Significant Diastolic Dysfunction Research Articles

Changes in heart rate variability and subclinical heart failure with preserved left ventricular ejection fraction in workers of the main professions at the coal industry

Introduction. The high prevalence of diseases of the circulatory system necessitates their detection and prevention at an early stage, especially in regions with high industrial potential. The occurrence of subclinical heart failure depends on a cascade of processes that are already occurring in the body and may eventually manifest themselves in clinically pronounced diseases. One of the possible mechanisms of its development is a violation of the balance of the autonomic nervous system with a violation of adaptive capabilities to the labour process, characterized by severe physical overloads among miners. The study aims to evaluate changes in heart rate variability in workers of the main professions at the coal industry with signs of heart failure with a preserved left ventricular ejection fraction. Materials and methods. The study included 78 employees of the main professions at the coal industry. Specialists performed ultrasound examination of the heart according to generally accepted methods with the study of longitudinal deformation of the myocardium. The concentration of NT-proBNP in the blood serum was determined by solid-phase enzyme immunoassay. The authors also conducted an analysis of heart rate variability, determined temporal, spectral and linear parameters. Results. Specialists revealed a decrease in longitudinal myocardial deformation in 38.5% of the examined patients, signs of diastolic dysfunction in 41%; in these groups, a tendency to increase the concentration of NT-proBNP was revealed. In the examined miners with heart failure with preserved ejection fraction, they revealed a significant decrease in the SDNN index and an increase in IC values. The increase in DFA and LF/HF indicators reflects a vegetative imbalance towards sympathetic activation observed in all surveyed miners. Limitations. This study is limited to a sample of employees of the main professions of the coal industry undergoing periodic medical examination at the Research Institute of Complex Problems of Hygiene and Occupational Diseases. Conclusion. The revealed relationship between indicators of heart failure and heart rate variability (SDNN, LF/HF, DFA and IC) in miners allows us to identify a group of people at greatest risk of adverse outcomes. Ethics. The study was conducted in compliance with the standards of the Bioethical Committee of the Research Institute of Complex Problems of Hygiene and Occupational Diseases, established in accordance with the Helsinki Declaration of the World Medical Association "Ethical Principles of Conducting medical Research with human participation as a subject" as amended in 2013 and the "Rules of Good Clinical Practice" approved by Order No. 200n of the Ministry of Health of the Russian Federation dated 04/01/2016. The subjects signed an informed consent to participate in the study.

High-Intensity interval training improves global longitudinal strain in patients with metabolic syndrome and high risk of heart failure

Abstract Background Metabolic syndrome (MS) has been associated with the development of myocardial dysfunction which can lead to heart failure (HF). It is possible to detect early signs of myocardial dysfunction by assessing the global longitudinal strain (GLS) in a transthoracic echocardiography. A reduced GLS is considered as a predictor of HF development. Preventive strategies are recommended in patients with MS to avoid the progression to HF. Although exercise improves cardiovascular and metabolic health in MS patients, it is unknown whether exercise can affect the evolution of GLS in a group of patients with MS who are under medical treatment. Purpose To assess the prevalence of myocardial dysfunction (i.e., reduced GLS) in a heterogeneous group of patients with MS who are under medical treatment, and to test in these patients if 16 weeks of high-intensity interval training (HIIT) can improve the GLS. Methods Seventy-seven volunteers with MS and without signs or symptoms of HF were randomized in one of two 16-week intervention: i). HIIT in stationary bikes 3 sessions/week, 50 minutes/session + medical treatment (HIIT group), or ii). medical treatment (CONTROL). Maximal oxygen consumption (VO2max), and GLS together with rutinary echocardiographic parameters were assessed before and after intervention. The effect of HIIT compared to CONTROL was analyzed by a split-plot ANOVA to compare the effects of time (pre vs. post) and group (HIIT vs. CONTROL), and the interaction between the two factors. Results Before intervention 48.9% of participants from the HIIT group, and 46.7% from the CON group had a reduced GLS (i.e., >17% for men and >18% for women). However, none of them had a reduced left ventricular ejection fraction (LVEF), signs of diastolic dysfunction or an abnormal VO2max (less than 80% of predicted VO2max). After the 16-week intervention, only individuals from the HIIT group improved their VO2max (time*group P<0.001). LVEF did not improve in any of the experimental groups (time P=0.278) HIIT group improved their GLS by 0.51%, whereas CONTROL group improved it by 0.05% without reaching statistical significance (time*group P=0.186). However, a subgroup analysis of GLS conducted among the participants from the HIIT group discriminated by their pre-intervention values (GLS normal or reduced), showed that individuals with reduced GLS improved significantly by 1,41% (P=0.001) whereas those with a normal GLS improved by 0.14% without reaching statistical significance (P=0.736, time*group P=0.009). Conclusions Myocardial dysfunction assessed by GLS is present in MS even in the absence of symptoms, diastolic dysfunction, or reductions in the LVEF. HIIT can reduce the risk of HF development by improving GLS in patients with MS and early signs of myocardial dysfunction.A. Overall changes in GLSB. Subgroup analysis of GLS pre vs. post

Cardiac morphology and function in patients with primary biliary cholangitis (PBC) without cirrhosis

Abstract Background Primary biliary cholangitis (PBC) is a chronic, autoimmune liver disease causing destruction of the small intralobular bile ducts in the liver. PBC patients can also develop extrahepatic manifestations. Though patients with PBC have often elevated levels of serum lipids, data concerning cardiac involvement is inconsistent and cardiovascular changes may be underdiagnosed. Purpose The purpose of the study was to assess cardiac morphology and function in patients with PBC without cirrhosis and comparison with control subjects. Methods We studied 52 females with PBC, and included in the analysis 22 females without cirrhosis, who were compared to 44 healthy female controls matched for age (53.4 ± 9.2 and 51 ± 8.3 yrs., respectively, p =0.312). Transthoracic echocardiography (TTE) was performed with the analysis of the left ventricular (LV) global longitudinal strain (GLS) and myocardial work. Additionally, impedance cardiography was conducted, with the analysis of the autonomic function using BRS (baroreceptor sensitivity), HRV (heart rate variability) and BPV (blood pressure variability). Results Systolic blood pressure (SBP), diastolic blood pressure (DBP) and heart rate (HR) differed between PBC and control group (128 ± 17 mmHg vs. 116 ± 11 mmHg, p=0.007 and 78± 12 mmHg vs. 75 ± 8 mmHg, p=0.024, and 73.5 ± 12 bpm vs. 71 ± 8 bpm , p=0.024, respectively). PBC group had larger diameter of the cardiac chambers when adjusted for body surface area (BSA), including left atrium (LA/BSA) and right ventricle (RV/BSA), as well as left ventricular mass (LWMI) and relative wall thickness (RWT), with no difference in the left ventricular end diastolic diameter (LVEDD/BSA). LV ejection fraction (EF) measured by bi-plane Simpson method was higher in PBC group. LV diastolic function parameters (E/A, E/e’) differed in patients with PBC when compared with controls, however, without signs of diastolic dysfunction. LV GLS indices (GLSAVG, GLSLAX, GLS4C, GLS2C) were significantly higher in PBC group, as well as global myocardial work indexes: global myocardial work (GWI) and global constructive work (GCW). Non-invasive autonomic assessment showed lower BPV in patients with PBC without cirrhosis, but no differences in baroreceptor sensitivity and HRV. Impedance cardiography did not show differences between both groups. Conclusion Our study shows that PBC patients without cirrhosis are characterized by remodeling and functional changes of the heart, when compared to age-matched controls. These changes could imply hyperkinetic circulation even before the development of cirrhosis in PBC patients.

Gradual hypertensive response in aortic alterations and myocardial inflammatory activation in progressing HFpEF in mice

Abstract Introduction Hypertension is the most common comorbidity in patients affected by heart failure with preserved ejection fraction (HFpEF). Early effects of pressure overload and its contribution to the gradual development of cardiac and vascular pathology leading to HFpEF are not well recognized, as patients are diagnosed when the disease has already advanced and show symptoms. Several hypertensive HFpEF mouse models possessing the hallmarks of the clinical-like phenotype are available. Nonetheless, initial and gradual pathological manifestations of hypertensive HFpEF have not been comprehensively described. Purpose This study aimed to investigate the gradual progression of HFpEF phenotype development in mice from the early manifestation of cardiac and vascular pathology to global cardiac dysfunction to multiorgan syndrome in response to hypertension. Methods Hypertensive HFpEF was induced by angiotensin II infusion in C57BL/6JOlaHsd 18-20-week-old male mice that were given low, moderate and high doses (0.5mg/kg/day - 1.5 mg/kg/day) subcutaneously for 4 weeks. Cardiac physiology and alterations in haemodynamics were assessed with echocardiography of heart and aorta, weekly ECG monitoring, and blood pressure measurements from the mouse tail. Extensive histology and immunohistochemistry analyses of cardiac tissue, microvasculature, lungs and kidneys were performed. Results In the low dose group, loss of aortic wall flexibility and presence of aortic root dilatation were detected. This group also demonstrated initiation of concentric remodelling process with the upsurge in macrophage infiltration in myocardium, but the signs of diastolic dysfunction were not yet present. The high dose group exhibited characteristic HFpEF features with diastolic dysfunction, left ventricular hypertrophy and fibrosis. Pathology in cardiac conduction system was noticed in all groups, with prominent ECG waveform abnormalities already on week one. However, only the high dose group experienced non-recovery in impulse propagation, accompanied by significant prolongation of ventricular depolarization. Conclusion This study demonstrates that change in aortic root dimensions and aortic wall dynamics are the first hypertension-sensitive alterations together with myocardial inflammatory cell infiltration that may contribute to myocardial remodelling and subsequent development of HFpEF and systemic effects. Hypertensive angiotensin II-induced HFpEF is a relevant mouse model, recapitulating not only hallmarks of cardiac pathology but also an extensive range of vascular and multiorgan alterations, demonstrating similarities with the clinical phenotype.

Diastolic dysfunction and survival in patients with preserved or mildly reduced left ventricular ejection fraction

Abstract Background Left ventricular ejection fraction (LVEF) is relatively indiscriminate for prognosis in patients with preserved or mildly reduced LVEF (>40%) following myocardial infarction (MI). Aims This study sought to determine the value of guideline-based assessment of diastolic dysfunction (DD) in predicting all-cause and cardiac mortality in patients with a first-ever MI and LVEF>40%. Methods A retrospective single centre study involving 2234 patients with a first-ever MI (STEMI or NSTEMI) with LVEF>40% was performed. Clinical, angiographic, and echocardiographic data were obtained from prospectively maintained institutional databases. Outcomes data were obtained from the state-wide registry. Echocardiography was performed early post-admission for all patients. Significant diastolic dysfunction (DD) was defined as grade 2+3 diastolic dysfunction according to current American Society of Echocardiography/ European Association of Cardiovascular Imaging guidelines. Results The mean age of patients was 61.4±12.3 years, 70.7% were males, and 12.1% had 3-vessel disease. The mean LVEF was 55.8±7.2% and 9.1% had significant DD. At a median follow up of 4.5 years, there were 219 deaths (46 cardiac deaths). On Cox proportional hazards multivariable analyses incorporating significant clinical, angiographic, and echocardiographic variables, significant DD was an independent predictor of both all-cause (HR 2.01,95%CI 1.37-2.94, p<0.001) and cardiac (HR 3.97,95%CI 1.98-7.99, p<0.001) mortality. Conclusions Significant DD is an independent predictor of all-cause and cardiac mortality following MI in patients with preserved or mildly reduced LVEF and thus effectively re-stratifies prognosis in a subgroup where the LVEF is relatively indiscriminate for survival. The benefit of further investigation and/or treatment in this subgroup needs further study.

Challenges in the diagnostics of mantle cell lymphoma in an elderly comorbid patient

We present a case of a rare lymphoproliferative disease diagnosed while differentiating between the causes of exudative-constrictive pericarditis. An 83-year old man was hospitalized with shortness of breath, edema and newly diagnosed atrial fibrillation (AF). Initially, the signs and symptoms were interpreted as manifestations of heart failure due to old myocardial infarction, arterial hypertension and AF. However, no significant systolic or diastolic dysfunction of the left ventricle and valve disease were identified and natriuretic peptide level was normal. Despite treatment, dyspnea and edema persisted, and pleural effusion (requiring drainage) and pericardial effusion increased. Repeated echocardiography showed signs of exudative-constrictive pericarditis. We consequently excluded the infectious (tuberculosis) and non-infectious (electrolyte disorders, hypothyroidism, solid tumors) etiologies of effusion. Taking into account the long-standing mediastinal lymphadenopathy (the patient had been previously examined, but the cause not identified), anemia, episodes of low-grade fever, weight loss, and polyneuropathy, a lymphoproliferative disease was suspected. Serum protein electrophoresis identified an M spike in the gamma globulin region. Immunophenotyping of peripheral blood lymphocytes and immunohistochemical examination of bone marrow confirmed the diagnosis of mantle cell lymphoma. The patient was referred for specialized treatment. At 5 months of the follow-up, the therapy was successful, the patient was stable with no cardiac complaints, no edema, and no new AF episodes. The case demonstrates the need to strictly follow differential diagnostic algorithms to identify the causes of nonspecific symptoms beyond one medical specialty.

Aging reveals a sex-dependent susceptibility of sarcospan-deficient mice to cardiometabolic disease.

Numerous genes including sarcospan (SSPN) have been designated as obesity-susceptibility genes by human genome-wide association studies. Variants in the SSPN locus have been linked with sex-dependent obesity-associated traits; however, this association has not been investigated in vivo. To delineate the role SSPN plays in regulating metabolism with potential to impact cardiac function, we subjected young and aged global SSPN-deficient (SSPN-/-) male and female mice to obesogenic conditions (60% fat diet). We hypothesized that loss of SSPN combined with metabolic stress would increase susceptibility of mice to cardiometabolic disease. Baseline and end-point assessments of several anthropometric parameters were performed including weight, glucose tolerance, and fat distribution of mice fed control (CD) and high-fat (HFD) diet. Doppler echocardiography was used to monitor cardiac function. White adipose and cardiac tissues were assessed for inflammation by histological, gene expression, and cytokine analysis. Overall, SSPN deficiency protected both sexes and ages from diet-induced obesity, with a greater effect in females. SSPN-/- HFD mice gained less weight than wild-type (WT) cohorts, while SSPN-/- CD groups increased weight. Furthermore, aged SSPN-/- mice developed glucose intolerance regardless of diet. Echocardiography showed preserved systolic function for all groups; however, aged SSPN-/- males exhibited significant increases in left ventricular mass (CD) and signs of diastolic dysfunction (HFD). Cytokine analysis revealed significantly increased IL-1α and IL-17Α in white adipose tissue from young SSPN-/- male mice, which may be protective from diet-induced obesity. Overall, these studies suggest that several sex-dependent mechanisms influence the role SSPN plays in metabolic responses that become evident with age.NEW & NOTEWORTHY Young and aged sarcospan (SSPN)-deficient mice were examined to assess the role of SSPN in obesity and cardiometabolic disease. Both sexes displayed a "leaner" phenotype in response to high-fat diet (HFD). Notably, several sex differences were identified in aged SSPN-deficient mice: 1) females developed glucose intolerance (control and HFD) and 2) males exhibited increased left ventricular mass (control) and diastolic dysfunction (HFD). Therefore, we conclude that SSPN exerts a sex-dependent influence on obesity-associated diseases.

First report of the clinical characteristics and outcomes of cardiac amyloidosis in Saudi Arabia.

Cardiac amyloidosis (CA) is a potentially fatal multisystemic disease that remains significantly underdiagnosed, particularly in the Middle East. This study aims to evaluate the prevalence and clinical characteristics of CA in a high-risk population at a tertiary centre in Saudi Arabia. This cross-sectional, retrospective, single-centre study was conducted at a tertiary hospital in Riyadh, Saudi Arabia. We reviewed the medical records of heart failure patients seen between August 2018 and July 2022 who exhibited red flags for CA and subsequently underwent CA screening. Red flags that prompted the workup included at least two of the following factors: the presence of unilateral or bilateral carpal tunnel syndrome, a family history of transthyretin amyloid (ATTR) amyloidosis and specific electrocardiographic features (relative/absolute low QRS voltage, pseudoinfarct pattern and atrioventricular/interventricular conduction abnormalities). Echocardiographic red flags included mainly increased wall thickness (≥12mm), significant diastolic dysfunction, reduced left ventricular (LV) longitudinal function, right ventricular (RV) dysfunction and elevated right atrial (RA)/pulmonary artery (PA) pressure. Cardiac magnetic resonance (CMR) red flags included aspects similar to those in an echocardiogram as well as a subendocardial or transmural late gadolinium enhancement (LGE) pattern. These patients were assessed for CA through technetium-99m pyrophosphate ([99mTc]Tc-PYP) bone scintigraphy, serum and urine protein electrophoresis with immunofixation and a serum-free light chain assay. A total of 177 patients were screened, of which 21.0 (11.9%) patients were diagnosed with transthyretin amyloid CA (ATTR-CA) and 13 (7.3%) patients were diagnosed with light chain CA (AL-CA). Compared with patients with negative/equivocal [99mTc]Tc-PYP scans (grades 0-1), patients with positive [99mTc]Tc-PYP scans (grades 2-3) were older (78.0 vs. 68.0years, P<0.001), had higher levels of troponin (P=0.003) and N-terminal pro-brain natriuretic peptide (NT-proBNP) (P<0.001), had a higher LV mass index (P<0.001), displayed a more depressed global longitudinal strain (GLS) (P<0.001) with a greater prevalence of a relative apical sparing pattern (P<0.001) and demonstrated a higher incidence of first-degree atrioventricular block (P=0.008) and low voltage patterns on electrocardiography (P<0.001). Patients with ATTR-CA and AL-CA were more likely to have a subendocardial or transmural LGE pattern on CMR (P<0.001) and had a significantly lower overall survival (P<0.001) when compared with other heart failure aetiologies. This is the first study to describe the clinical characteristics and outcomes of CA in the Middle East and Saudi Arabia. The prevalence of CA among screened heart failure patients here aligns with major international studies, suggesting significant underdiagnosis in the region. Therefore, larger multicentric studies and regional screening programmes are urgently needed to accurately characterize the epidemiology and outcomes of CA in the Middle East.

Right ventricular diastolic adaptation to pressure overload in different rat strains.

Different rat strains are used in various animal models of pulmonary hypertension and right ventricular (RV) failure. No systematic assessment has been made to test differences in RV response to pressure overload between rat strains. We compared RV adaptation to pulmonary trunk banding (PTB) in Wistar (W), Sprague Dawley (SD), and Fischer344 (F) rats by hemodynamic profiling focusing on diastolic function. Age-matched male rat weanlings were randomized to sham surgery (W-sham, n = 5; SD-sham, n = 4; F-sham, n = 4) or PTB (W-PTB, n = 8; SD-PTB, n = 8; F-PTB, n = 8). RV function was evaluated after 5 weeks by echocardiography, cardiac MRI, and invasive pressure-volume measurements. PTB caused RV failure and increased RV systolic pressures four-fold in all three PTB groups compared with sham. W- and SD-PTB had a 2.4-fold increase in RV end-systolic volume index compared with sham, while F-PTB rats were less affected. Diastolic and right atrial impairment were evident by increased RV end-diastolic elastance, filling pressure, and E/e' in PTB rats compared with sham, again F-PTB the least affected. In conclusions, PTB caused RV failure with signs of diastolic dysfunction. Despite a similar increase in RV systolic pressure, F-PTB rats showed less RV dilatation and a more preserved diastolic function compared with W- and SD-PTB.

Echocardiographic assessment of right ventricular performance in COVID-19 related acute respiratory distress syndrome: the importance of systo-diastolic interaction.

The cardiac manifestations of COVID-19 have been described in patients with acute respiratory distress syndrome (ARDS) admitted to intensive care unit (ICU). The presence and impact of right ventricular (RV) diastolic function and performance has not been studied in this population yet. We describe the prevalence of RV diastolic dysfunction, assessed by the pulmonary valve pre-ejection A wave (PV A wave), and the RV systo-diastolic interaction, using the RV total isovolumic time (t-IVT), in COVID-19 ARDS. Prospective observational study enrolling patients with moderate to severe COVID-19 ARDS admitted to ICU who underwent a transthoracic echocardiogram within 24h of ICU admission and at least a second one during the ICU stay. Respiratory, hemodynamic and biochemistry parameters were collected. 163 patients (age 61.0 ± 9.3years, 72% males) were enrolled. 36 patients (22.1%) had RV dysfunction, 45 (27.1%) LV systolic dysfunction. 73 patients (44.7%) had PV A wave. The RV t-IVT correlated with TAPSE at ICU admission (p < 0.002; r -0.61), presence of PV A wave (p < 0.001; r 0.78), peak inspiratory pressure (PIP) (p < 0.001; r 0.42), PEEP (p < 0.001; r 0.68), dynamic driving pressure (DDP) (p < 0.001; r 0.58), and PaO2/FiO2 ratio (p < 0.01; r -0.35). The presence of PV A wave was associated with higher PIP (p < 0.001; r 0.45), higher PEEP (p < 0.001; r 0.56), higher DDP (p < 0.01, r 0.51), and lower PaO2/FiO2 ratio (p < 0.001; r -0.49). RV t-IVT and the presence of PV A wave are non-invasive means to describe a significant RV diastolic dysfunction and may be consider descriptive signs of RV performance in COVID-19 ARDS.

Sex Differences in Alcohol-related Cardiomyopathy

Alcohol-related Cardiomyopathy (ACM) manifests in humans with a significant history of alcohol use and is characterized by ventricular dilation and cardiac function impairment. Although the most common age group for ACM is males between the ages of 30-55, women require a lesser lifetime alcohol exposure to develop ACM than men. The objective of this study is to assess sexual differences in a mouse model of chronic plus binge alcohol consumption. We hypothesize that female mice exposed to chronic plus binge alcohol will not develop as severe cardiac dysfunction as their male counterparts. In this study, male (n=19) and female (n=14) C57BL/6J mice were provided chronic plus binge alcohol feeding. After 5 days of acclimation to the liquid diet, mice are fed ad libitum 5% ethanol (EtOH) liquid or isocaloric control liquid diet for 30 days. At 10 and 30 days, mice received an oral binge dose of EtOH (5 g/kg body weight), or isocaloric maltose dextrin solution (9 g/kg body weight). Noninvasive cardiac structural and functional data were obtained via echocardiography at baseline and following binges. After 30 days, cardiac hemodynamics was measured by open chest left ventricle catheterization. Two-way ANOVA with Tukey’s post hoc analysis was performed for each cardiac parameter, and significance was defined as p&lt;0.05. Male EtOH mice exhibited a significant decrease in stroke work (1119 ± 297 mmHg/mL when compared to male controls, 1622 ± 365 mmHg/mL; p= 0.03). Female EtOH mice had a nonsignificant decrease in stroke work (1242 ± 374 mmHg/mL when compared to female controls, 1423 ± 469 mmHg/mL; p= 0.80). Maximum left ventricular pressure was decreased 20% in male EtOH mice (p=0.003) but increased 10% in female EtOH mice (p=0.46). The maximum rate of pressure change within the ventricle was 24% lower in the male EtOH mice (p=0.02) and 9% higher in female EtOH mice (p=0.87). The minimum rate of pressure change within the ventricle was 24% higher in male EtOH mice (p=0.02) and 17% lower in female ETOH mice (p=0.44). After 30 days of EtOH exposure, male mice showed significant systolic and diastolic dysfunction. Female mice on the other hand, did not show substantial cardiac dysfunction after chronic plus binge ethanol exposure. Further experiments involving qPCR of proinflammatory and profibrotic markers will elucidate the molecular mechanism of sex differences in ACM development. R21AA029747 (JG &amp; CB) &amp; T32AA007577. This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

EARLY OUTCOME OF LEFT VENTRICULAR FUNCTION AFTER CORONARY ARTERY BYPASS SURGERY: A SINGLE-CENTER EXPERIENCE

Patients with ischemic heart disease and low ejection fraction often exhibit improved outcomes following coronary artery bypass grafting (CABG). Our study aimed to assess the impact of CABG on left ventricular (LV) systolic function and identify predictors of adverse postoperative outcomes. We conducted a prospective cross-sectional study involving 110 CABG patients with a mean age of 56.1 ± 12.2 years and preoperative left ventricular ejection fraction (LVEF) below 50%. Patients were categorized into two groups: group I (n=76, LVEF &gt; 35%) and group II (n=34, LVEF &lt; 35%). In group II, there was a significantly higher prevalence of diabetes mellitus (DM) (p = 0.05) and Euro SCORE II compared to group I (p &lt; 0.001). However, other clinical predictors showed no significant difference between the two groups. Both groups exhibited a significant improvement in LVEF post-surgery (p = 0.05), with comparable in-hospital mortality rates recorded. The study identified DM, significant diastolic dysfunction, and intra-aortic balloon pump (IABP) insertion as predictors of in-hospital mortality (p = 0.001, 0.03, and &lt; 0.001, respectively). These findings suggest a noticeable enhancement in LV systolic function post-CABG, contributing to improved survival rates. However, patients with DM, significant diastolic dysfunction, and those requiring IABP insertion during the perioperative period are at higher risk of mortality. Therefore, targeted attention and specialized care are essential for optimizing outcomes in these high-risk patients.

Current ideas about the role of ranolazine in patients’ treatment with angina pectoris

The article presents modern views on the role of the anti-ischemic agent, ranolazine, in the treatment of a wide range of patients with angina pectoris. It also provides data on a percentage increase in the number of patients with chronic coronary artery disease who need improved anti-ischemic therapy. The need to use alternative agents for the treatment of angina, which is highlighted in the article, is determined by a percentage increase in the number of elderly and senile patients with angina, as such patients often have concomitant diseases that limit the use of haemodynamic anti-ischemic agents. The authors consider various pathophysiological links in the development of myocardial ischemia, which may become the background for choosing a specific anti-ischemic agent. Amongst others, the article provides evidence data on the effectiveness of the usage of ranolazine in patients with angina pectoris and myocardial ischemia, but in the absence of coronary artery obstruction. The mechanisms of action of ranolazine, which determine both its anti-ischemic and pleiotropic effects, are discussed in detail. Special effects of ranolazine that may be beneficial for patients with coronary artery disease and clinically significant diastolic dysfunction are observed. This effect consisted of a positive effect of ranolazine on the left ventricular diastolic function. Data on the cost-effectiveness of the usage of ranolazine in the treatment of angina pectoris are provided. The antiarrhythmic action of ranolazine is considered separately. The article discusses the tolerability of ranolazine and its possible side effects. The all-round good tolerability and high safety of ranolazine in a wide range of patients with coronary artery disease are emphasized.

Real-time cardiovascular magnetic resonance imaging for non-invasive characterisation of heart failure with preserved ejection fraction: final outcomes of the HFpEF stress trial

BackgroundThe diagnosis of heart failure with preserved ejection fraction (HFpEF) remains challenging. Recently, the HFpEF Stress Trial demonstrated feasibility and accuracy of non-invasive cardiovascular magnetic resonance (CMR) real-time (RT) exercise-stress atrial function imaging for early identification of HFpEF. However, no outcome data have yet been presented.MethodsThe HFpEF Stress Trial (DZHK-17) prospectively recruited 75 patients with dyspnea on exertion and echocardiographic preserved EF and signs of diastolic dysfunction (E/eʹ > 8). 68 patients entered the final study cohort and were characterized as HFpEF (n = 34) or non-cardiac dyspnea (n = 34) according to pulmonary capillary wedge pressure (HFpEF: PCWP rest: ≥ 15 mmHg stress: ≥ 25 mmHg). These patients were contacted by telephone and hospital charts were reviewed. The clinical endpoint was cardiovascular events (CVE).ResultsFollow-up was performed after 48 months; 1 patient was lost to follow-up. HFpEF patients were more frequently compared to non-cardiac dyspnea (15 vs. 8, p = 0.059). Hospitalised patients during follow-up had higher H2FPEF scores (5 vs. 3, p < 0.001), and impaired left atrial (LA) function at rest (p ≤ 0.002) and stress (p ≤ 0.006). Impairment of CMR-derived atrial function parameters at rest and during exercise-stress (p ≤ 0.003) was associated with increased likelihood for CVE. CMR-Feature Tracking LA Es/Ee (p = 0.016/0.017) and RT-CMR derived LA long axis strain (p = 0.003) were predictors of CVE independent of the presence of atrial fibrillation.ConclusionsLeft atrial function emerged as the strongest predictor for 4-year outcome in the HFpEF Stress Trial. A combination of rest and exercise-stress LA function quantification allows accurate diagnostic and prognostic stratification in HFpEF.Clinicaltrials.gov: NCT03260621.Graphical abstract

Anti-signal recognition particle antibodies induce cardiac diastolic dysfunction via oxidative stress injury.

Anti-signal recognition particle (SRP) antibodies, markers of immune-mediated necrotising myopathy, are reportedly related to cardiac involvement; however, whether they are pathogenic to the myocardium remains unclear. We aimed, therefore, to explore the pathogenicity of anti-SRP antibodies against the myocardium through in vivo and in vitro studies. Total immunoglobulin G (IgG), purified from patients with positive anti-SRP antibodies, was passively transferred into C57BL/6 mice. Cardiac function was evaluated via echocardiography and the ventricular pressure-volume loop; cardiac histological changes were analysed using haematoxylin-eosin staining, picrosirius red staining, immunofluorescence and immunohistochemistry. Additionally, reactive oxygen species (ROS) formation was evaluated by dihydroethidium (DHE) staining; mitochondrial morphology and function were evaluated using transmission electron microscopy and seahorse mitochondrial respiration assay, respectively. The myositis cohort at our centre was subsequently reviewed in terms of cardiac assessments. After the passive transfer of total IgG from patients with positive anti-SRP antibodies, C57BL/6 mice developed significant left ventricular diastolic dysfunction (LVDD). Transcriptomic analysis and corresponding experiments revealed increased oxidative stress and mitochondrial damage in the hearts of the experimental mice. Cardiomyocytes exposed to anti-SRP-specific IgG, however, recovered normal mitochondrial metabolism after treatment with N-acetylcysteine, an ROS scavenger. Moreover, patients positive for anti-SRP antibodies manifested worse diastolic but equivalent systolic function compared to their counterparts after propensity score matching. Anti-SRP antibodies may play a pathogenic role in the development of LVDD by promoting ROS production and subsequent myocardial mitochondrial impairment. The inhibition of oxidative stress was effective in reversing anti-SRP antibody-induced LVDD.

Obesity and heart failure with preserved ejection fraction.

Aim: To perform an overall assessment of heart failure with preserved ejection fraction (HFpEF) adults with central obesity. Materials and Methods: We enrolled HFpEF patients with central obesity (n =73, mean age 52.4 ± 6.3 years) and without obesity (n =70, mean age 51.9 ± 7.1 years) and compared with an age-matched healthy subjects who had not suffered from HF (n = 69, mean age 52.3 ± 7.5 years). Physical examination, routine laboratory tests such as fasting blood glucose, fasting insulin, insulin resistance (HOMA) index, serum lipids, haemoglobin, creatinine, ALT, AST, uric acide, hs CRP, TSH, N-terminal proB-type natriuretic peptide (NT-proBNP) and standard transthoracic echocardiogram (2D and Doppler) examinations were performed and assessed. Results: The average values of diastolic blood pressure (DBP), glucose and lipid profiles, uric acide, hs CRP were found to be significantly higher among obese patients with HFpEF than non-obese. Despite more severe symptoms and signs of HF, obese patients with HFpEF had lower NT-proBNP values than non-obese patients with HFpEF (129±36.8 pg/ml, 134±32.5 pg/ml vs 131±30.4 pg/ml, 139±33.8 pg/ml respectively; p < 0.05). However, it was found that patients with high central (visceral) adiposity have more pronounced obesity-related LV diastolic dysfunction, lower E/e' ratio, lower mitral annular lateral e' velocity, an increased LV diastolic dimension and LV mass index. Compared with non-obese HFpEF and control subjects, obese patients displayed greater right ventricular dilatation (base, 35±3.13 mm, 36±4.7 mm vs 33±2.8 mm, 34±3.2 mm and 29±5.3 mm, 30±3.9 mm; length, 74±5 mm, 76±8 mm vs 67±4 mm, 69±6 mm and 60±3 mm, 61±5 mm respectively; p < 0.05), more right ventricular dysfunction (TAPSE 16±2 mm, 15±3 mm vs 17±2 mm, 17±1 mm and 19±2 mm, 20±3 mm respectively; p < 0.05). Conclusions: Obese patients with HFpEF have higher diastolic BP, atherogenic dyslipidemia, insulin resistance index values and greater systemic inflammatory biomarkers, despite lower NT-proBNP values, which increase the risk of cardiovascular events in future. Echocardiography examination revealed not only significant LV diastolic dysfunction, but also displayed greater RV dilatation and dysfunction.

Speckle-Tracking Analysis of the Right and Left Heart after Peak Exercise in Healthy Subjects with Type 1 Diabetes: An Explorative Analysis of the AppEx Trial.

In eight healthy participants with Type 1 diabetes (T1D) exercise-related dynamic cardiac remodeling was analyzed by performing two-dimensional echocardiography, including deformation analysis of the left-ventricular (LV) global longitudinal strain (LV-GLS), and the deformation pattern of the left atrium (LA) and right ventricle (RV) at rest and post-peak performance on a bicycle. The feasibility echocardiographic speckle-tracking analysis was performed on eight asymptomatic participants with T1D (n = 8, male n = 5, age: 23-65 years). The obtained echocardiographic data were compared for various echocardiographic parameters at rest and post exercise. Across our participating T1D individuals no structural echocardiographic abnormalities of concern could be revealed. All participating T1D subjects showed preserved contractile reserve of the LV and no significant diastolic dysfunction. Significant differences were found for the phasic LA contractile strain pattern at rest and post exercise (p < 0.001), whereby the dynamic RV (p = 0.5839 and p = 0.7419) and LV strain pattern (p = 0.5952) did not reveal significant differences in comparison to resting conditions. This descriptive secondary outcome analysis describes preserved contractile reserve of the LV and elucidates dynamic modification of the phasic LA contractile deformation pattern in asymptomatic T1D individuals after exhaustive exercise on a bicycle.

Cardiovascular magnetic resonance rest and exercise-stress left atrioventricular coupling index to detect diastolic dysfunction

Abstract Background Left atrial and ventricular (LA/LV) dysfunction are inter-linked in heart failure with preserved ejection fraction (HFpEF), however little is known about their inter-play and relation to cardiac decompensation. We hypothesized that cardiovascular magnetic resonance (CMR) left atrioventricular coupling index (LACI) would identify pathophysiological alterations in HFpEF and be amenable to rest and ergometer-stress CMR. Methods Patient with exertional dyspnoea, signs of diastolic dysfunction (E/e’ ≥8) and preserved EF (≥50%) on echocardiography were prospectively recruited and classified as HFpEF (n=34) or non-cardiac dyspnoea (NCD, n=34) according to pulmonary capillary wedge pressure (PCWP) on right heart catheterisation (rest/stress: ≥15/25 mmHg). LA and LV volumes were assessed on short-axis real-time cine sequences at rest and during exercise-stress. LACI was defined as the ratio of the LA/LV end-diastolic volume. Cardiovascular hospitalisation (CVH) was assessed after 24 months. Results Volume-derived LA (p≥0.008) but not LV (p≥0.347) morphology and function at rest and during exercise-stress detected significant differences comparing HFpEF and NCD. There was impaired atrio-ventricular coupling in HFpEF at rest (LACI 45.7 vs 31.6 %, p&amp;lt;0.001) and during exercise-stress (45.7 vs 27.9 %, p&amp;lt;0.001). LACI correlated with PCWP at rest (r=0.48, p&amp;lt;0.001) and during exercise-stress (r=0.55, p&amp;lt;0.001). At rest, LACI was the only volumetry derived parameter to differentiate NCD and HFpEF patients which were identified using exercise-stress thresholds (p=0.001). Resting and exercise-stress LACI dichotomised at their medians were associated CVH (p≤0.005). Conclusions Assessment of LACI is a simple approach for LA/LV coupling quantification and allows easy and fast identification of heart failure with preserved ejection fraction (HFpEF).

Vitronectin promotes TTR deposition and mitochondrial damage in ATTR-CA mice

Abstract Background Transthyretin cardiac amyloidosis (ATTR-CA) is an increasingly recognized disorder that leads to heart failure and cardiovascular death. However, the pathogenesis of ATTR-CA is still poorly understood. Vitronectin (VTN), a common component of the extracellular matrix, has been reported to be associate with amyloidosis. However, the role of VTN in TTR deposition has not been clarified. Purpose Here we aimed to elucidate the TTR deposition mechanism in ATTR-CA and test therapeutic interventions using a gene-edited ATTR-CA mice model. Methods We used CRISPR/Cas9-mediated genome engineering to create humanized wild-type TTR knock-in mice (hTTRWT). Cardiac function was examined by echocardiography and pressure-volume analysis. VTN expression was assessed by immunofluorescence and western blotting. Interactions among VTN and TTR are analyzed with in vitro pull-down and co-immunoprecipitation (Co-IP) assays. Recombinant TTR protein was added in the culture of VTN overexpressed mice primary cardiomyocytes (CMs) to simulate the TTR deposition process in vitro. Mitochondrial function was determined by the Seahorse assay and mitochondrial ultrastructure was evaluated with the transmission electron microscope.Additionally, we assessed the mitochondrial damage with mitoSOX staining. Results In the hTTRWT group, pressure-volume analysis and echocardiography revealed significant diastolic dysfunction and increased left ventricle chamber stiffness at 52 weeks. Compared to WT group, the hTTRWT group showed a dramatic elevation of VTN in hearts. Co-IP and pull-down assays confirmed a direct interaction between VTN and TTR. In cultured CMs exposed to recombinant TTR protein, VTN overexpression promotes the deposition of TTR. Damaged mitochondrial ultrastructure, elevated oxidative stress and decreased mitochondrial numbers were found. In accordance with observed mitochondrial abnormalities, seahorse experiments demonstrated impaired mitochondrial respiration capacity. Conclusion These results suggest that the VTN contributes to ATTR-related pathological and cardiac function changes and mitochondrial dysfunction as a contributor of disease progression from ATTR-CA to heart failure.

Therapeutic Aspects of Prunus cerasus Extract in a Rabbit Model of Atherosclerosis-Associated Diastolic Dysfunction.

This study evaluates the potential therapeutic effects of anthocyanin-rich Prunus cerasus (sour cherry) extract (PCE) on atherosclerosis-associated cardiac dysfunction, described by the impairment of the NO-PKG (nitric oxide-protein kinase G) pathway and the antioxidant capacity. Initially, a rabbit model of atherosclerotic cardiovascular disease was established by administering a cholesterol-rich diet, enabling the examination of the impact of 9 g/kg PCE on the pre-existing compromised cardiovascular condition. After that, the animals were divided into four groups for 12 weeks: the (1) untreated control group; (2) PCE-administered healthy rabbits; (3) hypercholesterolemic (HC) group kept on an atherogenic diet; and (4) PCE-treated HC group. Dyslipidemia, impaired endothelial function, and signs of diastolic dysfunction were evident in hypercholesterolemic rabbits, accompanied by a reduced cardiac expression of eNOS (endothelial nitric oxide synthase), PKG, and SERCA2a (sarco/endoplasmic reticulum calcium ATPase 2a). Subsequent PCE treatment improved the lipid profile and the cardiac function. Additionally, PCE administration was associated with elevated myocardial levels of eNOS, PKG, and SERCA2a, while no significant changes in the vascular status were observed. Western blot analysis further revealed hypercholesterolemia-induced increase and PCE-associated reduction in heme oxygenase-1 expression. The observed effects of anthocyanins indicate their potential as a valuable addition to the treatment regimen for atherosclerosis-associated cardiac dysfunction.