A Longitudinal Study.

Impaired left ventricular (LV) relaxation is indicative of grade I diastolic dysfunction, which is mainly assessed by late diastolic transmitral flow velocity (E/A ratio). Although the E/A ratio has important diagnostic and prognostic implications with cardiac outcomes, the causal link between abnormal E/A ratio and left ventricle remodeling (LV remodeling) remains unclear. A longitudinal analysis of 869 eligible women aged ≥45 years, who had received echocardiography scans as well as 5-year follow-up assessments between 2015 and 2020. Women with pre-existing cardiac abnormalities including grade II/III diastolic dysfunction as diagnosed by echocardiography, or structural heart disease were excluded. E/A abnormality was defined as baseline E/A ratio <0.8. The classification of LV remodeling was based on the measurements of left ventricular mass index (LVMI) and relative wall thickness (RWT). Logistic and linear regression models were used. Among the 869 women (60.71±10.01 years), 164 (18.9%) had developed LV remodeling after the 5-year follow-up. The proportion of women with E/A abnormality versus non-abnormality was also significantly different (27.13% vs 16.59%, P=0.007). Multivariable-adjusted regression models showed that E/A abnormality (OR: 4.14, 95%Cl:1.80-9.20, P=0.009) was significantly associated with higher risk of concentric hypertrophy (CH) after follow-up. No such association was found in either concentric remodeling (CR) or eccentric hypertrophy (EH). Higher baseline E/A ratio was correlated with lower ΔRWT during the 5-year follow-up (β=-0.006 m/s, 95% CI: -0.012 to -0.002, P=0.025), which was independent of demographics and biological factors. E/A abnormality is associated with a higher risk of CH. Higher baseline E/A ratio may be associated with decreased relative changes in RWT.

Metabolic perturbations in hypertrophic cardiomyopathy – Insights from human induced pluripotent stem cell-derived cardiomyocytes

Hypertrophic cardiomyopathy (HCM) is one of the most commonly inherited cardiac disorders, and is defined as left ventricular hypertrophy without chamber dilation in the absence of an identifiable cause. It is characterised by cardiomyocyte hypertrophy and disarray, interstitial fibrosis, impaired left ventricular relaxation, and diastolic dysfunction, which can manifest in exercise intolerance, angina, dyspnoea, dizziness, syncope, or sudden cardiac death.

White Coat Hypertension: When Office Blood Pressure Impacts Cardiac Mechanics More Than Ambulatory. Is This Really So?

Hypertensive heart disease, characterized by left ventricular (LV) hypertrophy, left atrial enlargement, and LV dysfunction, represents a relatively advanced stage of hypertension-mediated organ damage (HMOD) typically associated with unrecognized or inadequately controlled systemic hypertension. However, a growing amount of evidence supports the view that subtle cardiac morphofunctional abnormalities such as LV concentric remodeling and mild impairment in LV relaxation can develop very early in the natural history of hypertension. Furthermore, an increased risk of initial cardiac HMOD has also been reported for long-held innocent conditions such as prehypertension and white coat hypertension (WCH). WCH is a common condition in which blood pressure (BP) measured in the medical environment is elevated while ­out-of-office BP (i.e., home and/or ambulatory BP [ABP]) is ­normal.1 The relationship between WCH and cardiac HMOD, an intermediate step linking hypertension with overt cardiovascular disease, has been investigated by numerous individual studies and their meta-analyses. Pooled data from 25 studies, including a total of 7.382 untreated individuals (2.493 true normotensives, 1.705 WCH, and 3.184 sustained hypertensives), showed that LV mass index (LVMI) gradually increased from normotensive, WCH, to sustained hypertensive patients. A meta-regression analysis restricted to WCH group documented a significant direct correlation between LVMI and office systolic BP (r = 0.42, P < 0.01); this was not the case for daytime systolic BP (r = 0.18, P = 0.17). Of note, the meta-analysis suggested that LV relaxation (in parallel with a greater left atrial size) but not LV ejection fraction (LVEF) was impaired in WCH.2

Annotation and quality assessment of left ventricular filling and relaxation pattern using one-dimensional convolutional neural network

Abstract Funding Acknowledgements Type of funding sources: Public grant(s) – National budget only. Main funding source(s): National Institute For Health Research (NIHR), UK Introduction Aberrations in left ventricular (LV) filling or relaxation – known as diastolic dysfunction – occur in heart failure with preserved ejection fraction. CMR is the reference modality for the assessment of ventricular systolic function, however, its role in evaluation of diastolic function is limited at present. One promising technique to assess diastolic function by CMR is the derivation of LV filling and emptying rates from the volume-time curves of cine images. Purpose To automatically assess the quality of LV filling-rate curves and annotate the peak emptying and filling rates. Methods A previously-described deep-learning network was used to automatically segment the entire cardiac cycle captured by short-axis SSFP cine images from the UK Biobank1. The LV filling-rate curves derived from the volume-time data were smoothed with Savitzky–Golay filter. The peak emptying rate (PER), early peak filling rate (PFR-E) and late peak filling rate (PFR-A) were first annotated by a simple peak finding algorithm from Python Scipy signal module. The preliminary annotated curves were reviewed by five human experts (i) to check for peak-annotation errors and (ii) to provide the curve quality score ranging from 1 to 3 for each peak (score 1 denotes good quality, score 2 represents moderate quality and score 3 indicates poor quality). Higher total score (minimum = 3, maximum = 9), therefore, represents poorer overall curve quality. This expert-annotated dataset was used to train two separate one-dimensional convolutional neural networks (1D-CNN) (Figure 1) for peak annotation and curve quality assessment (QA) using Tensorflow library in Python. Results The data from 6,328 LV filling-rate curves were split into the training and testing sets (80:20). The fine-tuned 1D-CNN comprising six hidden layers with two residual connections annotated the PER, PFR-E and PFR-A with the test-set accuracy of 95%, 95% and 98%, respectively. A second trained 1D-CNN for QA based on similar architecture predicted the overall curve quality score with a small error rate (mean absolute error: 0.46, mean squared error: 0.68). These two networks were used to quality check and label 19,409 UK Biobank CMR studies (See Figure 2 for exemplary results). After removing data from poor-quality curves (quality score ≥ 5), 18,735 studies remained. The mean±standard deviation of PER, PFR-E and PFR-A are 461±110 ml/s, 359±117 ml/s and 336±120 ml/s, respectively. Ageing is associated with lower PFR-E (−58.4 ml/s, 95% confidence interval [CI]: −56.1 to −60.7 ml/s per decade increment) and higher PFR-A (18.3 ml/s, 95% CI: 15.8 to 20.8 ml/s per decade increment). Conclusion The 1D-CNN models can be used to automatically grade the quality of LV filling rate curves and label important diastolic parameters with a high level of accuracy. The derived data recapitulate impaired LV relaxation pattern associated with ageing and can be used as surrogate indices of diastology by CMR. Figure 1Figure 2

FC026: Chronic High Phosphate Level Impairs Cardiac Health

Abstract BACKGROUND AND AIMS Patients with chronic kidney disease (CKD) suffer from disturbed mineral metabolism in which the chronic phosphate load leads to the elevation of the phosphaturic hormones parathyroid hormone (PTH) and fibroblast growth factor 23 (FGF23). Persistent hyperphosphatemia predisposes to cardiovascular events and increased morbidity and mortality rates. It is discussed that even in the general population, consumption of highly processed food increases phosphate level, which in turn may increase cardiovascular risk. Here, we aim to elucidate the pathological mechanisms of how chronic high phosphate intake mediates cardiac remodeling and dysfunction, respectively. METHOD Male C57BL/6 wild type mice received a high phosphate diet containing 2% inorganic phosphate (HPD) or a 0.8% normal phosphate diet (NPD) for 6 months. Echocardiographic analysis and ex-vivo measurements in cardiomyocytes using IonOptix system were assessed to evaluated cardiac function and contractility. Bulk RNA sequencing of whole heart tissue followed by pathway analysis was done to identify affected relevant signaling pathways, which were verified by in vitro studies using neonatal rat ventricular myocytes (NRVM). RESULTS Chronic phosphate overload resulted in increased level of serum and urinary phosphate and high plasma PTH and FGF23 concentrations. HPD caused impaired heart function as shown by reduced ejection fraction, increased end-systolic volumes and enlarged systolic left ventricular internal diameter accompanied by impaired left ventricular relaxation as seen in Doppler echocardiography. Histological analysis showed increased cardiomyocyte area and length in HPD-fed mice compared with NPD demonstrating cellular hypertrophy. RNA sequencing revealed differentially expressed genes of calcium signaling pathways in the HPD group. Besides, immunoblot analysis of whole heart tissue showed altered Phospholamban activity after 6 months of HPD compared with NPD, indicating altered calcium pump in cardiomyocytes. Preliminary analysis of sarcomere movements and changes of intracellular calcium levels in single cardiomyocytes isolated from NPD and HPD mice after 6 months suggested impaired contractility. Detailed results will be presented here. In vitro stimulation of isolated NRVM with high phosphate induced a hypertrophic growth response, verifying a direct effect of high phosphate on the heart. CONCLUSION HPD in mice causes a dilated cardiac phenotype including cellular hypertrophy, altered contractility and differentially expressed genes involved in calcium signaling pathways, indicating that a chronic high phosphate load is harmful for the heart also in the general population.

Restructuring the Heart From Failure to Success: Role of Structural Interventions in the Realm of Heart Failure.

Heart failure through the spectrum of reduced (HFrEF), mid-range (or mildly reduced or HFmEF), and preserved ejection fraction (HFpEF), continues to plague patients' quality of life through recurrent admissions and high mortality rates. Despite tremendous innovation in medical therapy, patients continue to experience refractory congestive symptoms due to adverse left ventricular remodeling, significant functional mitral regurgitation (FMR), and right-sided failure symptoms due to significant functional tricuspid regurgitation (FTR). As most of these patients are surgically challenging for open cardiac surgery, the past decade has seen the development and evolution of different percutaneous structural interventions targeted at improving FMR and FTR. There is renewed interest in the sphere of left ventricular restorative devices to effect reverse remodeling and thereby improve effective stroke volume and patient outcomes. For patients suffering from HFpEF, there is still a paucity of disease-modifying effective medical therapies, and these patients continue to have recurrent heart failure exacerbations due to impaired left ventricular relaxation and high filling pressures. Structural therapies involving the implantation of inter-atrial shunt devices to decrease left atrial pressure and the development of implantable devices in the pulmonary artery for real-time hemodynamic monitoring would help redefine treatment and outcomes for patients with HFpEF. Lastly, there is pre-clinical data supportive of soft robotic cardiac sleeves that serve to improve cardiac function, can assist contraction as well as relaxation of the heart, and have the potential to be customized for each patient. In this review, we focus on the role of structural interventions in heart failure as it stands in current clinical practice, evaluate the evidence amassed so far, and review promising structural therapies that may transform the future of heart failure management.

Comparative Assessment of Echocardiographic Patterns Among Chronic Myeloid Leukemia Patients on Tyrosine Kinase Inhibitor and Healthy Controls.

PurposeChronic myeloid leukemia (CML) is one of the common hematological malignancies in Nigeria. Cardiac abnormalities are associated with CML irrespective of treatment with tyrosine kinase inhibitors such as imatinib, which is available gratis in Nigeria.ObjectiveTo assess the prevalence and patterns of cardiac dysfunction among patients with CML irrespective of treatment with imatinib using transthoracic echocardiography, and 12-lead surface electrocardiography.Patients and MethodsCML patients without Imatinib, CML patients with imatinib, and apparently healthy (age- and sex-matched) controls were 70 each in the study. Various echocardiographic parameters were measured and data obtained were analyzed, and the level of significance was taken as p < 0.05.ResultsOf 70 CML patients with imatinib, 54.3% were men and 45.7% were women, while the CML group without imatinib had 62.9% men and 37.1% women, non-CML control had 54.3% men and 45.7% women. The average hematocrit was significantly lower in the CML group without Imatinib compared with the other groups (p<0.001). And, 12.9% and 17.1% of CML groups with and without imatinib had LVH, respectively, and none of the non-CML controls had LVH (P<0.041). Impaired left ventricular relaxation in 25.71% and 28.57% of CML patients with and without imatinib respectively but only 8.57% of the non-CML control had impaired left ventricular relaxation (p=0.236). Mitral valve regurgitation was the most frequent valvular abnormality across the groups. Pulmonary hypertension in 17.4% and 20% of CML patients with and without imatinib, respectively, but none of the non-CML controls had pulmonary hypertension (p<0.001). Pericardial effusion in 32.86% and 45.71% of CML patients with and without imatinib, respectively, but none of the non-CML controls had pericardial effusion (p<0.001). There was no significant difference in the QTC interval across the three groups.ConclusionCardiac abnormalities are present in CML patients with or without Imatinib treatment, with significant prevalence than what is seen in the non-CML control group.

Aortic Stiffness and Pulsatile Pressures as Potential Mediators of Chronic Kidney Disease Induced Impaired Diastolic Function.

PurposeWe assessed whether aortic stiffness and pulsatile pressures can mediate chronic kidney disease (CKD)-associated impaired diastolic function.Participants and MethodsIn 276 black Africans including 46 CKD (19 non-dialysis; 27 dialysis) and 230 control subjects, pulse wave velocity (PWV) estimated aortic stiffness and pulsatile pressures (forward and backward wave pressure, central systolic blood pressure (CSBP) and pulse pressure (CPP)) were determined by applanation tonometry; e’ as an index of left ventricular active relaxation and E/e’ as a measure of left ventricular filling pressure or passive relaxation were evaluated by echocardiography.ResultsIn age, sex, traditional cardiovascular risk factor and mean arterial pressure (MAP) adjusted regression models, CKD was inversely associated with e’ (p = 0.03) and directly with E/e’ (p < 0.01). The CKD-e’ relationship was attenuated and no longer significant (p = 0.31) upon additional adjustment for aortic PWV but not pulsatile pressures (p = 0.03–0.05). In product of coefficient mediation analysis, PWV accounted for 47.6% of the CKD-e’ association. CSBP (22.9%) and CPP (18.6%) but not PWV (11.3%) accounted for a significant and relevant proportion of the CKD-E/e’ relationship. However, CKD remained strongly associated with E/e’ independent of aortic function measures (p < 0.01). Treatable covariates that were or tended to be consistently associated with diastolic function included MAP (p < 0.01) and diabetes (p = 0.02–0.07) for the CKD-e’ and CKD-E/e’ relations, respectively.ConclusionAortic stiffness rather than pulsatile pressures mediates CKD-related impaired left ventricular active relaxation. By contrast, aortic pulsatile pressures (and not stiffness) contribute to CKD-related left ventricular filling pressures but do not fully account for the respective association.

Hypertension-mediated organ damage in masked hypertension.

Masked hypertension - a blood pressure (BP) phenotype characterized by a clinic BP in the normal range but elevated BP outside the office - is associated with early hypertension-mediated organ damage. This study examined early target organ manifestations of masked hypertension diagnosed by home (HBPM) and ambulatory (ABPM) BP monitoring. Left ventricular (LV) structure and diastolic function measured by echocardiography, microalbuminuria, and coronary artery calcification were evaluated in 420 patients with high clinic BP (SBP 120-150 mmHg or DBP 80-95 mmHg). Evidence of hypertension-mediated organ damage was compared in patients with sustained normotension, masked hypertension, and sustained hypertension based on measurements by HBPM, daytime ABPM, and 24-h ABPM. The 420 participants averaged 48 (12) [mean (SD)] years of age; the average clinic BP was 130 (13)/81 (8) mmHg. In individuals with masked hypertension diagnosed by HBPM, indexed LV mass, relative wall thickness, and e' and E/e' (indices of LV relaxation), were generally intermediate between values observed in normotensives and sustained hypertensive patients, and were significantly greater in masked hypertension than normotensives. Similar trends were observed when masked hypertension was diagnosed by ABPM but a diagnosis of masked hypertension was not as reliably associated with LV remodeling or impaired LV relaxation in comparison to normotensives. There were trends towards greater likelihoods of detectable urinary microalbumin and coronary calcification in masked hypertension than in normotensives. These results support previous studies demonstrating early hypertension-mediated organ damage in patients with masked hypertension, and suggest that HBPM may be superior to ABPM in identifying patients with masked hypertension who have early LV remodeling and diastolic LV dysfunction.

Серцева недостатність зі збереженою фракцією викиду лівого шлуночка

Серцева недостатність зі збереженою фракцією викиду лівого шлуночка є частим явищем, що спостерігається в осіб похилого віку. Вона супроводжується артеріальною гіпертензією та гіпертрофією лівого шлуночка. До симптомів відносять ригідність стінок лівого шлуночка з компенсаторним збільшенням тиску наповнення і знижену здатність збільшувати ударний об’єм за законом Франка Старлінга. Прогнози практично такі ж невтішні, як і при серцевій недостатності зі зниженою фракцією викиду, що певною мірою відображає наявність супутніх захворювань. До встановлення діагнозу серцевої недостатності зі збереженою фракцією викиду важливо виключити кардіологічну природу захворювання. Через неспецифічність симптомів серцевої недостатності необхідно знайти об’єктивне підтвердження діастолічної дисфункції, що за відсутності даних, отриманих інвазивно, має бути підтверджена з використанням ехокардіографії, при якій будуть виявлені ознаки підвищеного тиску наповнення лівого шлуночка, порушення його розслаблення чи збільшення його діастолічної ригідності. Лікування серцевої недостатності зі збереженою фракцією викиду симптоматичне, із застосуванням тих же препаратів, що і при серцевій недостатності зі зниженою фракцією викиду.

Cardiac phenotypes in the acute-phase of microscopic polyangiitis involves dilatation of the left atrium caused by LV diastolic dysfunction

Abstract Background Microscopic polyangiitis (MPA) is a type of primary systemic vasculitis that affects various organs, especially the lungs and kidneys. However, few reports regarding cardiac features of MPA patients were found. Purpose We aim to investigate the echocardiographic parameters of acute-phase MPA. Methods and results This single-center retrospective study included 15 patients with MPA (Mean age at 72.2±7.1 years, women 73.3%) who underwent echocardiography within two weeks of commencing steroid therapy for induction or reinduction. The echocardiography parameters of the patients were compared with those of 30 age and sex-matched controls. In the MPA group, the commonly affected organs were kidneys (93.3%) and lungs (46.7%); 5 patients (33.3%) had a history of hypertension, which had a similar frequency as the control group. No significant difference in left ventricular (LV) diameter, LV ejection fraction, e', or inferior vena cava diameter was observed between the two groups. However, the MPA group showed significantly higher left atrial (LA) diameter (p=0.033) and LA volume index (p=0.001), as well as higher early diastolic filling velocity (E-wave, p=0.015; E/A, p=0.043; E/e', p=0.041), diastolic pulmonary venous flow velocity (p=0.013), trans-tricuspid pressure gradient (p=0.019), and shorter deceleration time (p=0.038), associated with mildly thicker ventricular walls of left ventricle (LV) than the control group. Moreover, serum levels of C-reactive protein showed significant correlation between E wave (r=0.58, p=0.023), E/A (r=0.67, p=0.006), and deceleration time (r=−0.69, p=0.005) in the MPA group. These results may indicate that in MPA, increased LV stiffness, rather than impairment of LV relaxation was contributed to LV diastolic function, resulting in LA enlargement. Conclusion Patients with acute-phase MPA had LA dilatation associated with LV diastolic dysfunction. This finding indicates the importance of cardiac assessment in patients with MPA. Funding Acknowledgement Type of funding sources: None.

Weighted Gene Co-Expression Network Analysis Identifies ANGPTL4 as a Key Regulator in Diabetic Cardiomyopathy via FAK/SIRT3/ROS Pathway in Cardiomyocyte.

BackgroundDiabetic cardiomyopathy (DbCM) is characterized by initial impairment of left ventricular relaxation followed by contractile dysfunction. Despite intensive research, the exact mechanism remains so far unsolved.MethodsWe constructed weighted gene co-expression network analysis (WGCNA) to screen gene modules that were closely related with DbCM based on the GSE5606 dataset, which contained expression data of the cardiac left ventricle in a rodent model of streptozotocin (STZ)-induced DbCM. Then, the most related hub gene, angiopoietin-like 4 (ANGPTL4), was selected for functional ex vivo and in vitro assays. In our experiments, STZ-induced diabetic mice (C57BL/6J) and human cardiomyocytes (AC16) were used to study the functional roles and potential mechanisms of ANGPTL4 in DbCM.ResultsWGCNA analysis revealed the yellow and green modules were most correlated with DbCM, and identified ANGPTL4 as one of the most significantly upregulated hub genes (ANGPTL4, ACOT1, DECR1, HMGCS2, and PDK4). Consistent with the bioinformatic analysis, the amount of ANGPTL4 was significantly upregulated in diabetic mouse heart. DbCM group, compared with the control group, had increased phosphorylation of focal adhesion kinase (FAK), reduced SIRT3 expression, increased SOD2 acetylation, upregulated NADPH oxidase activation, elevated reactive oxygen species (ROS) produciton, and enhanced apoptosis in the diabetic mouse heart. Moreover, ANGPTL4 induced apoptosis via FAK/SIRT3/ROS pathway in human cardiomyocytes (AC16) under high glucose condition in vitro.These effects were abrogated by treatment of two independent siRNA for ANGPTL4, whereas exogenous recombinant ANGPLT4 protein treatment exacerbated those effects in AC16.ConclusionWe found ANGPTL4, ACOT1, DECR1, HMGCS2, and PDK4 were significantly increased in diabetic heart. ANGPTL4 could promote cardiac apoptosis via a FAK/SIRT3/ROS dependent signaling pathway in DbCM.