Fatal Heart Failure Research Articles

Modern epidemiology of heart failure with reduced and preserved ejection fraction in population-wide linked electronic health records: a study of 208815 heart failure patients in England

Abstract Background The modern epidemiology of heart failure (HF) with reduced ejection fraction (HFrEF) and preserved ejection fraction (HFpEF) is yet to be studied on a population-wide scale in the United Kingdom, particularly in the post-COVID-19 era. Purpose To explore the post-pandemic epidemiology and outcomes of HFrEF and HFpEF in population-wide electronic health records (EHRs). Methods We accessed data in the National Health Service England’s Secure Data Environment for England via the British Heart Foundation Data Science Centre CVD-COVID-UK/COVID-IMPACT Consortium. We used EHRs for 57 million individuals to identify patients aged ≥18 years, of known sex, who were diagnosed with HF as the primary condition in any inpatient hospital stay from 01 Jan 2020 to 27 Feb 2023. By linking HF admissions with the National Heart Failure Audit, six other National Institute for Cardiovascular Outcomes Research audits, and the General Practice Extraction Service Data for Pandemic Planning and Research, we classified HF into HFrEF and HFpEF based on recorded left ventricular ejection fraction (LVEF; ≤40% and >40% respectively) or documented diagnosis. We compared characteristics of these groups and used Cox proportional hazards models, adjusted for key confounders, to examine differences in cause-specific mortality and hospitalisation outcomes. Results Over 3.2 years, we identified 208815 patients with a HF hospitalisation. 86110 (41%) patients had HFrEF, 65735 (31%) had HFpEF, and 56970 (27%) could not be categorised. Compared to patients with HFrEF, patients with HFpEF were older (mean [SD], 80.5 [10.9] vs 75.6 [13.6] years), more often female (n [%], 35990 [54.8] vs 30835 [35.8]), and less deprived (n [%] in the least-deprived Index of Multiple Deprivation 2019 quintile, 12275 [18.7] vs 15055 [17.5]; Table). Over a median follow-up of 11 months among patients with HFrEF and HFpEF, 99740 patients were re-hospitalised (66%) and 71075 (47%) died. Risks of all-cause, cardiovascular, non-cardiovascular, and heart-failure re-hospitalisations were all higher in patients with HFpEF compared with patients with HFrEF (Figure). The risk of all-cause mortality was modestly higher in patients with HFpEF (HR 1.04, 95% CI 1.02–1.06; Figure). Risks of death due to cardiovascular disease overall, fatal myocardial infarction, and fatal HF were higher among patients with HFrEF. In contrast, risks of death due to non-cardiovascular causes were higher in patients with HFpEF. There were no differences in risk of death due to COVID-19. Conclusions Unlike previous epidemiological surveys of HF, patients with HFpEF appear to face worse prognosis and risk-adjusted disease trajectories compared with those with HFrEF after hospitalisation in this population-wide study. Excess mortality in HFpEF appears driven by higher risk of non-cardiovascular mortality. However, post-discharge survival is poor regardless of LVEF and represents an ongoing target for quality improvement efforts.

Venetoclax plus decitabine as a bridge to allogeneic haematopoietic stem-cell transplantation in older patients with acute myeloid leukaemia (VEN-DEC GITMO): final report of a multicentre, single-arm, phase 2 trial

Access to allogeneic haematopoietic stem-cell transplantation (HSCT) remains challenging for older patients (aged >60 years) with acute myeloid leukaemia. We aimed to evaluate the efficacy of venetoclax plus decitabine as first-line therapy and bridge to transplantation in this patient population. This multicentre, single-arm, phase 2 trial was conducted in 20 Gruppo Italiano Trapianto Midollo Osseo (GITMO) centres in Italy. Patients aged ≥60 and <75 years, with newly diagnosed acute myeloid leukaemia categorised as intermediate or high risk according to 2016 WHO and 2017 European LeukemiaNet, an ECOG performance status of less than 2, and considered fit for allogeneic HSCT were included. Patients received oral venetoclax with a 3-day ramp-up: 100 mg on day 1, 200 mg on day 2, and 400 mg once per day from day 3 of cycle one, and then every 28 days of each cycle (two to four in total). Decitabine was administered intravenously at a dose of 20 mg/m2 from days 1 to 5 every 28 days. At cycle one, patients were admitted to hospital for a minimum of 24 h, whereas subsequent cycles could be administered on an outpatient basis. Two additional cycles were allowed while waiting for allogeneic HSCT or for those with no response or partial response after cycle two. The primary endpoint was the proportion of patients who had allogeneic HSCT performed during first complete remission, assessed in all patients who received at least one dose of the study medication. This study was registered with ClinicalTrials.gov (NCT04476199, ongoing) and EudraCT (2020-002297-26). Between June 1, 2021, and Dec 30, 2022, 93 patients were enrolled and started venetoclax plus decitabine induction (44 [47%] at intermediate risk and 49 [53%] at high risk). The median age was 68·5 (IQR 60·3-74·7). All 93 participants were White, of whom 43 (46%) were female and 50 (54%) were male. The median follow-up was 236 days (IQR 121-506). 64 (69%) of 93 patients reached complete remission and 53 (57%) underwent allogeneic HSCT in complete remission. 53 (83%) of 64 with a complete remission underwent allogeneic HSCT. Five (8%) of 64 patients in complete remission relapsed before transplantation and four died as a consequence. Adverse events (grade ≥3) occurred in 49 (53%) of 93 patients. The most common adverse events were infections (including pneumonia, bacterial sepsis, and SARS-CoV-2 causing seven deaths among 28 [57%] of 49 patients), neutropenia (17 [35%]), thrombocytopenia (two [4%], including one fatal CNS bleeding), and cardiac events (four [8%], including one fatal heart failure). No treatment-related deaths were observed. Venetoclax plus decitabine induction can significantly enhance the feasibility of allogeneic HSCT in older patients with acute myeloid leukaemia who are deemed fit for transplantation. AbbVie and Johnson & Johnson.

Effectiveness of polypill for primary and secondary prevention of cardiovascular disease: a pragmatic cluster-randomised controlled trial (PolyPars)

BackgroundWe aimed to investigate the effectiveness of fixed-dose combination therapy (polypill) for primary and secondary prevention of major cardiovascular diseases in a typical rural setting.MethodsThe PolyPars Study is a two-arm...

Nuclear receptor Rev-erbα role in fine-tuning erythropoietin gene expression

AbstractThe regulation of red blood cell (RBC) homeostasis by erythropoietin (EPO) is critical for O2 transport and maintaining the adequate number of RBCs in vertebrates. Therefore, dysregulation in EPO synthesis results in disease conditions such as polycythemia in the case of excessive EPO production and anemia, which occurs when EPO is inadequately produced. EPO plays a crucial role in treating anemic patients; however, its overproduction can increase blood viscosity, potentially leading to fatal heart failure. Consequently, the identification of druggable transcription factors and their associated ligands capable of regulating EPO offers a promising therapeutic approach to address EPO-related disorders. This study unveils a novel regulatory mechanism involving 2 pivotal nuclear receptors (NRs), Rev-ERBA (Rev-erbα, is a truncation of reverse c-erbAa) and RAR-related orphan receptor A (RORα), in the control of EPO gene expression. Rev-erbα acts as a cell-intrinsic negative regulator, playing a vital role in maintaining erythropoiesis at the correct level. It accomplishes this by directly binding to newly identified response elements within the human and mouse EPO gene promoter, thereby repressing EPO production. These findings are further supported by the discovery that a Rev-erbα agonist (SR9011) effectively suppresses hypoxia-induced EPO expression in mice. In contrast, RORα functions as a positive regulator of EPO gene expression, also binding to the same response elements in the promoter to induce EPO production. Finally, the results of this study revealed that the 2 NRs, Rev-erbα and RORα, influence EPO synthesis in a negative and positive manner, respectively, suggesting that the modulating activity of these 2 NRs could provide a method to target disorders linked with EPO dysregulation.

The biased apelin receptor agonist, MM07, reverses Sugen/hypoxia-induced pulmonary arterial hypertension as effectively as the endothelin antagonist macitentan.

Introduction: Pulmonary arterial hypertension (PAH) is characterised by endothelial dysfunction and pathological vascular remodelling, resulting in the occlusion of pulmonary arteries and arterioles, right ventricular hypertrophy, and eventually fatal heart failure. Targeting the apelin receptor with the novel, G protein-biased peptide agonist, MM07, is hypothesised to reverse the developed symptoms of elevated right ventricular systolic pressure and right ventricular hypertrophy. Here, the effects of MM07 were compared with the clinical standard-of-care endothelin receptor antagonist macitentan. Methods: Male Sprague-Dawley rats were randomised and treated with either normoxia/saline, or Sugen/hypoxia (SuHx) to induce an established model of PAH, before subsequent treatment with either saline, macitentan (30mg/kg), or MM07 (10mg/kg). Rats were then anaesthetised and catheterised for haemodynamic measurements, and tissues collected for histopathological assessment. Results: The SuHx/saline group presented with significant increases in right ventricular hypertrophy, right ventricular systolic pressure, and muscularization of pulmonary arteries compared to normoxic/saline controls. Critically, MM07 was as at least as effective as macitentan in significantly reversing detrimental structural and haemodynamic changes after 4weeks of treatment. Discussion: These results support the development of G protein-biased apelin receptor agonists with improved pharmacokinetic profiles for use in human disease.

(1041) - Fatal Right Heart Failure Due to Pulmonary Tumor Emboli Syndrome in a Patient with Undiagnosed Colon Cancer

(1041) - Fatal Right Heart Failure Due to Pulmonary Tumor Emboli Syndrome in a Patient with Undiagnosed Colon Cancer

Legacy benefits of blood pressure treatment on cardiovascular events are primarily mediated by improved blood pressure variability: the ASCOT trial.

Visit-to-visit systolic blood pressure variability (BPV) is an important predictor of cardiovascular (CV) outcomes. The long-term effect of a period of blood pressure (BP) control, but with differential BPV, is uncertain. Morbidity and mortality follow-up of UK participants in the Anglo-Scandinavian Cardiac Outcomes Trial-Blood Pressure-Lowering Arm has been extended for up to 21 years to determine the CV impact of mean systolic blood pressure (SBP) control and BPV during the trial, and amongst those allocated to amlodipine- and atenolol-based treatment. Eight thousand five hundred and eighty hypertensive participants (4305 assigned to amlodipine ± perindopril-based and 4275 to atenolol ± diuretic-based treatment during the in-trial period (median 5.5 years) were followed for up to 21 years (median 17.4 years), using linked hospital and mortality records. A subgroup of participants (n = 2156) was followed up 6 years after the trial closure with a self-administered questionnaire and a clinic visit. In-trial mean SBP and standard deviation of visit-to-visit SBP as a measure of BPV, were measured using >100 000 BP measurements. Cox proportional hazard models were used to estimate the risk [hazard ratios (HRs)], associated with (i) mean with SBP and BPV during the in-trial period, for the CV endpoints occurring after the end of the trial and (ii) randomly assigned treatment to events following randomization, for the first occurrence of pre-specified CV outcomes. Using BP data from the in-trial period, in the post-trial period, although mean SBP was a predictor of CV outcomes {HR per 10 mmHg, 1.14 [95% confidence interval (CI) 1.10-1.17], P < .001}, systolic BPV independent of mean SBP was a strong predictor of CV events [HR per 5 mmHg 1.22 (95% CI 1.18-1.26), P < .001] and predicted events even in participants with well-controlled BP. During 21-year follow-up, those on amlodipine-based compared with atenolol-based in-trial treatment had significantly reduced risk of stroke [HR 0.82 (95% CI 0.72-0.93), P = .003], total CV events [HR 0.93 (95% CI 0.88-0.98), P = .008], total coronary events [HR 0.92 (95% CI 0.86-0.99), P = .024], and atrial fibrillation [HR 0.91 (95% CI 0.83-0.99), P = .030], with weaker evidence of a difference in CV mortality [HR 0.91 (95% CI 0.82-1.01), P = .073]. There was no significant difference in the incidence of non-fatal myocardial infarction and fatal coronary heart disease, heart failure, and all-cause mortality. Systolic BPV is a strong predictor of CV outcome, even in those with controlled SBP. The long-term benefits of amlodipine-based treatment compared with atenolol-based treatment in reducing CV events appear to be primarily mediated by an effect on systolic BPV during the trial period.

Sodium butyrate alleviates right ventricular hypertrophy in pulmonary arterial hypertension by inhibiting H19 and affecting the activation of let-7g-5p/IGF1 receptor/ERK

Pulmonary arterial hypertension (PAH) is a complex and fatal cardio-pulmonary vascular disease. Decompensated right ventricular hypertrophy (RVH) caused by cardiomyocyte hypertrophy often leads to fatal heart failure, the leading cause of mortality among patients. Sodium butyrate (SB), a compound known to reduce cardiac hypertrophy, was examined for its potential effect and the underlying mechanism of SB on PAH-RVH. The in vivo study showed that SB alleviated RVH and cardiac dysfunction, as well as improved life span and survival rate in MCT-PAH rats. The in vivo and in vitro experiments showed that SB could attenuate cardiomyocyte hypertrophy by reversing the expressions of H19, let-7g-5p, insulin-like growth factor 1 receptor (IGF1 receptor), and pERK. H19 inhibition restored the level of let-7g-5p and prevented the overexpression of IGF1 receptor and pERK in hypertrophic cardiomyocytes. In addition, dual luciferase assay revealed that H19 demonstrated significant binding with let-7g-5p, acting as its endogenous RNA. Briefly, SB attenuated PAH-RVH by inhibiting the H19 overexpression, restoring the level of let-7g-5p, and hindering IGF1 receptor/ERK activation.

Elevated SLC40A1 impairs cardiac function and exacerbates mitochondrial dysfunction, oxidative stress, and apoptosis in ischemic myocardia.

Iron homeostasis is crucial for optimal cardiac function. Iron deficiency and overload have been linked to the development of cardiomyopathy and heart failure (HF) via intricate mechanisms. Although the crucial role of SLC40A1 in iron metabolism by facilitating the efflux of cellular iron has been confirmed, its specific molecular functions in cardiovascular diseases remain poorly understood. In this study, we generated mice with inducible cardiomyocyte-specific overexpression of SLC40A1 for the first time. The overexpression of SLC40A1 in the cardiomyocytes of adult mice resulted in significant iron deficiency, leading to mitochondrial dysfunction, oxidative stress, and apoptosis, subsequently resulting in the development of fatal HF. Notably, SLC40A1 upregulation was observed in the ischemic region during the initial phase of myocardial infarction (MI), contributing to iron loss in the cardiomyocytes. Conversely, the cardiomyocyte-specific knockdown of SLC40A1 improved cardiac dysfunction after MI by enhancing mitochondrial function, suppressing oxidative stress, and reducing cardiomyocytes apoptosis. Mechanistically, Steap4 interacted with SLC40A1, facilitating SLC40A1-mediated iron efflux from cardiomyocytes. In short, our study presents evidence for the involvement of SLC40A1 in the regulation of myocardial iron levels and the therapeutic benefits of cardiomyocyte-specific knockdown of SLC40A1 in MI in mice.

The prognostic association of atrial fibrillation on heart failure hospitalizations after acute myocardial infarction

Abstract Aims The association of atrial fibrillation (AF) with heart failure (HF) specific hospitalizations after acute myocardial infarction (AMI) is unclear. We aim to study the association of AF and 6-month HF hospitalization after an AMI in a large American cohort. Methods and Results Adult survivors of a AMI hospitalization without cardiogenic shock were identified from the 2019 US Nationwide Readmissions Database. The unadjusted association of AF (pre-existing and denovo) with baseline characteristics and primary outcome of rate of 6-month HF admission, and secondary outcomes of fatal HF admission, composite of HF peri-AMI or a 6-month HF admission, and a composite of 6-month HF or death during a non−HF-related admission was evaluated using chi square tests or t-tests, and independent associations of AF on outcomes were evaluated using multivariable logistic regression. Cox proportional hazards models were used to identify the association of AF on cumulative incidence risk on HF readmission. Of 262,390 AMI survivors, AF was present in 18.0%. By 6-months, HF hospitalization occurred in 5.4% of all patients. AF was associated with a higher adjusted risk for 6-month HF admission (OR 1.42, 95% CI: 1.34-1.50). In the adjusted time-to-event analysis, AF was associated with a higher risk for 6-month HF readmission (HR 1.39, 95% CI 1.31-1.46, P&amp;lt;0.001). AF was associated with a higher risk for fatal HF and the composite outcomes. Conclusions AF was present in 1 in 6 AMI survivors without cardiogenic shock and AF was associated with a higher risk of HF hospitalization in the subsequent 6-month period.Cumulative Incidence CurvesOutcomes Table

Leisure time and occupational physical activity, overall and cardiovascular mortality: a 24-year follow-up in the OPERA study

Background In earlier studies, the health benefits of physical activity have only been related to leisure time physical activity (LTPA). High occupational physical activity (OPA) might even be harmful. The current physical activity recommendations do not separate the OPA and LTPA. We investigated the effect of LTPA and OPA on cardiovascular morbidity and mortality during long-term follow-up. We also examined how heavy work affects the benefits of leisure time exercise. Material and methods The study was part of the OPERA study and the baseline examinations were conducted between the years 1991 and 1993. The Follow-up of events continued until the end of the year 2020. Study subjects (n = 1044) were divided into four groups according to their LTPA (“no exercise”, “irregular”, “regular” and “heavy regular”) and into three groups according to their OPA (“no activity”, “mild” and “heavy”). The amount of exercise was self-reported and the exercise status was defined at the beginning of the study. Study subjects were followed up for their overall mortality (26 years), fatal and non-fatal CVD events (24 and 20 years) and heart failure (20 years). The survival analysis was performed using Kaplan–Meier curves and Cox-proportional hazard models. Results “Heavy” OPA group subjects belonging to the “irregular” (less than 1–2 times 30 min exercise per week) LTPA group experienced the lowest overall mortality compared to other LTPA groups. Also, overall mortality was increased in the “mild” (p = 0.002) and CVD mortality in the” heavy” (p = 0.005) OPA group compared to “no activity”. The incidence of heart failure was increased in the “no exercise” LTPA compared to the “heavy regular” (p = 0.015) group. Conclusions Study subjects who were in physically demanding occupations (heavy OPA) seemed to benefit from less LTPA than WHO currently recommends. Thus we suggest targeting different LTPA recommendations to different OPA groups.

Endogenous interleukin-22 prevents cardiac rupture after myocardial infarction in mice.

Myocardial infarction (MI) can result in fatal myocardial rupture or heart failure due to adverse remodeling and dysfunction of the left ventricle. Although recent studies have shown that exogenous interleukin (IL)-22 shows cardioprotective effect after MI, the pathophysiological significance of endogenous IL-22 is unknown. In this study, we investigated the role of endogenous IL-22 in a mouse model of MI. We produced MI model by permanent ligation of the left coronary artery in wild-type (WT) and IL-22 knock-out (KO) mice. The post-MI survival rate was significantly worse in IL-22KO mice than in WT mice due to a higher rate of cardiac rupture. Although IL-22KO mice exhibited a significantly greater infarct size than WT mice, there was no significant difference in left ventricular geometry or function between WT and IL-22KO mice. IL-22KO mice showed increase in infiltrating macrophages and myofibroblasts, and altered expression pattern of inflammation- and extracellular matrix (ECM)-related genes after MI. While IL-22KO mice showed no obvious changes in cardiac morphology or function before MI, expressions of matrix metalloproteinase (MMP)-2 and MMP-9 were increased, whereas that of tissue inhibitor of MMPs (TIMP)-3 was decreased in cardiac tissue. Protein expression of IL-22 receptor complex, IL-22 receptor alpha 1 (IL-22R1) and IL-10 receptor beta (IL-10RB), were increased in cardiac tissue 3 days after MI, regardless of the genotype. We propose that endogenous IL-22 plays an important role in preventing cardiac rupture after MI, possibly by regulating inflammation and ECM metabolism.

Evaluating the effectiveness of an apelin analog as a potential treatment for pulmonary arterial hypertension using a sugen-hypoxia rat model

Background: Pulmonary arterial hypertension (PAH) is a debilitating syndrome characterized by heightened pulmonary arterial pressures, and adverse pulmonary vascular remodeling. Eventually, the right ventricle (RV) decompensates, and fatal right heart failure ensues. Existing treatments for PAH are ineffective at improving survival. Apelin is an endogenous cardioprotective peptide, and disruption of apelin signaling was associated with the development of PAH. Restoring the activity of the apelin pathway is a promising approach in reversing the arteriopathy underlying PAH to protect the RV. The salutary actions of apelin are limited by its short half-life; recently, apelin analogs designed with extended half-lives offer a novel therapeutic avenue requiring further testing. Objective: Our project aims to evaluate the effectiveness of an apelin analog as a potential treatment for PAH using a Sugen-Hypoxia (SuHx) rat model of PAH which recapitulates disease characteristics seen in humans. We hypothesize that the apelin analog treatment will improve pulmonary hemodynamics and preserve RV adaptation in rats exposed to SuHx and assuage the pulmonary arteriopathy seen in PAH rats. Experimental design: Male Sprague Dawley rats aged 9 weeks were randomly split into a placebo or treated PAH group. For 3 weeks, a control group was kept within normal room air while the placebo and treated PAH rats were kept in a hypoxia chamber (10% O 2 ). Placebo and treated rats were injected with SU5416 (20 mg/kg, SQ) once at the start of the 3 weeks to induce disease. The normoxic period lasted 5 weeks following the 3 weeks of hypoxia. Treated rats received apelin analog (0.5 μmol/kg, IV, b.i.d.) for the final 3 weeks of normoxia; the placebo group received the same dose of saline. Results: At endpoint, glomerular filtration rate (GFR) measurements showed that placebo treated (PAH-P) PAH rats had reduced GFR while apelin treated (PAH-A) PAH rats had recovered GFR. Echocardiography revealed that PAH-A rats had improved cardiac function compared to PAH-P rats. RV Pressure-volume loop surgeries showed that PAH-A rats had ameliorated RV hemodynamic pressures in contrast to PAH-P rats. Histological analysis demonstrated reduced cardiac fibrosis and hypertrophy, and fewer formations of pulmonary vascular lesions within PAH-A rats compared to PAH-P rats. Single nucleus RNA sequencing performed on RV and lung tissue delineated mitigation of disease progression within the PAH-A group compared to PAH-P rats. Electrocardiography recordings showed more severe electrical remodeling in the PAH-P group compared to the PAH-A rats. Conclusions &amp; significance: Rats with PAH treated with apelin had overall improved cardiopulmonary health outcomes compared to placebo treated PAH rats. The results of this study provide insight into the beneficial role of the apelin pathway in the setting of PAH to propose a new treatment for patients with PAH to improve their duration and quality of life. Canadian Institutes of Health Research Grant This is the full abstract presented at the American Physiology Summit 2023 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.

Impact of residual pulmonary hypertension on long-term outcomes after pulmonary endarterectomy in the modern era.

Residual pulmonary hypertension (PH) negatively impacts long-term results following pulmonary endarterectomy (PEA) for chronic thromboembolic pulmonary hypertension (CTEPH). We sought to reveal whether modern PH therapy with PH-targeted medicine and balloon pulmonary angioplasty (BPA) improved long-term results of residual PH after PEA. Long-term findings of 80 patients who survived PEA between 2011 and 2019 were retrospectively investigated. One month after PEA, 30 patients developed residual PH defined as mean pulmonary artery pressure (mPAP) ≥25 mmHg, of whom 23 were treated by PH-targeted medicine and 9 by BPA. Patients with residual PH acquired considerably better functional status and exercise capacity after PEA, however, exhibited significantly worse survival rates than those without. Eleven patients died during follow-up: 8 patients with residual PH and 3 controls. Among patients with residual PH, the deceased had a significantly lower %decrease in mPAP from 1 month to 1 year following PEA (7.4 [-32.6 to 8.0] % vs. 10.4 [3.7-27.8] %, p = 0.03) and higher mPAP at 1 year following PEA (39.5 [33.25-42.5] vs. 27 [26-34] mmHg, p < 0.01) despite PH-targeted medicine than the survived. No patients passed away from right heart failure, and there was no difference between the groups in CTEPH-related mortality. Modern PH therapy was used to address the majority of residual PH. Long-term survival after PEA was negatively impacted by residual PH, but it appeared that long-term mortality was also correlated with unrelieved residual PH despite PH-targeted medicine. Modern PH therapy may have enhanced functional status and excercise capacity, and averted fatal right heart failure.

Peripartum Cardiomyopathy Due to Gestational Hypertension and Tocolytic Therapy

Introduction: Peripartum cardiomyopathy (PPCM) is a rare and sometimes fatal systolic heart failure that affects women during late pregnancy or the early postpartum period. Risk factors contributing to this condition are: advanced maternal age, multiparity, administration of tocolytic agents, underlying cardiac disease, iatrogenic volume overload, preeclampsia, hypertension and In patients with gestational hypertension (GH) and other risk factors close monitoring is mandatory during pregnancy as well as in the postpartum period. Case report: A 38 year- old patient previously treated for endometriosis, infertility and GH was transferred from the Clinic of Gynecology due to diagnosed congestive heart failure. Five days prior admission she gave birth to her first child. Prior delivery she was treated with tocolytic therapy. She received methyldopa due to GH, that was abruptly discontinued after her delivery. Echocardiography on admission revealed moderately reduced left ventricular systolic function with an ejection fraction (EF) of 37% with dilated left ventricle (LV) and pulmonary artery hypertension (PAH) secondary to left ventricular failure. During hospitalization the patient was with signs of volume overload, but with well response on parenteral diuretic therapy. She was additionally treated with guideline recommended heart failure therapy. The controlled echocardiography showed improvement of the left ventricular function with an EF of 42%. Conclusion: PPCM is a rare condition with high morbidity and mortality. An LVEF &lt;30%, marked LV dilatation, LV end-diastolic diameter &gt;6.0 cm, and RV involvement are associated with adverse outcomes. Although delivery of the fetus and the placenta trigger resolution of symptoms and recovery to the nonpregnant state of various organism, the contrary happens with blood pressure. Its peaking time is three to six days after delivery. Hypertension medication must not be immediately terminated. Prolonged tocolytic therapy are a risk factor for PPCM due to causing decreased baroreflex sensitivity Patients with risk factors should be closely monitored for eventual cardiac complications.

The importance of caveolin as a target in the prevention and treatment of diabetic cardiomyopathy.

The diabetic population has been increasing in the past decades and diabetic cardiomyopathy (DCM), a pathology that is defined by the presence of cardiac remodeling and dysfunction without conventional cardiac risk factors such as hypertension and coronary heart diseases, would eventually lead to fatal heart failure in the absence of effective treatment. Impaired insulin signaling, commonly known as insulin resistance, plays an important role in the development of DCM. A family of integral membrane proteins named caveolins (mainly caveolin-1 and caveolin-3 in the myocardium) and a protein hormone adiponectin (APN) have all been shown to be important for maintaining normal insulin signaling. Abnormalities in caveolins and APN have respectively been demonstrated to cause DCM. This review aims to summarize recent research findings of the roles and mechanisms of caveolins and APN in the development of DCM, and also explore the possible interplay between caveolins and APN.

Peripartum Cardiomyopathy Due to Gestational Hypertension and Tocolytic Therapy

BACKGROUND: Peripartum cardiomyopathy (PPCM) is a rare and sometimes fatal systolic heart failure that affects women during late pregnancy or the early postpartum period. The risk factors contributing to this condition are advanced maternal age, multiparity, administration of tocolytic agents, underlying cardiac disease, iatrogenic volume overload, preeclampsia, and hypertension. In patients with gestational hypertension (GH) and other risk factors, close monitoring is mandatory during pregnancy as well as in the postpartum period. CASE REPORT: A 38-year-old patient previously treated for endometriosis, infertility, and GH was transferred from the clinic of gynecology due to diagnosed congestive heart failure. 5 days before admission, she gave birth to her first child. Before delivery, she was treated with tocolytic therapy. She received methyldopa due to GH which was abruptly discontinued after her delivery. Echocardiography on admission revealed moderately reduced left ventricular (LV) systolic function with an ejection fraction (EF) of 37% with dilated left ventricle (LV) and pulmonary artery hypertension secondary to LV failure. During hospitalization, the patient was with signs of volume overload, but with a good response on parenteral diuretic therapy. She was additionally treated with guideline-recommended heart failure therapy. The controlled echocardiography showed improvement of LV function with an EF of 42%. CONCLUSION: PPCM is a rare condition with high morbidity and mortality. An LVEF &lt;30%, marked LV dilatation, LV end-diastolic diameter &gt;6.0 cm, and RV involvement are associated with adverse outcomes. Although delivery of the fetus and the placenta triggers the resolution of symptoms and recovery to the nonpregnant state of various organisms, the contrary happens with blood pressure. Its peak time is 3–6 days after delivery. Hypertension medication must not be immediately terminated. Prolonged tocolytic therapy is a risk factor for PPCM due to causing decreased baroreflex sensitivity. Patients with risk factors should be closely monitored for eventual cardiac complications.

Prediction of vascular events in individuals with atherosclerotic lesions of various vascular basins: results of a 3-year prospective follow-up

Introduction. Today, cardiovascular diseases occupy a leading position in the structure of mortality, both in Russia and throughout the world. Every year more than 17 million people die from cardiac pathology, according to the World Health Organization, an increase in morbidity and mortality is expected in the future, which is explained, first of all, by an increase in the number of patients with diabetes and obesity.Aim. Development of optimal approaches to predicting cardiovascular events and unfavorable outcomes in patients with peripheral atherosclerosis during a 3-year prospective follow-up.Materials and methods. The study included 519 patients with atherosclerotic lesions of various vascular regions, of which 360 (69.4%) were men, 159 (30.6%) were women. The average age of the examined patients was 60.0 ± 8.7 years.Results. In the course of the analysis, it was noted that a factor such as the percentage of table stenosis of the left coronary artery (p = 0.013) influenced the risk of developing non-fatal cases of heart failure in patients with peripheral atherosclerosis. With regard to the end point – fatal cases of heart failure, the following factors demonstrated their statistical significance: age of onset of arterial hypertension, years (p = 0.020); history of chronic heart failure (p = 0.020); left atrial size, mm (p = 0.025); degree of stenosis of the posterior lateral branch, % (p = 0.038); presence of atherosclerotic lesions in the region of the posterior interventricular branch (p = 0.002); number of affected vascular beds (p = 0.044).Conclusions. Using logistic regression equations, original mathematical tools have been developed to assess the risk of developing both fatal and non-fatal heart failure in patients with peripheral atherosclerosis.

Body composition and heart failure subtypes in the UK Biobank: a prospective study of 500,000 adults

Abstract Background Obesity has been associated with increased heart failure (HF) risk. However, the shape and strength of associations between different adiposity measures and HF subtypes remain unclear. Purpose This study investigated associations between various adiposity measures and incidence of different HF subtypes. Methods In 2006–2010, 502,599 adults (age 40–70 years) were recruited from UK general population. Resurvey on a subset of 20,346 participants was conducted in 2012–13. Participants were followed up by linkage to electronic health records. Analyses exclude participants with major cardiac and vascular diseases at baseline. Regression dilution ratios (RDR) of the different adiposity measures were calculated using Pearson's correlation method to obtain usual levels of each adiposity measure. Association between usual levels of adiposity measures (body mass index [BMI], waist circumference [WC] and waist-hip ratio [WHR]) and incident HF subtypes were determined using Cox proportional hazards regression models. Hazard ratios (HRs) are presented as per equivalent 5 usual BMI units higher adiposity measure. Results After exclusions, 428,087 individuals (mean age 55.9 years, 56% women) remained. Over a median follow-up of 12.8 years, there were 8,669 first-ever incident HF events (5205 in men and 3464 in women). Increasing usual levels of adiposity measures were positively and log-linearly associated with increased risk of HF. Associations were notably stronger for central adiposity, e.g. WC (HR per usual 12.2 units 1.66, 95% CI 1.62–1.70) compared with BMI (HR per usual 5 units 1.56, 95% CI 1.53–1.60). Compared to individuals within the lowest quintile of each adiposity measure, Individuals within the highest quintile of BMI had an adjusted HR (aHR) of 2.65 (95% CI, 2.54–2.75), those within highest quintile of WC had aHR of 3.21 (95% CI, 3.07–3.36) while those within highest quintile of WHR had aHR of 3.34 (95% CI, 3.16–3.53). Among HF aetiologic subtypes, hypertensive HF (HR per usual 12.2 WC units 2.09, 95% CI 1.92–2.27; HR per usual 5 BMI units 1.91, 95% CI 1.78–2.04) and mixed aetiology HF (HR per usual 12.2 WC units 1.89, 95% CI 1.82–1.96; HR per usual 5 BMI units 1.66, 95% CI 1.61–1.71) showed stronger association with adiposity while ischaemic HF (HR per usual 12.2 WC units 1.27, 95% CI 1.21–1.34; HR per usual 5 BMI units 1.21, 95% CI 1.16–1.27) and valvular HF (HR per usual 12.2 WC units 1.21, 95% CI 1.08–1.36; HR per usual 5 BMI units 1.18, 95% CI 1.06–1.31) showed weaker association with adiposity. HF with preserved ejection fraction (HFpEF) showed stronger association with adiposity than HF with reduced ejection fraction (HFrEF) while non-fatal HF showed stronger association with adiposity than fatal HF. Conclusions Adiposity measures especially central adiposity showed stronger association with hypertensive HF and mixed aetiology HF than ischaemic and valvular HF; and are strongly associated with HFpEF than HFrEF. Funding Acknowledgement Type of funding sources: Public Institution(s). Main funding source(s): Nuffield Department of Population Health Doctoral Scholarship

Double chambered left ventricle-Two chambers are not better than one.

In this month's Journal,1 Ali and colleagues present a case series consisting of two adults who underwent surgical resection for a double chamber left ventricle (DCLV). The first case was an 18-year-old female with several years of progressive chest pain and dyspnea who was ultimately found to have both a double chamber right ventricle (DCRV) and DCLV after transthoracic echocardiography (TTE) and cardiac catheterization. She underwent surgical resection of the fibromuscular bands in both ventricles with an uncomplicated postoperative course. The second case was a 27-year-old male with a history of supravalvular aortic stenosis that had been previously addressed who on TTE was found to have aortic regurgitation, aortic stenosis, and DCLV with elevated left ventricular outflow tract and accessory chamber (AC) gradients. He underwent mechanical aortic valve replacement, ascending aorta replacement, and muscle bundle excision with a course notable for delayed sternal closure and retroperitoneal hematoma. Both patients had technically successful operations with band resection and appropriate biventricular function confirmed on TTE. Both survived their index operations and had resolution of their symptoms, with the second patient dying at 6 months due to complications from anticoagulation. The authors should be congratulated for the successful identification and operative treatment of these patients. DCLV is an incredibly rare diagnosis and is even less common than its counterpart DCRV—which is seen in less than 2% of all congenital cardiac anomalies.2 Ali and colleagues successfully differentiated DCLV from other similar pathologies such as left ventricular aneurysms and left ventricular diverticulum. This is critical given their difference in etiology and overall management. Those with asymptomatic DCLV do not require surgical intervention. Symptoms are rare but can present as fatal tachyarrhythmias or heart failure. Patients can also be found to have mid-ventricular obstructions, particularly those with superior–inferior arrangements according to Bao et al.3 Those who are intervened upon typically undergo resection with patch reconstruction or cardiac transplant for large communications.4 Furthermore, diagnosing DCLV can be a challenge in and of itself. Some patients, including the second case of this study, have previous imaging that does not confirm the presence of DCLV.5 This just reiterates the importance of having a high clinical suspicion. Nevertheless, TTE is typically the first test performed and serves as a fairly reliable starting point. Bao et al.3 showed that in their series of nine patients, eight were correctly diagnosed during their initial TTE. Although a tissue diagnosis would be the best confirmatory test, a second imaging modality is typically used to confirm the diagnosis. The authors used cardiac catheterization and magnetic resonance imaging (MRI) in their first and second case, respectively, as their second modality of choice. The advantages of cardiac MRI are stated throughout the literature. It offers high inherent contrast resolution, good spatial and temporal resolutions, a wide field of view, multiplanar imaging capabilities, and the absence of radiation.4, 6 Gadolinium is particularly useful as a similar enhancement of the AC wall compared to the remainder of the left ventricular myocardium supports the diagnosis of DCLV.7 We (Figure 1) commend the authors on their work with this complex patient population. Both cases presented were unique and challenging. The authors demonstrated the ability to address DCLV in addition to the patient's existing congenital abnormalities. Furthermore, they demonstrate the ability to do so through both a transaortic and transmitral approach. DCLV is an incredibly rare diagnosis, making it difficult to establish practice guidelines. One should always pause when deciding when and how to operate on these patients. Still, Ali and colleagues add to the body of literature that suggests operating on DCLV can be done safely and that patients may derive a meaningful benefit. This work was supported by a research grant from NHLBI/NIH (No. T32HL007849). The content is solely the responsibility of the authors and does not represent the official views of the National Institutes of Health. The authors declare no conflict of interest.