Ventricular Relaxation Research Articles

MO158: The Association of Left Ventricular Diastolic Dysfunction and Heart Failure in Patients with Chronic Kidney Disease

Abstract BACKGROUND AND AIMS Chronic kidney disease (CKD) has been linked with an increased risk of cardiovascular events, especially in dialysis population. According to literature data, in the patients with CKD heart function disturbances are twice as common as in the general population [1]. Bearing in the mind that left ventricular hypertrophy (and abnormal left ventricular relaxation) is considered to be one of the most important parameters for the occurrence of cardiovascular disease in CKD [2], the aim of our study was to evaluate the association of left ventricular diastolic dysfunction with heart failure in CKD patients. METHOD The research was conducted as a prospective observational study which included 30 patients with CKD, stage III and IV according KDIGO [3], and left ventricular diastolic dysfunction, and 30 control subjects who also had left ventricular diastolic dysfunction but without CKD. Pulse-wave (PW) Doppler echocardiography in the apical four-chamber view and tissue Doppler imaging were performed to assess left ventricular function [4]. The measurements of mitral inflow by PW Doppler covered early (E-wave) and late (A-wave) diastolic feeling velocities, peak early diastolic velocity at the septal (e′septal) and lateral (e′lateral) mitral annular sites, and E/A ratio. RESULTS A comparison of left ventricular function parameters between two groups of study participants indicated that left ventricular ejection fraction (0.57 ± 0.05% versus 0.61 ± 0.03%) was statistically reduced in CKD patients compared to control subjects (P < .001). Contrary, left ventricular mass index (119.8 ± 27.0 g/m2 versus 100.8 ± 20.4 g/m2P = .003) and interventricular septum thickness (11.8 ± 1.4 mm versus 10.8 ± 1.5 mm, P = .012) were significantly higher in the patients with CKD. There were no significant differences in values of left ventricular end-diastolic (53.7 ± 4.6 mm versus 54.2 ± 3.5 mm, P = .636) and left ventricular end-systolic (34.7 ± 4.5 mm versus 35.7 ± 2.3 mm, P = .265) dimension between CKD patients and controls. The mitral inflow imaging pointed to more pronounced left ventricular diastolic dysfunction in CKD patients than in the subjects without CKD: e′septal (P = .009) and e′lateral (P < .001) velocity. E/A ratio showed no markedly deviation between two study groups (P = .787). On the other hand, when we analysed the frequency of heart failure, it was noted that newly developed episodes of cardiac decompensation were more frequent in patients with CKD than in the control group (Chi square = 6.667, P = .010). Regression analysis confirmed the predictive significance of left ventricular echosonographic characteristics on the occurrence of heart failure in patients with CKD (OR 1.56, 95% CI 1.11‒2.18, P = .011 for left ventricular mass index; OR 1.68, 95% CI 1.01‒2.80, P = .048 for e′). CONCLUSION Heart failure is more common in patients with CKD than in patients with normal kidney function. There is a positive relationship between the presence of left ventricular diastolic dysfunction and the occurrence of heart failure in patients with CKD.

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

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

Non-invasive assessment of left ventricular relaxation property using color M-mode-derived intraventricular pressure gradients in cats

IntroductionDiastolic dysfunction is an early clinical feature of feline hypertrophic cardiomyopathy (HCM). The left ventricular filling in early diastole is facilitated by the diastolic intraventricular pressure gradient (IVPG). The study objectives were to evaluate color Doppler M-mode-derived IVPG calculation in cats as a non-invasive assessment of the left ventricular relaxation property to determine the normal ranges of peak IVPG in cats and investigate the influence of left ventricular function and heart rate (HR). AnimalsOne hundred and six client-owned apparently healthy cats. MethodsProspective cross-sectional study. Quantitative analysis of color Doppler M-mode images was used to estimate total and segmental IVPGs non-invasively. ResultsThe total IVPG was 0.76 mmHg (95% reference interval (RI): 0.28–1.29 mmHg), the basal IVPG 0.34 mmHg (95% RI: 0.07–0.63 mmHg), and the mid-apical IVPG 0.42 mmHg (95% RI: 0.15–0.71 mmHg). Total and segmental IVPG increased with HR (P < 0.003), while segmental percent IVPG was HR independent. A short isovolumic relaxation time (IVRT) and a high mitral annular velocity in early diastole were associated with an increase in total IVPG (P = 0.008 and P = 0.009, respectively) adjusted for HR. An increase in IVPG was associated with an increase in mitral inflow velocity (P < 0.001). ConclusionsFeline IVPGs increase with HR and a short IVRT, which was believed to be a normal physiologic adrenergic response associated with an increased sympathetic tone. Future studies of segmental IVPG changes in feline HCM are needed to evaluate the clinical applicability of color Doppler M-mode estimated IVPGs in feline cardiology.

Preservation of Nitric Oxide Synthase Activity Required for Beneficial Effects of Hypothermic Oxygenated Perfusion in Cardiac Grafts Obtained with DCD

<h3>Purpose</h3> Cardiac donation after circulatory death (DCD) is a promising option to increase graft availability. We recently reported that cardiac graft preservation with hypothermic oxygenated perfusion (HOPE) between graft procurement and normothermic reperfusion improves graft recovery as compared to preservation with cold static storage (CSS), the current clinical standard. As the precise mechanisms remain incompletely characterized, we investigated the role of preserved nitric oxide synthase (NOS) activity during HOPE on its beneficial effects. <h3>Methods</h3> Using an adult rat model of DCD, hearts underwent in-situ ischemia (21 minutes), were explanted for a cold storage period (30 minutes), and then reperfused under normothermic conditions (60 minutes) with left ventricular loading. Three cold storage conditions were compared: CSS, HOPE, and HOPE with L-NAME (NOS inhibitor). To evaluate potential confounding effects of high coronary flow during early reperfusion in HOPE hearts, bradykinin (BK) was administered to normalize coronary perfusion to HOPE levels in two additional groups (CSS and HOPE with L-NAME). <h3>Results</h3> Cardiac recovery was significantly improved in HOPE vs. CSS hearts, as determined by cardiac output, left ventricular work (heart rate-developed pressure product), contraction and relaxation rates, as well as coronary flow and oxygen efficiency (oxygen consumption per work performed; p<0.05). Strikingly, the addition of L-NAME during HOPE largely abolished its beneficial effects, even when early reperfusion coronary flow was normalized to HOPE levels with BK. Furthermore, preliminary experiments demonstrate a tendency for reduced release of cell death markers in hearts treated with HOPE compared to all other groups. <h3>Conclusion</h3> HOPE provides superior preservation of ventricular and vascular function, as well as improved metabolic recovery, compared to the current clinical standard (CSS). Importantly, preservation of NOS activity during the cold storage period is required for the protective effects of HOPE. The application of HOPE prior to normothermic reperfusion is a promising approach to help optimize cardiac graft recovery following warm ischemia in DCD cardiac grafts.

Left Ventricular Diastolic Dysfunction in Chronic Thromboembolic Pulmonary Hypertension

<h3>Purpose</h3> Impairment of left ventricular (LV) relaxation is associated with increased mortality after surgical treatment of pulmonary hypertension (PH). We sought to describe the pathophysiology of LV diastolic dysfunction in a porcine model of chronic thromboembolic pulmonary hypertension (CTEPH). The reversibility of LV diastolic dysfunction was investigated in patients with CTEPH after pulmonary endarterectomy (PEA). <h3>Methods</h3> CTEPH was induced in 2-month-old Large White piglets (PH group, n=6) by ligation of the left pulmonary artery (PA) followed by weekly embolization of right lower lobe for 5 weeks using a strong tissue glue (N-acetyl cyanoacrylate). These animals were compared to sham-operated animals (controls, n=6). LV diastolic function was assessed using echocardiography and conductance catheter measurements. LV fibrosis was investigated at 6 weeks using red Sirius staining of myocardial tissues. Echocardiographic measurements for LV diastolic function were retrospectively analyzed in 102 patients, before and after PEA. <h3>Results</h3> Mean PA pressure was higher at 6 weeks in PH animals compared to controls (28.5 [28.0; 34.2] vs. 14.0 [12.5; 14.0] mmHg, p<0.01). Increased end-diastolic LV pressure was observed in PH group (21.9 [18.1; 22.7] vs. 12.2 [11.7; 13.8] mmHg, p=0.013), along with a marked decrease in the curve-fitting constant (c) and the maximum rate of LV filling (dV/dt_max), respectively by 49% (p=0.03) and 74% (p=0.014). Stiffness constant ß was strongly correlated with Doppler imaging index E/A (r=-0.94, p=0.015). Mean LV fibrosis score was significantly higher in PH group at 6 weeks (5.11±0.89% vs. 3.29±1.14%, p<0.01). Pre-operative impairment of LV filling pattern was remarkable in patients with CTEPH (E/A = 0.81±0.32; E/E'=6.42±2.84), and significantly improved at 7 days post PEA (+30%, p<0.001). At 6 months, E/A ratio was significantly higher (0.91 [0.75; 1.20] vs. 0.76 [0.66; 0.94], p=0.05) but remained abnormal, despite significant decrease in mean pulmonary vascular resistance (7.3 ±3.1WU vs. 3.8±1.5WU, p<0.001). <h3>Conclusion</h3> Impaired myocardial stiffness was associated with LV fibrosis in our piglet model of CTEPH. Mild LV diastolic dysfunction was observed at 6 months in patient with CTEPH despite significant decrease in RV pressure overload after PEA. Myocardial fibrosis may be responsible for persistent abnormal LV relaxation.

Non-Invasive Surveillance for Cardiac Allograft Rejection Using an Echocardiographic Rejection Score in Pediatric Heart Transplant Recipients

<h3>Purpose</h3> Cardiac allograft rejection post heart transplant (HT) remains a significant cause of morbidity and mortality in pediatric HT recipients. Endomyocardial biopsy is the gold standard for diagnosis, but is invasive, expensive, and not without risks. We examine the correlation between a non-invasive echocardiographic ejection score (ERS) and clinical and echocardiographic (echo) evidence of rejection. <h3>Methods</h3> All pediatric HT patients followed at our institution who had surveillance echo using the ERS were retrospectively enrolled. Rejection is defined as any changes in clinical or echo parameters resulting in augmented immunosuppression or administration of steroids, biologics, or plasmapheresis. ERS, left ventricular relaxation index (LVRI), RR interval, diastolic time, and atrioventricular valve regurgitation were obtained from the echo reports. The ERS is scored from 0-10 and is stratified as follows: 0-4: no rejection; 5-6: possible rejection necessitating closer follow up or consideration of other clinical factors; ≥7: automatic rejection. <h3>Results</h3> Sixty-six patients were followed over an 8 year period. Mean age at HT was 6.81 years (range 22 days - 21 years). Thirty-five (53%) patients were male. Primary indication for HT was cardiomyopathy in 54.5% (n=36), congenital heart disease in 44% (n=29), and other in 1.5% (n=1). Fifty-eight episodes of acute or ongoing rejection were treated based on clinical evidence. The ERS correlated weakly with LVRI (r = -.191, p < .01), RR interval (r = .117, p <.01), diastolic time (r = .159, p <.01), and new onset mitral or tricuspid regurgitation (MR/TR) (r = .168, p <.01). The ERS did not correlate with rejection identified by changes in clinical status alone (r = .015, p = .428). <h3>Conclusion</h3> ERS appears to be a useful non-invasive diagnostic tool for early detection of rejection in heart transplant pediatric patients. A larger study is needed to determine the diagnostic utility of this non-invasive ERS.

Overview of Restrictive Cardiomyopathies.

Restrictive cardiomyopathy (RCM) includes a heterogeneous group of diseases that cause increased myocardial stiffness, leading to impaired ventricular relaxation and severe diastolic dysfunction. Given that it is the least common type of cardiomyopathy, it can be a diagnostic challenge due to its varied pathogenesis, clinical presentation, and diagnostic evaluation. In this review, we provide an overview of different etiologies of RCM and examine the diagnostic and treatment approaches for various types.

Myxomatous Degeneration of Atrioventricular Valves in a Crab-eating fox (Cerdocyon thous) - Echodopplercardiography Diagnosis

Background: The myxomatosis degeneration is a degenerative cardiac valve disease, with a higher incidence in male and senile canids. The diagnosis is made by a doppler echocardiography exam. Although there are few reports on the occurrence of cardiopathies in wild dogs (Cerdocyon thous), some studies on their cardiological parameters can be found. Considering this, and knowing that the cardiopathies in wild canids are common post mortem findings, the objective of this study is to describe the echocardiography diagnosis of a case of myxomatous degeneration of the atrioventricular valves in 1 wild dog (Cerdocyon thous) living in captivity.Case: It was treated at the Diagnostic Imaging Department of the Veterinary Hospital of the Federal University of Mato Grosso (HOVET-UFMT), 1 wild dog (C. thous), male, living in captivity with approximately 10-year-old, directed by the Center of Medicine and Research in Wild Animals of Cuiabá, to perform echocardiography exam. The patient was submitted to anesthesia for proper examination, which was used Esaote® machine model MyLabFive VET with sector scan transducer (4.0 -7.5 MHz). The longitudinal, transverse and apical scan planes were obtained through left and right parasternal windows. The evaluation of M mode exposed ejection fraction and shortening increased, of 81% and 47%, respectively, however it showed no increase in systolic and diastolic values of left ventricle, nor in right cavities on subjective evaluation. The relation between the left atrium (LA) and the aorta (Ao) remained normal, at 1.2 mm, with dimensions of 13.4 mm from the AO and 16.3 mm from LA, compatible with species parameters or domestic canines. The atrioventricular valves showed thickening and irregularities in their cusps, with great intensity in the left atrioventricular valve (LAV). The Doppler mode analysis revealed a turbulent systolic flow into the left atrium and right atrium, constituting transvalvular LAV and right atrioventricular valve- (RAV) regurgitation, both observed through the blood flow in colored Doppler and measured through the reflux velocity of 4.02 m/s of LAV and 2.17 m/s of RAV by the continuous Doppler, showing insufficiency of intense degree of LAV and moderate degree of RAV, no evidence of pulmonary hypertension. On the other hand, the relation between wave E and wave A (E/A) was 1.0, with increased transvalvular velocities and values of 0.95 m/s for wave E and A. The isovolumetric mitral relaxation time was approximately 76 m/s. The value of the pressure derivative (dp) in relation to time (dt) dp/dt measured from the LAV reflux was 1257 mmHg, within the limit considered normal for canines. Four months after the diagnosis, the patient died due to complications of chronic renal failure.Discussion: Despite being a commonly diagnosed pathology in domestic canids, the myxomatous degeneration of atrioventricular valves is still little reported in wild canids. The evaluation of the results showed that although there was severe LAV regurgitation, there was no hypertrophy or compensatory dilation of the left cavities. However, there was a compensatory increase in the shortening fraction together with the ventricular relaxation deficit. The diagnosis of this condition in Cerdocyon thous demonstrates that the pathology can affect animals of advanced age and that its incidence needs to be determined in these captive species, in order to understand the real impact of this disease in these populations. Keywords: cardiopathies, cardiac valve disease, degenerative disease, cardiological parameters, wild dog. Título: Degeneração mixomatosa das válvulas atrioventriculares em cachorro-do-mato (Cerdocyon thous) - diagnóstico ecocardiográfico Descritores: cardiopatias, doença valvular cardíaca, doença degenerativa, parâmetros cardiológicos, canídeo selvagem.

Effect of hyperhomocysteinemia on rat cardiac sarcoplasmic reticulum.

Increased concentration of plasma homocysteine (Hcy) is an independent risk factor of cardiovascular disease, yet the mechanism by which hyperhomocysteinemia (HHcy) causes cardiac dysfunction is largely unknown. The aim of present study was to investigate the contribution of sarcoplasmic reticulum to impaired cardiac contractile function in HHCy. HHcy-induced by subcutaneous injection of Hcy (0.45μmol/g of body weight) twice a day for a period of 2weeks resulted in significant decrease in developed left ventricular pressure and maximum rate of ventricular relaxation. Our results show that abundances of SR Ca2+-handling proteins, Ca2+-ATPase (SERCA2), calsequestrin and histidine-rich calcium-binding protein are significantly reduced while the content of phospholamban is unchanged. Moreover, we found that increased PLN:SERCA2 ratio results in the inhibition of SERCA2 activity at low free Ca2+ concentrations. We further discovered that HHcy is not associated with increased oxidative stress in SR. Taken together, these findings suggest that disturbances in SR Ca2+ handling, caused by altered protein contents but not oxidative damage, may contribute to impaired cardiac contractility in HHcy.

Reversed Apico-Basal Myocardial Relaxation Sequence During Exercise in Long QT Syndrome Mutations Carriers With History of Previous Cardiac Events.

BackgroundRecent echocardiography studies in inherited long QT syndrome (LQTS) have shown left ventricular (LV) myocardial relaxation disturbances to follow markedly prolonged and dispersed mechanical contraction.AimWe used speckle-tracking echocardiography to assess disturbances in LV myocardial relaxation sequence during exercise and their relationship to symptoms.MethodsForty seven LQTS patients (45 ± 15 years, 25 female and 20 symptomatic, LVEF: 65 ± 6%) and 35 controls underwent exercise echocardiogram using Bruce protocol. ECG and echo parameters were recorded at rest, peak exercise (p.e.) and recovery.ResultsBetween patients and controls there were no differences in age, gender, HR or LVEF. At p.e, patients had longer time to LV longitudinal ESR (tESR) at all three LV segments; basal (p < 0.0001), mid- cavity (p = 0.03) and apical (p = 0.03) whereas at rest such difference was noted only at base (p = 0.0007). Patients showed reversed apico-basal relaxation sequence (ΔtESRbase–apex) with early relaxation onset occurring later at base than at apex, both at rest (49 ± 43 vs. –29 ± 19 ms, p < 0.0001) and at p.e. (46 ± 38 vs. –40 ± 22 ms, p < 0.0001), particularly in symptomatic patients (69 ± 44 vs. 32 ± 26, p < 0.0007). ΔtESRbase–apex correlated with longer QTc interval, lower ESR and attenuated LV stroke volume.ConclusionLQTS patients show reversed longitudinal relaxation sequence, which worsens with exercise, particularly in those with previous cardiac events.

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

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

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

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

Lipids: a Potential Molecular Pathway Towards Diastolic Dysfunction in Youth-Onset Type 2 Diabetes.

Obesity and type 2 diabetes (T2D) with onset in youth are emerging public health concerns. Youth with obesity and T2D are at risk for the development of heart failure with preserved ejection fraction (HFpEF) due to diabetes-related cardiomyopathy with evidence of precursor stages, namely diastolic dysfunction, present in youth. We review the literature regarding diastolic dysfunction in youth with obesity and T2D; discuss the potential mechanisms including the role of lipids, contractile proteins and their post-translational modifications, and conclude with studies to guide future treatments. The diabetes milieu namely hyperglycemia, hyperinsulinemia, and lipotoxicity favor development of diastolic dysfunction and HFpEF. Recent studies show HFpEF is associated with slow left ventricular relaxation and sarcomere stiffness induced by reduced calcium (Ca2+) and β-adrenergic responses. There are currently no effective therapies available for treating HFpEF. Targeting the sarcomere is an area of ongoing research.

Platelet-rich plasma exhibits anti-inflammatory effect and attenuates cardiomyocyte damage by reducing NF-κB and enhancing VEGF expression in isoproterenol induced cardiotoxicity model.

The present study investigated the cardioprotective effects of activated platelet-rich plasma (PRP) on high dose isoproterenol (ISO) induced cardiotoxicity. ISO was injected at a dose of 85 mg/kg/day, s.c. for 2 days. Cardiac function parameters including dp/dt max/min, left ventricular end diastolic pressure (LVEDP), relaxation constant (tau) and electrocardiogram (ECG) changes, anti-oxidant and membrane bound enzymes assays, pro-inflammatory cytokine levels, collagen content, immunohistochemical staining/gene expression of vascular endothelial growth factor (VEGF), cTnI (cardiac troponin I), NF-κB (nuclear factor kappa B), Smad-2/3, TGF-β (transforming growth factor), collagen-1/3 proteins were evaluated. PRP and platelet-poor plasma (PPP) were injected intramyocardially (200 μl in each ventricle region) 3 h after first dose of ISO under anesthesia. ISO injection induced cardiac dysfunction, hypertrophy, fibrosis, necrosis due to decline in anti-oxidant capacity, enhanced NF-κB and reduced cTnI immunostaining. However, the PRP injection attenuated these cardiac pathological changes by exerting anti-inflammatory properties and promoting cardiomyocyte repair.

Peri-operative changes in diastolic function and outcomes in congenital aortic valve surgery.

BackgroundThe ratio of early diastolic mitral inflow velocity (E) to early diastolic mitral annular tissue velocity (e’), or E/e’, is an echocardiographic measure of left ventricular filling pressure. Peri‐operative changes in E/e’ and association with outcomes have been demonstrated in adults undergoing surgery for aortic stenosis (AS). We sought to explore changes in E/e’ and other diastolic indices in the setting of congenital AS surgery and to assess for association with post‐operative outcomes among children and young adults.MethodsA retrospective, single‐center study was performed among patients 6 months to 30 years of age who underwent congenital AS surgery from 2006 to 2018. Tissue Doppler indices were collected from pre‐ and post‐operative echocardiograms. Post‐operative outcomes were reviewed.ResultsSixty‐six subjects with subvalvar (45%), valvar (47%), and supravalvar (8%) AS underwent surgery at a median age of 9.5 years (IQR: 4.0–14.8). Pre‐operatively, the lateral E/e’ ratio was 8.6 (6.7–11.0); 33% had E/e’≥10. Post‐operatively, the lateral e’ decreased to 9.9 cm/s (8.0–11.4), the E/e’ ratio increased to 10.4 (8.3–13.1); and 53% had E/e’≥10 (p‐values < 0.0001, 0.0072, and < 0.001, respectively). Pre‐operative lateral e’ correlated modestly with duration of intubation (ρ = −0.24, p‐value 0.048) and post‐operative lateral e’ correlated modestly with duration of intubation and length of hospital stay (ρ = −0.28 and −0.26, p‐values = 0.02 and 0.04, respectively).ConclusionsChildren and young adults who underwent congenital AS surgery had echocardiographic evidence of diastolic dysfunction pre‐operatively that worsened post‐operatively. Lateral e’ may be a sensitive indicator of impaired ventricular relaxation in these patients and may impact duration of intubation and hospital stay.

Effect of soya phosphatidylcholine and possible underlying mechanism on ischemia/reperfusion injury in isolated perfused rat heart: an experimental and computational study.

This study was designed to assess the effect of soya phosphatidylcholine (SPC) against ischemia/reperfusion (I/R) injury and the possible underlying mechanism using experimental and computational studies. I/R injury was induced by global ischemia for 30min followed by reperfusion for 120min. The perfusion of the SPC was performed for 10min before inducing global ischemia. In the mechanistic study, the involvement of specific cellular pathways was identified using various inhibitors such as ATP-dependent potassium channel (KATP) inhibitor (glibenclamide), protein kinase C (PKC) inhibitor (chelerythrine), non-selective nitric oxide synthase inhibitor (L-NAME), and endothelium remover (Triton X-100). The computational study of various ligands was performed on toll-like receptor 4 (TLR4) protein using AutoDock version 4.0. SPC (100 μM) significantly decreased the levels of cardiac damage markers and %infarction compared with the vehicle control (VC). Furthermore, cardiodynamics (indices of left ventricular contraction (dp/dtmax), indices of left ventricular relaxation (dp/dtmin), coronary flow, and antioxidant enzyme levels were significantly improved as compared with VC. This protective effect was attenuated by glibenclamide, chelerythrine, and Triton X-100, but it was not attenuated by L-NAME. The computational study showed a significant bonding affinity of SPC to the TLR4-MD2 complex. Thus, SPC reduced myocardial I/R injury in isolated perfused rat hearts, which might be governed by the KATP channel, PKC, endothelium response, and TLR4-MyD88 signaling pathway.

The Relationship Between Coronary Artery Tortuosity And Left Ventricular Diastolic Functions

Introduction: We aimed to evaluate the relationship between coronary tortuosity and left ventricular relaxation disorder using conventional and new diastolic function parameters evaluated with echocardiography. Methods: A total of 131 patients who underwent coronary angiography for suspected coronary artery disease were included in the study. We compared diastolic function parameters obtained in echocardiography of the patients with coronary artery tortuosity (CAT) and normal coronary arteries. Results: There was no correlation between conventionally measured diastolic functions and coronary tortuosity. However, we obtained significant findings with new diastolic function parameters such as myocardial performance index (MPI), early mitral inflow velocity, and mitral annular early diastolic velocity (E/e΄). Especially, in patients who had moderate or severe coronary tortuosity, there was a significant increase in anterior and septal wall MPI. The E/e΄ ratio was found to be significantly higher in patients with moderate–severe coronary tortuosity. Discussion and Conclusion: CAT is common in invasive cardiology. Tissue Doppler echocardiography may be useful in determining diastolic dysfunction in these patients.

Chemotherapy-Induced Arrhythmias.

Cardio-oncology is a subspeciality within cardiology that has developed primarily as a consequence of the cardiovascular implications of cancer and its therapeutics. Arrhythmias are increasingly recognized as an adverse feature of many chemotherapeutic agents. This relationship is poorly defined and studied in the literature compared with other side effects of chemotherapy. In this review, we appraise the published literature on arrhythmogenic consequences of chemotherapeutic agents and summarize the available evidence. Atrial fibrillation (AF) and other supraventricular tachycardias are frequently observed in patients receiving chemotherapy. High rates of AF are seen with certain agents such as tyrosine kinase inhibitors eg, ibrutinib and the mechanism for this is poorly defined but likely related to off-target effects. The management of AF in cardio-oncology is similar to that of the noncancer patient with certain nuances. Mainly that bleeding and stroke risk stratification tools are not validated in the cancer population. In this patient cohort, treatment decisions are usually led by anecdotal evidence rather than an evidence base. This leads to treatment heterogeneity between clinicians. Furthermore, various drug interactions can limit the choice of therapy, particularly with respect to anticoagulant drugs. Many chemotherapeutic agents have been implicated in QT interval (A Measurement calculated from the start of the Q wave to the end of the T wave on the electrocardiogram approximating the time taken for ventricular relaxation.) of these, arsenic trioxide and several tyrosine kinase inhibitors are classic culprits. In patients receiving these agents, it is advisable to perform a baseline electrocardiogram and monitor the QT interval. If the (QT interval corrected for heart rate) increases by 60 milliseconds from baseline or is greater than 500 milliseconds, it is advisable to suspend treatment temporarily. Moving forward, further trials are required in the field of cardio-oncology to better understand the relationship between chemotherapeutic agents and arrhythmia.

Effect of arterial hypertension on quality of life and anxiety in middle-aged patients with breast cancer

BACKGROUND: Arterial hypertension is one of the key risk factors for the development of cardiotoxicity in cancer patients. The importance for patients with left breast cancer is due to the possibility of the heart getting into the radiation area during treatment. The use of a method for assessing the quality of life and symptoms of anxiety can help improve treatment in such patients by increasing the interaction between a physician and a patient.&#x0D; AIM: The aim of the study is to assess the quality of life and the level of anxiety in patients with breast cancer, depending on the presence of arterial hypertension.&#x0D; MATERIALS AND METHODS: 67 patients with HER2neu negative cancer of the left breast have been examined. The average age is 42 (47; 63). All the patients after radical mastectomy and a course of chemotherapy with the inclusion of doxorubicin in a cumulative dose of no more than 360 mg/m2 have been hospitalized for 3D conformal radiation therapy. The first group included 32 patients with grade III comorbid hypertension; the second group included 35 patients without hypertension. The examination included an assessment of the status of an oncological patient according to the ECOG scale, echocardiography with an assessment of diastolic function, determination of the level of reactive and personal anxiety according to the Spielberger Khanin scale and quality of life using the SF-36 questionnaire.&#x0D; RESULTS: In the group of the patients with combined hypertension, left ventricular hypertrophy has been detected in 48 % of cases. In the patients of both groups with preserved ejection fraction, type I diastolic dysfunction has been detected (E/A 1): in the patients of the first group in 59.4 % of cases, in the patients of the second 31.4 % of cases. The difference obtained is due to the effect of hypertension on the left ventricular relaxation disorder. The level of reactive anxiety was significantly higher in the patients of the first group and amounted to 43.8 (41.2; 46.2) versus 38.4 (32.7; 42.6) points in the second group. The level of personal anxiety was high in the patients of both groups, which can be explained by the predominant influence of cancer. In the patients of both groups, there was a decrease in indicators according to the SF-36 questionnaire on all scales. The most significant changes have been obtained on the scales of physical functioning, role-based physical functioning, pain, vitality and general health. Cancer patients with concomitant hypertension rated their health status lower, while they are more likely to note a decrease in daily role activity as a result of their emotional state.&#x0D; CONCLUSIONS: The data obtained indicate that arterial hypertension has a significant negative effect on the level of reactive anxiety and quality of life indicators of breast cancer patients, which is of great importance in the formation of a patient-oriented approach to the therapeutic support of specific treatment in such patients.

Mid-Diastolic Events (L Events): A Critical Review.

Mid-diastolic events (L events) include three phenomena appreciable on echocardiography occurring during diastasis: mid-diastolic transmitral flow velocity (L wave), mid-diastolic mitral valve motion (L motion), and mid-diastolic mitral annular velocity (L’ wave). L wave is a known marker of advanced diastolic dysfunction in different pathological clinical settings such as left ventricle and atrial remodeling, overloaded states, and cardiomyopathies. Patients with L events have poor outcomes with a higher risk of developing heart failure symptoms and arrhythmic complications, including sudden cardiac death. The exact mechanism underlying the genesis of mid-diastolic events is not fully understood, just as the significance of these events in healthy young people or their presence at the tricuspid valve level. We also report an explicative case of a patient with L events studied using speckle tracking imaging of the left atrium and ventricle at the same reference heartbeat supporting the hypothesis of a post-early diastolic relaxation or a “two-step” ventricular relaxation for L wave genesis. Our paper seeks to extend knowledge about the pathophysiological mechanisms on mid-diastolic events and summarizes the current knowledge.