Cardiac Function Parameters Research Articles

Clinical, laboratory, electrocardiogaphic and multimodality imaging outcome predictors in cardiac amyloidosis

Abstract Background Cardiac affectation in amyloidosis is presented among 50% patients what implies worse prognostic. Early diagnosis and prognostic stratification is mandatory after the appearance of new therapies that could modify the course of the disease. Purpose The aim of the present study was to evaluate the main outcome predictors with multiparametric approach including clinical, laboratory, electrocardiographic and imaging parameters in patients with cardiac amyloidosis (CA). Methods We recruited patients (p) prospectively followed in our cardiomyopathy unit, for a mean period of 10 years (from 2010 to 2020) who were diagnosed with CA. Baseline clinical, laboratory and echocardiographic data were obtained. We collected cardiovascular risk factors and previous events. We performed a multimodality imaging study including echocardiogram (TTE) and cardiac magnetic resonance (CMR). TTE hallmarks of CA were recorded, as well as CMR parameters of cardiac function, myocardial mass and tissue characterization. Finally we evaluated the parameters related with mortality in the follow-up. Results A total of 98 p were included, with a mean age of 67.5±16.9 years old. Mean follow-up was 42,2±32 months. 22 p (24,4%) had light-chain amyloidosis (AL), 34 p (37,8%) wild type transthyretin amyloidosis (ATTRwt) and 34 p (37,8%) familiar transthyretin amyloidosis (ATTRm). 43p (47.78%) died in the follow-up. Factors related with mortality in the the follow-up where the age (HR 1.08, ppresence of hypertension (HR 2.81, p=0,002) diabetes (HR 3.12, p=0,001) and previous stroke (HR 2.69, p=0,01); NYHA class at diagnosis (HR 2.49, p<0.001), low voltage (HR 2.31, p=0,008) and pseudoinfarct pattern at ECG (HR 1.9, p=0,003); elevated BNP (HR 10.29, p<0.001) and creatinine (HR 1.42, p=0,02); septum (HR 1.09, p=0,001) and posterior wall (HR 1,14, p<0,001)thickness, left ventricular ejection fraction (HR 0.96, p=0,0031) global longitudinal strain (HR 1.18, p<0.001), ratio E/A (HR 2.29, p<0,001) and E/e' (HR 1.13, p=0,003) and left atrium size (HR 1,05, p=0,006) at echo; and the presence of left atrium fibrosis (HR 4.17, p>0,001) and extension of late gadolinium enhancement (HR 1,06, p=0,03) at CMR. When evaluated within a multivariate analysis in a Cox regression model, the independent variables associated with mortality were NYHA class at diagnosis (p=0.002) and amyloidosis type (p=0.002) ATTRm had a better prognosis than ATTRwt and AL (Log-rank p<0.001). Conclusion Mortality in cardiac amyloid patients is high. Clinical parameters like hypertension, diabetes, previous stroke and NYHA class at diagnosis; laboratory parameters like BNP and creatinine, main systolic and diastolic function at TTE, presence of auricular fibrosis and extension of late gadolinium enhancement at CRM are related with mortality in the follow-up. Among different types of CA, patients with ATTRm had a better prognosis, which may have therapeutic implications with the appearance of new therapies. Funding Acknowledgement Type of funding sources: None. Mortality

Left ventricular diastolic function during pregnancy: insights from conventional and speckle tracking echo parameters

Abstract Introduction Profound changes occur in the cardiovascular system during pregnancy, regarding to induce cardiac pumping function. Although LV systolic and diastolic function have been thoroughly studied using conventional indices, speckle tracking parameters of cardiac function are not well described. Purpose The aim of our study was to evaluate the LV diastolic function during an uncomplicated pregnancy using both traditional and newer speckle tracking parameters. Methods We prospectively enrolled 40 consecutive pregnant women in whom serial echocardiographic evaluation was performed in each pregnancy trimester (1st: 8th–12th week, 2nd: 22th–26th week, 3rd: 32–36th week) and 6 months after delivery. Mitral inflow velocities (E, A), mitral annulus TDI velocities (E', A'), ratio E/A and E/E' and untwisting velocity rate were measured after cautious selection of studies with legible images in. Results The peak E transmitral inflow velocity during early diastole decreased significantly during pregnancy especially between 2nd and 3rd trimester and increased again postpartum (p1-2=0.475, p2-3<0.05 p3-4<0.05). The peak A flow velocity during atrial contraction did not change significantly during pregnancy (p1-2=0.333, p2-3=0.952, p3-4=0.989). As a result, E/A ratio was decreasing as pregnancy was advancing (p1-2=0.964, p2-3<0.05, p3-4=0.240). TDI E' early diastolic velocity was decreased especially in the 3rd trimester and recovered postpartum (p1-2=0.138, p2-3<0.01, p3-4<0.01) while E/E' ratio was increased especially in the 2nd trimester (p1-2<0.05, p2-3=0.572, p3-4=0.021, p1-4=0.383) and also recovered postpartum. Peak untwisting velocity rate demontrated a progressive decrease during pregnancy, although not statistically significant. There was a trend towards recovery in the puerperium (p1-2=0.072, p2-3=0.679, p3-4=0.052, p1-4=0.929) (Table 1). Conclusion Our study demonstrated that diastolic function seems to be impaired during an uncomplicated pregnancy. However all the conventional and newer speckle tracking indices of diastolic function remain in normal range. Postpartum appears to be a recovery process in all parameters. Funding Acknowledgement Type of funding sources: None.

OC15.04: Fetal cardiac remodelling after maternal SARS‐CoV‐2 infection during pregnancy

To assess fetal cardiac structure and function in pregnancies with maternal COVID-19 infection, according to disease severity and gestational age at infection. Multicentric prospective cohort study including singleton pregnant women with confirmed SARS-CoV-2 infection (clinical, nasopharyngeal PCR or serologic test) at 5 hospitals in Spain, from April 2020 to April 2021. Pregnancies were subdivided according to the severity of maternal COVID-19 disease following NIH Classification. Fetal cardiac morphometry and function were evaluated in the third trimester, once COVID-19 symptoms ceased and at least 4 weeks after maternal infection. Echocardiography was performed in 269 fetuses including 70 asymptomatic patients (26.0%), 168 mild (62.5%) and 31 moderate/severe COVID-19 disease (one critical) (11.5%). Maternal infection occurred in the first trimester in 73 (27.1%) cases, in the second trimester in 158 (58.9%), and 38 (14.1%) cases during the third trimester. No significant differences were observed in fetal cardiac morphometric or functional parameters according to maternal severity of COVID-19 (table 1) or trimester of infection, except for increased septal thickness in fetuses of mothers with moderate/severe COVID-19. Fetal cardiac function was mostly preserved after severe maternal SARS-CoV-2 infection. Further studies are warranted to elucidate the implications of increased fetal septal thickness in cases of severe maternal COVID-19.

Necrostatin-1 reduces cardiac and mitochondrial dysfunction in prediabetic rats.

High-fat diet (HFD) consumption induces prediabetes and left ventricular dysfunction through many pathways including cell death pathway like necroptosis. Although the benefit of necroptosis inhibitor (necrostatin-1 or Nec-1) in the brain of prediabetic rats was shown, the effects of Nec-1 on cardiac autonomic function, blood pressure, cardiac function, along with its mechanistic insight have not been investigated. Male Wistar rats were fed with either a normal diet (n = 8) or HFD (n = 24) for 12 weeks to induce prediabetes. Prediabetic rats were randomly assigned into three interventional groups (n = 8/group): (1) vehicle, (2) Nec-1 (1.65 mg/kg, sc injection), and (3) metformin (300 mg/kg, oral gavage feeding). Treatments lasted for 8 weeks. Normal saline was given to normal diet-fed rats and vehicle group. Metabolic parameters, cardiac function and biochemical parameters were assessed. Prediabetic rats exhibited peripheral metabolic impairment as indicated by increased body weight, hyperinsulinemia with euglycemia, and dyslipidemia. Prediabetic rats also had cardiac autonomic imbalance, high blood pressure, and cardiac dysfunction, together with cardiac mitochondrial dysfunction, mitochondrial dynamic imbalance, and increased necroptosis and apoptosis. Treatment with Nec-1 did not affect peripheral metabolic parameters, however, it effectively reduced cardiac autonomic imbalance, blood pressure, and cardiac dysfunction via reducing cardiac inflammation, necroptosis, mitochondrial dysfunction, and increased mitochondrial fusion. Treatment with metformin reduced peripheral metabolic impairment and cardiac dysfunction via decreased cardiac mitochondrial dysfunction, mitochondrial dynamic imbalance, and apoptosis. In summary, Nec-1 directly suppressed necroptosis, cardiac mitochondrial dysfunction, and increased mitochondrial fusion independent of peripheral metabolic function, leading to an improved cardiac function in prediabetic rats.

Heart function assessment during aging in apolipoprotein E knock-out mice

BACKGROUND: Apolipoprotein (apo) E isoforms have strong correlations with metabolic and cardiovascular diseases. However, it is not clear if apoE has a role in development of non-ischemic cardiomyopathy. Our study aims to analyze the involvement of apoE in non-ischemic cardiomyopathy. METHODS AND RESULTS: Serial echo-cardiographic measurements were performed in old wildtype and apoE deficient (apoE-/-) mice. Morphological and functional cardiac parameters were in normal range in both groups at the age of 12 month. At the age of 18 months, both groups had shown ventricular dilation and increased heart rates. However, the apoE-/- mice presented signs of diastolic dysfunction by hypertrophic changes in left ventricle, due probably to arterial hypertension. The right ventricle was not affected by age or genotype. CONCLUSION: Even in the absence of high fat diet, apoE deficiency in mice induces mild changes in the cardiac function of the left ventricle during aging, by developing diastolic dysfunction, which leads to heart failure with preserved ejection fraction. However, further studies are necessary to conclude over the role of apoE in cardiac physiology and its involvement in development of heart failure.

Aortic Root Dilatation Is Attenuated with Diabetes but Is Not Associated with Renal Progression in Chronic Kidney Disease.

Patients with chronic kidney disease (CKD) often have cardiac functional and structural abnormalities which can lead to adverse cardiovascular outcomes. In this study, we investigated associations between diabetes mellitus (DM) and cardiac functional and structural parameters in patients with CKD focusing on aortic root diameter (ARD). We also investigated associations of renal outcomes with DM and cardiac functional and structural characteristics. We enrolled 419 patients with CKD stage 3–5 were enrolled. ARD was normalized to body surface area (BSA) (ARD/BSA), and the rate of decline in renal function was assessed by the estimated glomerular filtration rate (eGFR) slope (mL/min/1.73 m2/year). ARD/BSA ≥2.1 cm/m2 in men or ≥2.2 cm/m2 in women was defined as indicating aortic root dilatation. The patients with DM had lower ARD/BSA, higher left atrial dimension (LAD), lower left ventricular ejection fraction, lower ratio of peak early transmitral filling wave velocity to peak late transmitral filling wave velocity, and higher left ventricular relative wall thickness, than those without DM. After multivariable analysis, DM (vs. non-DM; coefficient β, −0.060; p = 0.018) was significantly associated with low ARD/BSA. Significantly fewer patients with DM had aortic root dilatation compared to those without DM (14.3% vs. 23.1%, p = 0.022). In the patients with DM, there were significant associations between a high left ventricular mass index (LVMI) (per 1 g/m2, β, −0.016; p = 0.040) and high LAD (per 1 cm; β, −1.965; p < 0.001) with a low eGFR slope. However, other parameters, including ARD/BSA, were not associated with eGFR slope. Furthermore, there were no associations between eGFR slope and any of the echocardiographic parameters in the patients without DM. Aortic root dilatation was attenuated in the patients with DM, but it was not associated with a decline in renal function. However, high LAD and LVMI were associated with rapid renal function decline in the CKD patients with DM.

Association of Adiponectin, Leptin and Resistin Plasma Concentrations with Echocardiographic Parameters in Patients with Coronary Artery Disease.

The imbalanced network of adipokines may contribute to the development of systemic low-grade inflammation, metabolic diseases and coronary artery disease (CAD). In the last decade, three classic adipokines—adiponectin, leptin and resistin—have been of particular interest in studies of patients with CAD due to their numerous properties in relation to the cardiovascular system. This has directed our attention to the association of adipokines with cardiac structure and function and the development of heart failure (HF), a common end effect of CAD. Thus, the purpose of this study was to analyse the associations of plasma concentrations of adiponectin, leptin and resistin with parameters assessed in the echocardiographic examinations of CAD patients. The presented study enrolled 167 Caucasian patients (133 male; 34 female) with CAD. Anthropometric, echocardiographic and basic biochemical measurements, together with plasma concentrations of adiponectin, leptin and resistin assays, were performed in each patient. Adiponectin concentrations were negatively associated with left ventricular ejection fraction (LVEF) and shortening fraction (LVSF), and positively associated with mitral valve E/A ratio (E/A), left ventricular end-diastolic volume (LVEDV), left ventricular end-diastolic diameter (LVEDD), left ventricular end-systolic diameter LVESD, and left atrium diameter (LAD). Resistin concentrations were negatively associated with E/A. Leptin concentrations, although correlated with HF severity assessed by the New York Heart Association (NYHA) Functional Classification, were not independently associated with the echocardiographic parameters of cardiac structure or function. In conclusion, adiponectin and resistin, but not leptin, are associated with the echocardiographic parameters of cardiac remodelling and dysfunction. These associations suggest that adiponectin and resistin might be involved in mechanisms of cardiac remodelling or compensative response. We also suggest the possible benefits of adiponectin and resistin level measurements in the monitoring of patients with CAD.

Study design for a randomized crossover study investigating myocardial strain analysis in patients with coronary artery disease at hyperoxia and normoxemia prior to coronary artery bypass graft surgery (StrECHO-O2)

BackgroundSupplemental oxygen (O2) is used routinely during anesthesia. In the treatment of acute myocardial infarction, it has been established that hyperoxia is to be avoided, whereas information on benefit and risk of hyperoxia in patients with stable coronary artery disease (CAD) remain scarce, especially in the setting of general anesthesia. This study will compare the immediate effects of normoxemia and hyperoxia on cardiac function, with a primary focus on changes in peak longitudinal left-ventricular strain, in anesthetized stable chronic CAD patients using peri-operative transesophageal echocardiography (TEE). MethodsA single-center randomized cross-over clinical trial will be conducted, enrolling 106 patients undergoing elective coronary artery bypass graft surgery. After the induction of anesthesia and prior to the start of surgery, cardiac function will be assessed by 2D and 3D TEE. Images will be acquired at two different oxygen states for each patient in randomized order. The fraction of inspired oxygen (FIO2) will be titrated to a normoxemic state (oxygen saturation of 95–98%) and adjusted to a hyperoxic state (FIO2 = 0.8). TEE images will be analyzed in a blinded manner for standard cardiac function and strain parameters. ConclusionBy using myocardial strain assessed by TEE, early and subtle signs of biventricular systolic and diastolic dysfunction can be promptly measured intraoperatively prior to the onset of severe signs of ischemia. The results may help anesthesiologists to better understand the effects of FIO2 on cardiac function and potentially tailor oxygen therapy to patients with CAD undergoing general anesthesia.

CHRONIC OBSTRUCTIVE PULMONARY DISEASE: GRADING OF SEVERITY AS REFLECTED BY SHORT TERM HEART RATE VARIABILITY.

Chronic obstructive pulmonary disease (COPD) is a broad spectrum respiratory illness where there are structural and functional changesin the lungs. According to WHO, COPD is a leading global burden and by 2030 it will be the third leading cause of death worldwide. The structural and functional changes in the lungs in COPD patients tend to inuence the cardiac autonomic functions and heart rate variability (HRV). Previousstudiesshow that there is decrease in heart rate variability in COPD patients. In many previousstudies, it isfound that results ofshort term HRV analysis of 5minutes is comparable to standard 24hours HRV analysis and is very patient friendly and reproducible procedure to analyse the cardiac autonomic functions. So determination of parameters of cardiac autonomic functions with the help of short term HRV analysis in COPD patients is helpful in determining the pathophysiology and subsequent management of such patients. A Descriptive and observational study was conducted upon 100 previously diagnosed COPD patients at the Autonomic function research Laboratory, Department of Physiology, R G Kar Medical College and Hospital, Kolkata, West Bengal. The study includes short term (5min) HRV analysis in COPD patients between the age group 18years and 60years after fullling appropriate inclusion and exclusion criteria and the results were analyzed using proper statistical software. After analysis of different data it was found that there is decrease in heart rate variability (in both Time domain and Frequency domain analysis) in case of COPD and also the decrease is more in case of increasing severity grading of COPD. Sympathetic activity increases and vagal or parasympathetic activity upon heart rate decreases with the increase in COPD grading. Further studies with more number of subjects will be helpful in assessing pathophysiology and management of COPD patients with the help of HRV analysis.

Impact of Different Approaches to Kidney Transplant with and without Chronic Hemodialysis on Cardiac Function and Morphology: A Case-Control Study.

Patients with end-stage renal disease have higher cardiovascular morbidity and mortality compared with the general population. Preemptive kidney transplant (KTx) has been shown to be associated with improved survival, better quality of life, lower healthcare burden, and reduced cardiovascular risk. In this case–control study, we investigated the cardiovascular benefits of two approaches to KTx: with and without previous chronic hemodialysis. We enrolled 21 patients who underwent preemptive KTx and 21 matched controls who received chronic hemodialysis before KTx. Cardiac morphological and functional parameters were assessed by echocardiography. Overall, patients undergoing preemptive KTx showed less extensive cardiac damage compared with controls, as evidenced by higher global longitudinal strain, peak atrial and contractile strain, and early diastolic mitral annular velocity as well as a lower left ventricular mass, left atrial volume index, and the ratio of mitral inflow early diastolic velocity to the mitral annular early diastolic velocity. In the multivariable analysis, the presence of chronic hemodialysis prior to KTx was an independent determinant of post-transplant cardiac functional and structural remodeling. These findings may have important clinical implications, supporting the use of preemptive KTx as a preferred treatment strategy in patients with end-stage renal disease.

Sex differences in cardiopulmonary effects of acute bromine exposure.

Accidental occupational bromine (Br>2>) exposures are common, leading to significant morbidity and mortality; however, the specific effects of Br>2> inhalation in female victims are unclear. Our studies demonstrated that acute high-concentration Br>2> inhalation is fatal, and cardiac injury and dysfunction play an important role in Br>2> toxicity in males. In this study, we exposed female Sprague Dawley rats, age-matched to those males from previously studied, to 600ppm Br>2> for 45min and assessed their survival, cardiopulmonary injury and cardiac function after exposure. Br>2> exposure caused serious mortality in female rats (59%) 48h after exposure. Rats had severe clinical distress, reduced heart rates and oxygen saturation after Br>2> inhalation as was previously reported with male animals. There was significant lung injury and edema when measured 24h after exposure. Cardiac injury biomarkers were also significantly elevated 24h after Br>2> inhalation. Echocardiography and hemodynamic studies were also performed and revealed that the mean arterial pressure was not significantly elevated in females. Other functional cardiac parameters were also altered. Aside from the lack of elevation of blood pressure, all other changes observed in female animals were also present in male animals as reported in our previous study. These studies are important to understand the toxicity mechanisms to generate therapies and better-equip first responders to deal with these specific scenarios after bromine spill disasters.>.

Differences in biomarkers of cardiac dysfunction in cord blood between normal pregnancies and pregnancies complicated by maternal diabetes

The aim of this study was to compare biomarkers of cardiac dysfunction in cord blood in women with uncomplicated pregnancies and pregnancies complicated by maternal pre-gestational and gestational diabetes and to correlate these findings with fetal echocardiography parameters of cardiac function. Fetal echocardiographic assessment was performed longitudinally on 78 fetuses in the normal cohort and 32 in the diabetic cohort by measuring tricuspid annular plane systolic excursion, mitral annular plane systolic excursion, myocardial performance index, interventricular septum (IVS) thickness and left fractional shortening between July 2015 and December 2017. Cord blood samples were obtained at birth and levels of troponin I (TnI), B-type natriuretic peptide (BNP) and the amnio terminal segment of its prohormone measured. Women with diabetes had significantly higher median body mass index and mean z-scores for BNP. Significant associations were observed between maternal diabetes and obesity and cord-blood BNP z-scores. The effect of diabetes on TnI levels were similar, with mean values higher in women with gestational diabetes compared to normal pregnancies; however, this difference did not reach statistical significance. These biomarker findings correlated with an increased IVS thickness in the diabetic group. No difference was demonstrated in the other cardiac function parameters measured. Biochemical markers of cardiac dysfunction are elevated in infants of diabetic and obese mothers and correlated with increased IVS thickness.

Mitigation of late cardiovascular effects of oxygen ion radiation by γ-tocotrienol in a mouse model

Purpose: While there is concern about degenerative tissue effects of exposure to space radiation during deep-space missions, there are no pharmacological countermeasures against these adverse effects. γ-Tocotrienol (GT3) is a natural form of vitamin E that has anti-oxidant properties, modifies cholesterol metabolism, and has anti-inflammatory and endothelial cell protective properties. The purpose of this study was to test whether GT3 could mitigate cardiovascular effects of oxygen ion (16O) irradiation in a mouse model. Materials and methods: Male C57BL/6 J mice were exposed to whole-body 16O (600 MeV/n) irradiation (0.26–0.33 Gy/min) at doses of 0 or 0.25 Gy at 6 months of age and were followed up to 9 months after irradiation. Animals were administered GT3 (50 mg/kg/day s.c.) or vehicle, on Monday – Friday starting on day 3 after irradiation for a total of 16 administrations. Ultrasonography was used to measure in vivo cardiac function and blood flow parameters. Cardiac tissue remodeling and inflammatory infiltration were assessed with histology and immunoblot analysis at 2 weeks, 3 and 9 months after radiation. Results: GT3 mitigated the effects of 16O radiation on cardiac function, the expression of a collagen type III peptide, and markers of mast cells, T-cells and monocytes/macrophages in the left ventricle. Conclusions: GT3 may be a potential countermeasure against late degenerative tissue effects of high-linear energy transfer radiation in the heart.

Effects of exercise training on heart rate variability in children and adolescents with pulmonary arterial hypertension: a pilot study.

Pulmonary arterial hypertension (PAH) is often associated with cardiac autonomic dysfunction, and heart rate variability (HRV) as marker of cardiac autonomic function is even related to disease severity. Knowledge about the effects of physical activity on HRV is limited in these patients. We aimed to assess whether HRV parameters can be influenced by a supervised exercise training program and whether respective changes are related to levels of activity. Six children and adolescents with moderate PAH (3 female, mean age 15.0±4.4 years; mean pulmonary to systemic arterial pressure ratio 0.5±0.2) performed supervised endurance and resistance training for 16 weeks. PAH-specific targeted medication remained unchanged during the study period. HRV was assessed before training and after 16 weeks of training by the use of ECG Move accelerometers. HRV indices included: standard deviation of normal-to-normal (NN) intervals (SDNN), square root of the mean of the sum of the squares of differences between successive NN-intervals (RMSSD), proportion of the number of pairs of successive normal-to-normal intervals that differ by more than 50 ms divided by total number of normal-to-normal interval (pNN50), and the Baevsky stress index (BSI) calculated by the histogram method. Before and after the training program, SDNN, RMSSD and pNN50 correlated with the level of physical activity. Mean values of SDNN, RMSSD and pNN50 did not change significantly due to the training program. Notably, activity level depending SDNN increased markedly after the exercise program (during activity +12.4%, at rest +6.6% and reclining +8.1%, Hedge's g of 0.28, 0.14 and 0.27, respectively). BSI decreased during activity due to the training program reflecting a reduction of stress level (Hedge's g -0.87 indicating an effect of clinical relevance). According to the experience of this pilot study a workout program of 16 weeks revealed an activity level dependent effect on parameters of autonomic cardiac function in children and adolescents with PAH. This mechanism might contribute to the positive effects of exercise training in patients with PAH.

A prognostic staging system for light-chain amyloidosis using hepatic and renal indicator data from 1,064 Chinese patients.

BackgroundLight-chain (AL) amyloidosis frequently involves severe multiple end-organ damage, thus affecting prognosis. As the current disease staging system is based only on cardiac indicators, we propose a new staging system based on multiple organ indicators to supplement the existing system.MethodsPatients with AL amyloidosis (n=1,064) from 18 Chinese hospitals were enrolled and divided into test and validation cohorts (4:1). Multivariate analyses were performed to identify the clinical and laboratory factors for inclusion in the new staging system.ResultsA score of 1 was assigned for each of the following—the difference between the involved and uninvolved free light chains ≥100 mg/L, estimated glomerular filtration rate (eGFR) <60 mL/min/1.73 m2, total bilirubin (Tbil) ≥18 µmol/L, cardiac troponin I ≥0.06 µg/L, and N-terminal pro-brain natriuretic peptide (NT-proBNP) ≥3,600 pg/mL—to divide the patients into five disease stages (0 to IV). There were 220 (20.7%), 291 (27.3%), 251 (23.6%), 178 (16.7%), and 124 (11.7%) patients with stage 0, I, II, III, and IV disease, respectively. Patients with stage II, III, and IV disease had a median overall survival (OS) of 56.9 months [95% confidence interval (CI), 33.9–not reached (NR)], 18.6 months (95% CI, 33.9–NR), and 6.5 months (95% CI, 8.0–24.6) (P<0.001), respectively. The 3-year survival estimates for patients with stages 0, I, II, III, and IV were 90.7%, 71.4%, 59.4%, 39.0%, and 22.1%, respectively.ConclusionsThe new staging system has been developed that incorporates plasma cell-related characteristics in addition to cardiac, renal, and hepatic function parameters. It enhances the risk stratification of patients with AL amyloidosis and is useful when multiple organs are involved.

Relationship of myocardial fibrosis markers with cardiac structural and functional parameters in patients with post-myocardial

Abstract Funding Acknowledgements Type of funding sources: None. Background. In recent years much attention has been paid to cardiac remodelling processes. Many studies provide convincing evidence for the role of aldosterone and tissue inhibitor of matrix metalloproteinase-1 (TIMP-1) in the processes of structural changes in the heart and vessels, which is of particular importance in cardiovascular remodeling in patients with hypertension, acute myocardial infarction, postinfarction cardiosclerosis and chronic heart failure. Aim of the study. To investigate the association of myocardial fibrosis markers (TIMP-1 and aldosterone) with cardiac structural and functional parameters. Methods and materials. We examined 40 patients with an average age of 56.4 ± 4.8 years who had had myocardial infarction more than 1 year before (mean 2.2 ± 0.8 years before). Plasma aldosterone concentration was determined using enzyme immunoassay using a DRG (Germany) EIA-4128 reagent kit. The reference values are 40-310 pg/ml. Tissue inhibitor of matrix metalloproteinase-1 concentrations were measured using DSL kits (USA). The reference values were 92-116 ng/ml. All patients underwent echocardiography to assess the structural and functional parameters of the heart. Correlation analysis with Pearson or Spearman correlation coefficient calculation was used to determine the relationships between quantitative parameters. Differences were considered statistically significant if the probability of their absolutely random nature did not exceed 5% (p &amp;lt; 0.05). Results. During the study, TIMP-1 concentration had a direct statistically significant medium correlation with LV end-diastolic size (r = 0.39, p = 0.012). The analysis also revealed significant correlations of TIMP-1 concentration with LV end-diastolic size (r = 0.33, p = 0.037), with LV end-systolic volume (r = 0.41, p = 0.009), with LV myocardial mass (r = 0.48, p = 0.008), with LV ejection fraction (r=-0.36, p = 0.024). No statistically significant correlations were found with other structural and functional left ventricular indices during the study. Statistical correlation analysis of the relationship between plasma concentration of aldosterone and structural-functional parameters of the left ventricle (according to the results of echocardiography), statistically significant correlations with ejection fraction (r = 0.39, p = 0.035), LV myocardial mass (r = 0.60, p = 0.001), LV myocardial mass index (r = 0.51, p = 0.004), LV interventricular septal thickness (r = 0.45, p = 0.007) were found. No statistically significant correlations with plasma aldosterone concentration were found with the other left ventricular structural and functional indices during the study. Conclusions. The concentrations of aldosterone and tissue inhibitor of matrix metalloproteinase-1 have links with many structural and functional parameters of the heart, which confirms their importance in the structural rearrangement (remodelling) of the cardiovascular system in patients after myocardial infarction.

Rabphilin silencing causes dilated cardiomyopathy in a Drosophila model of nephrocyte damage

Heart failure (HF) and the development of chronic kidney disease (CKD) have a direct association. Both can be cause and consequence of the other. Many factors are known, such as diabetes or hypertension, which can lead to the appearance and/or development of these two conditions. However, it is suspected that other factors, namely genetic ones, may explain the differences in the manifestation and progression of HF and CKD among patients. One candidate factor is Rph, a gene expressed in the nervous and excretory system in mammals and Drosophila, encoding a Rab small GTPase family effector protein implicated in vesicular trafficking. We found that Rph is expressed in the Drosophila heart, and the silencing of Rph gene expression in this organ had a strong impact in the organization of fibers and functional cardiac parameters. Specifically, we observed a significant increase in diastolic and systolic diameters of the heart tube, which is a phenotype that resembles dilated cardiomyopathy in humans. Importantly, we also show that silencing of Rabphilin (Rph) expression exclusively in the pericardial nephrocytes, which are part of the flies' excretory system, brings about a non-cell-autonomous effect on the Drosophila cardiac system. In summary, in this work, we demonstrate the importance of Rph in the fly cardiac system and how silencing Rph expression in nephrocytes affects the Drosophila cardiac system.

Unilateral Ureteral Obstruction for 28 Days in Rats Is Not Associated with Changes in Cardiac Function or Alterations in Mitochondrial Function.

Simple SummaryThis work shows that renal damage produced by the demonstration of unilateral ureteral obstruction (UUO) is not related to cardiac dysfunction or the change in mitochondrial bioenergetics parameters, despite the inflammatory state.Our work evaluated cardiac function and mitochondrial bioenergetics parameters in hearts from male Wistar rats subjected to the UUO model during 28 days of progression. We measured markers of kidney damage and inflammation in plasma and renal fibrosis by histological analysis and Western blot. Cardiac function was evaluated by echocardiography and proteins involved in cardiac damage by Western blot. Oxygen consumption and transmembrane potential were monitored in cardiac mitochondria using high-resolution respirometry. We also determined the activity of ATP synthase and antioxidant enzymes such as glutathione peroxidase, glutathione reductase, and catalase. Our results show that, although renal dysfunction is established in animals subjected to ureteral obstruction, cardiac function is maintained along with mitochondrial function and antioxidant enzymes activity after 28 days of injury evolution. Our results suggest that renocardiac syndrome might develop but belatedly in obstruction-induced renal damage, opening the opportunity for treatment to prevent this condition.

Mitochondria damage in ambient particulate matter induced cardiotoxicity: Roles of PPAR alpha/PGC-1 alpha signaling

Particulate matter (PM) had been associated with cardiotoxicity, while the mechanism of toxicity has yet to be elucidated, with mitochondria dysfunction as a potential candidate. To investigate the potential cardiotoxic effects of ambient PM exposure and assess the damage to cardiac mitochondria, C57/B6 mice were exposed to filtered air or real ambient PM for three or six weeks. Furthermore, to reveal the role of peroxisome proliferators-activated receptor alpha (PPAR alpha) in PM exposure induced cardiotoxicity/mitochondria damage, animals were also co-treated with PPAR alpha agonist WY 14,643 or PPAR alpha antagonist GW 6471. Cardiotoxicity was assessed with echocardiography and histopathology, while mitochondria damage was evaluated with mitochondria membrane potential measurement and transmission electron microscopy. Potential impacts of PM exposure to PPAR alpha signaling were detected with co-immunoprecipitation and western blotting. The results indicated that exposure to ambient PM exposure induced cardiotoxicity in C57/B6 mice, including altered cardiac functional parameters and morphology. Cardiac mitochondria damage is detected, in the form of compromised mitochondria membrane potential and morphology. Molecular investigations revealed disruption of PPAR alpha interaction with peroxisome proliferator-activated receptor gamma coactivator-1A (PGC-1a) as well as altered expression levels of PPAR alpha downstream genes. Co-treatment with WY 14,643 alleviated the observed toxicities, while co-treatment with GW 6471 had mixed results, exaggerating most cardiotoxicity and mitochondrial damage endpoints but alleviating some cardiac functional parameters. Interestingly, WY 14,643 and GW 6471 co-treatment seemed to exhibit similar regulative effects towards PPAR alpha signaling in animals exposed to PM. In conclusion, ambient PM exposure indeed induced cardiotoxicity in C57/B6 mice, in which cardiac mitochondria damage and disrupted PPAR alpha signaling are contributors.

Fetal cardiac Doppler changes in gestational diabetic pregnancies and its relationship with perinatal outcomes.

To examine the structural and functional changes of the fetal heart in gestational diabetes mellitus (GDM) and to evaluate the power of fetal cardiac Doppler parameters in predicting adverse perinatal outcomes in this group of pregnancy. Within the study's scope, 36 cases in the A1 GDM group, 33 cases in the A2 GDM group, and 124 cases in the control group were evaluated. The relationship between structural and functional fetal cardiac parameters and perinatal outcomes was evaluated via fetal echocardiography. Fetal left ventricular myocardial performance index (MPI) values were found to be statistically significantly higher when compared between the A1 GDM and A2 GDM groups and the control group (p = 0.000 and p = 0.000, respectively), while the E/A ratio was found to be significantly lower (p = 0.000 and p = 0.000, respectively). It was determined that the maternal blood HbA1c level showed a significant negative correlation with the fetal cardiac E/A ratio and a significant positive correlation with isovolumetric relaxation time and MPI (p = 0.000, p = 0.000, and p = 0.000, respectively). Adverse perinatal outcome rate was higher in the diabetic group (46.4%-22.6%). When the cases with GDM were examined in terms of perinatal outcomes, it was observed that there was a significant difference in HbA1c levels, E/A ratio, and MPI values between the cases in the group with adverse perinatal outcomes and the group with normal results (p = 0.001, p = 0.000, and p = 0.000, respectively). The strong relationship between abnormal cardiac function and adverse perinatal outcomes suggest that cardiac Doppler may be a valuable tool for fetal monitoring and management for the GDM patient group.