Ventricular Malfunction Research Articles

Kaempferol protects against cardiovascular abnormalities induced by nitric oxide deficiency in rats by suppressing the TNF-α pathway

Kaempferol is a natural flavonoid compound that exhibits various pharmacological actions. However, there are few reports regarding the role of kaempferol in cardiovascular abnormalities. This study aimed to assess whether kaempferol could prevent cardiovascular malfunction and hypertrophy provoked by chronic inhibition of nitric oxide (NO) formation in rats. Rats (180–200 g) were treated daily with Nω-nitro-L-arginine methyl ester hydrochloride (L-NAME) (40 mg/kg, in drinking water) for five weeks concomitant with kaempferol (oral administration) at a dose of 20 mg/kg or 40 mg/kg or lisinopril (5 mg/kg). Kaempferol partially prevented the progression of hypertension provoked by NO inhibition (p < 0.05). Left ventricular malfunction and hypertrophy present in hypertensive rats were alleviated by concurrent administration of kaempferol (p < 0.05). Furthermore, L-NAME rats had increased sympathetic nerve-mediated vasoconstriction and decreased acetylcholine-induced vasorelaxation and aortic wall thickening, which were resolved by kaempferol treatment (p < 0.05). Kaempferol restored tissue superoxide formation, malondialdehyde, catalase activity, plasma nitric oxide metabolites, tumor necrosis factor-alpha (TNF-α) and interleukin-6 in L-NAME rats (p < 0.05). Overexpression of tumor necrosis factor receptor 2 (TNFR2), phosphatidylinositol 3-kinases (PI3K), AKT serine/threonine kinase 1 (Akt1) and smad2/3 in heart tissue and upregulation of tumor necrosis factor receptor 1 (TNFR1), phosphorylated nuclear factor-kappaB (p–NF–κB) and transforming growth factor beta 1 (TGF-β1) in vascular tissue were suppressed by kaempferol (p < 0.05). In conclusion, kaempferol exerts antihypertensive, cardioprotective, antioxidant, and anti-inflammatory effects in NO-dependent hypertensive rats. The underlying mechanisms of kaempferol in preventing cardiovascular changes induced by L-NAME were due to the suppression of the TNF-α pathway.

Efficacy of Sacubitril/Valsartan versus Losartan in Heart Failure Patients with Respect to Improvements in Ejection Fraction and New York Heart Association Functional Class

Background: Heart failure (HF) is a complicated clinical disease that develops when the Left ventricular becomes symptomatic due to anatomical or functional ventricular malfunction. The symptoms emerge from a cardiac output that is insufficient to meet the body's metabolic needs. Globally, HF has emerged as a major health issue, with an estimated prevalence of &gt;37.7 million. While HF with reduced ejection fraction (HFrEF) is more frequently seen in Indian patients, HF with preserved EF seems to be more prevalent in the western population. Objective: This study was conducted to determine the efficacy of sacubitril/valsartan (S/V) versus losartan in patients with HF with respect to improvements in EF and New York Heart Association (NYHA) functional class symptoms. Materials and Methods: A prospective cohort study was conducted on 62 HF patients who are either on angiotensin receptor-neprilysin inhibitor or angiotensin receptor blocker therapy for a period of 6 months, i.e., November 2021 to April 2022, who attended the Inpatient Cardiology Department of Narayana Medical College and Hospital. By using a semi-structured questionnaire, the data was gathered. The 2013 edition of Microsoft Excel and SPSS version 20.0 software were used for data analysis. Results: Subjects in the S/V group showed a 56% reduction in subjects with HFrEF from the beginning to end of the follow-up, while subjects in the losartan group showed only 16% reduction. With respect to NYHA functional class, subjects in the S/V group showed greater reduction in subjects in NYHA class III and NYHA class IV by the end of follow-up when compared to the losartan group. Conclusion: S/V showed better efficacy in improving EF and NYHA functional class when compared to losartan.

High Sensitivity Troponin in Infarcted Patients with History of Myocardial In-farction

Design of the Study: Historical Cohort.&#x0D; Objectives: This study aimed to verify which risk factors contribute to increase hs-cTnI in patients with Myocardial Infarcion with ST segment elevation, to ana-lyze which prognostic impacts it may have and to evaluate troponin levels in pa-tients that had previous acute myocardial infarction and assess how this com-pared to patients without previous history of an acute event.&#x0D; Methodology: It was assessed medical records of patients admitted in the Cor-onary Unit of the Hospital de Clínicas (HC-UFPR) in Curitiba, South of Brazil, diagnosed with ST segment elevation Myocardial Infarction and whose serum levels of high sensitivity troponin I (hs-cTnI) were collected at admission moment. The select data were: gender, age, high blood pressure, smoking, diabetes, previous myocardial infarction, dyslipidemia and serum levels of high sensitivity troponin I. For prognostic proposes, it was analysed intra-hospital death and ventricular function, based on left ventricular ejection fraction.&#x0D; Findings: Patients admitted with previous myocardial infarction had lower levels of hs-TnI. Gender, age, presence of high blood pressure, tabagism, diabetes and dyslipidemia didn’t reveal correlation with troponin values, allowing the in-ference that high sensitivity troponin values at first presentation of these patients have no direct relation to these variables. Regarding prognosis, levels of high sensitivity troponin could not be associated to mortality or ventricular malfunction.&#x0D; Conclusions: At admission, high-sensitivity troponin I levels were lower in pa-tients with prior myocardial infarction.&#x0D; Relevance: This work correlates the values of the high-sensitivity troponin of patients with ST segment Elevation Myocardial Infarction to cardiovascular risks factors and to the prognosis of these patients. This approach is not found in cur-rent medical literature, whose works mainly relates to acute events.

Supervised learning approach for tracking quality determination of transmural and segmental time strain curves: A feasibility study

Quantitative assessment of global and regional left ventricle function by means of myocardial strain estimation has been widely discussed as promising clinical diagnostic markers of left ventricular malfunction. These markers are provided to the clinicians without much feedback regarding their reliability, which may lead to erroneous diagnosis. Therefore, this study aims to classify the calculated strain curves into reliable or artefactual ones, before their clinical adaptation.A supervised machine learning approach is utilized for the classification process. A total of 6,552 strain curves were used, for which a visual labeling protocol was defined and utilized by two experts.An inter-observer labeling concordance of 93% was obtained, and a classification accuracy of 90% was achieved with a specificity of 92% and sensitivity of 78%.This classification tool may enhance the reliability of the estimations of global, transmural and regional strain curves, by automatically classifying them into physiological or artefactual curves.

ASSA13-13-2 OptiVol Fluid Index Predicts Acute Decompensation of Heart Failure with High Unexplained Events Rate

<h3>Background and Objective</h3> Intrathoracic impedance monitoring system had emerged as a new promising technique for detection impending heart failure (HF). Most commonly reported sensitivity in trials ranging between 76% and 83%. As all these researches carried out in patients with left ventricular malfunction, it is unknown the practical value of this system involving patients with preserved or regained left ventricular function. The aim of this study is to investigate the incidence of OptiVol alert episodes in real world clinical practise. <h3>Methods</h3> 43 patients (mean age 57 ± 15 years, LVEF 33 ± 14%) undertook ICD or CRT-D implantation with feature of intrathoracic impedance monitoring system (Medtronic Inc, Minneapolis, MN, US) in our single centre from Sep 2010 to Oct 2012. All patients required in-office follow-up regularly and routinely in month 3, 6, 12 and every 12 months after that. Once alert events occurred and reported, unscheduled follow-up arranged. History taking, device interrogation, NT-proBNP measurement and echocardiogram were collected during each clinic interview. Worsening HF was defined as hospitalisation or presentation of symptoms or signs of HF. <h3>Results</h3> 54 alert events and 14 adjudicated worsening HF detected within 288 ± 163 days follow-up duration. 11 (20.4%) alert episodes associated with acute decompensation in 9 patients with a positive predictive value of 78.6%. 43 audible alerts showed no connexion to worsening HF. The unexplained alerts rate was 79.6% and 1.27 per person-year. 37 alarm alerts detected in patients with EF with HF, 17 alerts detected in patients with LVEF ≥45% and 2 associated with HF. There was no significant difference between the two groups (9/37 versus 2/17, p = 0.47). <h3>Conclusions</h3> Patients with normal or nearly normal left ventricular systolic function also exhibited considerable alert events. OptiVol fluid index predicted cardiac worsening events with high unexplained detection rate and any alert need to be analysed with great caution. Efforts to improve the specificity of this monitoring system represent a significant aspect in future study.

Loss of Cardiac microRNA-Mediated Regulation Leads to Dilated Cardiomyopathy and Heart Failure

Heart failure is a deadly and devastating disease that places immense costs on an aging society. To develop therapies aimed at rescuing the failing heart, it is important to understand the molecular mechanisms underlying cardiomyocyte structure and function. microRNAs are important regulators of gene expression, and we sought to define the global contributions made by microRNAs toward maintaining cardiomyocyte integrity. First, we performed deep sequencing analysis to catalog the miRNA population in the adult heart. Second, we genetically deleted, in cardiac myocytes, an essential component of the machinery that is required to generate miRNAs. Deep sequencing of miRNAs from the heart revealed the enrichment of a small number of microRNAs with one, miR-1, accounting for 40% of all microRNAs. Cardiomyocyte-specific deletion of dgcr8, a gene required for microRNA biogenesis, revealed a fully penetrant phenotype that begins with left ventricular malfunction progressing to a dilated cardiomyopathy and premature lethality. These observations reveal a critical role for microRNAs in maintaining cardiac function in mature cardiomyocytes and raise the possibility that only a handful of microRNAs may ultimately be responsible for the dramatic cardiac phenotype seen in the absence of dgcr8.

The Kidney

Today, it is universally acknowledged that, in hypertension, the kidney is both culprit and victim.1 Kidney malfunction causes hypertension, and hypertension, in turn, aggravates chronic kidney disease (CKD) and accelerates its progression. High blood pressure (frank hypertension and blood pressure values in the high normal range) are clearly correlated to progressive kidney injury, both in experimental2 and in clinical3 observations. All of the current guidelines4,5 recommend lowering of systolic blood pressure to 130 or 125 mm Hg in CKD, and even lower values are recommended if the target level of proteinuria of <1 g per 24 hours has not been achieved.4 There is good evidence of “renoprotection” by lowering blood pressure in patients with renal disease, at least in the presence of proteinuria.3 In CKD patients without proteinuria, eg, autosomal polycystic kidney disease, further renoprotection cannot be achieved by lowering blood pressure below the target blood pressure recommended in patients without CKD6; nevertheless, these patients have a markedly elevated cardiovascular risk, and more stringent lowering of blood pressure is desirable, because, eg, reduction of left ventricular hypertrophy as an index of cardiovascular risk had been documented in such patients.6 The worldwide problem of neglect of hypertension and of insufficient implementation of antihypertensive treatment in CKD patients prompted the International Society of Nephrology and the International Federation of Kidney Foundations to devote this year’s World Kidney Day (http://www.worldkidneyday.org) on March 12th to the issue …

Echocardiographic Evaluation of the Evolutionary Changes After Heart Transplantation

Aim To undertake an evolutionary analysis of echocardiographic examinations carried out during follow-up of cardiac transplant patients. Materials and methods The study included 193 consecutive patients transplanted between August 1998 and December 2004. We excluded pediatric, cardiopulmonary, and repeat transplants. Four echocardiographic examinations were analyzed per patient (first, second, third quarter and the last study carried out; average time from transplant: 1115 ± 681 days). The total number of examinations was 772. The evaluated variables were thickness of walls and diameters of the cavities, systolic and diastolic functions, pericardial effusion, and number of rejections. Results The isovolumetric relaxation time showed reduced values during early echocardiography with subsequent increases during evolution (first echocardiogram: 92 ± 16 vs final echocardiogram 101 ± 16 ms; P < .0001). Right ventricular function showed initial deterioration with subsequent recovery (first echocardiogram: 16% vs final echocardiogram: 8%; P < .05); moreover, the existence of delayed malfunction of the right ventricle was correlated with a higher incidence of transplant rejection ( P < .01). Pericardial effusion was initially present with a tendency to reduce over time (first echocardiogram: 58% vs final echocardiogram: 12%; P < .0001). There was no difference in the other variables. Conclusions Cardiac transplant patients undergo evolutionary echocardiogram alterations that were mainly early and normalized as of the first quarter. The most usual changes in this period were restrictive isovolumetric behavior accompanied by some degree of depressed right ventricular function. Right ventricular malfunction during late evolution was correlated with a higher incidence of transplant rejection during follow-up.

Myocardial motion analysis from B-mode echocardiograms

The quantitative assessment of cardiac motion is a fundamental concept to evaluate ventricular malfunction. We present a new optical-flow-based method for estimating heart motion from two-dimensional echocardiographic sequences. To account for typical heart motions, such as contraction/expansion and shear, we analyze the images locally by using a local-affine model for the velocity in space and a linear model in time. The regional motion parameters are estimated in the least-squares sense inside a sliding spatiotemporal B-spline window. Robustness and spatial adaptability is achieved by estimating the model parameters at multiple scales within a coarse-to-fine multiresoluion framework. We use a wavelet-like algorithm for computing B-spline-weighted inner products and moments at dyadic scales to increase computational efficiency. In order to characterize myocardial contractility and to simplify the detection of myocardial dysfunction, the radial component of the velocity with respect to a reference point is color coded and visualized inside a time-varying region of interest. The algorithm was first validated on synthetic data sets that simulate a beating heart with a speckle-like appearance of echocardiograms. The ability to estimate motion from real ultrasound sequences was demonstrated by a rotating phantom experiment. The method was also applied to a set of in vivo echocardiograms from an animal study. Motion estimation results were in good agreement with the expert echocardiographic reading.

Renal dysfunction as a novel risk factor: Microalbuminuria and cardiovascular risk

only for elevated glucose or BMI values; the correlation extends well into the range of normal values. Apparently, the metabolic syndrome and microalbuminuria are tightly correlated with each other. This relation is of considerable interest because in patients with renal disease insulin resistance is found even in the very early stages [10], and even when GFR is still within the normal range (unpublished observations). Conversely, in a population sample it was found that insulin resistance (according to the HOMA index) was associated with a higher risk of chronic kidney disease [11]. The information obtained from microalbuminuria cannot be replaced by estimating the glomerular filtration rate. Although the reports in the literature are not entirely consistent, the study in Groningen showed that with increasing quantiles of urinary albumin excretion, the creatinine clearance tended to be higher and was lower only in the uppermost quantiles [12]. Although the creatinine clearance is not a reliable index of glomerular filtration, this observation would be plausible in view of a similar relation between GFR and albuminuria noted previously in diabetic patients [13]. There has been much discussion whether microalbuminuria reflects primarily a generalized endothelial cell dysfunction, as suggested by the Steno hypothesis [14], or whether it reflects a podocyte defect, as proposed more recently [15]. The observation that the rate of albumin escape from the plasma space is increased in patients with microalbuminuria [16] argues for the former possibility. The observation that the risk of being microalbuminuric was significantly higher for carriers of the Q-genotype of the 229 polymorphism of the podocin gene at any given level of body mass index or other correlates of microalbuminuria is more in favor of a podocyte problem [15].

Early increase in blood pressure and diastolic left ventricular malfunction in patients with glomerulonephritis

In patients with diabetic nephropathy blood pressure increases progressively before the conventional threshold of normal blood pressure (140/90 mm Hg) is transgressed. In patients with glomerulonephritis, no information on this point is available. To clarify this issue we sequentially examined 20 untreated patients with biopsy-proven primary chronic glomerulonephritis (GN) who had casual blood pressure below 140/90 mm Hg and normal GFR by inulin clearance. Patients were compared with normotensive healthy controls who were matched for BMI, gender and age. We measured ambulatory 24-hour blood pressure (SpaceLab system), echocardiography (ASE criteria, Acuson 128 XP 10), CIn and CPAH, urinary Na excretion, PRA and insulin concentration. In patients with GN, the median 24 hour (P < 0.0005), daytime (P < 0.001) and nocturnal sleeping time (P < 0.0001) MAP values were significantly higher than in matched controls (daytime, mean 97 mm Hg, 85 to 106 GN vs. 89 controls range 82 to 102; nocturnal sleeping time, mean 80.3 mm Hg, 71 to 89.5 GN vs. 73 controls, range 63 to 84). Echocardiographic examination showed significantly greater posterior wall thickness (P < 0.01) and ventricular septal thickness (P < 0.003). In addition the early diastolic to late diastolic (E/A) ratio of mitral valve peak inflow velocity was significantly (P < 0.0008) lower in patients. The data point to left ventricular wall thickening accompanied by LV diastolic malfunction. The study documents elevated ambulatory blood pressure in patients with primary chronic glomerulonephritis despite normal body weight and normal GFR. This is associated with evidence of target organ damage in the heart. The findings suggest that in patients with glomerulonephritis blood pressure increases initially within the normotensive range. This observation in conjunction with evidence of early target organ changes provides an argument for early antihypertensive intervention, but controlled trials to test efficacy and safety of this proposal are necessary.

Effects of Platelet-Activating Factor on Myocardial Contraction and Myocardial Relaxation of Isolated Perfused Guinea Pig Hearts

Platelet-activating factor (PAF) is an important mediator of cardiovascular shock owing to immunologic reactions, including anaphylaxis and endotoxaemia. Previous studies have shown that PAF is a potent cardio-depressive agent causing a marked coronary constriction and a sustained impairment of myocardial contractility. In this study, we attempted to characterize further the prolonged PAF effects on coronary circulation and myocardial contractile force in isolated guinea pig hearts perfused at constant pressure (60 cm H2O) or constant flow which was adjusted to a level of 100% above basal flow. In addition, the PAF-induced changes of ventricular systolic and diastolic function were distinguished. In the hearts perfused at constant pressure, PAF induced a dose-dependent (0.57, 5.7, and 57 pmol/min) decrease of coronary flow rates, left ventricular pressure (LVP), LV contraction (peak positive dP/dt) and LV relaxation (peak negative dP/dt). The decrement of peak negative dP/dt was more pronounced than that of peak positive dP/dt. Maintenance of coronary flow rates only attenuated, but did not suppress, the PAF-induced ventricular malfunction, and it improved ventricular relaxation less than it did ventricular contraction. Pretreatment with the PAF antagonist WEB 2086 (19.7 nmol/min) almost completely abolished the effects of the highest PAF dose on coronary circulation and ventricular contractile parameters. We conclude that the cardiodepressive effects of PAF are due to coronary constriction and direct contractile events. Furthermore, PAF impairs ventricular diastolic function more than ventricular systolic function.

Valvular aortic stenosis. A clinical and hemodynamic profile of patients.

We retrospectively reviewed the clinical and hemodynamic findings in 397 patients with valvular aortic stenosis at their first hemodynamic evaluation. This series is considered representative of aortic stenosis because it is heavily weighted toward older patients (average age, 61.1 years) and severe aortic stenosis (87.3% of patients had aortic valve area less than 1 cm2). We identified two categories of symptoms: angina and syncope, which develop during a fully compensated stage of aortic stenosis ("prefailure symptoms"); and dyspnea or congestive failure, which signifies various degrees of left ventricular malfunction. The preponderance of soft or medium intensity systolic murmur and normal or widened pulse pressure emphasizes the changing clinical picture of aortic stenosis in an aging population. Coexisting coronary artery disease was found in 60% of patients, but those with and without coronary disease did not differ significantly, even in the presence of angina.

Dialysis Hypotension—Is It Related to Diastolic Left Ventricular Malfunction?

Dialysis Hypotension—Is It Related to Diastolic Left Ventricular Malfunction?

The “bad” left ventricle: Results of coronary surgery and effect on late survival

Between 1968 and 1971, 252 patients with severe ventricular malfunction underwent revascularization surgery. By means of single-plane ventriculography, the ventricle was divided into six segments, three anteriorly and three inferiorly, and ejection fractions were calculated. Patients were classified into four groups according to these observations. Results were assessed in regard to relief of angina, graft patency status, surgical mortality rate, and survival as determined by actuarial life-table analysis. These results were then compared to over-all medical and surgical experience contained in the Milwaukee Cardiovascular Data Registry as well as to other reported series of medical treatment for similar degrees of coronary artery disease and impairment of left ventricular function. Comparison between the surgical and medical series suggests improved survival and improved quality of life in the surgically treated patients. Thus many patients with severe ventricular malfunction, especially if associated with angina, can be reasonably considered candidates for surgery.

Isolated aortic stenosis in the neonate. Natural history and hemodynamic considerations.

We have reviewed the clinical and catheterization data and pathologic findings in ten infants under one month of age with isolated severe aortic valve stenosis. All presented with evidence of progressive cardiac failure and diminished cardiac output. A hyperdynamic right ventricular impulse was present in nine infants who were subsequently shown to have a left-to-right atrial shunt, through a stretched patent foramen ovale. Calculated aortic valve area ranged from 0.12 cm 2 /m 2 to 0.29 cm 2 /m 2 . Three patients died prior to surgical intervention because of low cardiac output and refractory metabolic acidosis. Aortic valvotomy was attempted in the remaining seven. Five died intraoperatively or in the immediate postoperative period and one other died six months after surgery. Necropsy was obtained in all nine patients who died. We believe that, in this group, the clinical course reflects fetal and postnatal hemodynamics. We have discussed the probable hemodynamic factors which occur and have related them to the morphological development of aortic stenosis in these infants. The poor prognosis of these patients probably results from a combination of factors which include left ventricular outflow obstruction, often associated with a small aortic annulus, a markedly thickened left ventricle, and left ventricular malfunction secondary to subendocardial ischemia and/or endocardial fibroelastosis.

Surgical resection of nonfunctioning ventricular segments

Summary When significant occlusive disease of the anterior descending branch of the left coronary artery occurs, it often produces localized ventricular malfunction on the anterolateral aspect of the left ventricle. This malfunction may be manifest as severe dyskinesia, akinesia, or asynergic contraction. Modern technics of ventriculography and coronary cinearteriography allow the diagnosis of segmental ventricular malfunction. When these malfunctioning areas are located on the anterolateral aspect of the left ventricle they are accessible for surgical excision. Clinically significant noncontracting segments of the left ventricle produce measurable reduction of cardiac output and the patients are usually in chronic borderline left heart failur, unable to increase their cardiac output. This report covers our experience with resection of noncontracting segments of the left ventricle, which has included thirty-three cases. One of these was excision of an acute paradoxing myocardial infarct which occurred during open heart surgery for valve replacement. Concomitant operations for myocardial revascularization were carried out in many of these patients. This disease process appears to be progressive and an aggressive surgical approach is indicated.