Left Ventricular Contractile Function Research Articles

Remodelling and functional features of the left ventricle in miners

Introduction. Diseases of the circulatory system are the main cause of mortality in the employable population. Preserving occupational longevity involves the identification of early signs of myocardial damage by modern techniques, which will allow taking a fresh look at the prevention of cardiovascular pathology in people engaged in harmful working conditions. Materials and methods. The study included two hundred thirty six miners of average age of 47.1±0.36 years who underwent periodic medical examination at the Institute clinic. The work experience in hazardous occupation conditions was 22.7±0.6 years. The study was based on transthoracic echocardiography using tissue Dopplerography and speckle tracking technology. Results. Concentric remodelling of the left ventricle was detected in 25.9% of the miners. Arterial hypertension was revealed in 65.6% of the miners with concentric remodelling of the left ventricle versus 34.3% of the miners with its normal geometry (p=0.00002). There were no significant differences in the left ventricular contractile function indices in the groups. In both groups, diastolic dysfunction type 1 was predominantly detected, which was significantly more common in the miners with concentric remodelling of the left ventricle (62.3% and 42.0%, p=0.006). Pseudonormal type of diastolic dysfunction occurred in 8.2% of the group with concentric remodelling versus 5.14% with normal left ventricular geometry, p= 0.38. Limitations. The study was limited by the number of the examined persons undergoing periodic medical examination at the Research Institute for Complex Problems of Hygiene and Occupational Diseases. Conclusion. Remodelling of the left ventricular myocardium in miners did not correlate with a decrease in the longitudinal deformation of the left ventricle, which indicates the possible influence of harmful occupational factors on the development of its systolic dysfunction. Diastolic dysfunction of the left ventricle had a clear relationship with remodelling of the left ventricular myocardium. In this regard, it is recommended to conduct echocardiography during an in-depth periodic medical examination of miners with long-term work experience to identify a risk group for developing cardiovascular accidents.

Chronic sleep fragmentation reduces left ventricular contractile function and alters gene expression related to innate immune response and circadian rhythm in the mouse heart

Sleep disorders have emerged as a widespread public health concern, primarily due to their association with an increased risk of developing cardiovascular diseases. Our previous research indicated a potential direct impact of insufficient sleep duration on cardiac remodeling in children and adolescents. Nevertheless, the underlying mechanisms behind the link between sleep fragmentation (SF) and cardiac abnormalities remain unclear. In this study, we aimed to investigate the effects of SF interventions at various life stages on cardiac structure and function, as well as to identify genes associated with SF-induced cardiac dysfunction. To achieve this, we established mouse models of chronic SF and two-week sleep recovery (SR). Our results revealed that chronic SF significantly compromised left ventricular contractile function across different life stages, leading to alterations in cardiac structure and ventricular remodeling, particularly during early life stages. Moreover, microarray analysis of mouse heart tissue identified two significant modules and nine hub genes (Ddx60, Irf9, Oasl2, Rnf213, Cmpk2, Stat2, Parp14, Gbp3, and Herc6) through protein–protein interaction analysis. Notably, the interactome predominantly involved innate immune responses. Importantly, all hub genes lost significance following SR. The second module primarily consisted of circadian clock genes, and real-time PCR validation demonstrated significant upregulation of Arntl, Dbp, and Cry1 after SF, while subsequent SR restored normal Arntl expression. Furthermore, the expression levels of four hub genes (Ddx60, Irf9, Oasl2, and Cmpk2) and three circadian clock genes (Arntl, Dbp, and Cry1) exhibited correlations with structural and functional echocardiographic parameters. Overall, our findings suggest that SF impairs left ventricular contractile function and ventricular remodeling during early life stages, and this may be mediated by modulation of the innate immune response and circadian rhythm. Importantly, our findings suggest that a short period of SR can alleviate the detrimental effects of SF on the cardiac immune response, while the influence of SF on circadian rhythm appears to be more persistent. These findings underscore the importance of good sleep for maintaining cardiac health, particularly during early life stages.

Influence of mitral transcatheter edge-to-edge repair in patients with severe mitral regurgitation on left ventricle function

Aim. To study the changes of left ventricular (LV) contractile function in patients with severe mitral valve (MV) insufficiency with assessment of global longitudinal strain (GLS) indicators and LV myocardial function after the mitral transcatheter edge-to-edge repair (TEER) within 12-month follow-up.Material and methods. The study consisted of 43 patients with severe mitral regurgitation (MR) as follows: 23 patients with functional MR (FMR), 20 patients with degenerative MR (DMR). A comprehensive echocardiographic study, including speckle tracking echocardiography, was performed at baseline, 4-5 days, 6 and 12 months after TEER. Standard structural and functional indicators of the LV, LV GLS and myocardial performance parameters were assessed.Results. The early postoperative period (4-5 days) was characterized by a decrease in global constructive work (GCW) (FMR group — from 977 [684; 1253] to 857 [736; 1488] mm Hg%, (p=0,038); DMR group — from 1458 [1283; 1848] to 1350 [1010; 1488] mm Hg% (p=0,011)), an increase in global wasted work (GWW) (FMR group — from 177 [130; 280] to 336 [242; 388] mm Hg% (p=0,004); DMR group — from 128 [81; 172] to 216 [164; 279] mm Hg% (p=0,043)), which was accompanied by a decrease in myocardial efficiency (FMR group — from 81,5 [77; 87] to 76 [73; 79]%, (p=0,021); DMR group — from 90 [85; 93] to 82 [79; 85]% (p=0,018)). After 12-month follow-up, there was a significant increase in GCW relative to the initial values in both cohorts of patients as follows: FMR group — to 1128 [890; 1711] mm Hg% (p=0,048); DMR group — to 1818 [1478; 2034] mm Hg% (p<0,001). There was also an increase in GWW in the FMR group to 255 [214; 363] mm Hg% (p=0,024) and in the DMR group to 230 [140; 270] mm Hg% (p=0,043). There were no significant improvement of LV GLS in both groups.Conclusion. The early postoperative period after TEER was characterized by a temporary deterioration in all LV performance parameters, which recovered by 6 and 12 months of follow-up. Myocardial function restoration by one year of follow-up was noted due to an increase in GCW. LV GLS and ejection fraction did not change significantly by 1 year of follow-up compared to baseline values.

Correlation of left ventricular contractile function with the presence of collateral coronary circulation in non-reperfused acute myocardial infarction

To assess the association between coronary collateral circulation and ventricular contractile function in patients with non-reperfused acute myocardial infarction. A retrospective and descriptive clinical study was conducted on patients with ST-elevation myocardial infarction (STEMI) at a reference cardiovascular center, from January 2006 to December 2022. Coronary angiographies and echocardiograms were reviewed to evaluate coronary collateral circulation and ventricular function, respectively. Patients were divided into groups based on the presence of collateral circulation. Both groups were compared and mortality during the index hospitalization was analyzed. Out of a total of 14,985 patients with acute coronary syndrome, 8134 (54.3%) had the diagnosis of STEMI. We excluded 12,880, leaving a total of 2105 non-reperfused STEMI patients who underwent coronary angiography, revealing lesions. There were more patients without collateral circulation: 1547 (73.5%) vs. 558 (26.5%) (p = 0.025). Patients without collateral circulation had a higher left ventricular ejection fraction (median of 47% vs. 42%; p < 0.001). Mortality in patients with collateral circulation was higher compared to those without it (11.6% vs. 9.8%; p = 0.225), but statistical significance was not reached. Non-reperfused STEMI patients did not show protection from collateral circulation when assessing left ventricular systolic function. We did not find a difference in mortality compared to the population without development of collateral circulation.

Progressive Left Ventricular Remodeling for Predicting Mortality in Children With Dilated Cardiomyopathy: The Pediatric Cardiomyopathy Registry.

Pediatric dilated cardiomyopathy often leads to death or cardiac transplantation. We sought to determine whether changes in left ventricular (LV) end-diastolic dimension (LVEDD), LV end-diastolic posterior wall thickness, and LV fractional shortening (LVFS) over time may help predict adverse outcomes. We studied children up to 18 years old with dilated cardiomyopathy, enrolled between 1990 and 2009 in the Pediatric Cardiomyopathy Registry. Changes in LVFS, LVEDD, LV end-diastolic posterior wall thickness, and the LV end-diastolic posterior wall thickness:LVEDD ratio between baseline and follow-up echocardiograms acquired ≈1 year after diagnosis were determined for children who, at the 1-year follow-up had died, received a heart transplant, or were alive and transplant-free. Within 1 year after diagnosis, 40 (5.0%) of the 794 eligible children had died, 117 (14.7%) had undergone cardiac transplantation, and 585 (73.7%) had survived without transplantation. At diagnosis, survivors had higher median LVFS and lower median LVEDD Z scores. Median LVFS and LVEDD Z scores improved among survivors (Z score changes of +2.6 and -1.1, respectively) but remained stable or worsened in the other 2 groups. The LV end-diastolic posterior wall thickness:LVEDD ratio increased in survivors only, suggesting beneficial reverse LV remodeling. The risk for death or cardiac transplantation up to 7 years later was lower when LVFS was improved at 1 year (hazard ratio [HR], 0.83; P=0.004) but was higher in those with progressive LV dilation (HR, 1.45; P<0.001). Progressive deterioration in LV contractile function and increasing LV dilation are associated with both early and continuing mortality in children with dilated cardiomyopathy. Serial echocardiographic monitoring of these children is therefore indicated. URL: https://www.clinicaltrials.gov; Unique identifier: NCT00005391.

Protective effects of 4-methylumbelliferone on myocardial ischemia/reperfusion injury in rats through inhibition of oxidative stress and downregulation of TLR4/NF-κB/NLRP3 signaling pathway.

Myocardial ischemia-reperfusion injury (MI/R) has been found to be one of the important risk factors for global cardiac mortality and morbidity. The study was conducted to inquire into the protective effect of 4-methylumbilliferon (4-MU) against MI/R in rats and clarify its potential underlying mechanism. Animals were divided into four groups (n = 15) including sham, MI/R, MI/R + vehicle, and MI/R + 4-MU. MI/R was established in Wistar rats by occluding the left anterior descending (LAD) coronary artery for 30min. 4-MU (25mg/kg) was injected intraperitoneally before the induction of reperfusion. Cardiac function, fibrosis, oxidant/antioxidant markers, and inflammatory cytokines were evaluated using echocardiography, ELISA, and Western blot assay. As a result of MI/R induction, a decrease in left ventricular contractile function occurred along with increased cardiac fibrosis and tissue damage. The serum levels of TNF-α, IL-1β, and IL-18 increased, while IL-10 decreased. Oxidant/antioxidant changes were evident with increased MDA levels and decreased GSH, SOD, and CAT in the MI/R group. Furthermore, the protein levels of TLR4, NF-κB, and NLRP3 were significantly increased in the heart tissue of MI/R group. Treatment with 4-MU significantly prevented the reduction of cardiac contractile function and its pathological changes as a result of MI/R by inhibiting the increase of serum inflammatory factors and improving the oxidant/antioxidant balance probably through the TLR4/NF-κB/NLRP3 axis. The results of a current study showed that 4-MU had a potential ability to attenuate the cardiac injury by reducing oxidative stress and inflammation in a TLR4/NF-κB/NLRP3-dependent mechanism.

Analysis of Myocardial Left Ventricular Deformation During the Third Trimester of Healthy Pregnancy

Background: Pregnancy, a distinctive physiologic state, that associated with multiple changes in the several body systems. One of the affected systems is cardiovascular system , with volume overload being one of the typical adaptation encountered during pregnancy, with chronic volume overload being one of the characteristic changes experienced during pregnancy. However, the effect of these changes on left ventricular myocardial contractile function has not been fully illustrated. Aim: To assess the maternal cardiac function during the third trimester of healthy pregnancy using Speckle Tracking echocardiography. Patient and Methods: This cross sectional study was carried out in Al-Furat teaching hospital in the time period from 1st of April 2022 to 30 of May 2023. A total of 150 women were studied, they were classified into two groups: 75 pregnant women with normal singleton pregnancy at their third trimester served as study group and 75 non pregnant women served as control group. Clinical evaluation, anthropometric assessments, and two-dimensional M-mode and Doppler echocardiography as well as Speckle Tracking echocardiographic study had been done for each one of them to assess the left ventricular systolic function. Results: The two groups showed significant difference in accordance with weight , height &amp; BMI. Global longitudinal strain (GLS) was significantly different between the study groups . Its Average value was decrease to -20.3 compared with -25.3 in control group. Besides, apical long-axis , three-, and four-chamber strain showed significant changes as well. With lowest strain value was the apical long-axes -18.96 in comparison with the control. Conclusion: Left ventricular global longitudinal strain (GLS) shows significant reduction during the third trimester of healthy pregnancy ,this reduction in LV thickening is one of the cardiac adaptation throughout the pregnancy.

The Influence of Carbohydrate Metabolism Disorders on the Course of Perioperative Period in Cardiac Surgery Patients with Post-Infarction Left Ventricular Aneurysms

The aim. To study the impact of carbohydrate metabolism disorders on perioperative period in cardiac surgery pa-tients with post-infarction left ventricular (LV) aneurysms.&#x0D; Materials and methods. Retrospective analysis of perioperative period in random 132 patients with post-infarction LV aneurysms of various locations, who were operated on and discharged from the department of surgical treatment of ischemic heart disease of the National Amosov Institute of Cardiovascular Surgery of the National Academy of Medical Sciences of Ukraine. Disorders of carbohydrate metabolism (DCM) were detected in 98 (74.2%) patients, among whom type 2 diabetes mellitus (DM) was diagnosed in 34 (25.7%) patients, impaired glucose tolerance (IGT) in 64 (48.5%). All the patients underwent general clinical examination, electrocardiography, echocardiography, coronary angiography and surgical treatment.&#x0D; Results. When analyzing the clinical picture in patients with post-infarction LV aneurysms, painless myocardial isch-emia was diagnosed in 41 (31.06%) patients, among whom type 2 DM in 11 (26.8%) cases and IGT in 18 (43.9%). No statistically significant difference was found in patients with and without DCM in the LV contractile function, presence of LV thrombosis, atrial fibrillation, chronic kidney disease, stenosis of brachiocephalic arteries and arteries of the lower extremities, gouty arthritis, and body weight. Intraoperatively, diameter of the coronary arteries in patients with type 2 DM was slightly smaller compared to patients without DCM. Its increase in cases of calcification of coronary arteries and aorta among patients of the study group with DCM was statistically insignificant. A careful analysis of the postoperative period in patients with and without DCM showed a statistically significant occurrence of paroxysms of atrial fibrillation in 30 (90.9%) and 3 (9.1%) cases, respectively (p=0.0115). The patients with DCM had longer stay in the intensive care unit: 4.03 ± 2.3 vs. 3.2 ± 1.3 days (p=0.0483). Acute kidney injury in the early postoperative period occurred in 8 (6.06%) patients, including 5 (62.5%) with type 2 DM (p=0.0142). Sternal wound infection occurred in 2 (1.5%) patients with type 2 DM (p=0.0156).&#x0D; Conclusions. Among cardiac surgical patients with postinfarction LV aneurysms, the major part is formed by patients with DCM (74.2%), the presence of which complicates the course of the postoperative period with the development of paroxysms of atrial fibrillation (p=0.0115), acute kidney injury (p=0.0142), sternal wound infection (p=0.0156), a long stay in the intensive care unit (p=0.0483).

The Role of Arterial Elasticity in Determining the Degree of Chronic Heart Failure in Myocardial Infarction.

Aim To study the left ventricular (LV) contractile and pumping function during the recovery phase following ligation of the anterior descending coronary artery (CA).Material and methods Cardiodynamic parameters were studied in Wistar rats 2-4 weeks after experimental myocardial infarction (MI). MI was induced by ligation of the anterior descending CA under zoletil anesthesia. LV catheterization was performed with a standard FTH-1912B-8018 PV catheter inserted into the LV through the right carotid artery.Results After the induction of MI, the mortality rate of animals was 50%. Survived animals developed significant LV dilatation and a decrease in ejection fraction (EF) by an average of 31%. However, major indexes of the pumping function, including minute volume, heart work, and maximum ejection velocity, were within a normal range whereas the maximum filling velocity was almost doubled. Approximately 50% of hearts with dilated LV had normal EF, delayed relaxation, and increased LV diastolic pressure, which qualified this group as a diastolic dysfunction group. The systolic dysfunction group with EF less than 50% of normal had similar values of myocardial contractility and relaxation but differed from the diastolic dysfunction group in more than 50% reduced maximum LV ejection velocity and 1.7 times increased elasticity of the arterial wall. A close inverse correlation was found between these values (r= -0.91).Conclusion The study results showed that, with a similar myocardial contractile function, the cardiac pumping function is determined by the elasticity of the aortic wall. Therefore, restriction of reactive fibrosis during MI is an important task of modern cardiology.

Underprescribing of cardioprotective novel antidiabetic drugs in marginalized patients with type II diabetes mellitus

Abstract Background Cardiovascular disease is the most common cause of increased mortality in patients with type 2 diabetes mellitus (T2DM). Novel antidiabetic agents such as sodium-glucose co-transporter 2 (SGLT-2) inhibitors and glucagon-like peptide 1 (GLP-1) agonists were shown to reduce this risk. SGLT-2 inhibitors are considered a secondary treatment option in patients with heart failure with reduced ejection fraction (HFrEF) in patients with or without T2DM. In patients with T2DM, these medications not only reduce hyperglycemia but also reduce the progression of chronic kidney disease (CKD). GLP-1 agonists are indicated for treatment of not only T2DM, but also obesity, and were shown to improve left ventricular ejection fraction, myocardial contractility, and endothelial function. The literature suggests that there may be disparities in prescribing patterns in marginalized populations. Objective The purpose of this study was to conduct a retrospective chart review to assess the adherence to the new guidelines regarding the use of SGLT2 inhibitors and GLP-1 agonists in marginalized patients with T2DM. Methods The study was conducted at a resident-run clinic that serves a large number of under-resourced individuals. Inclusion criteria included patients between the ages of 18 and 75 with T2DM seen in the clinic within 18 months prior to the start of the study with an A1c greater than 9.0. Exclusion criteria included patients with type 1 diabetes mellitus and patients with T2DM under care of endocrinology. We performed retrospective chart review to determine providers’ prescription practices. We created electronic patient database for this study. Results The data showed that 26.87% (n= 381) of the clinic’s population had an A1c greater than 9.0, of those 343 patients met the inclusion criteria. About 7.87% (27/343) of patients were identified with HFrEF. Of those, only 40.74% (11/27) were found to be on an SGLT2 inhibitor. Patients with CKD constituted 17.49% (60/343) of patients, and only 16.67% (10/60) of those were on an SGLT2 inhibitor. We identified 27.70% (95/343) of patients with a BMI between 30-35, and 30.32% (104/343) with a BMI greater than 35, but only 56.84% and 64.42% of those, respectively, were on a GLP-1 agonist. The patients that were not on the cardioprotective agents were 50.19% (135/269), 11.15% (9/269), and 12.64% (34/269) African American, Hispanic, and Asian American, respectively. Conclusions This study demonstrates that SGLT2 inhibitors and GLP-1 agonists are underprescribed in marginalized patients diagnosed with T2DM, even in those with the additional indication of heart failure and CKD. Most of those patients are of racial minorities. There are a number of barriers that could be contributing to the poor adherence to the guidelines in this population. Our next step is to analyze those barriers and develop a quality improvement project that would improve guideline-directed therapy for this under-resourced population.

Impact of hypertension on mean transvalvular gradients in aortic stenosis Lessons learned from in silico modelling

Abstract Introduction The influence of hypertension on the diagnostic assessment of aortic stenosis (AS) severity is unclear, yet clinically relevant. To clarify the effect of hypertension on transvalvular gradients, requires a better understanding of the impact that blood pressure change has on mean flow rate. Also, the effect of various degrees of AS severity, the valve geometry and intrinsic left ventricular contractile function (elastance) on this interaction, needs to be clarified. Existing clinical research on this topic is limited by not incorporating the full complement of factors that influences the directionality and magnitude of mean transvalvular gradient change for any given change in blood pressure. Purpose To use validated flow dynamics modelling grounded in fundamental physics principles to create a digital platform where various parameters can be manipulated to quantify the effects of bloodpressure change on mean transvalvular gradients in various pathological states. Methods A validated, zero-dimensional electro-hydraulic analogue computer model of the human cardiovascular circulatory system was generated. It was used to assess the impact of blood pressure changes on left ventricular pressure and transvalvular gradients at various flow rates, left ventricular elastances, a range of aortic valve areas and for different aortic valve morphologies. Results Mean transvalvular gradients are flow dependent. The impact of hypertension on mean flow rate (MFR), and hence on mean gradient (MG), is influenced by the aortic valve area as well as the underlying left ventricular elastance (Figure 1). Subsequently, the relationship between MFR and MG could be modelled (Figure 2). Generally, for a given change in systemic arterial pressure, the impact on MG will be the most marked for lower flow rate states such as is expected in more severe degrees of AS and for worse intrinsic left ventricular (LV) contractility. Furthermore, for a constant hemodynamic valve area, the hydraulic valve orifice area was found to be smaller in rheumatic AS compared to degenerative AS. This results in less susceptibility to blood pressure induced changes in mean transvalvular gradient. Similarly, the size of the aortic root was found to be inversely related to the susceptibility to induce a change in mean gradient for a change in blood pressure. Conclusion The interaction between hypertension and mean gradients in AS is complex. The current work places previous recommendations in perspective by quantifying the magnitude of the effect that a change in blood pressure has on mean gradient in various pathophysiological states. By doing so it provides more granularity into this multifaceted interaction compared to previously oversimplified deductions from clinical studies. The findings of this study creates a basic science framework based on first principles that dictates the scope of parameters that should be considered in future clinical research on the topic.Modelling 1Modelling 2

Exploring the mechanisms responsible for afterload mismatch in severe aortic stenosis

Abstract Introduction Afterload mismatch (AM) is defined as a reduced ejection fraction (EF) in the setting of severe aortic stenosis (AS) (aortic valve area (AVA) of &amp;lt; 1cm2), but with transaortic pressure gradients in the severe range. The pathomechanism underlying the impaired EF remains unclear, especially with regards to the impact of ventricular hypertrophy and fibrosis, the role of afterload, and the integrity of the intrinsic contractile myocardial strength in AM. This knowledge gap unmasks a lack of understanding into the natural disease progression in AS. Purpose To characterise the morphological and functional contractile mechanics that distinguishes patients with reduced EF from patients with preserved EF in the setting of AS with high transvalvular gradients. Methods A prospective comparative analysis was performed on 21 sequential cases of patients with severe AS, 9 with AM (AVA &amp;lt; 1.0cm2; MG &amp;gt; 40mmHg; EF &amp;lt; 50%) and 12 with normal flow high gradient (NFHG) AS (AVA &amp;lt; 1.0cm2; MG &amp;gt; 40mmHg; EF &amp;gt; 50%). Patients with concomitant valve lesions or previously diagnosed myocardial infarction, were excluded. Myocardial morphology, function and tissue characteristics were evaluated using a) transthoracic echocardiography, b) cardiac magnetic resonance imaging, and c) an invasive hemodynamic study with pressure-volume loop derived data. Results Intrinsic load independent contractile muscle function parameters were similar between AM and NFHG AS (p-value non-significant for cardiac index, dP/dT(max), preload recruitable stroke work slope, end systolic pressure volume relationship slope and Starling contractile index slope). Afterload indices as assessed by peak systolic wall stress and valvuloarterial impedance were significantly higher in AM cases compared to NFHG AS (32.5 vs 19.9 N/cm2; p &amp;lt; 0.01 and 4.8 vs 3.4mmHg/ml; P = 0.05). This was driven by disproportionally higher degrees of valvular stenosis in the AM group (valve area 0.46 vs 0.78cm2; p &amp;lt; 0.01). The AM group expressed a more advanced disease phenotype with more symptoms (NYHA 3.3 vs 2.3; p=0.02), more pulmonary hypertension (50 vs 30mmHg; p=0.04), and more extensive myocardial fibrosis (24% vs 13% of left ventricular mass; p=0.03) (see Figure 1). Neither more severe LVH nor higher degrees of fibrosis in the AM group, was associated with a demonstrable impairment in the intrinsic contractile muscle function. Conclusion Our data suggest that the central problem in AM is related to an excessively increased afterload, primarily driven by more severe valvular stenosis, with preserved intrinsic left ventricular contractile function. AM is characterised by more severe myocardial fibrosis, as a marker of a more advanced disease phenotype, but this did not translate into worse intrinsic contractile muscle function. The known time dependence of progressive valvular stenosis and myocardial fibrosis would suggest that AM is an intermediate phase between NFHG AS and so-called low flow low gradient severe AS.A more advanced phenotype

Calcium handling dysfunction and cardiac damage following acute ventricular preload challenge in the dystrophin-deficient mouse heart.

Duchenne muscular dystrophy (DMD) is the most common muscular dystrophy and is caused by mutations in the dystrophin gene. Dystrophin deficiency is associated with structural and functional changes of the muscle cell sarcolemma and/or stretch-induced ion channel activation. In this investigation, we use mice with transgenic cardiomyocyte-specific expression of the GCaMP6f Ca2+ indicator to test the hypothesis that dystrophin deficiency leads to cardiomyocyte Ca2+ handling abnormalities following preload challenge. α-MHC-MerCreMer-GCaMP6f transgenic mice were developed on both a wild-type (WT) or dystrophic (Dmdmdx-4Cv) background. Isolated hearts of 3-7-mo male mice were perfused in unloaded Langendorff mode (0 mmHg) and working heart mode (preload = 20 mmHg). Following a 30-min preload challenge, hearts were perfused in unloaded Langendorff mode with 40 μM blebbistatin, and GCaMP6f was imaged using confocal fluorescence microscopy. Incidence of premature ventricular complexes (PVCs) was monitored before and following preload elevation at 20 mmHg. Hearts of both wild-type and dystrophic mice exhibited similar left ventricular contractile function. Following preload challenge, dystrophic hearts exhibited a reduction in GCaMP6f-positive cardiomyocytes and an increase in number of cardiomyocytes exhibiting Ca2+ waves/overload. Incidence of cardiac arrhythmias was low in both wild-type and dystrophic hearts during unloaded Langendorff mode. However, after preload elevation to 20-mmHg hearts of dystrophic mice exhibited an increased incidence of PVCs compared with hearts of wild-type mice. In conclusion, these data indicate susceptibility to preload-induced Ca2+ overload, ventricular damage, and ventricular dysfunction in male Dmdmdx-4Cv hearts. Our data support the hypothesis that cardiomyocyte Ca2+ overload underlies cardiac dysfunction in muscular dystrophy.NEW & NOTEWORTHY The mechanisms of cardiac disease progression in muscular dystrophy are complex and poorly understood. Using a transgenic mouse model with cardiomyocyte-specific expression of the GCaMP6f Ca2+ indicator, the present study provides further support for the Ca2+-overload hypothesis of disease progression and ventricular arrhythmogenesis in muscular dystrophy.

Chest compression rates of 60/min versus 90/min during neonatal cardiopulmonary resuscitation: a randomized controlled animal trial.

To compare chest compression (CC) rates of 60/min with 90/min and their effect on the time to return of spontaneous circulation (ROSC), survival, hemodynamic, and respiratory parameters. We hypothesized that asphyxiated newborn piglets that received CC at 60/min vs. 90/min during cardiopulmonary resuscitation would have a shorter time to ROSC. Newborn piglets (n = 7/group) were anesthetized, tracheotomized and intubated, instrumented and exposed to 45 min normocapnic hypoxia followed by asphyxia and cardiac arrest. Piglets were randomly allocated to a CC rate of 60/min or 90/min. CC was performed using an automated CC machine using CC superimposed with sustained inflation. Hemodynamic parameters, respiratory parameters, and applied compression force were continuously measured. The mean (IQR) time to ROSC was 97 (65-149) s and 136 (88-395) s for CC rates of 60/min and 90/min, respectively (p = 0.31). The number of piglets that achieved ROSC was 5 (71%) and 5 (71%) with 60/min and 90/min CC rates, respectively (p = 1.00). Hemodynamic parameters (i.e., diastolic and mean blood pressure, carotid blood flow, stroke volume, end-diastolic volume, left ventricular contractile function) and respiratory parameters (i.e., minute ventilation, peak inflation and peak expiration flow) were all similar with a CC rate of 60/min compared to 90/min. Time to ROSC, hemodynamic, and respiratory parameters were not significantly different between CC rates of 60/min vs. 90/min. Different CC rates during neonatal resuscitation warrant further investigation.

Phenotyping heart failure by echocardiography: imaging of ventricular function and haemodynamics at rest and exercise.

Traditionally, congestive heart failure (HF) was phenotyped by echocardiography or other imaging techniques according to left ventricular (LV) ejection fraction (LVEF). The more recent echocardiographic modality speckle tracking strain is complementary to LVEF, as it is more sensitive to diagnose mild systolic dysfunction. Furthermore, when LV systolic dysfunction is associated with a small, hypertrophic ventricle, EF is often normal or supernormal, whereas LV global longitudinal strain can reveal reduced contractility. In addition, segmental strain patterns may be used to identify specific cardiomyopathies, which in some cases can be treated with patient-specific medicine. In HF with preserved EF (HFpEF), a diagnostic hallmark is elevated LV filling pressure, which can be diagnosed with good accuracy by applying a set of echocardiographic parameters. Patients with HFpEF often have normal filling pressure at rest, and a non-invasive or invasive diastolic stress test may be used to identify abnormal elevation of filling pressure during exercise. The novel parameter LV work index, which incorporates afterload, is a promising tool for quantification of LV contractile function and efficiency. Another novel modality is shear wave imaging for diagnosing stiff ventricles, but clinical utility remains to be determined. In conclusion, echocardiographic imaging of cardiac function should include LV strain as a supplementary method to LVEF. Echocardiographic parameters can identify elevated LV filling pressure with good accuracy and may be applied in the diagnostic workup of patients suspected of HFpEF.

A new perspective on an old method: gated SPECT imaging for left ventricular contractile function assessment.

The ejection fraction (LVEF) is a commonly used marker of left ventricular function. However, because it is strongly influenced by loading conditions, it can be inaccurate in representing cardiac contractility. We therefore evaluated a gated SPECT based tool to simultaneously assess preload, afterload, and contractility. Using gated SPECT-determined ventricular volumes and arterial tension measurements, we calculated ventricular and arterial elastance (Ev and Ea), as well as end-diastolic volumes, which are surrogates for contractility, afterload, and preload, respectively. We applied this protocol to 1462 consecutive patients and assessed the ventricular function in patients with and without myocardial infarction. The median LVEF was 68% (IQR 62-74%). Patients with infarction exhibited decreased contractility (ventricular elastance of 3mmHg/ml vs. 6mmHg/ml), compensated by an increase of preload (end-diastolic volume of 100ml vs. 78ml) and a decrease in afterload (arterial elastance of 1.8mmHg/ml vs. 2.2ml/mmHg). These interactions yielded a preserved ejection fraction in both groups. Gated SPECT-measured volumes were consistent with values reported in the literature. In addition, the combination of nuclear imaging and arterial tension measurement accounted for not only the ejection fraction but also the loading context, providing a more accurate representation of cardiac contractility.

Clinical and hemodynamic particularities of patients with acute ST-segment elevation myocardial infarction subjected to late interventional treatment

To save the viability of the ischemic myocardium in a patient with ST-segment elevation myocardial infarction and improve the survival, coronary blood flow must be restored as soon as possible, preferably within the first 12 hours after the onset of pain. The current dilemma of interventional cardiologists is the decision about the possibility of performing interventional myocardial reperfusion in the patients with delayed presentation (more than 12 hours from the onset) and establishing the predictive factors of the procedures performed in this category of patients. In ths study 63 patients with STEMI were included, divided into 2 groups: the first one included 33 patients presentetd at the emergency department within the first 12 hours after the onset of STEMI, and the second group consited of 30 subjects with STEMI in whom the first medical contact was more than 12 hours after the onset of symptoms. The groups were compared with each other according to the well-established criteria. The primary end points were the assessment of major cardiovascular events (MACE), as well of ventricular myocardium remodeling/reverse-remodeling and predictors of interventional procedures. The improvement of left ventricular myocardial contractile function (LVEF), seems to be associated with early myocardial revascularization. Early presentation in STEMI can be considered an independent predictor of the improvement of the regional kinetics affected by AMI. The contractile function of the LV myocardium represented by the ejection fraction is considered an independent predictor of long-term and short-term mortality in patients with STEMI. The preliminary results of the research highlight the applicative value of PCI procedures also for patients with delayed presentation - more than 12 hours from the onset of the disease and the first medical contact.

Optimal reperfusion time in patients with non-ST elevation acute myocardial infarction and low ischemic risk

The aim of the study was to identify the optimal time window for performing effective percutaneous coronary reperfusion in patients with non-ST-segment elevation acute myocardial infarction (NSTEMI) who are part of the low ischemic risk group. 252 patients with NSTEMI and low ischemic risk who underwent coronary angioplasty up to 30 days after the onset of the infarction were evaluated the second day post-procedurally and at a distance of 6 months. The general group was randomized depending on the echocardiographic evolution. 131 patients with unfavorable evolution and 121 with more complete restoration of left ventricular contractile function. The time windows from the onset of myocardial infarction symptoms in which percutaneous myocardial reperfusion was applied were studied. Following the study, the time interval of 73 hours -14 days proved to be optimal in which a more favorable clinical and echocardiographic evolution is ensured.

Endovascular aortic repair impact on myocardial contractility: A prospective study.

This study aimed to estimate if the altered sphygmic wave transmission may affect the left ventricular (LV) contractile function in patients undergoing endovascular aortic repair (EVAR). A prospective single-centre study was carried out on consecutive patients undergoing EVAR for abdominal aortic aneurysm. A preoperative and 6-month single photon emission computed tomography (SPECT) with arterial stiffness measurement were performed to evaluate variations in pressure wave curve and myocardial perfusion parameters. From 2018 to 2020 a total of 16 patients were included in the study. Among the parameters evaluated, we found a measurable reduction of the reflected wave transit time from pre- to postoperative period, for both stress (115.13 ± 7.2 ms-111.1 ± 7.0 ms, p = .08) and rest SPECT acquisitions (115.3 ± 6.2 ms-112.2 ± 5.6 ms, p = .1). Unidirectional increase of both LV end-systolic volume (34 ± 9 mL-39 ± 8 mL, p = .02) and end-diastolic volume (85 ± 34 mL-89 ± 29 mL, p = .6) was also observed. Lastly, the ratio between the end-systolic pressure and the end-systolic volume (maximal systolic myocardial stiffness) decreased from 3.6 ± 1.5 mmHg/mL to 2.66 ± .74 mmHg/mL (p = .03). Our data showed that EVAR induced an altered transmission of the sphygmic wave associated with an early LV contractile impairment.

Trimethylamine-N-oxide paradoxically depresses contractile function while activating mitochondrial respiration in mouse hearts.

Trimethylamine-N-oxide (TMAO) is an end-product of gut-microbiome metabolism linked to cardiovascular disease (CVD). However, precise cardiovascular influences of the TMAO concentrations reported in early or severe disease remain to be detailed. We investigated acute effects of TMAO on cardiac contractile, coronary and mitochondrial function. Male C57Bl/6 mouse hearts were Langendorff perfused to assess concentration-dependent effects of TMAO (1-300 µM) on left ventricular (LV) function, coronary flow and select protein expression. Effects of 10 and 100 µM TMAO on LV mitochondrial function were examined via respirometry. TMAO at 10-300 µM concentration-dependently depressed LV contractile function, with coronary flow paralleling changes in isovolumic pressure development. Direct coronary effects were evident at >30 µM TMAO in hearts performing minimal isovolumic work, though this response was reduced by >65%. In contrast, exposure to 10 or 100 µM TMAO increased mitochondrial complex I, II and maximal respiratory fluxes while appearing to reduce outer membrane integrity. Expression of phospho-AMPKα and total GSK-3β declined. Acute exposure to TMAO levels reported in advanced CVD significantly inhibits cardiac contractility and induces modest coronary constriction while paradoxically over-activating mitochondrial respiration.