Systolic Dysfunction Research Articles

Dapagliflozin alleviates high-fat-induced obesity cardiomyopathy by inhibiting ferroptosis.

Dapagliflozin (Dapa) is a novel hypoglycaemic agent with multiple cardiovascular protective effects, and it is widely used in treatment of heart failure patients, but whether it can improve obese phenotype of heart failure and its mechanism is still unclear. Ferroptosis is an iron dependent form of cell death and has been proved to be an important role in heart failure. The aim of this study is to determine whether Dapa improves obesity-related heart failure by regulating ferroptosis in high-fat diet rats. Male SD rats were fed a high-fat diet for 12 weeks and confirmed of obese heart failure by metabolic parameters and cardiac ultrasound. Being overweight by 20% compared with the normal group, with elevated systolic blood pressure and abnormal levels of insulin and blood lipid (TG and LDL-c), is recognized as obesity. The obese rats with reduced EF, FS, and E/A shown on ultrasound are defined as the obese heart failure (OHF) group. Histological tests confirmed the more pronounced cardiac fibrosis, mitochondrial volume and collagen deposition in OHF group. Dapa treatment effectively reduced body weight, INS, ISI/IRI index, TG and HDL-C levels (P < 0.05). Also, Dapa administration can slightly decrease the SBP and DBP levels; however, there was no statistical difference among those four groups. Furthermore, Dapa treatment can significantly improve high-fat induced systolic and diastolic dysfunction via regulating cardiac histological abnormalities, including less obvious mitochondrial swelling, muscle fibre dissolution and collagen deposition. Additionally, genes from the OHF group were used by GO enrichment analysis, and it shows that ferroptosis metabolic pathway participated in the development of obese phenotype of heart failure. More importantly, Dapa significantly inhibited Fe2+ and MDA levels (P < 0.05), but augmented GSH content (P < 0.05). In addition, the mRNAs and protein expression of some important regulators of ferroptosis, like GPX4, SLC7A11, FTH1 and FPN1, were all decreased after Dapa intervention. Dapa improved high-fat induced obese cardiac dysfunction via regulating ferroptosis pathway.

Effects of sex and obesity on immune checkpoint inhibition-related cardiac systolic dysfunction in aged mice.

Despite accumulating data on underlying mechanisms, the influence of sex and prevalent cardio-metabolic co-morbidities on the manifestation and severity of immune checkpoint inhibitor (ICI)-induced cardiotoxicity has not been well defined. To elucidate whether sex and prevalent cardio-metabolic co-morbidities affect ICI-induced cardiotoxicity, we randomized 17-month-old male and female mice to receive control diet (CON) or high-fat diet (HFD) + L-NAME-a well-established mouse model of cardio-metabolic co-morbidities-for 17weeks (n = 5-7), and evaluated markers of T-cell function in the spleen. As expected, HFD + L-NAME significantly increased body- and heart weight, and serum cholesterol levels, and caused no systolic dysfunction, however, led to diastolic dysfunction, cardiomyocyte hypertrophy, and increased fibrosis only in males compared to corresponding CON. Western blot analyses of splenic immune checkpoint protein levels showed differential expression depending on sex and prevalent cardio-metabolic co-morbidities, suggesting T-cell exhaustion in both sexes on HFD + L-NAME, but more pronounced in males. In a sub-study with a similar setup, we tested cardiotoxic manifestations of ICI by treating mice with anti-PD-1 monoclonal antibody (ICI) for the last 2weeks of diet administration (n = 5-7). After 2weeks of ICI treatment, cardiac systolic functions significantly decreased in CON, but not in HFD + L-NAME groups of both sexes compared to baseline (before ICI administration). In conclusion, in this exploratory study using aged mice, we describe for the first time that ICI-related systolic dysfunction is diminished in both sexes when obesity and hypercholesterolemia are present, possibly due to obesity-related T-cell exhaustion.

The accuracy of respiratory muscle strength in identifying systolic dysfunction in patients with Chagas cardiomyopathy

Purpose To verify the accuracy of respiratory muscle strength in identifying systolic dysfunction in patients with Chagas cardiomyopathy (ChC), and to validate optimal cutoff points based on respiratory muscle strength. Methods First, 72 patients with ChC were enrolled and underwent echocardiography and assessment of respiratory muscle strength by manovacuometry. Inspiratory and expiratory muscle strength was defined by maximal inspiratory pressure (MIP) and maximal expiratory pressure (MEP), respectively. Systolic dysfunction was defined by left ventricular ejection fraction (LVEF) values below 52% (for men) or 54% (for women). Then, the validation of the cutoff points was verified by the percentage of true and false positives in another 30 ChC patients. Results The MIP showed adequate accuracy (p = 0.004) in identifying patients with systolic dysfunction (AUC = 0.73). The MEP did not show satisfactory accuracy in identifying those patients. The optimal MIP cutoff point to identify systolic dysfunction in ChC was ≤62 cmH2O, with a positive predictive value of 87%. In the validation analysis, MIP values below 62 cmH2O were able to identify 77% of patients with systolic dysfunction. Conclusion MIP has potential value in identifying systolic dysfunction in patients with ChC. This finding may aid in screening and risk stratification when echocardiography is not available.

New left ventricular thrombus and embolic events in left ventricular dysfunction postmyocardial infarction

Background: We aimed to assess the incidence and evolution of new left ventricular thrombus (LVT), and the incidence of manifest systemic embolism, in patients with severe left ventricular (LV) systolic dysfunction postacute anterior myocardial infarction (MI) who had been discharged on dual antiplatelet therapy. Methods: We prospectively included consecutive patients with postacute anterior MI and LV ejection fraction (LVEF) ≤35% or apical aneurysms or large infarctions with LVEF ≤40%. Transthoracic echocardiography (TTE) confirmed no LVT before hospital discharge, and a second TTE was performed at 30 days and a third one at 3 months. All TTE studies were prespecified to assess LVT, and the patients were screened for the development of clinically manifest systemic embolisms. Results: Two hundred and two consecutive patients (males 93%; mean age 55.2±6.4 years; mean LVEF 29.5±5.0%) were included. At 30 days (interquartile range: 2837 days), a new LVT was detected in 12 (5.9%) patients. Oral anticoagulant was added to all patients with LVT, and aspirin was continued in 5 (42.7%) patients for a month. The 3month TTE showed favorable evolution of LV size, LVEF and apical wall motion score index compared to the baseline. At 3 months, the LVT disappeared in 7 (58.3%) patients and 5 patients still had a mural LVT of smaller size, and none got new LVT. Among the group without LVT, one patient had a stroke, and another had a myocardial infarction and died. Conclusions: In contemporary practice, and using routine TTE, the incidence of new LVT in patients with severe LV dysfunction postacute anterior MI is low. They have a favorable LVT evolution with minor risk for clinically manifest systemic embolism.

Comparison of Functional Echocardiographic Markers in Septic and Non-Septic Neonate

Background: Neonatal sepsis accounts for significant morbidity and mortality and its hemodynamics is complex. Functional echocardiography is emerging at a rapid pace and currently it is considered as a key tool for providing real time information on cardiovascular performance. Objective: To assess and compare functional Echocardiographic markers in septic and non-septic neonate. Methodology: This cross-sectional comparative study was conducted in the Department of Neonatology, BSMMU over an Eighteen-month period from March 2022 to August 2023. 25 neonates including term baby and preterm ≥ 34 weeks with early or late-onset sepsis satisfying the inclusion criteria were enrolled for the study and compared with same gestational age matched healthy control. Result: Comparison of functional echocardiographic parameters between two groups were statistically significant in respect to right and left ventricular output and tricuspid annular plane systolic excursion. Cardiac output was increased (rt. ventricular output 277.4 ± 74.2 Vs 209 ± 70, lt. ventricular output 339.5 ± 43.2 Vs 276 ± 74.9, p-values were 0.002 and 0.001 respectively) and tricuspid annular plane systolic excursion (0.49 ± 0.13 Vs 0.74 ± 0.34, p value 0.001) was decreased in septic neonate compared to healthy counterpart. The result was also statistically significant result in respect to right and left ventricular output and tricuspid annular plane systolic excursion (p-values were 0.039, 0.004 and 0.01) respectively in comparison between preterm septic and non-septic newborn. When compared between the term neonates (37 weeks to 40 weeks) of both groups, there were also statistically significant result in respect to right ventricular output, left ventricular output and tricuspid annular plane systolic excursion (p- values were 0.006,0.03 and 0.025) respectively. Conclusion: Significant cardiovascular changes like cardiac output and right ventricular systolic dysfunction evidenced by Functional Echocardiography, were common association of neonatal sepsis in comparison to non-septic neonate.

Clinical Features and Outcomes of Pediatric MYH7-Related Dilated Cardiomyopathy.

Although genetic variants in MYH7 are the most frequent cause of pediatric genetic dilated cardiomyopathy (DCM), there are no studies available describing this entity. We sought to describe clinical features, analyze variant location, and explore predictors of bad prognosis in pediatric MYH7-related DCM. We evaluated clinical records from 44 patients (24 men; median age at diagnosis, 0.54 [interquartile range, 0.01-10.8] years) with pathogenic/likely pathogenic variants in MYH7 diagnosed with DCM at pediatric age (<18 years) followed at 13 international centers. We also explored risk factors associated with a composite end point of end-stage heart failure defined as heart transplantation or heart failure-related death. Twenty-two patients (50%) were diagnosed at age <6 months, including 7 (16%) at birth. Left ventricular (LV) hypertrabeculation features were present in 15 (38%), particularly among patients with genetic variants in the head domain. After a median follow-up of 6.1 years (interquartile range, 1.9-13.4), 15 patients (36%) required a heart transplant (n=14) or died due to end-stage heart failure (n=1), 15 patients (36%) persisted with systolic dysfunction despite treatment, 12 (29%) had a significant increase in LV ejection fraction, and 2 were lost to follow-up. Overall, end-stage heart failure event rate was 25% at 5 years. New York Heart Association class III to IV (hazard ratio [HR], 7.67 [95% CI, 2.16-27.2]; P=0.002) and LV ejection fraction ≤35% (HR, 4.00 [95% CI, 1.11-14.4]; P=0.03) were the best predictors of bad prognosis. Pediatric MYH7-related DCM is characterized by early onset, frequent LV hypertrabeculation, and poor prognosis. Advanced New York Heart Association class and low LV ejection fraction emerged as predictors of end-stage heart failure.

Systolic and global right ventricular functions of children with bronchial asthma as compared with those of healthy controls using echocardiography: a single-centre cross-sectional observational study from Nigeria

BackgroundAsthma is the most prevalent chronic airway condition in children. It is characterised by hyperresponsiveness of the small airways leading to airway narrowing, which is usually reversible, with or without treatment. Asthma is known to cause right ventricular dysfunction, but not much is known of this effect among children with highest burden of asthma. The aim of this study is to compare the right ventricular functions of children with asthma, aged 6– ≤ 13 years, with those of their age and sex-matched apparently healthy control using transthoracic echocardiography. The systolic and global right ventricular functions were assessed using Tricuspid Annular Plane Systolic Function (TAPSE) and Tei index, respectively.ResultsSeventy cases and 68 controls were included in the final analysis of the results. The male-to-female ratios are 1.9:1 and 2:1 for the cases and controls, respectively, and their mean age were 8.82 (± 2.28) and 9.05 (2.50) years. There was no statistically significant difference between their sex (X2\\documentclass[12pt]{minimal} \\usepackage{amsmath} \\usepackage{wasysym} \\usepackage{amsfonts} \\usepackage{amssymb} \\usepackage{amsbsy} \\usepackage{mathrsfs} \\usepackage{upgreek} \\setlength{\\oddsidemargin}{-69pt} \\begin{document}$${X}^{2}$$\\end{document}/P = 0.810/0.85) and their mean age (P = 0.554). The mean TAPSE of the cases (20.16 ± 2.15 mm) and the controls (20.28 ± 2.71 mm) did not differ significantly (P = 0.74), but the mean Tei index of the cases (0.56 ± 0.16) was significantly higher than that of the control (0.50 ± 0.10) (P = 0.007). Among the asthmatics, 17.1% (12/70) and 2.9% (2/70) had global and systolic RV dysfunctions, respectively; 2.9% (2/70) of the controls had RV global dysfunctions, but none had RV systolic dysfunction. The global dysfunction among the asthmatics was significantly associated with their age range and frequency of hospitalisation (X2\\documentclass[12pt]{minimal} \\usepackage{amsmath} \\usepackage{wasysym} \\usepackage{amsfonts} \\usepackage{amssymb} \\usepackage{amsbsy} \\usepackage{mathrsfs} \\usepackage{upgreek} \\setlength{\\oddsidemargin}{-69pt} \\begin{document}$${X}^{2}$$\\end{document} /p of 6.051/0.014 and 7.209/0.021, respectively), and significantly correlates with their Body Mass Index, and peripheral oxygen saturation (r/P of −0.236/0.049 and − 2.490/0.038, respectively). None of the participants had right ventricular systolic dysfunction.ConclusionThis study shows that asthmatic patients have global RV dysfunction, and it is suggested that better control of asthma would preserve cardiac function.

Spleen tyrosine kinase: a novel pharmacological target for sepsis-induced cardiac dysfunction and multi-organ failure

Sepsis is a systemic condition caused by a dysregulated host response to infection and often associated with excessive release of proinflammatory cytokines resulting in multi-organ failure (MOF), including cardiac dysfunction. Despite a number of effective supportive treatments (e.g. ventilation, dialysis), there are no specific interventions that prevent or reduce MOF in patients with sepsis. To identify possible intervention targets, we re-analyzed the publicly accessible Gene Expression Omnibus accession GSE131761 dataset, which revealed an increased expression of spleen tyrosine kinase (SYK) in the whole blood of septic patients compared to healthy volunteers. This result suggests a potential involvement of SYK in the pathophysiology of sepsis. Thus, we investigated the effects of the highly selective SYK inhibitor PRT062607 (15mg/kg; i.p.) on sepsis-induced cardiac dysfunction and MOF in a clinically-relevant, murine model of sepsis. PRT062607 or vehicle (saline) was administered to 10-weeks-old C57BL/6 mice at 1h after the onset of sepsis induced by cecal ligation and puncture (CLP). Antibiotics (imipenem/cilastatin; 2mg/kg; s.c.) and analgesic (buprenorphine; 0.05mg/kg; i.p.) were administered at 6h and 18h post-CLP. After 24h, cardiac function was assessed in vivo by echocardiography and, after termination of the experiments, serum and cardiac samples were collected to evaluate the effects of SYK inhibition on the systemic release of inflammatory mediators and the degree of organ injury and dysfunction. Our results show that treatment of CLP-mice with PRT062607 significantly reduces systolic and diastolic cardiac dysfunction, renal dysfunction and liver injury compared to CLP-mice treated with vehicle. In addition, the sepsis-induced systemic inflammation (measured as an increase in inflammatory cytokines and chemokines in the serum) and the cardiac activation of NF-kB (IKK) and the NLRP3 inflammasome were significantly reduced in CLP-mice treated with PRT062607. These results demonstrate, for the first time, that SYK inhibition 1h after the onset of sepsis reduces the systemic inflammation, cardiac dysfunction and MOF, suggesting a potential role of the activation of SYK in the pathophysiology of sepsis. Novel therapeutic strategies that inhibit SYK activity may be of benefit in patients with diseases associated with local or systemic inflammation including sepsis.

Evaluation of subclinical LV systolic dysfunction by speckle tracking echocardiography in patients with Non-alcoholic fatty liver disease

Evaluation of subclinical LV systolic dysfunction by speckle tracking echocardiography in patients with Non-alcoholic fatty liver disease

Effects of systemic ventricular assist in failing Fontan patients: a theoretical analysis using a computational model

Mechanical circulatory support is a potential treatment for failing Fontan patients. In this study, we performed a theoretical analysis using a computational model to clarify the effects of systemic ventricular assist device (VAD) in failing Fontan patients. Cardiac chambers and vascular systems were described using the time-varying elastance model and modified Windkessel model, respectively. A VAD was simulated as a nonlinear function. In systolic and diastolic ventricular dysfunction and atrioventricular valve regurgitation models, systemic VAD increased the cardiac index and decreased the central venous pressure (CVP). However, in the high pulmonary vascular resistance model, CVP became extremely high above 15 mmHg to maintain the cardiac index when the pulmonary vascular resistance index (PVRI) was above 5 Wood units m2. In Fontan patients with ventricular dysfunction or atrioventricular valve regurgitation, systemic VAD efficiently improves the hemodynamics. In Fontan patients with PVRI of > 5 Wood units m2, systemic VAD seems ineffective.

Five-Year Outcomes with Self-expanding versus Balloon-expandable TAVI in Patients with Left Ventricular Systolic Dysfunction

The importance of transcatheter heart valve (THV) design on clinical outcome in patients with aortic stenosis (AS) and left ventricular (LV) systolic dysfunction remains unknown. We aimed to compare 5-year outcomes of patients with severe AS and reduced LV ejection fraction (LVEF), undergoing transcatheter aortic valve implantation (TAVI) with balloon-expandable vs. self-expanding THVs. In a retrospective analysis from the Bern TAVI registry, patients with LVEF <50% who underwent TAVI with either balloon-expandable or self-expanding THVs were included. A 1:1 propensity-score matching was performed to account for baseline differences between groups. A total of 759 patients were included between August 2007 and December 2022, and propensity-score matching resulted in 134 pairs. Technical success was achieved in over 85% of patients, and was similar in both groups. Self-expanding THVs were associated with a lower mean transvalvular gradient (7.1 ± 3.7 mmHg vs. 9.9 ± 4.3 mmHg; P <0.001) and a higher incidence of ≥mild-to-moderate paravalvular regurgitation (36.3% vs. 11.3%; P <0.001) compared to balloon-expandable THVs. At 5 years, patients treated with a self-expanding THV had higher all-cause mortality than those with a balloon-expandable THV (67.8% vs. 55.8%, HRadjusted: 1.44; 95% CI: 1.02-2.03; P = 0.037). There were no significant differences in other clinical outcomes up to 5 years between groups. In the setting of LV systolic dysfunction, patients treated with a self-expanding THV had higher risk of 5-year mortality compared to patients treated with a balloon-expandable THV. https://www. gov. NCT01368250.

Myxomatous mitral valve disease in Labrador Retrievers and Golden Retrievers.

To characterize myxomatous mitral valve disease (MMVD) in Labrador Retrievers (LRs) and Golden Retrievers (GRs). 52 LRs and 20 GRs diagnosed with MMVD composed a retrospective study sample (February 1, 2010, to July 31, 2021). Stored echocardiograms were remeasured. Dogs were staged by 2019 MMVD consensus guidelines. Mean age was 9.9 years in LRs and 9.5 years in GRs, with 31 of 52 LRs (59.6%) and 13 of 20 (65.0%) GRs being male. Forty-six LRs were stage B1 (88.5%), 3 were B2 (5.8%), and 3 were C (5.8%). Fourteen GRs were stage B1 (70.0%), 2 were B2 (10.0%), and 4 were C (20.0%). Of LRs and GRs in stage B2/C, 50% had systolic dysfunction. Atrial fibrillation (AF) and ventricular arrhythmias were identified in 2 of 52 (3.8%) and 10 of 52 (19.2%) LRs at initial diagnosis versus 3 of 20 (15.0%) and 3 of 20 (15.0%) GRs, respectively. All 5 AF dogs were stage C, with intermediate to high probability of pulmonary hypertension. Two additional GRs developed AF during follow-up; thus 5 of 6 (83.3%) stage B2/C GRs ultimately experienced AF. Subjective mitral valve thickening was frequent in both breeds (41/52 LRs [78.8%]; 18/20 GRs [90.0%]), while mitral valve prolapse was more common in LRs (22/52 [42.3%]) than GRs (5/20 [25.0%]). In LRs and GRs, MMVD was relatively late onset, with males overrepresented. Both breeds exhibited mitral valve thickening in association with MMVD, while LRs more commonly exhibited mitral valve prolapse. While most LRs and GRs with MMVD were stage B1, those in stage B2/C had increased prevalence of systolic dysfunction and AF.

Fibroblast-derived miR-425-5p alleviates cardiac remodelling in heart failure via inhibiting the TGF-β1/Smad signalling.

The pathological activation of cardiac fibroblasts (CFs) plays a crucial role in the development of pressure overload-induced cardiac remodelling and subsequent heart failure (HF). Growing evidence demonstrates that multiple microRNAs (miRNAs) are abnormally expressed in the pathophysiologic process of cardiovascular diseases, with miR-425 recently reported to be potentially involved in HF. In this study, we aimed to investigate the effects of fibroblast-derived miR-425-5p in pressure overload-induced HF and explore the underlying mechanisms. C57BL/6 mice were injected with a recombinant adeno-associated virus specifically designed to overexpress miR-425-5p in CFs, followed by transverse aortic constriction (TAC) surgery. Neonatal mouse CFs (NMCFs) were transfected with miR-425-5p mimics and subsequently stimulated with angiotensin II (Ang II). We found that miR-425-5p levels were significantly downregulated in HF mice and Ang II-treated NMCFs. Notably, fibroblast-specific overexpression of miR-425-5p markedly inhibited the proliferation and differentiation of CFs, thereby alleviating myocardial fibrosis, cardiac hypertrophy and systolic dysfunction. Mechanistically, the cardioprotective actions of miR-425-5p may be achieved by targeting the TGF-β1/Smad signalling. Interestingly, miR-425-5p mimics-treated CFs could also indirectly affect cardiomyocyte hypertrophy in this course. Together, our findings suggest that fibroblast-derived miR-425-5p mitigates TAC-induced HF, highlighting miR-425-5p as a potential diagnostic and therapeutic target for treating HF patients.

Successful management of complete heart block in checkpoint inhibitor induced myocarditis by left bundle branch area pacing: a case report

Abstract Background Optimal management of checkpoint inhibitor-induced complete heart block is unknown. Previous reports showed relatively high incidence of pacing failure due to the co-existing myocarditis. Case summary A 71-year-old male with a prior history of stage IV metastatic squamous cell lung cancer presents was admitted for dyspnoea and hypotension 10 days after checkpoint inhibitor treatment using pembrolizumab. He was found to have myocarditis, third-degree AV block, severe left ventricular systolic dysfunction with EF 35%, and required pressure support. A dual chamber pacemaker using left bundle branch area pacing (LBBAP) was urgently placed that immediately improved his haemodynamics. Both the cathode and anode were able to capture the ventricle at different pacing outputs. The patient was taken off all intravenous pressors and successfully transferred to a larger centre for further management of the myocarditis with no further arrhythmia or hypotension. Discussion In conclusion, because of the unique ability to capture a large amount of myocardium from both the tip and ring electrodes as well as the ability to deliver cardiac resynchronization therapy, LBBAP may be the preferred pacing strategy in patients who develop complete heart block due to checkpoint inhibitor-induced myocarditis.

Looking at Early Systolic Dysfunction in Chronic Kidney Disease: What's Next?

Looking at Early Systolic Dysfunction in Chronic Kidney Disease: What's Next?

Regional mechanical dyssynchrony and shortened systole are present in people with Takotsubo syndrome

Background:Takotsubo syndrome is characterized by transient regional systolic dysfunction, left ventricular (LV) dilatation, and edema, often occurring without obstructive coronary artery disease. The mechanisms underlying this stress-induced condition, especially the role of mechanical dyssynchrony in affecting systolic function, remain poorly understood.Methods:In our study, we evaluated global LV function and mechanical dyssynchrony in 24 Takotsubo patients compared to 20 controls by analyzing pressure-volume loops and time-varying elastance. Additionally, we monitored changes in LV segmental volume and internal flow.Results:Here we show a significant reduction in global myocardial contractility and pronounced mechanical dyssynchrony in Takotsubo syndrome, particularly in the mid and apical LV segments, without disturbances in electrical conduction.Conclusions:Our findings reveal substantial mechanical dyssynchrony in Takotsubo patients, characterized by increased internal flow and a shortened systolic ejection time. This indicates a mechanical basis for the inefficient LV function in Takotsubo syndrome, independent of electrical conduction abnormalities.

Diagnostic Value of Combined Light and Electron Microscopic Examination in Endomyocardial Biopsy in Patients with Cardiac Amyloidosis.

Despite advances in imaging techniques, endomyocardial biopsy remains the gold standard for confirming cardiac amyloidosis (CA) and defining the amyloid type. Electron microscopy may detect amyloid deposits with greater sensitivity than light microscopy; however, its capabilities have not been thoroughly investigated. Patients with pathologically diagnosed CA were prospectively enrolled. Myocardial specimens were collected from the right ventricular septum, and light and electron microscopy were performed on the samples to compare their efficacy in detecting amyloid deposits. Sixty-five patients were pathologically diagnosed with CA, including 13 with light-chain amyloidosis, 51 with transthyretin amyloidosis, and one with unclassified amyloidosis. Amyloid deposits were detected through both examinations in 60 (92.3%) of the 65 patients. However, they were detected through only light microscopy in two cases (3.1%) and only electron microscopy in three cases (4.6%). Patients with amyloid deposits detected through a single method had reduced thickness of the intraventricular septal wall (9.5 vs. 15.1 mm, p=0.001), lower left ventricular (LV) mass index (94 vs. 147 g/m2, p= 0.013), greater LV diastolic dimension (45 vs. 41 mm, p=0.044), lower LVEF (49% vs. 57%, p=0.004), lower mean pulmonary capillary wedge pressure (9 vs. 19 mmHg, p=0.021), and lower right atrial pressure (4 vs. 8 mmHg, p=0.043) than did those in whom they were detected using both methods. Concomitant use of electron microscopy may improve the detection rate of amyloid deposits and prevent CA misdiagnosis, especially in patients with atypical features such as mild hypertrophy or eccentric hypertrophy with LV systolic dysfunction.

Free Immunoglobulin Light Chains in Patients With Myocarditis: a New Biomarker of Inflammation and Heart Failure

To study the concentration of immunoglobulin free light chains (FLCs) in patients with myocarditis in comparison with non-inflammatory heart diseases, their relationship with inflammatory markers and the severity of chronic heart failure (CHF). This study included 77 patients (31 women, mean age 54.1±13.3 years): 41 patients with myocarditis verified by myocardial biopsy (n=18) or using a noninvasive diagnostic algorithm, 31 patients with noninflammatory CHF (comparison group), and 5 patients with monoclonal gammopathy identified during the study (4 of them were diagnosed with AL amyloidosis with heart damage). In the myocarditis group, CHF was diagnosed in 29 patients, mean stage IIA, functional class (FC) 2-3, with a mean left ventricular ejection fraction 43%. In the comparison group, patients had predominantly IIA stage, FC 2-3 CHF without systolic dysfunction. The blood concentration of kappa and lambda FLC types was measured with Cloneus S-FLC-K TIA Kit and Cloneus S-FLC-L TIA Kit. Concentrations were considered normal at FLC-kappa 4.84-14.20 mg/l, FLC-lambda 7.03-22.50 mg/l, and the FLC-kappa/lambda ratio 0.426-1.050. Increased FLC concentrations were found in 58% of patients with myocarditis and in 77% of patients in the comparison group. The FLC-lambda concentration was significantly higher in the comparison group; there were no significant differences between the groups in FLC-kappa and their ratio. The closest significant correlations in both groups and the entire cohort were noted between FLCs of either type and CHF, as well as the requirement for loop diuretics (correlation coefficients, 0.60-0.90), independent on the severity of systolic dysfunction. Myocarditis patients also showed correlations of FLCs with the titer of antibodies to cardiomyocyte nuclear antigens, levels of C-reactive protein, leukocytes, neutrophils, erythrocyte sedimentation rate, and the concentration of N-terminal fragment of brain natriuretic peptide. In a subgroup of 10 myocarditis patients who were treated with immunosuppressants, FLCs of both types were significantly lower than in the comparison group; only with the persistence of severe CHF was an increase in FLCs noted. An increased FLC concentration can be considered as an important pathogenesis component that reflects both the specific mechanisms of myocarditis and the severity of CHF. In the absence of a statistically significant increase in general inflammatory markers in the blood of myocarditis patients, the measurement of FLCs can be used as an additional diagnostic marker and predictor of the decompensated variant of the course of myocarditis. However, the diagnostic and prognostic significance of FLC concentration in patients without CHF requires a further study.

Common Echocardiographic Diagnoses in Patients at Tertiary Care Center: An Observational Study

Introduction: Echocardiography is an indispensable tool for the diagnosis and management of cardiac patients. It is important to know the spectrum of cardiac abnormalities detected by echocardiography for the proper management of patients. The aim of this study was to evaluate the echocardiographic diagnosis of patients at a multispecialty tertiary care hospital and find out the prevalence of various cardiac diseases diagnosed via echocardiography.Methods: This was a retrospective cross sectional study carried out at the Echocardiography lab of National Academy of Health Sciences. Records of all patients who had done Echocardiography from February 2024 to April 2024 were analyzed. Ethical approval was obtained from Institutional Review Committee (Reference Number:1231/2080/81).Results: Out of 3593 cases, there were 1750 (48.71%) female and 1843 (51.29%) male. Normal echocardiographic study was seen in 1184 (32.95%). Mean age was 56.13±17.38 years. Left ventricle diastolic dysfunction was seen among 1428 (39.74%), followed by tricuspid regurgitation 1026 (28.55%) and pulmonary hypertension 497 (13.83%). Other findings were, left ventricular hypertrophy 204 (5.67%), Left ventricular systolic dysfunction 165 (4.59%), rheumatic heart disease 102 (2.83%) and, congenital heart disease was the lowest documented finding, seen in 30 (0.83%).Conclusions: Most common diseases diagnosed by echocardiography in our study were, diastolic dysfunction, tricuspid regurgitation and pulmonary hypertension.

No Difference in Systolic Dysfunction from Left Ventricular Pressure-Volume Loop’s Area and Stroke Work Between Chronic Late Load vs. Early Systolic LV Load in Porcine Model

&amp;lt;i&amp;gt;Background: &amp;lt;/i&amp;gt;in increased LV afterload as in hypertension, early systolic LV dysfunction (SD) in late compares to early peak systolic LV load for P-V area, stroke work, potential energy with effective LV work (EW) is not being defined (aortic stenosis, arterial hypertension or coarctation of the aorta) in LVH remodeling. &amp;lt;i&amp;gt;Objectives:&amp;lt;/i&amp;gt; to assess in porcine model how LV stroke work, PVA and EW are related to LVH remodeling in developing early SD with HF, between 4&amp;lt;sup&amp;gt;th&amp;lt;/sup&amp;gt; vs 8&amp;lt;sup&amp;gt;th&amp;lt;/sup&amp;gt; week in chronic LL compares to EL. It is suggested that reduced proximal thoracic or asc. aortic compliance results with myocardial ischemia. However, difference for LV O&amp;lt;sub&amp;gt;2&amp;lt;/sub&amp;gt; demand and effective LV work in different LV afterload is not understood in early development systolic HF. &amp;lt;i&amp;gt;Methods:&amp;lt;/i&amp;gt; in fourteen domestic male pigs (28±3 kg) with moderate descending aortic banding having chronic late LV load (LL=8) or ascending aortic stenosis with early systolic LV load (EL=6) SD was assessed, from PVA, in invasive LV pressure-volume loops’ measurements, at 4&amp;lt;sup&amp;gt;th&amp;lt;/sup&amp;gt; vs. 8&amp;lt;sup&amp;gt;th&amp;lt;/sup&amp;gt; week, to assess LV maximal ESPVR, with Millar 5Fr P-V pig-tailed conductance catheter. LV stroke work, and pressure-volume area PVA, reflecting the maximal LV O&amp;lt;sub&amp;gt;2&amp;lt;/sub&amp;gt; demand were assessed in chronic LL compares to EL from nonlinear regression analysis of maximal LV end-systolic stiffness, in special software. For variance analysis, two-way repeated measures ANOVA was performed, with normality assessment. Results are means±(SEM) or medians for significant p&amp;lt;0.05. &amp;lt;i&amp;gt;Results: &amp;lt;/i&amp;gt;LV PVA was not different, in LL compared to EL at 4&amp;lt;sup&amp;gt;th&amp;lt;/sup&amp;gt; vs. 8&amp;lt;sup&amp;gt;th&amp;lt;/sup&amp;gt; week. LV stroke work with effective works were not different and potential energy, neither were changed between 4&amp;lt;sup&amp;gt;th&amp;lt;/sup&amp;gt; vs. 8&amp;lt;sup&amp;gt;th&amp;lt;/sup&amp;gt; week. No difference was found in different LV afterload, in both indexed and absolute LVO&amp;lt;sub&amp;gt;2&amp;lt;/sub&amp;gt; demand, in LL vs. EL at 4&amp;lt;sup&amp;gt;th&amp;lt;/sup&amp;gt; or 8&amp;lt;sup&amp;gt;th&amp;lt;/sup&amp;gt; week. Indexed PVA parameters with LV stroke work, effective work and potential energy were not different or changed in LL compares to EL between 4&amp;lt;sup&amp;gt;th&amp;lt;/sup&amp;gt; vs. 8&amp;lt;sup&amp;gt;th&amp;lt;/sup&amp;gt; weeks, normalized per body surface-area (in m&amp;lt;sup&amp;gt;2&amp;lt;/sup&amp;gt;). &amp;lt;i&amp;gt;Conclusion:&amp;lt;/i&amp;gt; Both absolute and indexed LV stroke work, potential LV energy, PVA with EW and maximum LV O&amp;lt;sub&amp;gt;2&amp;lt;/sub&amp;gt; demand are not different in LL compares to EL at 4&amp;lt;sup&amp;gt;th&amp;lt;/sup&amp;gt; vs. 8&amp;lt;sup&amp;gt;th&amp;lt;/sup&amp;gt; week of LVH remodeling, indicating no difference in early SD development in increased late vs. early LV afterload.