Global Heart Research Articles

Stress and Heart in Remodeling Process: Multiple Stressors at the Same Time Kill.

Myocardial remodeling is developed by increased stress in acute or chronic pathophysiologies. Stressed heart morphology (SHM) is a new description representing basal septal hypertrophy (BSH) caused by emotional stress and chronic stress due to increased afterload in hypertension. Acute stress cardiomyopathy (ASC) and hypertension could be together in clinical practice. Therefore, there are some geometric and functional aspects regarding this specific location, septal base under acute and chronic stress stimuli. The findings by our and the other research groups support that hypertension-mediated myocardial involvement could be pre-existed in ASC cases. Beyond a frequently seen predominant base, hyperkinetic tissue response is detected in both hypertension and ASC. Furthermore, hypertension is the responsible factor in recurrent ASC. The most supportive prospective finding is BSH in which a hypercontractile base takes a longer time to exist morphologically than an acutely developed syndrome under both physiologic exercise and pressure overload by transaortic binding in small animals using microimaging. However, cardiac decompensation with apical ballooning could mask the possible underlying hypertensive disease. In fact, enough time for the assessment of previous hypertension history or segmental analysis could not be provided in an emergency unit, since ASC is accepted as an acute coronary syndrome during an acute episode. Additional supportive findings for SHM are increased stress scores in hypertensive BSH and the existence of similar tissue aspects in excessive sympathetic overdrive like pheochromocytoma which could result in both hypertensive disease and ASC. Exercise hypertension as the typical form of blood pressure variability is the sum of physiologic exercise and pathologic increased blood pressure and results in increased mortality. Hypertension is not rare in patients with a high stress score and leads to repetitive attacks in ASC supporting the important role of an emotional component as well as the potential danger due to multiple stressors at the same time. In the current review, the impact of multiple stressors on segmental or global myocardial remodeling and the hazardous potential of multiple stressors at the same time are discussed. As a result, incidentally determined segmental remodeling could be recalled in patients with multiple stressors and contribute to the early and combined management of both hypertension and chronic stress in the prevention of global remodeling and heart failure.

Characteristics, management, and outcomes in women and men with congestive heart failure in 40 countries at different economic levels: an analysis from the Global Congestive Heart Failure (G-CHF) registry

There is a paucity of data on the clinical characteristics, management, and outcomes of women compared with men with heart failure in low-income and middle-income countries compared with high-income countries. We examined sex differences in risk factors, clinical characteristics, and treatments, and prospectively assessed the risk of heart failure hospitalisation and mortality in patients with heart failure in 40 high-income, middle-income, and low-income countries. Participants aged 18 years or older with heart failure were enrolled from Dec 20, 2016, to Sept 9, 2020 in the prospective Global Congestive Heart Failure (G-CHF) study from 257 centres in 40 high-income, middle-income, and low-income countries. Participants were followed up until May 25, 2023. We recorded the demographic characteristics, medical history, and treatments of participants. We prospectively recorded data on heart failure hospitalisation and mortality by sex in the overall study, according to country economic status, and according to level of left ventricular ejection fraction (LVEF). 23 341 participants (9119 [39·1%] women and 14 222 [60·1%] men) were recruited and followed up for a mean of 2·6 years (SD 1·4). The mean age of women in the study was 62 years (SD 17) compared with 64 years (14) in men. Fewer women than men had an LVEF of 40% or lower (51·7% women vs 66·2% men). By contrast, more women than men had an LVEF of 50% or higher (33·2% women vs 18·6% men). Hypertensive heart failure was the most common aetiology in women (25·5% women vs 16·8% men), whereas ischaemic heart failure was the most common aetiology in men (45·6% men vs 26·6% women). Signs and symptoms of congestion were more common in women than men: 42·6% of women had a New York Heart Association functional class of III or IV compared with 37·9% of men. The use of heart failure medications and cardiac tests did not differ systematically between the sexes, although implantable cardioverter defibrillator (ICD) implantation was lower among women than men (8·7% women vs 17·2% men). The adjusted risk of heart failure hospitalisation was similar in women and men (women-to-men adjusted hazard ratio [HR] 0·99 [95% CI 0·92-1·05]). This pattern was consistent within groups of countries categorised by economic status, geographical region, and by LVEF level. However, women had a lower adjusted risk of mortality (women-to-men adjusted HR 0·79 [95% CI 0·75-0·84]) despite adjustments for prognostic factors-a pattern which was consistently observed across groups of countries irrespective of economic status, geography, and LVEF levels of patients. The underlying cause of heart failure and ejection fraction phenotype differ between women and men, as do the severity of symptoms. Heart failure treatments (except ICD use) were not consistently in favour of one sex. Paradoxically, while the rates of hospitalisations were similar among women and men, the risk of death was lower among women. These patterns were consistent regardless of the economic status of the countries. The higher mortality among men is unexplained and warrants further study. Bayer.

Learning from our differences: insights from a global heart failure registry

Learning from our differences: insights from a global heart failure registry

Pancreatic iron in pediatric transfusion-dependent beta-thalassemia patients: A longitudinal MRI study.

In pediatric transfusion-dependent thalassemia (TDT) patients, we evaluated the prevalence, pattern, and clinical associations of pancreatic siderosis and the changes in pancreatic iron levels and their association with baseline and changes in total body iron balance. We considered 86 pediatric TDT patients consecutively enrolled in the Extension-Myocardial Iron Overload in Thalassemia Network. Iron overload (IO) was quantified by R2* magnetic resonance imaging (MRI). Sixty-three (73%) patients had pancreatic IO (R2*>38Hz). Global pancreas R2* values were significantly correlated with mean serum ferritin levels, MRI liver iron concentration (LIC) values, and global heart R2* values. Global pancreas R2* values were significantly higher in patients with altered versus normal glucose metabolism. Thirty-one patients also performed the follow-up MRI at 18±3months. Higher pancreatic R2* values were detected at the follow-up, but the difference versus the baseline MRI was not significant. The 20% of patients with baseline pancreatic IO showed no pancreatic IO at the follow-up. The 46% of patients without baseline pancreatic IO developed pancreatic siderosis. The changes in global pancreas R2* between the two MRIs were not correlated with baseline serum ferritin levels, baseline, final, and changes in MRI LIC values, or baseline pancreatic iron levels. In children with TDT, pancreatic siderosis is a frequent finding associated with hepatic siderosis and represents a risk factor for myocardial siderosis and alterations of glucose metabolism. Iron removal from the pancreas is exceptionally challenging and independent from hepatic iron status.

Septic cardiomyopathy-diagnosis and estimation of disease severity

The relevance of septic cardiomyopathy is frequently underestimated due to the complexity of the pattern of cardiac injury and the corresponding difficulties in quantifying the degree of functional impairment. Account of the methods for diagnosis and severity classification of septic cardiomyopathy. Literature review and analysis of the main findings. Septic cardiomyopathy is characterized by both systolic and diastolic impairment of not only the left, but also the right ventricle, as well as by sinus-tachycardiomyopathy (≥ 90-95beats/min) of variable degree. Sepsis-related organ failure assessment (SOFA) score, left ventricular ejection fraction (LVEF), ECG and cardiac biomarkers do not help in grading severity of septic cardiomyopathy. For that purpose either asophisticated echocardiography diagnosis is mandatory, or the measurement of those global heart function parameters which take into account the dependency of cardiac output on afterload, in view of the pronounced vasodilatation in sepsis and septic shock, is needed. Asuitable parameter on the basis of cardiac output measurement is afterload-related cardiac performance (ACP), which gives the percentage of cardiac output in aseptic patient related to the cardiac output ahealthy heart pumps when challenged by afall in systemic vascular resistance to the same extent. The calculation of ACP shows that at least one in two septic patients suffers from impaired heart function and that mortality increases as severity increases. Simple parameters like LVEF are not apt for diagnosis nor for disease severity classification of septic cardiomyopathy. For that purpose either sophisticated echocardiography techniques or load-independent parameters-best validated-ACP measurements are appropriate.

Subclinical cardiac impairments in fetuses conceived through assisted reproductive technology by speckle tracking echocardiography.

To evaluate the changes of cardiac morphology and function in fetuses conceived through assisted reproductive technologies (ART) by speckle tracking echocardiography. A retrospective study was conducted in 101 spontaneously conceived (SC) fetuses and 99 ART-conceived ones. Fetal echocardiography was performed, fetal cardiac morphology and function were analyzed using two-dimensional speckle tracking software, including global sphericity index (GSI), global longitudinal strain (GLS), fractional area change (FAC) of the left and right ventricles, as well as segmental sphericity index (SI), end-diastolic diameter (ED), and fractional shortening (FS) in 24 segments. Compared to the SC fetuses, the ART-conceived fetuses exhibited decreased GSI (median [interquartile range], 1.22 [1.16-1.27] vs. 1.18 [1.11-1.24], p=0.007), decreased right ventricular GLS (24.9 [21.5-27.6] vs. 23.2 [20.4-26.8], p=0.026), and decreased right ventricular FAC (mean±standard deviation, 39.7±6.4 vs. 37.2±7.1, p=0.003). Analysis of the 24 segments showed that ART-conceived fetuses had reduced SI in the apical segments of right ventricle and increased ED in several segments of the right ventricle. Fetuses conceived through ART had a more spherical shape of the global heart and predominantly right-sided cardiac remodeling and systolic function impairment.

Intensity Distribution of Collegiate Cross-Country Competitions.

The primary purpose of the current investigation was to perform an intensity distribution analysis of a collegiate cross-country (CC) competition, with a secondary purpose to compare race times (RT) with modeled performance times (MPT). Participants completed an incremental treadmill test to determine gas exchange threshold (GET), while the three-minute all-out test was conducted on a 400 m outdoor track to determine critical velocity (CV) and D prime (D'). GET and CV were used as physiological markers for the intensity zones based on heart rate (HR) and running velocity (RV), while CV and D' were used to determine modeled performance times. Participants wore a Global Positioning System (GPS) watch and heart rate (HR) monitor during competition races. Statistically, less time was spent in HR Zone 1 (12.1% ± 13.7%) compared to Zones 2 (37.6% ± 30.2%) and 3 (50.3% ± 33.7%), while a statically greater amount of time was spent in RV Zone 2 (75.0% ± 20.7%) compared to Zones 1 (8.4% ± 14.0%) and 3 (16.7% ± 19.1%). RTs (1499.5 ± 248.5 seconds (s)) were statistically slower compared to MPTs (1359.6 ± 192.7 s). The observed differences in time spent in each zone are speculated to be related to the influence of environmental conditions on internal metrics and difference in the kinetics of HR and running velocity. Differences in RTs and MPTs are likely due to the MPT equation modeling all-out performance and not considering race strategies.

Dyslipidemia among HIV-infected patients in Ethiopia: a systematic review and meta-analysis

BackgroundDyslipidemia is responsible for more than half of the global ischemic heart disease (IHD) and more than 4 million deaths annually. Assessing the prevalence of dyslipidemia can be crucial in predicting the future disease development and possible intervention strategies. Therefore, this systematic review and meta-analysis was aimed at assessing the pooled prevalence of dyslipidemia in HIV-infected patients.MethodsElectronic databases such as EMBASE, Google Scholar, PubMed, Web of Science, ResearchGate, Cochrane Library, and Science Direct were searched for articles and grey literature. All relevant studies found until our search period of May 24, 2023 were included. The Newcastle–Ottawa Quality Assessment Scale was used to assess the quality of the included studies. The data were extracted in Microsoft Excel. The STATA version 14 software was used to conduct the meta-analysis. I2 and Cochran’s Q test were employed to assess the presence of heterogeneity between studies. Due to the presence of heterogeneity, a random effect model was used. The publication bias was assessed using the symmetry of the funnel plot and Egger's test statistics. Moreover, subgroup analysis, and sensitivity analysis were also done.ResultsA total of nine studies that reported the prevalence of dyslipidemia were included. The overall pooled prevalence of dyslipidemia among HIV-infected patients in Ethiopia was 67.32% (95% CI = 61.68%–72.96%). Furthermore, the overall pooled estimates of dyslipidemia among ART-taking and treatment-naïve HIV-infected patients were 69.74% (95% CI: 63.68–75.8, I2 = 87.2) and 61.46% (95% CI: 45.40–77.52, I2 = 90.3), respectively. Based on lipid profile fractionations, the pooled estimates for high total cholesterol (TC) were 39.08% (95% CI: 31.16–46.99), high triglycerides were 38.73% (95% CI: 28.58–48.88), high low density lipoprotein (LDL-c) was 28.40% (95% CI: 17.24–39.56), and low high density lipoprotein (HDL-c) was 39.42% (95% CI: 30.47–48.38).ConclusionMore than two-thirds of HIV-infected patients experienced dyslipidemia. Therefore, it's critical to regularly evaluate lipid alterations in HIV-infected patients in order to prevent the onset of atherosclerosis and other cardiovascular problems.

Acute and Transient Match-Related Fatigue in University Female Footballers

This study aimed to examine the acute fatigue response experienced by female footballers during and after match-play. Twenty university footballers completed three trials of a countermovement jump on a force platform pre- and post-match-play (35 observations). External and internal loads were recorded during match-play via global positioning systems (GPS) and heart rate (HR), respectively. Match-play loads were split into thirds and analyzed via linear mixed model. Pre- and postjump metrics (n = 16) were analyzed using a paired samples t test. Significant decrements were observed between the first and final third for all external load metrics apart from sprint distance and accelerations (p > .05). Relative concentric peak force (p = .035) was significantly increased postmatch, while a reduction was observed for relative concentric mean power (p = .034). The remaining 14 metrics did not display any significant changes (p > .05). The stability of countermovement jump (CMJ) performance pre- to postmatch alongside the reductions within match support the notion of transient fatigue. Moreover, coaches can use this data (i.e., transient fatigue) to inform tactics in female football (i.e., substitutions) and conditioning regimes.

Low Vitamin D Levels Are Associated with Increased Cardiac Iron Uptake in Beta-Thalassemia Major.

We evaluated the association of vitamin D and parathormone (PTH) levels with cardiac iron and function in beta-thalassemia major (β-TM) patients. Two-hundred and seventy-eight TM patients (39.04 ± 8.58 years, 56.8% females) underwent magnetic resonance imaging for the assessment of iron overload (T2* technique), biventricular function parameters (cine images), and replacement myocardial fibrosis (late gadolinium enhancement technique). Vitamin D levels were deficient (<20 ng/dL) in 107 (38.5%) patients, insufficient (20-30 ng/dL) in 96 (34.5%) patients, and sufficient (≥30 ng/dL) in 75 (27.0%) patients. Deficient vitamin D patients had a significantly higher frequency of myocardial iron overload (MIO; global heart T2* < 20 ms) than patients with sufficient and insufficient vitamin D levels and a significantly higher left ventricular end-diastolic volume index and mass index than patients with sufficient vitamin D levels. PTH was not associated with cardiac iron, function, or fibrosis. In the multivariate regression analysis, vitamin D, serum ferritin, and pancreatic iron levels were the strongest predictors of global heart T2* values. In receiver operating characteristic curve analysis, a vitamin D level ≤ 17.3 ng/dL predicted MIO with a sensitivity of 81.5% and a specificity of 75.3% (p < 0.0001). In TM, the periodic and regular assessment of vitamin D levels can be beneficial for the prevention of cardiac iron accumulation and subsequent overt dysfunction.

Contrasting patterns of symptoms compared to mortality in women and men with Congestive Heart Failure (the G-CHF registry)

Abstract Background There is a paucity of data on the clinical characteristics, management, and outcomes of women compared with men with heart failure, especially in low-and middle-income countries. Purpose In this study from the Global Congestive Heart Failure registry, we examined sex differences in risk factors, clinical characteristics, treatments, and the risk of heart failure hospitalization and mortality by country economic status and by left ventricular ejection fraction (LVEF) category. Methods In the prospective Global-Congestive Heart Failure (G-CHF) study, participants with established heart failure were considered for inclusion from 40 high-, middle-, and low-income countries. We recorded information on the demographic characteristics, medical history, and treatments of participants. We report data on heart failure hospitalization and mortality by sex overall, by country economic status, and by LVEF category. Results From December 2016 to July 2022, 23,000 participants were recruited and followed up. The average age of women in the study was 62 years compared to 64 years in men. Fewer women than men had a LVEF ≤40 (51.7% women vs 66.3% men). By contrast, more women than men had an LVEF≥ 50 (33.2% women vs 18.6% men). Hypertensive heart failure was the most common etiology in women (25.5% women vs 16.8% men), and ischemic heart failure was the most common etiology in men (45.6% men vs 26.6% women). Signs and symptoms of heart failure were more common in women than men: 42.6% of women were NYHA functional class III/IV compared to 37.9% of men. Among participants with a LVEF &amp;lt;35, use of implantable cardiac defibrillator (ICD) was lower in women than men in the overall study (8.7% women vs 17.2% men), and within countries categorized by economic status. However, the use of heart failure medicines and cardiac tests did not differ systematically by sex. Differences by sex were not observed in the adjusted risk of heart failure hospitalization overall (women-to-men adjusted hazard ratio 1.0 (95% CI 0.94 to 1.07)). This pattern was consistent within countries categorized by economic status, geographic region, and by LVEF category. Women had a lower adjusted risk of mortality overall (women-to-men adjusted hazard ratio 0.82 (95% CI 0.77 to 0.87), which was consistently observed within countries categories by economic status, geographic region, and LVEF levels. Conclusions There are differences between women and men in heart failure symptoms, underlying causes, ejection fraction categories, and use of an ICD. However, use heart failure medications, cardiac tests, and hospitalization were similar in women and men; but women had a lower risk of death.

Intracardiac thrombosis and vascular involvement in Behcet's syndrome: two sides of the same coin?

Abstract Background Behçet’s syndrome (BS) is a complex and relapsing vasculitis that affects vessels of all kinds and sizes. Intracardiac thrombosis (ICT) is a rare but serious complication of the disease, that usually presents with vascular lesions. However, its pathogenesis remains unclear and the link between these manifestations is yet not fully clarified. Objectives Our work aims to describe the clinical characteristics, imaging features, therapeutic management, and outcomes of BS patients with ICT. And secondly, to shed some light on the relation between ICT and the vascular involvement of the disease. Methods We retrospectively conducted a descriptive and monocentric study including 531 BS patients admitted to our department between 2010 and 2022. Results Twelve cases of ICT were enrolled (2%). Patients were mostly males (91.6%), with a mean age of 29 ± 6 years (20 – 41). Past history of lower extremity deep vein thrombosis (DVT) related to BS was frequently reported (41%). ICT was the revealing manifestation of the disease in 50% of the cases. In the other half, it occurred after a median of 4 years following BS onset. Symptoms were dyspnea (50%), chest pain (50%), dry cough (40%), and hemoptysis (30%). Signs of right (33%) and global (17%) heart failure were found. Concomitant noncardiovascular manifestations were mainly mucocutaneous (80%). Inflammatory parameters were always raised with a median ESR of 48 mm/h and CRP of 52 mg/l. Hemostasis parameters were within the normal ranges for all patients. High levels of BNP and Troponin were detected in respectively 50% and 16% of the cases. On echocardiography, ICT was located in the right heart (100%), with an extension to the inferior vena cava (50%). Multiple thrombi were visualized in three cases. The associated cardiac lesions were pericardial effusion (50%), tricuspid (50%) and mitral insufficiency (10%), endomyocardial fibrosis (10%), myocarditis (10%), and ischemic coronaropathy (8%). Pulmonary hypertension (75%) and right dilatation (58%) were frequent, with persevered systolic function (100%). On Chest CTA, pulmonary artery thrombosis (70%) and aneurysms (50%) were observed. Peripheral DVT was also common (41%). All patients were treated with colchicine, glucocorticoids, and immunosuppressants: cyclophosphamide (n=11), and TNF-alpha inhibitor (n=1). Curative anticoagulation was prescribed in half of the cases. Outcomes were: complete remission (n=9), partial remission (n=2), and relapse (n=1). No death was recorded. Conclusion ICT in BS is a life-threatening event that occurs in the first years of the disease onset, among young men with vascular lesions, especially of the pulmonary arteries and vena cava. We believe that this strong association is highly suggestive that, unlike other thrombotic diseases, ICT in BS is a direct consequence of the underlying vasculitis. Hence, prompt and adequate management with immunosuppressive therapy is usually associated with good outcomes.Clinical baseline characteristicsCardiac and vascular manifestations

Enhancing autophagic flux via FYCO1 confers protection against adverse cardiac remodeling in response to myocardial ischemia

Abstract Background Dysregulation of autophagy is known to have detrimental effects on cardiac function. Yet, the autophagy-lysosome pathway in the context of ischemia is still widely unexplored. Fyco1 is highly expressed in the heart and facilitates transport of autophagosomes in cardiomyocytes, thereby enhancing global autophagic flux. Purpose The purpose of our study was to study the potentially beneficial effects of activation of autophagy via FYCO1 on cardiac remodeling post myocardial infarction. Methods FYCO1-Tg mice were crossbred with RFP-EGFP-LC3-Tg reporter mice (FYCO1-TGxRGFP) to enable analysis of autophagic flux in vivo using confocal microscopy. Myocardial ischemia was induced by permanent ligation of left anterior descending artery (LAD). Mice were analyzed 3 and 30 days post LAD ligation. Cardiac function (ejection fraction, EF) was measured by echocardiography. Fibrosis and Infarct size (%) were assessed in Masson’s Trichrome staining. Autophagy activity was analysed by Western blot for p62 and LC3 II. Furthermore, Evans blue/TTC staining was performed to assess the area at risk and to define perfused, ischemic and necrotic area post LAD ligation. Results Under conditions of FYCO1 overexpression isolated cardiomyocytes were capable to remain a status of activated autophagy in hypoxia; presented with significantly increased protein levels of p62 (ctrl: 1±0,02; OE: 3,1±0,4) and LC3 II (ctrl: 1±0,05; OE: 5,5±0,4). In FYCO1-TGxRGFP mice we observed an overall increased autophagic flux demonstrated by significantly increased p62 expression (WT LAD: 2,9±0,4; TG LAD:4,0±0,5) and LC3 II protein levels (WT LAD: 1,6±0,2; TG LAD:14,0±1,4) post LAD ligation. While WT mice revealed accumulation of autolysosomes 30 days post LAD ligation as assessed by confocal microscopy (WT autophagosomes: 1±0,4; WT autolysosomes: 38,6±3,8), in FYCO1-TGxRGFP mice the ratio between autophagosomes and autolysosomes remained even (TG autophagosomes:43,3±5,1; TG autolysosomes: 73,5±12,4), suggesting preservation of adequate autophagic flux. In Evans blue/TTC staining, FYCO1-TGxRGFP mice demonstrated comparable ischemic but a markedly decreased necrotic area (ischemic: 1,9±1,8%; necrotic: 37,1±11,5%) of the LV as compared to WT (ischemic: 2,1±1,9%; necrotic: 53,4±31,4%). Fibrosis (WT: 19,6±1,8%; TG: 10,6±1,6%) and infarct size (WT: 34,5 ±3,9%; TG: 5,5±2%) was found significantly decreased in FYCO1-TGxRGFP-mice. Importantly, global heart function of FYCO1-TGxRGFP-mice was significantly improved post LAD compared to WT (EF WT: 36,7±6,3%; TG: 46,3±18,3%). Conclusion Our study demonstrates that activation of autophagy via FYCO1 protects against accumulation of autolysosomes and therefore protects against adverse cardiac remodeling and improves cardiac function post myocardial ischemia. These findings may offer translational potential in enhancing autophagic flux in the context of myocardial ischemia.

FUDNC1 ameliorates doxorubicin-induced cardiotoxicity by restoring MERCs structure and blocked autophagic flux

Abstract Background Doxorubicin (DOX)-induced cardiotoxicity (DIC) is frequently observed in clinical practice. Autophagy dysregulation is known to be a mechanism of DIC. Mitochondrial-Endoplasmic Reticulum Contact sites (MERCs) is where autophagy initiates and autophagosomes form. However, the role of MERCs in autophagy dysregulation in DIC remains elusive. FUNDC1 is a mitochondria outer membrane protein that serves as a mitophagy receptor as well as a tethering protein of MERCs. Purpose The aim of our study was to investigate the effect of DOX on MERCs and explore whether it is involved in the dysregulation of autophagy. Our hypothesis is that FUNDC1 overexpression ameliorates DIC by restoring MERCs structure and dysregulated autophagic flux. Method We use confocal microscopy and transmission electron microscopy to assess MERCs structure. Overall autophagic flux was analyzed by RFP-EGFP-LC3B fluorescence assay and western blotting for LC3BII. A total dose of 15 mg/kg of doxorubicin was administrated in C57BL/6J mice to construct a DIC model in vivo. Adeno-associated virus (AAV) was used to cardiac-specifically overexpress FUNDC1. Cardiac remodeling was evaluated by Masson’s trichrome staining. Cardiac function (left ventricle ejection fraction, LVEF; left ventricle fraction shortening, LVFS) was measured by echocardiography. Results DOX treatment led to a significant downregulation of multiple tethering proteins (including FUNDC1) of MERCs and inhibition of MERCs formation, as demonstrated by decreased colocalization coefficients of mitochondria and endoplasmic reticulum in cardiomyocytes. The overexpression of FUNDC1 abolished DOX-induced inhibition on MERCs formation. In addition, DOX treatment blocked the normal autophagic flux, as demonstrated by the decreased autophagosome synthesis and impaired autophagosome turnover. Maintaining the MERCs structure by FUNDC1 overexpression was able to restore the blocked autophagic flux mentioned above. Moreover, FUNDC1 overexpression restored the blocked autophagic flux in vivo, as demonstrated by the increased LC3B turnover compared to the DOX treatment group. Importantly, global heart function of FUNDC1 overexpressed mice was significantly improved post DOX treatment compared to the Wildtype DOX treatment group, as demonstrated by the increased LVEF and LVFS. In addition, LV fibrosis level was found to be significantly decreased in FUNDC1 overexpressed mice treated with DOX compared to the Wildtype DOX treatment group. Conclusion We reported for the first time that the impaired MERCs formation in DOX-treated cardiomyocytes and revealed that restoring the disrupted MERCs structure by FUNDC1 overexpression was able to revert the blocked autophagic flux induced by DOX treatment. Furthermore, cardiac-specific overexpression of FUNDC1 protected DOX-treated mice against adverse cardiac remodeling and improved cardiac function. These findings may shed light on the prevention and treatment of DIC.Figure

Effect of dapagliflozin in patients in Asia with heart failure with mildly reduced or preserved ejection fraction: insights from DELIVER

Abstract Background A large and growing fraction of the global heart failure (HF) population lives in Asia. One-fifth of participants in the DELIVER (Dapagliflozin Evaluation to Improve the Lives of Patients with Preserved Ejection Fraction Heart Failure) trial were enrolled from Asia, providing a rich source of contemporary data to understand their unique clinical profiles and responses to sodium-glucose cotransporter 2 (SGLT2) inhibition. Purpose To assess the differences in clinical characteristics, outcomes, and response to dapagliflozin in patients from Asia vs outside Asia among patients with HF with mildly reduced or preserved ejection fraction in the DELIVER trial. Methods DELIVER was a global randomized clinical trial enrolling across 353 sites in 20 countries. Baseline clinical characteristics from patients enrolled in DELIVER trial were compared between patients in Asia vs outside Asia. The primary outcome was a composite of worsening HF or cardiovascular (CV) death. The effect of dapagliflozin on primary and secondary outcomes were compared in patients in Asia vs outside Asia. Results Among 6,263 participants in the DELIVER trial, 1,226 (19.6%) were enrolled in Asia (310 in China, 422 in Japan, and 318 in Taiwan, and 176 in Vietnam). Compared to patients outside Asia, participants from Asia were similar in age, more likely to be men with previous HF hospitalization, less likely to have obesity, diabetes, hypertension, or history of myocardial infarction, and had lower symptom burden despite similar natriuretic peptide levels (Figure 1). After adjusting for age, sex, and baseline LVEF, those in Asia faced similar risks of HF events but lower risk of mortality compared with those enrolled outside Asia (all-cause mortality Asia vs. outside Asia: HR 0.60, 95% confidence interval [CI] 0.49 – 0.72, Table 1). Within Asia, all-cause mortality was highest in Vietnam (6.8 per 100 person-year [py]), followed by Taiwan (6.7 per 100 py), Japan (3.5 per 100 py) and China (3.3 per 100 py). Dapagliflozin reduced the primary outcome in participants enrolled in Asia (hazard ratio [HR] 0.89, 95% CI 0.67-1.18) and outside Asia (HR 0.80, 95% CI 0.71 – 0.92) to a similar extend (P-interaction = 0.54, Figure 1). Similarly, region did not modify the treatment effect of dapagliflozin on CV death, HF hospitalization, all-cause death, CV death and recurrent HF events, or changes in Kansas City Cardiomyopathy Questionnaire scores (P-interaction &amp;gt; 0.30 for all). Serious adverse events and rates of drug discontinuation were also balanced in both treatment arms, irrespective of enrollment in Asia vs. outside Asia. Conclusions In the global DELIVER trial, dapagliflozin reduced the risk of CV death or HF events and was well tolerated both among participants enrolled in Asia and other geographic regions.Figure 1Table 1

COVID-19-induced cardiovascular complexities

This study aimed to investigate the features of the clinical course of COVID-19 in combination with the pathology of the cardiovascular system (CVS). A prospective study was carried out. The main group (n=150) consisted of patients with changes in the cardiovascular system associated with COVID-19, i.e. newly diagnosed CV pathology, and patients with exacerbation of cardiac pathology against the background of COVID-19. The comparison group (n=154) included patients with COVID-19, but without any significant concomitant cardiac pathology. The average age of patients in the main group was 67.7 years (from 47 to 86 years), in the comparison group of 66.1 years (from 48 to 88 years). The study groups were representative and did not differ statistically in the nature of COVID-19 symptoms and the degree of lung involvement. Among the cardiac pathology, progressing or first occurring against the background of infection with COVID-19, in most cases, arterial hypertension of II-III degree (60.0%), coronary heart disease (48.7%), arrhythmias (23.3%) were diagnosed. Echocardiographic abnormalities included right ventricular dysfunction (22.7%), left ventricular contractility disorders (18.7%), with decreased ejection fraction (17.3%), diastolic dysfunction (14.0%), and toxic myocarditis (7.3%). The most significant risk factors were the presence of a burdened medical history (RR=10.39), elevated body mass index over 30 (RR=2.63) and diabetes mellitus (RR=1.55). In patients with COVID-19 in combination with CVS pathology, a relatively high incidence of acute onset (64.0% vs. 44.2%; p&lt;0.001), respiratory failure (83.7% vs. 62.0%; p&lt;0.001), admission to the intensive care unit (25.3% vs. 11.7%; p=0.004), development of acute respiratory distress syndrome (20.0% vs. 9.1%; p=0.012), hospital mortality (10.7% vs. 2.7%; p=0.006). Cardiac manifestations of COVID-19 included focal or global myocardial inflammation, ventricular dysfunction, heart failure, and arrhythmias. A high frequency of acute onset of the disease, respiratory failure and hospital mortality is determined.

COVID-19-induced cardiovascular complexities

This study aimed to investigate the features of the clinical course of COVID-19 in combination with the pathology of the cardiovascular system (CVS). A prospective study was carried out. The main group (n=150) consisted of patients with changes in the cardiovascular system associated with COVID-19, i.e. newly diagnosed CV pathology, and patients with exacerbation of cardiac pathology against the background of COVID-19. The comparison group (n=154) included patients with COVID-19, but without any significant concomitant cardiac pathology. The average age of patients in the main group was 67.7 years (from 47 to 86 years), in the comparison group of 66.1 years (from 48 to 88 years). The study groups were representative and did not differ statistically in the nature of COVID-19 symptoms and the degree of lung involvement. Among the cardiac pathology, progressing or first occurring against the background of infection with COVID-19, in most cases, arterial hypertension of II-III degree (60.0%), coronary heart disease (48.7%), arrhythmias (23.3%) were diagnosed. Echocardiographic abnormalities included right ventricular dysfunction (22.7%), left ventricular contractility disorders (18.7%), with decreased ejection fraction (17.3%), diastolic dysfunction (14.0%), and toxic myocarditis (7.3%). The most significant risk factors were the presence of a burdened medical history (RR=10.39), elevated body mass index over 30 (RR=2.63) and diabetes mellitus (RR=1.55). In patients with COVID-19 in combination with CVS pathology, a relatively high incidence of acute onset (64.0% vs. 44.2%; p&lt;0.001), respiratory failure (83.7% vs. 62.0%; p&lt;0.001), admission to the intensive care unit (25.3% vs. 11.7%; p=0.004), development of acute respiratory distress syndrome (20.0% vs. 9.1%; p=0.012), hospital mortality (10.7% vs. 2.7%; p=0.006). Cardiac manifestations of COVID-19 included focal or global myocardial inflammation, ventricular dysfunction, heart failure, and arrhythmias. A high frequency of acute onset of the disease, respiratory failure and hospital mortality is determined.

Improving cardiovascular outcomes for patients with heart failure in sub-Saharan Africa: conference proceedings of the 2022 Nigerian Cardiovascular Symposium.

The Nigerian Cardiovascular Symposium is an annual conference held in partnership with cardiologists in Nigeria and the diaspora to provide updates in cardiovascular medicine and cardiothoracic surgery with the aim of optimising cardiovascular care for the Nigerian population. This virtual conference (due to the COVID-19 pandemic) has created an opportunity for effective capacity building of the Nigerian cardiology workforce. The objective of the conference was for experts to provide updates on current trends, clinical trials and innovations in heart failure, selected cardiomyopathies such as hypertrophic cardiomyopathy and cardiac amyloidosis, pulmonary hypertension, cardiogenic shock, left ventricular assist devices and heart transplantation. Furthermore, the conference aimed to equip the Nigerian cardiovascular workforce with skills and knowledge to optimise the delivery of effective cardiovascular care, with the hope of curbing 'medical tourism' and the current 'brain drain' in Nigeria. Challenges to optimal cardiovascular care in Nigeria include workforce shortage, limited capacity of intensive care units, and availability of medications. This partnership represents a key first step in addressing these challenges. Future action items include enhanced collaboration between cardiologists in Nigeria and the diaspora, advancing participation and enrollment of African patients in global heart failure clinical trials, and the urgent need to develop heart failure clinical practice guidelines for Nigerian patients.

THE PART OF HYPERTENSION IN HEART FAILURE IN NIGERIA

Objective: The objective of this study was to determine the part of hypertension among the heart failure cause in Nigeria. It was a retrospective study realized to January to December 2020 in Nigeria. Design and method: A total of 294 patients with heart failure were selected. Between them 26.5%{78) had hypertension like of heart failure. The sex-ratio was 0.73 and mean,s age of patients was 60.8 + 12.2 years. Results: Thirsty three cases of dyspnea (42.3%) and 31 cases (39.7) and respectively of class lll and IV of New York Heart Association were observed. Global heart failure was found in 45 cases (57.7%) and it concern left ventricular only in 33 cases(42.3%). Age = 50 years (74.4%), overweight (60.3%) and alcohol (42.3%) were the most risk factors noted. Clinical evolution was favourable in most cases. Also we noted a death rate of 5.1% and 7.9% and re-hospitalization in the year. Conclusions: Education and early management of patients with high blood pressure are necessary to reduce risk of complication.

Changing the trajectory of heart failure and saving lives: a look at the 25in25 global initiative

In this month's column, BANCC secretary Claire Lawson and junior secretary Carys Barton report back from the 25in25 global heart failure summit held in London in March.