Association between Cardiac Outcomes and Indoxyl Sulfate Levels in Hemodialysis Patients: A Cross-sectional Study

Objective Indoxyl sulfate (IS) is a protein-bound uremic toxin that is associated with cardiovascular events and mortality in hemodialysis (HD) patients. However, the factors affecting the levels of IS are currently unclear. This study aimed to investigate the factors influencing serum IS concentrations in HD patients. Methods We included 100 HD patients from Guangdong Provincial People’s Hospital. Baseline characteristics, including sex, age, clinical features, duration of HD, echocardiography findings, electrocardiogram results, and biochemical indicators, were collected and analyzed in relation to serum total-form IS levels. Results Among all 100 patients, serum IS levels were significantly higher in patients aged ≥ 60 years, males, and patients with mitral regurgitation and inadequate dialysis. Among patients aged < 60 years, IS levels were significantly higher among patients with mitral regurgitation compared with those without. Furthermore, multiple linear regression analysis identified sex, age, ventricular septal thickness, and mitral regurgitation as factors independently associated with serum IS (STDβ = −0.475, 0.162, −0.153, 0.142, and 0.136, respectively; all P < 0.05) adjusted for body mass index, smoking, and fasting plasma glucose. Conclusions Male sex, age ≥ 60 years, ventricular septal thickness, and mitral regurgitation are factors associated with high total serum IS concentrations in Chinese HD patients. Elevated IS levels may play a role in the process of mitral regurgitation in HD patients < 60 years old.

The value of the spatial QRS–T angle for assessing the severity of heart damage in patients with arterial hypertension

Aim To study the relationship between clinical, echocardiographic, and laboratory indexes with increased QRS–T spatial angle (sQRS–T) in patients with arterial hypertension (AH).Material and methods The study included 160 patients with AH, 61 (38 %) men and 99 (62 %) women aged 58 [49; 67] years. Patients with ischemic heart disease or His bundle blocks were not included. Echocardiography was used to determine the left ventricular end-diastolic dimension (LV EDD), left ventricular posterior wall thickness (LVPWT), interventricular septal thickness (IVST), relative wall thickness (RWT), left ventricular myocardial mass (LVMM), and LVMM index (LVMMI). Also, the following indexes were analyzed: office systolic and diastolic blood pressure (SBP, DBP), disease duration, body mass index, plasma levels of glucose, cholesterol, and creatinine, and glomerular filtration rate. The QRS-T spatial angle was calculated as an angle between the integral vectors QRS and T using a vectorcardiogram derived from a 12-lead digital electrocardiogram. Data are presented as median (25th percentile; 75th percentile].Results The QRS-T spatial angle for the group was 65 [43; 90]°. The QRS–T spatial angle increased with increases in the AH grade (grade 1 AH, 55 [37; 74]°; grade 2 AH, 60 [41; 82]°; grade 3 AH, 88 [62; 107]°; р<0.0001); the AH stage (stage 1, 50 [41; 77]°; stage 2, 68 [44; 93]°; stage 3, 78 [59; 110]°; р=0.0002), and the cardiovascular risk degree (low and moderate risk, 49 [37; 70]°, high risk, 62 [43; 88]° (р=0.005); very high risk, 88 [61; 117]° vs. high risk, 62 [43; 88]° (р=0.0002). The QRS–T spatial angle was greater with diabetes mellitus (78 [60; 117]°) than without it (63 [43; 89]°) (р=0.03). Weak but significant correlations were found between sQRS–T and body mass index (r=0.2; p<0.01), SBP (r=0.4; p<0.0001), DBP (r=0.2; p<0.01), LV EDD (r=0.2; p<0.01), LV PWT (r=0.3; p<0.001), IVST (r=0.3; p<0.001), LVMM (r=0.3; p<0.001), LVMMI (r=0.3; p<0.001), and blood glucose (r=0.2; p<0.01).Conclusion In patients with AH, a large QRS-T spatial angle is related with significantly higher values of SBP and DBP, LV dimension, blood glucose, and body mass index.

Idiopathic pericardial effusion in patients with hypertrophic cardiomyopathy

The aims of this study were to examine the prevalence of moderate to large (moderate–large) idiopathic pericardial effusion (i-PEF) in patients with hypertrophic cardiomyopathy (HCM) and to identify clinical and echocardiographic hemodynamic profiles associated with pericardial effusion. A total of 292 adult patients with HCM were studied. Fifteen patients with a history of factors associated with pericardial effusion including myocardial infarction, heart surgery or cardiac procedure within the last 12 months, autoimmune disease, hydralazine use, chronic kidney disease stage 3–4, tuberculosis, and malignancy were excluded. Of 277 eligible patients with HCM, 11 patients (4%) with moderate-large i-PEF were identified. Clinical tamponade was present in 1 patient. Compared to patients with HCM who had no or small pericardial effusion, patients with moderate-large i-PEF were younger and more likely to have right ventricular (RV) hypertrophy and reverse septal curvature. These patients also exhibited a greater maximal septal thickness, mean and systolic pulmonary pressure, and right atrial pressure (p < 0.05 for all). Pericardial fluid analysis and histopathological exams were performed in 7 and 3 patients, respectively. All examinations revealed transudative and nonspecific etiology of pericardial effusion. Idiopathic pericardial effusion and cardiac tamponade in patients with HCM was uncommon. The pathophysiology involved in pericardial effusion remains undetermined. Patients with moderate-large i-PEF frequently exhibited a phenotype of pulmonary hypertension and RV pressure overload.

Surgical Septal Myectomy for Hypertrophic cardiomyopathy. The Iranian Experience

Introduction Hypertrophic obstructive cardiomyopathy (HOCM) is a hereditary heart muscle disorder characterized by significant myocardial hypertrophy. we assessed perioperative and long-term follow-up data of Iranian HOCM patients who underwent SM in 2 pioneering centers. Methods Clinical data of patients with HOCM septal myectomy are collected. Thirty-day outcome and long-term follow-up data for recurrence of gradient and mortality are reported. Results Ninety-six patients in two different centers enrolled in the study. Most patients of 52 patients in center 1 were male (34/52 [65.3%]).and the mean age was of 36.7 ± 19 years. Syncope before admission was reported in 5.7%, the mean left ventricular ejection fraction on admission was 53 ± 8%, the mean left ventricular outflow tract gradient was 66.3 ± 20.4 mm Hg, and the mean preoperativeseptal thickness was 25.4 ± 6.7 mm. A redo SM was performed in 3 patients (5.8%), mitral valve repair in 5 patients (9.6%), and atrioventricular repair in 5 patients (9.6%). A residual systolic anterior motion was detected in 4 patients (7.7%), the mean postoperative septal thickness was 19 ± 6 mm (25.1% septal thickness reduction), and in-hospital mortality was 5.8% (n = 3). A longer-term follow-up showed death in 3 patients (5.8%) and late recurrent left ventricular outflow tract obstruction in 1 patient. Conclusions Transaortic myectomy is an effective surgery with acceptable early and late mortality rates. Improvements in functional status are seen in almost all patients. Appropriate SM is crucial to a good clinical outcome. Long-term survival is excellent and cardiac sudden death is extremely rare after a good surgical treatment.

Myocardial Work Does Not Have Additional Diagnostic Value in the Assessment of ATTR Cardiac Amyloidosis

Background: Reduced LV longitudinal strain (GLS) and increased relative apical sparing (RELAPS) and increased wall thickness have been proposed as features for transthyretin cardiac amyloidosis (ATTR-CA). Myocardial work (MW) has recently been shown as useful afterload independent disease marker, hence we aimed to investigate its use in differentiating ATTR-CA from heart failure with increased septal thickness but no cardiac amyloidosis (CA) (HFnCA). Methods: This study included patients with HF and increased septal thickness ≥ 14 mm. We included 59 patients with hereditary (ATTRv) and 27 wild type transthyretin amyloidosis (ATTRwt) described as ATTR-CA based on DPD scintigraphy. We also enrolled 30 non-amyloidosis heart failure patients with negative DPD scintigraphy, as a control group. Myocardial work (MW) was used to assess the index (GWI), constructive (GCW) and wasted (GWW) work. Relative wall thickness (RWT) and relative apical sparing (RELAPS) were tested as conventional measures. Results: The RWT and RELAPS were higher in ATTR-CA (p < 0.001) and predicted ATTR-CA (RWT; AUC = 0.84, p < 0.001) and RELAPS (AUC = 0.81, p < 0.001). MW; GWI (p = 0.04), GCW (p = 0.03), GWW (p = 0.001) were all lower in ATTR-CA compared with HFnCA but only GWW predicted ATTR-CA, (AUC = 0.75, p < 0.001). Binary logistic univariate regression analysis showed RWT (p = 0.003, β = 16.2) and RELAPS (p = 0.003, β = 2.3) to be associated with ATTR-CA but not MW. GWI and GCW correlated with NT-proBNP (p < 0.05) and Troponin (p < 0.01), but not RWT or RELAPS. Conclusion: Myocardial work had lower accuracy, compared to RWT or RELAPS, in identifying ATTR-CA but was better related to biomarkers. Thus, MW assessment is unlikely to have additional value in improving the diagnosis of heart failure due to ATTR-CA.

Massive Myocardial Calcification—A Heart Of Stone!

A 71-year-old female was admitted in the emergency room after effort-related syncope. She had past medical history of obesity and hypertension treated with lercanidipine. No relevant family history. Physical examination revealed systolic murmur (grade 2/6). ECG showed sinus rhythm and left bundle brunch block (Supplementary figure). Lab results were unremarkable including troponin I. Transthoracic echocardiography (TTE) revealed moderate left ventricular (LV) hypertrophy [septal thickness 14 mm (normal: 6–9mm)], extensive mitral annulus calcification (MAC) with exuberant myocardial calcification at the level of posterior leaflet that invaded adjacent LV walls, systolic anterior motion of the anterior mitral leaflet causing LV outflow tract (LVOT) obstruction (maximum gradient 34 mmHg) and moderate mitral regurgitation (MR) (Panel A). Exercise echocardiogram provoked LVOT gradient &gt;100mmHg and severe MR. Continuous ECG monitoring during 13 days demonstrated no arrhythmic events. Cardiac CT showed multiple calcifications extending from mitral annulus to LV anterior and lateral walls and cardiac MRI was compatible with caseous MAC (Panels B-F). Coronary angiography showed 50% stenosis of mid left anterior descending artery. Normal thoracic CT and ACE, and negative IGRA excluded sarcoidosis and tuberculosis. Comprehensive study, including calcium metabolism and autoantibodies, excluded metabolic and inflammatory aetiologies of myocardial calcification, which was assumed as dystrophic in the context of MAC. No syncope occurred after bisoprolol 2.5 mg, oral rehydration and discontinuation of lercanidipine. However, rest and exercise TTE failed to show improvement of LVOT gradient or MR and patient remained on NYHA class II-III, despite maximal tolerated dose of bisoprolol (5 mg), being therefore referred to cardiac surgery.

Association of Maternal Gestational Weight Gain With Left Ventricle Geometry and Function in Offspring at 4 Years of Age: A Prospective Birth Cohort Study

Background: Maternal gestational weight gain (GWG) may be associated with cardiovascular diseases in the offspring from childhood to adulthood. We aimed to investigate the association between maternal GWG and the left ventricle (LV) geometry and function in the offspring, and explore the influence of the intrauterine environment on early childhood cardiac change.Methods: Data of 981 mother-offspring pairs from the Shanghai Birth Cohort was used. Maternal pre-pregnancy weight and height, weight in the first trimester (≤ 12 weeks), and before delivery were measured. The echocardiography, blood pressure, and anthropometry assessment were evaluated in the offspring at 4 years of age.Results: Interventricular septal thickness during diastole had a significantly positive correlation with total GWG [β = 0.009, (0.001, 0.017)]. In the second and third trimesters, LV mass index [β = 0.149, (0.015,0.282)], interventricular septal thickness in systole [β = 0.027, (0.011,0.043)], and in diastole [β = 0.014, (0.005,0.023)] were positively associated with GWG. The risks of eccentric [OR = 1.115, (1.232, 1.010)] and concentric hypertrophy [OR = 1.133, (1.259,1.018)] increased with the elevation of maternal GWG.Conclusions: This study suggested that the excessive maternal GWG was associated with the thickening of the interventricular septum in the offspring, especially during the second and third trimesters. Excessive GWG in the second and third trimesters was a risk factor for LV eccentric and concentric hypertrophy in the offspring.

Sirolimus Suppresses Phosphorylation of Cofilin and Reduces Interstitial Septal Thickness in Sporadic Lymphangioleiomyomatosis

Sporadic lymphangioleiomyomatosis (S-LAM) is a rare lung disease characterized by the proliferation of smooth muscle-like LAM cells and progressive cystic destruction. Sirolimus, a mammalian target of rapamycin (mTOR) inhibitor, has a proven efficacy in patients with LAM. However, the therapeutic mechanisms of sirolimus in LAM remain unclear. We aimed to evaluate sirolimus-related lung parenchymal changes and the potential effect in LAM cells and modulating pathological cystic destruction. Lung specimens were examined for histopathological changes by HMB45 staining and compared the LAM patients treated with and without sirolimus. We detected the overexpression of mTOR, HMB45, and phosphorylation of cofilin (p-cofilin) in LAM patients. Sirolimus showed efficacy in patients with LAM, who exhibited a reduced expression of mTOR and p-cofilin as well as reduced interstitial septal thickness. In addition, sirolimus suppresses mTOR and p-cofilin, thus suppressing the migration and proliferation of LAM cells isolated from the patient’s lung tissue. This study demonstrates that interstitial septal thickness, as determined by histological structural analysis. Sirolimus effectively reduced the expression of p-cofilin and interstitial septal thickness, which may be a novel mechanism by sirolimus. Moreover, we develop a new method to isolate and culture the LAM cell, which can test the possibility of medication in vitro and impact this current study has on the LAM field. The development of approaches to interfere with mTOR-cofilin1-actin signaling may result in an option for S-LAM therapy.

Chitin-Derived AVR-48 Prevents Experimental Bronchopulmonary Dysplasia (BPD) and BPD-Associated Pulmonary Hypertension in Newborn Mice

Bronchopulmonary dysplasia (BPD) is the most common complication of prematurity and a key contributor to the large health care burden associated with prematurity, longer hospital stays, higher hospital costs, and frequent re-hospitalizations of affected patients through the first year of life and increased resource utilization throughout childhood. This disease is associated with abnormal pulmonary function that may lead to BPD-associated pulmonary hypertension (PH), a major contributor to neonatal mortality and morbidity. In the absence of any definitive treatment options, this life-threatening disease is associated with high resource utilization during and after neonatal intensive care unit (NICU) stay. The goal of this study was to test the safety and efficacy of a small molecule derivative of chitin, AVR-48, as prophylactic therapy for preventing experimental BPD in a mouse model. Two doses of AVR-48 were delivered either intranasally (0.11 mg/kg), intraperitoneally (10 mg/kg), or intravenously (IV) (10 mg/kg) to newborn mouse pups on postnatal day (P)2 and P4. The outcomes were assessed by measuring total inflammatory cells in the broncho-alveolar lavage fluid (BALF), chord length, septal thickness, and radial alveolar counts of the alveoli, Fulton’s Index (for PH), cell proliferation and cell death by immunostaining, and markers of inflammation by Western blotting and ELISA. The bioavailability and safety of the drug were assessed by pharmacokinetic and toxicity studies in both neonatal mice and rat pups (P3-P5). Following AVR-48 treatment, alveolar simplification was improved, as evident from chord length, septal thickness, and radial alveolar counts; total inflammatory cells were decreased in the BALF; Fulton’s Index was decreased and lung inflammation and cell death were decreased, while angiogenesis and cell proliferation were increased. AVR-48 was found to be safe and the no-observed-adverse-effect level (NOAEL) in rat pups was determined to be 100 mg/kg when delivered via IV dosing with a 20-fold safety margin. With no reported toxicity and with a shorter half-life, AVR-48 is able to reverse the worsening cardiopulmonary phenotype of experimental BPD and BPD-PH, compared to controls, thus positioning it as a future drug candidate.

A Study of Echocardiographic Changes in Patients with Newly Diagnosed Primary Hypothyroidism: A Cross-sectional Study

Background: Hypothyroidism is known to cause reversible cardiac dysfunction in humans. Thyroid hormone alters the cardiovascular hemodynamics. This study was performed to assess echocardiographic changes in untreated newly diagnosed primary hypothyroid states as such studies are scarce in our setting.Methods: This hospital based cross-sectional study was conducted among 71 patients with newly diagnosed primary hypothyroidism who presented to the medicine outpatient department, at Universal College of Medical Sciences and Teaching Hospital (UCMS-TH), Bhairahawa, Nepal from December 2018 to June 2020 after taking ethical clearance from institutional review committee (UCMS/IRC/212/18). Thyroid function test and echocardiography were carried out in patients under study. The data was analyzed with SPSS Version 16.Results: A total of 71 patients (52 females and 19 males) with primary hypothyroidism were enrolled for the study. Among these 58 cases were overt/clinical hypothyroidism, and 13 cases were subclinical hypothyroidism. Echocardiography was abnormal in 63.4% of cases with 43.7% showing diastolic dysfunction, 18.3% diastolic interventricular septal thickness abnormality, 8.5% diastolic left ventricular posterior wall thickness abnormality, and 8.4% pericardial effusion. Conclusion: Our study found diastolic dysfunction, diastolic interventricular septal thickness abnormality, diastolic left ventricular posterior wall thickness abnormality, and pericardial effusion as the common echocardiographic change in patients with newly diagnosed primary hypothyroidism. Therefore, our study highlights the need for cardiac evaluation of patients with primary hypothyroidism so that early intervention can be performed to improve the clinical outcome.