Risk Factor For Heart Failure Research Articles

DNMT3A-mutant clonal haematopoiesis and the recovery of patients with acute ST-elevation myocardial infarction

Abstract Funding Acknowledgements Type of funding sources: Foundation. Main funding source(s): British Heart foundation Background Haematopoietic stem cells can acquire mutations and produce mutant blood cells. When this occurs in the absence of overt blood disease, it is clonal haematopoiesis of indeterminate potential (CHIP). CHIP is a novel, independent risk factor for ischaemic heart disease and heart failure (HF)(1). However, the molecular mechanisms are poorly understood. Myocardial infarction (MI) is a leading cause of HF due to ventricular remodelling and scar formation(2). We postulate CHIP mutations result in aberrant inflammation that contributes to maladaptive ventricular remodelling following MI. We investigated clinical outcomes and immune cell biology in CHIP and non-CHIP patients (pts) with acute ST-segment elevation MI (STEMI). Purpose Identify and quantify mutations with variant allele frequency (VAF)≥1% in STEMI pts. Assess leukocyte mutational burden. Investigate transcription profiles and leukocyte function in CHIP and non-CHIP STEMI pts. Methods 119 pts diagnosed with STEMI were prospectively recruited (REC19/SC/0362). We collected clinical data, including echocardiogram (echo) parameters and isolated plasma and peripheral blood mononucleated cells (PBMCs) from blood collected 48-96 hours post onset of chest pain. PBMCs were screened for mutations and analysed by flow cytometry. We assessed CHIP VAF with digital droplet PCR in flow-sorted monocytes (Mono), T and B-cells. We performed single-cell RNAseq (10x Genomics) on PBMCs. Luminex or ELISA kits were used to measure plasma proteins. Results 59/119 recruited pts had CHIP (VAF≥1%). CHIP pts were significantly older than non-CHIP pts. DNMT3A was the most commonly mutated gene (28%), followed by TET2 (17%) and ASXL1 (5.3%). 53 pts had impaired LV ejection fraction (LVEF) at admission and a follow-up Echo at median 4.6 months (2.5-8 IQR) post STEMI. They were classified as responder (R) n=24, Δ LVEF≥5% or non-responder (NR) n=29, ΔLVEF<5%. Pts with DNMT3A CHIP were 12 times more likely to be NR (p=0.02). Baseline LVEF was similar in CHIP and non-CHIP pts, but ΔLVEF was significantly reduced in DNMT3A vs non-CHIP pts (p<0.01). DNMT3A mutations were highest in Mono (mean VAF 6.3%), present in B cells (3%) but rare in T cells (1.7%). Within the Mono population, DNMT3A mutant pts had significantly higher proportions of classical Mono compared to non-CHIP (p=0.02). Using scRNAseq, we computed Mono trajectories and differential gene expression. Compared to non-CHIP, DNMT3A-mutant samples upregulated receptor for advanced glycation end-products (RAGE) and toll-like receptor signaling gene signatures. Despite this, we did not observe raised leukocyte count or detect increased levels of inflammatory cytokines in DNMT3A-mutant pts plasma samples. Conclusions DNMT3A CHIP is associated with poor LVEF recovery post-STEMI due to a dysregulated inflammatory response to acute myocardial injury. Furthermore, our data suggests that this may occur via different mechanisms than non-CHIP NR.

Development and validation of a nomogram model for all-cause mortality risk in patients with chronic heart failure and atrial fibrillation

BackgroundAs the global aging process continues to accelerate, heart failure (HF) has become an important cause of increased morbidity and mortality in elderly patients. Chronic atrial fibrillation (AF) is a major risk factor for HF. Patients with HF combined with AF are more difficult to treat and have a worse prognosis. The aim of this study was to explore the risk factors for 1-year mortality in patients with HF combined with AF and to develop a risk prediction assessment model.MethodsWe recruited hospitalized patients with HF and AF who received standardized care in the Department of Cardiology at Shengjing Hospital of China Medical University from January 2013 to December 2018. The patients were randomly divided into modeling and internal validation groups using a random number generator at a 1:1 ratio. Multivariate Cox regression analysis was used to identify risk factors for all-cause mortality during a one-year follow-up period. Then, a nomogram was constructed based on the weights of each index and validated. Receiver operating characteristic curve, the area under the curve (AUC), decision curve, and calibration curve analyses for survival were used to evaluate the model’s predictive and clinical validities and calibration.ResultsWe included 3,406 patients who met the eligibility criteria; 1,703 cases each were included in the modeling and internal validation groups. Eight statistically significant predictors were identified: age, sex, New York Heart Association cardiac function class III or IV, a history of myocardial infarction, and the albumin, triglycerides, N-terminal pro-b-type natriuretic peptide, and blood urea nitrogen levels. The AUCs were 0.793 (95% confidence interval: 0.763–0.823) and 0.794 (95% confidence interval: 0.763–0.823) in the modeling and validation cohorts, respectively.ConclusionsWe present a predictive model for all-cause mortality in patients with coexisting HF and AF comprising eight key factors. This model gives clinicians a simple assessment tool that may improve the clinical management of these patients.

Gender cardiology: clinical and pathophysiological features of the course the main diseases in women

Coronary heart disease is the leading cause of death for both women and men. Older women, when coronary heart disease first appears, have more comorbidities and usually complain of atypical symptoms. Mortality and hospitalization rates caused by acute myocardial infarction are higher for women. It should be noted that adherence to secondary prevention for women is lower.Female predominance has been noted in idiopathic pulmonary arterial hypertension (IPAH), hereditary pulmonary hypertension, and collagenosisassociated pulmonary arterial hypertension. However, according to the latest data of the European register COMPERA, gender differences disappear for elderly patients and for the patients having concomitant diseases. The more frequent occurrence of cardiomyopathies among women is considered. Peripartum cardiomyopathy associated with pregnancy and childbirth, and Takotsubo cardiomyopathy due to psychoemotional status, in particular a stressful situation, determines a woman's further prognosis. Arrythmias are explained by changes in hormonal status during pregnancy, menopause, or are associated with the onset of the underlying disease.Heart failure usually affects both sexes equally, with women more likely to suffer from HFpEF and men from HFrEF. The classic cardiovascular, gender, and social risk factors for cardiovascular disease and heart failure have a different meaning for women than for men. It is necessary to take into account the parameters for EchoCG diagnostics for women, since the size of the women heart is smaller.

Sodium-glucose cotransporter-2 inhibitors improve cardiovascular outcomes post-acute coronary syndrome complicated by acute heart failure.

Acute coronary syndrome (ACS) remains a risk factor for heart failure (HF). Therefore, we aimed to assess the cardioprotective role of sodium-glucose cotransporter-2 (SGLT2) inhibitors post-ACS in patients with acute HF (AHF) and diabetes. We conducted a retrospective observational cohort study employing propensity score matching. This study involved patients with diabetes admitted with ACS complicated by AHF, defined as either new clinical HF requiring diuretics during the index admission or having an ejection fraction (EF) of <40%. The study population was divided into two groups; (1) SGLT2 inhibitor users and (2) SGLT2 inhibitor non-users. The Cox proportional hazard regression analysis was used to evaluate the outcomes. A total of 465 patients (93% male; mean age, 55 ± 10 years) were included in this study. Using a 1 : 1 propensity score matching, 78 patients were included per arm with an absolute standardized difference of <0.1 for all baseline characteristics. The use of SGLT2 inhibitors resulted in lower composite outcomes of ACS, HF hospitalization, and all-cause mortality at 1 month and 12 months [1 month: 2.6% vs. 11.5%, HR = 0.20 (0.04-0.94), p = 0.041; 12 months: 14.1% vs. 23.1%, HR = 0.46 (0.22-0.99), p = 0.046]. The findings suggest that SGLT2 inhibitors may confer cardioprotective effects in ACS-induced AHF, thereby widening the spectrum for indications of SGLT2 inhibitors.

Cancer as an Individual Risk Factor for Heart Failure: A Review of Literature.

The intricate relationship between cancer and cardiovascular diseases (CVD), notably heart failure (HF), is gaining attention in the medical field. This literature review explores the intricate interplay between cancer and CVD, particularly HF, emphasizing their significant impact on global mortality and comorbidity. While preventive measures have contributed to reducing their incidence, challenges persist in predicting and managing cancer-related complications. This review article delves into various risk factors associated with both cancer and HF, including lifestyle factors, genetic predispositions, and immune system dysregulation. It highlights emerging evidence suggesting a direct interaction between cancer and HF, with studies indicating an elevated risk of mortality from cancer in patients with HF and vice versa. Pathological mechanisms such as inflammation, oxidative stress, and tissue hypoxia are implicated in cancer-induced cardiac dysfunction, underscoring the need for comprehensive clinical investigations and ethical considerations in patient care. The review also discusses the potential role of biomarkers in risk assessment, early detection of cardiotoxicity, and understanding common pathophysiological links between cancer and HF, paving the way for multifaceted preventive and therapeutic approaches.

Possible Role of Gut Microbiota Alterations in Myocardial Fibrosis and Burden of Heart Failure in Hypertensive Heart Disease.

Epidemiological studies have revealed that hypertensive heart disease is a major risk factor for heart failure, and its heart failure burden is growing rapidly. The need to act in the face of this threat requires first an understanding of the multifactorial origin of hypertensive heart disease and second an exploration of new mechanistic pathways involved in myocardial alterations critically involved in cardiac dysfunction and failure (eg, myocardial interstitial fibrosis). Increasing evidence shows that alterations of gut microbiota composition and function (ie, dysbiosis) leading to changes in microbiota-derived metabolites and impairment of the gut barrier and immune functions may be involved in blood pressure elevation and hypertensive organ damage. In this review, we highlight recent advances in the potential contribution of gut microbiota alterations to myocardial interstitial fibrosis in hypertensive heart disease through blood pressure-dependent and blood pressure-independent mechanisms. Achievements in this field should open a new path for more comprehensive treatment of myocardial interstitial fibrosis in hypertensive heart disease and, thus, for the prevention of heart failure.

Sodium-glucose exchanger 2 inhibitor canagliflozin promotes mitochondrial metabolism and alleviates salt-induced cardiac hypertrophy via preserving SIRT3 expression

IntroductionExcess salt intake is not only an independent risk factor for heart failure, but also one of the most important dietary factors associated with cardiovascular disease worldwide. Metabolic reprogramming in cardiomyocytes is an early event provoking cardiac hypertrophy that leads to subsequent cardiovascular events upon high salt loading. Although SGLT2 inhibitors, such as canagliflozin, displayed impressive cardiovascular health benefits, whether SGLT2 inhibitors protect against cardiac hypertrophy-related metabolic reprogramming upon salt loading remain elusive. ObjectivesTo investigate whether canagliflozin can improve salt-induced cardiac hypertrophy and the underlying mechanisms. MethodsDahl salt-sensitive rats developed cardiac hypertrophy by feeding them an 8% high-salt diet, and some rats were treated with canagliflozin. Cardiac function and structure as well as mitochondrial function were examined. Cardiac proteomics, targeted metabolomics and SIRT3 cardiac-specific knockout mice were used to uncover the underlying mechanisms. ResultsIn Dahl salt-sensitive rats, canagliflozin showed a potent therapeutic effect on salt-induced cardiac hypertrophy, accompanied by lowered glucose uptake, reduced accumulation of glycolytic end-products and improved cardiac mitochondrial function, which was associated with the recovery of cardiac expression of SIRT3, a key mitochondrial metabolic regulator. Cardiac-specific knockout of SIRT3 not only exacerbated salt-induced cardiac hypertrophy but also abolished the therapeutic effect of canagliflozin. Mechanistically, high salt intake repressed cardiac SIRT3 expression through a calcium-dependent epigenetic modifications, which could be blocked by canagliflozin by inhibiting SGLT1-mediated calcium uptake. SIRT3 improved myocardial metabolic reprogramming by deacetylating MPC1 in cardiomyocytes exposed to pro-hypertrophic stimuli. Similar to canagliflozin, the SIRT3 activator honokiol also exerted therapeutic effects on cardiac hypertrophy. ConclusionCardiac mitochondrial dysfunction caused by SIRT3 repression is a critical promotional determinant of metabolic pattern switching underlying salt-induced cardiac hypertrophy. Improving SIRT3-mediated mitochondrial function by SGLT2 inhibitors-mediated calcium handling would represent a therapeutic strategy against salt-related cardiovascular events.

Estrogen Regulation of PAD2 and Citrullination in the Aging Female Heart

Advanced age is the primary risk factor for heart failure, an enormous public health burden. With aging, men tend to develop systolic dysfunction whereas women are predisposed to develop diastolic dysfunction. Despite these known phenotype differences, underlying molecular mechanisms of sex differences in cardiac aging are unknown. Citrullination, a post-translational modification catalyzed by the peptidylarginine deiminases (PAD) enzyme family, is positively regulated by the sex hormone estrogen (E2) suggesting a potential novel mechanism of age-related cardiac functional changes in women. We hypothesized that PAD expression and citrullination are sexually dimorphic with aging such that as E2 levels decline, so too does citrullination, thus contributing to diastolic dysfunction. We quantified expression of PAD2, the primary cardiac isoform, in female young reproductively competent adult (3 months) and aged (21 months) C57Bl6 mice. Consistent with clinical reports, in our model of aging, female mice developed diastolic dysfunction, with a prolonged linear phase relaxation (54.0 ± 1.7 msec, adult and 66.0 ± 3.3 msec aged, p&lt;0.05). PAD2 expression decreased with age in the female heart, concomitant with decreases in myocardial protein citrullination. To identify potential mechanisms of differential citrullination by age, we performed cit-mass spectrometry. Adult female mice had higher overall citrullination patterns than aged females with enrichment of citrullinated proteins in metabolic, mitochondrial, and sarcomeric pathways. In reproductively competent adult females, cardiac PAD2 expression was higher during estrus compared to diestrus. To confirm direct regulation of PAD2 by E2, a cohort of adult mice underwent ovariectomy (OVX) with or without E2 replacement, provided orally in the water (0.5μM E2) for three weeks. Exogenous E2 supplementation post-OVX increased uterine weight and PAD2 expression, further confirming positive regulation by E2. Together, we suggest that hormonally regulated changes in PAD2 and citrullination with age contribute to sex-specific cardiac aging. Ongoing experiments will directly test the role of PAD2 in the heart by generation of a novel myocyte specific PAD2 deleted mouse across the female lifespan. This abstract was made possible by an Institutional Development Award (IDeA) from the National Institute of General Medical Sciences of the National Institutes of Health under 2P20GM103432. This work was supported by the National Institutes of Health [K01 AG058810 DRB, [K01 AG066845 KCW]. 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.

Novel Role of YAP1 in Regulating Blood Pressure and Vascular Tone

Introduction: Hypertension is a major risk factor for occlusive vascular diseases, myocardial infarction, heart failure, stroke, and chronic kidney disease. In the U.S., ~30% of adults suffer from hypertension. Merely half of the individuals with hypertension have their blood pressure under control, despite the wide range of antihypertensive medications available, indicating an urgent need for a better understanding of the underlying causes of hypertension to identify novel therapeutic strategies for its treatment and prevention. Recent genome-wide association study (GWAS) has identified an unexpected association between a loss-of-function SNP in the YAP1 gene locus and decreased blood pressure (BP). Moreover, de novo analysis of publicly available RNAseq data revealed that the vascular tissues of hypertensive mice treated with Ang-II exhibit increased YAP1 expression. Suggesting a novel role of YAP1 in blood pressure regulation. However, whether Vascular smooth muscle cell (VSMC) expressed YAP1 has a specific role in VSMC contraction and BP regulation remains completely unknown. Therefore, we hypothesized that YAP1 could play a key role in regulating blood pressure. Methodology: We have generated a novel inducible SM-specific- Yap1 Knockout ( YAP1 iKO) mouse model and employed a pharmacological inhibitor of YAP1, Verteporfin, to delineate the functional role of VSMC-expressed YAP1 in hypertension in regulating vascular tone and BP. Vascular reactivity experiments were performed using wire myography. BP was measured in ambulant mice via radiotelemetry. In vitro gain- and loss-of-function studies utilizing human coronary artery SMCs were conducted to examine the impact of YAP1 on contractility signaling components using western blotting. Results: Consistent with GWAS and RNAseq data, we found that YAP1 is upregulated in vascular tissues of spontaneously hypertensive rats (SHRs). Using aortic rings from WT mice, we discovered that Verteporfin significantly reduced vasoconstrictive responses to Phenylephrine or Serotonin but did not alter endothelium-dependent vasorelaxant responses to Acetylcholine, suggesting a specific role of YAP1 in VSMCs. Consistently, YAP1 iKO exhibited attenuated responses to vasoconstrictors in isolated conduit and resistance vessels. Importantly, radiotelemetry studies demonstrated for the first time that YAP1 iKO mice exhibit a hypotensive phenotype. Mechanistically, YAP1 gain- and loss-of-function studies in human VSMCs showed that YAP1 activates multiple signaling pathways that play a key role in VSMC contractility including RhoA/ROCK1/actin polymerization and PKC/ERK signaling pathways. Summary/Conclusion: This is the first study to demonstrate that inhibition of SM-specific-Yap1 expression regulates BP and vascular tone, likely via the regulation of contractile machinery components. Together, our data suggest that YAP1 is a promising novel therapeutic target for ameliorating hypertension. This work is supported by a grant from National Heart, Lung, and Blood Institute (R00HL153896). 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.

RIGHT VENTRICLE IN PATIENTS WITH ARTERIAL HYPERTENSION AND B STAGE HEART FAILURE

Objective: According to ACC/AHA Heart failure (HF) classification the A stage of HF is a high risk for HF but without structural heart disease or symptoms; B stage is a structural heart disease but without signs or symptoms of HF. One of the most important risk factors of HF is Arterial Hypertension (AH). There is no information about Right Ventricular (RV) structure and function, in patients with stage A and B of HF. The aim of our research was to study RV structure and function in patients with AH and stage A or B HF. Design and method: We studied 163 patients with AH (female-76, male 87). 45 in stage A and 118 in stage B HF. All patients undergone standard EchoCG examination. RV outflow tract (RVout) was examined by M-mode from parasternal short axis and PW TDI from subcostal position (RVoutTDI). The shape of RWoutTDI was different from the Tricuspid anulus TDI. It consists from positive isometric contraction (ICTs), isotonic contraction (s), negative early diastolic (e) late (a) diastolic waves velocities, two negative (e1) positive (e2) isometric relaxation waves. We measured the pick velocities of these waves in cm/sec and isometric contraction (ICT), ejection (RVET) and isometric relaxation time (IRT) intervals in msec. On M-mode EcoCG of RVoutRV we measured Diastolic Diameter (Dd) systolic diameter (Ds), fractional shortening (RWoutFS) and RW wall systolic excursion (RWexc). Results: We did not find any significant differences between in RV EcoCG, RVout, RVoutTRI and Tricuspid annulus TDI parameters between the A and B Heart Failure groups in patients wit Arterial Hypertension. Conclusions: There is no difference in EchoCG parameters between A and B Heart Failure groups in patients with Arterial Hypertension.

High Variability of Body Mass Index Is Independently Associated With Incident Heart Failure.

Heart failure (HF) is a serious condition with increasing prevalence, high morbidity, and increased mortality. Obesity is an established risk factor for HF. Fluctuation in body mass index (BMI) has shown a higher risk of cardiovascular outcomes. We investigated the association between BMI variability and incident HF. In the UK Biobank, we established a prospective cohort after excluding participants with prevalent HF or cancer at enrollment. A total of 99 368 White participants with ≥3 BMI measures during >2 years preceding enrollment were included, with a median follow-up of 12.5 years. The within-participant variability of BMI was evaluated using standardized SD and coefficient of variation. The association of BMI variability with incident HF was assessed using Fine and Gray's competing risk model, adjusting for confounding factors and participant-specific rate of BMI change. Higher BMI variability measured in both SD and coefficient of variation was significantly associated with higher risk in HF incidence (SD: hazard ratio [HR], 1.05 [95% CI, 1.03-1.08], P<0.0001; coefficient of variation: HR, 1.07 [95% CI, 1.04-1.10], P<0.0001). Longitudinal health records capture BMI fluctuation, which independently predicts HF incidence.

Risk Factors of Postoperative Acute Heart Failure in Elderly Patients After Hip Fracture Surgery.

Background Postoperative acute heart failure (AHF) in elderly patients after hip fracture surgery is a common complication. Therefore, this study aimed to identify the risk factor of AHF after hip fracture surgery among the older population. Methods This retrospective cohort study was performed on 88 admitted patients whose hip fractures were fixed via internal fixation surgery in a tertiary care hospital in Rawalpindi, Pakistan, from January 2022 to March 2023. Recruitment of patients was made through established inclusion and exclusion criteria. Ethical approval and informed consent were also gained before the data collection. A self-designed form was used to collect data. Data analysis was carried out in the IBM SPSS Statistics for Windows, Version 25 (Released 2017; IBM Corp., Armonk, New York, United States). Both descriptive and inferential statistics were applied to compare the attributes of the patients with AHF and patients without AHF. Multivariate logistic regression was used to evaluate the association between the postoperative AHF and its potential risk factors. Results Out of 88 enrolled patients, 12 (13.64%) had developed postoperative AHF. Age ≥ 65 years (OR = 2.606, 95% CI = 1.035~4.160, p = 0.010), anemia (OR = 3.178, 95% CI = 1.847~5.990, p = 0.029), hypertension (OR = 2.019, 95% CI = 1.110~4.034, p = 0.012), diabetes mellitus (OR = 2.003, 95% CI = 1.115~4.012, p = 0.015), hypoalbuminemia (OR = 2.486, 95% CI = 1.218~4.619, p = 0.030), and operation time ≥ 120 minutes (OR = 1.702, 95% CI = 1.099~2.880, p = 0.018), were the risk factors of postoperative AHF in elderly patients after hip fracture surgery. Conclusions In the study population, the incidence of postoperative heart failure was significant and age ≥ 65 years, anemia, hypertension, diabetes mellitus, hypoalbuminemia, and operation time ≥ 120 were significantly involved in the development of it. Preoperative identification and management of AHF risk factors could lead to the prevention of postoperative complications.

Gut Microbiome and Its Role in Valvular Heart Disease: Not a "Gutted" Relationship.

The role of the gut microbiome (GM) and oral microbiome (OM) in cardiovascular disease (CVD) has been increasingly being understood in recent years. It is well known that GM is a risk factor for various CVD phenotypes, including hypertension, dyslipidemia, heart failure and atrial fibrillation. However, its role in valvular heart disease (VHD) is less well understood. Research shows that, direct, microbe-mediated and indirect, metabolite-mediated damage as a result of gut dysbiosis and environmental factors results in a subclinical, chronic, systemic inflammatory state, which promotes inflammatory cell infiltration in heart valves and subsequently, via pro-inflammatory molecules, initiates a cascade of reaction, resulting in valve calcification, fibrosis and dysfunction. This relationship between GM and VHD adds a pathophysiological link to the pathogenesis of VHD, which can be aimed therapeutically, in order to prevent or regress any risk for valvular pathologies. Therapeutic interventions include dietary modifications and lifestyle interventions, in order to influence environmental factors that can promote gut dysbiosis. Furthermore, the combination of probiotics and prebiotics, as well as fecal m transplantation and targeted treatment with inducers or inhibitors of microbial enzymes have showed promising results in animal and/or clinical studies, with the potential to reduce the inflammatory state and restore the normal gut flora in patients. This review, thus, is going to discuss the pathophysiological links behind the relationship of GM, CVD and VHD, as well as explore the recent data regarding the effect of GM-altering treatment in CVD, cardiac function and systemic inflammation.

The Role of Gut Microbiota and Its Metabolites in Patients with Heart Failure.

Heart failure (HF) is a significant health concern; early detection and prevention are crucial. Recent studies suggest that the gut microbiota and its metabolites may influence HF development and risk factors. We explored this relationship by examining changes in gut microbiota composition and metabolite levels in HF patients. HF patients often exhibit decreased alpha and beta diversity compared to controls, suggesting lower bacterial richness and community variation. Changes in specific bacterial phyla were observed, with decreases in Firmicutes (e.g., Ruminococcus) and Bacteroidetes (e.g., Prevotella) and increases in Proteobacteria (e.g., Escherichia, Shigella, and Klebsiella) and Actinobacteria. Gut-microbiota-related metabolites have been identified, potentially affecting various body systems, including the cardiovascular system. Among these are short-chain fatty acids (SCFAs), betaine, trimethylamine N-oxide (TMAO), phenylalanine, tryptophan-kynurenine, and phenylacetylgutamine (PAGIn). Although SCFAs positively affect our organisms, patients with HF have been observed to experience a decline in bacteria responsible for producing these chemical compounds. There have been indications of possible links between betaine, TMAO, phenylalanine, tryptophan-kynurenine, PAGIn, and heart failure. TMAO and phenylalanine, in particular, show promise as potential prognostic factors. However, their clinical significance has not yet been thoroughly evaluated and requires further investigation.

Outcomes in patients treated with loop diuretics without a diagnosis of heart failure: a retrospective cohort study

BackgroundLoop diuretics are commonly prescribed in the community, not always to patients with a recorded diagnosis of heart failure (HF). The rate of HF events in patients prescribed loop diuretics...

A Fast-Growing Myxoma of the Left Atrium.

Myxoma of the left atrium is a less typical cause of mitral obstruction. If this develops, a flash pulmonary oedema can be the first manifestation. We present a case report of a 50-year-old woman who was admitted to our internal department because of dyspnoea. The patient overcame a stroke three years before the index hospitalisation with a negative transthoracic echocardiography. By anamnesis and physical examination, an exacerbation of COPD was assumed, and the patient was treated accordingly. As the patient showed numerous risk factors for heart failure with preserved ejection fraction, transthoracic echocardiography was performed. A large polypoid mass was found in the left atrium, which caused severe mitral obstruction. Subsequent transoesophageal echocardiography confirmed this finding. The patient underwent urgent cardiac surgery, and the tumour was successfully resected. A histological examination revealed a cardiac myxoma. After the cardiac surgery the patient felt well, and no recurrence of the tumour occurred. We provide a case report of a fast-growing myxoma that was incidentally found in a patient with dyspnoea. We highlight the fast growth rate of the tumour and the potential for misdiagnosed signs of pulmonary oedema caused by mitral obstruction. Myxomas are the most common primary tumours of the heart, which can manifest a variety of symptoms such as fever, weight loss, thromboembolism, or mitral obstruction.The symptoms of acute exacerbation of COPD and cardiogenic pulmonary oedema can overlap and can be difficult to differentiate by anamnesis and physical examination alone.Transthoracic echocardiography has a high sensitivity for cardiac masses and is the examination of choice when these are suspected.

Premature ventricular complexes: Assessing burden density in a large national cohort to better define optimal ECG monitoring duration

BackgroundPremature ventricular contraction (PVC) burden is a risk factor for heart failure and cardiovascular death in patients with structural heart disease. Long-term electrocardiographic monitoring can have a significant impact on PVC burden evaluation by further defining PVC distribution patterns. ObjectiveThis study aimed to ascertain the optimal duration of electrocardiographic monitoring to characterize PVC burden and to understand clinical characteristics associated with frequent PVCs and nonsustained ventricular tachycardia in a large US cohort. MethodsCommercial data (iRhythm’s Zio patch) from June 2011 to April 2022 were analyzed. Inclusion criteria were age >18 years, PVC burden ≥5%, and wear period ≥13 days. PVC burden cutoffs were determined on the basis of AHA/ACC/HRS guidelines for very frequent PVCs (10,000–20,000 during 24 hours). Patients were assigned to categories by PVC densities: low, <10%; moderate, 10% to <20%; and high, ≥20%. Mean measured error was assessed at baseline and daily until the wear period’s end for overall PVC burden and different PVC densities. ResultsAnalysis of 106,705 patch monitors revealed a study population with mean age of 70.6 ± 14.6 years (33.6% female). PVC burden was higher in male patients and those >65 years of age. PVC burden mean error decreased from 2.9% at 24 hours to 1.3% at 7 days and 0.7% at 10 days. Number of ventricular tachycardia episodes per patient increased with increasing PVC burden (P < .0001). ConclusionExtending ambulatory monitoring beyond 24 hours to 7 days or more improves accuracy of assessing PVC burden. Ventricular tachycardia frequency and duration vary by initial PVC density, highlighting the need for prolonged cardiac monitoring.

Toward a Universal Definition of Etiologies in Heart Failure: Categorizing Causes and Advancing Registry Science.

Heart failure (HF) is a well-described final common pathway for a broad range of diseases however substantial confusion exists regarding how to describe, study, and track these underlying etiologic conditions. We describe (1) the overlap in HF etiologies, comorbidities, and case definitions as currently used in HF registries led or managed by members of the global HF roundtable; (2) strategies to improve the quality of evidence on etiologies and modifiable risk factors of HF in registries; and (3) opportunities to use clinical HF registries as a platform for public health surveillance, implementation research, and randomized registry trials to reduce the global burden of noncommunicable diseases. Investment and collaboration among countries to improve the quality of evidence in global HF registries could contribute to achieving global health targets to reduce noncommunicable diseases and overall improvements in population health.

Causal relationship between nutritional assessment phenotypes and heart failure: A Mendelian randomization study

IntroductionMalnutrition is strongly associated with heart failure (HF); however, the causal link remains unclear. We used Mendelian randomization (MR) to infer causal associations between different nutritional assessment phenotypes and HF and to analyze whether these associations were mediated by common HF risk factors. MethodsTwo-sample bidirectional MR was used to infer causal associations between nutritional assessment phenotypes and HF. Mutual influences between different nutritional assessment phenotypes and potential correlations were estimated using multivariate MR methods. Two-step MR was used to quantify the mediating effects of common HF risk factors on the causal associations. ResultsThree phenotypes were positively associated with the development of HF: waist circumference (WC) (odds ratio [OR] = 1.74; 95% confidence interval [CI], 1.60–1.90; P = 3.95 × 10−39), body mass index (BMI) (OR = 1.70; 95%CI, 1.60–1.80; P = 1.35 × 10−73), and whole body fat mass (WBFM) (OR = 1.54; 95%CI, 1.44–1.65; P = 4.82 × 10−37). Multivariate MR indicated that WBFM remained positively associated with HF after conditioning on BMI and WC (OR = 2.05; 95%CI, 1.27–3.31; P = 0.003). Three phenotypes were negatively correlated with the development of HF: usual walking pace (UWP) (OR = 0.40; 95%CI, 0.27–0.60; P = 8.41 × 10−6), educational attainment (EA) (OR = 0.73; 95%CI, 0.67–0.79; P = 2.27 × 10−13), and total cholesterol (TC) (OR = 0.90; 95%CI, 0.84–0.96; P = 4.22 × 10−3). There was a bidirectional causality between HF and UWP (Effect estimate = −0.03; 95%CI, −0.05 to −0.01; P = 1.95 × 10−3). Mediation analysis showed that common risk factors for HF (hypertension, coronary artery disease, cardiomyopathy, and valvular heart disease) mediated these causal associations (all P < 0.05). ConclusionsBMI, WC, and WBFM are potential risk factors for HF, and the correlation between WBFM and HF was significantly stronger than that between BMI and WC, and HF. EA, UWP, and TC are potential protective factors against HF. Common risk factors for HF mediate these causal pathways. Early identification of potential risk or protective factors for HF patients from the dimension of nutritional status is expected to further improve patient outcomes.

An Underappreciated Risk Factor for Heart Failure—Financial Toxicity

An Underappreciated Risk Factor for Heart Failure—Financial Toxicity